79C3C34C52B45572883A05D425EB0F82
Scientific and Ethical Approaches for Observational Exposure Studies
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| Indicators in focus are typically shown highlighted in yellow; |
Peer Indicators (that share the same Vulnerability association) are shown highlighted in pink; |
"Outside" Indicators (those that do NOT share the same Vulnerability association) are shown highlighted in green; |
Trigger Words/Phrases are shown highlighted in gray. |
Link to Orphaned Trigger Words (Appendix (Indicator List, Indicator Peers, Trigger Words, Type/Vulnerability/Indicator Overlay)
Applicable Type / Vulnerability / Indicator Overlay for this Input
Political / Criminal Convictions
Searching for indicator prisoners:
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p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
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p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
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p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
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p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
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p.000038: subjects rule is completely consistent with the HHS rule in adding additional protections for pregnant women and
p.000038: fetuses involved in observational research (40 CFR
p.000038: 26.304 and 45 CFR 46.204). These additional protections (specified in 45 CFR 46.204 subparagraphs a
p.000038: through j) reflect the CIOMS recommendations by requiring: availability of data from previously conducted
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
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p.000054: or affiliated with the research study, to be available for translations.
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
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p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
p.000055: dialogue . . . involving the disclosure and exchange of relevant information” (IOM, 2002): it is not
p.000055: simply having a consent form signed. The process is most effective when the researcher spends time with
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p.000058: payments. They also recommend that the policies disclose any recompense in a full and open
p.000058: process,22 while not overemphasizing any recompense.
p.000058: Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
p.000058: benefits, or they may be particularly vulnerable to undue influence resulting from the offer of a payment for
p.000058: research participation. In addition, payments made directly to parents or guardians could alter
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
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p.000060: participants and provide information on grievance procedures and research-related injuries. These questions
p.000060: could be addressed to the IRB, an ombudsman, an ethics committee, or other knowledgeable
p.000060: administrative body. Consent documents are expected to have at least two names with appropriate
p.000060: telephone contact information⎯one that can provide information regarding the research and
p.000060: another that can provide information regarding their rights as research participants. Grievance
p.000060: procedures should be structured so that grievances reach the approving IRBs and sponsoring
p.000060: organizations.
p.000060:
p.000060: 5.3.1 Ombudsman
p.000060: An ombudsman is a neutral independent advocate for research participants (and their families or guardians, where
p.000060: applicable). Institutions and IRBs may recommend or require the use of an ombudsman in
p.000060: certain types of research studies, particularly those seeking to study vulnerable populations.
p.000060: Ombudsmen can fill several roles as participant advocates. They may be an independent source of information
p.000060: regarding the study. They may be present during the informed consent process to ensure that risks, benefits,
p.000060: and study requirements are communicated correctly and understood by potential participants
p.000060: or their guardians. An ombudsman may be used in studies involving prisoners or military personnel to
p.000060: ensure that there is no coercion to participate. And the ombudsman may
p.000060:
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p.000061: communicate problems or grievances raised by research participants to the IRB and sponsoring organization.
p.000061:
p.000061: 5.3.2 Community Advisory Board
p.000061: CABs can help ensure that participant rights are considered and addressed during the study design and can
p.000061: play an important role in monitoring the research process. Community members may choose to seek
p.000061: information about the study from the advisory panel, as an independent entity, before deciding whether to enroll.
p.000061: Representatives from such advisory boards can be included in the research team that designs the study (see
p.000061: Section 2.3). The role of CABs is more fully discussed in Section 6.
p.000061:
p.000061: 5.4 Creating a Supportive Environment for Research and Interaction
p.000061: It is recommended that researchers and institutions strive to create a supportive environment for research
p.000061: and interaction with research participants and communities. At the personal level,
p.000061: this means researchers building trust with individuals and treating them with respect. Following the IOM
p.000061: recommendations about the informed consent process⎯that it “should be an on-going, interactive dialogue between
p.000061: research staff and research participants involving the disclosure and exchange of relevant information,
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p.000061: Director’s Council of Public Representatives (COPR) (NIH, 2005). Although the advice from this workshop was
p.000061: developed in the context of NIH-supported clinical research, many of the recommendations are applicable to
p.000061: observational human exposure studies and human subject research in general. A summary
p.000061: of
p.000061: recommendations from the report for enhancing public trust is provided in Appendix D. The recommendations are
p.000061: focused on the following areas.
p.000061: • Building trust through community partnerships
p.000061: • Building relationships with patients (participants) (True partnerships with patients may not be possible,
p.000061: but bidirectional relationships must be enhanced.)
p.000061: • Building partnerships with community providers
p.000061: • Building trust in scientists
p.000061: • Building trust in the (EPA) and scientific research.
p.000061:
p.000061: 5.5 Recruitment Strategies
p.000061: Many strategies are used to select and recruit people into research studies requiring human participation. The IRB is
p.000061: responsible for reviewing the selection process to ensure that it is, above all, equitable. The requirement for
p.000061: IRB review is stated in 40 CFR 26.111(a)3.
p.000061: Selection of subjects is equitable. In making this assessment, the IRB should take into account the
p.000061: purposes of the research and the setting in which the research will be conducted and should be particularly cognizant
p.000061: of the special problems of research involving vulnerable populations, such as children, prisoners,
p.000061: pregnant women, mentally disabled persons, or economically or educationally disadvantaged
p.000061: persons.
p.000061: The IRB guidebook is an excellent resource for consideration of concerns and elements for equitable
p.000061: participant selection (U.S. HHS, 1993). It states that “Defining the appropriate group of subjects
p.000061: for a research project involves a variety of factors⎯ requirements of scientific design,
p.000061: susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness.” The IRB
p.000061: guidebook raises a number of points to consider in the process for selection of human participants (see Text Box
p.000061: 5-5).
p.000061: Various participant recruitment strategies may be used depending on the type of research being performed and the
p.000061: population of interest. This section addresses the strategies and approaches for identifying and contacting people and
p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
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p.000062:
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p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
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p.000118: United States Environmental Protection Agency
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p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
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Political / Illegal Activity
Searching for indicator crime:
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p.000045: researchers may decide to use materials prepared by other organizations that have expertise regarding
p.000045: a particular hazard.
p.000045: Another important element of planning for field data collection and training of research staff is on hazards and
p.000045: situations that the field staff may encounter during their field work. Although the previous discussion highlights the
p.000045: need to be prepared to report potentially negligent or illegal behaviors, these same behaviors may place the
p.000045: research staff in imminent danger during the conduct of their work in residences and communities. The research team
p.000045: should develop a plan for identifying potential situations, hazards, and dangers that may place the
p.000045: research team at risk of imminent harm. This should generally involve working with
p.000045: community representatives to identify the hazards and situations that may be of concern. For example, a
p.000045: researcher’s observation of illegal drugs in a study residence may place the researcher in potential
p.000045: danger. Similarly, if studies are conducted in areas with high crime rates, researchers need to be aware of
p.000045: the potential dangers and have a plan for addressing them. In some cases, situations may arise
p.000045: because of to inadvertent actions. For example, if an area has a high rate of daytime break- ins, the presence
p.000045: of researchers in the area may trigger calls to local authorities when the researchers, who are
p.000045: strangers, are observed in the neighborhood. Feedback from the community representatives should be solicited when
p.000045: developing a plan for responding to situations such as these. Comprehensive training should be developed for
p.000045: research field staff to assist them in identifying potentially dangerous situations and in responding to
p.000045: such situations.
p.000045:
p.000045: 4.4 Third-Party Issues
p.000045: Third-party issues can arise in observational human exposure studies in two ways. First, the study may collect
p.000045: limited information about or related to individuals other than the study participants. Second,
p.000045: study activities may affect or involve people or organizations other than the study participants.
p.000045: Examples of activities that may involve or affect third parties in observational human exposure studies
p.000045: could include, but are not limited to the following types.
p.000045: • Asking the participant about demographic, occupational, smoking, or product use information for
p.000045: other household members
p.000045: • Collecting residential environmental samples in multiperson households
p.000045:
p.000045:
p.000046: 46
p.000046:
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Searching for indicator illegal:
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p.000045: (2) conditions of neglect that may adversely impact study participants or third parties,
p.000045: (3) environmental hazards and situations that may be associated with imminent harm (e.g., combustible
p.000045: materials near an open flame, unsecured firearms accessible to very young children),
p.000045: (4) policies and procedures for reporting or intervention by members of the research team, and
p.000045: (5) local and state reporting requirements.
p.000045: It is advisable that this training be developed in consultation with community representatives who can
p.000045: provide input on potential hazards and situations that may be encountered in the study community,
p.000045: local norms and attitudes about potential interventions and reporting, and local agencies available to assist on
p.000045: these types of issues. It is also especially important to consider
p.000045: staff experience and training in hazard communication. Consistency in communication is very important, and
p.000045: researchers may decide to use materials prepared by other organizations that have expertise regarding
p.000045: a particular hazard.
p.000045: Another important element of planning for field data collection and training of research staff is on hazards and
p.000045: situations that the field staff may encounter during their field work. Although the previous discussion highlights the
p.000045: need to be prepared to report potentially negligent or illegal behaviors, these same behaviors may place the
p.000045: research staff in imminent danger during the conduct of their work in residences and communities. The research team
p.000045: should develop a plan for identifying potential situations, hazards, and dangers that may place the
p.000045: research team at risk of imminent harm. This should generally involve working with
p.000045: community representatives to identify the hazards and situations that may be of concern. For example, a
p.000045: researcher’s observation of illegal drugs in a study residence may place the researcher in potential
p.000045: danger. Similarly, if studies are conducted in areas with high crime rates, researchers need to be aware of
p.000045: the potential dangers and have a plan for addressing them. In some cases, situations may arise
p.000045: because of to inadvertent actions. For example, if an area has a high rate of daytime break- ins, the presence
p.000045: of researchers in the area may trigger calls to local authorities when the researchers, who are
p.000045: strangers, are observed in the neighborhood. Feedback from the community representatives should be solicited when
p.000045: developing a plan for responding to situations such as these. Comprehensive training should be developed for
p.000045: research field staff to assist them in identifying potentially dangerous situations and in responding to
p.000045: such situations.
p.000045:
p.000045: 4.4 Third-Party Issues
p.000045: Third-party issues can arise in observational human exposure studies in two ways. First, the study may collect
p.000045: limited information about or related to individuals other than the study participants. Second,
p.000045: study activities may affect or involve people or organizations other than the study participants.
p.000045: Examples of activities that may involve or affect third parties in observational human exposure studies
p.000045: could include, but are not limited to the following types.
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Political / Indigenous
Searching for indicator indigenous:
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p.000077: public health: The role of action-oriented partnerships. J Public Health Manag Pract 7(2):21-32.
p.000077:
p.000077:
p.000078: 78
p.000078:
p.000078: U.S. EPA, Office of Environmental Justice Resources:
p.000078: Executive Office of the President. (1997). Environmental Justice: Guidance under the National Environmental Policy Act.
p.000078: Council on Environmental Quality, pp. 7-17).
p.000078: Available: http://epa.gov/compliance/resources/policies/ej/ej_guidance
p.000078: _nepa_ceq1297.pdf
p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2006). Future mechanisms to enhance stakeholder involvement
p.000078: and engagement to address environmental justice: A letter report. Available:
p.000078: http://epa.gov/compliance/resources/publications/ej/nejac/st akeholder-involv-9-27-06.pdf
p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2004). Environmental justices and federal facilities:
p.000078: Recommendations for improving stakeholder relations between federal facilities and environmental justice communities.
p.000078: Waste and Facility Siting Subcommittee, Federal Facilities Working Group. Available:
p.000078: http://www.epa.gov/compliance/resources/publications/ej/n ejac/ffwg-final-rpt-102504.pdf
p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2004). Meaningful involvement and fair treatment by tribal
p.000078: environmental regulatory programs. Indigenous Peoples Subcommittee. Available:
p.000078: http://epa.gov/compliance/resources/publications/ej/nejac/ip s-final-report.pdf
p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2000). Guide on consultation and collaboration with Indian
p.000078: tribal governments and the public participation of indigenous groups and tribal members in environmental decision
p.000078: making. Indigenous Peoples Subcommittee.
p.000078: Available: http://www.lm.doe.gov/env_justice/pdf/ips_consultation_gu ide.pdf
p.000078: NEJAC (National Environmental Justice Advisory Council) (2000). NEJAC May 200 Meeting Report. Environmental Justice and
p.000078: Community-Based Health Model Discussion. Available: http://epa.gov/compliance/resources/publications/ej/nejac/co
p.000078: mmunity-based-health-recom-report.pdf
p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2000). The model plan for public participation. The Public
p.000078: Participation and Accountability Subcommittee. EPA 300/K-00-001. Available:
p.000078: http://epa.gov/compliance/resources/publications/ej/nejac/m odel-public-part-plan.pdf
p.000078:
p.000078: U.S. EPA (U.S. Environmental Protection Agency). (2008). The Environmental Justice Strategic Enforcement Assessment
p.000078: Tool (EJSEAT). Available: http://www.epa.gov/compliance/resources/policies/ej/ej seat.html
p.000078:
p.000078: U.S. EPA (U.S. Environmental Protection Agency). (2006). Environmental Justice Collaborative Problem-Solving
p.000078: Cooperative Agreement Program FACT SHEET. Office of Environmental Justice. Available:
p.000078: http://www.epa.gov/compliance/resources/publications/ej/fa ctsheets/fact-sheet-ej-cps-grants-6-13-06.pdf
p.000078:
...
Searching for indicator native:
(return to top)
p.000070: which the individual is acting (ERG, 2007).
p.000070:
p.000070: 6.2.2 Identifying Who Represents the Community
p.000070: To sufficiently represent the community, an individual has to have not only the right to speak for the
p.000070: community’s interests (a right afforded by legitimate membership in the group) but also should be able
p.000070: to describe those interests on behalf of the community. Identifying those who represent the community is
p.000070: not simply a matter of identifying the most vocal activists because those individuals do not necessarily
p.000070: represent the interests of the entire community. In fact, several individuals may be necessary to adequately
p.000070: represent the diversity of viewpoints within a community; in such cases, a CAB may be appropriate (ERG, 2007).
p.000070: One of the researcher’s first steps should be asking the potential participants from the community who they see
p.000070: as a
p.000070:
p.000070:
p.000071: 71
p.000071:
p.000071: legitimate representative (i.e., someone who can speak for them). Corburn cites an example of a locale
p.000071: in Brooklyn, NY, that contained individuals with widely different backgrounds. It was impossible to
p.000071: identify appropriate spokespeople, or even to define the nature of the community, without talking with
p.000071: community members (Corburn, 2007).
p.000071: The NRC & IOM (2005) Report also discusses the issue of who can represent the identified community. Some
p.000071: communities may have a formal governmental structure and a recognized political authority (e.g.,
p.000071: Native American tribes). Other communities may have clearly identifiable leaders (e.g., religious communities),
p.000071: whereas still other communities have no formal leadership structure at all. Whether there is a
p.000071: legitimate political authority or some other hierarchal leadership structure, the goal is to seek community input
p.000071: as to who best represents the interests of the community with regard to the proposed research project,
p.000071: rather than selecting those who are favorable to the research project. The NRC & IOM report cautions against
p.000071: the ethically questionable practice of seeking out population spokespeople and research participants
p.000071: whose positive response to a research plan can be predicted in advance and refers the reader to an article on this
p.000071: topic by Juengst (2000).
p.000071: With multiple sources of leadership and authority in many communities, careful consideration should be given
p.000071: to what aspect of the community a particular person will represent, and what efforts may be needed to ensure
p.000071: that the entire range of views in a community are obtained. Researchers should consider reaching out to multiple
p.000071: organizations such as churches, social service agencies, community-based organizations, and tenant and
p.000071: other community advocacy groups.
p.000071:
p.000071: 6.2.3 Building Relationships and Trust
p.000071: A key first step in developing trust is to establish a relationship with the community before the study. Trust must be
...
Political / criminal
Searching for indicator criminal:
(return to top)
p.000042: • Restricting access to identifying information to only those requiring access
p.000042: • Assigning codes to participants, data, and samples rather than using identifiers
p.000042: • Physically separating identifying information and linkage files from other study information
p.000042: • Securing identifying information in locked files with limited access
p.000042: • Restricting identifying information from computers that are networked with other computers or electronic systems
p.000042: • Restricting identifying information from computers that are not kept in secure locations with limited access
p.000042: • Training research staff members on human subject protection and on information security procedures
p.000042:
p.000042:
p.000042: Another step that can help protect confidentiality is to obtain a Certificate of Confidentiality. Certificates of
p.000042: Confidentiality are issued by NIH (2002) to protect identifiable research information from forced disclosure.
p.000042: They allow the investigator and others who have access to research records to refuse to disclose identifying
p.000042: information on research participants in any civil, criminal, administrative, legislative, or other
p.000042: proceeding, whether at the Federal, State, or local level. Certificates of Confidentiality may be granted for studies
p.000042: collecting information that, if disclosed, could have adverse consequences for subjects or damage
p.000042: their financial standing, employability, insurability, or reputation. By protecting researchers and
p.000042: institutions from being
p.000042:
p.000042:
p.000043: 43
p.000043:
p.000043: compelled to disclose information that would identify research subjects, Certificates of Confidentiality
p.000043: help achieve the research objectives and promote participation in studies by assuring
p.000043: confidentiality and privacy to participants. Any research project that collects sensitive, personally identifiable
p.000043: information and that has been approved by an IRB is eligible for a certificate. Identifying information is broadly
p.000043: defined as any item or combination of items in the research data that could lead directly or indirectly to the
p.000043: identification of a research subject.
p.000043: Federal funding is not a prerequisite for a certificate. A Certificate of Confidentiality does not
p.000043: diminish, however, the investigator’s need to protect the personally identifiable information as
p.000043: described above.
p.000043:
p.000043: 4.2.2 Confidentiality of Participation
p.000043: In some types of research, the knowledge that a person is participating in a particular research study
...
Political / displaced
Searching for indicator displaced:
(return to top)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
...
Political / nomad
Searching for indicator nomads:
(return to top)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
...
Political / political affiliation
Searching for indicator party:
(return to top)
p.000035: 35
p.000035: 3.1. Identification of Vulnerable Groups
p.000035: 35
p.000035: vii
p.000035:
p.000035: 3.2. Justification for Involving Vulnerable Persons in Observational Research 36
p.000035: 3.3. Minimal Risk and Vulnerable Groups
p.000037: 37
p.000037: 3.4. Research Involving Children
p.000037: 37
p.000037: 3.5. Women as Research Subjects
p.000038: 38
p.000038: 3.6. Other Potentially Vulnerable Groups
p.000039: 39
p.000039: 4. Privacy, Confidentiality, and Other Concerns Related to Observational
p.000039: Human Exposure Studies
p.000041: 41
p.000041: 4.1. Privacy Issues
p.000041: 41
p.000041: 4.2. Confidentiality
p.000042: 42
p.000042: 4.2.1. Confidentiality of Information
p.000043: 43
p.000043: 4.2.2. Confidentiality of Participation
p.000044: 44
p.000044: 4.3. Collateral Observations
p.000044: 44
p.000044: 4.3.1. Potential Nonstudy Hazards in the Residence 44
p.000044: 4.3.2. Collateral Observations with Mandated Reporting Requirements 45
p.000044: 4.3.3. Hazard Communication
p.000045: 45
p.000045: 4.3.4. Planning and Staff Training
p.000046: 46
p.000046: 4.4. Third-Party Issues
p.000046: 46
p.000046: 4.4.1. Determining Whether a Third Party Is a Human Subject 47
p.000046: 4.4.2. Informing Third Parties of Research Activities 47
p.000046: 4.4.3. Research Results and Third Parties
p.000047: 47
p.000047: 4.5. Data and Safety Monitoring and Oversight
p.000048: 48
p.000048: 5. Creating an Appropriate Relationship Between the Participant and Researcher 51
p.000048: 5.1. Informed Consent
p.000052: 52
p.000052: 5.1.1. Information
p.000052: 52
p.000052: 5.1.2. Comprehension
p.000054: 54
p.000054: 5.1.3. Voluntary Participation
p.000055: 55
p.000055: 5.2. Payments to Research Participants
p.000056: 56
p.000056: 5.2.1. Types and Amounts of Payments Offered in Research Studies 56
p.000056: 5.2.2. Regulations and Guidance Regarding Payment to Research Participants 58
p.000056: 5.2.3. Payments When Children or Other Vulnerable Populations Are Involved 59
p.000056: 5.2.4. Payments in Observational Human Exposure Studies 61
p.000056: 5.3. Research Rights and Grievance Procedures
p.000061: 61
p.000061: 5.3.1. Ombudsman
p.000061: 61
p.000061: 5.3.2. Community Advisory Board
p.000062: 62
p.000062: 5.4. Creating a Supportive Environment for Research and Interaction 62
p.000062: 5.5. Recruitment Strategies
p.000062: 62
p.000062: 5.6. Retention Strategies
p.000063: 63
p.000063: 5.7. Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk 64
...
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
p.000003: range of risks associated with participation and the voluntary nature of participation, and provides
p.000003: essential protections to the participant. Recent observations by various national and international review
p.000003: committees on the appropriate level of payment to research participants are presented. This is a
p.000003: complex ethical issue, balancing the issue of fairness against the possibility of undue influence
p.000003: and the loss of free consent. Other topics include participant recruitment, retention strategies, research
p.000003: rights, and grievance procedures.
...
p.000008: D. These sections apply to all research either conducted or funded by EPA and are, therefore, directly applicable to
p.000008: NERL’s observational human exposure studies.4 Subpart B prohibits EPA from conducting or supporting research
p.000008: that involves intentional exposure of “a pregnant woman (and, thereby, her fetus), a nursing woman,
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
p.000008: from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in specified
p.000008: rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in this
p.000008: document.
p.000008: 5 The Glossary (Appendix F) lists definitions for a number of important terms; definitions that come from the
p.000008: regulatory language are identified with their specific CFR citation.
p.000008: about the most recent thinking and guidance on protection of human subjects.
p.000008: The Belmont Report (U.S. DHEW, 1979) is a foundational document in the development of the ethics of human
p.000008: subjects research in the United States. Because of the adverse publicity and political embarrassment arising
p.000008: from the unethical treatment of African- American men in the Tuskegee Syphilis Study, Congress passed
p.000008: the National Research Act of 1974, which called on the Department of Health, Education, and Welfare (DHEW) to
p.000008: codify its rules on human subjects research and established the National Commission for the Protection of
p.000008: Human Subjects of Biomedical and Behavioral Research. The commission was charged with identifying the
p.000008: basic ethical principles that should underlie human subjects research. The commission published the
...
p.000009: unaffiliated with the research
p.000009: Provision of information to subjects about the purpose of the research and its procedures, potential risks, benefits,
p.000009: and alternatives, so that the individual understands this information and can make a voluntary decision whether to
p.000009: enroll and continue to participate
p.000009: Respect for subjects by
p.000009: • permitting withdrawal from the research,
p.000009: • protecting privacy through confidentiality,
p.000009: • informing subjects of newly discovered risks or benefits,
p.000009: • informing subjects of results of the research, and
p.000009: • maintaining welfare of subjects.
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: Collectively, these documents have reaffirmed the basic ethical principles asserted in the Belmont Report
p.000010: and have attempted, in some cases, to expand scientific and ethical reasoning and understanding to define
p.000010: approaches for dealing with additional elements of human subjects research. These additional
p.000010: elements, which often have been identified because of specific incidents or case studies, include issues
p.000010: such as those described below.
p.000010: • Payment to participants⎯How much is adequate and fair, without being an undue inducement?
p.000010: • Non-study hazards⎯What is the researcher’s responsibility to identify hazards in the home that are
p.000010: not part of the study?
p.000010: • Third-party issues⎯Are there people other than the participant who may be impacted during the study and by the
p.000010: study results? If so, what needs to be done to protect their interests and to respect them as persons?
p.000010: • Community involvement⎯How should the community be involved in the design
p.000010: and implementation of studies?
p.000010: These documents, together with EPA’s regulatory requirements for the protection of human subjects, serve as
p.000010: important references for the subsequent sections of this document (see Table 1-4).
p.000010:
p.000010: 1.3 Purpose of This Document
p.000010: This document is meant to serve as a resource of current scientific and ethical information for
p.000010: NERL researchers as they develop and conduct observational human exposure studies. The increased
p.000010: scrutiny of research studies involving human participants makes it imperative that researchers ensure that
p.000010: their research protocols for protection of human subjects in observational human exposure studies
p.000010: incorporate the most up-to-date ethical approaches. Protocols for protecting study participants in
p.000010: research studies have been developed by experts in both academia and various Federal agencies and adopted
p.000010: by the research community because they ensure that observational research meets the highest
p.000010: ethical and scientific standards. However, because ethical and scientific approaches for human
...
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000012: 12
p.000012:
p.000012: address all of the relevant issues for their particular study to ensure that the specific elements of
p.000012: the study will safeguard and protect the human research subjects.
p.000012: In addition to being an information resource for NERL researchers, this document provides useful
p.000012: information for contractors and grantees funded by NERL to consider during the design and implementation of
p.000012: their exposure science research. Although not its intended audience, this document also may prove to be useful
p.000012: to other researchers, within and outside of EPA, who are involved in observational human exposure
p.000012: studies.
p.000012:
p.000012: 1.4 Process for Developing the Document
p.000012: This document was written by exposure science researchers in EPA’s NERL, with substantial input from experts
p.000012: within and outside of the Agency. Information relevant to the process and the document has been routinely
p.000012: posted on the EPA Web site at http://www.epa.gov/nerl/sots.
p.000012: NERL staff began this work by hosting a series of stakeholder meetings in the summer of 2006 to seek
...
p.000012: discussed in several sections. Appendixes include additional descriptions of NERL observational human
p.000012: exposure studies, details about the process for developing this document, a list of acronyms and abbreviations,
p.000012: a glossary, and other supplemental information. The main body of the document includes the following
p.000012: sections.
p.000012: • Introduction, Purpose, and Scope (Section 1) lays out the background for observational human exposure studies,
p.000012: the scope of the document, and some of the important scientific and ethical issues that are critical to human
p.000012: subjects and observational research.
p.000012:
p.000012:
p.000012:
p.000013: 13
p.000013:
p.000013: • Study Conceptualization and Planning (Section 2) establishes that ethical concerns are to be incorporated in
p.000013: the scientific effort from the very beginning and includes ethical issues such as justifying the study
p.000013: because of its social and scientific merit and ensuring scientific validity and independent review.
p.000013: • Protection of Vulnerable Groups (Section 3) discusses some of the special protections afforded to vulnerable groups
p.000013: by EPA’s human subjects rules and the ethical issues of involving such groups in observational research.
p.000013: • Ensuring Privacy and Confidentiality (Section 4) lays out the ethical issues and the regulatory requirements,
p.000013: including observations of nonstudy hazards and the recently discussed issues of third-party involvement or
p.000013: concerns.
p.000013: • The Relationship Between the Participant and the Researcher (Section 5) builds on the ethical principles of
p.000013: respect for persons and beneficence to discuss the issues around recruitment, informed consent,
p.000013: payment, and the researcher’s need to support the welfare of the participants.
p.000013: • Community and Stakeholder Relationships (Section 6) begins with the principles of fairness, justice, and
p.000013: equity and of respect for persons to develop approaches to demonstrate respect for culture
p.000013: and to empower the participants’ community to endure, including the need to build trust in the community and
p.000013: with stakeholders through open and honest communications and legitimate power sharing.
p.000013: • Strategies for Effective Communication (Section 7) builds on the presumption of an ongoing, interactive
p.000013: dialogue and exchange of ideas between researchers and the participants, community, and stakeholders and focuses
p.000013: on steps that the researcher needs to take for effective communications. The section discusses communication
p.000013: strategies, implementation plans, communication tools, reporting of results, and approaches for
p.000013: effective communications, two-way communications between the researchers, participants, community, and other
p.000013: stakeholders.
p.000013:
p.000013: References
p.000013: Beauchamp TL, Childress, JF (2001). Principles of Biomedical Ethics: Fifth Edition. New York, NY: Oxford University
p.000013: Press.
p.000013:
...
p.000031: – the monitoring and oversight team can ensure that participants are free to withdraw from the
p.000031: research at any time; are fully informed about the technical study results; understand any new
p.000031: information about relevant risks and benefits; and that the privacy and confidentiality of
p.000031: the subjects is properly protected. Through these efforts, the monitoring and oversight team will ensure that
p.000031: the welfare of the research subjects remains a focus of the study effort.
p.000031:
p.000031: Text Box 2-7. Examples of Issues That May Cause a Study To Be Stopped Early
p.000031: • Participant recruiting and enrollment⎯low response rates, disproportionate enrollment of select groups, problems
p.000031: associated with advertising, inadequate selection criteria
p.000031: • Informed consent⎯difficulties with the process and materials, poor comprehension
p.000031: • Participation⎯poor response to questionnaires, poor compliance with researcher requests in data collection
p.000031: activities
p.000031: • Burden⎯higher than predicted
p.000031: • Changes in participant behaviors⎯potential changes because of participation in the study
p.000031: • Grievances⎯participant issues
p.000031: • Retention⎯high dropout rates
p.000031: • Community issues⎯poor interactions, lack of support
p.000031: • Third-party issues⎯problems with landlords, spouses, or others
p.000031: • Collateral observations⎯identification of nonstudy hazards, difficulty reporting
p.000031: • Unanticipated results⎯high contaminant concentrations measured, unexpected results
p.000031: • New data indicating that participation in the study (or observations measured in the study) represent a risk to
p.000031: participants or others
p.000031:
p.000031:
p.000031:
p.000031: References
p.000031: Castelloe, JM (2000). Sample size computations and power analysis with the SAS system. Paper 265-25 in Proceedings of
p.000031: the 25th Annual SAS Users Group International Conference. Cary, NC: SAS Institute, Inc. Available:
p.000031: http://support.sas.com/rnd/app/papers/powersamplesize.pdf [accessed 16 April 2008].
p.000031:
p.000031: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of
p.000031: Human Subjects. U.S. Code of Federal Regulations. Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/
p.000031: 40cfr26_06.html [accessed 12 June 2007].
p.000031:
p.000031: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000031: Biomedical Research Involving Human Subjects.
p.000031: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000031:
p.000031: Coggon D, Rose G, Barker DJP (1997). Epidemiology for the Uninitiated, Fourth Edition. London: BMJ Publishing Group
...
p.000040: setting” (p. 64, NRC & IOM, 2005). The legal precept of freedom from unreasonable search and
p.000040: seizure and the historic and deeply rooted principle that “a man’s home is his castle” contribute to a belief in the
p.000040: “sanctity of the home” (see the discussion on pp. 62-66, NRC & IOM, 2005).
p.000040: The joint NRC and IOM report Ethical Considerations for Research on Housing-Related Health
p.000040: Hazards Involving Children discusses the ethical issues associated with entering a participant’s home to conduct
p.000040: research and explores the researchers’ responsibilities that derive from conducting research in people’s homes
p.000040: (NRC & IOM, 2005). These housing-related discussions are particularly relevant to observational human
p.000040: exposure studies, which often include environmental and
p.000040: biological measurements in people’s homes or personal locations. Many of the topics identified in that report are
p.000040: discussed in this section (Text Box 4-1).
p.000040:
p.000040:
p.000040: Text Box 4-1. Topics in Section 4
p.000040: Privacy Issues Confidentiality
p.000040: Confidentiality of Information Confidentiality of Participation
p.000040: Collateral Observations
p.000040: Potential Nonstudy Hazards in the Residence Collateral Observations with Mandated Reporting
p.000040: Requirements
p.000040: Hazard Communication Planning and Staff Training
p.000040: Third-Party Issues
p.000040: Determining Whether a Third Party is a Human Subject Informing Third Parties of Research Activities Research Results
p.000040: and Third Parties
p.000040: Data and Safety Monitoring and Oversight
p.000040:
p.000040:
p.000040:
p.000040: 4.1 Privacy Issues
p.000040: Privacy refers to an expectation that a person is free from intrusion into personal matters and is free from the
p.000040: presence or view of others. The Institutional Review Board Guidebook defines privacy as “control over the
p.000040: extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with
p.000040: others” (U.S. HHS, 1993). Beauchamp and Childress find that the right to privacy is based on the principle of
p.000040: respect for autonomy. “We often respect persons by respecting their autonomous wishes not to be observed, touched, or
p.000040: intruded upon…. A loss of privacy occurs if others use any of several forms of access, including intervening in zones
p.000040: of secrecy, anonymity, seclusion, or solitude” (pp. 295-296, Beauchamp and Childress, 2001).
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041: Although research participants may agree to allow researchers to enter their home or other zone of personal space
p.000041: to conduct their research measurements, they have not abrogated their right to privacy. “When individuals
p.000041: voluntarily grant others some form of access to themselves, their act is an exercise of the
p.000041: right to privacy, not a waiver of that right” (p. 297, Beauchamp and Childress, 2001). Researchers should remember
...
p.000045: should develop a plan for identifying potential situations, hazards, and dangers that may place the
p.000045: research team at risk of imminent harm. This should generally involve working with
p.000045: community representatives to identify the hazards and situations that may be of concern. For example, a
p.000045: researcher’s observation of illegal drugs in a study residence may place the researcher in potential
p.000045: danger. Similarly, if studies are conducted in areas with high crime rates, researchers need to be aware of
p.000045: the potential dangers and have a plan for addressing them. In some cases, situations may arise
p.000045: because of to inadvertent actions. For example, if an area has a high rate of daytime break- ins, the presence
p.000045: of researchers in the area may trigger calls to local authorities when the researchers, who are
p.000045: strangers, are observed in the neighborhood. Feedback from the community representatives should be solicited when
p.000045: developing a plan for responding to situations such as these. Comprehensive training should be developed for
p.000045: research field staff to assist them in identifying potentially dangerous situations and in responding to
p.000045: such situations.
p.000045:
p.000045: 4.4 Third-Party Issues
p.000045: Third-party issues can arise in observational human exposure studies in two ways. First, the study may collect
p.000045: limited information about or related to individuals other than the study participants. Second,
p.000045: study activities may affect or involve people or organizations other than the study participants.
p.000045: Examples of activities that may involve or affect third parties in observational human exposure studies
p.000045: could include, but are not limited to the following types.
p.000045: • Asking the participant about demographic, occupational, smoking, or product use information for
p.000045: other household members
p.000045: • Collecting residential environmental samples in multiperson households
p.000045:
p.000045:
p.000046: 46
p.000046:
p.000046: • Collecting environmental samples in common areas of multifamily housing units
p.000046: • Collecting personal or environmental samples in a day care, school, health care, or occupational setting
p.000046: • Measuring chemical occurrences or concentrations that may be of interest or import to other
p.000046: household members or to the community
p.000046: • Collecting activity or dietary information about a community
p.000046: It is important for researchers and research staff to understand whether and to what extent the research
p.000046: involves or affects third parties, and how third-party involvement might affect the study participants. Several
p.000046: examples of possible third-parties are listed in Text Box 4-5. Study planning; IRB review; and communication
p.000046: before, during, and after the study should take third- party issues into account.
p.000046:
p.000046: Text Box 4-5. Possible Third-Parties in Exposure Studies
p.000046: • Household members not enrolled in the study
p.000046: • Relatives
p.000046: • Care givers for children or elders
p.000046: • School staff
p.000046: • Employers
p.000046: • Other members of the community
p.000046: • Building managers or facility operators
p.000046: • Landlords
p.000046:
p.000046:
p.000046:
p.000046: 4.4.1 Determining Whether a Third Party Is a Human Subject
p.000046: It is up to the IRB to determine whether a third party is a human subject afforded human
p.000046: subject protections under the Common Rule. A third party would meet the Common Rule definition of
p.000046: a human subject [40 CFR 26.102(f)] if individually identifiable private information about them is collected
p.000046: (CFR, 2006). When this occurs, the informed consent of the third party must be obtained, or, if certain criteria are
p.000046: met, the IRB may determine that informed consent may be waived. It can be difficult to determine whether information
p.000046: about a third party is both individually identifiable and private. Discussions of this issue and
p.000046: recommendations for determining whether third-party information is identifiable and private have been
p.000046: submitted to the HHS Office of Human Research Protections by NIH (2001) and by the National Human
p.000046: Research Protections Advisory Committee (NHRPAC, 2002).
p.000046: Whether or not a third party is determined to be a human subject, the researcher should treat
p.000046: research
p.000046: information about a third party as confidential.
p.000046:
p.000046: 4.4.2 Informing Third Parties of Research Activities
p.000046: Obtaining permission from or informing third parties of certain types of activities may be needed in some
p.000046: observational human exposure studies. For example, household members living with a study participant need to
p.000046: be informed about home study visits and residential sample collection activities. Study activities that
p.000046: occur outside of the participant’s home or yard may require informing or gaining permission from third
p.000046: parties. A study may include collection of environmental samples (i.e., ambient air, dust, soil) from outdoor
p.000046: common areas of multifamily housing where the study participant lives. Issues regarding privacy, permission, and
p.000046: payments for third parties in housing-related studies have been discussed in the NRC & IOM (2005) report.
p.000046: Observational human exposure studies also may include cases when study participants are asked
p.000046: to collect personal samples (i.e., wearing a personal air monitor) over a time period that includes time
p.000046: they spend in a school, day care, or workplace. Such monitoring might require informing or
p.000046: gaining permission from an organization’s staff or an employer. In each case, the researcher and IRB have to
p.000046: consider whether obtaining permission from or informing a third party is appropriate and, if so, to define the
p.000046: procedures for doing so. The researcher and IRB have to also consider the potential impact of third-party
p.000046: knowledge of research activities on confidentiality and risk for the study participant and have to ensure that it is
p.000046: clearly and fully explained in the informed consent process.
p.000046:
p.000046: 4.4.3 Research Results and Third Parties
p.000046: Prior to initiating a research study, researchers should consider whether research results may
p.000046: be provided to third parties. In some studies, there may be reasons to inform household members living with a
p.000046: study participant about specific residential measurement results. In community research studies, aggregated or
p.000046: summary research results may provide a benefit to the community. In this case, it would be beneficial to seek
p.000046: out the advice of community representatives regarding results reporting prior to the study. Researchers
p.000046: also should determine whether there are State or local reporting requirements for some types of
p.000046: measurement results above specified action levels (i.e., blood-lead levels, heavy metal concentration in soil).
p.000046: It is important that the researcher and IRB ensure that confidentiality and privacy of study
p.000046: participants are carefully
p.000046:
p.000046:
p.000047: 47
p.000047:
p.000047: considered in any case where reporting study results to third parties is contemplated or may be required. Ideally,
p.000047: the informed consent process would make clear whether, under what conditions, and how research results might be
p.000047: provided to third parties.
p.000047:
p.000047: 4.5 Data and Safety Monitoring and Oversight
...
p.000048: Emanuel, EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000048:
p.000048: NCI (National Cancer Institute) (2001). Essential Elements of a Data and Safety Monitoring Plan for Clinical Trials
p.000048: Funded by the National Cancer Institute. Available: http://www3.cancer.gov/rrp/dsm_ess.html [accessed April 2007].
p.000048:
p.000048: NEI (National Eye Institute) (2001). National Eye Institute Guidelines for Data Monitoring and Oversight of
p.000048: Observational Studies. Available: http://www.nei.nih.gov/funding/datastudies.asp [accessed April 2007].
p.000048:
p.000048: NHLBI (National Heart Lung and Blood Institute) (2007). Monitoring Boards for Data and Safety (Interim Policy). Policy
p.000048: effective date: 14 May 2007. Available: http://public.nhlbi.nih.gov/ocr/home/GetPolicy.aspx?id=8 [accessed September
p.000048: 2007].
p.000048:
p.000048: NHRPAC (National Human Research Protections Advisory Committee) (2002). Clarification of the status of third parties
p.000048: when referenced by human subjects in research. Available: http://www.hhs.gov/ohrp/nhrpac/documents/third.pdf [accessed
p.000048: April 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (2002). Extramural Projects - Application Instructions (03/15/2002) - Detailed
p.000048: Application Instructions for Certificate of Confidentiality Involving Extramural Research Projects. Certificates of
p.000048: Confidentiality. Available: http://grants.nih.gov/grants/policy/coc/index.htm. [accessed April 2007]
p.000048:
p.000048: NIH (National Institutes of Health) (2001). Protection of third party information in research: Recommendations of the
p.000048: National Institutes of Health to the Office for Human Research Protections. Available:
p.000048: http://bioethics.od.nih.gov/nih_third_party_rec.html [accessed March 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (1998). NIH Guide: NIH Policy for Data and Safety Monitoring. Available:
p.000048: http://grants.nih.gov/grants/guide/notice-files/not98 084.html [accessed April 2007].
p.000048:
p.000048: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000048: Housing-Related Health Hazards Involving Children.
p.000048: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed
p.000048: June 2007].
p.000048:
p.000048:
p.000048:
p.000048:
p.000049: 49
p.000049:
p.000049: U.S. FDA (U.S. Food and Drug Administration) (2001). Draft Guidance for Clinical Trial Sponsors on the Establishment of
p.000049: Clinical Trial Data Monitoring Committees. U.S. Department of Health and Human Services, Food and Drug Administration,
p.000049: Rockville, MD. Available: http://www.fda.gov/cber/gdlns/clindatmon.pdf. [accessed April 2007].
p.000049: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000049: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000049: [accessed June 2007].
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
...
p.000057: regulations do discuss providing additional safeguards for subjects vulnerable to coercion or undue
p.000057: influence [40 CFR 26.111(b)]. The NIH IRB guidebook advises IRBs to determine whether the rewards offered for
p.000057: participation in research constitute undue influence (U.S. HHS, 1993). According to the IRB guidebook undue
p.000057: inducement might blind prospective subjects to risks, impair their ability to exercise proper judgment, or may
p.000057: cause people to lie or to withhold information that would make them ineligible to enroll or continue
p.000057: participation.
p.000057: The U.S. Food and Drug Administration (FDA) has provided guidance for investigators and IRBs for clinical research
p.000057: studies (FDA, 1998). The guidance states that “payment to research subjects for participation in studies is not
p.000057: considered a benefit, it is a recruitment incentive.” FDA expects payments to accrue as the study progresses and not
p.000057: to be contingent on completing the study, although a “small proportion as an incentive for
p.000057: completion of the study is acceptable.” The guidance is concerned with the issue of coercion or undue influence, and
p.000057: it recognizes the IRB as the responsible party for deciding what is or is not acceptable.
p.000057: The U.S. Office of Management and Budget (OMB) develops standards and guidelines for statistical surveys performed by
p.000057: the Federal government. Under Guideline 2.3.2, OMB states that, while incentives are not typically used in Federal
p.000057: surveys, agencies may consider use of respondent incentives if they believe incentives would be necessary
p.000057: to use for a particular survey to achieve data of sufficient quality for their intended use (OMB,
p.000057: 2006a). OMB requires that agencies provide a justification for giving incentives to respondents.
p.000057: Some
p.000057: of the factors cited by OMB to be addressed include those particularly relevant to observational
p.000057: human exposure studies, including unusual reporting burdens (keeping data logs for extended periods,
p.000057: coordinating study team visits, participating in a medical examination, etc.), complex study designs (such as
p.000057: studies requiring ongoing participation of respondents), and past experience, especially when there is
p.000057: evidence of attrition or poor response rates (OMB, 2006b). Although OMB primarily considers incentives with
p.000057: regard to survey response rates and data quality, researchers need to consider payments to
p.000057: participants, including participation incentives, in the broader context discussed in this section.
p.000057: CIOMS also provides guidance and commentary on this issue in the International Ethical Guidelines for Biomedical
p.000057: Research Involving Human Subjects (2002). Guideline 7 and the associated commentary emphasize that payments to
...
p.000072: boundaries of privacy (crucial when designing sampling strategies) of different groups (Israel et al., 2005b, Chapter
p.000072: 11).
p.000072: Vega (1992) provides a thorough discussion of the theoretical and pragmatic implications of
p.000072: cultural diversity for community research and explains that researchers should interact with
p.000072: communities using methods that promote understanding and demonstrate sensitivity and competence in
p.000072: working with diverse
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073: cultures (e.g., with respect to class, gender, ethnicity, race, age, and sexual orientation). To aid in this
p.000073: process, researchers should include sufficient time in their project timeline to interact and dialogue with the
p.000073: community before the study begins to understand the cultural issues that may affect the research. Researchers and the
p.000073: results of their work are expected to promote a strengthening of the community; however, it should be recognized
p.000073: that, given the heterogeneity and the diverse views within a community, the study findings potentially may
p.000073: conflict with the desires of the community or may promote feelings of anger or distrust among members
p.000073: of the community with each other. Enlisting the services of a third-party evaluator/mediator may be
p.000073: useful for sustaining positive relations between all research participants and the community at
p.000073: large.
p.000073: The Research Triangle Park Particulate Matter Panel Study (Williams et al., 2003), a NERL investigation of PM
p.000073: and related pollutants involving African-Americans in North Carolina, demonstrated an effective strategy for using
p.000073: communication to address cultural differences between the community and research personnel. Before beginning
p.000073: the research, the study design included time and a budget for building collaborations with
p.000073: organizations having close ties with the African- American community to establish trust between
p.000073: the community and research team. Using input from the community partner organizations, the
p.000073: researchers developed a systematic communication plan to establish rapport with the community and to guide
p.000073: interaction between study participants and the key study personnel. A well-designed and culturally sensitive
p.000073: communication plan was integral to the success of the study. Eighty percent of the original participants
p.000073: completed the four- season study (Williams et al., 2003).
p.000073:
p.000073: 6.2.6 Honesty, Power Relationships, and Partnerships
p.000073: The NRC & IOM report (NRC & IOM, 2005) describes a relational paradigm that acknowledges that research
p.000073: is part of a broader societal context, with the conduct of research often mirroring a system in which
...
p.000081: communications will be developed with each group, and the timing of the communications. It is likely
p.000081: that most studies will involve the individuals, community groups and stakeholders shown in Text
p.000081: Box 7-3.
p.000081:
p.000082: 82
p.000082:
p.000082:
p.000082: Text Box 7-3. Individuals and Groups Involved in Communications
p.000082: • Principal investigator—the researcher with ultimate responsibility for the study
p.000082: • Research team
p.000082: • Study participants
p.000082: • Third parties associated with study participants (e.g., spouse, children, landlords)
p.000082: • Community representatives
p.000082: • Community members
p.000082: • Governments (local, State, and Federal)
p.000082: • Study institution management
p.000082: • Study sponsors or funding organization
p.000082: • Organizations with interest in the participants, the community, or the research question
p.000082: • Stakeholders that may be impacted by the results of the study
p.000082: • The scientific community
p.000082: • Media
p.000082: • The general public
p.000082:
p.000082: The study participants are a key group involved in communications during a study and are easily identified.
p.000082: Similarly, it is generally not difficult to identify the third parties associated with the study participants,
p.000082: because these groups must be identified when considering ethical issues in the study and when developing the
p.000082: human subjects research protocol. Research teams should ensure that the communication strategy includes the
p.000082: strategy and approach for third-party communications.
p.000082: As discussed in Section 6, it is critical that community representatives are identified early in
p.000082: the scoping and planning phase of the study. It is important that researchers are informed about the community
p.000082: in which they will conduct the study and understand the unique characteristics and culture of the community and
p.000082: the potential study participants to develop effective bidirectional communications. When
p.000082: possible, researchers should identify other research organizations who have worked in the community and attempt
p.000082: to gather information from them on the nature of the community, who represents the community, and what
p.000082: communication strategies have been used previously in the community. Understanding how the community
p.000082: defines itself or thinks of itself is critical to establishing effective communications.
p.000082: Identification of all relevant stakeholder groups may be more difficult. As defined in Section 6, the term
p.000082: stakeholder is used here to identify a person or group who has a valid interest in an activity or
p.000082: decision, but who does not speak directly for the community or the participants. There may be many
p.000082: organizations who consider themselves as stakeholders that represent the
p.000082: interests of the community, the participants, or the research problem. For example, there are many
p.000082: nonprofit organizations that advocate for the protection of children’s health. When conducting an
...
p.000097: would not meet the authors’ intentions regarding “observational human exposure studies” as they are defined
p.000097: in this document. An intervention study, such as described in these two examples, does not involve
p.000097: observing people’s exposures in their everyday environments, as they go about their normal activities. In
p.000097: an intervention study, either the participant’s environment (cleaning of the household surfaces) or their
p.000097: behavior (wearing a particle mask) has been manipulated by the researcher. Secondly, the objective of these
p.000097: studies is not to understand exposures in everyday environments but would use changes in exposure
p.000097: to test the effectiveness of an intervention strategy. Such a study is not addressed in this document.
p.000097: Observational human exposure studies, as used by the authors of this document, generally meet the
p.000097: regulatory definition of observational research. But, not all studies meeting the CFR definition of
p.000097: observational research would be considered by the authors to be observational human exposure studies.
p.000097:
p.000097: Examples of NERL Observational Human Exposure Studies
p.000097: NERL and its predecessor organizations have
p.000097: conducted observational human exposure studies since 1980. Table A-1 lists many of those that NERL has
p.000097: conducted, supported, or participated in since 1980. The table gives the name of the study, dates, sample
p.000097: size, then type of study, a brief explanation of the research, and NERL’s role therein. The table represents a
p.000097: variety of first-party or second-party research efforts. In many cases, NERL staff would design,
p.000097: oversee, and, if possible, participate directly in the study (first-party), but often contractor
p.000097: support would be needed to accomplish the field sampling or some of the sample analysis. In other
p.000097: cases, NERL researchers would solicit proposals for exposure research to be conducted to address specific
p.000097: exposure issues and then would fund researchers in academia or at nonprofit institutions to design and
p.000097: conduct the research (second-party research). In a few cases, grants might already be in place with research
p.000097: institutions, and NERL simply would augment the pre-existing funding to expand the exposure component
p.000097: (second-party). Some other cases involve research efforts initiated by other Federal agencies with which NERL
p.000097: would collaborate and participate in directly (first-party).
p.000097: An examination of the entries in the table shows that most of the agents being studied were chemicals, often
p.000097: air pollutants or pesticides. A few of the entries indicate that other agents, for example, molds and fungi or other
p.000097: microbes, were the subject of the study. The largest number of the studies involved small numbers
p.000097: of participants and often were designed to determine whether or not a method for collecting
p.000097: exposure-related data or samples was feasible or burdensome. Most of the smaller studies used convenience samples.
p.000097: Studies, like DEARS, CTEPP, NHEXAS, and TEAM, which
p.000097: involved large numbers of participants, employed randomized or probability-based approaches
p.000097: for selecting participants.
p.000097: Table A-2 shows the types of samples that often have been collected in NERL’s observational human
p.000097: exposure studies. Some of the samples, like air concentrations or surface wipes, allow NERL staff
p.000097: to determine the concentration of the studied chemicals in the environmental media with which the participants
p.000097: may come into contact. Other items, like time activity diaries or videotaping children to measure the amount of
p.000097: hand-to-mouth activity, allow NERL researchers to understand how people may come into contact with the agent
p.000097: and to estimate the duration or frequency of a potential exposure. Still other measures, like personal
p.000097: samplers or biological samples, represent an attempt to determine a time-integrated measure of exposure. NERL
p.000097:
p.000097:
p.000098: 98
p.000098:
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p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
p.000008: from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in specified
p.000008: rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in this
p.000008: document.
p.000008: 5 The Glossary (Appendix F) lists definitions for a number of important terms; definitions that come from the
p.000008: regulatory language are identified with their specific CFR citation.
p.000008: about the most recent thinking and guidance on protection of human subjects.
p.000008: The Belmont Report (U.S. DHEW, 1979) is a foundational document in the development of the ethics of human
p.000008: subjects research in the United States. Because of the adverse publicity and political embarrassment arising
p.000008: from the unethical treatment of African- American men in the Tuskegee Syphilis Study, Congress passed
p.000008: the National Research Act of 1974, which called on the Department of Health, Education, and Welfare (DHEW) to
p.000008: codify its rules on human subjects research and established the National Commission for the Protection of
p.000008: Human Subjects of Biomedical and Behavioral Research. The commission was charged with identifying the
p.000008: basic ethical principles that should underlie human subjects research. The commission published the
p.000008: Belmont Report in 1979. This report established three basic principles: (1) respect for
p.000008: persons; (2) beneficence; and (3) justice, which have become the cornerstones for regulations involving
p.000008: human subjects (see Table 1-2).
p.000008: In 1981, the Department of Health and Human Services (HHS) issued regulations based on the Belmont Report. Ten
p.000008: years later, the core HHS regulations (Subpart A) were adopted by almost all of the Federal
p.000008: departments and agencies that conducted or sponsored human subjects research as the “Common Rule.”
p.000008: Since 1991, ethical thought and regulatory processes for the protection of human subjects have continued to
...
p.000067: consultation and review, membership on community advisory boards, and involvement in a community-based
p.000067: participatory research process” if that is used (p. 83, NRC & IOM, 2005). In addition, IRBs may
p.000067: seek additional community representation on the IRB panel.
p.000067: The Centers for Disease Control and Prevention (CDC) recommends nine governing principles for
p.000067: “outsiders.” To help alleviate these potential issues, researchers should ensure an equitable
p.000067: distribution of paid research work among different communities within the larger community as to not promote a
p.000067: perceived bias among community members. Additionally, when possible, researchers should make efforts
p.000067: to provide payments to community members employed as research staff through community partner
p.000067: organizations to prevent conflict of interest issues. Refer to Section 5 for further discussion on
p.000067: remuneration of community members as research participants.
p.000067:
p.000067:
p.000067: Text Box 6-2. Community Engagement Principles for Researchers
p.000067: (From CDC, 1997)
p.000067: Requirement Explanation
p.000067:
p.000067: Clarity Clear communication of the study objectives, research goals, and the populations or
p.000067: communities of interest.
p.000067:
p.000067: engaging communities in health-related research (see Text Box 6-2). Health research is a “privileged and
p.000067: empowered activity in that the researchers have special
p.000067: Knowledge of the Community
p.000067: Familiarity with the economic conditions, political structures, demographics, history, past research experiences, and
p.000067: research perceptions of the community.
p.000067:
p.000067: access to resources and sensitive information about people and, through the analysis and presentation
p.000067: of findings, are able to influence the way people think and have considerable influence on decisions regarding
p.000067: the allocation of resources” (CDC, 1997). Regardless of the approach utilized to involve the community in research,
p.000067: whether the process employs community-based participatory research (CBPR) or another community
p.000067: engagement method, researchers should guide their interactions with community members using these
p.000067: underlying principles to promote the aforementioned ethical principles of respect of persons, fairness, and
p.000067: beneficence.
p.000067: One form of community involvement is to include qualified members of the community on the research staff.
p.000067: Section 2 advocates community representatives as part of the research team. Paid research staff members from
p.000067: the community could serve as valuable consultants for protocol development and research design, including how to
p.000067: collect the data, how to recruit and retain participants, and how to interpret and disseminate the
p.000067: results. However, including paid research staff from the community may introduce a conflict of interest among
...
p.000070: and the community members overlap in particular individuals, it is important to distinguish the role in
p.000070: which the individual is acting (ERG, 2007).
p.000070:
p.000070: 6.2.2 Identifying Who Represents the Community
p.000070: To sufficiently represent the community, an individual has to have not only the right to speak for the
p.000070: community’s interests (a right afforded by legitimate membership in the group) but also should be able
p.000070: to describe those interests on behalf of the community. Identifying those who represent the community is
p.000070: not simply a matter of identifying the most vocal activists because those individuals do not necessarily
p.000070: represent the interests of the entire community. In fact, several individuals may be necessary to adequately
p.000070: represent the diversity of viewpoints within a community; in such cases, a CAB may be appropriate (ERG, 2007).
p.000070: One of the researcher’s first steps should be asking the potential participants from the community who they see
p.000070: as a
p.000070:
p.000070:
p.000071: 71
p.000071:
p.000071: legitimate representative (i.e., someone who can speak for them). Corburn cites an example of a locale
p.000071: in Brooklyn, NY, that contained individuals with widely different backgrounds. It was impossible to
p.000071: identify appropriate spokespeople, or even to define the nature of the community, without talking with
p.000071: community members (Corburn, 2007).
p.000071: The NRC & IOM (2005) Report also discusses the issue of who can represent the identified community. Some
p.000071: communities may have a formal governmental structure and a recognized political authority (e.g.,
p.000071: Native American tribes). Other communities may have clearly identifiable leaders (e.g., religious communities),
p.000071: whereas still other communities have no formal leadership structure at all. Whether there is a
p.000071: legitimate political authority or some other hierarchal leadership structure, the goal is to seek community input
p.000071: as to who best represents the interests of the community with regard to the proposed research project,
p.000071: rather than selecting those who are favorable to the research project. The NRC & IOM report cautions against
p.000071: the ethically questionable practice of seeking out population spokespeople and research participants
p.000071: whose positive response to a research plan can be predicted in advance and refers the reader to an article on this
p.000071: topic by Juengst (2000).
p.000071: With multiple sources of leadership and authority in many communities, careful consideration should be given
p.000071: to what aspect of the community a particular person will represent, and what efforts may be needed to ensure
p.000071: that the entire range of views in a community are obtained. Researchers should consider reaching out to multiple
p.000071: organizations such as churches, social service agencies, community-based organizations, and tenant and
p.000071: other community advocacy groups.
p.000071:
p.000071: 6.2.3 Building Relationships and Trust
p.000071: A key first step in developing trust is to establish a relationship with the community before the study. Trust must be
p.000071: built; it cannot be assumed. This relationship involves not only listening to community input but
p.000071: actually taking it into consideration (ERG, 2007). A long history of research with no direct benefits and
p.000071: no feedback of results to the community, however, has contributed to a general mistrust of
...
Political / vulnerable
Searching for indicator vulnerable:
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p.000001: As EPA employees, NERL scientists face both regulatory and moral obligations to ensure the protection of the
p.000001: human subjects participating in observational research. The regulatory requirements are set forth in
p.000001: EPA’s human subjects regulations (40 CFR 26). NERL scientists are resolved to meet both the “letter” of the law as set
p.000001: forth in the regulations and also the “spirit” that derives from the most up-to-date thinking and consensus on
p.000001: these sensitive issues. This document provides information on regulatory requirements and the state of
p.000001: the science for a number of issues associated with observational human exposure studies to help NERL scientists meet
p.000001: their goal of conducting these studies based on the most up-to-date and sound science and the highest ethical
p.000001: standards.
p.000001: To gather information for the scientific and ethical approaches for observational human exposure studies,
p.000001: NERL convened an expert panel workshop on November 28 and 29, 2006, to discuss the state of the science. The 11-member
p.000001: panel discussed their ideas for the content of this document and the state of the science for various elements
p.000001: of observational human exposure studies. The panel agreed that the document planned by EPA should
p.000001: include the following six major topic areas:
p.000001: (1) identifying elements to be considered in study conceptualization,
p.000001: (2) ensuring protection of vulnerable groups,
p.000001: (3) addressing privacy and other concerns related to observational human exposure studies,
p.000001: (4) creating an appropriate relationship between the participant and investigator,
p.000001:
p.000001:
p.000001: iv
p.000001:
p.000001: (5) building and maintaining appropriate community and stakeholder relationships, and
p.000001: (6) designing and implementing strategies for effective communication.
p.000001: The structure and content of the current document follow the recommendations of the Expert Panel. These
p.000001: recommendations include pragmatic steps that NERL scientists can undertake during the development and
p.000001: implementation of observational human exposure studies.
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
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p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: v
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Acknowledgments
p.000001:
p.000001:
p.000001: This document was developed through the joint efforts of many U.S. Environmental Protection Agency (EPA)
p.000001: staff. Roy Fortmann, Larry Cupitt, Kent W. Thomas, and Peter Egeghy, researchers in the National Exposure
p.000001: Research Laboratory, were primary authors of the document. Linda Sheldon provided input to the
p.000001: development of the document and contributed through discussions with the authors on issues associated with
...
p.000019: 2.2. Ensuring Scientific Validity of the Research Study 20
p.000019: 2.2.1. Study Design
p.000020: 20
p.000020: 2.2.2. Feasibility
p.000021: 21
p.000021: 2.2.3. Sample Size Determination
p.000022: 22
p.000022: 2.2.4. Representativeness of the Sample
p.000022: 22
p.000022: 2.2.5. Information Collection Rule
p.000023: 23
p.000023: 2.2.6. Quality Assurance Project Plan
p.000024: 24
p.000024: 2.2.7. The Study Design Document
p.000024: 24
p.000024: 2.3. Ethical Issues in Ensuring Fair Subject Selection
p.000024: 24
p.000024: 2.4. Ensuring a Favorable Risk-Benefit Ratio
p.000025: 25
p.000025: 2.4.1. Designing in Benefits for the Participants
p.000025: 25
p.000025: 2.4.2. Assessing Benefits and Risks of Study Participation 25
p.000025: 2.5. Independent Scientific and Ethical Review
p.000026: 26
p.000026: 2.5.1. Scientific Peer Review
p.000027: 27
p.000027: 2.5.2. Conflicts of Interest
p.000027: 27
p.000027: 2.5.3. Develop the Human Subjects Protocol for Institutional Review Board Review 28
p.000027: 2.5.4. Ethical Review
p.000029: 29
p.000029: 2.5.5. Internal U.S. EPA Review of Scientific and Ethical Issues 29
p.000029: 2.6. Informed Consent
p.000029: 29
p.000029: 2.7. Ensuring That Participant Behaviors Are Not Changed Adversely Because of
p.000029: Being in the Study
p.000030: 30
p.000030: 2.8. Criteria and Standards for Monitoring Scientific and Ethical Issues 30
p.000030: 3. Ensuring Protection of Vulnerable Groups
p.000035: 35
p.000035: 3.1. Identification of Vulnerable Groups
p.000035: 35
p.000035: vii
p.000035:
p.000035: 3.2. Justification for Involving Vulnerable Persons in Observational Research 36
p.000035: 3.3. Minimal Risk and Vulnerable Groups
p.000037: 37
p.000037: 3.4. Research Involving Children
p.000037: 37
p.000037: 3.5. Women as Research Subjects
p.000038: 38
p.000038: 3.6. Other Potentially Vulnerable Groups
p.000039: 39
p.000039: 4. Privacy, Confidentiality, and Other Concerns Related to Observational
p.000039: Human Exposure Studies
p.000041: 41
p.000041: 4.1. Privacy Issues
p.000041: 41
p.000041: 4.2. Confidentiality
p.000042: 42
p.000042: 4.2.1. Confidentiality of Information
p.000043: 43
p.000043: 4.2.2. Confidentiality of Participation
p.000044: 44
p.000044: 4.3. Collateral Observations
p.000044: 44
p.000044: 4.3.1. Potential Nonstudy Hazards in the Residence 44
p.000044: 4.3.2. Collateral Observations with Mandated Reporting Requirements 45
p.000044: 4.3.3. Hazard Communication
p.000045: 45
p.000045: 4.3.4. Planning and Staff Training
p.000046: 46
p.000046: 4.4. Third-Party Issues
p.000046: 46
p.000046: 4.4.1. Determining Whether a Third Party Is a Human Subject 47
p.000046: 4.4.2. Informing Third Parties of Research Activities 47
p.000046: 4.4.3. Research Results and Third Parties
p.000047: 47
p.000047: 4.5. Data and Safety Monitoring and Oversight
p.000048: 48
p.000048: 5. Creating an Appropriate Relationship Between the Participant and Researcher 51
p.000048: 5.1. Informed Consent
p.000052: 52
p.000052: 5.1.1. Information
p.000052: 52
p.000052: 5.1.2. Comprehension
p.000054: 54
p.000054: 5.1.3. Voluntary Participation
p.000055: 55
p.000055: 5.2. Payments to Research Participants
p.000056: 56
p.000056: 5.2.1. Types and Amounts of Payments Offered in Research Studies 56
p.000056: 5.2.2. Regulations and Guidance Regarding Payment to Research Participants 58
p.000056: 5.2.3. Payments When Children or Other Vulnerable Populations Are Involved 59
p.000056: 5.2.4. Payments in Observational Human Exposure Studies 61
p.000056: 5.3. Research Rights and Grievance Procedures
p.000061: 61
p.000061: 5.3.1. Ombudsman
p.000061: 61
p.000061: 5.3.2. Community Advisory Board
p.000062: 62
p.000062: 5.4. Creating a Supportive Environment for Research and Interaction 62
p.000062: 5.5. Recruitment Strategies
p.000062: 62
p.000062: 5.6. Retention Strategies
p.000063: 63
p.000063: 5.7. Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk 64
p.000063: 6. Building and Maintaining Appropriate Community and Stakeholder Relationships 67
p.000063: 6.1. Approaches to Community Involvement
p.000068: 68
p.000068: 6.2. Issues in Community Involvement
p.000071: 71
p.000071: 6.2.1. Defining “Community”
p.000071: 71
p.000071: 6.2.2. Identifying Who Represents the Community 71
p.000071: 6.2.3. Building Relationships and Trust
p.000072: 72
p.000072: 6.2.4. Importance of Language and Communications with the Community 73
p.000072: 6.2.5. Recognizing and Addressing Cultural Differences 73
p.000072: 6.2.6. Honesty, Power Relationships, and Partnerships 74
p.000072: 6.2.7. Building a Lasting Infrastructure
p.000074: 74
p.000074: 6.3. Community Involvement in Observational Human Exposure Studies 75
...
p.000117: the protection of the human subjects participating in their observational research. The
p.000117: regulatory requirements are set forth in EPA’s human subjects regulations (40 CFR 26). The moral
p.000117: obligations derive from the ethical principles of biomedical ethics. NERL scientists and managers are
p.000117: resolved to meet both the “letter” of the law as set forth in the regulations and also the “spirit” that
p.000117: derives from the most up-to-date thinking and consensus on these sensitive issues.
p.000117: This document provides information on regulatory requirements and ethical issues to consider when
p.000117: performing human subjects research. Knowledge about these requirements and issues will help NERL scientists meet
p.000117: their goal of conducting observational human exposure studies based on the most up-to-date and sound science
p.000117: and the highest ethical scientific standards.
p.000117: The ethical and moral issues associated with human subjects research has long been the subject of a great deal
p.000117: of thought and discussion, both in the United States and abroad. Issues in biomedical ethics continue to be
p.000117: discussed and debated in today’s headlines. Spurred by the atrocities of World War II concentration camps and by
p.000117: the disclosure of unethical treatment of undereducated African-American men and
p.000117: other vulnerable groups by medical staff in the United States, the U.S. and world communities were prompted
p.000117: to establish ethical principles for medical and scientific experiments that involve people as
p.000117: participants. In the United States, the Belmont Report (U.S. DHEW, 1979) is the foundational document in the
p.000117: development of the
p.000117:
p.000117:
p.000001: 1
p.000001:
p.000001: ethics of human subjects research. This report lays out the fundamental ethical principles behind research
p.000001: that involves humans as research subjects. These three basic principles, (1) respect for persons, (2) beneficence,
p.000001: and
p.000001: (3) justice, have become the cornerstones for regulations involving human subjects. Ethicists have expanded on
p.000001: those principles since 1979, translating them into ethical requirements that any human subjects research must be both
p.000001: ethically acceptable and scientifically sound.1 EPA’s Science Advisory Board has affirmed, “Bad
p.000001: science is always unethical” (U.S. EPA, 2000).
p.000001: In an effort to ensure that NERL’s observational human exposure studies are founded on the ethical
p.000001: principles of respect for persons, beneficence and nonmaleficence, and justice and adhering to the
p.000001: principle that bad science is always unethical, scientists and managers from NERL have assembled this
p.000001: document as a resource and reference for NERL exposure scientists. These same scientists and managers have sought
...
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
...
p.000009: additional emphasis on the welfare of the subjects.
p.000009: More recently, there has been increased scrutiny and discussions of the ethics of research involving human
p.000009: participants,6 and a number of respected institutions have
p.000009:
p.000009:
p.000009: 6 The term “human participants” often is used in this document. It denotes the importance of the study participant
p.000009: being actively engaged in a partnership with the researchers to address the objectives and goals of the study. The term
p.000009: should be considered to be synonymous with the term “human subject” as used in the Common Rule and in documents used to
p.000009: describe regulatory requirements for studies involving human subjects.
p.000009: Social or scientific value
p.000009:
p.000009: Scientific validity
p.000009:
p.000009:
p.000009: Fair subject selection
p.000009:
p.000009:
p.000009: Favorable risk- benefit ratio
p.000009:
p.000009:
p.000009: Independent review
p.000009:
p.000009:
p.000009:
p.000009: Informed consent
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Respect for potential and enrolled subjects
p.000009: that will improve health and well-being or increase knowledge
p.000009: Use of accepted scientific principles and methods, including statistical techniques, to produce reliable and valid data
p.000009: Selection of subjects so that stigmatized and vulnerable individuals are not targeted for risky research, and the rich
p.000009: and socially powerful are not favored for potentially beneficial research
p.000009: Minimization of risks; enhancement of potential benefits and risks to the subject are proportionate to the benefits to
p.000009: the subject and to society
p.000009: Review of the design of the research trial, its proposed subject population, and risk-benefit ratio by individuals
p.000009: unaffiliated with the research
p.000009: Provision of information to subjects about the purpose of the research and its procedures, potential risks, benefits,
p.000009: and alternatives, so that the individual understands this information and can make a voluntary decision whether to
p.000009: enroll and continue to participate
p.000009: Respect for subjects by
p.000009: • permitting withdrawal from the research,
p.000009: • protecting privacy through confidentiality,
p.000009: • informing subjects of newly discovered risks or benefits,
p.000009: • informing subjects of results of the research, and
p.000009: • maintaining welfare of subjects.
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: Collectively, these documents have reaffirmed the basic ethical principles asserted in the Belmont Report
p.000010: and have attempted, in some cases, to expand scientific and ethical reasoning and understanding to define
p.000010: approaches for dealing with additional elements of human subjects research. These additional
p.000010: elements, which often have been identified because of specific incidents or case studies, include issues
p.000010: such as those described below.
...
p.000012: This document was written by exposure science researchers in EPA’s NERL, with substantial input from experts
p.000012: within and outside of the Agency. Information relevant to the process and the document has been routinely
p.000012: posted on the EPA Web site at http://www.epa.gov/nerl/sots.
p.000012: NERL staff began this work by hosting a series of stakeholder meetings in the summer of 2006 to seek
p.000012: input on the content and format of the document. In November 2006, NERL convened an expert panel to
p.000012: provide its advice and guidance about the scope and content of this document. The Expert Panel consisted of
p.000012: 11 nationally recognized authorities in diverse fields: exposure science, environmental health,
p.000012: bioethics, epidemiology law, community-based research, research in minority communities, public health,
p.000012: toxicology, pediatrics, children’s environmental health, etc. Details about the Expert Panel and the workshop can
p.000012: be found in Appendix B. The summary report from the Expert Panel may be accessed
p.000012: online at http://www.epa.gov/nerl/sots/workshop-report.pdf.
p.000012: The structure and content of the current report follow the recommendations of the Expert
p.000012: Panel. Specifically, the Expert Panel recommended that this document should include the following six major
p.000012: topic areas:
p.000012: (1) elements to be considered in study conceptualization,
p.000012: (2) ensuring protection of vulnerable groups,
p.000012: (3) addressing privacy and other concerns related to observational human exposure studies,
p.000012: (4) creating an appropriate relationship between the participant and investigator,
p.000012: (5) building and maintaining appropriate community and stakeholder relationships, and
p.000012: (6) designing and implementing strategies for effective communication.
p.000012: These recommendations include pragmatic steps that NERL scientists can undertake during the development and
p.000012: implementation of observational human exposure studies. Note that each step may require consideration and
p.000012: application of multiple ethical and scientific principles, and the same ethical principle may
p.000012: be fundamental to several of the topic areas. As a result, the same ethical principle may be discussed in
p.000012: several sections throughout this document.
p.000012: Using the advice of the Expert Panel, an internal review draft of the document was written. Based on the
p.000012: comments from internal EPA reviewers, the internal review draft was revised, and an external review draft
p.000012: was prepared. The external review draft was submitted for peer review by EPA’s Human Subjects Review
p.000012: Board (HSRB), a Federal advisory committee consisting of a panel of experts chartered to review and advise the Agency
p.000012: on the scientific and ethical underpinnings of human subjects research efforts. The external review draft
p.000012: also was announced in the Federal Register and made available for public review and comment. The document
p.000012: subsequently was revised in response to comments from the HSRB and from the public in
...
p.000012: The document is organized along the lines that the Expert Panel recommended. It has seven sections, an
p.000012: introduction followed by a section addressing each of the major topic areas. The content of each section also
p.000012: is based on recommendations from the Expert Panel Workshop. Because the authors concluded that
p.000012: the discussion for each topic area needed to be complete in and of itself (i.e., capable of standing
p.000012: independently without having to reference other sections), there may be some issues or topics that are
p.000012: discussed in several sections. Appendixes include additional descriptions of NERL observational human
p.000012: exposure studies, details about the process for developing this document, a list of acronyms and abbreviations,
p.000012: a glossary, and other supplemental information. The main body of the document includes the following
p.000012: sections.
p.000012: • Introduction, Purpose, and Scope (Section 1) lays out the background for observational human exposure studies,
p.000012: the scope of the document, and some of the important scientific and ethical issues that are critical to human
p.000012: subjects and observational research.
p.000012:
p.000012:
p.000012:
p.000013: 13
p.000013:
p.000013: • Study Conceptualization and Planning (Section 2) establishes that ethical concerns are to be incorporated in
p.000013: the scientific effort from the very beginning and includes ethical issues such as justifying the study
p.000013: because of its social and scientific merit and ensuring scientific validity and independent review.
p.000013: • Protection of Vulnerable Groups (Section 3) discusses some of the special protections afforded to vulnerable groups
p.000013: by EPA’s human subjects rules and the ethical issues of involving such groups in observational research.
p.000013: • Ensuring Privacy and Confidentiality (Section 4) lays out the ethical issues and the regulatory requirements,
p.000013: including observations of nonstudy hazards and the recently discussed issues of third-party involvement or
p.000013: concerns.
p.000013: • The Relationship Between the Participant and the Researcher (Section 5) builds on the ethical principles of
p.000013: respect for persons and beneficence to discuss the issues around recruitment, informed consent,
p.000013: payment, and the researcher’s need to support the welfare of the participants.
p.000013: • Community and Stakeholder Relationships (Section 6) begins with the principles of fairness, justice, and
p.000013: equity and of respect for persons to develop approaches to demonstrate respect for culture
p.000013: and to empower the participants’ community to endure, including the need to build trust in the community and
p.000013: with stakeholders through open and honest communications and legitimate power sharing.
p.000013: • Strategies for Effective Communication (Section 7) builds on the presumption of an ongoing, interactive
p.000013: dialogue and exchange of ideas between researchers and the participants, community, and stakeholders and focuses
p.000013: on steps that the researcher needs to take for effective communications. The section discusses communication
...
p.000015: (HSRRO). The HSRRO, located in the EPA Office of the Science Advisor, ensures that Agency studies comply with
p.000015: the Common Rule and all directives of 40 CFR 26 providing guidance and principles to govern Federal agency
p.000015: sponsored human subject research.. Only after HSRRO approval can any research actually begin. As the NERL study
p.000015: is implemented, project data and concerns of the participants will be monitored on a continuing basis and
p.000015: compared with previously established standards and
p.000015:
p.000015:
p.000017: 17
p.000017:
p.000017:
p.000017: Table 2.1. Seven Requirements for Determining Whether a Research Trial is Ethical
p.000017: From Emanuel, Wendler, and Grady (2000)
p.000017: Requirement Explanation
p.000017: Topics in this Section
p.000017:
p.000017:
p.000017: Social or scientific value
p.000017:
p.000017: Evaluation of a treatment, intervention, or theory that will improve health and well-being or increase knowledge
p.000017:
p.000017: Defining the study problem Justifying the study Identifying a research team
p.000017:
p.000017:
p.000017: Scientific validity
p.000017:
p.000017: Use of accepted scientific principles and methods, including statistical techniques, to produce reliable and valid data
p.000017:
p.000017: Study design Feasibility
p.000017: Sample size determination Representativeness of the sample Information collection rule
p.000017: Quality assurance Study design document
p.000017:
p.000017:
p.000017: Fair subject selection
p.000017:
p.000017: Selection of subjects so that stigmatized and vulnerable individuals are not targeted for risky research, and the rich
p.000017: and socially powerful are not favored for potentially beneficial research
p.000017:
p.000017: Ethical issues in fair subject selection
p.000017:
p.000017:
p.000017: Favorable risk- benefit ratio
p.000017:
p.000017: Minimization of risks; enhancement of potential benefits and risks to the subject are proportionate to the benefits to
p.000017: the subject and to society
p.000017:
p.000017: Designing in benefits for participants
p.000017: Assessing benefits and risks of study participation
p.000017:
p.000017:
p.000017: Independent review
p.000017:
p.000017: Review of the design of the research trial, its proposed subject population, and risk-benefit ratio by individuals
p.000017: unaffiliated with the research
p.000017:
p.000017: Scientific peer review Conflicts of interest
p.000017: Developing the protocol for ethical review Ethical review
p.000017: EPA review of scientific and ethical issues
p.000017:
p.000017:
p.000017: Informed consent
p.000017:
p.000017: Provision of information to subjects about the purpose of the research, its procedures, potential risks, benefits, and
p.000017: alternatives, so that the individual understands this information and can make a voluntary decision whether to enroll
p.000017: and continue to participate
p.000017:
p.000017: Informed consent
p.000017: Ensuring that participant behaviors are not adversely changed
p.000017:
p.000017:
p.000017: Respect for potential and enrolled subjects
p.000017:
p.000017: Respect for subjects by
p.000017: • permitting withdrawal from the research,
...
p.000023: scientific and ethical standards. The research team can meet regularly to specifically evaluate the plan. It
p.000023: should be noted that a study design is not the same as an implementation plan. The latter includes an even
p.000023: greater level of detail describing how the study will be performed and includes protocols and
p.000023: operating procedures. Text Box 2-4 lists a number of elements that may be appropriate to include in a study design.
p.000023:
p.000023: 2.3 Ethical Issues in Ensuring Fair Subject Selection
p.000023: One of the ethical principles of human subjects research is that selection of participants should be fair. In
p.000023: Section 2.2.4, the discussion centers on understanding what population or cohort the participants in a research
p.000023: study represents, and how such a selection may be influenced by the research questions and
p.000023: study objectives. That consideration actually represents the first component of ensuring that subject selection is
p.000023: fair. That is, the scientific goals of the study should be the primary basis for determining what groups or
p.000023: individuals should be recruited and enrolled in a study. Participants should not be recruited either because of
p.000023: privilege or because of vulnerability or their inability to look out for their own interests properly.
p.000023: Similarly, groups or individuals should not be excluded peremptorily without consideration of the risks and
p.000023: benefits to them as individuals. Section 3 of this document discusses protection of
p.000023: vulnerable groups and concludes that NERL researchers should include vulnerable groups in observational
p.000023: human exposure studies only if their participation is critical to the success and applicability of the
p.000023: research. Even then, EPA and NERL researchers will have to meet stringent standards for protecting the rights and
p.000023: safety of the vulnerable participants. “The essence of
p.000023:
p.000023:
p.000023: Text Box 2-4. Elements That May Be Included in a Study Design
p.000023: • Introduction and background, including the purpose and scope of the study
p.000023: • The desired outputs and outcomes of the study, including the objectives and the hypotheses to be tested
p.000023: • A brief description or overview of the study
p.000023: • The technical approach and conceptual model that accounts for
p.000023: – sources of the chemicals being studied;
p.000023: – potential routes and pathways of exposure;
p.000023: – factors that may impact exposure and other relevant stressors;
p.000023: – selection and characteristics of the study participants; eligibility criteria; and recruitment, retention, and
p.000023: payment approaches;
p.000023: – justification for sample size, the methodology for selecting participants, and the sampling methods;
p.000023: – characteristics of the community in which the study will be performed;
p.000023: – environmental conditions, factors, or end points to be measured, including sampling and analysis approaches and
p.000023: methods (with description of expected performance);
p.000023: – survey design and questionnaires and other survey instruments, as applicable (with description of prior use and
p.000023: validation in similar studies);
p.000023: – pilot studies that may be undertaken;
p.000023: – quality assurance project plan and quality control;
p.000023: – timeframe for the study;
p.000023: – exposure scenarios to be considered;
p.000023: – burden of the study on the participants;
p.000023: – resources available; and
p.000023: – feasibility
p.000023: • Discussion of alternative study designs and approaches considered and reasons for rejecting other approaches and
p.000023: selecting the one proposed
p.000023: • An analysis plan that considers
p.000023: – Information and data needs, including data storage, security, access, and release;
p.000023: – nature of the measurement data (e.g., variability, quality assurance);
p.000023: – how the collected data will be used, and how the proposed analyses will address objectives of the study; and
p.000023: – hypotheses to be tested and statistical power and sample size required to test the hypotheses
p.000023: • Resources required or available
p.000023: • Project organization and management, including team members and roles and responsibilities
p.000023: • Schedule
p.000023:
p.000023: fairness in human subjects research is that scientific goals, considered in dynamic interaction with
p.000023: the potential for and distribution of risks and benefits, should guide the selection of subjects.”
p.000023: (Emmanuel et al, 2000). On the other hand, as discussed in Section 3, many study problems specifically
p.000023: address exposures of vulnerable groups to chemicals and other stressors. Researchers should not avoid
p.000023: research studies that will,
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024: of necessity, include vulnerable groups to address the study hypotheses or objectives simply to avoid the more
p.000024: stringent requirements for working with these groups.
p.000024:
p.000024: 2.4 Ensuring a Favorable Risk-Benefit Ratio
p.000024: 2.4.1 Designing in Benefits for the Participants
p.000024: Study designs vary depending on the objectives of the study, existing knowledge on the research question, and
p.000024: the hazard being studied (NRC & IOM, 2005). Recent ethical discussions about study designs in human subjects
p.000024: research (cf., Recommendation 7.1, p. 143, NRC & IOM [2005] and Emanuel et al. [2000]) support the development
p.000024: of innovative study designs to maximize the benefit9 to the study participants, as well as to
p.000024: the community and the greater society beyond. Observational human exposure studies generally collect data that
p.000024: contribute to generalizable knowledge that will benefit the community and society as a whole, but they often do not
p.000024: provide obvious direct benefit to study participants. Therefore, it is important to include elements
p.000024: in the study design that can offer benefits to the participants wherever possible. This is not always
p.000024: straightforward, but one way that participants, as well as communities, can benefit from these studies is
p.000024: by incorporating strong educational components into the conduct of the research. For example, brochures, videos,
p.000024: and other materials that educate study participants on safety around the home or on how to reduce their
...
p.000027: identifies a number of topics that should be considered in development of the human subjects research protocol.
p.000027: In addition, the authors’ experience leads them to suggest that three additional topics beyond those from
p.000027: the CIOMS (2002) document also may need to be considered in a human subjects protocol: (1) approaches to
p.000027: minimize changes in participant behavior because of participation in the study (see Section 2.3.4);
p.000027: (2) approaches to minimize therapeutic misconception (see Section 5.4.1); and (3) actions to involve
p.000027: the community in a community-based participatory research
p.000027:
p.000027: Text Box 2-5. Potential Topics in a Human Subjects Research Protocol
p.000027: 1. Title
p.000027: 2. Summary in lay language
p.000027: 3. Justification for the study
p.000027: 4. Ethical issues and proposed resolution
p.000027: 5. Summary of previous research
p.000027: 6. Affirmation of Belmont Principles and 40 CFR 26 compliance
p.000027: 7. Previous history or use of the protocol
p.000027: 8. Information on the location and demographics of research
p.000027: 9. Information on funding organization, researcher partners, and collaborators
p.000027: 10. Names, qualifications, and experience of investigators
p.000027: 11. Objectives, hypotheses, assumptions, and variables
p.000027: 12. Study design
p.000027: 13. Sample size and power and statistical analysis plan
p.000027: 14. Criteria and justification for subject selection
p.000027: 15. Justification for use of vulnerable groups, if any
p.000027: 16. Process of recruitment
p.000027: 17. Actions to involve the community in a community-based participatory research program
p.000027: 18. Description and explanation of any and all interventions
p.000027: 19. Measurements or data to be collected
p.000027: 20. Any clinical or other tests
p.000027: 21. Rules or criteria for removing subjects or terminating the study
p.000027: 22. Adverse events and unanticipated problems⎯reporting and responses
p.000027: 23. Potential benefits to subjects or others
p.000027: 24. Expected benefits of the research to the population
p.000027: 25. Informed consent process and responsibilities
p.000027: 26. Protections for the consent/assent of vulnerable participants
p.000027: 27. Efforts to minimize “therapeutic misconception”
p.000027: 28. Approaches to minimize changes in participant behavior
p.000027: 29. Payments
p.000027: 30. Plans for informing subjects about items that could affect subjects’ willingness to continue in the study
p.000027: 31. Plans to inform subjects about the results of the study
p.000027: 32. Privacy and confidentiality
p.000027: 33. Security of personal information and when, how, and by whom private information can be revealed
p.000027: 34. All foreseen uses of personal data or biological materials
p.000027: 35. Procedures for data and safety monitoring and oversight of the study and the criteria for identifying, reporting,
p.000027: and responding to adverse events, including ethical breaches, environmental measures in excess of reporting standards,
p.000027: and collateral observations, and criteria for prematurely terminating the study if necessary
p.000027: 36. A list of the references cited in the protocol
p.000027: 37. The source and amount of funding
p.000027: 38. Protocols for dealing with financial or other conflicts of interest
p.000027: 39. Schedule
p.000027: 40. Arrangements with sponsors regarding publication rights and procedures
p.000027: 41. Reasons for not publishing the study findings
p.000027: 42. Procedures for preventing falsification of data
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028: (CBPR) effort, as appropriate (see Section 6, especially Section 6.10).
p.000028:
p.000028: 2.5.4 Ethical Review
p.000028: In the United States, ethical reviews of studies involving human subjects are performed by IRBs.
p.000028: The Common Rule specifies requirements (40 CFR 26.107 –
...
p.000032: [accessed June 2007].
p.000032: U.S. EPA (U.S. Environmental Protection Agency) (2000). Comments on the use of data from the testing of human subjects:
p.000032: A report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. Environmental Protection Agency,
p.000032: Science Advisory Board. EPA-SAB-EC-00-017. Available: http://www.epa.gov/scipoly/sap/meetings/1999/november/e c0017.pdf
p.000032: [accessed 16 April 2008].
p.000032:
p.000032: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000032: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000032: [accessed 12 June 2007].
p.000032:
p.000032: Van Belle G, Fisher L (2004). Biostatistics: A Methodology for the Health Sciences (2nd Edition) Hoboken, NJ: John
p.000032: Wiley & Sons.
p.000032:
p.000032: Wackerly DD, Mendenhall W, Scheaffer RL (2001). Mathematical Statistics with Applications (6th Edition). Pacific Grove,
p.000032: CA: Duxbury Press.
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: SECTION 3
p.000033: Ensuring Protection of Vulnerable Groups
p.000033:
p.000033:
p.000033:
p.000033: Concern for the protection of vulnerable groups is fundamental to modern ethical thought and guidelines.
p.000033: The Belmont Report was “meant to provide broad principles that could be used to generate specific
p.000033: rules and regulations in response to [U.S.] research scandals such as Tuskegee and Willowbrook.11 It
p.000033: focuses on informed consent, favorable risk-benefit ratio, and the need to ensure that vulnerable
p.000033: populations are not targeted for risky research” [emphasis added] (Emanuel et al., 2000).
p.000033: The Common Rule requires IRBs to assure that “additional safeguards have been included in the study to protect
p.000033: the rights and welfare of these [vulnerable] subjects” [at 40 CFR 26.111(b) in CFR, 2006a]. If an
p.000033: observational human exposure study includes vulnerable research participants, it is essential that the investigators be
p.000033: cognizant of the special issues and requirements of research involving vulnerable populations. Researchers
p.000033: have to justify the involvement of vulnerable populations in the research study and
p.000033: include the appropriate safeguards for protection of their safety and welfare. The Common Rule protections are
p.000033: discussed further in the IRB guidebook (U.S. HHS, 1993). EPA regulations include not only the general
p.000033: protections for vulnerable populations found in the Common Rule (Subpart A) but also define
p.000033: additional protections for children and for pregnant or nursing women (and their fetus or nursing child)
p.000033: in Subparts B, C, and D (CFR, 2006a).
p.000033: The section begins by identifying or defining vulnerable groups and then discusses ethical issues that
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
p.000035: broader definition of vulnerability as it relates to education, economics, social status, and other factors. As
p.000035: shown in Text Boxes 3-1 and 3-2 and described above, the concept of vulnerability is broader than that
p.000035: presented in the Common Rule. It is not adequate to simply check the list in Text Box 3-1 to identify if a potentially
p.000035: vulnerable group is included in an observational study. The researchers should assess the potential
p.000035: vulnerability of a study population within the study by evaluating the characteristics (e.g., socioeconomic
p.000035: status) of the study population within the context of the study by considering the various design elements of the
p.000035: study, as discussed in Section 2.
p.000035: 12 In the commentary on Guideline 13 in CIOMS (2002), the committee states that the central problem presented by plans
p.000035: to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
p.000035: the CIOMS document (Guidelines 14 and 15) and include children, and persons who, because of mental or behavioral
p.000035: disorders, are incapable of giving informed consent. Ethical justification of their involvement usually requires that
p.000035: • the research could not be carried out equally well with less vulnerable subjects;
p.000035: • the research is intended to obtain knowledge that will lead to improved diagnosis, prevention, or treatment of
p.000035: diseases or other health problems characteristic of, or unique to, the vulnerable class—either the actual subjects or
p.000035: other similarly situated members of the vulnerable class;
p.000035: • research subjects and other members of the vulnerable class from which subjects are recruited will ordinarily be
p.000035: assured reasonable access to any diagnostic, preventive, or therapeutic products that will become available as a
p.000035: consequence of the research;
p.000035: • the risks attached to interventions or procedures that do not hold out the prospect of direct health-related
p.000035: benefit will not exceed those associated
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036: CIOMS recommendations, although written to address biomedical research, also generally are
p.000036: applicable to observational human exposure studies. The authors of this document consider the CIOMS
p.000036: requirement that the research could not be carried out equally well with less vulnerable subjects
p.000036: to be particularly important. EPA and NERL researchers should include vulnerable groups in
p.000036: observational human exposure studies only if their participation is critical to the success and
p.000036: applicability of the research. Even then, EPA and NERL researchers will have to meet stringent standards for
p.000036: protecting the rights and safety of the vulnerable participants. For example, EPA regulations
p.000036: governing observational research with children are even more stringent than the CIOMS guideline.
p.000036: If such research does not hold out the prospect of direct benefit to the child, no increase whatsoever over
p.000036: minimal risk is permitted.
p.000036: However, many observational human exposure studies are developed specifically to study the exposures of
p.000036: selected vulnerable groups to chemicals and other environmental stressors in everyday environments. So,
p.000036: researchers should be prepared to address the issues associated with vulnerable groups in
p.000036: observational research. Furthermore, as discussed in Section 3.4, there has been increased concern in recent years that
p.000036: exclusion of vulnerable groups from research studies is not ethical. Failure to conduct research with vulnerable groups
p.000036: may deprive them of the benefits of research. NIH, for example, has a policy (NIH, 1998) with a
p.000036: goal of increasing participation of children in research.
p.000036:
p.000036: 3.3 Minimal Risk and Vulnerable Groups
p.000036: EPA has codified protections for children, pregnant or nursing women, and fetuses in Subparts B, C, and D of the EPA
p.000036: human subjects rule (40 CFR 26). Subpart B strictly prohibits research involving intentional exposure of children
p.000036: or pregnant or nursing women (and, therefore, exposure of her fetus).
p.000036: EPA’s regulations do allow for observational research involving fetuses and pregnant women (40 CFR 26
p.000036: Subpart C) or children (40 CFR 26 Subpart D) but with additional protections in place and with
p.000036: strict limitations on research that presents more than minimal
p.000036: risk (CFR, 2006a).13 When considering vulnerable groups, The Institutional Review Board Guidebook (U.S. HHS,
p.000036: 1993) states that “IRBs should therefore determine whether the proposed subject population would be more sensitive or
p.000036: vulnerable to the risks posed by the research as a result of their general condition or disabilities. If so, the
p.000036: procedures would constitute more than minimal risk for those subjects.”
p.000036: When conducting observational human exposure studies, it is recommended that researchers consult these
p.000036: regulations and guidebooks. NERL researchers also will need to ensure that all of the requirements in Subparts B, C,
p.000036: and D of the EPA Human Subjects Rule are met.
p.000036:
p.000036: 3.4 Research Involving Children
p.000036: Children long have been recognized as a vulnerable group in research studies. EPA and HHS both extend special
p.000036: protections to children (CFR, 2006a,b). There are many books, reports, and research manuscripts that
p.000036: specifically address issues associated with research involving children (e.g., NRC & IOM, 2005; IOM,
p.000036: 2004; Kodish, 2005; NRC, 2003; AAP, 2003).
p.000036: CIOMS has drafted guidelines for including children in biomedical research (Guideline 14, CIOMS, 2002). The
p.000036: guidelines require an investigator to provide the assurances shown in Text Box 3-3 before undertaking
p.000036: research involving children.
p.000036:
p.000036: Text Box 3-3. Assurances Required by CIOMS Before Research Involving Children May Begin
p.000036: • the research might not equally well be carried out with adults;
p.000036: • the purpose of the research is to obtain knowledge relevant to the health needs of children;
p.000036: • a parent or legal representative of each child has given permission;
p.000036: • the agreement (assent) of each child has been obtained to the extent of the child’s capabilities; and
...
p.000036: encountered in daily life or during the performance of routine physical or psychological examinations or tests.”
p.000036:
p.000036:
p.000037: 37
p.000037:
p.000037: some cases, are higher) from those of adults. Children are behaviorally and physiologically different
p.000037: from adults. Their interaction with their environment, through activities such as playing on floors, mouthing of
p.000037: hands and objects, and handling of food, may increase contact with contaminated surfaces. Children
p.000037: have proportionately higher breathing rates, relative surface area, and food intake requirements
p.000037: that also may increase exposure. Differences in absorption, metabolism, storage, and excretion
p.000037: may result in higher biologically effective doses to target tissues. Immature organ systems may be more
p.000037: susceptible to toxicological challenges. Windows of vulnerability, when specific toxicants may permanently
p.000037: alter the function of an organ system, are thought to exist at various stages of development. Because
p.000037: the factors influencing children’s exposures to chemicals are not characterized well (Cohen Hubal et
p.000037: al., 2000), it is sometimes important that observational human exposure studies involve children.
p.000037: Because children are so vulnerable, there long has been concern about including them in research studies,
p.000037: and biomedical research often excluded children. However, in recent years, there has been concern
p.000037: that excluding children from research is not ethical. NIH’s Policy and Guidelines on the Inclusion of
p.000037: Children as Participants in Research Involving Human Subjects (NIH, 1998) has a goal of increasing
p.000037: participation of children in research. The policy of NIH is that children must be included in all human
p.000037: subjects research conducted or supported by NIH, unless there are scientific and ethical reasons
p.000037: not to include them. Proposals or applications to NIH for research have to present an acceptable
p.000037: justification if children will be excluded from a research study. Of course, as discussed above, if the research
p.000037: topic is irrelevant to children, the CIOMS guidelines would recommend that they be excluded from the
p.000037: research.
p.000037: Observational human exposure studies conducted by NERL are not expected to involve greater than minimal risk. It
p.000037: will be the responsibility of the NERL researchers to present adequate information for the IRB to
...
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
p.000037: biomedical research because of the potential for becoming pregnant during a study. The document continues, “A
p.000037: general policy of excluding from such clinical trials women biologically capable of becoming pregnant is
p.000037: unjust in that it deprives women as a class of persons of the benefits of new knowledge derived from the
p.000037: trials.” The second relevant CIOMS guideline, number 17, asserts that, if involved in a research study,
p.000037: pregnant women should be fully informed, and included only if the
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: research benefits pregnant women and is thoroughly supported by reliable evidence in animal studies.
...
p.000038: behind the guidelines generally may be applicable to observational human exposure studies. EPA’s human
p.000038: subjects rule is completely consistent with the HHS rule in adding additional protections for pregnant women and
p.000038: fetuses involved in observational research (40 CFR
p.000038: 26.304 and 45 CFR 46.204). These additional protections (specified in 45 CFR 46.204 subparagraphs a
p.000038: through j) reflect the CIOMS recommendations by requiring: availability of data from previously conducted
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
p.000038: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle A Department of Health and Human Services Part 46 Protection
p.000038: of Human Subjects. U.S. Code of Federal Regulations. Available:
p.000038: http://www.access.gpo.gov/nara/cfr/waisidx_06/45cfr46_06.ht ml [accessed 13 June 2007].
p.000038:
p.000038: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000038: Biomedical Research Involving Human Subjects.
p.000038: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000038:
p.000038: Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry MR, Rigas ML, Zartarian VG, Freeman NCG (2000).
...
p.000047:
p.000047: 4.5 Data and Safety Monitoring and Oversight
p.000047: The Common Rule requires for IRB approval that, “When appropriate, the research plan makes adequate
p.000047: provision for monitoring the data collected to ensure the safety of subjects.” [40 CFR 26.111(a)(6)].
p.000047: Data and safety monitoring plans (DSMPs) are developed and applied in all clinical trial
p.000047: research studies. Clinical trials are prospective studies designed to answer specific questions about the effects or
p.000047: impact of particular biomedical or behavioral interventions. The DSMPs are used to insure the safety of
p.000047: participants, the validity of data, and appropriate termination of studies for which significant risks
p.000047: or benefits have been uncovered or when it appears that the trial cannot be concluded successfully
p.000047: (NIH, 1998; NCI, 2001; U.S. FDA, 2001). Depending on the study scope and potential risks and benefits, a
p.000047: data safety monitoring board (DSMB) may be created to assess procedures for data and safety monitoring
p.000047: and to independently assess safety and outcomes on an ongoing basis during the study.
p.000047: Formal independent monitoring boards or committees, like DSMBs, have not seen widespread use in
p.000047: observational human exposure studies, although much of the information included in DSMPs often has been
p.000047: captured in the research protocols. Researchers and IRBs may, however, consider using monitoring and oversight boards
p.000047: to help assure participant safety and research integrity in observational human exposure studies,
p.000047: particularly in complex longitudinal studies and in studies that include vulnerable subjects.
p.000047: At least two NIH institutes have developed guidelines for monitoring and oversight in
p.000047: the observational research that they sponsor.
p.000047: (1) The National Heart, Lung, and Blood Institute (NHLBI) has developed an interim policy on the
p.000047: creation and role of observational study monitoring boards (OSMBs) for observational research
p.000047: sponsored by that institute (NHLBI, 2007). OSMBs may be established for large or complex studies on a case-by-case
p.000047: basis. The role of the OSMB is “to help assure the integrity of the study by closely monitoring data
p.000047: acquisition for comprehensiveness, accuracy, and timeliness; and monitoring other concerns such as
p.000047: participant confidentiality.”
p.000047: (2) The National Eye Institute (NEI) has developed guidelines for data monitoring and oversight
p.000047: committees (DMOCs) for observational research (NEI, 2001). The role of the DMOC is to “assist the NEI and the
p.000047: study investigators in protecting the interests of study participants and in preserving the integrity and
p.000047: credibility of the study.”
p.000047: When appropriate, formal procedures for routine monitoring of scientific and ethical issues will need to be
p.000047: incorporated into observational research and approved by the IRB to ensure participant safety and the integrity of
p.000047: the research. Even though most observational human exposure studies are considered low-risk, there is often a need to
p.000047: determine whether appropriate threshold values for biological or environmental levels of chemicals exist or can be
...
p.000054: protections. Researchers should make plans for trained staff or trained community members, associated
p.000054: or affiliated with the research study, to be available for translations.
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
p.000055: dialogue . . . involving the disclosure and exchange of relevant information” (IOM, 2002): it is not
p.000055: simply having a consent form signed. The process is most effective when the researcher spends time with
p.000055: potential participants to discuss the study and to answer questions.
p.000055:
p.000055: 5.2 Payments to Research Participants
p.000055: The decision whether to pay research participants, including the appropriate level of payment,20 is
p.000055: a complex ethical issue. Monetary or nonmonetary payments are not ethical if they constitute an
p.000055: undue inducement for participants to assume research risks that they would not otherwise accept. On the other
p.000055: hand, it may be ethically appropriate to offer reasonable payments in some research studies. Indeed,
p.000055: payment of human subjects for their participation in scientific research is a common practice in the United
p.000055: States, with a history of well over 100 years (Grady, 2005). The difficulty for researchers and IRBs is that
p.000055: there is often little clear and uniform guidance for determining what constitutes “undue inducement”
p.000055: or “reasonable” payment for any particular research study, population, and level of risk. Additional
p.000055: considerations regarding payment to participants arise when working with vulnerable populations, including
p.000055: children.
p.000055:
p.000055:
p.000055:
p.000055:
p.000055: 20 There are many terms that may be found in the literature to describe both monetary and nonmonetary payments, like
p.000055: payment, remuneration, compensation, recompense, incentive, inducement, reimbursement, and reward. Each of these words
p.000055: has its own definition, and each word also may carry specific connotations. In general, these terms refer to money or
p.000055: other items that “are often given to acknowledge the time and inconvenience of participating in research or to
p.000055: reimburse participants for any costs they incur. The term compensation is often used in the context of compensation for
p.000055: research-related injuries” (p. 112, NRC & IOM, 2005). The authors have chosen to use “payment” as the general term for
p.000055: monetary and nonmonetary items provided to research subjects for their participation in the research. They may
p.000055: occasionally refer to compensation for research-related injuries, but the text should make it clear when they do.
p.000055: 5.2.1 Types and Amounts of Payments Offered in Research Studies
p.000055: Payments have been offered in a wide variety of research studies, ranging from clinical trials
p.000055: to behavioral and social research to observational human exposure studies. Payments can take various
p.000055: forms, including monetary payments (e.g., cash, gift certificates, reimbursement for expenses),
p.000055: nonmonetary payments (e.g., gifts, valuable information), or nothing at all (e.g., for a sense of
p.000055: altruism). Grady (2005) has described payment for the participation of research subjects as serving
...
p.000056: of discomfort and burden, costs to participants, and population characteristics. However, large
p.000056: differences in payment levels have been found even in multisite studies in which the same protocol is
p.000056: administered across all sites.
p.000056: Grady et al. (2005) performed a survey of practices for paying research participants in the United States in
p.000056: Phase 1 to 4 clinical trials and physiologic, behavioral, and other types of research. Across 467
p.000056: studies of varying complexity that included payments, the median
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: payment was $155 (mean $266, range $5 to $2,000). The basis for dollar amounts was infrequently described, with
p.000057: 19% of the payments based on time, and 12% based on the procedures. In a model of payment factors,
p.000057: studies with some prospect of therapeutic benefit, studies having at least one invasive procedure, and studies with
p.000057: greater numbers of clinic visits were significantly associated with higher dollar amounts. About 9.5%
p.000057: of the studies offered completion bonuses, and a similar percentage offered escalating payments for
p.000057: followup study visits.
p.000057:
p.000057: 5.2.2 Regulations and Guidance Regarding Payment to Research Participants
p.000057: There is little specific guidance regarding payments in Federal human research regulations. The Common Rule and
p.000057: additional human subjects protections do not directly address payments to research participants, but the
p.000057: regulations do discuss providing additional safeguards for subjects vulnerable to coercion or undue
p.000057: influence [40 CFR 26.111(b)]. The NIH IRB guidebook advises IRBs to determine whether the rewards offered for
p.000057: participation in research constitute undue influence (U.S. HHS, 1993). According to the IRB guidebook undue
p.000057: inducement might blind prospective subjects to risks, impair their ability to exercise proper judgment, or may
p.000057: cause people to lie or to withhold information that would make them ineligible to enroll or continue
p.000057: participation.
p.000057: The U.S. Food and Drug Administration (FDA) has provided guidance for investigators and IRBs for clinical research
p.000057: studies (FDA, 1998). The guidance states that “payment to research subjects for participation in studies is not
p.000057: considered a benefit, it is a recruitment incentive.” FDA expects payments to accrue as the study progresses and not
p.000057: to be contingent on completing the study, although a “small proportion as an incentive for
p.000057: completion of the study is acceptable.” The guidance is concerned with the issue of coercion or undue influence, and
p.000057: it recognizes the IRB as the responsible party for deciding what is or is not acceptable.
p.000057: The U.S. Office of Management and Budget (OMB) develops standards and guidelines for statistical surveys performed by
...
p.000058: for reasonable expenses that are necessary for research participation. The specifics may vary, but
p.000058: examples of reasonable expenses are costs of transportation to the research site, parking, lodging, meals,
p.000058: and babysitting. Other payments are never appropriate in pediatric research, for example, paying parents
p.000058: for the use of their child in research” (pp. 225-6, IOM, 2004).21
p.000058: The IOM committee recommends establishing policies on acceptable and unacceptable types of
p.000058: payments. They also recommend that the policies disclose any recompense in a full and open
p.000058: process,22 while not overemphasizing any recompense.
p.000058: Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
p.000058: benefits, or they may be particularly vulnerable to undue influence resulting from the offer of a payment for
p.000058: research participation. In addition, payments made directly to parents or guardians could alter
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
p.000058: gestures of appreciation, investigators may also—if they minimize the potential for undue influence—act ethically to
p.000058: reduce certain barriers to research participation when they
...
p.000060: subject” [40 CFR 26.116(a)(7)].
p.000060: Information about the research often best can be answered by the researcher. However, it may benefit
p.000060: researchers and participants if information about the research can be obtained from or confirmed by a trusted
p.000060: independent person or organization. Participants also need to know how they can contact
p.000060: someone, independent from the researcher, who can answer questions concerning the rights of research
p.000060: participants and provide information on grievance procedures and research-related injuries. These questions
p.000060: could be addressed to the IRB, an ombudsman, an ethics committee, or other knowledgeable
p.000060: administrative body. Consent documents are expected to have at least two names with appropriate
p.000060: telephone contact information⎯one that can provide information regarding the research and
p.000060: another that can provide information regarding their rights as research participants. Grievance
p.000060: procedures should be structured so that grievances reach the approving IRBs and sponsoring
p.000060: organizations.
p.000060:
p.000060: 5.3.1 Ombudsman
p.000060: An ombudsman is a neutral independent advocate for research participants (and their families or guardians, where
p.000060: applicable). Institutions and IRBs may recommend or require the use of an ombudsman in
p.000060: certain types of research studies, particularly those seeking to study vulnerable populations.
p.000060: Ombudsmen can fill several roles as participant advocates. They may be an independent source of information
p.000060: regarding the study. They may be present during the informed consent process to ensure that risks, benefits,
p.000060: and study requirements are communicated correctly and understood by potential participants
p.000060: or their guardians. An ombudsman may be used in studies involving prisoners or military personnel to
p.000060: ensure that there is no coercion to participate. And the ombudsman may
p.000060:
p.000060:
p.000060:
p.000061: 61
p.000061:
p.000061: communicate problems or grievances raised by research participants to the IRB and sponsoring organization.
p.000061:
p.000061: 5.3.2 Community Advisory Board
p.000061: CABs can help ensure that participant rights are considered and addressed during the study design and can
p.000061: play an important role in monitoring the research process. Community members may choose to seek
p.000061: information about the study from the advisory panel, as an independent entity, before deciding whether to enroll.
p.000061: Representatives from such advisory boards can be included in the research team that designs the study (see
p.000061: Section 2.3). The role of CABs is more fully discussed in Section 6.
p.000061:
p.000061: 5.4 Creating a Supportive Environment for Research and Interaction
p.000061: It is recommended that researchers and institutions strive to create a supportive environment for research
...
p.000061: the Report and Recommendations on Public Trust in Clinical Research for the NIH Director from the
p.000061: Director’s Council of Public Representatives (COPR) (NIH, 2005). Although the advice from this workshop was
p.000061: developed in the context of NIH-supported clinical research, many of the recommendations are applicable to
p.000061: observational human exposure studies and human subject research in general. A summary
p.000061: of
p.000061: recommendations from the report for enhancing public trust is provided in Appendix D. The recommendations are
p.000061: focused on the following areas.
p.000061: • Building trust through community partnerships
p.000061: • Building relationships with patients (participants) (True partnerships with patients may not be possible,
p.000061: but bidirectional relationships must be enhanced.)
p.000061: • Building partnerships with community providers
p.000061: • Building trust in scientists
p.000061: • Building trust in the (EPA) and scientific research.
p.000061:
p.000061: 5.5 Recruitment Strategies
p.000061: Many strategies are used to select and recruit people into research studies requiring human participation. The IRB is
p.000061: responsible for reviewing the selection process to ensure that it is, above all, equitable. The requirement for
p.000061: IRB review is stated in 40 CFR 26.111(a)3.
p.000061: Selection of subjects is equitable. In making this assessment, the IRB should take into account the
p.000061: purposes of the research and the setting in which the research will be conducted and should be particularly cognizant
p.000061: of the special problems of research involving vulnerable populations, such as children, prisoners,
p.000061: pregnant women, mentally disabled persons, or economically or educationally disadvantaged
p.000061: persons.
p.000061: The IRB guidebook is an excellent resource for consideration of concerns and elements for equitable
p.000061: participant selection (U.S. HHS, 1993). It states that “Defining the appropriate group of subjects
p.000061: for a research project involves a variety of factors⎯ requirements of scientific design,
p.000061: susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness.” The IRB
p.000061: guidebook raises a number of points to consider in the process for selection of human participants (see Text Box
p.000061: 5-5).
p.000061: Various participant recruitment strategies may be used depending on the type of research being performed and the
p.000061: population of interest. This section addresses the strategies and approaches for identifying and contacting people and
p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
p.000062: 1. Who will bear the burden? Who will reap the benefits?
p.000062: 2. Is there a disproportionate burden on any single group?
p.000062: 3. Is the proposed subject population required or justified?
p.000062: 4. Are there susceptible groups of people who should be excluded from the research?
p.000062: 5. Are anticipated benefits distributed fairly? Do others have a greater need to receive any of the anticipated
p.000062: benefits?
p.000062: 6. Are the research burdens distributed fairly?
p.000062: 7. Will any special physiological, psychological, or social characteristics of the subject group pose special risks
p.000062: for them?
p.000062: 8. Would it be possible to conduct the study with other, less vulnerable subjects?
p.000062: 9. Has the selection process overprotected potential subjects who are considered vulnerable (e.g., children,
p.000062: cognitively impaired, economically or educationally disadvantaged persons, patients of researchers, seriously ill
p.000062: persons), so that they are denied opportunities to participate in research?
p.000062: 10. If the subjects are susceptible to pressures, are there mechanisms to reduce the pressures or minimize their
p.000062: impact?
p.000062:
p.000062:
p.000062: Some of the common approaches for identifying and making initial contact with potential participants include, but are
p.000062: not limited to
p.000062: • direct telephone or in-person contact with a person selected through a statistical sampling process
p.000062: to obtain a representative sample of the population being studied;
p.000062: • use of print or other media advertisements, often used to recruit people in a community with specific
p.000062: characteristics;
p.000062: • advertisement or word-of-mouth contacts through community groups, civic organizations, or other types of
p.000062: organizations; and
p.000062: • recruitment at physicians’ offices, hospitals, and clinics or at churches, schools, or other
p.000062: social institutions, either in person or through the use of advertisements or study brochures.
p.000062: CABs can be consulted regarding proposed approaches for recruitment in community-based
p.000062: research. All procedures and materials for participant recruitment are reviewed and approved by the IRB prior to
p.000062: implementation. Some of the materials prepared for recruitment might include the following.
...
p.000089: exposure either are not available or difficult to measure or interpret. In these cases, measurements in
p.000089: environmental media may be the best exposure metric. Whatever metric is chosen, it is important that the
p.000089: chemical analyses can be performed relatively quickly to reduce such exposures as quickly as possible.
p.000089: The second, and more difficult, step in developing the reporting protocol is to determine the
p.000089: level of concern that triggers reporting of the concentration to the study participant. For some environmental
p.000089: media, such as drinking water, EPA (2007) has established maximum contaminant levels that can be used as
p.000089: triggers for reporting. For example, if the researcher measures a level of arsenic in drinking water above
p.000089: 0.010 mg/L, he or she would be expected to report the level to the study participant. For other environmental media,
p.000089: such as air, there are few applicable standards. The National Ambient Air Quality Standards might be
p.000089: used for the criteria pollutants. Guidelines for occupational exposures, such as threshold limit
p.000089: values (TLVs) and biological exposure indices (BEIs) published by the
p.000089:
p.000089:
p.000090: 90
p.000090:
p.000090: American Conference of Governmental Industrial Hygienists (ACGIH, 2008) also may be used. TLVs are not
p.000090: standards; ACGIH formulates a conclusion on the level of exposure that the typical worker can experience without
p.000090: adverse health effects. Many people would argue that the TLVs are not conservative enough for the average
p.000090: population, particularly not for vulnerable lifestages (e.g., children, the elderly) and TLVs are only for
p.000090: exposure by inhalation. WHO (2005) also publishes air quality guidelines. These types of guidelines can be used to
p.000090: advise study participants if their exposures are high relative to the guidelines. Reporting levels should
p.000090: be conservative, but not so low that reporting the level to the participant causes unwarranted concern and
p.000090: stress. For other environmental media measured in observational human exposure studies, such
p.000090: as house dust or surface wipes, the measurement results cannot be used easily to estimate exposures, and they
p.000090: are a poor metric if used alone.
p.000090: An alternative approach to comparison of measurement results against available guidelines and
p.000090: standards is the comparison of measurements in biological fluids to measurement data available from the
p.000090: National Health and Nutrition Examination Survey (NHANES). For example, results of measurements of
p.000090: chemicals or their metabolites in urine or blood can be compared to different percentiles (e.g., the
p.000090: 95th) reported in the NHANES national reports (CDC, 2005). This type of comparison shows that the participant’s
p.000090: measurements are at the high end of the distribution of the NHANES data, suggesting that action may need to be
p.000090: taken to mitigate exposures. However, researchers need to be judicious in the selection of the exposure
p.000090: metric. Biomarkers in blood and biomarkers in urine can be very different exposure metrics and may represent
...
p.000108: observational human exposure studies. The authors recognize that this document may also prove to be
p.000108: useful to others involved in exposure science research, but the document is not meant to represent an
p.000108: official Agency “guidance document” and should not be used that way. This document does not provide solutions to
p.000108: the scientific and ethical issues that will undoubtedly arise as such studies are undertaken: no document could
p.000108: provide all of the answers in advance or develop a comprehensive checklist for all such studies.
p.000108: Rather, this document attempts to identify the types of issues that will need to be considered and addressed as NERL
p.000108: researchers plan and implement observational human exposure studies. The researchers will need to work with others
p.000108: – the study team, IRB members, EPA Human Subjects Research Review Official (HSRRO), the participants
p.000108: and their community, and other stakeholders – to identify and address all of the relevant
p.000108: issues for their particular study in order to ensure that the specific elements of the study will
p.000108: safeguard and protect the human research subjects.
p.000108: Charge to the Human Studies Review Board
p.000108: The draft document on Scientific and Ethical Approaches for Observational Exposure Studies consists of
p.000108: the following seven sections:
p.000108: 1. Introduction
p.000108: 2. Elements to be Considered in Study Conceptualization and Planning
p.000108: 3. Ensuring Protection of Vulnerable Groups
p.000108: 4. Privacy, Confidentiality, and Other Concerns Related to Observational Human Exposure Measurement Studies
p.000108: 5. Creating an Appropriate Relationship Between Participant and Investigator
p.000108: 6. Building and Maintaining Appropriate Community and Stakeholder Relationships
p.000108: 7. Designing and Implementing Strategies for Effective Communication
p.000108:
p.000108: The Human Studies Review Board is asked to address the following questions for each section of the draft
p.000108: document:
p.000108: 1. One of the goals of the document is identify the major scientific and ethical areas and issues that researchers
p.000108: should address in the design and implementation of observational human exposure measurement studies, with the emphasis
p.000108: on the areas requiring ethical considerations. Does each section identify the major areas and issues where ethical
p.000108: considerations should be addressed?
p.000108: 2. The document is intended to serve as a reference and resource of information that researchers can use in the design
p.000108: and implementation of observational exposure studies. For each section, are there additional sources of information
p.000108: that should be considered for inclusion?
p.000108: 3. Is the information presented accurately and clearly in each section?
p.000108:
p.000108:
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p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109: Appendix C
p.000109: Recommended Content of a Human Subjects Protocol
p.000109:
p.000109:
p.000109:
...
p.000109: (6) A statement that the principles of the Belmont Report and requirements specified in 40 CFR 26 will
p.000109: be implemented
p.000109: (7) An account of previous submissions of the protocol for ethical review and their outcomes
p.000109: (8) A brief description of the sites where the research is to be conducted, including information about the
p.000109: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000109: epidemiological information about the population to be studied
p.000109: (9) The names and addresses of the funding organization, research partners, and collaborators
p.000109: (10) The names, addresses, institutional affiliations, qualifications, and experience of the
p.000109: principal investigator and other investigators
p.000109: (11) The objectives of the study, its hypotheses or research questions, its assumptions, and
p.000109: its variables
p.000109: (12) A detailed description of the design of the study
p.000109: (13) The number of research subjects needed to achieve the study objective, and how this was determined
p.000109: statistically
p.000109: (14) The criteria for inclusion or exclusion of potential subjects and justification for the exclusion of
p.000109: any groups on the basis of age, sex, social or economic factors, or other reasons
p.000109: (15) The justification for involving as research subjects any persons with limited capacity to consent or
p.000109: members of vulnerable social groups and a description of special measures to minimize risks and
p.000109: discomfort to such subjects
p.000109: (16) The process of recruitment (e.g., advertisements) and the steps to be taken to protect privacy and
p.000109: confidentiality during recruitment
p.000109: (17) A description and explanation of any and all interventions
p.000109: (18) The measurements to be performed in the study, including environmental and biological sample
p.000109: collection, and other data and information that will be collected
p.000109: (19) If applicable, clinical and other tests involving the study participants that are to be carried out
p.000109: (20) The rules or criteria according to which subjects may be removed from the study or the study may be
p.000109: terminated
p.000109: (21) The methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000109: complications
p.000109: (22) The potential benefits of the research to subjects and to others
p.000109: (23) The expected benefits of the research to the population, including new knowledge that the study
p.000109: might generate
p.000109:
p.000109:
p.000109:
p.000111: 111
p.000111:
p.000111: (24) The means proposed to obtain individual informed consent and the procedure planned to communicate information to
p.000111: prospective subjects, including the name and position of the person responsible for obtaining consent
p.000111: (25) When a prospective subject is not capable of informed consent, satisfactory assurance
...
p.000117: exposure of a human subject [40 CFR 26.302]
p.000117: Privacy. Control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or
p.000117: intellectually) with others
p.000117: Research. A systematic investigation, including research development, testing, and evaluation, designed to develop or
p.000117: contribute to generalizable knowledge
p.000117: Research involving intentional exposure of a human subject. A study of a substance in which the exposure to the
p.000117: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
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p.000118: United States Environmental Protection Agency
p.000118:
p.000118:
p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
...
Searching for indicator vulnerability:
(return to top)
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
...
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
...
p.000023: programs and QAPPs is outside of the scope of this document. There are many good references on the topic,
p.000023: including the EPA Web site, www.epa.gov/quality/.
p.000023:
p.000023: 2.2.7 The Study Design Document
p.000023: The study design document should contain sufficient detail to allow independent review and assessment of the scientific
p.000023: soundness of the study and the approaches that will be followed to ensure that the study meets the highest
p.000023: scientific and ethical standards. The research team can meet regularly to specifically evaluate the plan. It
p.000023: should be noted that a study design is not the same as an implementation plan. The latter includes an even
p.000023: greater level of detail describing how the study will be performed and includes protocols and
p.000023: operating procedures. Text Box 2-4 lists a number of elements that may be appropriate to include in a study design.
p.000023:
p.000023: 2.3 Ethical Issues in Ensuring Fair Subject Selection
p.000023: One of the ethical principles of human subjects research is that selection of participants should be fair. In
p.000023: Section 2.2.4, the discussion centers on understanding what population or cohort the participants in a research
p.000023: study represents, and how such a selection may be influenced by the research questions and
p.000023: study objectives. That consideration actually represents the first component of ensuring that subject selection is
p.000023: fair. That is, the scientific goals of the study should be the primary basis for determining what groups or
p.000023: individuals should be recruited and enrolled in a study. Participants should not be recruited either because of
p.000023: privilege or because of vulnerability or their inability to look out for their own interests properly.
p.000023: Similarly, groups or individuals should not be excluded peremptorily without consideration of the risks and
p.000023: benefits to them as individuals. Section 3 of this document discusses protection of
p.000023: vulnerable groups and concludes that NERL researchers should include vulnerable groups in observational
p.000023: human exposure studies only if their participation is critical to the success and applicability of the
p.000023: research. Even then, EPA and NERL researchers will have to meet stringent standards for protecting the rights and
p.000023: safety of the vulnerable participants. “The essence of
p.000023:
p.000023:
p.000023: Text Box 2-4. Elements That May Be Included in a Study Design
p.000023: • Introduction and background, including the purpose and scope of the study
p.000023: • The desired outputs and outcomes of the study, including the objectives and the hypotheses to be tested
p.000023: • A brief description or overview of the study
p.000023: • The technical approach and conceptual model that accounts for
p.000023: – sources of the chemicals being studied;
p.000023: – potential routes and pathways of exposure;
p.000023: – factors that may impact exposure and other relevant stressors;
p.000023: – selection and characteristics of the study participants; eligibility criteria; and recruitment, retention, and
p.000023: payment approaches;
...
p.000027: 34. All foreseen uses of personal data or biological materials
p.000027: 35. Procedures for data and safety monitoring and oversight of the study and the criteria for identifying, reporting,
p.000027: and responding to adverse events, including ethical breaches, environmental measures in excess of reporting standards,
p.000027: and collateral observations, and criteria for prematurely terminating the study if necessary
p.000027: 36. A list of the references cited in the protocol
p.000027: 37. The source and amount of funding
p.000027: 38. Protocols for dealing with financial or other conflicts of interest
p.000027: 39. Schedule
p.000027: 40. Arrangements with sponsors regarding publication rights and procedures
p.000027: 41. Reasons for not publishing the study findings
p.000027: 42. Procedures for preventing falsification of data
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028: (CBPR) effort, as appropriate (see Section 6, especially Section 6.10).
p.000028:
p.000028: 2.5.4 Ethical Review
p.000028: In the United States, ethical reviews of studies involving human subjects are performed by IRBs.
p.000028: The Common Rule specifies requirements (40 CFR 26.107 –
p.000028: 115) for IRB membership, IRB functions and operations, IRB review of research, and other details related to IRB review
p.000028: and approval of research. Emanuel states that “the independent ethical review of [human subjects
p.000028: research] should involve individuals with training in science, statistics, ethics, and law, as well as
p.000028: reflective citizens who understand social values, priorities, and the vulnerability and concerns of
p.000028: potential subjects” (Emanuel et al., 2000). It is beyond the scope of this document to include
p.000028: detailed discussions on IRB membership, operations, processes, etc. The reader is referred to the Common
p.000028: Rule, as well as a number of other available references (e.g., OHRP, 2007; CFR, 2006; U.S. HHS,
p.000028: 1993; NRC, 2003).
p.000028: It is essential that research with human subjects be carried out or strictly supervised by suitably
p.000028: trained, qualified, and experienced investigators. For all research subject to the Common Rule, these qualified
p.000028: researchers are expected to prepare a human subjects research protocol (as in Section 2.5) and to submit
p.000028: the protocol to be ethically and scientifically appraised by one or more suitably constituted IRBs,
p.000028: independent of the investigators.
p.000028: There are a number of other issues associated with IRBs that may impact researchers
p.000028: conducting observational human exposure studies. As an example, there has been concern about the transparency of
p.000028: IRBs. Questions have been raised about what information the IRB should make available to the public
p.000028: regarding membership on the IRB for review of individual projects, the discussions held with the
p.000028: researchers, the IRB’s concerns about the research protocol, the researchers’ response, etc.
p.000028: Should this information be documented in files that the researchers can make available to the
p.000028: participants, community, stakeholders, and the public? At the present time, there is no clear approach as
...
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
...
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
p.000035: broader definition of vulnerability as it relates to education, economics, social status, and other factors. As
p.000035: shown in Text Boxes 3-1 and 3-2 and described above, the concept of vulnerability is broader than that
p.000035: presented in the Common Rule. It is not adequate to simply check the list in Text Box 3-1 to identify if a potentially
p.000035: vulnerable group is included in an observational study. The researchers should assess the potential
p.000035: vulnerability of a study population within the study by evaluating the characteristics (e.g., socioeconomic
p.000035: status) of the study population within the context of the study by considering the various design elements of the
p.000035: study, as discussed in Section 2.
p.000035: 12 In the commentary on Guideline 13 in CIOMS (2002), the committee states that the central problem presented by plans
p.000035: to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
p.000035: the CIOMS document (Guidelines 14 and 15) and include children, and persons who, because of mental or behavioral
p.000035: disorders, are incapable of giving informed consent. Ethical justification of their involvement usually requires that
p.000035: • the research could not be carried out equally well with less vulnerable subjects;
...
p.000036: • when the prospective subjects are either incompetent or otherwise substantially unable to give informed consent,
p.000036: their agreement will be supplemented by the permission of their legal guardians or other appropriate representatives.
p.000036:
p.000036:
p.000036: 13 Minimal risk is defined at 40 CFR 26.102(i) and again at 40 CFR 26.402(g). It “means that the probability and
p.000036: magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily
p.000036: encountered in daily life or during the performance of routine physical or psychological examinations or tests.”
p.000036:
p.000036:
p.000037: 37
p.000037:
p.000037: some cases, are higher) from those of adults. Children are behaviorally and physiologically different
p.000037: from adults. Their interaction with their environment, through activities such as playing on floors, mouthing of
p.000037: hands and objects, and handling of food, may increase contact with contaminated surfaces. Children
p.000037: have proportionately higher breathing rates, relative surface area, and food intake requirements
p.000037: that also may increase exposure. Differences in absorption, metabolism, storage, and excretion
p.000037: may result in higher biologically effective doses to target tissues. Immature organ systems may be more
p.000037: susceptible to toxicological challenges. Windows of vulnerability, when specific toxicants may permanently
p.000037: alter the function of an organ system, are thought to exist at various stages of development. Because
p.000037: the factors influencing children’s exposures to chemicals are not characterized well (Cohen Hubal et
p.000037: al., 2000), it is sometimes important that observational human exposure studies involve children.
p.000037: Because children are so vulnerable, there long has been concern about including them in research studies,
p.000037: and biomedical research often excluded children. However, in recent years, there has been concern
p.000037: that excluding children from research is not ethical. NIH’s Policy and Guidelines on the Inclusion of
p.000037: Children as Participants in Research Involving Human Subjects (NIH, 1998) has a goal of increasing
p.000037: participation of children in research. The policy of NIH is that children must be included in all human
p.000037: subjects research conducted or supported by NIH, unless there are scientific and ethical reasons
p.000037: not to include them. Proposals or applications to NIH for research have to present an acceptable
...
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
p.000038: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle A Department of Health and Human Services Part 46 Protection
p.000038: of Human Subjects. U.S. Code of Federal Regulations. Available:
p.000038: http://www.access.gpo.gov/nara/cfr/waisidx_06/45cfr46_06.ht ml [accessed 13 June 2007].
p.000038:
p.000038: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000038: Biomedical Research Involving Human Subjects.
p.000038: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000038:
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p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
p.000117:
p.000118: 118
p.000118:
...
Health / Cognitive Impairment
Searching for indicator cognitive:
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p.000058: The IOM committee recommends establishing policies on acceptable and unacceptable types of
p.000058: payments. They also recommend that the policies disclose any recompense in a full and open
p.000058: process,22 while not overemphasizing any recompense.
p.000058: Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
p.000058: benefits, or they may be particularly vulnerable to undue influence resulting from the offer of a payment for
p.000058: research participation. In addition, payments made directly to parents or guardians could alter
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
...
p.000084: communications with the public. That memorandum stated, “By using plain language, we send a
p.000084: clear message about what the Government is doing, what it requires and what services it offers. Plain language
p.000084: saves the Government and the private sector time, effort, and money.” Plain language is reader friendly and designed to
p.000084: increase the participant’s understanding of the communication material. It serves as a means by which lay
p.000084: audiences can access and understand scientific information. Researchers desiring to use plain language in
p.000084: their verbal and written communications with communities must decide on key messages to include and
p.000084: delete unnecessary descriptive, bureaucratic, or jargon-filled language. Researchers should use words that
p.000084: commonly are understood, rather than difficult abstract terms and concepts. A friendly,
p.000084: conversational tone is used to engage the lay audience, rather than a formal, scholarly tone that
p.000084: distances the community. Stableford and Mettger (2007) argue that proficiency in creating appropriate plain
p.000084: language materials is an acquired skill that requires knowledge and experience. “It is both an art and
p.000084: a science, requiring the ability to simultaneously think about the cognitive, emotional, and visual appeal of the
p.000084: piece as well as applying research- based strategies to ensure a truly easy-to-read and understand print
p.000084: material.”
p.000084: The Department of Health and Human Services (HHS) has developed a Web site that specifically
p.000084: address the issues related to “plain language” (see
p.000084: http://www.health.gov/communication/literacy/plainlang uage/PlainLanguage.htm). The site includes a list of
p.000084: references and other helpful resources.
p.000084: To maintain community engagement through the
p.000084: research process, it is critical that communications are at the appropriate level, and that materials are written at a
p.000084: reading level that is appropriate to the audience. For the nonscientist, many IRBs and other groups target
p.000084: materials to be used with participants and communities at a reading level no higher than the 8th grade to
p.000084: improve the likelihood of comprehension. In some communities, however, other factors, like primary languages other than
p.000084: English, educational disadvantages, etc., may require communications materials to be written in
p.000084: alternate languages and at different reading levels. The issue is comprehension, as was discussed in
p.000084: Section 5.1.2. Empirical testing of communication methods and content is essential to ensure
p.000084: comprehension (Health Canada, 2006).
p.000084: Researchers also should recognize that in this information age, dissemination of
...
Searching for indicator impaired:
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p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
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p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
p.000062: 1. Who will bear the burden? Who will reap the benefits?
p.000062: 2. Is there a disproportionate burden on any single group?
p.000062: 3. Is the proposed subject population required or justified?
p.000062: 4. Are there susceptible groups of people who should be excluded from the research?
p.000062: 5. Are anticipated benefits distributed fairly? Do others have a greater need to receive any of the anticipated
p.000062: benefits?
p.000062: 6. Are the research burdens distributed fairly?
p.000062: 7. Will any special physiological, psychological, or social characteristics of the subject group pose special risks
p.000062: for them?
p.000062: 8. Would it be possible to conduct the study with other, less vulnerable subjects?
p.000062: 9. Has the selection process overprotected potential subjects who are considered vulnerable (e.g., children,
p.000062: cognitively impaired, economically or educationally disadvantaged persons, patients of researchers, seriously ill
p.000062: persons), so that they are denied opportunities to participate in research?
p.000062: 10. If the subjects are susceptible to pressures, are there mechanisms to reduce the pressures or minimize their
p.000062: impact?
p.000062:
p.000062:
p.000062: Some of the common approaches for identifying and making initial contact with potential participants include, but are
p.000062: not limited to
p.000062: • direct telephone or in-person contact with a person selected through a statistical sampling process
p.000062: to obtain a representative sample of the population being studied;
p.000062: • use of print or other media advertisements, often used to recruit people in a community with specific
p.000062: characteristics;
p.000062: • advertisement or word-of-mouth contacts through community groups, civic organizations, or other types of
p.000062: organizations; and
p.000062: • recruitment at physicians’ offices, hospitals, and clinics or at churches, schools, or other
p.000062: social institutions, either in person or through the use of advertisements or study brochures.
p.000062: CABs can be consulted regarding proposed approaches for recruitment in community-based
p.000062: research. All procedures and materials for participant recruitment are reviewed and approved by the IRB prior to
p.000062: implementation. Some of the materials prepared for recruitment might include the following.
p.000062: • Recruitment scripts⎯prepared scripts used for in- person or telephone study information and recruitment
p.000062: contacts
p.000062: • Printed materials⎯brochures, flyers, newspaper advertisements, letters, and information articles
...
p.000117: in the study. The studies involve interaction with study participants but do not involve intervention or manipulation
p.000117: of the factors being studied, and there is no attempt by the researcher to affect the outcome.
p.000117: Observational research. Any human research that does not meet the definition of research involving intentional
p.000117: exposure of a human subject [40 CFR 26.302]
p.000117: Privacy. Control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or
p.000117: intellectually) with others
p.000117: Research. A systematic investigation, including research development, testing, and evaluation, designed to develop or
p.000117: contribute to generalizable knowledge
p.000117: Research involving intentional exposure of a human subject. A study of a substance in which the exposure to the
p.000117: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
...
Health / Comatose
Searching for indicator comatose:
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p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
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p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
...
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
...
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
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p.000118:
p.000118: United States Environmental Protection Agency
p.000118:
p.000118:
p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
...
Health / Drug Usage
Searching for indicator drug:
(return to top)
p.000019: scientific integrity of the research, including developing the conceptual model8 for the effort and
p.000019: devising a reliable sampling and analysis plan. Stakeholder input is critical to assuring that the generalizable
p.000019: research information from the study actually will be applicable for addressing the study problem. Community
p.000019: input is particularly important during the planning stage because the community representatives
p.000019: can provide valuable information about the community members (the future study cohort), the cultures of
p.000019: the community, community values, community concerns, feasibility of working in the community, information
p.000019: needed to develop the technical approach, and information on important factors like pollutant sources and
p.000019: other stressors in the community. (Additional considerations for communicating and
p.000019: working with both the participants and the community in which they live are the topics of Sections 5 through 7 of
p.000019: this document.)
p.000019: In developing the study design and the human subjects protocol, the research team often will have
p.000019: to deal with a variety of complex issues, including how to maximize benefits for participants, the community, and
p.000019: the stakeholders, and how to ensure the integrity, generalizability, and representativeness of the study.
p.000019:
p.000019: 2.2.1 Study Design
p.000019: In epidemiology, the concept of study design has been structured to include (1) experimental studies, like drug
p.000019: trials, where the variables are isolated and controlled (See discussion on experimental studies in
p.000019: Appendix A.) and (2) observational studies where the variables are not controlled intentionally, but are simply
p.000019:
p.000019:
p.000019: 8 A conceptual framework or model is often an effective approach to describe the relationship between the predicted
p.000019: exposures of the population and the population stressors, laying out the predicted pathways and routes of exposure
p.000019: (e.g., see Cohen Hubal et al., 2000). A conceptual model often is illustrated by a block diagram that represents the
p.000019: major scientific processes and interactions. The model is often very useful in developing an analysis plan that
p.000019: describes the hypotheses or objectives of the study, identifies the data needed to address the objectives, and
p.000019: specifies the analyses that will be done to test the hypotheses or address the objectives.
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: observed along with the outcome or response measures. Clearly, the NERL human exposure observational studies
p.000020: (see Table A-1) fall into the latter category. Such studies may be cross-sectional studies (where a subset of the
p.000020: population is observed at the same time); cohort studies (which measure the same variables and response measures
p.000020: in a group of people repeatedly over time); case control studies (where the observed population is
p.000020: separated into two groups based on the outcome or response measure [the case group and the control group], and
p.000020: exposure variables between the two groups are analyzed for differences); or studies that combine
p.000020: approaches. The research may collect data from the participants once (e.g., in a large-scale,
p.000020: randomized design to collect a representative sample of the population, like many of the National Human
p.000020: Exposure Assessment Survey [NHEXAS] studies); over a few days (e.g., NERL’s Particulate Matter [PM]
p.000020: panel studies); from a cohort in different seasons or years (e.g., NERL’s Detroit Exposure Aerosol Research
p.000020: Study [DEARS]; the NHEXAS study in Maryland); or a series of cross-sectional studies repeated one after another with a
p.000020: different group of participants each time. (This latter case often is necessitated to minimize time and expenses
p.000020: associated with being in the field and because of limitations of sampling equipment or field
p.000020: technicians to assist in the collection of the data.)
p.000020: Although much of the literature on study design involves experimental studies (like drug trials), there is much
p.000020: that can be learned about the design of observational studies in epidemiology,
p.000020: including understanding their strengths and weaknesses. Web sites, like “Epidemiology for the Uninitiated” (Coggin
p.000020: et al., 1997, available at www.bmj.com/epidem/epid.html), provide useful basic information on important topics
p.000020: for observational studies and their design.
p.000020: The specific details of the study design and the sampling approach to be used will depend very much on the
p.000020: objectives to be achieved in the study. Based on the objectives, a good study design must first clearly state
p.000020: the research question (or hypothesis to be tested) and must also define in advance what outcome or
p.000020: response measure will be used to test the question or hypothesis. Study designs that are vague or which propose
p.000020: to test some outcome measures against a variety of potential factors do not represent sound science.
p.000020: Statistically, a correlation is likely to be found between an outcome and some factor if enough factors are
p.000020: tested—whether there is an actual biological or physical relationship or not. This highlights the importance of
p.000020: statistics as an integral part of the study design process. Including individuals
p.000020: with appropriate statistical knowledge and experience on the research team from its very beginning is critical to a
p.000020: scientifically sound study design. (See, for example, Dallal, 2001, “Some Aspects of Study Design” in The
p.000020: Little Handbook of Statistical Practice at www.StatisticalPractice.com, and at
p.000020: www.tufts.edu/~gda llal/LHSP.HTM).
...
p.000048: 2007].
p.000048:
p.000048: NHRPAC (National Human Research Protections Advisory Committee) (2002). Clarification of the status of third parties
p.000048: when referenced by human subjects in research. Available: http://www.hhs.gov/ohrp/nhrpac/documents/third.pdf [accessed
p.000048: April 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (2002). Extramural Projects - Application Instructions (03/15/2002) - Detailed
p.000048: Application Instructions for Certificate of Confidentiality Involving Extramural Research Projects. Certificates of
p.000048: Confidentiality. Available: http://grants.nih.gov/grants/policy/coc/index.htm. [accessed April 2007]
p.000048:
p.000048: NIH (National Institutes of Health) (2001). Protection of third party information in research: Recommendations of the
p.000048: National Institutes of Health to the Office for Human Research Protections. Available:
p.000048: http://bioethics.od.nih.gov/nih_third_party_rec.html [accessed March 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (1998). NIH Guide: NIH Policy for Data and Safety Monitoring. Available:
p.000048: http://grants.nih.gov/grants/guide/notice-files/not98 084.html [accessed April 2007].
p.000048:
p.000048: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000048: Housing-Related Health Hazards Involving Children.
p.000048: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed
p.000048: June 2007].
p.000048:
p.000048:
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p.000049:
p.000049: U.S. FDA (U.S. Food and Drug Administration) (2001). Draft Guidance for Clinical Trial Sponsors on the Establishment of
p.000049: Clinical Trial Data Monitoring Committees. U.S. Department of Health and Human Services, Food and Drug Administration,
p.000049: Rockville, MD. Available: http://www.fda.gov/cber/gdlns/clindatmon.pdf. [accessed April 2007].
p.000049: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000049: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000049: [accessed June 2007].
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p.000050: SECTION 5
p.000050: Creating an Appropriate Relationship Between the Participant and Researcher
p.000050:
p.000050:
p.000050:
p.000050: In observational human exposure studies, the researcher and the participant routinely interact
p.000050: with each other, often in the participant’s home or other private setting and often repeatedly over a
p.000050: number of days. The nature and setting of the interactions mean that exposure researchers should give special
p.000050: consideration to the many scientific and ethical issues that shape the relationship between participants and
p.000050: the researchers. In these studies, it is recommended that a strong relationship, built on
...
p.000057: studies with some prospect of therapeutic benefit, studies having at least one invasive procedure, and studies with
p.000057: greater numbers of clinic visits were significantly associated with higher dollar amounts. About 9.5%
p.000057: of the studies offered completion bonuses, and a similar percentage offered escalating payments for
p.000057: followup study visits.
p.000057:
p.000057: 5.2.2 Regulations and Guidance Regarding Payment to Research Participants
p.000057: There is little specific guidance regarding payments in Federal human research regulations. The Common Rule and
p.000057: additional human subjects protections do not directly address payments to research participants, but the
p.000057: regulations do discuss providing additional safeguards for subjects vulnerable to coercion or undue
p.000057: influence [40 CFR 26.111(b)]. The NIH IRB guidebook advises IRBs to determine whether the rewards offered for
p.000057: participation in research constitute undue influence (U.S. HHS, 1993). According to the IRB guidebook undue
p.000057: inducement might blind prospective subjects to risks, impair their ability to exercise proper judgment, or may
p.000057: cause people to lie or to withhold information that would make them ineligible to enroll or continue
p.000057: participation.
p.000057: The U.S. Food and Drug Administration (FDA) has provided guidance for investigators and IRBs for clinical research
p.000057: studies (FDA, 1998). The guidance states that “payment to research subjects for participation in studies is not
p.000057: considered a benefit, it is a recruitment incentive.” FDA expects payments to accrue as the study progresses and not
p.000057: to be contingent on completing the study, although a “small proportion as an incentive for
p.000057: completion of the study is acceptable.” The guidance is concerned with the issue of coercion or undue influence, and
p.000057: it recognizes the IRB as the responsible party for deciding what is or is not acceptable.
p.000057: The U.S. Office of Management and Budget (OMB) develops standards and guidelines for statistical surveys performed by
p.000057: the Federal government. Under Guideline 2.3.2, OMB states that, while incentives are not typically used in Federal
p.000057: surveys, agencies may consider use of respondent incentives if they believe incentives would be necessary
p.000057: to use for a particular survey to achieve data of sufficient quality for their intended use (OMB,
p.000057: 2006a). OMB requires that agencies provide a justification for giving incentives to respondents.
p.000057: Some
p.000057: of the factors cited by OMB to be addressed include those particularly relevant to observational
p.000057: human exposure studies, including unusual reporting burdens (keeping data logs for extended periods,
p.000057: coordinating study team visits, participating in a medical examination, etc.), complex study designs (such as
...
p.000064: June 2007].
p.000064:
p.000064: OMB (Office of Management and Budget). (2006a). Standards and Guidelines for Statistical Surveys. Section 2.3, Data
p.000064: Collection Methodology. http://www.whitehouse.gov/omb/inforeg/statpolicy/standard s_stat_surveys.pdf
p.000064:
p.000064: OMB (Office of Management and Budget). (2006b). Questions and Answers When Designing Surveys for Information
p.000064: Collection. Office of Information and Regulatory Affairs. January, 2006.
p.000064: http://www.whitehouse.gov/omb/inforeg/pmc_survey_guidanc e_2006.pdf
p.000064:
p.000064: Paasche-Orlow MK, Taylor HA, Brancati FL (2003). Readability standards for informed-consent forms as compared with
p.000064: actual readability. N Engl J Med 348(8):721 6.
p.000064:
p.000064: Russell ML, Moralejo DG, Burgess ED. (2000). Paying research subjects: participants' perspectives. J Med Ethics
p.000064: 26(2):126-30.
p.000064:
p.000064: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979). The Belmont Report: Ethical Principles and
p.000064: Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: National Commission for the Protection
p.000064: of Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
p.000064: [accessed June 2007].
p.000064:
p.000064: U.S. FDA (U.S. Food and Drug Administration) (1998). Information Sheets: Guidance for Institutional Review Boards and
p.000064: Clinical Investigators 1998 Update. U.S. Food and Drug Administration, Washington, DC. Available:
p.000064: http://www.fda.gov/oc/ohrt/irbs/toc4.html [accessed May 2007].
p.000064:
p.000064: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000064:
p.000064:
p.000065: 65
p.000065:
p.000065: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000065: [accessed 12 June 2007].
p.000065:
p.000065: VanderWalde A (2005). Undue inducement: the only objection to payment? Am J Bioethics 5(5):25-27.
p.000065: Weise KL, Smith ML, Maschke KJ, Copeland L (2002). National practices regarding payment to research subjects for
p.000065: participating in pediatric research. Pediatrics 110(3):577-582.
p.000065:
p.000065: Wendler D, Rackoff JE, Emanuel EJ, Grady C (2002). The ethics of paying for children’s participation in research. J
p.000065: Pediatr 141(2):166-171.
p.000065:
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p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: SECTION 6
p.000066: Building and Maintaining Appropriate Community and Stakeholder Relationships
p.000066:
p.000066:
p.000066:
...
p.000077: Children. Washington, DC. Available: http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=22521.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2005). Guidance on Selecting Age Groups for Monitoring and Assessing
p.000077: Childhood Exposures to Environmental Contaminants. Risk Assessment Forum, Washington, D.C. EPA/630/P-03/003F.
p.000077: Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=146583.
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). Considerations for Developing Alternative Health Risk
p.000077: Assessment Approaches for Addressing Multiple Chemicals, Exposures, and Effects. External Review Draft. 71 FR 16306.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). Paper on Tribal Issues Related to Tribal Traditional Lifeways,
p.000077: Risk Assessment, and Health and Well Being: Documenting What We’ve Heard. The National EPA-Tribal Science Council.
p.000077: Available: http://epa.gov/osp/tribes/tribal/TribalIssues.pdf.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). EPA’s Public Involvement Policy. Available:
p.000077: http://www.epa.gov/publicinvolvement/policy2003/index.htm.
p.000077:
p.000077: U.S. Food and Drug Administration (FDA). Exception from informed consent requirements for emergency research. 21 CFR §
p.000077: 50.24
p.000077:
p.000077: University of Kansas Community Tool Box. Available: http://ctb.ku.edu/en/tablecontents/.
p.000077:
p.000077: University of Washington Community-Campus Partners for Health, Available: http://depts.washington.edu/ccph/index.html.
p.000077:
p.000077: Veazie MA, Teufel-Shone NI, Silverman G, Connolly A, Warne S, King B, et al. (2001). Building community capacity in
p.000077: public health: The role of action-oriented partnerships. J Public Health Manag Pract 7(2):21-32.
p.000077:
p.000077:
p.000078: 78
p.000078:
p.000078: U.S. EPA, Office of Environmental Justice Resources:
p.000078: Executive Office of the President. (1997). Environmental Justice: Guidance under the National Environmental Policy Act.
p.000078: Council on Environmental Quality, pp. 7-17).
p.000078: Available: http://epa.gov/compliance/resources/policies/ej/ej_guidance
p.000078: _nepa_ceq1297.pdf
p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2006). Future mechanisms to enhance stakeholder involvement
p.000078: and engagement to address environmental justice: A letter report. Available:
p.000078: http://epa.gov/compliance/resources/publications/ej/nejac/st akeholder-involv-9-27-06.pdf
p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2004). Environmental justices and federal facilities:
...
p.000093: environmental or biological samples and information for the purpose of quantifying the contact between the
p.000093: participant and the agent being studied. Observational human exposure studies are inherently the process
p.000093: of watching people in context—in their natural environment, doing routine activities—and collecting
p.000093: the
p.000093:
p.000093:
p.000095: 95
p.000095:
p.000095: samples and relevant information from them and from their surroundings to measure and calculate
p.000095: the exposures that occurred in the same context.
p.000095: Scientific Study Design: From a scientific study design perspective, an observational study of the sort
p.000095: being considered in this document is one where the researcher does not control the variables but,
p.000095: rather, observes both the variable and the outcome and tries to infer the relationship between the variable
p.000095: and the outcome. This contrasts with a controlled study where the researcher isolates and controls
p.000095: one or more variables in a systematic way to assess the impact of changes in the variables on an
p.000095: outcome measure. Consider the intervention study examples cited in the section on regulatory
p.000095: distinctions below (cleaning a house to reduce exposure in the residence and wearing a particle mask to reduce
p.000095: exposure to smoke from forest fires). In those cases, participants would be assigned either to receive the
p.000095: intervention (treatment) or not (the control group). The outcomes (exposures) would be measured and compared
p.000095: between the two groups to assess the effectiveness of the intervention. Similarly, drug trials would randomly
p.000095: assign participants to receive either a test medication or a placebo. The medical outcome (e.g., pain
p.000095: relief, blood pressure, cholesterol levels in blood) would then be measured for all participants,
p.000095: and the outcomes compared between the treated group (getting the test medication) and the control
p.000095: group (receiving the placebo).
p.000095: Controlled studies are often desirable in science because, when properly designed, they provide
p.000095: unambiguous estimates of the impact of unique variables on the outcome (even if the impact of one variable could
p.000095: normally be overwhelmed by other factors) and eliminate the need for alternate explanations of
p.000095: the experimental results (because other factors are held constant). However, controlled studies are
p.000095: not always possible. They may be unethical (e.g., to “treat” a group of women with abortions to test if there
p.000095: is a linkage between having had an abortion and breast cancer), impractical (e.g., to follow a cohort large
p.000095: enough to yield statistically significant results in a test of rare side effects to a medication), or just
p.000095: impossible to accomplish (e.g., to measure nutritional levels of a population in the middle of a war zone).
p.000095: As a consequence, much medical research is observational in the scientific sense being considered
p.000095: here. Public health data represent observations of health outcomes, but the factors that may have led
...
p.000113: ACGIH American Conference of Governmental Industrial Hygienists AHS Agricultural Health
p.000113: Study
p.000113: ATSDR Agency for Toxic Substances and Disease Registry BEI biological exposure index
p.000113: CAB community advisory board
p.000113: CBPR community-based participatory research CDC Centers for Disease Control and
p.000113: Prevention CFR Code of Federal Regulations
p.000113: CIOMS Council for International Organizations of Medical Sciences
p.000113: COPR National Institutes of Health Director’s Council of Public Representatives CPSC
p.000113: Consumer Product Safety Commission
p.000113: CTEPP Children’s Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants
p.000113: DEARS Detroit Exposure and Aerosol Research Study DHEW U.S. Department of Health, Education,
p.000113: and Welfare DMOC data monitoring and oversight committee
p.000113: DNA deoxyribonucleic acid
p.000113: DSMB data safety monitoring board DSMP data and safety monitoring plan
p.000113: EHCRB environmental health and community review board EPA U.S. Environmental Protection
p.000113: Agency
p.000113: ERG Eastern Research Group
p.000113: FCN Federal Communicators Network
p.000113: FDA Food and Drug Administration
p.000113: HHS U.S. Department of Health and Human Services HSRB Human Studies Review Board
p.000113: HSRRO Human Subjects Research Review Official
p.000113: HUD U.S. Department of Housing and Urban Development ICR information collection
p.000113: request
p.000113: IOM Institute of Medicine
p.000113: IRB institutional review board
p.000113: NAS National Academy of Sciences
p.000113: NBAC National Bioethics Advisory Commission NCI National Cancer Institute
p.000113: NCS National Children’s Study
p.000113: NEI National Eye Institute
p.000113: NEJAC National Environmental Justice Advisory Council NERL National Exposure Research
p.000113: Laboratory
p.000113:
p.000113:
p.000115: 115
p.000115:
p.000115: NGO Nongovernmental organization
p.000115: NHANES National Health and Nutrition Examination Survey NHAPS National Human Activity Pattern
p.000115: Study
p.000115: NHEXAS The National Human Exposure Assessment Survey NHLBI National Heart, Lung, and Blood
p.000115: Institute
p.000115: NHRPAC National Human Research Protections Advisory Committee NIH National Institutes of
p.000115: Health
p.000115: NRC National Research Council
p.000115: OHRP Office for Human Research Protections OMB Office of Management and Budget OSMB
p.000115: observational study monitoring board PM particulate matter
p.000115: Q&As questions and answers
p.000115: QAPP quality assurance project plan
...
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p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
p.000003: range of risks associated with participation and the voluntary nature of participation, and provides
p.000003: essential protections to the participant. Recent observations by various national and international review
p.000003: committees on the appropriate level of payment to research participants are presented. This is a
p.000003: complex ethical issue, balancing the issue of fairness against the possibility of undue influence
p.000003: and the loss of free consent. Other topics include participant recruitment, retention strategies, research
p.000003: rights, and grievance procedures.
p.000003: Section 6. Building and maintaining appropriate community and stakeholder relationships: Involving
p.000003: the community in the research effort to improve the research both scientifically and ethically.
p.000003: Various approaches are discussed related to issues such as defining the community, identifying who
p.000003: represents the community, recognizing and addressing cultural differences, and the importance of language,
p.000003: power relationships, and partnerships.
p.000003: Section 7. Designing and implementing strategies for effective communication: Ongoing, interactive
p.000003: dialogue among researchers, participants, the community, stakeholders, and the public to
p.000003: establish effective communications and to foster a relationship of trust. To facilitate information dissemination
p.000003: to participants, communities, and stakeholders, this section of the document describes communication
p.000003: strategies, implementation plans, communication groups, timetables, communication materials, and other
p.000003: tools available to researchers.
p.000003: This document does not and, indeed, could not provide solutions to all scientific and ethical issues that may
p.000003: arise as observational human exposure studies are undertaken. No document could identify and address all
p.000003: potential issues in advance, nor is it possible to develop a comprehensive checklist for all such studies.
...
p.000007: (2) that proposed research be reviewed by an independent oversight group referred to
p.000007: as an institutional review board (IRB) and approved only if risks to subjects have been minimized, and
p.000007: risks are reasonable in relation to anticipated benefits, if any, to the subjects and to the importance of the
p.000007: knowledge that may realistically be expected to result.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008: Table 1-1. Examples of the Impact of Observational Human Exposure Studies on Pollution Levels and Regulatory Actions
p.000008: Pollutant Observational Study Result
p.000008: Impact/Action/Result
p.000008:
p.000008: Particulate Matter (PM)
p.000008: Observational panel studies demonstrated the appropriateness of ambient measurement of fine particles as a surrogate
p.000008: for a population’s longitudinal exposure to fine PM.
p.000008: Resolved questions in NAS review of PM science and provided a “generally consistent finding that ambient particle
p.000008: concentrations are a key determinant of the longitudinal variation in personal exposure.” (NRC, 2004). These results
p.000008: have been instrumental in support of the National Ambient Air Quality Standard for PM (U.S. EPA, 1999).
p.000008:
p.000008:
p.000008: Volatile Organic Compounds (VOCs)
p.000008:
p.000008: EPA's Total Exposure Assessment Methodology (TEAM) studies found levels of about a dozen common organic pollutants to
p.000008: be 2- to 5-times higher inside homes than outside. Use of products containing organic chemicals may result in very high
p.000008: and persistent pollutant levels.
p.000008:
p.000008: EPA, States, and the Consumer Product Safety Commission worked together to influence manufacturers to voluntarily
p.000008: reduce emissions of toxic chemicals from consumer products, building materials, and furnishings, and to develop
p.000008: mitigation strategies and educational materials to teach people how to reduce their contact with chemicals indoors. As
p.000008: a result, contact with toxic chemicals indoors has been reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html).
p.000008:
p.000008:
p.000008: Formaldehyde
p.000008:
p.000008: Studies found elevated formaldehyde levels indoors and helped identify indoor sources.
p.000008:
p.000008: EPA worked with HUD, CPSC, and other agencies to limit formaldehyde in building or consumer products and to educate the
p.000008: public on how to reduce exposures (see www. epa.gov/iaq/formalde.html).
p.000008:
p.000008:
p.000008: EPA has adopted additional protections for children and pregnant or nursing mothers in Subparts B through
p.000008: D. These sections apply to all research either conducted or funded by EPA and are, therefore, directly applicable to
p.000008: NERL’s observational human exposure studies.4 Subpart B prohibits EPA from conducting or supporting research
p.000008: that involves intentional exposure of “a pregnant woman (and, thereby, her fetus), a nursing woman,
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
...
p.000029: productivity studies from 1927 to 1932. Similarly, some changes in participant behaviors may change the
p.000029: observations, measurements, and conclusions from observational human exposure studies. For
p.000029: example, participants may do more cleaning in their home because they do not want the researchers to think they are
p.000029: poor housekeepers; this could affect the measurement of environmental concentrations in the home. In a
p.000029: study of chemicals from consumer products, participants may think that because the researchers are
p.000029: studying the products, the products must be harmful. Therefore, study participants may elect not to use the products
p.000029: during the study in the same manner as they would normally. Alternatively, prospective participants may
p.000029: choose to use more of the household product to qualify for the
p.000029: study. As a result, the participant’s exposure to the chemicals could be either more or less than “normal.”
p.000029: Any change in a participant’s behavior that is related to the research question being addressed in the study
p.000029: may impact the study results. Researchers should try to anticipate how a study may impact participant behaviors and
p.000029: ensure that the study design and implementation protocols do not cause changes in behavior that may cause
p.000029: harm to a participant during a study. A number of study elements with the potential to influence
p.000029: participants’ behavior are listed in Text Box 2-6.
p.000029:
p.000029: Text Box 2-6. Study Elements That Could Affect People’s Behavior
p.000029: • Eligibility criteria
p.000029: • Recruiting approach and materials
p.000029: • Enrollment approach
p.000029: • Payments
p.000029: • Retention strategy
p.000029: • Types of measurements made and data collected
p.000029: • Protocols for data collection
p.000029: • Protocols for visits to homes
p.000029: • Interactions with participants
p.000029: • Communications
p.000029:
p.000029:
p.000029: It is very difficult to predict in advance how these elements may be interpreted and acted on by
p.000029: the participants. Researchers may learn from the experiences of others, including the “lessons learned” from
p.000029: experts and their publications. They may wish to engage the community representatives (see Section 6) in a
p.000029: thorough discussion of the issue. Community-based focus groups or pilot studies also may demonstrate how the
p.000029: various elements of the study may have an unintended impact. Additionally, researchers can be very careful
p.000029: in the informed consent process (see Section 5.1), to ensure that participants not only know, but that they
p.000029: understand the facts of the study (Gilbert, 2006), and that they comprehend that the goal is to observe and
p.000029: measure the participant’s exposures during their normal, everyday activities.
p.000029:
p.000029: 2.8 Criteria and Standards for Monitoring Scientific and Ethical Issues
p.000029: Ethical requirements do not end when the participants sign the consent form and agree
...
p.000037: justification if children will be excluded from a research study. Of course, as discussed above, if the research
p.000037: topic is irrelevant to children, the CIOMS guidelines would recommend that they be excluded from the
p.000037: research.
p.000037: Observational human exposure studies conducted by NERL are not expected to involve greater than minimal risk. It
p.000037: will be the responsibility of the NERL researchers to present adequate information for the IRB to
p.000037: demonstrate that the research does not involve greater than minimal risk. Researchers designing observational
p.000037: research studies should carefully evaluate the risks and benefits specific to their study and the
p.000037: participants involved. In developing the study design and human subjects protocols, researchers need to
p.000037: ensure that the protocols ensure the protection of the rights and welfare of the participant children, and that
p.000037: risks and harm are minimized. The perception of risks and benefits, both by
p.000037: the individual and by the family or community, may influence the risk-benefit determination. It may prove
p.000037: useful for the research team to consult with other experienced researchers who have conducted
p.000037: similar studies and with members of the IRB to ensure that the information included in the human subjects
p.000037: research protocol is adequate for the IRB’s review.
p.000037: It is recommended that researchers consider all of the potential issues associated with involvement
p.000037: of children in their studies in developing the study design and research protocols, including the role of the
p.000037: family. EPA’s human subjects rule for observational research not involving greater than minimal risk to
p.000037: children (40 CFR 26.404) (i.e., the kinds of observational human exposure studies that NERL exposure research
p.000037: is likely to entail) focuses on obtaining assent of the children and permission of their parents or guardians. But the
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
...
p.000050: the document.
p.000050: This relationship should be established on the ethical values of respect for the participant’s autonomy and
p.000050: respect for their welfare. Emanuel and his co-authors find that these two ethical values translate into
p.000050: specific responsibilities for an ethical researcher in regard to informed consent and respect for potential and
p.000050: enrolled subjects (Emanuel et al., 2000). They describe the ethical principles for these responsible actions thusly,
p.000050: “Respect for potential and enrolled subjects is justified by multiple principles including beneficence,
p.000050: nonmaleficence, and respect for persons. Permitting subjects to withdraw and providing them additional information
p.000050: learned from the research are key aspects of respecting subject autonomy. Protecting confidentiality and monitoring
p.000050: well-being are motivated by respect for persons, beneficence, and nonmaleficence.” Section 4 already has
p.000050: described some of the particular concerns regarding privacy, confidentiality, and other issues
p.000050: related to observational human exposure studies. This section further describes elements of the relationship
p.000050: between researchers and participants that are important to consider and address during design and
p.000050: implementation of a study.
p.000050: Of course, the relationship between the researchers
p.000050: and the individual participants does not exist in isolation. The researcher-participant relationship may influence
p.000050: and be influenced by the relationship with the community in which the participant lives.
p.000050: Good, two- way communications are critical for the development and nourishment of an appropriate
p.000050: researcher-participant relationship. Although those two topics are the subject of the next sections of this document,
p.000050: elements from those topics unavoidably will color the discussions in this section as well.
p.000050: Researcher training is a key component for conducting research that incorporates human
p.000050: subject protections and fosters appropriate researcher-participant relationships. Most organizations require basic
p.000050: human subjects training on the essential elements for processes and procedures for research with human subjects. More
p.000050: in-depth training will improve researcher understanding in areas of the informed consent process, observational
p.000050: techniques, community-based research, and other topic areas. Such training will benefit principal
p.000050: investigators throughout the research study from the design stage through communication of research results.
p.000050: Training is also important for staff that will work directly or indirectly with research participants
p.000050: or their samples and data. This document can be used as both a training tool for researchers as well as a
p.000050: resource for designing training courses. There are a number of sources of training on human
p.000050: subjects protection. The Collaborative Institutional Training Initiative (CITI,
...
p.000051: Ethics Review Boards should ensure that the focus of both the informed consent process and the consent forms is on
p.000051: informing and protecting participants, not the research institution.
p.000051: (2) Strengthen Process of Parental Permission and Children’s Assent if Children Are Involved in Research (NRC & IOM,
p.000051: 2005)
p.000051: The process begins with a community-based discussion and concludes with an assurance that individual parents understand
p.000051: the essential elements of the research.
p.000051: Educate parents on issues critical to informed decision making and assess their degree of understanding.
p.000051: Use informational materials in the form that is most appropriate to convey information to potential participants.
p.000051: Consult with community representatives to ensure that information is complete, clear, and understandable, and that any
p.000051: payment will not be exploitive.
p.000051: Expand the perspective about what information about risks and benefits is needed to make an informed choice.
p.000051: Ethically, it is critical to assure that participants and parents understand the crucial features of the research
p.000051: effort.
p.000051: (3) Informed Consent Is a Decision To Participate by an Informed, Competent Individual Without Undue Coercion,
p.000051: Influence, or Intimidation (CIOMS, 2002)
p.000051: Informed consent is a process that takes time and resources.
p.000051: It is not a ritual recitation of text from a form but informative communication in language that suits the individual’s
p.000051: level of understanding.
p.000051: Consent is ethically obtained, considering language and cultural issues, and is documented.
p.000051: Material changes in conditions or procedures require that informed consent be renewed.
p.000051: Consent should explain how samples will be used in current research, and, if applicable, how samples may be used in
p.000051: future research.
p.000051:
p.000051:
p.000051:
p.000051: 5.1.1 Information
p.000051: Some items that researchers should keep in mind as they provide information to the study participants are
p.000051: summarized below. These items may be based on regulatory requirements or currently may
p.000051: be recommendations as ethical “best practices.”
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: Text Box 5-2. Common Rule Requirements:
p.000052: Elements of Informed Consent
p.000052: (1) An explanation of the purposes of the research
p.000052: (2) The expected duration of the subject's participation
...
p.000055: 2000; VanderWalde, 2005; Weise et al., 2002; Wendler et al., 2002). A number of specific issues or
p.000055: concerns regarding participant payments have been identified. Many researchers and ethicists argue that it
p.000055: is often appropriate to provide reasonable payment and have done so for many years. In the view of an NRC expert
p.000055: panel, the principles of “justice, fairness, and gratitude support payment to those who bear the burdens
p.000055: of research on behalf of society” (NRC, 2004).
p.000055: Direct reimbursement may be made to participants for out-of-pocket expenses for costs directly associated
p.000055: with participation in a study. These might include transportation costs, parking fees, or child
p.000055: care costs. When payment for time and burden is provided, it is often in the form of monetary
p.000055: payments. Different approaches may be considered for determining reasonable amounts for payment,
p.000055: including a set payment for each visit, a small daily payment, payment at the prevailing minimum hourly
p.000055: wage, or payment at some other hourly rate appropriate for the community⎯perhaps a
p.000055: prevailing rate for unskilled labor (Emanuel, 2004). Incentives to encourage enrollment are
p.000055: sometimes used when participants will receive little or no direct benefit from the research and can take
p.000055: the form of monetary or non-monetary payments. Incentives are kept modest so as not to impart undue
p.000055: influence. Researchers need to consider the possible effects of incentive payments on the potential
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056:
p.000056: Text Box 5-3. Payments for Participation of Research Subjects
p.000056: (based on Grady, 2005)
p.000056: Payment Serves As Amount Determined By Potential Advantages
p.000056: Potential Disadvantages
p.000056:
p.000056: Incentive Supply and demand; market rates
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Compensation Standardized “wage” for time and effort, suggested to be commensurate with wages for
p.000056: unskilled, but essential jobs; additional payment for extra burdens such as endurance of uncomfortable procedures
p.000056: (a) More rapid recruitment
p.000056: (b) Completion bonuses encourage subject retention and high completion rate
p.000056: (c) Possibility of profit for participants
p.000056: (d) Little or no financial sacrifice by subject
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: (a) Recognizes contributions of participants
p.000056: (b) Uniform payment across studies
p.000056: (c) Equal pay for equal work
p.000056: (d) Less risk of undue inducement
p.000056: (a) Undue inducement possibly resulting in incomplete assessment of risks and benefits by subject; subject concealing
p.000056: information to ensure enrollment and retention
p.000056: (b) Competition between studies; better funded studies more likely to meet recruitment goals
p.000056: (c) Different levels of payment at different locations for multicenter research because of supply and demand
p.000056: (a) May have little impact on recruitment
...
p.000056: differences in payment levels have been found even in multisite studies in which the same protocol is
p.000056: administered across all sites.
p.000056: Grady et al. (2005) performed a survey of practices for paying research participants in the United States in
p.000056: Phase 1 to 4 clinical trials and physiologic, behavioral, and other types of research. Across 467
p.000056: studies of varying complexity that included payments, the median
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: payment was $155 (mean $266, range $5 to $2,000). The basis for dollar amounts was infrequently described, with
p.000057: 19% of the payments based on time, and 12% based on the procedures. In a model of payment factors,
p.000057: studies with some prospect of therapeutic benefit, studies having at least one invasive procedure, and studies with
p.000057: greater numbers of clinic visits were significantly associated with higher dollar amounts. About 9.5%
p.000057: of the studies offered completion bonuses, and a similar percentage offered escalating payments for
p.000057: followup study visits.
p.000057:
p.000057: 5.2.2 Regulations and Guidance Regarding Payment to Research Participants
p.000057: There is little specific guidance regarding payments in Federal human research regulations. The Common Rule and
p.000057: additional human subjects protections do not directly address payments to research participants, but the
p.000057: regulations do discuss providing additional safeguards for subjects vulnerable to coercion or undue
p.000057: influence [40 CFR 26.111(b)]. The NIH IRB guidebook advises IRBs to determine whether the rewards offered for
p.000057: participation in research constitute undue influence (U.S. HHS, 1993). According to the IRB guidebook undue
p.000057: inducement might blind prospective subjects to risks, impair their ability to exercise proper judgment, or may
p.000057: cause people to lie or to withhold information that would make them ineligible to enroll or continue
p.000057: participation.
p.000057: The U.S. Food and Drug Administration (FDA) has provided guidance for investigators and IRBs for clinical research
p.000057: studies (FDA, 1998). The guidance states that “payment to research subjects for participation in studies is not
p.000057: considered a benefit, it is a recruitment incentive.” FDA expects payments to accrue as the study progresses and not
p.000057: to be contingent on completing the study, although a “small proportion as an incentive for
p.000057: completion of the study is acceptable.” The guidance is concerned with the issue of coercion or undue influence, and
p.000057: it recognizes the IRB as the responsible party for deciding what is or is not acceptable.
p.000057: The U.S. Office of Management and Budget (OMB) develops standards and guidelines for statistical surveys performed by
p.000057: the Federal government. Under Guideline 2.3.2, OMB states that, while incentives are not typically used in Federal
p.000057: surveys, agencies may consider use of respondent incentives if they believe incentives would be necessary
p.000057: to use for a particular survey to achieve data of sufficient quality for their intended use (OMB,
...
p.000060: duplicate diet samples; collection of environmental samples inside and outside the home; completing
p.000060: questionnaires, food diaries, and time- activity diaries; and providing urine, blood, saliva, or hair
p.000060: samples. Monetary payments often have been included in these studies, with the level of payment
p.000060: related to the number of study days or visits or the specific kinds of environmental and biological
p.000060: samples and information that are collected or provided. Payment for direct participant costs has been included
p.000060: in some studies, such as a reasonable payment for providing researchers with duplicate diet samples.
p.000060: NERL scientists should review the commentary and recommendations in the literature before devising a
p.000060: payment program as part of a research protocol, especially the two recent National Academies of Science
p.000060: documents, Ethical Issues in Housing-Related Health Hazard Research Involving Children (NRC and IOM, 2005)
p.000060: and Ethical Conduct of Clinical Research Involving Children (IOM, 2004). They should seek
p.000060: guidance from EPA’s HSRRO to determine EPA’s latest policies and guidance in this regard. Input also should be sought
p.000060: from community representatives to ensure that any payment is adequate to compensate for expenses and reward
p.000060: participation, but that the payment is not so high as to constitute undue influence or coercion in the
p.000060: community. If the study includes several followup visits over a long term, NERL researchers should ensure that payment
p.000060: is made incrementally as the NRC & IOM committee suggested. NERL scientists also should adopt the IOM
p.000060: Recommendations 6.1 and 6.2, including ensuring that any payment should be for appropriate purposes
p.000060: and age-appropriate, and that the process should be open and fully disclosed, while not overly
p.000060: emphasizing payments during the recruiting or informed consent phases. The final decisions about the ethics of
p.000060: payments rest with the IRB, which will review, modify as needed, and approve the research protocol, and with the EPA
p.000060: HSRRO, who has final authority to approve, modify, or disapprove all of NERL’s human subjects research
p.000060: efforts.
p.000060: 5.3 Research Rights and Grievance Procedures
p.000060: Protecting the research rights of participants and providing independent access to information regarding
p.000060: those rights and to grievance procedures is an important element in developing and maintaining appropriate
p.000060: participant-investigator relationships. As part of the informed consent process, the Common Rule
p.000060: requires “An explanation of whom to contact for answers to pertinent questions about the research and
...
p.000062: Some of the common strategies for maintaining high retention rates in longitudinal studies are listed in Text
p.000062: Box 5-6.
p.000062:
p.000062: Text Box 5-6. Common Strategies for Maintaining High Retention Rates in Longitudinal Studies
p.000062: • Developing and maintaining a strong study identity
p.000062: • Building participant trust
p.000062: • Communicating regularly with participants
p.000062: • Providing feedback that is of use to participants
p.000062: • Maintaining confidentiality
p.000062: • Incorporating active participant tracking mechanisms
p.000062: • Maintaining reasonable levels of burden
p.000062: • Providing periodic tokens of appreciation
p.000062: • Providing reasonable levels of payment at each time point, sometimes including escalating payments or a higher
p.000062: final payment for completion of all study activities
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000063: 63
p.000063:
p.000063: It is important that strategies that use payments to encourage retention should be carefully
p.000063: scrutinized against the possibility that they will result in undue influence or diminish voluntary
p.000063: participation. Payments that cover expenses and for time and burden at each visit have to be reasonable, and
p.000063: researchers and IRBs should consider whether the cumulative level of payments over time or the use of escalating
p.000063: payments or final bonus payments might present undue influence on decisionmaking regarding
p.000063: participation. Participants have to feel capable of withdrawing from participation at any time, and escalating
p.000063: payments or completion bonuses can impact decisions to withdraw. Withholding all payment until all study
p.000063: visits are completed or making payment contingent on completing all activities is not an acceptable practice in
p.000063: most longitudinal studies because it can diminish the capacity for voluntary participation. (See the
p.000063: discussion about payment issues in long-term studies in Section 5.2.3.)
p.000063: People are more likely to continue active participation in longitudinal studies when they
p.000063: believe that the research is important, and that they are making a valuable contribution, are receiving regular
p.000063: feedback, and are treated with courtesy and respect by researchers. Observational human exposure studies
p.000063: sometimes involve substantial burdens of time and effort. Over long periods, this level of burden can reduce retention.
p.000063: It may be necessary to develop novel methods that reduce participant time and effort or to focus the study
p.000063: design so that fewer study procedures are implemented at any time point. Because the time needed to analyze
p.000063: samples, verify results, and perform data analyses can be long, it may be difficult to provide timely
p.000063: feedback to participants in observational human exposure studies. Researchers might consider including
p.000063: simple measures that can provide immediate and useful information of value to participants to
p.000063: encourage continued participation. Effective use of these strategies will reduce the need for
...
p.000067: “outsiders.” To help alleviate these potential issues, researchers should ensure an equitable
p.000067: distribution of paid research work among different communities within the larger community as to not promote a
p.000067: perceived bias among community members. Additionally, when possible, researchers should make efforts
p.000067: to provide payments to community members employed as research staff through community partner
p.000067: organizations to prevent conflict of interest issues. Refer to Section 5 for further discussion on
p.000067: remuneration of community members as research participants.
p.000067:
p.000067:
p.000067: Text Box 6-2. Community Engagement Principles for Researchers
p.000067: (From CDC, 1997)
p.000067: Requirement Explanation
p.000067:
p.000067: Clarity Clear communication of the study objectives, research goals, and the populations or
p.000067: communities of interest.
p.000067:
p.000067: engaging communities in health-related research (see Text Box 6-2). Health research is a “privileged and
p.000067: empowered activity in that the researchers have special
p.000067: Knowledge of the Community
p.000067: Familiarity with the economic conditions, political structures, demographics, history, past research experiences, and
p.000067: research perceptions of the community.
p.000067:
p.000067: access to resources and sensitive information about people and, through the analysis and presentation
p.000067: of findings, are able to influence the way people think and have considerable influence on decisions regarding
p.000067: the allocation of resources” (CDC, 1997). Regardless of the approach utilized to involve the community in research,
p.000067: whether the process employs community-based participatory research (CBPR) or another community
p.000067: engagement method, researchers should guide their interactions with community members using these
p.000067: underlying principles to promote the aforementioned ethical principles of respect of persons, fairness, and
p.000067: beneficence.
p.000067: One form of community involvement is to include qualified members of the community on the research staff.
p.000067: Section 2 advocates community representatives as part of the research team. Paid research staff members from
p.000067: the community could serve as valuable consultants for protocol development and research design, including how to
p.000067: collect the data, how to recruit and retain participants, and how to interpret and disseminate the
p.000067: results. However, including paid research staff from the community may introduce a conflict of interest among
p.000067: community members: community representatives may feel a greater allegiance to the researchers providing the payment
p.000067: and be less inclined to uphold the interests of the community. In addition, the community may come to view
p.000067: the paid research staff from the community as
p.000067: Visibility Travel to the community, interact with formal
p.000067: and informal leadership, and establish relationships to build trust.
p.000067:
p.000067: Acceptance Acknowledge, without judging, the assets and deficits of the community.
p.000067:
...
p.000069: governmental agencies, and academia. The CAAA partnership credits community involvement as active research
p.000069: partners in the research process with the success of the project to acquire “more relevant exposure data for
p.000069: the study of children in urban neighborhoods” and to provide “immediate knowledge and understanding of the outcomes
p.000069: and results of the combined environmental health analysis to the communities” (Keeler et al., 2002). There are,
p.000069: however, several drawbacks to utilizing CBPR methods that researchers should consider before developing a
p.000069: CBPR project. CBPR is time consuming (develop partnership, establish and agree on research aims and
p.000069: objectives, disseminate results to the community using appropriate methods, and review
p.000069: manuscripts and presentations) and not conducive to situations where rapid decisions are necessary given a
p.000069: tight timeline. Weighing the research need versus the community’s desire for an intervention is the
p.000069: greatest source of tension in conducting CBPR (Israel et al.,
p.000069: 2005b).
p.000069: One additional opportunity for community input may involve participation on an IRB. IRBs are required by the
p.000069: Common Rule to have members who are sensitive to “community attitudes” [40 CFR 26.107(a)]. How they meet this
p.000069: obligation is totally at their discretion, and NERL researchers have no influence. There have been a number of
p.000069: recent articles in the literature about IRBs that have envisioned a need for more regulatory reform
p.000069: (Ledford, 2007). Ideally, the IRB should take into account the views of the community. Quinn
p.000069: (2004) argues for extending protections now reserved for individuals to groups (populations and
p.000069: communities) through CABs. Her argument is that there are “ethical issues related to research with
p.000069: communities that are distinctly different from the ethical issues related to research with individuals.”
p.000069: CAB members have to be educated on human subjects’ protections, should represent their communities
p.000069: honestly, and need to be willing to interact with researchers on complex research issues.
p.000069: Gilbert (2006) goes even further. He suggests supplementing or even replacing traditional IRBs with
p.000069: environmental health and community review boards (EHCRBs). He argues that traditional IRBs
p.000069: are inadequate for the review of community-based research because they were developed to address issues related to
p.000069: individuals involved in research projects, not communities. He proposes EHCRBs that combine
p.000069: the fundamental and ethical concept of traditional IRBs with an expanded ethical construct of dignity,
p.000069: veracity, sustainability, and justice, with added emphasis on community. He envisions that an
p.000069: EHCRB would function as an IRB with the requirements and responsibilities for review for the
...
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
p.000070: sense of community was nurtured among the farmworkers collectively (O’Fallon and Dearry, 2002).
p.000070: Understanding and describing a community (CDC, 1997) involves exploring factors related to
p.000070: • people (including socioeconomics and demographics, health status, and cultural and ethnic characteristics),
p.000070: • location (geographic boundaries),
p.000070: • commonalities (including shared values, interests, and motivating forces), and
p.000070: • power relationships (including formal and informal lines of authority and influence, stakeholder relationships, and
p.000070: resource flows).
p.000070: It is important to distinguish between stakeholders and the community, but both should be engaged at some point
p.000070: in the course of a study. Stakeholders are groups or organizations that may affect, be affected by, or perceive
p.000070: themselves to be affected by a decision or activity. Stakeholders may have a direct or indirect interest in the
p.000070: “matter” of interest. They may include individuals; environmental, social, or community
p.000070: nongovernment organizations (NGOs); government entities; businesses; and industry. Stakeholders include
p.000070: business, industry, and various levels of government. A critical difference between the community and
p.000070: stakeholders is that the community has a right to speak for its own interests, but stakeholders cannot
p.000070: represent or speak for the community. Although relationships with stakeholders can, at times, be
p.000070: confrontational, stakeholders often provide useful information and expertise. When stakeholders
p.000070: and the community members overlap in particular individuals, it is important to distinguish the role in
p.000070: which the individual is acting (ERG, 2007).
p.000070:
p.000070: 6.2.2 Identifying Who Represents the Community
p.000070: To sufficiently represent the community, an individual has to have not only the right to speak for the
p.000070: community’s interests (a right afforded by legitimate membership in the group) but also should be able
p.000070: to describe those interests on behalf of the community. Identifying those who represent the community is
p.000070: not simply a matter of identifying the most vocal activists because those individuals do not necessarily
...
p.000071: trust with all partners, and the establishment of the agreement helps reduce misunderstandings.
p.000071: Contracts or memorandums of understanding that outline the roles and expectations of the researcher and the
p.000071: community are discussed in both Minkler and Wallerstein (2003) and Israel et al. (2005b). An example
p.000071: outlining expectations in a partnership with tribal communities is presented in Appendix E of Minkler and
p.000071: Wallerstein (2003), whereas an example discussing access to data and authorship issues is presented
p.000071: in Appendix I of Israel et al. (2005b). An example of a memorandum of understanding between the
p.000071: University of Michigan School of Public Health, Detroiter’s Working for Environmental Justice, the Detroit
p.000071: Hispanic
p.000071:
p.000071:
p.000071:
p.000071: 23 For a more detailed description of each of the suggestions for enhancing trust, please see Chapter 3 of Israel et
p.000071: al. (2005).
p.000071:
p.000072: 72
p.000072:
p.000072: Development Corporation, and the Warren Conner Development Coalition for a study investigating asthma is
p.000072: available at http://depts.washington.edu/ccph/pdf_files
p.000072: /MOU10.pdf.
p.000072: Work within communities involves a considerable investment of researchers’ and residents’ time. It should be an
p.000072: ongoing, interactive exchange of information and ideas between the researchers and the community members,
p.000072: where voices are both heard and honored. Trust is fostered when all interested parties feel that they have
p.000072: influence, and that their input contributes to the community effort. The collaborations should be
p.000072: inclusive of the entire community, including those members with incompatible interests and perceptions. If
p.000072: participation, influence, and benefits are limited only to some of the partners, then distrust is likely, and
p.000072: the potential benefits of community involvement may be lost. Being inclusive can create some
p.000072: organizing challenges, but the benefit of effective community involvement “has the potential to
p.000072: lead to greater understanding of community perspectives of the risk and benefits of research, improve informed
p.000072: consent, increase study enrollment, enhance data validity and quality, and build trust for research” (NRC & IOM, 2005).
p.000072:
p.000072: 6.2.4 Importance of Language and Communications with the Community
p.000072: Even when all partners and community members are speaking the same language, some terms are not
p.000072: necessarily understood by all. Communications with participants should be reviewed by all partners to ensure
p.000072: that the language used will be appropriate for all participants. At times, one method to
p.000072: communicate research findings will not fit all community members and partners. Even among the partners,
p.000072: understanding each other’s meanings is essential, so that all partners can move forward with a common
p.000072: understanding (Israel et al., 2005b).
p.000072: Furthermore, Minkler and Wallerstein (2003) note that “research must be produced, interpreted, and
p.000072: disseminated to community members in clear, useful, and respectful language.” Researchers, and especially
...
p.000073: communication plan was integral to the success of the study. Eighty percent of the original participants
p.000073: completed the four- season study (Williams et al., 2003).
p.000073:
p.000073: 6.2.6 Honesty, Power Relationships, and Partnerships
p.000073: The NRC & IOM report (NRC & IOM, 2005) describes a relational paradigm that acknowledges that research
p.000073: is part of a broader societal context, with the conduct of research often mirroring a system in which
p.000073: power is unequally and perhaps unfairly distributed. The trust and mutual commitment required from
p.000073: the researchers and the community are subject to the overall power relations in society.24 The Expert Panel convened to
p.000073: discuss the content of this document recognized that
p.000073:
p.000073:
p.000073: 24 A discussion of the evolution of theories on power relations, including the contribution of feminism,
p.000073: poststructuralism, and postcolonialism, can be found in Minker and Wallerstein (2003, Chapter 2).
p.000073: the researchers have a variety of forms of power that needed to be understood and acted on ethically
p.000073: (ERG, 2007). One form of power is resources, both funds and access to resources and decisionmakers. Other forms of
p.000073: power may be more subtle, including expertise, which can intimidate or limit a participant’s choices.
p.000073: Peer pressure, fear of intimidation, expectations of benefits from the research, and power to
p.000073: stigmatize the community all, whether real or perceived, can influence the relationship between the
p.000073: researcher and the community. Many forms of power may be tipped toward the researcher, but the community often
p.000073: has power in the form of knowledge about the community that can impact the quality of the research effort. An ethical
p.000073: balance of power can lead to benefits for all partners (ERG, 2007).
p.000073: In describing principles in Methods in Community- Based Participatory Research for Health, Israel et al.
p.000073: (2005b) describe CBPR as facilitating “a collaborative, equitable partnership in all phases of research,
p.000073: involving an empowering and power-sharing process that attends to social inequalities.” One way to address the
p.000073: inequities is to ensure that the roles and responsibilities are mutually acceptable to all parties.
p.000073: Researchers involved in CBPR should recognize and address the inequalities, thereby promoting trust, mutual
p.000073: respect, open communication, information sharing, collaborative decisionmaking, and resource sharing.
p.000073: It is important that researchers recognize that partnerships with the community are ongoing processes that
p.000073: need to be monitored and maintained. As a study progresses, the dynamics of the partnership may change as roles
p.000073: and responsibilities for the partners change. All partners need to be willing to make the investment of time
p.000073: and resources necessary to maintain an effective partnership.
p.000073:
p.000073: 6.2.7 Building a Lasting Infrastructure
p.000073: Infrastructure is anything that builds the capacity of the community by providing its members with skills and
...
p.000095: is a linkage between having had an abortion and breast cancer), impractical (e.g., to follow a cohort large
p.000095: enough to yield statistically significant results in a test of rare side effects to a medication), or just
p.000095: impossible to accomplish (e.g., to measure nutritional levels of a population in the middle of a war zone).
p.000095: As a consequence, much medical research is observational in the scientific sense being considered
p.000095: here. Public health data represent observations of health outcomes, but the factors that may have led
p.000095: to or influenced those outcomes are not under the control of any researcher. Observational techniques long
p.000095: have been
p.000095: used in medical studies to infer information about the impacts of certain factors on health
p.000095: outcomes. Commonly used techniques include cohort studies, case- control studies, cross-sectional studies, case
p.000095: reports, case series, and descriptive studies (NEAC, 2006; Vandenbroucke et al., 2007).
p.000095: Observational human exposure studies as used in this document are considered to be observational from a
p.000095: scientific study design perspective because the variables leading to exposure are not controlled by the researchers.
p.000095: Most of the observational human exposure studies conducted by NERL to date have been cross-sectional
p.000095: studies (sometimes repeated several times). While a particular variable may not be controlled by
p.000095: the researcher, the study design (e.g., selection of the population to be studied, location of the
p.000095: research, data selection to exclude confounding factors) can sometimes influence the range of values over which a
p.000095: variable may be observed. For example, NERL’s observational human exposure studies to understand exposure to PM
p.000095: (see www.epa.gov/heasd/sources/projects_completed/pm_pa nel_studies.htm and www.epa.gov/heasd/sources/project
p.000095: s/a3a_understanding_airshed_sources.htm) have traditionally excluded homes with smokers from the
p.000095: study population to avoid cigarette smoke as a confounding factor in the studies.
p.000095: Observational Studies in Market Research, Ethnography, and the Common Vernacular:
p.000095: Observational market research can involve covert observation, overt observation, or
p.000095: researcher participation. Covert observation is said to have a “key advantage” that “the respondent or consumer is
p.000095: unaware that they are being observed, allowing their behavior to be observed naturally”
p.000095: (see http://www.asiamarketresearch.com/glossary/observatio nal-research.htm). This means that the
p.000095: subject’s behavior will be natural and uncontaminated by the researcher’s presence. On the other hand, covert
p.000095: observation may be construed to be deceitful and ethically questionable. Overt observations involve
p.000095: sampling surveys, polls, interviews, focus groups, etc. Validity of the data obtained this way may
p.000095: be shaded by people’s natural tendency to behave or respond ideally when they know they are being watched.
p.000095: Motorists routinely slow down when they think they are being observed by the police. Finally, the researcher may
p.000095: participate in the activity being observed. Ethnography is a long-term investigation of a group
...
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p.000006: and Childress, 2001). Ethical obligations have to be carefully considered as they relate to the
p.000006: scientific elements of these studies. Therefore, it is important that researchers recognize and understand these
p.000006: obligations and use the most up-to-date scientific and ethical approaches in the design and
p.000006: implementation of observational human exposure studies.
p.000006:
p.000006: 1.1 Observational Human Exposure Studies As we are using the term in this document, “observational
p.000006: human exposure studies” are studies that involve the collection of environmental samples, data, and
p.000006: information from study participants in their everyday environments as they go about their normal
p.000006: activities. These are studies where the NERL researchers do not intentionally try to control the study variables or
p.000006: outcomes, but instead merely observe both the variables and the outcomes. They involve neither the deliberate
p.000006: exposure of participants nor the control of environmental conditions in a way that impacts the
p.000006: participants’ naturally occurring exposures. This scientifically based definition needs to be distinguished
p.000006: at the outset from the broader regulatory term “observational” so that the scope and limits of this
p.000006: document are clear. EPA Regulation 40 CFR 26 (Protection of Human Subjects) at Subpart B, first, defines
p.000006: research involving intentional exposure of a human subject as “a study of a substance in which the exposure to the
p.000006: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000006: participation in the study” [40 CFR 26.202(a)]. It then goes on at Subpart C to define observational research as “any
p.000006: human research that does not meet the definition of research involving intentional exposure of a human
p.000006: subject” (40 CFR
p.000006:
p.000006:
p.000007: 7
p.000007:
p.000007: 26.302). By defining “observational” so broadly, a regulatory category is created that encompasses a range
p.000007: of study types whose only common feature is that they do not entail “intentional exposure” as defined in the
p.000007: regulations. Moreover, some of these “observational” study types do not involve the study of exposures at all but
p.000007: rather “observe” other sorts of phenomena. The observational human exposure studies with which we are concerned
p.000007: here, on the other hand, are exposure studies, but they represent a narrower group of studies as defined scientifically
p.000007: at the beginning of this paragraph. Although they would generally be expected to fall within the
p.000007: regulatory category of “observational research”, they are not synonymous with it. (For a more thorough
p.000007: discussion of the scientific and regulatory meanings of observational and exposure, with examples, please
p.000007: see Appendix A.)
p.000007: Observational human exposure studies are performed for many different purposes. They have been used
p.000007: extensively in the fields of social behavioral, economic, biological, medical, epidemiological, and
p.000007: exposure research to collect information that relates one or more variables (e.g., exposure to a chemical) to
...
p.000096: definition of an observational study, because the variable being studied, exposure to some agent, is not controlled by
p.000096: the NERL scientists. The observations are not covert, and they may or may not be noninvasive (e.g.,
p.000096: sometimes blood samples may be collected).
p.000096: Because NERL’s observational human exposure studies meet the definition of human subjects research as set forth
p.000096: in the Common Rule, there is also a regulatory requirement to meet the ethical and scientific standards set forth in
p.000096: EPA’s human subjects regulations and in Agency rules. The research protocol must be evaluated and approved
p.000096: by an IRB and by EPA’s Human Studies Research Review Official (HSRRO) before any human subjects research effort
p.000096: can take place. But, even more compelling to NERL managers and scientists is the fact that NERL cannot
p.000096: conduct observational human exposure studies without the participation of willing individuals. Indeed,
p.000096: without the research participants, NERL’s human exposure research would be nothing. This intimate
p.000096: involvement of research subjects in NERL’s research imposes moral and ethical obligations to deal with
p.000096: participants respectfully and to ensure their safety, protection, and well-being.
p.000096: Regulatory Distinction Between Intentional Exposure and Observational Research
p.000096: Intentional Exposure: The CFR states, “Research involving intentional exposure of a human subject
p.000096: means a study of a substance in which the exposure to the substance experienced by a human
p.000096: subject participating in the study would not have occurred but for the human subject’s participation in
p.000096: the study” [40 CFR 26.202(a)]. This definition sets forth two requirements regarding an
p.000096: intentional exposure: (1) the exposure has to be to a substance that is being studied, and (2) at least one
p.000096: aspect of the exposure to the substance being studied has to be attributable to the subject’s
p.000096: participation in the study.
p.000096: The first requirement means the objective of the study must be to understand the impact or exposure of
p.000096: the substance being studied. In observational human exposure studies, like those that NERL conducts, the
p.000096: research protocol may require the use of isopropyl alcohol or some other chemical to collect a
p.000096: personal sample (e.g., to sterilize the puncture site immediately prior to collection of a personal sample of
p.000096: blood drawn by a trained phlebotomist). Indeed, it would be both unethical and bad medical practice not
p.000096: to sterilize the puncture site before drawing blood. But this requirement does not constitute intentional
p.000096: exposure because the research is not the study of isopropyl alcohol but of some other agent. Incidental
p.000096: exposures to chemicals like isopropyl alcohol still must be considered from a safety perspective, pass both scientific
p.000096: and ethical review, and be approved by the IRB, but such incidental exposures do not constitute intentional
p.000096: exposure.
p.000096: The second requirement is that the exposure as experienced by the subject “would not have occurred but for the
p.000096: human subject’s participation in the study.” The two primary ways in which intentional exposure studies commonly meet
p.000096: this definition are by the direct introduction of the study substance into the research environment
p.000096: under the control of the research protocol or by scripting the participants’ activities in such a way that their
p.000096: contact with the study substance is determined by the research. Although either would be sufficient to meet
p.000096: the regulatory definition, many, if not most, intentional exposure studies attempt to control both.
p.000096: Because “exposure is quantified as the concentration of the agent in the medium in contact integrated over the
p.000096: time duration of that contact,” intentional exposure studies are usually more scientifically robust if both
p.000096: the concentration of the agent and the duration of the exposure are controlled by the research.
p.000096:
p.000096:
p.000096:
p.000097: 97
p.000097:
p.000097: Observational Research: In the language of the Code of Federal Regulations, “observational research means
p.000097: any human research that does not meet the definition of research involving intentional exposure of a
p.000097: human subject” (40 CFR 26.302).
p.000097: By this definition, observational research encompasses all human research that does not meet the
p.000097: definition of intentional exposure. As a consequence, it is a broad regulatory category that includes a variety of
p.000097: research domains, including human research that does not involve the study of exposures at all. This regulatory
p.000097: definition of observational is sufficiently broad, moreover, that it encompasses study types that
p.000097: this document is not intended to address. For example, it may be possible to design an intervention study that
p.000097: does not bring about or script in any way the participants’ exposure to a substance, but rather reduces or
p.000097: mitigates it. (Consider a study to test whether professional cleaning of the carpets, floors, walls, and
p.000097: other surfaces in a home might lead to a lower exposure to a residential contaminant or a study to determine if wearing
p.000097: a particle mask would reduce an individual’s exposure to smoke from forest fires.) Such a study
p.000097: might meet the regulatory definition of observational research (Note: The final decision in regard to whether
p.000097: any EPA study meets the definition of observational research resides with the Agency’s HSRRO), but it
p.000097: would not meet the authors’ intentions regarding “observational human exposure studies” as they are defined
p.000097: in this document. An intervention study, such as described in these two examples, does not involve
p.000097: observing people’s exposures in their everyday environments, as they go about their normal activities. In
p.000097: an intervention study, either the participant’s environment (cleaning of the household surfaces) or their
p.000097: behavior (wearing a particle mask) has been manipulated by the researcher. Secondly, the objective of these
p.000097: studies is not to understand exposures in everyday environments but would use changes in exposure
p.000097: to test the effectiveness of an intervention strategy. Such a study is not addressed in this document.
p.000097: Observational human exposure studies, as used by the authors of this document, generally meet the
p.000097: regulatory definition of observational research. But, not all studies meeting the CFR definition of
...
p.000117: Minimal risk. The probability and magnitude of harm or discomfort anticipated in the research are not greater in and
p.000117: of themselves than those ordinarily encountered in daily life or during the performance of routine physical or
p.000117: psychological examinations or tests [40 CFR 26.102(i)].
p.000117: Nonmaleficence. The proscription of deliberate infliction of harm on persons
p.000117: Observational human exposure study. Studies that involve collection of human exposure data (including environmental,
p.000117: biological, survey, activity, and various other forms of data) under real-world field conditions during normal
p.000117: participant day-to-day activities, with no additional exposures to the chemical being studied because of participation
p.000117: in the study. The studies involve interaction with study participants but do not involve intervention or manipulation
p.000117: of the factors being studied, and there is no attempt by the researcher to affect the outcome.
p.000117: Observational research. Any human research that does not meet the definition of research involving intentional
p.000117: exposure of a human subject [40 CFR 26.302]
p.000117: Privacy. Control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or
p.000117: intellectually) with others
p.000117: Research. A systematic investigation, including research development, testing, and evaluation, designed to develop or
p.000117: contribute to generalizable knowledge
p.000117: Research involving intentional exposure of a human subject. A study of a substance in which the exposure to the
p.000117: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
...
Searching for indicator usage:
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p.000104: eaten by participant and analyzed for pesticides, metals, etc. Includes drinking water samples as part of diet or other
p.000104: beverages consumed.
p.000104: Handled food Finger foods like cheese or luncheon meets that have been prepared and processed
p.000104: identically to foods children might eat to evaluate how much pollution may be removed from surfaces and ingested with
p.000104: the food.
p.000104: Human Activity Data
p.000104: Time-activity diaries Recall diaries to account for all times and activities in a day. Information
p.000104: includes location and activities.
p.000104: Activity loggers Device used to assess the nature of a person’s activities. Portable
p.000104: nephelometers have been used to keep up with people’s activities by showing when they were near PM sources.
p.000104: Accelerometers to measure level of activity of children at play. GIS and inertial devices to try to measure locations
p.000104: as a function of time of day.
p.000104: Questionnaires Query participants about things like daily activities for themselves or their
p.000104: children; housing characteristics; participant characteristics, including occupation, diet, smoking habits, hobbies,
p.000104: etc.; and recent use of pesticides or other consumer products.
p.000104: Videotaping Use videos to measure frequency and duration of mouthing activities in children.
p.000104: Household inventories Inventory consumer products in house. Use items to ask about usage frequency and
p.000104: history.
p.000104: Researcher observations Information about open doors and windows (air exchange), heating and cooking sources,
p.000104: pets, and other activities that may lead to potential exposures may be observed.
p.000104: Personal or Biological Samples
p.000104: Urine Urinary excretion of pollutants and their contaminants give important
p.000104: information about the nature of prior exposures and their magnitude.
p.000104: Personal air monitors Individual wears samplers on his/her person while going about normal activities to
p.000104: measure pollutants in breathing zone of individual.
p.000104: Hand wipes Hand wipes remove contaminants from skin surface. Analyze for pesticides, metals,
p.000104: organic chemicals, and use values to estimate dermal exposure and hand-to-mouth ingestion of pollutants.
p.000104: Dermal surrogates Participant may wear cotton garments or socks as a collector. Clothing is analyzed
p.000104: for pesticides, metals, organic chemicals, etc. Measured contaminant quantities are used to estimate potential for
p.000104: dermal exposure.
p.000104: Saliva samples Test for antibodies to infectious agents, suggesting prior exposure and infection
p.000104: by microbial agent. Blood Some epidemiological studies that NERL scientists have
p.000104: collaborated on have collected blood samples.
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000105: 105
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: Appendix B
...
Health / Healthy People
Searching for indicator volunteers:
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p.000103: matter, and air toxics. The study conducted
p.000103: (TACS) methods. identified microenvironmental
p.000103: factors affecting penetration of pollutants into homes and reduction of exposures to pollutants for asthmatic children
p.000103: (0-5 years of age).
p.000103:
p.000103: Pilot Study To Evaluate Data Collection Methods for Young Children’s and Household Activities
p.000103: Detroit Exposure and Aerosol Research Study (DEARS)
p.000103:
p.000103:
p.000103:
p.000103: Accelerometer Pilot Study
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: Pilot Study of Waterborne Infections
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004: 2004-2007
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002005: 2005
p.002005: 3 Homes
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.000150: 150
p.000150:
p.000150:
p.000150:
p.000150:
p.000150:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.001296: 1296
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Randomized household selection with qualification criteria; longitudinal
p.001296:
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Convenience, all volunteers from community using public water supply
p.001296: Pilot aggregate exposure study of three homes to assess burden of alternative exposure sample collection methods.
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Recruitment from seven distinct neighborhoods in Detroit required strong community relations and partnership with State
p.001296: and local organizations. This study monitored for air pollutants at the personal level and evaluates how well centrally
p.001296: located (ambient) monitors represent exposure at the residential and personal level. Sampling is for 5 days duration in
p.001296: summer and again in winter.
p.001296: Nine children <24 months old and their primary caregivers participated in this study to (a) determine if very young
p.001296: children will wear an accelerometer for relatively long periods of time and comply with the protocol for its use, (b)
p.001296: evaluate how well a caregiver can estimate the activity level of his/her infant or toddler when completing an
p.001296: exposure-oriented time-activity diary, and (c) compare accelerometer count output with caregiver-provided estimates of
p.001296: children's activity level.
p.001296: Measure antibodies in people’s saliva for antibodies to Cryptosporidium, Noroviruses, Rotaviruses, Helicobacter pylori,
p.001296: and Toxoplasma gondii before and after installation of an ultraviolet treatment system for a public water supply. Also
p.001296: served as test of methodology for detecting people’s prior exposure to infectious agents.
p.001296: NERL designed, contractor conducted
p.001296:
p.001296:
p.001296:
p.001296:
...
Health / Mentally Disabled
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p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
p.000003: range of risks associated with participation and the voluntary nature of participation, and provides
p.000003: essential protections to the participant. Recent observations by various national and international review
p.000003: committees on the appropriate level of payment to research participants are presented. This is a
...
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
...
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
...
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
p.000055: dialogue . . . involving the disclosure and exchange of relevant information” (IOM, 2002): it is not
p.000055: simply having a consent form signed. The process is most effective when the researcher spends time with
p.000055: potential participants to discuss the study and to answer questions.
p.000055:
p.000055: 5.2 Payments to Research Participants
...
p.000061: of
p.000061: recommendations from the report for enhancing public trust is provided in Appendix D. The recommendations are
p.000061: focused on the following areas.
p.000061: • Building trust through community partnerships
p.000061: • Building relationships with patients (participants) (True partnerships with patients may not be possible,
p.000061: but bidirectional relationships must be enhanced.)
p.000061: • Building partnerships with community providers
p.000061: • Building trust in scientists
p.000061: • Building trust in the (EPA) and scientific research.
p.000061:
p.000061: 5.5 Recruitment Strategies
p.000061: Many strategies are used to select and recruit people into research studies requiring human participation. The IRB is
p.000061: responsible for reviewing the selection process to ensure that it is, above all, equitable. The requirement for
p.000061: IRB review is stated in 40 CFR 26.111(a)3.
p.000061: Selection of subjects is equitable. In making this assessment, the IRB should take into account the
p.000061: purposes of the research and the setting in which the research will be conducted and should be particularly cognizant
p.000061: of the special problems of research involving vulnerable populations, such as children, prisoners,
p.000061: pregnant women, mentally disabled persons, or economically or educationally disadvantaged
p.000061: persons.
p.000061: The IRB guidebook is an excellent resource for consideration of concerns and elements for equitable
p.000061: participant selection (U.S. HHS, 1993). It states that “Defining the appropriate group of subjects
p.000061: for a research project involves a variety of factors⎯ requirements of scientific design,
p.000061: susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness.” The IRB
p.000061: guidebook raises a number of points to consider in the process for selection of human participants (see Text Box
p.000061: 5-5).
p.000061: Various participant recruitment strategies may be used depending on the type of research being performed and the
p.000061: population of interest. This section addresses the strategies and approaches for identifying and contacting people and
p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
p.000062: 1. Who will bear the burden? Who will reap the benefits?
p.000062: 2. Is there a disproportionate burden on any single group?
...
Searching for indicator mentally:
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p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
p.000003: range of risks associated with participation and the voluntary nature of participation, and provides
p.000003: essential protections to the participant. Recent observations by various national and international review
...
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
...
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
...
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
p.000055: dialogue . . . involving the disclosure and exchange of relevant information” (IOM, 2002): it is not
p.000055: simply having a consent form signed. The process is most effective when the researcher spends time with
...
p.000061: developed in the context of NIH-supported clinical research, many of the recommendations are applicable to
p.000061: observational human exposure studies and human subject research in general. A summary
p.000061: of
p.000061: recommendations from the report for enhancing public trust is provided in Appendix D. The recommendations are
p.000061: focused on the following areas.
p.000061: • Building trust through community partnerships
p.000061: • Building relationships with patients (participants) (True partnerships with patients may not be possible,
p.000061: but bidirectional relationships must be enhanced.)
p.000061: • Building partnerships with community providers
p.000061: • Building trust in scientists
p.000061: • Building trust in the (EPA) and scientific research.
p.000061:
p.000061: 5.5 Recruitment Strategies
p.000061: Many strategies are used to select and recruit people into research studies requiring human participation. The IRB is
p.000061: responsible for reviewing the selection process to ensure that it is, above all, equitable. The requirement for
p.000061: IRB review is stated in 40 CFR 26.111(a)3.
p.000061: Selection of subjects is equitable. In making this assessment, the IRB should take into account the
p.000061: purposes of the research and the setting in which the research will be conducted and should be particularly cognizant
p.000061: of the special problems of research involving vulnerable populations, such as children, prisoners,
p.000061: pregnant women, mentally disabled persons, or economically or educationally disadvantaged
p.000061: persons.
p.000061: The IRB guidebook is an excellent resource for consideration of concerns and elements for equitable
p.000061: participant selection (U.S. HHS, 1993). It states that “Defining the appropriate group of subjects
p.000061: for a research project involves a variety of factors⎯ requirements of scientific design,
p.000061: susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness.” The IRB
p.000061: guidebook raises a number of points to consider in the process for selection of human participants (see Text Box
p.000061: 5-5).
p.000061: Various participant recruitment strategies may be used depending on the type of research being performed and the
p.000061: population of interest. This section addresses the strategies and approaches for identifying and contacting people and
p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
p.000062: 1. Who will bear the burden? Who will reap the benefits?
...
Health / Mentally Incapacitated
Searching for indicator incapable:
(return to top)
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
...
p.000035: presented in the Common Rule. It is not adequate to simply check the list in Text Box 3-1 to identify if a potentially
p.000035: vulnerable group is included in an observational study. The researchers should assess the potential
p.000035: vulnerability of a study population within the study by evaluating the characteristics (e.g., socioeconomic
p.000035: status) of the study population within the context of the study by considering the various design elements of the
p.000035: study, as discussed in Section 2.
p.000035: 12 In the commentary on Guideline 13 in CIOMS (2002), the committee states that the central problem presented by plans
p.000035: to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
p.000035: the CIOMS document (Guidelines 14 and 15) and include children, and persons who, because of mental or behavioral
p.000035: disorders, are incapable of giving informed consent. Ethical justification of their involvement usually requires that
p.000035: • the research could not be carried out equally well with less vulnerable subjects;
p.000035: • the research is intended to obtain knowledge that will lead to improved diagnosis, prevention, or treatment of
p.000035: diseases or other health problems characteristic of, or unique to, the vulnerable class—either the actual subjects or
p.000035: other similarly situated members of the vulnerable class;
p.000035: • research subjects and other members of the vulnerable class from which subjects are recruited will ordinarily be
p.000035: assured reasonable access to any diagnostic, preventive, or therapeutic products that will become available as a
p.000035: consequence of the research;
p.000035: • the risks attached to interventions or procedures that do not hold out the prospect of direct health-related
p.000035: benefit will not exceed those associated
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036: CIOMS recommendations, although written to address biomedical research, also generally are
p.000036: applicable to observational human exposure studies. The authors of this document consider the CIOMS
p.000036: requirement that the research could not be carried out equally well with less vulnerable subjects
...
Health / Motherhood/Family
Searching for indicator family:
(return to top)
p.000026: study design.
p.000026: For research conducted or sponsored by NERL, human subjects research efforts will undergo both a
p.000026: scientific review and an ethical review. The director of
p.000026: the division conducting or funding the observational research is the manager with the primary
p.000026: responsibility for ensuring that the scientific and the ethical reviews are conducted, and that the review
p.000026: comments are properly addressed. The study design will be reviewed for scientific quality by
p.000026: independent and knowledgeable reviewers. Depending on the scope of the study, the appropriate NERL
p.000026: associate director or the NERL laboratory director will make the final determination about (1) the
p.000026: process for selecting scientific peer reviewers (including the range of disciplines to be
p.000026: included), (2) the nature and scope of the review process (e.g., charge to the reviewers and scope of the
p.000026: review; letter reviews, convening a peer panel, or both; the size and nature of the panel review; etc.),
p.000026: and (3) the adequacy of the responses to the scientific review.
p.000026:
p.000026: 2.5.2 Conflicts of Interest
p.000026: It is recommended that potential conflicts of interest among researchers or study participants be identified at all
p.000026: stages of study planning and implementation, but particularly early in the study during the planning stage. There
p.000026: can be many sources of potential conflicts of interest, including sources of project funding, pressures
p.000026: to publish, consulting arrangements of the investigators, employment of investigators’ family members with
p.000026: affected parties, participation in affected advocacy groups, collaborations or relationships with
p.000026: experts on the IRB or other independent review committees, institutional conflicts for any contractors
p.000026: who may be involved, or a wide range of other situations.
p.000026: Any situations that constitute actual conflicts of interest and all potential or apparent conflicts of interest
p.000026: must be reported to the IRB for their review and resolution. The CIOMS (2002) guidelines for
p.000026: research protocols involving human subjects specify that all sponsors of the research be identified,
p.000026: and that the protocol include actions to disclose and address potential conflicts of interest. Concerns about
p.000026: conflicts of interest also need to be identified and discussed with the researchers, community, and
p.000026: other stakeholders to make a determination of the existence of conflicts, and how they should be avoided or
p.000026: handled.
p.000026: Even if actual conflicts of interest do not exist, researchers should recognize that there can be perceived
p.000026: conflicts of interest that can be just as damaging as real conflicts of interest. Perceptions by
p.000026: participants, community members and representatives, stakeholder groups, and the public may be substantially
p.000026: different from the reality of the situation. This is especially likely to occur when external sources, such as
p.000026: industry, are
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027: involved in funding research. Even though researchers may develop agreements with funding organizations that
...
p.000037: not to include them. Proposals or applications to NIH for research have to present an acceptable
p.000037: justification if children will be excluded from a research study. Of course, as discussed above, if the research
p.000037: topic is irrelevant to children, the CIOMS guidelines would recommend that they be excluded from the
p.000037: research.
p.000037: Observational human exposure studies conducted by NERL are not expected to involve greater than minimal risk. It
p.000037: will be the responsibility of the NERL researchers to present adequate information for the IRB to
p.000037: demonstrate that the research does not involve greater than minimal risk. Researchers designing observational
p.000037: research studies should carefully evaluate the risks and benefits specific to their study and the
p.000037: participants involved. In developing the study design and human subjects protocols, researchers need to
p.000037: ensure that the protocols ensure the protection of the rights and welfare of the participant children, and that
p.000037: risks and harm are minimized. The perception of risks and benefits, both by
p.000037: the individual and by the family or community, may influence the risk-benefit determination. It may prove
p.000037: useful for the research team to consult with other experienced researchers who have conducted
p.000037: similar studies and with members of the IRB to ensure that the information included in the human subjects
p.000037: research protocol is adequate for the IRB’s review.
p.000037: It is recommended that researchers consider all of the potential issues associated with involvement
p.000037: of children in their studies in developing the study design and research protocols, including the role of the
p.000037: family. EPA’s human subjects rule for observational research not involving greater than minimal risk to
p.000037: children (40 CFR 26.404) (i.e., the kinds of observational human exposure studies that NERL exposure research
p.000037: is likely to entail) focuses on obtaining assent of the children and permission of their parents or guardians. But the
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
p.000037: biomedical research because of the potential for becoming pregnant during a study. The document continues, “A
...
p.000041: sensitive to and respectful of the host’s customs and values” (p. 65, NRC & IOM, 2005).
p.000041: By their very nature, observational human exposure studies encroach on the privacy of a research participant. Entry in
p.000041: a participant’s home (or other personal zones) does represent a loss of privacy, but researchers should be
p.000041: careful to ensure that their presence does not become a violation of the individual’s right to privacy. The
p.000041: relationship between the researcher and the participant may be complicated, and there may be conflicts between
p.000041: the researcher’s role and their ethical obligations (NRC & IOM, 2005). In entering a participant’s
p.000041: personal space, it may be difficult, or impossible, to avoid making observations unrelated to the research question,
p.000041: thereby further intruding on the participant’s personal privacy. Indeed, there may be ethical and legal
p.000041: obligations for the researchers to respond to those observations. Beauchamp and Childress suggest that “policies
p.000041: carefully specify the conditions of access that will and will not count as a loss of privacy or a violation of
p.000041: the right to privacy. The policy should accurately define the zones that are considered private and
p.000041: not to be invaded, and should also identify interests that legitimately may be balanced against privacy
p.000041: interests” (Beauchamp and Childress, 2001).
p.000041: Observational human exposure studies also may infringe on the privacy of other individuals, for example,
p.000041: other members of the participant’s family or household. Researchers should strive to minimize the intrusion and loss
p.000041: of privacy and to show respect for the privacy of study participants and third parties at all times (see Text
p.000041: Box 4-2 for a list of relevant privacy issues). It is incumbent on the researcher to recognize privacy issues
p.000041: in the design and implementation of the research study. The NRC & IOM report suggests that researchers
p.000041: anticipate the ethical issues that arise from conducting research in a person’s home, and that they take steps
p.000041: to correct them (1) by thinking through the issues as part of the study design; (2) by discussing the issues during the
p.000041: informed consent process; and (3) by ensuring that the frontline staff that enter a
p.000041: participant’s home “understand their role as members of the research team, how that role differs from the role of
p.000041: neighbor or friend, and how they should respond when they make observations that are not part
p.000041: of the protocol” (p. 66, NRC & IOM, 2005).
p.000041:
p.000041: Text Box 4-2. Privacy Issues
p.000041: • Researchers should develop an anticipatory plan for how to deal with privacy issues during the study. The plan
p.000041: should include a list of potential observations that could be of concern and a plan for how they will be handled.
p.000041: • The plan needs to address both the legal and ethical obligations of the researcher in response to situations where
p.000041: privacy is compromised.
p.000041: • Privacy issues will vary depending on the culture of the population being studied. What one individual or group
...
p.000043: identification of a research subject.
p.000043: Federal funding is not a prerequisite for a certificate. A Certificate of Confidentiality does not
p.000043: diminish, however, the investigator’s need to protect the personally identifiable information as
p.000043: described above.
p.000043:
p.000043: 4.2.2 Confidentiality of Participation
p.000043: In some types of research, the knowledge that a person is participating in a particular research study
p.000043: could, potentially, put the participant at risk for harm or distress. This topic is discussed in The
p.000043: Institutional Review Board Guidebook, with special emphasis on behavioral and social research that deals
p.000043: with sensitive topics (U.S. HHS, 1993). The guidebook describes the need for additional safeguards to
p.000043: protect and prevent disclosure of the identity of participants, including the use of Certificates of
p.000043: Confidentiality for sensitive matters.
p.000043: Observational human exposure studies often pose particular challenges with regard to limiting
p.000043: dissemination of the knowledge of an individual’s participation in the study. Visiting the
p.000043: research participant’s residence to collect samples or to make observations will necessitate informing
p.000043: other family members or occupants about the visit and study procedures. Research participants may be
p.000043: asked to wear personal monitors over time periods ranging from a day to a week or more. Wearing these devices
p.000043: in public places, schools, or workplaces may identify them as a study participant or generate questions
p.000043: regarding the activity. Field staff visits to the participant’s home or setting up outdoor sample collection
p.000043: devices around the home also might disclose their participation. And, in some cases, third parties outside of
p.000043: the home have to be asked for permission or be informed that monitoring activities are taking place.
p.000043: Researchers and IRBs should consider whether knowledge of an individual’s participation by others might
p.000043: create potential for harm or distress in an observational human exposure study. Such risks might
p.000043: be limited to possible discomfort in attracting unwanted
p.000043: attention; this may be particularly true for adolescents. However, in some cases, the potential risks
p.000043: could be greater, for example, in cases where participation could provoke an adverse reaction from a
p.000043: landlord or employer. Oftentimes study protocols can be structured to minimize these potential risks. Through the
p.000043: informed consent process, prospective participants should be made aware of the limits of the researcher’s ability to
...
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
p.000058: gestures of appreciation, investigators may also—if they minimize the potential for undue influence—act ethically to
p.000058: reduce certain barriers to research participation when they
p.000058: • reimburse reasonable expenses directly related to a child’s participation in research
p.000058: • provide reasonable, age-appropriate compensation for children based on the time involved in research that does not
p.000058: offer the prospect of direct benefit, and
p.000058: • offer evening or weekend hours, on-site child care, and other reasonable accommodations for parental work and
p.000058: family commitments.”
p.000058: 22 In recommending an open process, the IOM committee chose to reject the
p.000058: arguments from the American Academy of Pediatrics that “any token payment to children for participating in research
p.000058: should not be discussed with them until after research is completed for fear of unduly influencing their decisions
p.000058: (AAP, 2003)…. On balance, the committee agrees that it is best to mention token or other payments during the permission
p.000058: and assent processes” (p. 215, IOM, 2004).
p.000058: The IOM Recommendation 6.1 states, “Institutional review boards, research institutions, and sponsors of research that
p.000058: includes children and adolescents should adopt explicit written policies on acceptable and unacceptable types and
p.000058: amounts of payments related to research participation. These policies should specify that investigators
p.000058: • Disclose the amount, the recipient, the timing, and the purpose (e.g., an expense reimbursement or a token of
p.000058: appreciation to a child) of any payments as part of the process of seeking parents’ permission, and, as appropriate,
p.000058: children’s assent to research participation;
p.000058: • Avoid emphasis on payments or descriptions of payments as benefits of participating in research during the
p.000058: permission or assent procedures; and
p.000058: • Obtain institutional review board approval for the disclosure of information about payments in advertisements and
p.000058: in permission and assent forms and procedures.”
p.000058:
p.000058:
p.000059: 59
p.000059:
p.000059: participate in research are unacceptable. The European Union requires that clinical trials on minors
p.000059: be undertaken only if “no incentives or financial inducements are given except compensation”
p.000059: (European Parliament, 2001).
p.000059: Payment for participation of children in research also is discussed in the literature. Diekema
p.000059: (2005) emphasizes the need to ensure that payments do not distort parental decisionmaking and do not tempt
p.000059: parents to consider other issues than the welfare of their child. Similarly, Menikoff (2005) suggested that
p.000059: there need to be relatively robust protections in place to ensure that families do not change their behaviors
p.000059: to participate in a study. He suggested that these may include determining payment as a percentage of a family’s
p.000059: income and developing criteria for documenting that behaviors have not changed to be eligible for participation in a
p.000059: study. He suggested that, for a study of pesticides, potential study participants provide documentation (such as
p.000059: receipts) that they routinely have been using a commercial pesticide service. This may be difficult
p.000059: for potential participants to do if they do not save receipts, and it would exclude all potential
p.000059: participants who purchase products and apply pesticides themselves. This likely would affect the study
p.000059: objectives and generalizability of the data collected. A survey of investigators (Iltis et al., 2006) found that
p.000059: payments were made in 52% of the pediatric research studies surveyed, and that payment practices varied,
p.000059: as did the reasons for decisions regarding payments. They found a range of payment values separated
p.000059: across cash, gifts, items, vouchers, and other categories. A survey of IRBs (Weise et al., 2002) found that payment
p.000059: for participation in research was allowed by 66% of responding institutions, but that many IRBs did not have
p.000059: specific policies, and that there was considerable variability regarding the basis for decisions on
p.000059: payments in studies with children. The types of payments included money, certificates, and bonds with large
p.000059: ranges in the amounts of payments for approved pediatric research. This research shows a lack of consistency and
p.000059: the need for guidance and institutional policies that describe acceptable and unacceptable
...
p.000178: questionnaires, were administered to each selected subject and household, respectively, and meteorological and air
p.000178: exchange rate data were recorded for each monitored home.
p.000178: This survey collected 24-hour activity diaries and other questionnaire data from participants from 48 states. It was
p.000178: conducted as a next-day telephone recall interview.
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000100: 100
p.000100:
p.000100: Table A-1. (Continued)
p.000100: Study Date Size Type Brief Description
p.000100: NERL Role
p.000100: Agricultural 1993- 84 applicators AHS survey A large-scale, long-term ongoing study of
p.000100: Iowa and North Collaboration with Health Study present; and a subset is a
p.000100: Carolina pesticide applicators and farm families. This other agencies; (AHS)
p.000100: PES 1999- of family longitudinal collaborative effort involving the National Cancer Institute
p.000100: NERL led a
p.000100: 2003 members in study of (NCI), the National Institute of Environmental Health Sciences
p.000100: contractor-
p.000100: PES pesticide (NIEHS), the National Institute for Occupational Safety and
p.000100: conducted applicators in Health (NIOSH), and the U.S. Environmental Protection substudy called two
p.000100: states. Agency (EPA) examines how lifestyle habits, genetic factors, the Pesticide PES, led by and
p.000100: agricultural exposures contribute to the risk of disease Exposure Study.
p.000100: NERL, was a using questionnaire survey data from 89,658 participants. This
p.000100: cross- is the largest, most comprehensive study of agricultural health sectional ever conducted
p.000100: in the United States. The interagency exposure study. assessment study (Pesticide Exposure Study (PES)),
p.000100: led by
p.000100: NERL, was performed to assess exposures and exposure
p.000100: classification procedures used in the epidemiological study.
p.000100: The National 1995-1998 See specifics A Federal interagency research effort
p.000100: coordinated by EPA and EPA oversaw Human in entries
p.000100: consisting of four demonstration studies using probability- general design for Exposure
p.000100: below. based sampling designs conducted in partnership
p.000100: with other the research, then Assessment
p.000100: Federal agencies (CDC, FDA, and NIST), universities, and solicited, evaluated
...
p.000111: that permission will be obtained from a duly authorized person, or, in the case of a child who is sufficiently mature
p.000111: to understand the implications of informed consent but has not reached the legal age of consent,
p.000111: that knowing agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian
p.000111: or other duly authorized representative.
p.000111: (26) An account of any economic or other compensation or incentives to prospective subjects to participate, such as
p.000111: offers of cash payments, gifts, or free services or facilities, and of any financial
p.000111: obligations assumed by the subjects, such as payment for medical services
p.000111: (27) The plans and procedures and the persons responsible for communicating to
p.000111: subjects information arising from the study (on harm or benefit, for example) or from other research on the same
p.000111: topic that could affect subjects’ willingness to continue in the study
p.000111: (28) The plans to inform subjects about the results of the study
p.000111: (29) The provisions for protecting the confidentiality of personal data and respecting the privacy of subjects,
p.000111: including the precautions that are in place to prevent disclosure of the results of a
p.000111: subject’s genetic tests to immediate family relatives without the consent of the subject
p.000111: (30) Information about how the code, if any, for the subjects’ identity is established; where it will be
p.000111: kept; and when, how, and by whom it can be broken in the event of an emergency
p.000111: (31) Any foreseen further uses of personal data or biological materials
p.000111: (32) A description of the plans for statistical analysis of the study, including plans for interim analyses, if
p.000111: any, and criteria for prematurely terminating the study if necessary
p.000111: (33) A list of the references cited in the protocol
p.000111: (34) The source and amount of funding of the research, including the organization that is sponsoring the research
p.000111: and a detailed account of the sponsor’s financial commitments to the research institution,
p.000111: the investigators, the research subjects, and, when relevant, the community
p.000111: (35) The arrangements for dealing with financial or other conflicts of interest that might affect
p.000111: the judgment of investigators or other research personnel, including informing the institutional
p.000111: conflict-of-interest committee of such conflicts of interest; the communication by that committee of the
p.000111: pertinent details of the information to the ethical review committee; and the transmission by that committee to
p.000111: the research subjects of the parts of the information that it decides should be passed on to them
p.000111: (36) The time schedule for completion of the study
p.000111: (37) Particularly in the case of an industrial sponsor, a contract stipulating who possesses the
...
Health / Physically Disabled
Searching for indicator illness:
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p.000088: information on risk communication. Readers of this document should refer to her manuscript to determine
p.000088: which approach may be applicable to their particular study.
p.000088: During longitudinal studies with repeated measurements over months, seasons, or years, it
p.000088: is important that researchers commit to providing interim and ongoing results to participants and the community
p.000088: as the study proceeds. It is important to maintain the researcher-participant relationship throughout
p.000088: the study. This can be facilitated by keeping study participants informed of the study progress and of the
p.000088: interim results
p.000088: Researchers also should recognize that there may be potential risks to the study participants, third parties, or the
p.000088: community because of results generated from a study (refer to Text Box 7-7). Therefore, providing
p.000088: information to communities has to be done thoughtfully and with appropriate preparation. Processes should be
p.000088: developed that provide participants with the option to receive, or decline, study results. Researchers
p.000088: should work with community groups to determine how study results should be disseminated to the community
p.000088: and what communications strategies should be used.
p.000088:
p.000088: Text Box 7-7. Potential Harms of Sharing Research Results with Participants
p.000088: (Fernandez, Kodish, and Weijer, 2003)
p.000088: • Incorrect or harmful decisions based on uncertain or unreliable results
p.000088: • Causing distress for those participants who did not benefit from the research
p.000088: • Rekindling old memories and emotions, especially in the setting of serious illness
p.000088: • Emotional distress among community members
p.000088: • Possible discrimination in obtaining employment or insurance for a participant identified by the research to be at
p.000088: high risk of developing complications
p.000088: • Financial costs to participants and to researchers
p.000088:
p.000088: There are a variety of methods for providing study results to participants and the community. Fact
p.000088: sheets can be used to describe the study and provide general study findings to the community and
p.000088: stakeholders.
p.000088:
p.000088:
p.000089: 89
p.000089:
p.000089: Individualized fact sheets can be used to disseminate results to the individual participants. Meetings
p.000089: with study participants have been used to disseminate study information. Community meetings also can be
p.000089: used to provide updates on study progress and general results.
p.000089: Examples of the processes and the materials used for dissemination of information are included in case studies
p.000089: described by Israel et al. (2005) and others conducting CBPR studies.
p.000089: Overall study results generally are disseminated in peer-reviewed journal manuscripts and study reports. The
p.000089: availability of results published in manuscripts and reports has been greatly enhanced by posting them on
p.000089: Internet Web sites. For example, all EPA reports are now available electronically via EPA’s National Service
p.000089: Center for Environmental Publications Web site (http://www.epa.gov/ncepihom/).
p.000089:
p.000089: 7.8 Reporting Unanticipated Results or Observations
...
p.000009: Performed in the Raleigh, NC, area in homes with children 1 to 3 years old. Homeowners reported either professional or
p.000009: self applications of diazinon. Goals of the study were to evaluate methods to measure excess dietary exposures
p.000009: resulting from food-handling activities by young children during eating and to assess whether the Children’s Dietary
p.000009: Intake Model (CDIM) accurately represents total dietary exposures of children. Study resulted in refinements of model
p.000009: parameters for transfer and activity.
p.000009: Observational measurement study of exposure to chlorpyrifos among children 2-5 years of age in urban New Jersey homes
p.000009: following crack and crevice treatment by a professional applicator. Study investigated decay of pesticide levels over
p.000009: time, transfer of pesticide from microenvironmental media to child, and factors that affect transfer. Dermal transfer
p.000009: evaluated with surface wipes, hand wipes, dermal wipes, cotton garments, and videotaping.
p.000009: Physicians at Case-Western Reserve treating children with idiopathic pulmonary hemorrhage evaluated the nature of the
p.000009: fungus found in homes of the afflicted and control children to determine if Stachybotrys was a potential factor in the
p.000009: illness. Three of the 8 cases, and none of the controls, had Stachybotrys strains that potentially were implicated.
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: The largest children’s exposure study undertaken to date. It examines aggregate exposures of children 18 months to 5
p.000009: years to pollutants commonly found in everyday environments. The major objectives were to quantify children’s aggregate
p.000009: exposures, apportion exposure pathways, and identify important exposure media. Participants were recruited from 12
p.000009: urban and rural counties in North Carolina and Ohio using a random digit dialing method. Monitoring was performed at
p.000009: both daycare centers and homes. Samples collected include food, beverages, indoor air, outdoor air, hand wipes, dust,
p.000009: soil, transferable residues, floor and surface wipes, and urine. The samples were analyzed for more than 40 pollutants,
p.000009: including insecticides, phthalate esters, phenols, polychlorinated biphenyls, and PAHs.
p.000009: Scientists monitored air pollutants inside and outside vehicles of healthy highway patrol officers in North Carolina
p.000009: while troopers were on patrol for 9-hour shifts and examined cardiovascular effects. The findings indicated that people
p.000009: driving in motor vehicles are exposed to PM2.5 and other pollutants generated from motor vehicles, and that these
p.000009: exposures appear to cause cardiovascular changes.
p.000009:
p.000009:
p.000102: 102
p.000102: with contractor support; funded and collaborated on others with Harvard School of Public Health, University. of
p.000102: Washington, and NYU.
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL designed, contractor conducted
p.000102:
...
Searching for indicator physically:
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p.000040: research and explores the researchers’ responsibilities that derive from conducting research in people’s homes
p.000040: (NRC & IOM, 2005). These housing-related discussions are particularly relevant to observational human
p.000040: exposure studies, which often include environmental and
p.000040: biological measurements in people’s homes or personal locations. Many of the topics identified in that report are
p.000040: discussed in this section (Text Box 4-1).
p.000040:
p.000040:
p.000040: Text Box 4-1. Topics in Section 4
p.000040: Privacy Issues Confidentiality
p.000040: Confidentiality of Information Confidentiality of Participation
p.000040: Collateral Observations
p.000040: Potential Nonstudy Hazards in the Residence Collateral Observations with Mandated Reporting
p.000040: Requirements
p.000040: Hazard Communication Planning and Staff Training
p.000040: Third-Party Issues
p.000040: Determining Whether a Third Party is a Human Subject Informing Third Parties of Research Activities Research Results
p.000040: and Third Parties
p.000040: Data and Safety Monitoring and Oversight
p.000040:
p.000040:
p.000040:
p.000040: 4.1 Privacy Issues
p.000040: Privacy refers to an expectation that a person is free from intrusion into personal matters and is free from the
p.000040: presence or view of others. The Institutional Review Board Guidebook defines privacy as “control over the
p.000040: extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with
p.000040: others” (U.S. HHS, 1993). Beauchamp and Childress find that the right to privacy is based on the principle of
p.000040: respect for autonomy. “We often respect persons by respecting their autonomous wishes not to be observed, touched, or
p.000040: intruded upon…. A loss of privacy occurs if others use any of several forms of access, including intervening in zones
p.000040: of secrecy, anonymity, seclusion, or solitude” (pp. 295-296, Beauchamp and Childress, 2001).
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041: Although research participants may agree to allow researchers to enter their home or other zone of personal space
p.000041: to conduct their research measurements, they have not abrogated their right to privacy. “When individuals
p.000041: voluntarily grant others some form of access to themselves, their act is an exercise of the
p.000041: right to privacy, not a waiver of that right” (p. 297, Beauchamp and Childress, 2001). Researchers should remember
p.000041: that they are guests in the homes for a specific purpose. “When people visit a home, there are social
p.000041: expectations about what is acceptable behavior. People who are invited into a home are expected to be
p.000041: sensitive to and respectful of the host’s customs and values” (p. 65, NRC & IOM, 2005).
...
p.000042: to maintain confidentiality should be anticipated and disclosed to prospective subjects.”
p.000042: to identify an individual. Precise geographic location information may be sufficient to pinpoint a
p.000042: residence. Researchers may use several strategies to reduce the likelihood of indirect identification when
p.000042: study results are reported (see, also, Text Box 4-3).
p.000042: • Redact from publications, reports, or public data sets information that might be used to indirectly identify a
p.000042: research participant.
p.000042: • Generalize exact information; for example, replace birth date with age or year of birth or classify age as
p.000042: part of a range.
p.000042: • Aggregate information across individuals; for example, only report data in cells of sufficient size
p.000042: to make individual linkages unlikely.
p.000042: • Reduce the specificity of geographic coordinate information to a level that a specific residence or other
p.000042: location can not be identified.
p.000042:
p.000042: Text Box 4-3. Approaches for Protecting Personally Identifiable Information
p.000042: • Developing procedures for safeguarding information prior to collecting the information
p.000042: • Ensuring that data or samples are anonymous by not collecting or by destroying identifying information or linkages
p.000042: • Restricting access to identifying information to only those requiring access
p.000042: • Assigning codes to participants, data, and samples rather than using identifiers
p.000042: • Physically separating identifying information and linkage files from other study information
p.000042: • Securing identifying information in locked files with limited access
p.000042: • Restricting identifying information from computers that are networked with other computers or electronic systems
p.000042: • Restricting identifying information from computers that are not kept in secure locations with limited access
p.000042: • Training research staff members on human subject protection and on information security procedures
p.000042:
p.000042:
p.000042: Another step that can help protect confidentiality is to obtain a Certificate of Confidentiality. Certificates of
p.000042: Confidentiality are issued by NIH (2002) to protect identifiable research information from forced disclosure.
p.000042: They allow the investigator and others who have access to research records to refuse to disclose identifying
p.000042: information on research participants in any civil, criminal, administrative, legislative, or other
p.000042: proceeding, whether at the Federal, State, or local level. Certificates of Confidentiality may be granted for studies
p.000042: collecting information that, if disclosed, could have adverse consequences for subjects or damage
p.000042: their financial standing, employability, insurability, or reputation. By protecting researchers and
p.000042: institutions from being
p.000042:
p.000042:
...
p.000117: research involving human subjects, the principle refers primarily to distributive justice, which requires the equitable
p.000117: distribution of both the burdens and the benefits of participation in research. Differences in distribution of burdens
p.000117: and benefits are justifiable only if they are based on morally relevant distinctions among persons.
p.000117: Minimal risk. The probability and magnitude of harm or discomfort anticipated in the research are not greater in and
p.000117: of themselves than those ordinarily encountered in daily life or during the performance of routine physical or
p.000117: psychological examinations or tests [40 CFR 26.102(i)].
p.000117: Nonmaleficence. The proscription of deliberate infliction of harm on persons
p.000117: Observational human exposure study. Studies that involve collection of human exposure data (including environmental,
p.000117: biological, survey, activity, and various other forms of data) under real-world field conditions during normal
p.000117: participant day-to-day activities, with no additional exposures to the chemical being studied because of participation
p.000117: in the study. The studies involve interaction with study participants but do not involve intervention or manipulation
p.000117: of the factors being studied, and there is no attempt by the researcher to affect the outcome.
p.000117: Observational research. Any human research that does not meet the definition of research involving intentional
p.000117: exposure of a human subject [40 CFR 26.302]
p.000117: Privacy. Control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or
p.000117: intellectually) with others
p.000117: Research. A systematic investigation, including research development, testing, and evaluation, designed to develop or
p.000117: contribute to generalizable knowledge
p.000117: Research involving intentional exposure of a human subject. A study of a substance in which the exposure to the
p.000117: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
...
Health / Pregnant
Searching for indicator pregnant:
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p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
p.000003: range of risks associated with participation and the voluntary nature of participation, and provides
...
p.000008: Resolved questions in NAS review of PM science and provided a “generally consistent finding that ambient particle
p.000008: concentrations are a key determinant of the longitudinal variation in personal exposure.” (NRC, 2004). These results
p.000008: have been instrumental in support of the National Ambient Air Quality Standard for PM (U.S. EPA, 1999).
p.000008:
p.000008:
p.000008: Volatile Organic Compounds (VOCs)
p.000008:
p.000008: EPA's Total Exposure Assessment Methodology (TEAM) studies found levels of about a dozen common organic pollutants to
p.000008: be 2- to 5-times higher inside homes than outside. Use of products containing organic chemicals may result in very high
p.000008: and persistent pollutant levels.
p.000008:
p.000008: EPA, States, and the Consumer Product Safety Commission worked together to influence manufacturers to voluntarily
p.000008: reduce emissions of toxic chemicals from consumer products, building materials, and furnishings, and to develop
p.000008: mitigation strategies and educational materials to teach people how to reduce their contact with chemicals indoors. As
p.000008: a result, contact with toxic chemicals indoors has been reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html).
p.000008:
p.000008:
p.000008: Formaldehyde
p.000008:
p.000008: Studies found elevated formaldehyde levels indoors and helped identify indoor sources.
p.000008:
p.000008: EPA worked with HUD, CPSC, and other agencies to limit formaldehyde in building or consumer products and to educate the
p.000008: public on how to reduce exposures (see www. epa.gov/iaq/formalde.html).
p.000008:
p.000008:
p.000008: EPA has adopted additional protections for children and pregnant or nursing mothers in Subparts B through
p.000008: D. These sections apply to all research either conducted or funded by EPA and are, therefore, directly applicable to
p.000008: NERL’s observational human exposure studies.4 Subpart B prohibits EPA from conducting or supporting research
p.000008: that involves intentional exposure of “a pregnant woman (and, thereby, her fetus), a nursing woman,
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
p.000008: from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in specified
p.000008: rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in this
p.000008: document.
p.000008: 5 The Glossary (Appendix F) lists definitions for a number of important terms; definitions that come from the
...
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000012: 12
p.000012:
p.000012: address all of the relevant issues for their particular study to ensure that the specific elements of
p.000012: the study will safeguard and protect the human research subjects.
p.000012: In addition to being an information resource for NERL researchers, this document provides useful
p.000012: information for contractors and grantees funded by NERL to consider during the design and implementation of
p.000012: their exposure science research. Although not its intended audience, this document also may prove to be useful
p.000012: to other researchers, within and outside of EPA, who are involved in observational human exposure
p.000012: studies.
p.000012:
p.000012: 1.4 Process for Developing the Document
...
p.000033: populations are not targeted for risky research” [emphasis added] (Emanuel et al., 2000).
p.000033: The Common Rule requires IRBs to assure that “additional safeguards have been included in the study to protect
p.000033: the rights and welfare of these [vulnerable] subjects” [at 40 CFR 26.111(b) in CFR, 2006a]. If an
p.000033: observational human exposure study includes vulnerable research participants, it is essential that the investigators be
p.000033: cognizant of the special issues and requirements of research involving vulnerable populations. Researchers
p.000033: have to justify the involvement of vulnerable populations in the research study and
p.000033: include the appropriate safeguards for protection of their safety and welfare. The Common Rule protections are
p.000033: discussed further in the IRB guidebook (U.S. HHS, 1993). EPA regulations include not only the general
p.000033: protections for vulnerable populations found in the Common Rule (Subpart A) but also define
p.000033: additional protections for children and for pregnant or nursing women (and their fetus or nursing child)
p.000033: in Subparts B, C, and D (CFR, 2006a).
p.000033: The section begins by identifying or defining vulnerable groups and then discusses ethical issues that
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
...
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
...
p.000036: If such research does not hold out the prospect of direct benefit to the child, no increase whatsoever over
p.000036: minimal risk is permitted.
p.000036: However, many observational human exposure studies are developed specifically to study the exposures of
p.000036: selected vulnerable groups to chemicals and other environmental stressors in everyday environments. So,
p.000036: researchers should be prepared to address the issues associated with vulnerable groups in
p.000036: observational research. Furthermore, as discussed in Section 3.4, there has been increased concern in recent years that
p.000036: exclusion of vulnerable groups from research studies is not ethical. Failure to conduct research with vulnerable groups
p.000036: may deprive them of the benefits of research. NIH, for example, has a policy (NIH, 1998) with a
p.000036: goal of increasing participation of children in research.
p.000036:
p.000036: 3.3 Minimal Risk and Vulnerable Groups
p.000036: EPA has codified protections for children, pregnant or nursing women, and fetuses in Subparts B, C, and D of the EPA
p.000036: human subjects rule (40 CFR 26). Subpart B strictly prohibits research involving intentional exposure of children
p.000036: or pregnant or nursing women (and, therefore, exposure of her fetus).
p.000036: EPA’s regulations do allow for observational research involving fetuses and pregnant women (40 CFR 26
p.000036: Subpart C) or children (40 CFR 26 Subpart D) but with additional protections in place and with
p.000036: strict limitations on research that presents more than minimal
p.000036: risk (CFR, 2006a).13 When considering vulnerable groups, The Institutional Review Board Guidebook (U.S. HHS,
p.000036: 1993) states that “IRBs should therefore determine whether the proposed subject population would be more sensitive or
p.000036: vulnerable to the risks posed by the research as a result of their general condition or disabilities. If so, the
p.000036: procedures would constitute more than minimal risk for those subjects.”
p.000036: When conducting observational human exposure studies, it is recommended that researchers consult these
p.000036: regulations and guidebooks. NERL researchers also will need to ensure that all of the requirements in Subparts B, C,
p.000036: and D of the EPA Human Subjects Rule are met.
p.000036:
p.000036: 3.4 Research Involving Children
p.000036: Children long have been recognized as a vulnerable group in research studies. EPA and HHS both extend special
p.000036: protections to children (CFR, 2006a,b). There are many books, reports, and research manuscripts that
...
p.000037: is likely to entail) focuses on obtaining assent of the children and permission of their parents or guardians. But the
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
p.000037: biomedical research because of the potential for becoming pregnant during a study. The document continues, “A
p.000037: general policy of excluding from such clinical trials women biologically capable of becoming pregnant is
p.000037: unjust in that it deprives women as a class of persons of the benefits of new knowledge derived from the
p.000037: trials.” The second relevant CIOMS guideline, number 17, asserts that, if involved in a research study,
p.000037: pregnant women should be fully informed, and included only if the
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: research benefits pregnant women and is thoroughly supported by reliable evidence in animal studies.
p.000038: Although the CIOMS guideline specifically addresses biomedical research, the ethical concepts
p.000038: behind the guidelines generally may be applicable to observational human exposure studies. EPA’s human
p.000038: subjects rule is completely consistent with the HHS rule in adding additional protections for pregnant women and
p.000038: fetuses involved in observational research (40 CFR
p.000038: 26.304 and 45 CFR 46.204). These additional protections (specified in 45 CFR 46.204 subparagraphs a
p.000038: through j) reflect the CIOMS recommendations by requiring: availability of data from previously conducted
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
...
p.000051: be recommendations as ethical “best practices.”
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: Text Box 5-2. Common Rule Requirements:
p.000052: Elements of Informed Consent
p.000052: (1) An explanation of the purposes of the research
p.000052: (2) The expected duration of the subject's participation
p.000052: (3) A description of the procedures to be followed and identification of any experimental procedures
p.000052: (4) A description of any reasonably foreseeable risks or discomforts to the subject
p.000052: (5) A description of any reasonably expected benefits to the subject or others
p.000052: (6) A disclosure of appropriate alternative procedures that might be advantageous to the subject
p.000052: (7) A description of the extent that confidentiality will be maintained
p.000052: (8) For research involving more than minimal risk, an explanation about whether compensation or medical treatments
p.000052: are available if injury occurs
p.000052: (9) An explanation of whom to contact with questions about the research or to report a research-related injury
p.000052: (10) A statement that participation is voluntary, refusal to participate will involve no penalty, and the subject may
p.000052: discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled
p.000052: (11*) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or
p.000052: fetus, if the subject is or may become pregnant) that are currently unforeseeable
p.000052: (12*) Anticipated circumstances under which the subject's participation may be terminated by the investigator without
p.000052: regard to the subject's consent
p.000052: (13*) Any additional costs to the subject that may result from participation in the research
p.000052: (14*) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of
p.000052: participation by the subject
p.000052: (15*) A statement that significant new findings developed during the course of the research that may relate to the
p.000052: subject's willingness to continue participation will be provided to the subject.
p.000052: (16*) The approximate number of subjects in the study
p.000052: * Included if appropriate [40 CFR 26.116(b)]
p.000052:
p.000052:
p.000052:
p.000052: • The information “shall be in language understandable to the subject” (40 CFR 26.116). This may require forms
p.000052: to be written and administered in different languages during a study. For example, the National
p.000052: Children’s Study (NCS) plans to produce all consent materials in English and Spanish, with other
p.000052: translations made available as needed (NCS, 2007).
p.000052: Participants often find discussions with research staff more useful than written consent forms (p. 103, NRC & IOM,
p.000052: 2005). NCS plans to pilot test an interactive, computer-based audio/video consent tool and to compare it
...
p.000061: Director’s Council of Public Representatives (COPR) (NIH, 2005). Although the advice from this workshop was
p.000061: developed in the context of NIH-supported clinical research, many of the recommendations are applicable to
p.000061: observational human exposure studies and human subject research in general. A summary
p.000061: of
p.000061: recommendations from the report for enhancing public trust is provided in Appendix D. The recommendations are
p.000061: focused on the following areas.
p.000061: • Building trust through community partnerships
p.000061: • Building relationships with patients (participants) (True partnerships with patients may not be possible,
p.000061: but bidirectional relationships must be enhanced.)
p.000061: • Building partnerships with community providers
p.000061: • Building trust in scientists
p.000061: • Building trust in the (EPA) and scientific research.
p.000061:
p.000061: 5.5 Recruitment Strategies
p.000061: Many strategies are used to select and recruit people into research studies requiring human participation. The IRB is
p.000061: responsible for reviewing the selection process to ensure that it is, above all, equitable. The requirement for
p.000061: IRB review is stated in 40 CFR 26.111(a)3.
p.000061: Selection of subjects is equitable. In making this assessment, the IRB should take into account the
p.000061: purposes of the research and the setting in which the research will be conducted and should be particularly cognizant
p.000061: of the special problems of research involving vulnerable populations, such as children, prisoners,
p.000061: pregnant women, mentally disabled persons, or economically or educationally disadvantaged
p.000061: persons.
p.000061: The IRB guidebook is an excellent resource for consideration of concerns and elements for equitable
p.000061: participant selection (U.S. HHS, 1993). It states that “Defining the appropriate group of subjects
p.000061: for a research project involves a variety of factors⎯ requirements of scientific design,
p.000061: susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness.” The IRB
p.000061: guidebook raises a number of points to consider in the process for selection of human participants (see Text Box
p.000061: 5-5).
p.000061: Various participant recruitment strategies may be used depending on the type of research being performed and the
p.000061: population of interest. This section addresses the strategies and approaches for identifying and contacting people and
p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
...
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
p.000117:
p.000118: 118
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p.000118:
p.000118:
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p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118: United States Environmental Protection Agency
p.000118:
p.000118:
p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
...
Health / Terminally Ill
Searching for indicator terminally:
(return to top)
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
...
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
...
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
p.000117:
p.000118: 118
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p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118: United States Environmental Protection Agency
p.000118:
p.000118:
p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
...
Health / ill
Searching for indicator ill:
(return to top)
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
...
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
...
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
p.000062: 1. Who will bear the burden? Who will reap the benefits?
p.000062: 2. Is there a disproportionate burden on any single group?
p.000062: 3. Is the proposed subject population required or justified?
p.000062: 4. Are there susceptible groups of people who should be excluded from the research?
p.000062: 5. Are anticipated benefits distributed fairly? Do others have a greater need to receive any of the anticipated
p.000062: benefits?
p.000062: 6. Are the research burdens distributed fairly?
p.000062: 7. Will any special physiological, psychological, or social characteristics of the subject group pose special risks
p.000062: for them?
p.000062: 8. Would it be possible to conduct the study with other, less vulnerable subjects?
p.000062: 9. Has the selection process overprotected potential subjects who are considered vulnerable (e.g., children,
p.000062: cognitively impaired, economically or educationally disadvantaged persons, patients of researchers, seriously ill
p.000062: persons), so that they are denied opportunities to participate in research?
p.000062: 10. If the subjects are susceptible to pressures, are there mechanisms to reduce the pressures or minimize their
p.000062: impact?
p.000062:
p.000062:
p.000062: Some of the common approaches for identifying and making initial contact with potential participants include, but are
p.000062: not limited to
p.000062: • direct telephone or in-person contact with a person selected through a statistical sampling process
p.000062: to obtain a representative sample of the population being studied;
p.000062: • use of print or other media advertisements, often used to recruit people in a community with specific
p.000062: characteristics;
p.000062: • advertisement or word-of-mouth contacts through community groups, civic organizations, or other types of
p.000062: organizations; and
p.000062: • recruitment at physicians’ offices, hospitals, and clinics or at churches, schools, or other
p.000062: social institutions, either in person or through the use of advertisements or study brochures.
p.000062: CABs can be consulted regarding proposed approaches for recruitment in community-based
p.000062: research. All procedures and materials for participant recruitment are reviewed and approved by the IRB prior to
p.000062: implementation. Some of the materials prepared for recruitment might include the following.
p.000062: • Recruitment scripts⎯prepared scripts used for in- person or telephone study information and recruitment
p.000062: contacts
p.000062: • Printed materials⎯brochures, flyers, newspaper advertisements, letters, and information articles
p.000062: • Audio/visual materials⎯radio and television scripts, video segments, public service announcements
...
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
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p.000118:
p.000118:
p.000118: United States Environmental Protection Agency
p.000118:
p.000118:
p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
...
Health / patients in emergency situations
Searching for indicator emergencies:
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p.000091:
p.000091: ATSDR (Agency for Toxic Substances and Disease Registry) (2007). A Primer on Health Risk Communication Principles
p.000091: and Practices [online publication]. Available: http://www.atsdr.cdc.gov/risk/riskprimer/ [accessed 12 June 2007].
p.000091:
p.000091: CDC (Centers for Disease Control and Prevention) (2005). Third National Report on Human Exposure to Environmental
p.000091: Chemicals. National Center for Environmental Health, Atlanta, GA, NCEH Pub. No. 05 0570. Available:
p.000091: http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf [accessed 12 June 2007].
p.000091:
p.000091: Covello V, Allen F (1988). Seven Cardinal Rules of Risk Communication. OPA-87-020. U.S. Environmental Protection
p.000091: Agency, Office of Policy Analysis, Washington, DC. Distributed by the Pennsylvania Dept. of Environmental Resources.
p.000091: Available: http://www.epa.gov/stakeholders/pdf/risk.pdf [accessed 12
p.000091: June 2007].
p.000091:
p.000091: Covello VT, McCallum DB, Pavlova M (eds) (1989). Effective Risk Communication: the role and responsibility of
p.000091: Government and Non-Government Organizations. New York. NY: Plenum Press.
p.000091:
p.000091: Covello V, Minamyer S, Clayton K (2007). Effective risk and crisis communication during water security emergencies
p.000091: summary report of EPA sponsored message mapping.
p.000091: EPA/600/R-07/027. National Homeland Security Research Center, Office of Research and Development, U.S. Environmental
p.000091: Protection Agency, Washington, DC. Available: http://www.epa.gov/nhsrc/pubs/reportCrisisCom040207.pdf
p.000091:
p.000091: FCN (Federal Communicators Network) (2001). Communicators Guide For Federal, State, Regional, and Local Communicators
p.000091: by the Federal Communicators Network. Available: http://www.publicforuminstitute.org/activities/2002/fcn/co mmguid.pdf
p.000091: [accessed 12 June 2007].
p.000091:
p.000091: Fenske RA, Kissel JC, Lu C, Kalman DA, Simcox NJ, Allen EH, Keifer MC (2000) Biologically based pesticide dose
p.000091: estimates for children in an agricultural community.
p.000091: Environ Health Persp 108(6):515-20.
p.000091:
p.000091: Fernandez CV, Kodish E, Weijer C (2003). Informing study participants of research results: an ethical imperative. IRB
p.000091: 25(3):12-19.
p.000091:
p.000091: Health Canada (2006). The Strategic Risk Communications Framework. Available: http://www.riskcommunications.gc.ca
p.000091: [accessed 18
p.000091: September 2007].
p.000091:
p.000091: IOM (Institute of Medicine) (2002). Responsible Research: A Systems Approach to Protecting Research Participants.
p.000091: Daniel D. Federman, Kathi E. Hanna, and Laura Lyman
p.000091:
p.000091:
p.000092: 92
p.000092:
p.000092: Rodriguez (eds). Washington, DC: The National Academies Press.
p.000092:
p.000092: Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005). Methods in Community-Based Participatory Research for Health. San
p.000092: Francisco, CA: Jossey-Bass.
p.000092:
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Health / visual impairment
Searching for indicator blind:
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p.000056: studies of varying complexity that included payments, the median
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: payment was $155 (mean $266, range $5 to $2,000). The basis for dollar amounts was infrequently described, with
p.000057: 19% of the payments based on time, and 12% based on the procedures. In a model of payment factors,
p.000057: studies with some prospect of therapeutic benefit, studies having at least one invasive procedure, and studies with
p.000057: greater numbers of clinic visits were significantly associated with higher dollar amounts. About 9.5%
p.000057: of the studies offered completion bonuses, and a similar percentage offered escalating payments for
p.000057: followup study visits.
p.000057:
p.000057: 5.2.2 Regulations and Guidance Regarding Payment to Research Participants
p.000057: There is little specific guidance regarding payments in Federal human research regulations. The Common Rule and
p.000057: additional human subjects protections do not directly address payments to research participants, but the
p.000057: regulations do discuss providing additional safeguards for subjects vulnerable to coercion or undue
p.000057: influence [40 CFR 26.111(b)]. The NIH IRB guidebook advises IRBs to determine whether the rewards offered for
p.000057: participation in research constitute undue influence (U.S. HHS, 1993). According to the IRB guidebook undue
p.000057: inducement might blind prospective subjects to risks, impair their ability to exercise proper judgment, or may
p.000057: cause people to lie or to withhold information that would make them ineligible to enroll or continue
p.000057: participation.
p.000057: The U.S. Food and Drug Administration (FDA) has provided guidance for investigators and IRBs for clinical research
p.000057: studies (FDA, 1998). The guidance states that “payment to research subjects for participation in studies is not
p.000057: considered a benefit, it is a recruitment incentive.” FDA expects payments to accrue as the study progresses and not
p.000057: to be contingent on completing the study, although a “small proportion as an incentive for
p.000057: completion of the study is acceptable.” The guidance is concerned with the issue of coercion or undue influence, and
p.000057: it recognizes the IRB as the responsible party for deciding what is or is not acceptable.
p.000057: The U.S. Office of Management and Budget (OMB) develops standards and guidelines for statistical surveys performed by
p.000057: the Federal government. Under Guideline 2.3.2, OMB states that, while incentives are not typically used in Federal
p.000057: surveys, agencies may consider use of respondent incentives if they believe incentives would be necessary
p.000057: to use for a particular survey to achieve data of sufficient quality for their intended use (OMB,
p.000057: 2006a). OMB requires that agencies provide a justification for giving incentives to respondents.
p.000057: Some
...
Social / Access to Social Goods
Searching for indicator necessities:
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p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
...
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
p.000117:
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...
Searching for indicator access:
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p.000003: tools available to researchers.
p.000003: This document does not and, indeed, could not provide solutions to all scientific and ethical issues that may
p.000003: arise as observational human exposure studies are undertaken. No document could identify and address all
p.000003: potential issues in advance, nor is it possible to develop a comprehensive checklist for all such studies.
p.000003: Rather, this document attempts to present and discuss the types of ethical and scientific issues that will need
p.000003: to be considered and addressed as NERL researchers plan and implement observational human exposure studies. The
p.000003: researchers will need to work with others ― the study team, IRB members, EPA’s HSRRO, the participants
p.000003: and their community, and other stakeholders ― to identify and address all of the relevant issues
p.000003: for any particular study. The authors are confident that this document will be helpful to NERL scientists
p.000003: in their endeavors to assure that all of NERL’s observational human exposure studies will respect,
p.000003: safeguard, and protect the participants in that research.
p.000003:
p.000003: References
p.000003: Beauchamp TL, Childress, JF (2001). Principles of Biomedical Ethics: Fifth Edition. New York, NY: Oxford University
p.000003: Press.
p.000003:
p.000003: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000003: Subjects. U.S. Code of Federal Regulations.
p.000003: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2008). International Ethical Guidelines for
p.000003: Epidemiological Studies. World Health Organization. Geneva, Switzerland. Available:
p.000003: http://www.cioms.ch/080221feb_2008.pdf [accessed 25
p.000003: April 2008].
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000003: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000003:
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000004: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000004:
p.000004: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
p.000004:
p.000004: ERG (Eastern Research Group) (2007). Report on the Workshop to Discuss State-of-the-Science Approaches for
p.000004: Observational Exposure Measurement Studies. Held in Durham, North Carolina on November 28-29, 2006. Final Report:
p.000004: January 25, 2007. (PB2007-108905).
p.000004:
p.000004: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000004: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000004: [accessed 12 June 2007].
p.000004:
p.000004: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
...
p.000007: objectives, designs, and results of these studies.
p.000007: NERL researchers have conducted and relied on observational human exposure studies for more than three
p.000007: decades. Examples of studies conducted or funded by NERL are listed in Appendix A, Table A-1. Common goals in those
p.000007: studies included those that follow.
p.000007: • Identify which chemicals or other stressors that people are exposed to during their normal activities in the
p.000007: environments that they occupy.
p.000007: • Measure the concentrations of the chemicals to which people are exposed.
p.000007: • Identify the most important routes and pathways of exposure.
p.000007: • Identify the factors that impact people’s exposures (i.e., determine the when, why, how, and how much
p.000007: that people are exposed to chemicals in the environment).
p.000007: These studies involve many different types of data collection efforts and typically include
p.000007: observations,
p.000007: measurements, and information on the following items.
p.000007: • Chemical concentrations in environmental media (air, water, soil, floor dust, and dust on surfaces)
p.000007: • Chemical concentrations in the diet (food and beverages).
p.000007: • Biomonitoring (measurements of biomarkers of exposure in urine, blood, and saliva)
p.000007: • Time, location, and activity information
p.000007: • Information on personal activities, product use, diet, occupation, and other factors that may
p.000007: impact exposure
p.000007: • Information on the characteristics of the environments that study participants occupy (homes, schools,
p.000007: offices, public access buildings, etc.)
p.000007: The information obtained in observational human exposure studies is used to better understand people’s
p.000007: contact with chemicals in the environment and to improve exposure assessments and risk assessments.
p.000007: This information is also essential for developing risk mitigation strategies and for developing
p.000007: educational materials and programs for reducing exposures and risks to chemicals or other stressors in the
p.000007: environment (see Table 1-1).
p.000007:
p.000007: 1.2 Ethical Issues in Observational Human Exposure Studies
p.000007: By definition, observational human exposure studies involve human subjects. Whenever their research
p.000007: involves human subjects, EPA researchers are required to ensure the protection of the study participants
p.000007: by complying with the Agency’s human subjects rules as set forth in 40 CFR 26.
p.000007: The Common Rule (Subpart A of the rules) represents basic regulatory actions (common to more than
p.000007: a dozen Federal departments or agencies) that are intended to ensure the protection of all human subjects. The
p.000007: central requirements of the Common Rule are twofold:
p.000007: (1) that people who participate as subjects in covered research are selected equitably and give
...
p.000013: • Community and Stakeholder Relationships (Section 6) begins with the principles of fairness, justice, and
p.000013: equity and of respect for persons to develop approaches to demonstrate respect for culture
p.000013: and to empower the participants’ community to endure, including the need to build trust in the community and
p.000013: with stakeholders through open and honest communications and legitimate power sharing.
p.000013: • Strategies for Effective Communication (Section 7) builds on the presumption of an ongoing, interactive
p.000013: dialogue and exchange of ideas between researchers and the participants, community, and stakeholders and focuses
p.000013: on steps that the researcher needs to take for effective communications. The section discusses communication
p.000013: strategies, implementation plans, communication tools, reporting of results, and approaches for
p.000013: effective communications, two-way communications between the researchers, participants, community, and other
p.000013: stakeholders.
p.000013:
p.000013: References
p.000013: Beauchamp TL, Childress, JF (2001). Principles of Biomedical Ethics: Fifth Edition. New York, NY: Oxford University
p.000013: Press.
p.000013:
p.000013: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000013: Subjects. U.S. Code of Federal Regulations.
p.000013: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06
p.000013: .html [accessed 12 June 2007].
p.000013:
p.000013: CIOMS (The Council for International Organizations of Medical Sciences) (2008). International Ethical Guidelines for
p.000013: Epidemiological Studies. Geneva, Switzerland: CIOMS. Available: http://www.cioms.ch/080221feb_2008.pdf [accessed 25
p.000013: April 2008].
p.000013:
p.000013: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000013: Biomedical Research Involving Human Subjects.
p.000013: Geneva, Switzerland: CIOMS. Available: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000013:
p.000013: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000013:
p.000013: NEAC (National Ethics Advisory Committee) (2006). Ethical Guidelines for Observational Studies: Observational research
p.000013: audits and related activities. Wellington, New Zealand: Ministry of Health. Available:
p.000013: http://www.neac.health.govt.nz/moh.nsf/indexcm/neac resources-publications-ethicalguidelines.
p.000013:
p.000013: NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing Research
p.000013: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000013: [accessed 16 August 2007].
p.000013:
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p.000022: from which the participants were selected. Pilot studies performed to evaluate a method or to estimate
p.000022: the likely range of exposure concentrations often have employed either purposeful sampling, where
p.000022: the researchers use information on the relevant characteristics of the population to select those
p.000022: participants who will exhibit a wide range of activity levels or potential exposure concentrations, or
p.000022: convenience sampling, where the researchers select the most accessible members of a population
p.000022: NERL’s observational human exposure studies also have routinely collected information about the
p.000022: participants’ activities by using questionnaires and surveys. Survey design is both a science and an
p.000022: art because the design of surveys is based on statistics and science, but designing a good and effective questionnaire
p.000022: is often an art that requires understanding the individuals being surveyed. Text Box 2-3 identifies some of the
p.000022: areas of art involved in designing an effective questionnaire.
p.000022: Understanding the process for selecting participants and the statistical-scientific requirements of
p.000022: questionnaire design are both components of survey sampling and design. A variety of references can provide
p.000022: the researcher with information about the issues in survey sampling and
p.000022: design. (See http://home.ubalt.edu/ntsbarsh/Business-stat/stat data/Surveys.htm and
p.000022: www.statpac.com/surveys/, for example.) But the research team must include or have access to the appropriate
p.000022: survey statistics expertise as it plans the research study.
p.000022:
p.000022: Text Box 2-3. Questionnaire Considerations
p.000022: • Questions should be simple and in a language the individual can understand.
p.000022: • Questions should be unambiguous.
p.000022: • Questions should be relevant to the study.
p.000022: • Questions should not be too personal.
p.000022: • The questionnaire should be as short as possible.
p.000022: • The questions should not be leading (e.g., internally suggestive of the answer).
p.000022: • Questions should follow a logical order.
p.000022:
p.000022:
p.000022:
p.000022: 2.2.5 Information Collection Rule
p.000022: As Federal employees, NERL researchers also must be aware of Information Collection Rule requirements. The
p.000022: Paperwork Reduction Act stipulates that every Federal agency must obtain approval from OMB before collecting
p.000022: the same or similar information from 10 or more members of the public. An Information Collection Request (ICR)
p.000022: is required if the same or similar information is being collected from 10 or more non- Federal
p.000022: respondents within a 12-month period, even if the information collection is voluntary. Generally, any
p.000022: survey, questionnaire, monitoring, reporting, or recordkeeping requirement imposed on
p.000022: non-Federal respondents by EPA will require an ICR. Information collections associated with all cooperative
p.000022: agreements funded by the EPA require an ICR. When an ICR is required, it must be approved by OMB
p.000022: before the collection begins, regardless of whether the collection of information is mandatory, voluntary,
...
p.000023: • Introduction and background, including the purpose and scope of the study
p.000023: • The desired outputs and outcomes of the study, including the objectives and the hypotheses to be tested
p.000023: • A brief description or overview of the study
p.000023: • The technical approach and conceptual model that accounts for
p.000023: – sources of the chemicals being studied;
p.000023: – potential routes and pathways of exposure;
p.000023: – factors that may impact exposure and other relevant stressors;
p.000023: – selection and characteristics of the study participants; eligibility criteria; and recruitment, retention, and
p.000023: payment approaches;
p.000023: – justification for sample size, the methodology for selecting participants, and the sampling methods;
p.000023: – characteristics of the community in which the study will be performed;
p.000023: – environmental conditions, factors, or end points to be measured, including sampling and analysis approaches and
p.000023: methods (with description of expected performance);
p.000023: – survey design and questionnaires and other survey instruments, as applicable (with description of prior use and
p.000023: validation in similar studies);
p.000023: – pilot studies that may be undertaken;
p.000023: – quality assurance project plan and quality control;
p.000023: – timeframe for the study;
p.000023: – exposure scenarios to be considered;
p.000023: – burden of the study on the participants;
p.000023: – resources available; and
p.000023: – feasibility
p.000023: • Discussion of alternative study designs and approaches considered and reasons for rejecting other approaches and
p.000023: selecting the one proposed
p.000023: • An analysis plan that considers
p.000023: – Information and data needs, including data storage, security, access, and release;
p.000023: – nature of the measurement data (e.g., variability, quality assurance);
p.000023: – how the collected data will be used, and how the proposed analyses will address objectives of the study; and
p.000023: – hypotheses to be tested and statistical power and sample size required to test the hypotheses
p.000023: • Resources required or available
p.000023: • Project organization and management, including team members and roles and responsibilities
p.000023: • Schedule
p.000023:
p.000023: fairness in human subjects research is that scientific goals, considered in dynamic interaction with
p.000023: the potential for and distribution of risks and benefits, should guide the selection of subjects.”
p.000023: (Emmanuel et al, 2000). On the other hand, as discussed in Section 3, many study problems specifically
p.000023: address exposures of vulnerable groups to chemicals and other stressors. Researchers should not avoid
p.000023: research studies that will,
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024: of necessity, include vulnerable groups to address the study hypotheses or objectives simply to avoid the more
p.000024: stringent requirements for working with these groups.
p.000024:
p.000024: 2.4 Ensuring a Favorable Risk-Benefit Ratio
p.000024: 2.4.1 Designing in Benefits for the Participants
p.000024: Study designs vary depending on the objectives of the study, existing knowledge on the research question, and
p.000024: the hazard being studied (NRC & IOM, 2005). Recent ethical discussions about study designs in human subjects
...
p.000031: • Participation⎯poor response to questionnaires, poor compliance with researcher requests in data collection
p.000031: activities
p.000031: • Burden⎯higher than predicted
p.000031: • Changes in participant behaviors⎯potential changes because of participation in the study
p.000031: • Grievances⎯participant issues
p.000031: • Retention⎯high dropout rates
p.000031: • Community issues⎯poor interactions, lack of support
p.000031: • Third-party issues⎯problems with landlords, spouses, or others
p.000031: • Collateral observations⎯identification of nonstudy hazards, difficulty reporting
p.000031: • Unanticipated results⎯high contaminant concentrations measured, unexpected results
p.000031: • New data indicating that participation in the study (or observations measured in the study) represent a risk to
p.000031: participants or others
p.000031:
p.000031:
p.000031:
p.000031: References
p.000031: Castelloe, JM (2000). Sample size computations and power analysis with the SAS system. Paper 265-25 in Proceedings of
p.000031: the 25th Annual SAS Users Group International Conference. Cary, NC: SAS Institute, Inc. Available:
p.000031: http://support.sas.com/rnd/app/papers/powersamplesize.pdf [accessed 16 April 2008].
p.000031:
p.000031: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of
p.000031: Human Subjects. U.S. Code of Federal Regulations. Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/
p.000031: 40cfr26_06.html [accessed 12 June 2007].
p.000031:
p.000031: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000031: Biomedical Research Involving Human Subjects.
p.000031: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000031:
p.000031: Coggon D, Rose G, Barker DJP (1997). Epidemiology for the Uninitiated, Fourth Edition. London: BMJ Publishing Group
p.000031: Ltd. Available at http://www.bmj.com/epidem/epid.html [accessed 29
p.000031: January 2008].
p.000031:
p.000031: Cohen Hubal EA, Sheldon LS, Zufall, MJ, Burke JM, Thomas KW (2000). The challenge of assessing children’s residential
p.000031: exposure to pesticides. Journal of Exposure Analysis and Environmental Epidemiology 10(6 part 2): 638-649.
p.000031:
p.000031: Dallal, GE (2001). Some aspects of study design. In The Little Handbook of Statistical Practice at
p.000031: www.StatisticalPractice.com, and at http://www.tufts.edu/~gdallal/STUDY.HTM [accessed 29
p.000031: January 2008]
p.000031: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000031:
p.000031: Gilbert, SG (2006). Supplementing the traditional institutional review board with an environmental health and community
p.000031: review board. Environmental Health Perspectives 114(10): 1626-1629.
p.000031:
p.000031: Kraemer HC, Thiemann S (1987). How Many Subjects? Statistical Power Analysis in Research. Newbury Park, CA: Sage
p.000031: Publications.
p.000031:
...
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
p.000035: the CIOMS document (Guidelines 14 and 15) and include children, and persons who, because of mental or behavioral
p.000035: disorders, are incapable of giving informed consent. Ethical justification of their involvement usually requires that
p.000035: • the research could not be carried out equally well with less vulnerable subjects;
p.000035: • the research is intended to obtain knowledge that will lead to improved diagnosis, prevention, or treatment of
p.000035: diseases or other health problems characteristic of, or unique to, the vulnerable class—either the actual subjects or
p.000035: other similarly situated members of the vulnerable class;
p.000035: • research subjects and other members of the vulnerable class from which subjects are recruited will ordinarily be
p.000035: assured reasonable access to any diagnostic, preventive, or therapeutic products that will become available as a
p.000035: consequence of the research;
p.000035: • the risks attached to interventions or procedures that do not hold out the prospect of direct health-related
p.000035: benefit will not exceed those associated
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036: CIOMS recommendations, although written to address biomedical research, also generally are
p.000036: applicable to observational human exposure studies. The authors of this document consider the CIOMS
p.000036: requirement that the research could not be carried out equally well with less vulnerable subjects
p.000036: to be particularly important. EPA and NERL researchers should include vulnerable groups in
p.000036: observational human exposure studies only if their participation is critical to the success and
p.000036: applicability of the research. Even then, EPA and NERL researchers will have to meet stringent standards for
p.000036: protecting the rights and safety of the vulnerable participants. For example, EPA regulations
p.000036: governing observational research with children are even more stringent than the CIOMS guideline.
p.000036: If such research does not hold out the prospect of direct benefit to the child, no increase whatsoever over
...
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
p.000038: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle A Department of Health and Human Services Part 46 Protection
p.000038: of Human Subjects. U.S. Code of Federal Regulations. Available:
p.000038: http://www.access.gpo.gov/nara/cfr/waisidx_06/45cfr46_06.ht ml [accessed 13 June 2007].
p.000038:
p.000038: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000038: Biomedical Research Involving Human Subjects.
p.000038: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000038:
p.000038: Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry MR, Rigas ML, Zartarian VG, Freeman NCG (2000).
p.000038: Children’s exposure assessment: a review of factors influencing children’s exposure, and the data available to
p.000038: characterize and assess that exposure. Environ Health Perspect 108(6): 475-486.
p.000038:
p.000038: Emanuel EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000038:
p.000038: IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Washington, DC: The
p.000038: National Academies Press. Available: http://www.nap.edu/catalog.php?record_id=10958 [accessed 16 April 2008].
p.000038:
p.000038: Kodish E (Ed.) (2005). Ethics and Research with Children: A Case-Based Approach. New York: Oxford University Press.
p.000038:
p.000038: NBAC (National Bioethics Advisory Commission) (2001). Ethical and Policy Issues in Research Involving Human
p.000038: Participants, Volume I: Report and Recommendations of the National Bioethics Advisory Commission. Bethesda, MD:
...
p.000040: biological measurements in people’s homes or personal locations. Many of the topics identified in that report are
p.000040: discussed in this section (Text Box 4-1).
p.000040:
p.000040:
p.000040: Text Box 4-1. Topics in Section 4
p.000040: Privacy Issues Confidentiality
p.000040: Confidentiality of Information Confidentiality of Participation
p.000040: Collateral Observations
p.000040: Potential Nonstudy Hazards in the Residence Collateral Observations with Mandated Reporting
p.000040: Requirements
p.000040: Hazard Communication Planning and Staff Training
p.000040: Third-Party Issues
p.000040: Determining Whether a Third Party is a Human Subject Informing Third Parties of Research Activities Research Results
p.000040: and Third Parties
p.000040: Data and Safety Monitoring and Oversight
p.000040:
p.000040:
p.000040:
p.000040: 4.1 Privacy Issues
p.000040: Privacy refers to an expectation that a person is free from intrusion into personal matters and is free from the
p.000040: presence or view of others. The Institutional Review Board Guidebook defines privacy as “control over the
p.000040: extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with
p.000040: others” (U.S. HHS, 1993). Beauchamp and Childress find that the right to privacy is based on the principle of
p.000040: respect for autonomy. “We often respect persons by respecting their autonomous wishes not to be observed, touched, or
p.000040: intruded upon…. A loss of privacy occurs if others use any of several forms of access, including intervening in zones
p.000040: of secrecy, anonymity, seclusion, or solitude” (pp. 295-296, Beauchamp and Childress, 2001).
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041: Although research participants may agree to allow researchers to enter their home or other zone of personal space
p.000041: to conduct their research measurements, they have not abrogated their right to privacy. “When individuals
p.000041: voluntarily grant others some form of access to themselves, their act is an exercise of the
p.000041: right to privacy, not a waiver of that right” (p. 297, Beauchamp and Childress, 2001). Researchers should remember
p.000041: that they are guests in the homes for a specific purpose. “When people visit a home, there are social
p.000041: expectations about what is acceptable behavior. People who are invited into a home are expected to be
p.000041: sensitive to and respectful of the host’s customs and values” (p. 65, NRC & IOM, 2005).
p.000041: By their very nature, observational human exposure studies encroach on the privacy of a research participant. Entry in
p.000041: a participant’s home (or other personal zones) does represent a loss of privacy, but researchers should be
p.000041: careful to ensure that their presence does not become a violation of the individual’s right to privacy. The
p.000041: relationship between the researcher and the participant may be complicated, and there may be conflicts between
p.000041: the researcher’s role and their ethical obligations (NRC & IOM, 2005). In entering a participant’s
p.000041: personal space, it may be difficult, or impossible, to avoid making observations unrelated to the research question,
p.000041: thereby further intruding on the participant’s personal privacy. Indeed, there may be ethical and legal
p.000041: obligations for the researchers to respond to those observations. Beauchamp and Childress suggest that “policies
p.000041: carefully specify the conditions of access that will and will not count as a loss of privacy or a violation of
p.000041: the right to privacy. The policy should accurately define the zones that are considered private and
p.000041: not to be invaded, and should also identify interests that legitimately may be balanced against privacy
p.000041: interests” (Beauchamp and Childress, 2001).
p.000041: Observational human exposure studies also may infringe on the privacy of other individuals, for example,
p.000041: other members of the participant’s family or household. Researchers should strive to minimize the intrusion and loss
p.000041: of privacy and to show respect for the privacy of study participants and third parties at all times (see Text
p.000041: Box 4-2 for a list of relevant privacy issues). It is incumbent on the researcher to recognize privacy issues
p.000041: in the design and implementation of the research study. The NRC & IOM report suggests that researchers
p.000041: anticipate the ethical issues that arise from conducting research in a person’s home, and that they take steps
p.000041: to correct them (1) by thinking through the issues as part of the study design; (2) by discussing the issues during the
p.000041: informed consent process; and (3) by ensuring that the frontline staff that enter a
p.000041: participant’s home “understand their role as members of the research team, how that role differs from the role of
p.000041: neighbor or friend, and how they should respond when they make observations that are not part
p.000041: of the protocol” (p. 66, NRC & IOM, 2005).
p.000041:
...
p.000042: communicable diseases or evidence of child abuse or neglect. These and similar limits to the ability
p.000042: to maintain confidentiality should be anticipated and disclosed to prospective subjects.”
p.000042: to identify an individual. Precise geographic location information may be sufficient to pinpoint a
p.000042: residence. Researchers may use several strategies to reduce the likelihood of indirect identification when
p.000042: study results are reported (see, also, Text Box 4-3).
p.000042: • Redact from publications, reports, or public data sets information that might be used to indirectly identify a
p.000042: research participant.
p.000042: • Generalize exact information; for example, replace birth date with age or year of birth or classify age as
p.000042: part of a range.
p.000042: • Aggregate information across individuals; for example, only report data in cells of sufficient size
p.000042: to make individual linkages unlikely.
p.000042: • Reduce the specificity of geographic coordinate information to a level that a specific residence or other
p.000042: location can not be identified.
p.000042:
p.000042: Text Box 4-3. Approaches for Protecting Personally Identifiable Information
p.000042: • Developing procedures for safeguarding information prior to collecting the information
p.000042: • Ensuring that data or samples are anonymous by not collecting or by destroying identifying information or linkages
p.000042: • Restricting access to identifying information to only those requiring access
p.000042: • Assigning codes to participants, data, and samples rather than using identifiers
p.000042: • Physically separating identifying information and linkage files from other study information
p.000042: • Securing identifying information in locked files with limited access
p.000042: • Restricting identifying information from computers that are networked with other computers or electronic systems
p.000042: • Restricting identifying information from computers that are not kept in secure locations with limited access
p.000042: • Training research staff members on human subject protection and on information security procedures
p.000042:
p.000042:
p.000042: Another step that can help protect confidentiality is to obtain a Certificate of Confidentiality. Certificates of
p.000042: Confidentiality are issued by NIH (2002) to protect identifiable research information from forced disclosure.
p.000042: They allow the investigator and others who have access to research records to refuse to disclose identifying
p.000042: information on research participants in any civil, criminal, administrative, legislative, or other
p.000042: proceeding, whether at the Federal, State, or local level. Certificates of Confidentiality may be granted for studies
p.000042: collecting information that, if disclosed, could have adverse consequences for subjects or damage
p.000042: their financial standing, employability, insurability, or reputation. By protecting researchers and
p.000042: institutions from being
p.000042:
p.000042:
p.000043: 43
p.000043:
p.000043: compelled to disclose information that would identify research subjects, Certificates of Confidentiality
p.000043: help achieve the research objectives and promote participation in studies by assuring
p.000043: confidentiality and privacy to participants. Any research project that collects sensitive, personally identifiable
p.000043: information and that has been approved by an IRB is eligible for a certificate. Identifying information is broadly
p.000043: defined as any item or combination of items in the research data that could lead directly or indirectly to the
p.000043: identification of a research subject.
p.000043: Federal funding is not a prerequisite for a certificate. A Certificate of Confidentiality does not
p.000043: diminish, however, the investigator’s need to protect the personally identifiable information as
p.000043: described above.
p.000043:
p.000043: 4.2.2 Confidentiality of Participation
p.000043: In some types of research, the knowledge that a person is participating in a particular research study
...
p.000048: human requirements for adherence to the research protocol and compliance with ethical standards and with EPA’s
p.000048: human subjects rules
p.000048: • Ensuring that measurements and samples are collected as planned, and that data are reported on a timely basis
p.000048: • Evaluating whether the observed measurements exceed the pre-established threshold values and, if so,
p.000048: ensuring that reporting procedures and plans to respond to the potential risks are completed on a
p.000048: timely basis
p.000048: • Ensuring that quality assurance plans that define procedures for assessing and ensuring study
p.000048: protocol compliance are being met
p.000048: • Ensuring data quality targets are met through independent internal or external auditing
p.000048: requirements
p.000048: • Taking all warranted oversight actions to ensure the safety of the participants and the integrity of the
p.000048: study, including terminating the research study if appropriate
p.000048:
p.000048: References
p.000048: AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric Environmental Health. (2nd
p.000048: Edition). Elk Grove Village, IL: American Academy of Pediatrics.
p.000048:
p.000048: Beauchamp TL, Childress JF (2001). Principles of Biomedical Ethics. (5th Edition). New York, NY: Oxford University
p.000048: Press.
p.000048:
p.000048: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I⎯Environmental Protection Agency Part 26 Protection of Human
p.000048: Subjects. U.S. Code of Federal Regulations.
p.000048: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed August 2007].
p.000048:
p.000048: CIOMS (Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000048: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000048: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed June 2007].
p.000048: Emanuel, EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000048:
p.000048: NCI (National Cancer Institute) (2001). Essential Elements of a Data and Safety Monitoring Plan for Clinical Trials
p.000048: Funded by the National Cancer Institute. Available: http://www3.cancer.gov/rrp/dsm_ess.html [accessed April 2007].
p.000048:
p.000048: NEI (National Eye Institute) (2001). National Eye Institute Guidelines for Data Monitoring and Oversight of
p.000048: Observational Studies. Available: http://www.nei.nih.gov/funding/datastudies.asp [accessed April 2007].
p.000048:
p.000048: NHLBI (National Heart Lung and Blood Institute) (2007). Monitoring Boards for Data and Safety (Interim Policy). Policy
p.000048: effective date: 14 May 2007. Available: http://public.nhlbi.nih.gov/ocr/home/GetPolicy.aspx?id=8 [accessed September
p.000048: 2007].
p.000048:
p.000048: NHRPAC (National Human Research Protections Advisory Committee) (2002). Clarification of the status of third parties
p.000048: when referenced by human subjects in research. Available: http://www.hhs.gov/ohrp/nhrpac/documents/third.pdf [accessed
p.000048: April 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (2002). Extramural Projects - Application Instructions (03/15/2002) - Detailed
...
p.000054: will involve (NCS, 2007).
p.000054: • Development of written materials with appropriate languages and comprehension levels is only part of the
p.000054: communication challenge. In communities where languages other than English are spoken, it will be
p.000054: important that the research team be able to communicate orally with participants, often in ad hoc
p.000054: situations. Research protocols should address how translations will be accomplished. The use of
p.000054: untrained persons such as co-workers usually will not meet requirements for full understanding of human subject
p.000054: protections. Researchers should make plans for trained staff or trained community members, associated
p.000054: or affiliated with the research study, to be available for translations.
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
...
p.000060: guidance from EPA’s HSRRO to determine EPA’s latest policies and guidance in this regard. Input also should be sought
p.000060: from community representatives to ensure that any payment is adequate to compensate for expenses and reward
p.000060: participation, but that the payment is not so high as to constitute undue influence or coercion in the
p.000060: community. If the study includes several followup visits over a long term, NERL researchers should ensure that payment
p.000060: is made incrementally as the NRC & IOM committee suggested. NERL scientists also should adopt the IOM
p.000060: Recommendations 6.1 and 6.2, including ensuring that any payment should be for appropriate purposes
p.000060: and age-appropriate, and that the process should be open and fully disclosed, while not overly
p.000060: emphasizing payments during the recruiting or informed consent phases. The final decisions about the ethics of
p.000060: payments rest with the IRB, which will review, modify as needed, and approve the research protocol, and with the EPA
p.000060: HSRRO, who has final authority to approve, modify, or disapprove all of NERL’s human subjects research
p.000060: efforts.
p.000060: 5.3 Research Rights and Grievance Procedures
p.000060: Protecting the research rights of participants and providing independent access to information regarding
p.000060: those rights and to grievance procedures is an important element in developing and maintaining appropriate
p.000060: participant-investigator relationships. As part of the informed consent process, the Common Rule
p.000060: requires “An explanation of whom to contact for answers to pertinent questions about the research and
p.000060: human subjects’ rights, and whom to contact in the event of a research-related injury to the
p.000060: subject” [40 CFR 26.116(a)(7)].
p.000060: Information about the research often best can be answered by the researcher. However, it may benefit
p.000060: researchers and participants if information about the research can be obtained from or confirmed by a trusted
p.000060: independent person or organization. Participants also need to know how they can contact
p.000060: someone, independent from the researcher, who can answer questions concerning the rights of research
p.000060: participants and provide information on grievance procedures and research-related injuries. These questions
p.000060: could be addressed to the IRB, an ombudsman, an ethics committee, or other knowledgeable
p.000060: administrative body. Consent documents are expected to have at least two names with appropriate
p.000060: telephone contact information⎯one that can provide information regarding the research and
p.000060: another that can provide information regarding their rights as research participants. Grievance
...
p.000063: would not normally perform. Not only would this bias the study results but may lead to higher than
p.000063: normal levels of exposure. Alternatively, the act of studying one set of conditions or activities in an observational
p.000063: human exposure study could lead participants to assume that those conditions or activities involve substantial
p.000063: risk. In response, they subsequently may change their activities in ways that could lead to possibly higher
p.000063: risks. The potential for such unintentional outcomes is difficult for researchers to gauge but requires
p.000063: researcher caution in how information and results are conveyed. However, if the informed consent process is
p.000063: truly “an on-going, interactive dialogue . . . involving the disclosure and exchange of relevant
p.000063: information,” then such misunderstandings should be minimized.
p.000063:
p.000063: References
p.000063: AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric and Environmental Health. (2nd
p.000063: Edition). Elk Grove Village, IL: American Academy of Pediatrics.
p.000063:
p.000063: Ackerman TF (1989). An ethical framework for the practice of paying research subjects. IRB 11(4):1-4.
p.000063:
p.000063: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000063: Subjects. U.S. Code of Federal Regulations.
p.000063: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/ 40cfr26_06.html [accessed 12 June 2007].
p.000063:
p.000063: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000063: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000063: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000063:
p.000063: Diekema DS (2005) “Payments for Participation of Children in Research.” Chapter in: Kodish, E, Editor. Ethics and
p.000063: Research with Children: A Case-Based Approach. New York, NY: Oxford University Press. 143-160.
p.000063:
p.000063: Dickert N, Emanuel E, Grady C (2002). Paying research subjects: an analysis of current policies. Ann Intern Med
p.000063: 136(5):368-373.
p.000063:
p.000063: Emanuel EJ (2004). Ending concerns about undue inducement. J Law Med Ethics 32(1):100-105.
p.000063:
p.000063: Emanuel, EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000063:
p.000063:
p.000063:
p.000064: 64
p.000064:
p.000064: Erlen JA, Sauder RJ, Mellors MP (1999). Incentives in research: ethical issues. Orthop Nurs 18(2):84-87.
p.000064:
p.000064: European Parliament (2001). On the approximation of the laws, regulations, and administrative provisions of the Member
p.000064: States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products
...
p.000067: seek additional community representation on the IRB panel.
p.000067: The Centers for Disease Control and Prevention (CDC) recommends nine governing principles for
p.000067: “outsiders.” To help alleviate these potential issues, researchers should ensure an equitable
p.000067: distribution of paid research work among different communities within the larger community as to not promote a
p.000067: perceived bias among community members. Additionally, when possible, researchers should make efforts
p.000067: to provide payments to community members employed as research staff through community partner
p.000067: organizations to prevent conflict of interest issues. Refer to Section 5 for further discussion on
p.000067: remuneration of community members as research participants.
p.000067:
p.000067:
p.000067: Text Box 6-2. Community Engagement Principles for Researchers
p.000067: (From CDC, 1997)
p.000067: Requirement Explanation
p.000067:
p.000067: Clarity Clear communication of the study objectives, research goals, and the populations or
p.000067: communities of interest.
p.000067:
p.000067: engaging communities in health-related research (see Text Box 6-2). Health research is a “privileged and
p.000067: empowered activity in that the researchers have special
p.000067: Knowledge of the Community
p.000067: Familiarity with the economic conditions, political structures, demographics, history, past research experiences, and
p.000067: research perceptions of the community.
p.000067:
p.000067: access to resources and sensitive information about people and, through the analysis and presentation
p.000067: of findings, are able to influence the way people think and have considerable influence on decisions regarding
p.000067: the allocation of resources” (CDC, 1997). Regardless of the approach utilized to involve the community in research,
p.000067: whether the process employs community-based participatory research (CBPR) or another community
p.000067: engagement method, researchers should guide their interactions with community members using these
p.000067: underlying principles to promote the aforementioned ethical principles of respect of persons, fairness, and
p.000067: beneficence.
p.000067: One form of community involvement is to include qualified members of the community on the research staff.
p.000067: Section 2 advocates community representatives as part of the research team. Paid research staff members from
p.000067: the community could serve as valuable consultants for protocol development and research design, including how to
p.000067: collect the data, how to recruit and retain participants, and how to interpret and disseminate the
p.000067: results. However, including paid research staff from the community may introduce a conflict of interest among
p.000067: community members: community representatives may feel a greater allegiance to the researchers providing the payment
p.000067: and be less inclined to uphold the interests of the community. In addition, the community may come to view
...
p.000071: recommend attending to each other’s interests and needs by participating in activities beyond the
p.000071: specific work of the partnership.23 A history of prior positive working relationships is also beneficial
p.000071: (Israel et al., 1998).
p.000071: Trust cannot be separated from respect. Potential participants need to see researchers fostering respect for
p.000071: community members and leaders to gain trust. For example, meeting with key community leaders
p.000071: and groups in their surroundings helps to build trust for a true partnership. Such meetings provide
p.000071: organizers of engagement activities with more information about the community, its concerns, and factors
p.000071: that will facilitate and constrain participation. Once a successful rapport is established, the meetings
p.000071: and exchanges with community members can become an ongoing and substantive partnership (ERG, 2007).
p.000071: One mechanism for helping to build trust may be a contract with the community. A community contract outlines the
p.000071: roles and expectations of both the researcher and the community. Living up to these agreements builds
p.000071: trust with all partners, and the establishment of the agreement helps reduce misunderstandings.
p.000071: Contracts or memorandums of understanding that outline the roles and expectations of the researcher and the
p.000071: community are discussed in both Minkler and Wallerstein (2003) and Israel et al. (2005b). An example
p.000071: outlining expectations in a partnership with tribal communities is presented in Appendix E of Minkler and
p.000071: Wallerstein (2003), whereas an example discussing access to data and authorship issues is presented
p.000071: in Appendix I of Israel et al. (2005b). An example of a memorandum of understanding between the
p.000071: University of Michigan School of Public Health, Detroiter’s Working for Environmental Justice, the Detroit
p.000071: Hispanic
p.000071:
p.000071:
p.000071:
p.000071: 23 For a more detailed description of each of the suggestions for enhancing trust, please see Chapter 3 of Israel et
p.000071: al. (2005).
p.000071:
p.000072: 72
p.000072:
p.000072: Development Corporation, and the Warren Conner Development Coalition for a study investigating asthma is
p.000072: available at http://depts.washington.edu/ccph/pdf_files
p.000072: /MOU10.pdf.
p.000072: Work within communities involves a considerable investment of researchers’ and residents’ time. It should be an
p.000072: ongoing, interactive exchange of information and ideas between the researchers and the community members,
p.000072: where voices are both heard and honored. Trust is fostered when all interested parties feel that they have
p.000072: influence, and that their input contributes to the community effort. The collaborations should be
p.000072: inclusive of the entire community, including those members with incompatible interests and perceptions. If
p.000072: participation, influence, and benefits are limited only to some of the partners, then distrust is likely, and
p.000072: the potential benefits of community involvement may be lost. Being inclusive can create some
p.000072: organizing challenges, but the benefit of effective community involvement “has the potential to
...
p.000073: organizations having close ties with the African- American community to establish trust between
p.000073: the community and research team. Using input from the community partner organizations, the
p.000073: researchers developed a systematic communication plan to establish rapport with the community and to guide
p.000073: interaction between study participants and the key study personnel. A well-designed and culturally sensitive
p.000073: communication plan was integral to the success of the study. Eighty percent of the original participants
p.000073: completed the four- season study (Williams et al., 2003).
p.000073:
p.000073: 6.2.6 Honesty, Power Relationships, and Partnerships
p.000073: The NRC & IOM report (NRC & IOM, 2005) describes a relational paradigm that acknowledges that research
p.000073: is part of a broader societal context, with the conduct of research often mirroring a system in which
p.000073: power is unequally and perhaps unfairly distributed. The trust and mutual commitment required from
p.000073: the researchers and the community are subject to the overall power relations in society.24 The Expert Panel convened to
p.000073: discuss the content of this document recognized that
p.000073:
p.000073:
p.000073: 24 A discussion of the evolution of theories on power relations, including the contribution of feminism,
p.000073: poststructuralism, and postcolonialism, can be found in Minker and Wallerstein (2003, Chapter 2).
p.000073: the researchers have a variety of forms of power that needed to be understood and acted on ethically
p.000073: (ERG, 2007). One form of power is resources, both funds and access to resources and decisionmakers. Other forms of
p.000073: power may be more subtle, including expertise, which can intimidate or limit a participant’s choices.
p.000073: Peer pressure, fear of intimidation, expectations of benefits from the research, and power to
p.000073: stigmatize the community all, whether real or perceived, can influence the relationship between the
p.000073: researcher and the community. Many forms of power may be tipped toward the researcher, but the community often
p.000073: has power in the form of knowledge about the community that can impact the quality of the research effort. An ethical
p.000073: balance of power can lead to benefits for all partners (ERG, 2007).
p.000073: In describing principles in Methods in Community- Based Participatory Research for Health, Israel et al.
p.000073: (2005b) describe CBPR as facilitating “a collaborative, equitable partnership in all phases of research,
p.000073: involving an empowering and power-sharing process that attends to social inequalities.” One way to address the
p.000073: inequities is to ensure that the roles and responsibilities are mutually acceptable to all parties.
p.000073: Researchers involved in CBPR should recognize and address the inequalities, thereby promoting trust, mutual
p.000073: respect, open communication, information sharing, collaborative decisionmaking, and resource sharing.
p.000073: It is important that researchers recognize that partnerships with the community are ongoing processes that
p.000073: need to be monitored and maintained. As a study progresses, the dynamics of the partnership may change as roles
p.000073: and responsibilities for the partners change. All partners need to be willing to make the investment of time
...
p.000084: the media to maintain or increase interest in the study.
p.000084:
p.000084: 7.4 Communicating at Different Levels
p.000084: The diversity of interested people and groups often means that communications materials should be
p.000084: developed at different levels of scientific literacy. In any case, the materials should all be written in
p.000084: “plain language” that is honest and straightforward. Stableford and Mettger (2007) state that “plain language
p.000084: embodies clear communication.” Many researchers mistakenly believe that the term means just using simple words,
p.000084: or worse, ‘‘dumbing things down.’’ It actually refers to communications that engage and are accessible to
p.000084: the intended audience.
p.000084: A 1998 Presidential memorandum required that “plain language” be used in all governmental
p.000084: communications with the public. That memorandum stated, “By using plain language, we send a
p.000084: clear message about what the Government is doing, what it requires and what services it offers. Plain language
p.000084: saves the Government and the private sector time, effort, and money.” Plain language is reader friendly and designed to
p.000084: increase the participant’s understanding of the communication material. It serves as a means by which lay
p.000084: audiences can access and understand scientific information. Researchers desiring to use plain language in
p.000084: their verbal and written communications with communities must decide on key messages to include and
p.000084: delete unnecessary descriptive, bureaucratic, or jargon-filled language. Researchers should use words that
p.000084: commonly are understood, rather than difficult abstract terms and concepts. A friendly,
p.000084: conversational tone is used to engage the lay audience, rather than a formal, scholarly tone that
p.000084: distances the community. Stableford and Mettger (2007) argue that proficiency in creating appropriate plain
p.000084: language materials is an acquired skill that requires knowledge and experience. “It is both an art and
p.000084: a science, requiring the ability to simultaneously think about the cognitive, emotional, and visual appeal of the
p.000084: piece as well as applying research- based strategies to ensure a truly easy-to-read and understand print
p.000084: material.”
p.000084: The Department of Health and Human Services (HHS) has developed a Web site that specifically
p.000084: address the issues related to “plain language” (see
p.000084: http://www.health.gov/communication/literacy/plainlang uage/PlainLanguage.htm). The site includes a list of
p.000084: references and other helpful resources.
p.000084: To maintain community engagement through the
...
p.000085: regardless of the type of material, whether it is a direct mailing, a Web site, a news release, or a set of questions
p.000085: and answers (Q&As) used to respond to media or stakeholder inquiries. In developing the communication
p.000085: materials, the research staff should seek the assistance, advice, and input of people in their
p.000085: organization and community groups with experience in developing such materials. With all of these
p.000085: materials, the researchers should be concerned with how the materials could be misinterpreted, and whether
p.000085: there could be a perception that the study would not meet the highest scientific and ethical standards. In this age
p.000085: of rapid communications and increased accessibility to information, it is essential that communication materials
p.000085: are well developed, accurate, and understandable to all audiences that may read them.
p.000085: Research study Web sites are especially useful for communicating information about observational human
p.000085: exposure studies. Web sites should be developed early in
p.000085:
p.000085:
p.000086: 86
p.000086:
p.000086: the study to disseminate information to stakeholders and the community. Additionally, the sites can be set up with
p.000086: participant-only pages to provide more detailed information to study participants, including information
p.000086: on study protocols that require participant assistance (e.g., protocols for collecting urine
p.000086: samples, time/activity log entries). However, researchers need to ensure that Internet access is available to their
p.000086: intended audience and be prepared to provide alternative communication tools for those without such
p.000086: access.
p.000086: The plan for disseminating information from the study should be developed in the early design phases of the
p.000086: study and should be included in the study design document. Sufficient resources, both time and funding,
p.000086: need to be budgeted for this activity.
p.000086:
p.000086: 7.6 Informing the Study Participants and Communities
p.000086: Effective communications require that all parties, researchers and participants alike, involved in the
p.000086: communication understand the content and context of the information being exchanged. “When researchers
p.000086: discuss a planned study with community representatives, understand their concerns and needs, and respond to
p.000086: them, protocols can be strengthened both scientifically and ethically” (p. xii, NRC & IOM,
p.000086: 2005). Comprehension is one of the key pillars of informed consent, and it means that participants
p.000086: understand the key elements of the research. The most effective way to improve comprehension is by talking
p.000086: one-on-one with study participants.
p.000086: To accomplish that, the researchers need to make a commitment to communicating with both the study
p.000086: participants and the community to inform them of the study and provide training as appropriate. This can
p.000086: require a substantial investment of time and resources, but it is critical to the success of the study.
p.000086: Working with study participants to inform them about the study and the scientific basis of the study will have
p.000086: many benefits. The more educated the participant is about the purpose of the study and the activities to be
...
p.000097: involved large numbers of participants, employed randomized or probability-based approaches
p.000097: for selecting participants.
p.000097: Table A-2 shows the types of samples that often have been collected in NERL’s observational human
p.000097: exposure studies. Some of the samples, like air concentrations or surface wipes, allow NERL staff
p.000097: to determine the concentration of the studied chemicals in the environmental media with which the participants
p.000097: may come into contact. Other items, like time activity diaries or videotaping children to measure the amount of
p.000097: hand-to-mouth activity, allow NERL researchers to understand how people may come into contact with the agent
p.000097: and to estimate the duration or frequency of a potential exposure. Still other measures, like personal
p.000097: samplers or biological samples, represent an attempt to determine a time-integrated measure of exposure. NERL
p.000097:
p.000097:
p.000098: 98
p.000098:
p.000098: staff put all of this information together to estimate an individual participant’s exposure,
p.000098: either through relatively direct measures of exposure or through algorithms that combine the
p.000098: media concentrations measurements and the activity data.
p.000098:
p.000098: References
p.000098: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000098: Subjects. U.S. Code of Federal Regulations.
p.000098: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/ 40cfr26_06.html [accessed 12 June 2007].
p.000098:
p.000098: NEAC (National Ethics Advisory Committee) (2006). Ethical Guidelines for Observational Studies: Observational research
p.000098: audits and related activities. Wellington, New
p.000098: Zealand: Ministry of Health. Available: http://www.neac.health.govt.nz/moh.nsf/indexcm/neac
p.000098: resources-publications-ethicalguidelines.
p.000098:
p.000098: U.S. EPA (U.S. Environmental Protection Agency) (1992), Guidelines for Exposure Assessment. Environmental Protection
p.000098: Agency, Risk Assessment Forum, EPA/600/Z 92/001. Available: http://www.epa.gov/nceawww1/raf/pdfs/exposure.pdf
p.000098: [accessed 1 May 2008].
p.000098:
p.000098: Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, et al. (2007). Strengthening the Report of Observation
p.000098: Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Medicine 4(10): e297.
p.000098: doi:10.1371/journal.pmed.0040297.
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
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p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
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p.000098:
p.000098:
p.000098:
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p.000099: 99
p.000099:
p.000099: Table A-1. Examples of Observational Human Exposure Studies Conducted or Funded by NERL or Its Predecessor
p.000099: Organizations
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Social / Age
Searching for indicator age:
(return to top)
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
...
p.000042: epidemiologists and obtain such information, they need to be cognizant of the relevant ethical issues and of the CIOMS
p.000042: guidelines.
p.000042: 15 Guideline 18 states, “The investigator must establish secure safeguards of
p.000042: the confidentiality of subjects’ research data. Subjects should be told the limits, legal or other, to the
p.000042: investigators’ ability to safeguard confidentiality and the possible consequences of breaches of confidentiality.”
p.000042: Additional CIOMS commentary on the confidentiality guideline states, “Prospective subjects should be informed of limits
p.000042: to the ability of researchers to ensure strict confidentiality and of the foreseeable adverse social consequences of
p.000042: breaches of confidentiality. Some jurisdictions require the reporting to appropriate agencies of, for instance, certain
p.000042: communicable diseases or evidence of child abuse or neglect. These and similar limits to the ability
p.000042: to maintain confidentiality should be anticipated and disclosed to prospective subjects.”
p.000042: to identify an individual. Precise geographic location information may be sufficient to pinpoint a
p.000042: residence. Researchers may use several strategies to reduce the likelihood of indirect identification when
p.000042: study results are reported (see, also, Text Box 4-3).
p.000042: • Redact from publications, reports, or public data sets information that might be used to indirectly identify a
p.000042: research participant.
p.000042: • Generalize exact information; for example, replace birth date with age or year of birth or classify age as
p.000042: part of a range.
p.000042: • Aggregate information across individuals; for example, only report data in cells of sufficient size
p.000042: to make individual linkages unlikely.
p.000042: • Reduce the specificity of geographic coordinate information to a level that a specific residence or other
p.000042: location can not be identified.
p.000042:
p.000042: Text Box 4-3. Approaches for Protecting Personally Identifiable Information
p.000042: • Developing procedures for safeguarding information prior to collecting the information
p.000042: • Ensuring that data or samples are anonymous by not collecting or by destroying identifying information or linkages
p.000042: • Restricting access to identifying information to only those requiring access
p.000042: • Assigning codes to participants, data, and samples rather than using identifiers
p.000042: • Physically separating identifying information and linkage files from other study information
p.000042: • Securing identifying information in locked files with limited access
p.000042: • Restricting identifying information from computers that are networked with other computers or electronic systems
p.000042: • Restricting identifying information from computers that are not kept in secure locations with limited access
p.000042: • Training research staff members on human subject protection and on information security procedures
p.000042:
p.000042:
...
p.000058: payments. They also recommend that the policies disclose any recompense in a full and open
p.000058: process,22 while not overemphasizing any recompense.
p.000058: Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
p.000058: benefits, or they may be particularly vulnerable to undue influence resulting from the offer of a payment for
p.000058: research participation. In addition, payments made directly to parents or guardians could alter
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
p.000058: gestures of appreciation, investigators may also—if they minimize the potential for undue influence—act ethically to
p.000058: reduce certain barriers to research participation when they
p.000058: • reimburse reasonable expenses directly related to a child’s participation in research
p.000058: • provide reasonable, age-appropriate compensation for children based on the time involved in research that does not
p.000058: offer the prospect of direct benefit, and
p.000058: • offer evening or weekend hours, on-site child care, and other reasonable accommodations for parental work and
p.000058: family commitments.”
p.000058: 22 In recommending an open process, the IOM committee chose to reject the
p.000058: arguments from the American Academy of Pediatrics that “any token payment to children for participating in research
p.000058: should not be discussed with them until after research is completed for fear of unduly influencing their decisions
p.000058: (AAP, 2003)…. On balance, the committee agrees that it is best to mention token or other payments during the permission
p.000058: and assent processes” (p. 215, IOM, 2004).
p.000058: The IOM Recommendation 6.1 states, “Institutional review boards, research institutions, and sponsors of research that
p.000058: includes children and adolescents should adopt explicit written policies on acceptable and unacceptable types and
p.000058: amounts of payments related to research participation. These policies should specify that investigators
p.000058: • Disclose the amount, the recipient, the timing, and the purpose (e.g., an expense reimbursement or a token of
p.000058: appreciation to a child) of any payments as part of the process of seeking parents’ permission, and, as appropriate,
p.000058: children’s assent to research participation;
...
p.000060: samples and information that are collected or provided. Payment for direct participant costs has been included
p.000060: in some studies, such as a reasonable payment for providing researchers with duplicate diet samples.
p.000060: NERL scientists should review the commentary and recommendations in the literature before devising a
p.000060: payment program as part of a research protocol, especially the two recent National Academies of Science
p.000060: documents, Ethical Issues in Housing-Related Health Hazard Research Involving Children (NRC and IOM, 2005)
p.000060: and Ethical Conduct of Clinical Research Involving Children (IOM, 2004). They should seek
p.000060: guidance from EPA’s HSRRO to determine EPA’s latest policies and guidance in this regard. Input also should be sought
p.000060: from community representatives to ensure that any payment is adequate to compensate for expenses and reward
p.000060: participation, but that the payment is not so high as to constitute undue influence or coercion in the
p.000060: community. If the study includes several followup visits over a long term, NERL researchers should ensure that payment
p.000060: is made incrementally as the NRC & IOM committee suggested. NERL scientists also should adopt the IOM
p.000060: Recommendations 6.1 and 6.2, including ensuring that any payment should be for appropriate purposes
p.000060: and age-appropriate, and that the process should be open and fully disclosed, while not overly
p.000060: emphasizing payments during the recruiting or informed consent phases. The final decisions about the ethics of
p.000060: payments rest with the IRB, which will review, modify as needed, and approve the research protocol, and with the EPA
p.000060: HSRRO, who has final authority to approve, modify, or disapprove all of NERL’s human subjects research
p.000060: efforts.
p.000060: 5.3 Research Rights and Grievance Procedures
p.000060: Protecting the research rights of participants and providing independent access to information regarding
p.000060: those rights and to grievance procedures is an important element in developing and maintaining appropriate
p.000060: participant-investigator relationships. As part of the informed consent process, the Common Rule
p.000060: requires “An explanation of whom to contact for answers to pertinent questions about the research and
p.000060: human subjects’ rights, and whom to contact in the event of a research-related injury to the
p.000060: subject” [40 CFR 26.116(a)(7)].
p.000060: Information about the research often best can be answered by the researcher. However, it may benefit
p.000060: researchers and participants if information about the research can be obtained from or confirmed by a trusted
p.000060: independent person or organization. Participants also need to know how they can contact
...
p.000069:
p.000069:
p.000069:
p.000070: 70
p.000070:
p.000070: 6.2 Issues in Community Involvement
p.000070: There are a number of issues that need to be addressed in any efforts to ensure
p.000070: community involvement. The Expert Panel that was convened to advise NERL about scientific and ethical
p.000070: issues in observational human exposure studies discussed a number of challenges (ERG, 2007). The topics
p.000070: that the expert panel identified as issues are discussed below.
p.000070:
p.000070: 6.2.1 Defining “Community”
p.000070: “Community” refers to a group of people united by a shared attribute, and the attributes can be wide-ranging, such as
p.000070: geography, culture, social characteristics, values, interests, traditions, or experiences (ERG, 2007).
p.000070: Community can be defined broadly (as a system of interrelated groups operating to meet the needs of its
p.000070: members) or more narrowly (as the population from which study participants are selected). For observational
p.000070: field studies, the Expert Panel from the workshop suggested the narrow definition. A narrow
p.000070: definition allows social and cultural factors to be included but excludes government agencies, industry, and
p.000070: others who do not necessarily represent the interests of the participants (ERG, 2007).
p.000070: Central to the definition of a community is a sense of “who is included and who is excluded from
p.000070: membership” (NRC & IOM, 2005). A person may be a member of a community by choice, as with voluntary
p.000070: associations, or by virtue of their innate personal characteristics, such as age, gender, race, or
p.000070: ethnicity (NRC & IOM, 2005). As a result, individuals may belong to multiple communities at any one time. When
p.000070: initiating community engagement efforts, one should be aware of these complex associations in deciding which
p.000070: individuals to work with in the targeted community.
p.000070: Quandt et al. (2001) discuss a CBPR research project, Preventing Agricultural Chemical Exposure in
p.000070: North Carolina Farmworkers, where the process of defining a community was complicated by language,
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
...
p.000072: Building and maintaining appropriate community and stakeholder relationships requires acknowledgment of the
p.000072: diversity within communities with regard to many factors, including, but not limited to, race/ethnicity,
p.000072: religious beliefs, heritage, and lifestyles. Different groups in the study area may have different
p.000072: cultural norms and practices. The researchers should take these issues into consideration as they work in the
p.000072: community. Community partners can help researchers design the study to be attentive to the increasing
p.000072: heterogeneity of community groups (Minkler and Wallerstein, 2003, Chapter 4) and to the different
p.000072: boundaries of privacy (crucial when designing sampling strategies) of different groups (Israel et al., 2005b, Chapter
p.000072: 11).
p.000072: Vega (1992) provides a thorough discussion of the theoretical and pragmatic implications of
p.000072: cultural diversity for community research and explains that researchers should interact with
p.000072: communities using methods that promote understanding and demonstrate sensitivity and competence in
p.000072: working with diverse
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073: cultures (e.g., with respect to class, gender, ethnicity, race, age, and sexual orientation). To aid in this
p.000073: process, researchers should include sufficient time in their project timeline to interact and dialogue with the
p.000073: community before the study begins to understand the cultural issues that may affect the research. Researchers and the
p.000073: results of their work are expected to promote a strengthening of the community; however, it should be recognized
p.000073: that, given the heterogeneity and the diverse views within a community, the study findings potentially may
p.000073: conflict with the desires of the community or may promote feelings of anger or distrust among members
p.000073: of the community with each other. Enlisting the services of a third-party evaluator/mediator may be
p.000073: useful for sustaining positive relations between all research participants and the community at
p.000073: large.
p.000073: The Research Triangle Park Particulate Matter Panel Study (Williams et al., 2003), a NERL investigation of PM
p.000073: and related pollutants involving African-Americans in North Carolina, demonstrated an effective strategy for using
p.000073: communication to address cultural differences between the community and research personnel. Before beginning
p.000073: the research, the study design included time and a budget for building collaborations with
p.000073: organizations having close ties with the African- American community to establish trust between
p.000073: the community and research team. Using input from the community partner organizations, the
...
p.000077: Participación de La Communidad. U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response.
p.000077: Washington, DC. EPA 540-K 99-005, OWSER 9200.2-26K, PB99-963230. Available:
p.000077: http://www.epa.gov/superfund/community/today/pdfs/risk fs-0203.pdf
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2001). Improved Science-Based Environmental Stakeholder Processes: A
p.000077: Commentary by the EPA Science Advisory
p.000077: Board. EPA-SAB-EC-COM-01-006. EPA Science Advisory Board. Washington, DC. Available:
p.000077: http://yosemite.epa.gov/sab/sabproduct.nsf/CEE3F362F1A1 344E8525718E004EA078/$File/eecm01006_report_appna e.pdf
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2003). Framework for Cumulative Risk Assessment. Washington, DC:
p.000077: United States Environmental Protection Agency. EPA/600/P-02/001F. Available:
p.000077: http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=54944 .
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2003). Framework for Assessing Risks of Environmental Exposure to
p.000077: Children. Washington, DC. Available: http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=22521.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2005). Guidance on Selecting Age Groups for Monitoring and Assessing
p.000077: Childhood Exposures to Environmental Contaminants. Risk Assessment Forum, Washington, D.C. EPA/630/P-03/003F.
p.000077: Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=146583.
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). Considerations for Developing Alternative Health Risk
p.000077: Assessment Approaches for Addressing Multiple Chemicals, Exposures, and Effects. External Review Draft. 71 FR 16306.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). Paper on Tribal Issues Related to Tribal Traditional Lifeways,
p.000077: Risk Assessment, and Health and Well Being: Documenting What We’ve Heard. The National EPA-Tribal Science Council.
p.000077: Available: http://epa.gov/osp/tribes/tribal/TribalIssues.pdf.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). EPA’s Public Involvement Policy. Available:
p.000077: http://www.epa.gov/publicinvolvement/policy2003/index.htm.
p.000077:
p.000077: U.S. Food and Drug Administration (FDA). Exception from informed consent requirements for emergency research. 21 CFR §
p.000077: 50.24
p.000077:
p.000077: University of Kansas Community Tool Box. Available: http://ctb.ku.edu/en/tablecontents/.
p.000077:
...
p.000084: piece as well as applying research- based strategies to ensure a truly easy-to-read and understand print
p.000084: material.”
p.000084: The Department of Health and Human Services (HHS) has developed a Web site that specifically
p.000084: address the issues related to “plain language” (see
p.000084: http://www.health.gov/communication/literacy/plainlang uage/PlainLanguage.htm). The site includes a list of
p.000084: references and other helpful resources.
p.000084: To maintain community engagement through the
p.000084: research process, it is critical that communications are at the appropriate level, and that materials are written at a
p.000084: reading level that is appropriate to the audience. For the nonscientist, many IRBs and other groups target
p.000084: materials to be used with participants and communities at a reading level no higher than the 8th grade to
p.000084: improve the likelihood of comprehension. In some communities, however, other factors, like primary languages other than
p.000084: English, educational disadvantages, etc., may require communications materials to be written in
p.000084: alternate languages and at different reading levels. The issue is comprehension, as was discussed in
p.000084: Section 5.1.2. Empirical testing of communication methods and content is essential to ensure
p.000084: comprehension (Health Canada, 2006).
p.000084: Researchers also should recognize that in this information age, dissemination of
p.000084: informational materials may be rapid and widespread. Therefore, even documents intended for scientific peers may
p.000084: benefit by including summary information in an executive summary or preface that a lay reader can
p.000084: understand.
p.000084:
p.000084: 7.5 Communications Materials
p.000084: Researchers need to communicate clearly with the many groups listed in Section 7.2 to develop their
p.000084: relationship with the participants in the study, to develop their partnership with the community, to gain
p.000084: support from stakeholders, and to inform the public. To achieve the multiple purposes of communications
p.000084: during a research study and to communicate with many diverse groups, a variety of communications materials may
p.000084: need to be developed. Different materials have different purposes and different types of
p.000084: information to be communicated. Because of diversity in interested individuals and groups with
p.000084: respect to education, cultures, information needs, etc., the format and content of communication materials
p.000084: likely will need to be diverse. Text Box 7-4 list activities and materials that may be helpful in
p.000084: facilitating communications.
p.000084: By definition, communication is an exchange of information. This has to be the primary goal of
p.000084: communication activities. The accuracy and completeness of the information transferred is
p.000084: important. There are many different ways to communicate, the effectiveness of which varies substantially.
...
p.000085: accurate and complete information that is less likely to be misinterpreted by anyone who might
p.000085: pick up the brochure. Brochures and flyers that are used to announce a study or are used as recruiting tools
p.000085: should be carefully written in plain language to ensure that there is not a perception of activities that are
p.000085: unethical. For example, if flyers announcing a study state that study participants will be compensated, the flyer
p.000085: needs to ensure that the compensation is not the focus of the flyer, and that the payment does not appear to
p.000085: be excessive and coercive (see Section 5.2). Flyers announcing a study generally do not include the dollar
p.000085: amounts of payment.
p.000085: Researchers need to have similar concerns about all of the communication materials that are developed,
p.000085: regardless of the type of material, whether it is a direct mailing, a Web site, a news release, or a set of questions
p.000085: and answers (Q&As) used to respond to media or stakeholder inquiries. In developing the communication
p.000085: materials, the research staff should seek the assistance, advice, and input of people in their
p.000085: organization and community groups with experience in developing such materials. With all of these
p.000085: materials, the researchers should be concerned with how the materials could be misinterpreted, and whether
p.000085: there could be a perception that the study would not meet the highest scientific and ethical standards. In this age
p.000085: of rapid communications and increased accessibility to information, it is essential that communication materials
p.000085: are well developed, accurate, and understandable to all audiences that may read them.
p.000085: Research study Web sites are especially useful for communicating information about observational human
p.000085: exposure studies. Web sites should be developed early in
p.000085:
p.000085:
p.000086: 86
p.000086:
p.000086: the study to disseminate information to stakeholders and the community. Additionally, the sites can be set up with
p.000086: participant-only pages to provide more detailed information to study participants, including information
p.000086: on study protocols that require participant assistance (e.g., protocols for collecting urine
p.000086: samples, time/activity log entries). However, researchers need to ensure that Internet access is available to their
p.000086: intended audience and be prepared to provide alternative communication tools for those without such
p.000086: access.
p.000086: The plan for disseminating information from the study should be developed in the early design phases of the
p.000086: study and should be included in the study design document. Sufficient resources, both time and funding,
p.000086: need to be budgeted for this activity.
p.000086:
p.000086: 7.6 Informing the Study Participants and Communities
p.000086: Effective communications require that all parties, researchers and participants alike, involved in the
p.000086: communication understand the content and context of the information being exchanged. “When researchers
...
p.000178: North Carolina, and North Dakota in three phases.
p.000178: A separate VOC TEAM study was carried out in Baltimore, MD: Baltimore lacks the petroleum and chemical manufacturing
p.000178: plants present in most of the previous TEAM study sites and is more representative of many U.S. cities. Focused studies
p.000178: were also conducted in New Jersey and Los Angeles to further explore the sources and factors contributing to personal
p.000178: VOC exposures identified in the earlier TEAM studies.
p.000178: First attempt to develop a methodology for measuring the potential exposure of the general population to common
p.000178: household pesticides using probability-based sampling; questionnaire data collection; and personal monitoring of air,
p.000178: drinking water, food, and dermal contact. Conducted in Jacksonville, FL, and Springfield and Chicopee, MA, to capture
p.000178: high- and low-pesticide-use areas, respectively.
p.000178: A 9-home pilot study was conducted to evaluate monitoring methods in the field that may be used to assess the potential
p.000178: exposures of children aged 6 months to 5 years to pesticides found in the home environment. Newly developed methods
p.000178: were tested for measuring pesticide residues in indoor air, carpet dust, outdoor soil, and on children's hands.
p.000178: Information also was collected on household characteristics, pesticides used and stored at the residence, and
p.000178: children's activities.
p.000178: A study of nonsmokers age 10 years and older in Riverside, CA, in which indoor, outdoor, and personal monitoring of
p.000178: integrated particle mass over 12-hour day and night periods was conducted for PM10 and PM2.5. Polycyclic aromatic
p.000178: hydrocarbon and phthalate measurements were collected indoors and outdoors at a subset of 125 homes. A separate
p.000178: monitoring site provided ongoing 12-hour measurements of ambient particles throughout the study (48 days). Reference
p.000178: PM10 and dichotomous samplers were used at this site in addition to personal and stationary monitors identical to those
p.000178: used for participant monitoring. Nighttime and daytime recall time-activity questionnaires, as well as household
p.000178: questionnaires, were administered to each selected subject and household, respectively, and meteorological and air
p.000178: exchange rate data were recorded for each monitored home.
p.000178: This survey collected 24-hour activity diaries and other questionnaire data from participants from 48 states. It was
p.000178: conducted as a next-day telephone recall interview.
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000100: 100
p.000100:
...
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience, multiday pilot study to test methodology
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Case control study
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Randomized, cross- sectional
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience, longitudinal
p.000009: National Exposure Research Laboratory (NERL). A primary goal was to determine the relationships between personal
p.000009: exposures to particles and associated gases relative to stationary outdoor monitor concentrations in high-risk
p.000009: subpopulations and to identify human activity patterns that might contribute to personal exposure. The investigators
p.000009: varied study locations, monitoring seasons, and study populations.
p.000009: Susceptible subpopulations of interest included chronic obstructive pulmonary disease (COPD) patients, individuals with
p.000009: cardiovascular disease, the elderly, asthmatics, and African Americans with hypertension. Panels of healthy individuals
p.000009: also were included. Because the elderly is the subpopulation most sensitive to health effects associated with PM
p.000009: exposures, the majority of subjects were over age 65.
p.000009: Performed in the Raleigh, NC, area in homes with children 1 to 3 years old. Homeowners reported either professional or
p.000009: self applications of diazinon. Goals of the study were to evaluate methods to measure excess dietary exposures
p.000009: resulting from food-handling activities by young children during eating and to assess whether the Children’s Dietary
p.000009: Intake Model (CDIM) accurately represents total dietary exposures of children. Study resulted in refinements of model
p.000009: parameters for transfer and activity.
p.000009: Observational measurement study of exposure to chlorpyrifos among children 2-5 years of age in urban New Jersey homes
p.000009: following crack and crevice treatment by a professional applicator. Study investigated decay of pesticide levels over
p.000009: time, transfer of pesticide from microenvironmental media to child, and factors that affect transfer. Dermal transfer
p.000009: evaluated with surface wipes, hand wipes, dermal wipes, cotton garments, and videotaping.
p.000009: Physicians at Case-Western Reserve treating children with idiopathic pulmonary hemorrhage evaluated the nature of the
p.000009: fungus found in homes of the afflicted and control children to determine if Stachybotrys was a potential factor in the
p.000009: illness. Three of the 8 cases, and none of the controls, had Stachybotrys strains that potentially were implicated.
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: The largest children’s exposure study undertaken to date. It examines aggregate exposures of children 18 months to 5
p.000009: years to pollutants commonly found in everyday environments. The major objectives were to quantify children’s aggregate
p.000009: exposures, apportion exposure pathways, and identify important exposure media. Participants were recruited from 12
p.000009: urban and rural counties in North Carolina and Ohio using a random digit dialing method. Monitoring was performed at
p.000009: both daycare centers and homes. Samples collected include food, beverages, indoor air, outdoor air, hand wipes, dust,
...
p.000021: duplicate diet, cotton garment samples, and urine samples. A time- activity diary of the children’s activities was
p.000021: included.
p.000021: Work with Veteran’s Administration hospital staff. Cases of Legionnaires Disease were evaluated for potential for
p.000021: exposure from residential drinking water taps. In about 24% of the tested cases, homes were found to have Legionella
p.000021: bacteria in water taps at home, compared to their absence in other cases and in controls
p.000021: Incidental pesticide exposure measurement study of farmworkers’ children ages 5 to 35 mo. Purpose is the evaluation of
p.000021: methods for aggregate exposure measurements and the evaluation of pathways of exposure and important factors that
p.000021: affect exposure. Measurements include pesticide distributions in microenvironments where children spend time, transfer
p.000021: of pesticides from microenvironmental media to child, and factors that affect transfer.
p.000021:
p.000021:
p.000021:
p.000021: Study identified daycare centers with previously established contracts for routine monthly pesticide applications and
p.000021: conducted screening sampling in each to evaluate the distributions of transferable pesticide residues on floor surfaces
p.000021: where children spend time. One daycare was selected for intensive measurements, and children from different age groups
p.000021: volunteered to wear full-body cotton suits for short time periods while their activities were videotaped.
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000103: 103
p.000103: of molds/fungi and helped with lead and pesticide measurements.
p.000103:
p.000103:
p.000103: EPA conducted with contractor support
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: Multiagency effort; NERL was a participant and led the 9-home exposure component.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL funded IAG with VA to conduct study.
p.000103:
p.000103:
p.000103:
p.000103: EPA grant to UC Berkeley; NERL augmented the existing research effort.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL designed, contractor conducted
p.000103:
p.000103: Table A-1. (Continued)
p.000103: Study Date Size Type Brief Description
p.000103: NERL Role
p.000103: Tampa 2002 9 Residences Convenience Pilot study on methods for measuring personal,
p.000103: indoor NERL designed, Asthmatic sample,
p.000103: pilot residential, outdoor residential, and ambient combustion- contractor
p.000103: Children's Study study to test related products, particulate
p.000103: matter, and air toxics. The study conducted
p.000103: (TACS) methods. identified microenvironmental
p.000103: factors affecting penetration of pollutants into homes and reduction of exposures to pollutants for asthmatic children
p.000103: (0-5 years of age).
p.000103:
p.000103: Pilot Study To Evaluate Data Collection Methods for Young Children’s and Household Activities
p.000103: Detroit Exposure and Aerosol Research Study (DEARS)
p.000103:
p.000103:
p.000103:
p.000103: Accelerometer Pilot Study
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: Pilot Study of Waterborne Infections
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004: 2004-2007
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002005: 2005
p.002005: 3 Homes
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.000150: 150
p.000150:
p.000150:
p.000150:
p.000150:
p.000150:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.001296: 1296
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Randomized household selection with qualification criteria; longitudinal
p.001296:
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Convenience, all volunteers from community using public water supply
p.001296: Pilot aggregate exposure study of three homes to assess burden of alternative exposure sample collection methods.
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Recruitment from seven distinct neighborhoods in Detroit required strong community relations and partnership with State
p.001296: and local organizations. This study monitored for air pollutants at the personal level and evaluates how well centrally
...
p.000109: (4) The investigators’ views of the ethical issues and considerations raised by the study and,
p.000109: if appropriate, how it is proposed to deal with them
p.000109: (5) A summary of previous studies on the research problem, including unpublished studies known to the
p.000109: investigators, and information on previously published research on the topic
p.000109: (6) A statement that the principles of the Belmont Report and requirements specified in 40 CFR 26 will
p.000109: be implemented
p.000109: (7) An account of previous submissions of the protocol for ethical review and their outcomes
p.000109: (8) A brief description of the sites where the research is to be conducted, including information about the
p.000109: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000109: epidemiological information about the population to be studied
p.000109: (9) The names and addresses of the funding organization, research partners, and collaborators
p.000109: (10) The names, addresses, institutional affiliations, qualifications, and experience of the
p.000109: principal investigator and other investigators
p.000109: (11) The objectives of the study, its hypotheses or research questions, its assumptions, and
p.000109: its variables
p.000109: (12) A detailed description of the design of the study
p.000109: (13) The number of research subjects needed to achieve the study objective, and how this was determined
p.000109: statistically
p.000109: (14) The criteria for inclusion or exclusion of potential subjects and justification for the exclusion of
p.000109: any groups on the basis of age, sex, social or economic factors, or other reasons
p.000109: (15) The justification for involving as research subjects any persons with limited capacity to consent or
p.000109: members of vulnerable social groups and a description of special measures to minimize risks and
p.000109: discomfort to such subjects
p.000109: (16) The process of recruitment (e.g., advertisements) and the steps to be taken to protect privacy and
p.000109: confidentiality during recruitment
p.000109: (17) A description and explanation of any and all interventions
p.000109: (18) The measurements to be performed in the study, including environmental and biological sample
p.000109: collection, and other data and information that will be collected
p.000109: (19) If applicable, clinical and other tests involving the study participants that are to be carried out
p.000109: (20) The rules or criteria according to which subjects may be removed from the study or the study may be
p.000109: terminated
p.000109: (21) The methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000109: complications
p.000109: (22) The potential benefits of the research to subjects and to others
p.000109: (23) The expected benefits of the research to the population, including new knowledge that the study
p.000109: might generate
p.000109:
p.000109:
p.000109:
p.000111: 111
p.000111:
p.000111: (24) The means proposed to obtain individual informed consent and the procedure planned to communicate information to
p.000111: prospective subjects, including the name and position of the person responsible for obtaining consent
p.000111: (25) When a prospective subject is not capable of informed consent, satisfactory assurance
p.000111: that permission will be obtained from a duly authorized person, or, in the case of a child who is sufficiently mature
p.000111: to understand the implications of informed consent but has not reached the legal age of consent,
p.000111: that knowing agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian
p.000111: or other duly authorized representative.
p.000111: (26) An account of any economic or other compensation or incentives to prospective subjects to participate, such as
p.000111: offers of cash payments, gifts, or free services or facilities, and of any financial
p.000111: obligations assumed by the subjects, such as payment for medical services
p.000111: (27) The plans and procedures and the persons responsible for communicating to
p.000111: subjects information arising from the study (on harm or benefit, for example) or from other research on the same
p.000111: topic that could affect subjects’ willingness to continue in the study
p.000111: (28) The plans to inform subjects about the results of the study
p.000111: (29) The provisions for protecting the confidentiality of personal data and respecting the privacy of subjects,
p.000111: including the precautions that are in place to prevent disclosure of the results of a
p.000111: subject’s genetic tests to immediate family relatives without the consent of the subject
p.000111: (30) Information about how the code, if any, for the subjects’ identity is established; where it will be
p.000111: kept; and when, how, and by whom it can be broken in the event of an emergency
p.000111: (31) Any foreseen further uses of personal data or biological materials
...
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000116: 116
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116: Appendix F
p.000116: Glossary
p.000116:
p.000116:
p.000116:
p.000116: Agent. A chemical, mineralogical, biological, or physical entity that may cause deleterious effects in an organism
p.000116: after the organism is exposed to it [EPA/600/Z-92/001, May 1992].
p.000116: Assent. A child’s affirmative agreement to participate in research. Mere failure to object should not, absent
p.000116: affirmative agreement, be construed as assent [45 CFR 46.402(d)].
p.000116: Autonomy. The capability and capacity to govern oneself.
p.000116: Beneficence. The ethical obligation to maximize benefits and to minimize harms. This principle gives rise to norms
p.000116: requiring that the risks of research be reasonable in light of the expected benefits, that the research design be
p.000116: sound, and that the investigators be competent both to conduct the research and to safeguard the welfare of the
p.000116: research subjects. Beneficence further proscribes the deliberate infliction of harm on persons; this aspect of
p.000116: beneficence is sometimes expressed as a separate principle, nonmaleficence (do no harm).
p.000116: Child. A person who has not attained the age of 18 years [40 CFR 26.202(a)]
p.000116: Collateral observations. Potentially unsafe hazards, conditions, or situations unrelated to the research study that
p.000116: are observed by the research staff
p.000116: Common Rule. The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects.” It was
p.000116: adopted by more than a dozen Federal departments or agencies in 1991, with EPA adapting it in Title 40 CFR Part 26
p.000116: Subpart A.
p.000116: Community-based participatory research (CBPR). Collaborative research with a community in which the community is
p.000116: involved in all phases of the research.
p.000116: A fundamental concept is that the research aims to combine knowledge with action and to achieve social
p.000116: change to improve health outcomes and eliminate health disparities.
p.000116: Confidentiality. The keeping safe or not redisclosing by one of the parties in a confidential relationship information
p.000116: that originally was disclosed in the confidential relationship
p.000116: Environmental justice. The fair treatment and meaningful involvement of all people regardless of race, color, national
p.000116: origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations,
p.000116: and policies
p.000116: Exposure. Contact of a chemical, physical, or biological agent with the outer boundary of an organism (e.g., a
p.000116: person). Exposure is quantified as the concentration of the agent in the medium in contact integrated over the time
...
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p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
...
p.000008:
p.000008: EPA, States, and the Consumer Product Safety Commission worked together to influence manufacturers to voluntarily
p.000008: reduce emissions of toxic chemicals from consumer products, building materials, and furnishings, and to develop
p.000008: mitigation strategies and educational materials to teach people how to reduce their contact with chemicals indoors. As
p.000008: a result, contact with toxic chemicals indoors has been reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html).
p.000008:
p.000008:
p.000008: Formaldehyde
p.000008:
p.000008: Studies found elevated formaldehyde levels indoors and helped identify indoor sources.
p.000008:
p.000008: EPA worked with HUD, CPSC, and other agencies to limit formaldehyde in building or consumer products and to educate the
p.000008: public on how to reduce exposures (see www. epa.gov/iaq/formalde.html).
p.000008:
p.000008:
p.000008: EPA has adopted additional protections for children and pregnant or nursing mothers in Subparts B through
p.000008: D. These sections apply to all research either conducted or funded by EPA and are, therefore, directly applicable to
p.000008: NERL’s observational human exposure studies.4 Subpart B prohibits EPA from conducting or supporting research
p.000008: that involves intentional exposure of “a pregnant woman (and, thereby, her fetus), a nursing woman,
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
p.000008: from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in specified
p.000008: rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in this
p.000008: document.
p.000008: 5 The Glossary (Appendix F) lists definitions for a number of important terms; definitions that come from the
p.000008: regulatory language are identified with their specific CFR citation.
p.000008: about the most recent thinking and guidance on protection of human subjects.
...
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
...
p.000024: whether or not the children were involved in a research study. As a consequence, the study still
p.000024: would meet the regulatory criteria for minimal risk as long as the research itself introduced no risks over
p.000024: and above those minimal risks
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025: experienced by normal children living in safe healthy environments.
p.000025: However, the existence of greater than minimal background risks that are not introduced by the research,
p.000025: nonetheless, raises additional ethical considerations. The joint NRC & IOM Committee on Research on Housing- Related
p.000025: Health Hazards Involving Children discussed the ethical arguments that arise when scientists conduct research that
p.000025: observes children in poor-quality housing. They point out that a researcher’s first duty of beneficence
p.000025: under the Common Rule requires that the risks of the research actions be proportionate to
p.000025: [“reasonable in relation to”; 40 CFR 26.111(a)(2)] the benefits of the research, and that the risks be
p.000025: minimized. They acknowledge, however, that some have argued that the “best interests of the child” also obligates
p.000025: researchers to “rescue” children from harm and to provide better living conditions. They conclude that,
p.000025: properly applied, the ethical principle of beneficence does indeed direct researchers who observe serious harms
p.000025: to child subjects to take steps to try to prevent the harms. However, they also argue that the researcher’s duty does
p.000025: not extend to “personally and directly prevent harm by removing the child from the harmful environment” (p.
p.000025: 60, NRC & IOM, 2005). They conclude instead that “it is unrealistic and unfair to hold individual research
p.000025: investigators responsible for ameliorating the social circumstances that they study” and that “a nuanced
p.000025: balancing of the benefits and risks of research” is an ethically sound approach that is firmly established in
p.000025: Federal regulations (p. 60, NRC & IOM, 2005). Balancing the ethical obligation to mitigate risks or
p.000025: harms observed during research with the reasonable limits on an investigator’s moral responsibility for
p.000025: the social circumstances surrounding the research will be the subject of later sections of this
p.000025: document, particularly Section 4.3.1.
p.000025: Assessing the risks and benefits of the research study can be very difficult for the researchers, especially
p.000025: because the researchers and the community or participants may perceive the risks and benefits
p.000025: quite differently. (See the discussion in NRC & IOM [2005], for example.) To understand the
p.000025: community’s perspective better, the researcher may find it helpful to discuss the assessment of risks
p.000025: and benefits with members of the research team, community representatives, and relevant
p.000025: stakeholders. The research team should consider the use of a community advisory board (CAB) to provide
p.000025: input to the assessment of the risks and benefits of the study. The group could include individuals who are
p.000025: representative of the population to be studied, community representatives, exposure
...
p.000033: the rights and welfare of these [vulnerable] subjects” [at 40 CFR 26.111(b) in CFR, 2006a]. If an
p.000033: observational human exposure study includes vulnerable research participants, it is essential that the investigators be
p.000033: cognizant of the special issues and requirements of research involving vulnerable populations. Researchers
p.000033: have to justify the involvement of vulnerable populations in the research study and
p.000033: include the appropriate safeguards for protection of their safety and welfare. The Common Rule protections are
p.000033: discussed further in the IRB guidebook (U.S. HHS, 1993). EPA regulations include not only the general
p.000033: protections for vulnerable populations found in the Common Rule (Subpart A) but also define
p.000033: additional protections for children and for pregnant or nursing women (and their fetus or nursing child)
p.000033: in Subparts B, C, and D (CFR, 2006a).
p.000033: The section begins by identifying or defining vulnerable groups and then discusses ethical issues that
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
...
p.000035: consequence of the research;
p.000035: • the risks attached to interventions or procedures that do not hold out the prospect of direct health-related
p.000035: benefit will not exceed those associated
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036: CIOMS recommendations, although written to address biomedical research, also generally are
p.000036: applicable to observational human exposure studies. The authors of this document consider the CIOMS
p.000036: requirement that the research could not be carried out equally well with less vulnerable subjects
p.000036: to be particularly important. EPA and NERL researchers should include vulnerable groups in
p.000036: observational human exposure studies only if their participation is critical to the success and
p.000036: applicability of the research. Even then, EPA and NERL researchers will have to meet stringent standards for
p.000036: protecting the rights and safety of the vulnerable participants. For example, EPA regulations
p.000036: governing observational research with children are even more stringent than the CIOMS guideline.
p.000036: If such research does not hold out the prospect of direct benefit to the child, no increase whatsoever over
p.000036: minimal risk is permitted.
p.000036: However, many observational human exposure studies are developed specifically to study the exposures of
p.000036: selected vulnerable groups to chemicals and other environmental stressors in everyday environments. So,
p.000036: researchers should be prepared to address the issues associated with vulnerable groups in
p.000036: observational research. Furthermore, as discussed in Section 3.4, there has been increased concern in recent years that
p.000036: exclusion of vulnerable groups from research studies is not ethical. Failure to conduct research with vulnerable groups
p.000036: may deprive them of the benefits of research. NIH, for example, has a policy (NIH, 1998) with a
p.000036: goal of increasing participation of children in research.
p.000036:
p.000036: 3.3 Minimal Risk and Vulnerable Groups
p.000036: EPA has codified protections for children, pregnant or nursing women, and fetuses in Subparts B, C, and D of the EPA
...
p.000036: protections to children (CFR, 2006a,b). There are many books, reports, and research manuscripts that
p.000036: specifically address issues associated with research involving children (e.g., NRC & IOM, 2005; IOM,
p.000036: 2004; Kodish, 2005; NRC, 2003; AAP, 2003).
p.000036: CIOMS has drafted guidelines for including children in biomedical research (Guideline 14, CIOMS, 2002). The
p.000036: guidelines require an investigator to provide the assurances shown in Text Box 3-3 before undertaking
p.000036: research involving children.
p.000036:
p.000036: Text Box 3-3. Assurances Required by CIOMS Before Research Involving Children May Begin
p.000036: • the research might not equally well be carried out with adults;
p.000036: • the purpose of the research is to obtain knowledge relevant to the health needs of children;
p.000036: • a parent or legal representative of each child has given permission;
p.000036: • the agreement (assent) of each child has been obtained to the extent of the child’s capabilities; and
p.000036: • a child’s refusal to participate or continue in the research will be respected.
p.000036:
p.000036:
p.000036: The participation of children in some observational human exposure studies is critical to
p.000036: characterizing children’s exposures to chemicals in the environment. It is well recognized that children are not
p.000036: “little adults,”
p.000036: and that their
p.000036: exposures to chemicals differ (and, in
p.000036:
p.000036:
p.000036: with routine medical or psychological examination of such persons unless an ethical review committee authorizes a
p.000036: slight increase over this level of risk (Guideline 9); and,
p.000036: • when the prospective subjects are either incompetent or otherwise substantially unable to give informed consent,
p.000036: their agreement will be supplemented by the permission of their legal guardians or other appropriate representatives.
p.000036:
p.000036:
p.000036: 13 Minimal risk is defined at 40 CFR 26.102(i) and again at 40 CFR 26.402(g). It “means that the probability and
p.000036: magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily
p.000036: encountered in daily life or during the performance of routine physical or psychological examinations or tests.”
p.000036:
p.000036:
p.000037: 37
p.000037:
...
p.000037: family. EPA’s human subjects rule for observational research not involving greater than minimal risk to
p.000037: children (40 CFR 26.404) (i.e., the kinds of observational human exposure studies that NERL exposure research
p.000037: is likely to entail) focuses on obtaining assent of the children and permission of their parents or guardians. But the
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
p.000037: biomedical research because of the potential for becoming pregnant during a study. The document continues, “A
p.000037: general policy of excluding from such clinical trials women biologically capable of becoming pregnant is
...
p.000042: may sometimes lead to the indirect identification of the individual. Certain combinations of
p.000042: demographic information, for example, may make it relatively simple
p.000042:
p.000042:
p.000042: 14 Beauchamp and Childress (2001) discuss when one may be ethically justified in infringing on an individual’s privacy
p.000042: and confidentiality⎯for example, because of risks to others evidenced by biomarkers of infectious disease. They also
p.000042: discuss similar ethical issues that may arise in regard to genetic data. CIOMS (2002) Guideline 18 provides suggestions
p.000042: for safeguarding or disclosing genetic information. If exposure scientists collaborate with medical researchers or
p.000042: epidemiologists and obtain such information, they need to be cognizant of the relevant ethical issues and of the CIOMS
p.000042: guidelines.
p.000042: 15 Guideline 18 states, “The investigator must establish secure safeguards of
p.000042: the confidentiality of subjects’ research data. Subjects should be told the limits, legal or other, to the
p.000042: investigators’ ability to safeguard confidentiality and the possible consequences of breaches of confidentiality.”
p.000042: Additional CIOMS commentary on the confidentiality guideline states, “Prospective subjects should be informed of limits
p.000042: to the ability of researchers to ensure strict confidentiality and of the foreseeable adverse social consequences of
p.000042: breaches of confidentiality. Some jurisdictions require the reporting to appropriate agencies of, for instance, certain
p.000042: communicable diseases or evidence of child abuse or neglect. These and similar limits to the ability
p.000042: to maintain confidentiality should be anticipated and disclosed to prospective subjects.”
p.000042: to identify an individual. Precise geographic location information may be sufficient to pinpoint a
p.000042: residence. Researchers may use several strategies to reduce the likelihood of indirect identification when
p.000042: study results are reported (see, also, Text Box 4-3).
p.000042: • Redact from publications, reports, or public data sets information that might be used to indirectly identify a
p.000042: research participant.
p.000042: • Generalize exact information; for example, replace birth date with age or year of birth or classify age as
p.000042: part of a range.
p.000042: • Aggregate information across individuals; for example, only report data in cells of sufficient size
p.000042: to make individual linkages unlikely.
p.000042: • Reduce the specificity of geographic coordinate information to a level that a specific residence or other
p.000042: location can not be identified.
p.000042:
p.000042: Text Box 4-3. Approaches for Protecting Personally Identifiable Information
p.000042: • Developing procedures for safeguarding information prior to collecting the information
p.000042: • Ensuring that data or samples are anonymous by not collecting or by destroying identifying information or linkages
p.000042: • Restricting access to identifying information to only those requiring access
...
p.000043: the home have to be asked for permission or be informed that monitoring activities are taking place.
p.000043: Researchers and IRBs should consider whether knowledge of an individual’s participation by others might
p.000043: create potential for harm or distress in an observational human exposure study. Such risks might
p.000043: be limited to possible discomfort in attracting unwanted
p.000043: attention; this may be particularly true for adolescents. However, in some cases, the potential risks
p.000043: could be greater, for example, in cases where participation could provoke an adverse reaction from a
p.000043: landlord or employer. Oftentimes study protocols can be structured to minimize these potential risks. Through the
p.000043: informed consent process, prospective participants should be made aware of the limits of the researcher’s ability to
p.000043: protect knowledge of their participation in the study and of the possible risks of disclosure.
p.000043:
p.000043: 4.3 Collateral Observations
p.000043: In the course of conducting an observational human exposure study, research staff may observe potentially unsafe
p.000043: conditions or situations that are unrelated to the research study. Such “collateral observations” may
p.000043: involve physical hazards in the study participant’s residential environment or evidence of situations,
p.000043: such as child abuse, that have to be reported to proper authorities. In preparing for the
p.000043: research study, it is recommended that researchers carefully plan for possible collateral observations,
p.000043: including their identification, staff training, and hazard communication and reporting. This may be a major
p.000043: element in the data and safety monitoring and oversight for the study. The informed consent process
p.000043: should reflect procedures used to manage collateral observations. Potential participants should be
p.000043: informed of situations in which confidentiality might be breached, such as statutory requirements for reporting
p.000043: abuse or imminent harm to self or others.
p.000043:
p.000043: 4.3.1 Potential Nonstudy Hazards in the Residence
p.000043: Research staff conducting observational human exposure studies often will spend time in and around
p.000043: study participant residences. In the course of visiting a residence or conducting study-related
p.000043: observations, research staff may observe potential hazards unrelated to the research being performed (see Text Box
p.000043: 4-4). Some hazards may be associated with the potential for physical injury, whereas others may be related to
p.000043: exposure to chemical or biological agents. Some situations may be potential hazards only for young children,
...
p.000043: potential hazards in advance, develop responses to the risks, and submit the proposed plans to the IRB
p.000043: for review to ensure that they are appropriate “in the context of the research and the affected community.” The NRC
p.000043:
p.000043:
p.000044: 44
p.000044:
p.000044: & IOM also advise that field staff should be trained in how to assess and respond to
p.000044: such risks (Recommendations 7.3 and 7.4, NRC & IOM, 2005). For other behaviors and risks that
p.000044: have not been specifically identified in advance, procedures should be included in the data and safety monitoring
p.000044: and oversight provisions of the study design and research protocol to address these issues. The fundamental
p.000044: ethical principle of beneficence would motivate researchers who observe serious harms to take steps to try to prevent
p.000044: those harms, even for observations that are not directly related to the study. The steps that they may take can
p.000044: range from immediate action to prevent an imminent and serious danger to statutory reporting of
p.000044: observations (see Section 4.3.2) to reporting the observation to the data and safety monitoring and oversight
p.000044: authority for advice on how to respond (see Section 4.5). (The reader is also referred to pages 59-61 and 134-144 of
p.000044: the NRC & IOM [2005] report for a more thorough discussion of researchers’ responsibilities in such
p.000044: cases.)
p.000044:
p.000044: Text Box 4-4. Potential Hazards that Might Be Encountered in a Residential Environment
p.000044: • Unsecured firearm
p.000044: • Uncovered electrical outlets
p.000044: • Unprotected stairways
p.000044: • Missing child-protective cabinet latches
p.000044: • Lack of window guards
p.000044: • Missing or inoperable smoke alarm
p.000044: • Housing code violations
p.000044: • Chipping or flaking paint—potential for lead exposure in older homes
p.000044: • Malfunctioning or unvented combustion appliances—potential for carbon monoxide exposure
p.000044: • Unsecured poisons or other dangerous products
p.000044: • Excessive mold growth
p.000044:
p.000044:
p.000044: 4.3.2 Collateral Observations with Mandated Reporting Requirements
p.000044: Some collateral observations may have statutory requirements for reporting to designated authorities.
p.000044: Examples of such observations include
p.000044: • observed child or elder abuse or evidence of such abuse or neglect,
p.000044: • statements or actions of intent to harm self or others, and
p.000044: • certain communicable diseases.
p.000044: Because different reporting statutes pertain in different states, it is necessary for researchers to
p.000044: learn and understand the applicable reporting requirements for the study location. In the case of abuse, it is
p.000044: also
p.000044: important to understand what actions or situations are considered abusive in a particular state. Although direct
p.000044: physical harm or violence might be obvious to a research staff member, there are other conditions of neglect that
p.000044: might be more difficult to recognize or to know when to report.
p.000044: Study participants should be made aware of statutory requirements for reporting collateral observations as part of the
p.000044: informed consent process. Researchers should include the reporting requirements in the informed
p.000044: consent form (discussed in Section 5) and should ensure that the study participant fully comprehends this
p.000044: information and the impact on their privacy and confidentiality.
p.000044:
p.000044: 4.3.3 Hazard Communication
...
p.000045: understand and effectively implement the action, and whether unintended adverse consequences might
p.000045: result from taking an action. In some cases, it may be reasonable to refer the participant to another
p.000045: organization that can provide expert advice or assistance.
p.000045:
p.000045: 4.3.4 Planning and Staff Training
p.000045: As part of the study planning process and protocol development, it is important that researchers
p.000045: be cognizant of the kinds of collateral observations that might occur in the implementation of the study
p.000045: protocol and to develop plans as to how such observations would be handled. Researchers may choose to
p.000045: include a systematic approach in hazard identification, such as using a home-hazard checklist that becomes an
p.000045: ancillary part of the study protocol. Alternatively, collateral observations could be handled on a
p.000045: case-by-case basis.
p.000045: Staff experience and training is a critical consideration for managing collateral observations. Staff
p.000045: members that visit study participant residences may not have expertise or experience in identifying many of the
p.000045: potential hazards without adequate training. All staff involved in a study, particularly those responsible
p.000045: for field data collection, should be trained on identification and reporting of collateral observations. This
p.000045: training should be study specific and likely will include, but not be limited to
p.000045: (1) identification of actions (e.g., child abuse) that have (state-specific) statutory reporting requirements,
p.000045: (2) conditions of neglect that may adversely impact study participants or third parties,
p.000045: (3) environmental hazards and situations that may be associated with imminent harm (e.g., combustible
p.000045: materials near an open flame, unsecured firearms accessible to very young children),
p.000045: (4) policies and procedures for reporting or intervention by members of the research team, and
p.000045: (5) local and state reporting requirements.
p.000045: It is advisable that this training be developed in consultation with community representatives who can
p.000045: provide input on potential hazards and situations that may be encountered in the study community,
p.000045: local norms and attitudes about potential interventions and reporting, and local agencies available to assist on
p.000045: these types of issues. It is also especially important to consider
p.000045: staff experience and training in hazard communication. Consistency in communication is very important, and
p.000045: researchers may decide to use materials prepared by other organizations that have expertise regarding
p.000045: a particular hazard.
p.000045: Another important element of planning for field data collection and training of research staff is on hazards and
p.000045: situations that the field staff may encounter during their field work. Although the previous discussion highlights the
...
p.000052: (accessed September 12, 2007).
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053: participants and, if so, how and when (p. 101, NRC & IOM, 2005).
p.000053: • For studies involving children as participants, it generally is regarded as desirable that the
p.000053: informed consent process should involve both parents (assuming that there are two competent
p.000053: parents available), and that the consent of both parents be obtained, if possible. The IRB may decide
p.000053: that the permission of one parent is sufficient, but only when certain risk-benefit conditions are met.18
p.000053: • For studies involving children as participants, it is desirable for those children with sufficient capacity
p.000053: to be involved in the consent process. Moreover, it is generally accepted that the child’s assent be obtained
p.000053: whenever this is developmentally possible and otherwise appropriate. Under both the EPA Rule and the HHS
p.000053: Rule, the IRB is responsible for determining that adequate provisions have been made for soliciting the assent of the
p.000053: children when, in the judgment of the IRB, the children are capable of providing assent. Assent, however, may
p.000053: be waived in those restricted circumstances in which consent may be waived under the Common Rule. Those
p.000053: circumstances and the required IRB documentation are described in the Common Rule at 40 CFR 26.116(d).
p.000053: • The consent form should clearly state that participation is voluntary and that study
p.000053: participants may “discontinue participation at any time without any penalty or loss of benefits to which the
p.000053: subject is otherwise entitled” [40 CFR 26.116(a)(8)]. If a subject chooses to withdraw from a study, the
p.000053: consequences of their decision and the process for orderly withdrawal should be clearly
p.000053: explained [40 CFR 26.116(b)(4)].
p.000053: • The consent form should address any foreseeable potential future use of samples and data (CIOMS, 2002).
p.000053: For example, effects of environmental exposures on gene expression are potentially very important.
p.000053: Therefore, biologic specimens for DNA analysis may be obtained from participants in future studies. But, it
p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45 CFR 46.408(b)
p.000053: for all research with children. Under the EPA Rule, greater than minimal risk observational research with children that
p.000053: does not hold out the prospect of direct benefit to the child is not permitted under any circumstances. Under the HHS
p.000053: Rule, greater than minimal risk research involving children without the prospect of direct benefit is permitted in very
p.000053: limited circumstances, but the consent of both parents is required in those cases (unless one parent is deceased,
p.000053: unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and
p.000053: custody of the child).
p.000053: special concerns about the potential for discrimination, stigmatization, and impact on
p.000053: future employment or insurance. The informed consent process needs to explain what the plans may be
p.000053: for such specimens and recognize the rights of the subjects to decide about any such future use,
p.000053: including having the material destroyed. The informed consent process needs to explicitly discuss
p.000053: obtaining permission from participants on behalf of themselves and their child to obtain specimens for
p.000053: genetic analysis.
p.000053:
p.000053: 5.1.2 Comprehension
p.000053: Research participants frequently fail to understand the research protocols in which they agree to participate (NRC
p.000053: & IOM, 2005). In considering the ethical issues raised by the Grimes v. Kennedy Krieger case, the NRC & IOM
p.000053: committee “realized that the crucial issue regarding consent was not what information was
p.000053: contained in the consent forms, but rather what the parents understood about the study and the hazards
p.000053: present in the home before and after the study” (p. 19, NRC & IOM, 2005). The committee laments that “IRBs
p.000053: place their attention on consent forms rather than on the process of providing and discussing information” (p.
p.000053: 103, NRC & IOM, 2005). The IOM recommends that “the informed consent process should be an on-going,
p.000053: interactive dialogue between research staff and research participants involving the disclosure and exchange of
p.000053: relevant information, discussion of that information, and assessment of the individual’s understanding of
p.000053: the discussion” (Recommendation 4.1, IOM, 2002). These comments emphasize how important true two-way
p.000053: communication is to comprehension, the second pillar in the informed consent process.
...
p.000055: nonmonetary payments (e.g., gifts, valuable information), or nothing at all (e.g., for a sense of
p.000055: altruism). Grady (2005) has described payment for the participation of research subjects as serving
p.000055: from one to four purposes: (1) an incentive, (2) compensation, (3) reimbursement, or
p.000055: (4) reward. Text Box 5-3 describes the roles that payments may serve, together with potential advantages
p.000055: and disadvantages or ethical concerns. The text comes mostly from Grady (2005) but builds also on the NRC & IOM
p.000055: document and other writings. (A number of authors have addressed issues associated with payments,
p.000055: including Ackerman, 1989; Dickert et al., 2002; Emanuel 2004; Erlen et al., 1999; Fry et al.,
p.000055: 2005; Grady, 2005; Grady et al., 2005; Iltis et al., 2006; IOM, 2004; NRC & IOM, 2005; Russell et al.,
p.000055: 2000; VanderWalde, 2005; Weise et al., 2002; Wendler et al., 2002). A number of specific issues or
p.000055: concerns regarding participant payments have been identified. Many researchers and ethicists argue that it
p.000055: is often appropriate to provide reasonable payment and have done so for many years. In the view of an NRC expert
p.000055: panel, the principles of “justice, fairness, and gratitude support payment to those who bear the burdens
p.000055: of research on behalf of society” (NRC, 2004).
p.000055: Direct reimbursement may be made to participants for out-of-pocket expenses for costs directly associated
p.000055: with participation in a study. These might include transportation costs, parking fees, or child
p.000055: care costs. When payment for time and burden is provided, it is often in the form of monetary
p.000055: payments. Different approaches may be considered for determining reasonable amounts for payment,
p.000055: including a set payment for each visit, a small daily payment, payment at the prevailing minimum hourly
p.000055: wage, or payment at some other hourly rate appropriate for the community⎯perhaps a
p.000055: prevailing rate for unskilled labor (Emanuel, 2004). Incentives to encourage enrollment are
p.000055: sometimes used when participants will receive little or no direct benefit from the research and can take
p.000055: the form of monetary or non-monetary payments. Incentives are kept modest so as not to impart undue
p.000055: influence. Researchers need to consider the possible effects of incentive payments on the potential
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056:
p.000056: Text Box 5-3. Payments for Participation of Research Subjects
p.000056: (based on Grady, 2005)
p.000056: Payment Serves As Amount Determined By Potential Advantages
p.000056: Potential Disadvantages
p.000056:
p.000056: Incentive Supply and demand; market rates
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Compensation Standardized “wage” for time and effort, suggested to be commensurate with wages for
p.000056: unskilled, but essential jobs; additional payment for extra burdens such as endurance of uncomfortable procedures
p.000056: (a) More rapid recruitment
p.000056: (b) Completion bonuses encourage subject retention and high completion rate
...
p.000056: (b) Uniform payment across studies
p.000056: (c) Equal pay for equal work
p.000056: (d) Less risk of undue inducement
p.000056: (a) Undue inducement possibly resulting in incomplete assessment of risks and benefits by subject; subject concealing
p.000056: information to ensure enrollment and retention
p.000056: (b) Competition between studies; better funded studies more likely to meet recruitment goals
p.000056: (c) Different levels of payment at different locations for multicenter research because of supply and demand
p.000056: (a) May have little impact on recruitment
p.000056: (b) Might undercompensate some subjects in relation to regular wage and preferentially attract others
p.000056:
p.000056:
p.000056: Provide “wage” for time and effort; base level of payment on some small fraction of participant’s or the community’s
p.000056: income, or on an appropriate hourly rate for the location, or on community-input about the appropriate level of payment
p.000056: (a) Recognizes contributions of participants
p.000056: (b) Decreases potential that payment would be undue inducement in some communities or locations and insufficient in
p.000056: others
p.000056: (c) Provides equivalent payment for participation across communities and locations (markets)
p.000056: (d) Less risk of undue inducement across study
p.000056: (a) Different levels of payment at different locations in multicenter research or in different communities
p.000056: (b) Unequal pay for equal work may violate one’s sense of justice
p.000056:
p.000056:
p.000056: Reimbursement Actual out-of-pocket cost to
p.000056: participant related to participation, such as parking, transportation, child care, cost of food samples, etc.
p.000056: (a) Lowers barriers to participation
p.000056: (b) Reduces burden and impact of research on participants
p.000056: (a) Few disadvantages
p.000056: (b) Possible differences in costs experienced by different participants
p.000056:
p.000056:
p.000056: Reward Token of appreciation at end of study
p.000056: (a) Expresses gratitude for contribution made
p.000056: (b) Not market dependent
p.000056: (c) Avoids undue inducement
p.000056: (a) Probably no impact on recruitment
p.000056: (b) No basis for consistency
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: for differential recruitment that could result in bias in the study sample.
p.000056: Determining appropriate level of payments or incentives for participants in a research study is
p.000056: complex. “No bright line distinguishes proper and reasonable payments to parents and children
p.000056: from payments that are inappropriate” (p. 214, IOM, 2004). The ethical issue is at what level might a
p.000056: payment change from being an incentive (an encouragement) to participate and become an inducement (the
p.000056: cause or reason) for participation. Many research organizations and IRBs do not have written policies or
p.000056: guidelines
p.000056:
p.000056: regarding the determination of reasonable payment. Decisions often are made based on the level
p.000056: of discomfort and burden, costs to participants, and population characteristics. However, large
...
p.000058: participation in studies
p.000058: • The offer of payments may with low risk but no or few cause guardians or parents to
p.000058: direct benefits
p.000058: not act in the best interests of • It is the just and fair thing incompetent persons or children to do
p.000058: for those who bear in their care. burdens of research on
p.000058: • Persons in different behalf of society. circumstances may view the
p.000058: same amount of payment quite differently.
p.000058: • Payments may alter the composition of the study sample and potentially could compromise study integrity.
p.000058: activities is thus justified on the grounds of fairness” (p. 112, NRC & IOM, 2005).
p.000058: Similarly, the IOM Committee on Clinical Research Involving Children found that “certain types of
p.000058: payments to parents or adolescents are usually if not always acceptable, for example, reimbursement
p.000058: for reasonable expenses that are necessary for research participation. The specifics may vary, but
p.000058: examples of reasonable expenses are costs of transportation to the research site, parking, lodging, meals,
p.000058: and babysitting. Other payments are never appropriate in pediatric research, for example, paying parents
p.000058: for the use of their child in research” (pp. 225-6, IOM, 2004).21
p.000058: The IOM committee recommends establishing policies on acceptable and unacceptable types of
p.000058: payments. They also recommend that the policies disclose any recompense in a full and open
p.000058: process,22 while not overemphasizing any recompense.
p.000058: Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
...
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
p.000058: gestures of appreciation, investigators may also—if they minimize the potential for undue influence—act ethically to
p.000058: reduce certain barriers to research participation when they
p.000058: • reimburse reasonable expenses directly related to a child’s participation in research
p.000058: • provide reasonable, age-appropriate compensation for children based on the time involved in research that does not
p.000058: offer the prospect of direct benefit, and
p.000058: • offer evening or weekend hours, on-site child care, and other reasonable accommodations for parental work and
p.000058: family commitments.”
p.000058: 22 In recommending an open process, the IOM committee chose to reject the
p.000058: arguments from the American Academy of Pediatrics that “any token payment to children for participating in research
p.000058: should not be discussed with them until after research is completed for fear of unduly influencing their decisions
p.000058: (AAP, 2003)…. On balance, the committee agrees that it is best to mention token or other payments during the permission
p.000058: and assent processes” (p. 215, IOM, 2004).
p.000058: The IOM Recommendation 6.1 states, “Institutional review boards, research institutions, and sponsors of research that
p.000058: includes children and adolescents should adopt explicit written policies on acceptable and unacceptable types and
p.000058: amounts of payments related to research participation. These policies should specify that investigators
p.000058: • Disclose the amount, the recipient, the timing, and the purpose (e.g., an expense reimbursement or a token of
p.000058: appreciation to a child) of any payments as part of the process of seeking parents’ permission, and, as appropriate,
p.000058: children’s assent to research participation;
p.000058: • Avoid emphasis on payments or descriptions of payments as benefits of participating in research during the
p.000058: permission or assent procedures; and
p.000058: • Obtain institutional review board approval for the disclosure of information about payments in advertisements and
p.000058: in permission and assent forms and procedures.”
p.000058:
p.000058:
p.000059: 59
p.000059:
p.000059: participate in research are unacceptable. The European Union requires that clinical trials on minors
p.000059: be undertaken only if “no incentives or financial inducements are given except compensation”
p.000059: (European Parliament, 2001).
p.000059: Payment for participation of children in research also is discussed in the literature. Diekema
p.000059: (2005) emphasizes the need to ensure that payments do not distort parental decisionmaking and do not tempt
p.000059: parents to consider other issues than the welfare of their child. Similarly, Menikoff (2005) suggested that
p.000059: there need to be relatively robust protections in place to ensure that families do not change their behaviors
p.000059: to participate in a study. He suggested that these may include determining payment as a percentage of a family’s
p.000059: income and developing criteria for documenting that behaviors have not changed to be eligible for participation in a
p.000059: study. He suggested that, for a study of pesticides, potential study participants provide documentation (such as
p.000059: receipts) that they routinely have been using a commercial pesticide service. This may be difficult
p.000059: for potential participants to do if they do not save receipts, and it would exclude all potential
p.000059: participants who purchase products and apply pesticides themselves. This likely would affect the study
p.000059: objectives and generalizability of the data collected. A survey of investigators (Iltis et al., 2006) found that
p.000059: payments were made in 52% of the pediatric research studies surveyed, and that payment practices varied,
p.000059: as did the reasons for decisions regarding payments. They found a range of payment values separated
p.000059: across cash, gifts, items, vouchers, and other categories. A survey of IRBs (Weise et al., 2002) found that payment
p.000059: for participation in research was allowed by 66% of responding institutions, but that many IRBs did not have
p.000059: specific policies, and that there was considerable variability regarding the basis for decisions on
...
p.000091: credibility is determined by the public’s perceptions of the researchers’ knowledge and expertise, openness
p.000091: and honesty, and concern and care (Peters et al., 1997). These factors are important to consider in
p.000091: developing the information and approach that will be used to respond to criticism.
p.000091: There is a large volume of information available on “crisis communication” that the reader can use to
p.000091: develop a plan for anticipating and responding to criticism (e.g., FCN, 2001; ATSDR, 2007; U.S.
p.000091: HHS,
p.000091: 2002). The key is to be proactive and have a plan before any criticism is raised.
p.000091:
p.000091: 7.10 Responding to the Media, Public Inquiries, and Other Stakeholders
p.000091: Like crisis communications, the communication plan should include detailed plans for how to interact with the
p.000091: stakeholders, the media, and the public. Standard approaches have been developed for
p.000091: effective communications (e.g., the Federal Communicators Network's Communicators Guide [FCN, 2001]) with
p.000091: the media and will not be included in this document. A proactive plan, open and transparent
p.000091: communications, and easily to comprehend information will ensure effective communications with
p.000091: stakeholders and the public.
p.000091:
p.000091: References
p.000091: American Conference of Governmental Industrial Hygienists (ACGIH) (2008). TLV/BEI Resources. Available:
p.000091: http://www.acgih.org/tlv/.
p.000091:
p.000091: Alderson P (1995). Will you help us with our research? Arch Dis Child 72(6):541-42.
p.000091:
p.000091: Anderson B, Hall B (1995). Parents’ perceptions of decision making for children. J Law Med Ethics 23(1):15-9.
p.000091:
p.000091: ATSDR (Agency for Toxic Substances and Disease Registry) (2007). A Primer on Health Risk Communication Principles
p.000091: and Practices [online publication]. Available: http://www.atsdr.cdc.gov/risk/riskprimer/ [accessed 12 June 2007].
p.000091:
p.000091: CDC (Centers for Disease Control and Prevention) (2005). Third National Report on Human Exposure to Environmental
p.000091: Chemicals. National Center for Environmental Health, Atlanta, GA, NCEH Pub. No. 05 0570. Available:
p.000091: http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf [accessed 12 June 2007].
p.000091:
p.000091: Covello V, Allen F (1988). Seven Cardinal Rules of Risk Communication. OPA-87-020. U.S. Environmental Protection
p.000091: Agency, Office of Policy Analysis, Washington, DC. Distributed by the Pennsylvania Dept. of Environmental Resources.
p.000091: Available: http://www.epa.gov/stakeholders/pdf/risk.pdf [accessed 12
p.000091: June 2007].
p.000091:
p.000091: Covello VT, McCallum DB, Pavlova M (eds) (1989). Effective Risk Communication: the role and responsibility of
p.000091: Government and Non-Government Organizations. New York. NY: Plenum Press.
p.000091:
...
p.000009: also were included. Because the elderly is the subpopulation most sensitive to health effects associated with PM
p.000009: exposures, the majority of subjects were over age 65.
p.000009: Performed in the Raleigh, NC, area in homes with children 1 to 3 years old. Homeowners reported either professional or
p.000009: self applications of diazinon. Goals of the study were to evaluate methods to measure excess dietary exposures
p.000009: resulting from food-handling activities by young children during eating and to assess whether the Children’s Dietary
p.000009: Intake Model (CDIM) accurately represents total dietary exposures of children. Study resulted in refinements of model
p.000009: parameters for transfer and activity.
p.000009: Observational measurement study of exposure to chlorpyrifos among children 2-5 years of age in urban New Jersey homes
p.000009: following crack and crevice treatment by a professional applicator. Study investigated decay of pesticide levels over
p.000009: time, transfer of pesticide from microenvironmental media to child, and factors that affect transfer. Dermal transfer
p.000009: evaluated with surface wipes, hand wipes, dermal wipes, cotton garments, and videotaping.
p.000009: Physicians at Case-Western Reserve treating children with idiopathic pulmonary hemorrhage evaluated the nature of the
p.000009: fungus found in homes of the afflicted and control children to determine if Stachybotrys was a potential factor in the
p.000009: illness. Three of the 8 cases, and none of the controls, had Stachybotrys strains that potentially were implicated.
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: The largest children’s exposure study undertaken to date. It examines aggregate exposures of children 18 months to 5
p.000009: years to pollutants commonly found in everyday environments. The major objectives were to quantify children’s aggregate
p.000009: exposures, apportion exposure pathways, and identify important exposure media. Participants were recruited from 12
p.000009: urban and rural counties in North Carolina and Ohio using a random digit dialing method. Monitoring was performed at
p.000009: both daycare centers and homes. Samples collected include food, beverages, indoor air, outdoor air, hand wipes, dust,
p.000009: soil, transferable residues, floor and surface wipes, and urine. The samples were analyzed for more than 40 pollutants,
p.000009: including insecticides, phthalate esters, phenols, polychlorinated biphenyls, and PAHs.
p.000009: Scientists monitored air pollutants inside and outside vehicles of healthy highway patrol officers in North Carolina
p.000009: while troopers were on patrol for 9-hour shifts and examined cardiovascular effects. The findings indicated that people
p.000009: driving in motor vehicles are exposed to PM2.5 and other pollutants generated from motor vehicles, and that these
p.000009: exposures appear to cause cardiovascular changes.
p.000009:
p.000009:
p.000102: 102
p.000102: with contractor support; funded and collaborated on others with Harvard School of Public Health, University. of
p.000102: Washington, and NYU.
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL designed, contractor conducted
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL funded the Environmental and Occupational Health Sciences Institute (EOHSI).
p.000102:
p.000102:
p.000102:
p.000102: NERL staff collaborated with Case-Western Reserve University by conducting lab analysis for Stachybotrys.
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL designed, contractor conducted
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: EPA designed and conducted with contractor support
p.000102:
p.000102: Table A-1. (Continued)
p.000102: Study Date Size Type Brief Description
p.000102: NERL Role
p.000102: First National 2001 168 Child care Probability- A collaborative study with the Department
p.000102: of Housing and HUD and CPSC Environmental centers based
p.000102: Urban Development (HUD) and the Consumer Product Safety study. NERL Health Survey of
p.000102: selection on Commission (CPSC) of pesticide use and young children’s collaborated
p.000102: and
p.000102: Child Care national scale (less than 6 years old)
p.000102: potential exposure to pesticides and conducted analysis
p.000102:
p.000102: Centers (CCC)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: A Pilot Study Examining Translocation Pathways Following a Granular Application of Diazinon to Residential Lawns (PET)
p.000102: Biological and Environmental Monitoring for Organo- phosphate and Pyrethroid Pesticide Exposures in Children Living in
p.000102: Jacksonville, FL (JAX)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: Exposure Assessment for Community- Acquired Legionnaires Disease
p.000102: Center for the Health Assessment of Mothers and Children of Salinas Quantitative Exposure Assessment Study (CHAMACOS)
p.000102: Feasibility of Macroactivity Approach To Assess Dermal Exposure (Daycare)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 2002
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 6 Households
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 9 Households in NERL exposure component
p.002002:
...
p.000021: collected urine samples for CDC from 200 children visiting six public health clinics in Jacksonville, and collected
p.000021: environmental screening samples at approximately 25% of these children’s homes. A detailed aggregate exposure
p.000021: assessment at 9 homes was overseen by NERL and involved collection of surface wipes, transferable residues, air,
p.000021: duplicate diet, cotton garment samples, and urine samples. A time- activity diary of the children’s activities was
p.000021: included.
p.000021: Work with Veteran’s Administration hospital staff. Cases of Legionnaires Disease were evaluated for potential for
p.000021: exposure from residential drinking water taps. In about 24% of the tested cases, homes were found to have Legionella
p.000021: bacteria in water taps at home, compared to their absence in other cases and in controls
p.000021: Incidental pesticide exposure measurement study of farmworkers’ children ages 5 to 35 mo. Purpose is the evaluation of
p.000021: methods for aggregate exposure measurements and the evaluation of pathways of exposure and important factors that
p.000021: affect exposure. Measurements include pesticide distributions in microenvironments where children spend time, transfer
p.000021: of pesticides from microenvironmental media to child, and factors that affect transfer.
p.000021:
p.000021:
p.000021:
p.000021: Study identified daycare centers with previously established contracts for routine monthly pesticide applications and
p.000021: conducted screening sampling in each to evaluate the distributions of transferable pesticide residues on floor surfaces
p.000021: where children spend time. One daycare was selected for intensive measurements, and children from different age groups
p.000021: volunteered to wear full-body cotton suits for short time periods while their activities were videotaped.
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000103: 103
p.000103: of molds/fungi and helped with lead and pesticide measurements.
p.000103:
p.000103:
p.000103: EPA conducted with contractor support
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: Multiagency effort; NERL was a participant and led the 9-home exposure component.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL funded IAG with VA to conduct study.
p.000103:
p.000103:
p.000103:
p.000103: EPA grant to UC Berkeley; NERL augmented the existing research effort.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL designed, contractor conducted
p.000103:
p.000103: Table A-1. (Continued)
p.000103: Study Date Size Type Brief Description
p.000103: NERL Role
...
p.000109: (16) The process of recruitment (e.g., advertisements) and the steps to be taken to protect privacy and
p.000109: confidentiality during recruitment
p.000109: (17) A description and explanation of any and all interventions
p.000109: (18) The measurements to be performed in the study, including environmental and biological sample
p.000109: collection, and other data and information that will be collected
p.000109: (19) If applicable, clinical and other tests involving the study participants that are to be carried out
p.000109: (20) The rules or criteria according to which subjects may be removed from the study or the study may be
p.000109: terminated
p.000109: (21) The methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000109: complications
p.000109: (22) The potential benefits of the research to subjects and to others
p.000109: (23) The expected benefits of the research to the population, including new knowledge that the study
p.000109: might generate
p.000109:
p.000109:
p.000109:
p.000111: 111
p.000111:
p.000111: (24) The means proposed to obtain individual informed consent and the procedure planned to communicate information to
p.000111: prospective subjects, including the name and position of the person responsible for obtaining consent
p.000111: (25) When a prospective subject is not capable of informed consent, satisfactory assurance
p.000111: that permission will be obtained from a duly authorized person, or, in the case of a child who is sufficiently mature
p.000111: to understand the implications of informed consent but has not reached the legal age of consent,
p.000111: that knowing agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian
p.000111: or other duly authorized representative.
p.000111: (26) An account of any economic or other compensation or incentives to prospective subjects to participate, such as
p.000111: offers of cash payments, gifts, or free services or facilities, and of any financial
p.000111: obligations assumed by the subjects, such as payment for medical services
p.000111: (27) The plans and procedures and the persons responsible for communicating to
p.000111: subjects information arising from the study (on harm or benefit, for example) or from other research on the same
p.000111: topic that could affect subjects’ willingness to continue in the study
p.000111: (28) The plans to inform subjects about the results of the study
p.000111: (29) The provisions for protecting the confidentiality of personal data and respecting the privacy of subjects,
p.000111: including the precautions that are in place to prevent disclosure of the results of a
p.000111: subject’s genetic tests to immediate family relatives without the consent of the subject
...
p.000115: Study
p.000115: NHEXAS The National Human Exposure Assessment Survey NHLBI National Heart, Lung, and Blood
p.000115: Institute
p.000115: NHRPAC National Human Research Protections Advisory Committee NIH National Institutes of
p.000115: Health
p.000115: NRC National Research Council
p.000115: OHRP Office for Human Research Protections OMB Office of Management and Budget OSMB
p.000115: observational study monitoring board PM particulate matter
p.000115: Q&As questions and answers
p.000115: QAPP quality assurance project plan
p.000115: RfD reference dose
p.000115: SEAOES Scientific and Ethical Approaches for Observational Exposure Studies TEAL Tribal
p.000115: Efforts Against Lead
p.000115: TEAM Total Exposure Assessment Methodology TLV threshold limit value
p.000115: VOC volatile organic compound
p.000115: WHO World Health Organization
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000116: 116
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116: Appendix F
p.000116: Glossary
p.000116:
p.000116:
p.000116:
p.000116: Agent. A chemical, mineralogical, biological, or physical entity that may cause deleterious effects in an organism
p.000116: after the organism is exposed to it [EPA/600/Z-92/001, May 1992].
p.000116: Assent. A child’s affirmative agreement to participate in research. Mere failure to object should not, absent
p.000116: affirmative agreement, be construed as assent [45 CFR 46.402(d)].
p.000116: Autonomy. The capability and capacity to govern oneself.
p.000116: Beneficence. The ethical obligation to maximize benefits and to minimize harms. This principle gives rise to norms
p.000116: requiring that the risks of research be reasonable in light of the expected benefits, that the research design be
p.000116: sound, and that the investigators be competent both to conduct the research and to safeguard the welfare of the
p.000116: research subjects. Beneficence further proscribes the deliberate infliction of harm on persons; this aspect of
p.000116: beneficence is sometimes expressed as a separate principle, nonmaleficence (do no harm).
p.000116: Child. A person who has not attained the age of 18 years [40 CFR 26.202(a)]
p.000116: Collateral observations. Potentially unsafe hazards, conditions, or situations unrelated to the research study that
p.000116: are observed by the research staff
p.000116: Common Rule. The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects.” It was
p.000116: adopted by more than a dozen Federal departments or agencies in 1991, with EPA adapting it in Title 40 CFR Part 26
p.000116: Subpart A.
p.000116: Community-based participatory research (CBPR). Collaborative research with a community in which the community is
p.000116: involved in all phases of the research.
p.000116: A fundamental concept is that the research aims to combine knowledge with action and to achieve social
p.000116: change to improve health outcomes and eliminate health disparities.
p.000116: Confidentiality. The keeping safe or not redisclosing by one of the parties in a confidential relationship information
p.000116: that originally was disclosed in the confidential relationship
p.000116: Environmental justice. The fair treatment and meaningful involvement of all people regardless of race, color, national
p.000116: origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations,
p.000116: and policies
p.000116: Exposure. Contact of a chemical, physical, or biological agent with the outer boundary of an organism (e.g., a
...
Searching for indicator children:
(return to top)
p.000024: 24
p.000024: 2.4. Ensuring a Favorable Risk-Benefit Ratio
p.000025: 25
p.000025: 2.4.1. Designing in Benefits for the Participants
p.000025: 25
p.000025: 2.4.2. Assessing Benefits and Risks of Study Participation 25
p.000025: 2.5. Independent Scientific and Ethical Review
p.000026: 26
p.000026: 2.5.1. Scientific Peer Review
p.000027: 27
p.000027: 2.5.2. Conflicts of Interest
p.000027: 27
p.000027: 2.5.3. Develop the Human Subjects Protocol for Institutional Review Board Review 28
p.000027: 2.5.4. Ethical Review
p.000029: 29
p.000029: 2.5.5. Internal U.S. EPA Review of Scientific and Ethical Issues 29
p.000029: 2.6. Informed Consent
p.000029: 29
p.000029: 2.7. Ensuring That Participant Behaviors Are Not Changed Adversely Because of
p.000029: Being in the Study
p.000030: 30
p.000030: 2.8. Criteria and Standards for Monitoring Scientific and Ethical Issues 30
p.000030: 3. Ensuring Protection of Vulnerable Groups
p.000035: 35
p.000035: 3.1. Identification of Vulnerable Groups
p.000035: 35
p.000035: vii
p.000035:
p.000035: 3.2. Justification for Involving Vulnerable Persons in Observational Research 36
p.000035: 3.3. Minimal Risk and Vulnerable Groups
p.000037: 37
p.000037: 3.4. Research Involving Children
p.000037: 37
p.000037: 3.5. Women as Research Subjects
p.000038: 38
p.000038: 3.6. Other Potentially Vulnerable Groups
p.000039: 39
p.000039: 4. Privacy, Confidentiality, and Other Concerns Related to Observational
p.000039: Human Exposure Studies
p.000041: 41
p.000041: 4.1. Privacy Issues
p.000041: 41
p.000041: 4.2. Confidentiality
p.000042: 42
p.000042: 4.2.1. Confidentiality of Information
p.000043: 43
p.000043: 4.2.2. Confidentiality of Participation
p.000044: 44
p.000044: 4.3. Collateral Observations
p.000044: 44
p.000044: 4.3.1. Potential Nonstudy Hazards in the Residence 44
p.000044: 4.3.2. Collateral Observations with Mandated Reporting Requirements 45
p.000044: 4.3.3. Hazard Communication
p.000045: 45
p.000045: 4.3.4. Planning and Staff Training
p.000046: 46
p.000046: 4.4. Third-Party Issues
p.000046: 46
p.000046: 4.4.1. Determining Whether a Third Party Is a Human Subject 47
p.000046: 4.4.2. Informing Third Parties of Research Activities 47
p.000046: 4.4.3. Research Results and Third Parties
p.000047: 47
p.000047: 4.5. Data and Safety Monitoring and Oversight
p.000048: 48
p.000048: 5. Creating an Appropriate Relationship Between the Participant and Researcher 51
p.000048: 5.1. Informed Consent
p.000052: 52
p.000052: 5.1.1. Information
p.000052: 52
p.000052: 5.1.2. Comprehension
p.000054: 54
p.000054: 5.1.3. Voluntary Participation
p.000055: 55
p.000055: 5.2. Payments to Research Participants
p.000056: 56
p.000056: 5.2.1. Types and Amounts of Payments Offered in Research Studies 56
p.000056: 5.2.2. Regulations and Guidance Regarding Payment to Research Participants 58
p.000056: 5.2.3. Payments When Children or Other Vulnerable Populations Are Involved 59
p.000056: 5.2.4. Payments in Observational Human Exposure Studies 61
p.000056: 5.3. Research Rights and Grievance Procedures
p.000061: 61
p.000061: 5.3.1. Ombudsman
p.000061: 61
p.000061: 5.3.2. Community Advisory Board
p.000062: 62
p.000062: 5.4. Creating a Supportive Environment for Research and Interaction 62
p.000062: 5.5. Recruitment Strategies
p.000062: 62
p.000062: 5.6. Retention Strategies
p.000063: 63
p.000063: 5.7. Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk 64
p.000063: 6. Building and Maintaining Appropriate Community and Stakeholder Relationships 67
p.000063: 6.1. Approaches to Community Involvement
p.000068: 68
p.000068: 6.2. Issues in Community Involvement
p.000071: 71
p.000071: 6.2.1. Defining “Community”
p.000071: 71
p.000071: 6.2.2. Identifying Who Represents the Community 71
p.000071: 6.2.3. Building Relationships and Trust
p.000072: 72
p.000072: 6.2.4. Importance of Language and Communications with the Community 73
p.000072: 6.2.5. Recognizing and Addressing Cultural Differences 73
p.000072: 6.2.6. Honesty, Power Relationships, and Partnerships 74
p.000072: 6.2.7. Building a Lasting Infrastructure
p.000074: 74
p.000074: 6.3. Community Involvement in Observational Human Exposure Studies 75
...
p.000001: research question and justification of the research effort during the problem conceptualization phase. If human
p.000001: subjects research is justified for the study, the scientific and ethical approaches are described in the study
p.000001: design and the human subjects research protocol. The basic elements that should be included in the
p.000001: study design and in the human subjects research protocol are described, and researchers are advised to consider
p.000001: alternative and innovative study designs that maximize the benefits to the study participants and their
p.000001: community. Information is provided on both scientific peer review and ethical review, and the integration
p.000001: of the two. Mandated procedures for review by external peers, by Institutional Review Boards (IRBs),
p.000001: and by the EPA Human Subjects Research Review Official (HSRRO) are detailed.
p.000001:
p.000001: to the authors as they have developed this document. Those references are listed in Table 1-4,
p.000001: which is replicated below.
p.000001: The authors also have relied extensively on the
p.000001: Problem Conceptualization
p.000001:
p.000001: Planning
p.000001: Define & Justify the Study
p.000001:
p.000001: advice of an expert panel that convened in November 2006 to provide advice and guidance about the structure and
p.000001: content of this document. The Expert Panel consisted of 11 nationally recognized authorities from
p.000001: diverse fields ― exposure science, environmental health, bioethics, epidemiology, community-based research, law,
p.000001: research in minority communities, public health, toxicology, pediatrics, and children’s environmental
p.000001: health.
p.000001: The Expert Panel Workshop resulted in suggestions
p.000001: & Scoping
p.000001:
p.000001:
p.000001: Independent Review
p.000001:
p.000001:
p.000001: Agency HSRRO
p.000001: Review
p.000001: Develop Study Design
p.000001:
p.000001:
p.000001: Peer Review
p.000001: Scientific & Ethical Review
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: HSRRO
p.000001: Review
p.000001: Develop Human Subjects Protocol
p.000001:
p.000001:
p.000001: IRB Review
p.000001: Ethical & Scientific Review
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Disapprove No Study
p.000001:
p.000001: for both the structure and the content of this document (ERG, 2007). Following the advice of the Expert Panel,
p.000001:
p.000001: Implement Study
p.000001: Approve Conduct Study
p.000001:
p.000001: this document is organized in seven sections.
p.000001: & Monitor Progress
p.000001: Criteria OK
p.000001: Continue Study
p.000001: Implement
p.000001: & Monitor
p.000001: Criteria Exceeded
p.000001: Terminate Study
p.000001:
p.000001:
p.000001: 1 See, for example, the writings of Beauchamp and Childress in Principles of Biomedical Ethics (Beauchamp and
p.000001: Childress, 2001) and the discussion of “What Makes Clinical Research Ethical?” by Emanuel, Wendler, and Grady (Emanuel
p.000001: et al., 2000).
p.000001: Stages in the Development of a NERL Observational Human Exposure Study
p.000001:
p.000002: 2
p.000002:
p.000002:
p.000002: Table 1-4. Important References in Developing This Document:
p.000002: Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
...
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
...
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2008). International Ethical Guidelines for
p.000003: Epidemiological Studies. World Health Organization. Geneva, Switzerland. Available:
p.000003: http://www.cioms.ch/080221feb_2008.pdf [accessed 25
p.000003: April 2008].
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000003: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000003:
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000004: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000004:
p.000004: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
p.000004:
p.000004: ERG (Eastern Research Group) (2007). Report on the Workshop to Discuss State-of-the-Science Approaches for
p.000004: Observational Exposure Measurement Studies. Held in Durham, North Carolina on November 28-29, 2006. Final Report:
p.000004: January 25, 2007. (PB2007-108905).
p.000004:
p.000004: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000004: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000004: [accessed 12 June 2007].
p.000004:
p.000004: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000004: Housing-Related Health Hazards Involving Children.
p.000004: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000004: June 2007].
p.000004: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
p.000004: Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of Human Subjects
p.000004: of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 12 June
p.000004: 2007].
p.000004:
p.000004: U.S. EPA (U.S. Environmental Protection Agency) (2000) Comments on the Use of Data from the Testing of Human Subjects:
p.000004: A Report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. United States Environmental Protection
p.000004: Agency, Science Advisory Board, EPA-SAB-EC-00-017. Available: http://yosemite.epa.gov/sab/SABPRODUCT.NSF/E3AE0F3
p.000004: 0D7430436852571A7005325E8/$File/ec0017.pdf [accessed 12 June 2007].
p.000004:
p.000004: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000004: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000004: [accessed 12 June 2007].
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
...
p.000008: for a population’s longitudinal exposure to fine PM.
p.000008: Resolved questions in NAS review of PM science and provided a “generally consistent finding that ambient particle
p.000008: concentrations are a key determinant of the longitudinal variation in personal exposure.” (NRC, 2004). These results
p.000008: have been instrumental in support of the National Ambient Air Quality Standard for PM (U.S. EPA, 1999).
p.000008:
p.000008:
p.000008: Volatile Organic Compounds (VOCs)
p.000008:
p.000008: EPA's Total Exposure Assessment Methodology (TEAM) studies found levels of about a dozen common organic pollutants to
p.000008: be 2- to 5-times higher inside homes than outside. Use of products containing organic chemicals may result in very high
p.000008: and persistent pollutant levels.
p.000008:
p.000008: EPA, States, and the Consumer Product Safety Commission worked together to influence manufacturers to voluntarily
p.000008: reduce emissions of toxic chemicals from consumer products, building materials, and furnishings, and to develop
p.000008: mitigation strategies and educational materials to teach people how to reduce their contact with chemicals indoors. As
p.000008: a result, contact with toxic chemicals indoors has been reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html).
p.000008:
p.000008:
p.000008: Formaldehyde
p.000008:
p.000008: Studies found elevated formaldehyde levels indoors and helped identify indoor sources.
p.000008:
p.000008: EPA worked with HUD, CPSC, and other agencies to limit formaldehyde in building or consumer products and to educate the
p.000008: public on how to reduce exposures (see www. epa.gov/iaq/formalde.html).
p.000008:
p.000008:
p.000008: EPA has adopted additional protections for children and pregnant or nursing mothers in Subparts B through
p.000008: D. These sections apply to all research either conducted or funded by EPA and are, therefore, directly applicable to
p.000008: NERL’s observational human exposure studies.4 Subpart B prohibits EPA from conducting or supporting research
p.000008: that involves intentional exposure of “a pregnant woman (and, thereby, her fetus), a nursing woman,
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
...
p.000008: years later, the core HHS regulations (Subpart A) were adopted by almost all of the Federal
p.000008: departments and agencies that conducted or sponsored human subjects research as the “Common Rule.”
p.000008: Since 1991, ethical thought and regulatory processes for the protection of human subjects have continued to
p.000008: evolve and grow. For example, many ethicists expand the elements contained in the principle of
p.000008: beneficence from the Belmont Report into two principles:
p.000008: (1) beneficence, meaning to prevent or remove harm and
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: to maximize the possible benefits; and
p.000009: (2) nonmaleficence, meaning not to inflict harm (Beauchamp and Childress, 2001).
p.000009:
p.000009: Table 1-2. The Belmont Report— Principles and Recommendations
p.000009:
p.000009: Ethical Principle Regulatory Manifestation
p.000009: addressed many important scientific and ethical issues on this topic, including the National Research
p.000009: Council (NRC) in its report, Protecting Participants and Facilitating Social and Behavioral Sciences
p.000009: Research (NRC, 2003), a joint NRC and Institute of Medicine (NRC & IOM, 2005) committee in the report on
p.000009: Ethical Considerations for Research on Housing-Related Health Hazards Involving Children; the Council
p.000009: for
p.000009:
p.000009: Respect for Persons
p.000009: • Individuals should be treated as autonomous agents.
p.000009: • Persons with diminished autonomy are entitled to protection.
p.000009:
p.000009: Beneficence
p.000009: • Human subjects should not be harmed.
p.000009: • Research should maximize possible benefits and minimize possible harms.
p.000009: Justice
p.000009: • The benefits and risks of research must be distributed fairly.
p.000009: Informed Consent
p.000009: • Subjects must be given the opportunity to choose what will or will not happen to them
p.000009: • The consent process must include
p.000009: (1) information,
p.000009: (2) comprehension, and
p.000009: (3) voluntariness
p.000009: Assessment of Risks and Benefits
p.000009: • The nature and scope of risks and benefits must be assessed in a systematic manner.
p.000009:
p.000009:
p.000009: Selection of Subjects
p.000009: • There must be fair procedures and outcomes in the selection of research subjects.
p.000009: International Organizations of Medical Sciences (CIOMS) under the World Health Organization in
p.000009: its International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002) and
p.000009: in the International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008); and
...
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000012: 12
p.000012:
p.000012: address all of the relevant issues for their particular study to ensure that the specific elements of
p.000012: the study will safeguard and protect the human research subjects.
p.000012: In addition to being an information resource for NERL researchers, this document provides useful
p.000012: information for contractors and grantees funded by NERL to consider during the design and implementation of
p.000012: their exposure science research. Although not its intended audience, this document also may prove to be useful
p.000012: to other researchers, within and outside of EPA, who are involved in observational human exposure
p.000012: studies.
p.000012:
p.000012: 1.4 Process for Developing the Document
p.000012: This document was written by exposure science researchers in EPA’s NERL, with substantial input from experts
p.000012: within and outside of the Agency. Information relevant to the process and the document has been routinely
p.000012: posted on the EPA Web site at http://www.epa.gov/nerl/sots.
p.000012: NERL staff began this work by hosting a series of stakeholder meetings in the summer of 2006 to seek
p.000012: input on the content and format of the document. In November 2006, NERL convened an expert panel to
p.000012: provide its advice and guidance about the scope and content of this document. The Expert Panel consisted of
p.000012: 11 nationally recognized authorities in diverse fields: exposure science, environmental health,
p.000012: bioethics, epidemiology law, community-based research, research in minority communities, public health,
p.000012: toxicology, pediatrics, children’s environmental health, etc. Details about the Expert Panel and the workshop can
p.000012: be found in Appendix B. The summary report from the Expert Panel may be accessed
p.000012: online at http://www.epa.gov/nerl/sots/workshop-report.pdf.
p.000012: The structure and content of the current report follow the recommendations of the Expert
p.000012: Panel. Specifically, the Expert Panel recommended that this document should include the following six major
p.000012: topic areas:
p.000012: (1) elements to be considered in study conceptualization,
p.000012: (2) ensuring protection of vulnerable groups,
p.000012: (3) addressing privacy and other concerns related to observational human exposure studies,
p.000012: (4) creating an appropriate relationship between the participant and investigator,
p.000012: (5) building and maintaining appropriate community and stakeholder relationships, and
p.000012: (6) designing and implementing strategies for effective communication.
p.000012: These recommendations include pragmatic steps that NERL scientists can undertake during the development and
p.000012: implementation of observational human exposure studies. Note that each step may require consideration and
p.000012: application of multiple ethical and scientific principles, and the same ethical principle may
p.000012: be fundamental to several of the topic areas. As a result, the same ethical principle may be discussed in
p.000012: several sections throughout this document.
p.000012: Using the advice of the Expert Panel, an internal review draft of the document was written. Based on the
...
p.000013: April 2008].
p.000013:
p.000013: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000013: Biomedical Research Involving Human Subjects.
p.000013: Geneva, Switzerland: CIOMS. Available: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000013:
p.000013: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000013:
p.000013: NEAC (National Ethics Advisory Committee) (2006). Ethical Guidelines for Observational Studies: Observational research
p.000013: audits and related activities. Wellington, New Zealand: Ministry of Health. Available:
p.000013: http://www.neac.health.govt.nz/moh.nsf/indexcm/neac resources-publications-ethicalguidelines.
p.000013:
p.000013: NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing Research
p.000013: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000013: [accessed 16 August 2007].
p.000013:
p.000013: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000013: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000013: [accessed 12 June 2007].
p.000013:
p.000013: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000013: Housing-Related Health Hazards Involving Children.
p.000013: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000013: June 2007].
p.000013:
p.000013: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
p.000013: Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of Human Subjects
p.000013: of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 12 June
p.000013: 2007].
p.000013:
p.000013: U.S. EPA (U.S. Environmental Protection Agency) (1999). Air Quality Criteria for Particulate Matter. Environmental
p.000013: Protection Agency, National Center for Environmental
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014: Assessment, Office of Research and Development. EPA/600/P-99/002.
p.000014:
p.000014: U.S. EPA (U.S. Environmental Protection Agency) (1992). Guidelines for Exposure Assessment. Environmental Protection
p.000014: Agency, Risk Assessment Forum. EPA/600/Z 92/001. Available: http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_
p.000014: id=429103 [accessed 15 April 2008].
p.000014:
p.000014: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
...
p.000017: different fields of research—social behavioral, economic, biological, medical, epidemiological,
p.000017: and exposure science. NERL has used observational human exposure studies to understand how people come into
p.000017: contact with pollutants in their everyday lives, with the ultimate goal of protecting public health. NERL’s
p.000017: exposure research program addresses critical science needs directly related to Agency goals for protection of
p.000017: human health. The research program is driven by key exposure science questions that may be generated from a
p.000017: number of different sources, including legislative mandates (e.g., the Food Quality Protection
p.000017: Act, the
p.000017:
p.000017:
p.000018: 18
p.000018:
p.000018: Clean Air Act, the Safe Drinking Water Act), program offices or research planning groups in the
p.000018: Agency, scientific peers and researchers, or collaborators. Communities also may identify
p.000018: concerns about exposures in their locales. NERL’s observational human exposure studies collect data to improve
p.000018: exposure and risk assessments, to develop risk management strategies, and to substantiate informational
p.000018: and educational materials for use by EPA program offices (e.g., Office of Pollution Prevention and Toxic
p.000018: Substances, Office of Air and Radiation, Office of Children’s Health Protection).
p.000018: Emanuel et al. (2000) contend that an ethical research study must provide a worthwhile social or
p.000018: scientific value. Ideally, observational human exposure studies can provide both a scientific value and a social
p.000018: value to the participants and their community when feasible. Whenever possible, researchers should work
p.000018: with communities to develop studies that can help address community problems and maximize the
p.000018: benefit to the participants and the community, both of which also assume a burden for participation in a
p.000018: research study.
p.000018: The study problems addressed in past observational human exposure studies conducted or supported by NERL
p.000018: have varied substantially, as described in Appendix A of this document. As shown in Table A-1, NERL’s studies
p.000018: have addressed exposures to particulate matter (PM), air toxics, persistent organic chemicals, and nonpersistent
p.000018: chemicals including pesticides. The studies have examined single routes of exposure (air) and multimedia
p.000018: exposures, including dietary exposure. The studies range from small-scale pilot studies to large
p.000018: probability-based samples. They have included cross- sectional, longitudinal, and convenience samples. Table A-1
p.000018: demonstrates that many of the studies are small in scale and were intended to test a methodology to see if it may
p.000018: prove useful for a subsequent large-scale probabilistic human exposure research effort. Both
p.000018: small-scale and large-scale human exposure studies do involve human subjects. This means that the studies
...
p.000021: the number of samples and perhaps biasing the data.
p.000021: It is critical that sample size be determined at the time of study conceptualization and planning and
p.000021: not after the study already has been conducted. Researchers must include experts with the appropriate
p.000021: statistical expertise on the research team at its very inception. For additional information and insight, readers
p.000021: should refer to biostatistics books, Web sites, and other references (Lenth, 2001; Castelloe, 2000; Kraemer and
p.000021: Thiemann, 1987; Van Belle and Fisher, 2004; Wackerly et al., 2001; Dallal, 2001) about this very important topic.
p.000021:
p.000021: 2.2.4 Representativeness of the Sample
p.000021: In addition to concerns about the sample size being sufficient to provide statistically significant results,
p.000021: researchers also must be concerned about the individuals who participate in a study and of what group
p.000021: or population they may be representative. Research, as defined in the Common Rule, is “a
p.000021: systematic investigation … designed to develop or contribute to generalizable knowledge.” How
p.000021: “generalizable” the
p.000021:
p.000021:
p.000022: 22
p.000022:
p.000022: results of an observational study may be depends on the representativeness of the sample (the participants). A
p.000022: review of former NERL studies (Table A-1) shows a wide variety of approaches to selecting the participants,
p.000022: both probability sampling and nonprobability sampling. Some of the studies have involved randomized sampling (e.g.,
p.000022: NHAPS, NHEXAS), selecting a cohort of interest and then using a randomized sample (e.g., Children’s Total
p.000022: Exposure to Persistent Pesticides and Other Persistent Organic Pollutants [CTEPP], DEARS) or a
p.000022: convenience sample (e.g., some panel studies), purposeful selection (judgment sampling) by
p.000022: the research team (for methods testing studies), recruiting the whole population in a locale or of a particular
p.000022: cohort (e.g., as proposed for the National Children’s Study [NCS]), or simply a convenience sample (in small
p.000022: pilot studies).
p.000022: The approach used to select the participants has depended on the objectives of the study. Research to
p.000022: understand and describe the distribution of exposures in the general population (like NHEXAS) or of the
p.000022: population or cohort in a particular state or region (like CTEPP or Agricultural Health Study [AHS]), has
p.000022: required a large number of randomly-selected participants. Randomized selection is recognized
p.000022: as a valid statistical method to get a sample that is representative of the larger population
p.000022: from which the participants were selected. Pilot studies performed to evaluate a method or to estimate
p.000022: the likely range of exposure concentrations often have employed either purposeful sampling, where
p.000022: the researchers use information on the relevant characteristics of the population to select those
p.000022: participants who will exhibit a wide range of activity levels or potential exposure concentrations, or
p.000022: convenience sampling, where the researchers select the most accessible members of a population
p.000022: NERL’s observational human exposure studies also have routinely collected information about the
p.000022: participants’ activities by using questionnaires and surveys. Survey design is both a science and an
p.000022: art because the design of surveys is based on statistics and science, but designing a good and effective questionnaire
p.000022: is often an art that requires understanding the individuals being surveyed. Text Box 2-3 identifies some of the
...
p.000024:
p.000024: 2.4 Ensuring a Favorable Risk-Benefit Ratio
p.000024: 2.4.1 Designing in Benefits for the Participants
p.000024: Study designs vary depending on the objectives of the study, existing knowledge on the research question, and
p.000024: the hazard being studied (NRC & IOM, 2005). Recent ethical discussions about study designs in human subjects
p.000024: research (cf., Recommendation 7.1, p. 143, NRC & IOM [2005] and Emanuel et al. [2000]) support the development
p.000024: of innovative study designs to maximize the benefit9 to the study participants, as well as to
p.000024: the community and the greater society beyond. Observational human exposure studies generally collect data that
p.000024: contribute to generalizable knowledge that will benefit the community and society as a whole, but they often do not
p.000024: provide obvious direct benefit to study participants. Therefore, it is important to include elements
p.000024: in the study design that can offer benefits to the participants wherever possible. This is not always
p.000024: straightforward, but one way that participants, as well as communities, can benefit from these studies is
p.000024: by incorporating strong educational components into the conduct of the research. For example, brochures, videos,
p.000024: and other materials that educate study participants on safety around the home or on how to reduce their
p.000024: exposure to chemicals can be distributed during the study. EPA’s program offices, including the Office of
p.000024: Children’s Health Protection, the Office of Pollution Prevention and Toxics, the Office of Pesticide Programs,
p.000024: the Office of Drinking Water, and others have Web sites with substantial amounts of informational
p.000024: and educational materials available that could be distributed to study participants. Other organizations, such as
p.000024: the American Lung Association, the American Cancer Society, the American Academy of Pediatrics (AAP),
p.000024: and various environmental groups, have materials of which study participants may not be aware that could be used
p.000024: as educational materials when relevant.
p.000024: In addition, approaches that provide direct benefits to study participants will need to be tailored to
p.000024: the particular study population and community. Feedback from potential participants in focus groups and
p.000024: input from community representatives may be useful in identifying these approaches.
p.000024:
p.000024:
p.000024:
p.000024: 9 Payment to participants is never considered a benefit of a study.
p.000024: 2.4.2 Assessing Benefits and Risks of Study Participation
p.000024: For all research involving human participants, the Common Rule requires researchers to ensure that
p.000024: potential risks “are reasonable in relation to the anticipated benefits,” and that risks are
p.000024: minimized (40 CFR 26.111). It is most useful if the assessment of benefits and risks is begun early in
p.000024: the scoping and planning phase of a study.
p.000024: Unlike some biomedical research that involves the study of interventions or procedures that hold out the
p.000024: prospect of direct diagnostic, therapeutic, or preventative benefit for the study participants, observational
p.000024: human exposure studies often do not have a similar prospect of direct benefit to the participant. Therefore, the
p.000024: risk- benefit balance is based on the balance between the risks to the participants and the expected benefits to
p.000024: society (generalizable knowledge). The risks to participants must be reasonable [40 CFR 26.111(a)(2)] in
p.000024: relation to the importance of the knowledge gained. This assessment of the risk-benefit balance,
p.000024: therefore, needs to be performed in the initial planning of the study to be included in the justification for the
p.000024: study (Section 2.2).
p.000024: If there is no prospect of direct participant benefit, and the study participants are children, moreover, EPA
p.000024: is permitted to conduct or support only those observational human exposure studies that meet both the regulatory
p.000024: definition of “observational” and the regulatory definition of “minimal risk.” The latter is defined in
p.000024: the Common Rule at 40 CFR 26.102(i) and reiterated in Subpart D of the EPA Rule at 40 CFR 26.402(g):
p.000024: “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not
p.000024: greater in and of themselves than those ordinarily encountered in daily life or during the
p.000024: performance of routine physical or psychological examinations or tests.” In applying this definition, EPA
p.000024: adheres to the consensus standard that the reference population for this definition is normal children living
p.000024: in safe, healthy environments. In its discussion of the perception of risks and benefits, the NRC & IOM (2005) report
p.000024: on housing health hazards in children notes that the children participating in these studies may be at
p.000024: risk for physical harms or adverse health outcomes because they live in housing (or otherwise occupy
p.000024: environments) with health hazards. However, such risks are not introduced by the research but, rather, would be present
p.000024: whether or not the children were involved in a research study. As a consequence, the study still
p.000024: would meet the regulatory criteria for minimal risk as long as the research itself introduced no risks over
p.000024: and above those minimal risks
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025: experienced by normal children living in safe healthy environments.
p.000025: However, the existence of greater than minimal background risks that are not introduced by the research,
p.000025: nonetheless, raises additional ethical considerations. The joint NRC & IOM Committee on Research on Housing- Related
p.000025: Health Hazards Involving Children discussed the ethical arguments that arise when scientists conduct research that
p.000025: observes children in poor-quality housing. They point out that a researcher’s first duty of beneficence
p.000025: under the Common Rule requires that the risks of the research actions be proportionate to
p.000025: [“reasonable in relation to”; 40 CFR 26.111(a)(2)] the benefits of the research, and that the risks be
p.000025: minimized. They acknowledge, however, that some have argued that the “best interests of the child” also obligates
p.000025: researchers to “rescue” children from harm and to provide better living conditions. They conclude that,
p.000025: properly applied, the ethical principle of beneficence does indeed direct researchers who observe serious harms
p.000025: to child subjects to take steps to try to prevent the harms. However, they also argue that the researcher’s duty does
p.000025: not extend to “personally and directly prevent harm by removing the child from the harmful environment” (p.
p.000025: 60, NRC & IOM, 2005). They conclude instead that “it is unrealistic and unfair to hold individual research
p.000025: investigators responsible for ameliorating the social circumstances that they study” and that “a nuanced
p.000025: balancing of the benefits and risks of research” is an ethically sound approach that is firmly established in
p.000025: Federal regulations (p. 60, NRC & IOM, 2005). Balancing the ethical obligation to mitigate risks or
p.000025: harms observed during research with the reasonable limits on an investigator’s moral responsibility for
p.000025: the social circumstances surrounding the research will be the subject of later sections of this
p.000025: document, particularly Section 4.3.1.
p.000025: Assessing the risks and benefits of the research study can be very difficult for the researchers, especially
p.000025: because the researchers and the community or participants may perceive the risks and benefits
...
p.000031: participants or others
p.000031:
p.000031:
p.000031:
p.000031: References
p.000031: Castelloe, JM (2000). Sample size computations and power analysis with the SAS system. Paper 265-25 in Proceedings of
p.000031: the 25th Annual SAS Users Group International Conference. Cary, NC: SAS Institute, Inc. Available:
p.000031: http://support.sas.com/rnd/app/papers/powersamplesize.pdf [accessed 16 April 2008].
p.000031:
p.000031: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of
p.000031: Human Subjects. U.S. Code of Federal Regulations. Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/
p.000031: 40cfr26_06.html [accessed 12 June 2007].
p.000031:
p.000031: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000031: Biomedical Research Involving Human Subjects.
p.000031: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000031:
p.000031: Coggon D, Rose G, Barker DJP (1997). Epidemiology for the Uninitiated, Fourth Edition. London: BMJ Publishing Group
p.000031: Ltd. Available at http://www.bmj.com/epidem/epid.html [accessed 29
p.000031: January 2008].
p.000031:
p.000031: Cohen Hubal EA, Sheldon LS, Zufall, MJ, Burke JM, Thomas KW (2000). The challenge of assessing children’s residential
p.000031: exposure to pesticides. Journal of Exposure Analysis and Environmental Epidemiology 10(6 part 2): 638-649.
p.000031:
p.000031: Dallal, GE (2001). Some aspects of study design. In The Little Handbook of Statistical Practice at
p.000031: www.StatisticalPractice.com, and at http://www.tufts.edu/~gdallal/STUDY.HTM [accessed 29
p.000031: January 2008]
p.000031: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000031:
p.000031: Gilbert, SG (2006). Supplementing the traditional institutional review board with an environmental health and community
p.000031: review board. Environmental Health Perspectives 114(10): 1626-1629.
p.000031:
p.000031: Kraemer HC, Thiemann S (1987). How Many Subjects? Statistical Power Analysis in Research. Newbury Park, CA: Sage
p.000031: Publications.
p.000031:
p.000031: Lenth RV (2001). Some practical guidelines for effective sample size determination. American Statistician 55(3):
p.000031: 187-193. Available:
p.000031: http://www.stat.uiowa.edu/techrep/tr303.pdf [accessed 13
p.000031: June 2007].
p.000031:
p.000031: NRC (National Research Council) (2003). Protecting Participants and Facilitating Social and Behavioral Sciences
p.000031: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000031: [accessed 12 June 2007].
p.000031:
p.000031: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000031: Housing-Related Health Hazards Involving Children.
p.000031: Washington, DC: The National Academies Press. Available:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12 June 2007].
p.000032:
p.000032: OHRP (Office for Human Research Protections) (2007). U.S. Department of Health and Human Services [Online].
p.000032: Available: http://www.hhs.gov/ohrp/ [accessed 13 June 2007].
p.000032:
p.000032: Resnik DB, Wing S (2007). Lessons learned from the Children's Environmental Exposure Research Study. Am J Public Health
p.000032: 97(3): 414-8.
p.000032:
p.000032: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979). The Belmont Report: Ethical Principles and
p.000032: Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: National Commission for the Protection
p.000032: of Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
p.000032: [accessed June 2007].
p.000032: U.S. EPA (U.S. Environmental Protection Agency) (2000). Comments on the use of data from the testing of human subjects:
p.000032: A report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. Environmental Protection Agency,
p.000032: Science Advisory Board. EPA-SAB-EC-00-017. Available: http://www.epa.gov/scipoly/sap/meetings/1999/november/e c0017.pdf
p.000032: [accessed 16 April 2008].
p.000032:
p.000032: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000032: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000032: [accessed 12 June 2007].
p.000032:
p.000032: Van Belle G, Fisher L (2004). Biostatistics: A Methodology for the Health Sciences (2nd Edition) Hoboken, NJ: John
p.000032: Wiley & Sons.
p.000032:
...
p.000033: populations are not targeted for risky research” [emphasis added] (Emanuel et al., 2000).
p.000033: The Common Rule requires IRBs to assure that “additional safeguards have been included in the study to protect
p.000033: the rights and welfare of these [vulnerable] subjects” [at 40 CFR 26.111(b) in CFR, 2006a]. If an
p.000033: observational human exposure study includes vulnerable research participants, it is essential that the investigators be
p.000033: cognizant of the special issues and requirements of research involving vulnerable populations. Researchers
p.000033: have to justify the involvement of vulnerable populations in the research study and
p.000033: include the appropriate safeguards for protection of their safety and welfare. The Common Rule protections are
p.000033: discussed further in the IRB guidebook (U.S. HHS, 1993). EPA regulations include not only the general
p.000033: protections for vulnerable populations found in the Common Rule (Subpart A) but also define
p.000033: additional protections for children and for pregnant or nursing women (and their fetus or nursing child)
p.000033: in Subparts B, C, and D (CFR, 2006a).
p.000033: The section begins by identifying or defining vulnerable groups and then discusses ethical issues that
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
...
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
...
p.000035: shown in Text Boxes 3-1 and 3-2 and described above, the concept of vulnerability is broader than that
p.000035: presented in the Common Rule. It is not adequate to simply check the list in Text Box 3-1 to identify if a potentially
p.000035: vulnerable group is included in an observational study. The researchers should assess the potential
p.000035: vulnerability of a study population within the study by evaluating the characteristics (e.g., socioeconomic
p.000035: status) of the study population within the context of the study by considering the various design elements of the
p.000035: study, as discussed in Section 2.
p.000035: 12 In the commentary on Guideline 13 in CIOMS (2002), the committee states that the central problem presented by plans
p.000035: to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
p.000035: the CIOMS document (Guidelines 14 and 15) and include children, and persons who, because of mental or behavioral
p.000035: disorders, are incapable of giving informed consent. Ethical justification of their involvement usually requires that
p.000035: • the research could not be carried out equally well with less vulnerable subjects;
p.000035: • the research is intended to obtain knowledge that will lead to improved diagnosis, prevention, or treatment of
p.000035: diseases or other health problems characteristic of, or unique to, the vulnerable class—either the actual subjects or
p.000035: other similarly situated members of the vulnerable class;
p.000035: • research subjects and other members of the vulnerable class from which subjects are recruited will ordinarily be
p.000035: assured reasonable access to any diagnostic, preventive, or therapeutic products that will become available as a
p.000035: consequence of the research;
p.000035: • the risks attached to interventions or procedures that do not hold out the prospect of direct health-related
p.000035: benefit will not exceed those associated
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036: CIOMS recommendations, although written to address biomedical research, also generally are
p.000036: applicable to observational human exposure studies. The authors of this document consider the CIOMS
p.000036: requirement that the research could not be carried out equally well with less vulnerable subjects
p.000036: to be particularly important. EPA and NERL researchers should include vulnerable groups in
p.000036: observational human exposure studies only if their participation is critical to the success and
p.000036: applicability of the research. Even then, EPA and NERL researchers will have to meet stringent standards for
p.000036: protecting the rights and safety of the vulnerable participants. For example, EPA regulations
p.000036: governing observational research with children are even more stringent than the CIOMS guideline.
p.000036: If such research does not hold out the prospect of direct benefit to the child, no increase whatsoever over
p.000036: minimal risk is permitted.
p.000036: However, many observational human exposure studies are developed specifically to study the exposures of
p.000036: selected vulnerable groups to chemicals and other environmental stressors in everyday environments. So,
p.000036: researchers should be prepared to address the issues associated with vulnerable groups in
p.000036: observational research. Furthermore, as discussed in Section 3.4, there has been increased concern in recent years that
p.000036: exclusion of vulnerable groups from research studies is not ethical. Failure to conduct research with vulnerable groups
p.000036: may deprive them of the benefits of research. NIH, for example, has a policy (NIH, 1998) with a
p.000036: goal of increasing participation of children in research.
p.000036:
p.000036: 3.3 Minimal Risk and Vulnerable Groups
p.000036: EPA has codified protections for children, pregnant or nursing women, and fetuses in Subparts B, C, and D of the EPA
p.000036: human subjects rule (40 CFR 26). Subpart B strictly prohibits research involving intentional exposure of children
p.000036: or pregnant or nursing women (and, therefore, exposure of her fetus).
p.000036: EPA’s regulations do allow for observational research involving fetuses and pregnant women (40 CFR 26
p.000036: Subpart C) or children (40 CFR 26 Subpart D) but with additional protections in place and with
p.000036: strict limitations on research that presents more than minimal
p.000036: risk (CFR, 2006a).13 When considering vulnerable groups, The Institutional Review Board Guidebook (U.S. HHS,
p.000036: 1993) states that “IRBs should therefore determine whether the proposed subject population would be more sensitive or
p.000036: vulnerable to the risks posed by the research as a result of their general condition or disabilities. If so, the
p.000036: procedures would constitute more than minimal risk for those subjects.”
p.000036: When conducting observational human exposure studies, it is recommended that researchers consult these
p.000036: regulations and guidebooks. NERL researchers also will need to ensure that all of the requirements in Subparts B, C,
p.000036: and D of the EPA Human Subjects Rule are met.
p.000036:
p.000036: 3.4 Research Involving Children
p.000036: Children long have been recognized as a vulnerable group in research studies. EPA and HHS both extend special
p.000036: protections to children (CFR, 2006a,b). There are many books, reports, and research manuscripts that
p.000036: specifically address issues associated with research involving children (e.g., NRC & IOM, 2005; IOM,
p.000036: 2004; Kodish, 2005; NRC, 2003; AAP, 2003).
p.000036: CIOMS has drafted guidelines for including children in biomedical research (Guideline 14, CIOMS, 2002). The
p.000036: guidelines require an investigator to provide the assurances shown in Text Box 3-3 before undertaking
p.000036: research involving children.
p.000036:
p.000036: Text Box 3-3. Assurances Required by CIOMS Before Research Involving Children May Begin
p.000036: • the research might not equally well be carried out with adults;
p.000036: • the purpose of the research is to obtain knowledge relevant to the health needs of children;
p.000036: • a parent or legal representative of each child has given permission;
p.000036: • the agreement (assent) of each child has been obtained to the extent of the child’s capabilities; and
p.000036: • a child’s refusal to participate or continue in the research will be respected.
p.000036:
p.000036:
p.000036: The participation of children in some observational human exposure studies is critical to
p.000036: characterizing children’s exposures to chemicals in the environment. It is well recognized that children are not
p.000036: “little adults,”
p.000036: and that their
p.000036: exposures to chemicals differ (and, in
p.000036:
p.000036:
p.000036: with routine medical or psychological examination of such persons unless an ethical review committee authorizes a
p.000036: slight increase over this level of risk (Guideline 9); and,
p.000036: • when the prospective subjects are either incompetent or otherwise substantially unable to give informed consent,
p.000036: their agreement will be supplemented by the permission of their legal guardians or other appropriate representatives.
p.000036:
p.000036:
p.000036: 13 Minimal risk is defined at 40 CFR 26.102(i) and again at 40 CFR 26.402(g). It “means that the probability and
p.000036: magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily
p.000036: encountered in daily life or during the performance of routine physical or psychological examinations or tests.”
p.000036:
p.000036:
p.000037: 37
p.000037:
p.000037: some cases, are higher) from those of adults. Children are behaviorally and physiologically different
p.000037: from adults. Their interaction with their environment, through activities such as playing on floors, mouthing of
p.000037: hands and objects, and handling of food, may increase contact with contaminated surfaces. Children
p.000037: have proportionately higher breathing rates, relative surface area, and food intake requirements
p.000037: that also may increase exposure. Differences in absorption, metabolism, storage, and excretion
p.000037: may result in higher biologically effective doses to target tissues. Immature organ systems may be more
p.000037: susceptible to toxicological challenges. Windows of vulnerability, when specific toxicants may permanently
p.000037: alter the function of an organ system, are thought to exist at various stages of development. Because
p.000037: the factors influencing children’s exposures to chemicals are not characterized well (Cohen Hubal et
p.000037: al., 2000), it is sometimes important that observational human exposure studies involve children.
p.000037: Because children are so vulnerable, there long has been concern about including them in research studies,
p.000037: and biomedical research often excluded children. However, in recent years, there has been concern
p.000037: that excluding children from research is not ethical. NIH’s Policy and Guidelines on the Inclusion of
p.000037: Children as Participants in Research Involving Human Subjects (NIH, 1998) has a goal of increasing
p.000037: participation of children in research. The policy of NIH is that children must be included in all human
p.000037: subjects research conducted or supported by NIH, unless there are scientific and ethical reasons
p.000037: not to include them. Proposals or applications to NIH for research have to present an acceptable
p.000037: justification if children will be excluded from a research study. Of course, as discussed above, if the research
p.000037: topic is irrelevant to children, the CIOMS guidelines would recommend that they be excluded from the
p.000037: research.
p.000037: Observational human exposure studies conducted by NERL are not expected to involve greater than minimal risk. It
p.000037: will be the responsibility of the NERL researchers to present adequate information for the IRB to
p.000037: demonstrate that the research does not involve greater than minimal risk. Researchers designing observational
p.000037: research studies should carefully evaluate the risks and benefits specific to their study and the
p.000037: participants involved. In developing the study design and human subjects protocols, researchers need to
p.000037: ensure that the protocols ensure the protection of the rights and welfare of the participant children, and that
p.000037: risks and harm are minimized. The perception of risks and benefits, both by
p.000037: the individual and by the family or community, may influence the risk-benefit determination. It may prove
p.000037: useful for the research team to consult with other experienced researchers who have conducted
p.000037: similar studies and with members of the IRB to ensure that the information included in the human subjects
p.000037: research protocol is adequate for the IRB’s review.
p.000037: It is recommended that researchers consider all of the potential issues associated with involvement
p.000037: of children in their studies in developing the study design and research protocols, including the role of the
p.000037: family. EPA’s human subjects rule for observational research not involving greater than minimal risk to
p.000037: children (40 CFR 26.404) (i.e., the kinds of observational human exposure studies that NERL exposure research
p.000037: is likely to entail) focuses on obtaining assent of the children and permission of their parents or guardians. But the
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
...
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
p.000038: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle A Department of Health and Human Services Part 46 Protection
p.000038: of Human Subjects. U.S. Code of Federal Regulations. Available:
p.000038: http://www.access.gpo.gov/nara/cfr/waisidx_06/45cfr46_06.ht ml [accessed 13 June 2007].
p.000038:
p.000038: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000038: Biomedical Research Involving Human Subjects.
p.000038: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000038:
p.000038: Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry MR, Rigas ML, Zartarian VG, Freeman NCG (2000).
p.000038: Children’s exposure assessment: a review of factors influencing children’s exposure, and the data available to
p.000038: characterize and assess that exposure. Environ Health Perspect 108(6): 475-486.
p.000038:
p.000038: Emanuel EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000038:
p.000038: IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Washington, DC: The
p.000038: National Academies Press. Available: http://www.nap.edu/catalog.php?record_id=10958 [accessed 16 April 2008].
p.000038:
p.000038: Kodish E (Ed.) (2005). Ethics and Research with Children: A Case-Based Approach. New York: Oxford University Press.
p.000038:
p.000038: NBAC (National Bioethics Advisory Commission) (2001). Ethical and Policy Issues in Research Involving Human
p.000038: Participants, Volume I: Report and Recommendations of the National Bioethics Advisory Commission. Bethesda, MD:
p.000038: National Bioethics Advisory Commission. Available: http://www.bioethics.gov/reports/past_commissions/nbac_h
p.000038: uman_part.pdf [accessed 3 September 2007].
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000039: 39
p.000039:
p.000039: NIH (National Institutes of Health) (2002) Human Participant Protections Education for Research Teams [online
p.000039: tutorial].
p.000039:
p.000039: NIH (National Institutes of Health) (1998). NIH Policy and Guidelines on The Inclusion of Children as Participants in
p.000039: Research Involving Human Subjects. Available: http://grants.nih.gov/grants/guide/notice-files/not98 024.html [accessed
p.000039: 13 June 2007].
p.000039:
p.000039: NRC (National Research Council) (2003). Protecting Participants and Facilitating Social and Behavioral Sciences
p.000039: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000039: [accessed 12 June 2007].
p.000039: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000039: Housing-Related Health Hazards Involving Children.
p.000039: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000039: June 2007].
p.000039:
p.000039: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000039: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000039: [accessed 12 June 2007].
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
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p.000039:
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040: SECTION 4
p.000040: Privacy, Confidentiality, and Other Concerns Related to Observational Human Exposure Studies
p.000040:
p.000040:
p.000040:
p.000040: Observational human exposure studies are designed to describe people’s contact with pollutants as they go about
p.000040: their everyday lives. Of necessity then, these studies take place in the locations that participants often
p.000040: consider to be personal and private. Clinical research studies generally are conducted in a research
p.000040: facility, a clinic, a hospital, or some other institutional or medical setting. Survey research may be conducted by
p.000040: mail, over the phone, or in another “neutral” setting. But, observational human exposure studies are
p.000040: conducted in the participants’ “personal” environment⎯their home, daycare center, school, vehicle,
p.000040: workplace, or other environments that people occupy during their routine daily activities. This difference
p.000040: in the research setting means that researchers involved in observational human exposure studies have an
p.000040: even greater challenge in meeting the ethical obligation to respect the privacy of the participants.
p.000040: When exposure science researchers like those at NERL enter a home to carry out their studies, the
p.000040: “expectations and constraints may be strikingly different than when research is carried out in a medical
p.000040: setting” (p. 64, NRC & IOM, 2005). The legal precept of freedom from unreasonable search and
p.000040: seizure and the historic and deeply rooted principle that “a man’s home is his castle” contribute to a belief in the
p.000040: “sanctity of the home” (see the discussion on pp. 62-66, NRC & IOM, 2005).
p.000040: The joint NRC and IOM report Ethical Considerations for Research on Housing-Related Health
p.000040: Hazards Involving Children discusses the ethical issues associated with entering a participant’s home to conduct
p.000040: research and explores the researchers’ responsibilities that derive from conducting research in people’s homes
p.000040: (NRC & IOM, 2005). These housing-related discussions are particularly relevant to observational human
p.000040: exposure studies, which often include environmental and
p.000040: biological measurements in people’s homes or personal locations. Many of the topics identified in that report are
p.000040: discussed in this section (Text Box 4-1).
p.000040:
p.000040:
p.000040: Text Box 4-1. Topics in Section 4
p.000040: Privacy Issues Confidentiality
p.000040: Confidentiality of Information Confidentiality of Participation
p.000040: Collateral Observations
p.000040: Potential Nonstudy Hazards in the Residence Collateral Observations with Mandated Reporting
p.000040: Requirements
p.000040: Hazard Communication Planning and Staff Training
p.000040: Third-Party Issues
p.000040: Determining Whether a Third Party is a Human Subject Informing Third Parties of Research Activities Research Results
p.000040: and Third Parties
p.000040: Data and Safety Monitoring and Oversight
p.000040:
p.000040:
p.000040:
p.000040: 4.1 Privacy Issues
p.000040: Privacy refers to an expectation that a person is free from intrusion into personal matters and is free from the
p.000040: presence or view of others. The Institutional Review Board Guidebook defines privacy as “control over the
p.000040: extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with
...
p.000043: research study, it is recommended that researchers carefully plan for possible collateral observations,
p.000043: including their identification, staff training, and hazard communication and reporting. This may be a major
p.000043: element in the data and safety monitoring and oversight for the study. The informed consent process
p.000043: should reflect procedures used to manage collateral observations. Potential participants should be
p.000043: informed of situations in which confidentiality might be breached, such as statutory requirements for reporting
p.000043: abuse or imminent harm to self or others.
p.000043:
p.000043: 4.3.1 Potential Nonstudy Hazards in the Residence
p.000043: Research staff conducting observational human exposure studies often will spend time in and around
p.000043: study participant residences. In the course of visiting a residence or conducting study-related
p.000043: observations, research staff may observe potential hazards unrelated to the research being performed (see Text Box
p.000043: 4-4). Some hazards may be associated with the potential for physical injury, whereas others may be related to
p.000043: exposure to chemical or biological agents. Some situations may be potential hazards only for young children,
p.000043: whereas other conditions may present potential hazards for all residents or occupants.
p.000043: The NRC & IOM recommend that researchers should consider such foreseeable observations and
p.000043: potential hazards in advance, develop responses to the risks, and submit the proposed plans to the IRB
p.000043: for review to ensure that they are appropriate “in the context of the research and the affected community.” The NRC
p.000043:
p.000043:
p.000044: 44
p.000044:
p.000044: & IOM also advise that field staff should be trained in how to assess and respond to
p.000044: such risks (Recommendations 7.3 and 7.4, NRC & IOM, 2005). For other behaviors and risks that
p.000044: have not been specifically identified in advance, procedures should be included in the data and safety monitoring
p.000044: and oversight provisions of the study design and research protocol to address these issues. The fundamental
p.000044: ethical principle of beneficence would motivate researchers who observe serious harms to take steps to try to prevent
p.000044: those harms, even for observations that are not directly related to the study. The steps that they may take can
p.000044: range from immediate action to prevent an imminent and serious danger to statutory reporting of
p.000044: observations (see Section 4.3.2) to reporting the observation to the data and safety monitoring and oversight
p.000044: authority for advice on how to respond (see Section 4.5). (The reader is also referred to pages 59-61 and 134-144 of
p.000044: the NRC & IOM [2005] report for a more thorough discussion of researchers’ responsibilities in such
p.000044: cases.)
p.000044:
...
p.000044: threat to health or safety that staff would need to communicate immediately with the participant or take
p.000044: action to mitigate the threat. In some cases, such as instances of abuse with attendant statutory reporting
p.000044: requirements, it may be necessary to breach confidentiality. More often, however, a potential hazard identified as
p.000044: a result of collateral observation may not be an imminent threat or pose a potential risk that is situation
p.000044: dependent or is related to third parties. A number of considerations in hazard communication come
p.000044: into play regarding confidentiality, privacy, the ability of the researcher to provide accurate and
p.000044: effective information regarding the hazard and hazard mitigation, and the ability of the study participant or others
p.000044: to effectively mitigate the hazard without unintended adverse consequences. The National Academy of Sciences
p.000044: Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children, Youth, and
p.000044: Families discussed many of these issues in depth (NRC & IOM, 2005).
p.000044: Different communities, cultures, or demographic groups can have different risk perceptions, which may
p.000044: affect how collateral observations are assessed and reported from one study location to the next. The AAP
p.000044: Committee on Environmental Health has prepared information regarding perception, identification, and
p.000044: communication of environmental health risks (AAP, 2003). Researchers likely will benefit from including
p.000044: community members on the research team in developing the study design and research protocol or from
p.000044: consultation with community boards regarding identification of hazards and hazard communication.
p.000044:
p.000044:
p.000045: 45
p.000045:
p.000045: It is important that any advice that the researcher might provide to study participants regarding hazard
p.000045: mitigation should be carefully considered. Considerations in recommending an action may include
p.000045: whether the mitigation approach has been shown to be effective, whether the study participant can
p.000045: understand and effectively implement the action, and whether unintended adverse consequences might
p.000045: result from taking an action. In some cases, it may be reasonable to refer the participant to another
p.000045: organization that can provide expert advice or assistance.
p.000045:
p.000045: 4.3.4 Planning and Staff Training
...
p.000045: protocol and to develop plans as to how such observations would be handled. Researchers may choose to
p.000045: include a systematic approach in hazard identification, such as using a home-hazard checklist that becomes an
p.000045: ancillary part of the study protocol. Alternatively, collateral observations could be handled on a
p.000045: case-by-case basis.
p.000045: Staff experience and training is a critical consideration for managing collateral observations. Staff
p.000045: members that visit study participant residences may not have expertise or experience in identifying many of the
p.000045: potential hazards without adequate training. All staff involved in a study, particularly those responsible
p.000045: for field data collection, should be trained on identification and reporting of collateral observations. This
p.000045: training should be study specific and likely will include, but not be limited to
p.000045: (1) identification of actions (e.g., child abuse) that have (state-specific) statutory reporting requirements,
p.000045: (2) conditions of neglect that may adversely impact study participants or third parties,
p.000045: (3) environmental hazards and situations that may be associated with imminent harm (e.g., combustible
p.000045: materials near an open flame, unsecured firearms accessible to very young children),
p.000045: (4) policies and procedures for reporting or intervention by members of the research team, and
p.000045: (5) local and state reporting requirements.
p.000045: It is advisable that this training be developed in consultation with community representatives who can
p.000045: provide input on potential hazards and situations that may be encountered in the study community,
p.000045: local norms and attitudes about potential interventions and reporting, and local agencies available to assist on
p.000045: these types of issues. It is also especially important to consider
p.000045: staff experience and training in hazard communication. Consistency in communication is very important, and
p.000045: researchers may decide to use materials prepared by other organizations that have expertise regarding
p.000045: a particular hazard.
p.000045: Another important element of planning for field data collection and training of research staff is on hazards and
p.000045: situations that the field staff may encounter during their field work. Although the previous discussion highlights the
p.000045: need to be prepared to report potentially negligent or illegal behaviors, these same behaviors may place the
p.000045: research staff in imminent danger during the conduct of their work in residences and communities. The research team
p.000045: should develop a plan for identifying potential situations, hazards, and dangers that may place the
...
p.000045: study activities may affect or involve people or organizations other than the study participants.
p.000045: Examples of activities that may involve or affect third parties in observational human exposure studies
p.000045: could include, but are not limited to the following types.
p.000045: • Asking the participant about demographic, occupational, smoking, or product use information for
p.000045: other household members
p.000045: • Collecting residential environmental samples in multiperson households
p.000045:
p.000045:
p.000046: 46
p.000046:
p.000046: • Collecting environmental samples in common areas of multifamily housing units
p.000046: • Collecting personal or environmental samples in a day care, school, health care, or occupational setting
p.000046: • Measuring chemical occurrences or concentrations that may be of interest or import to other
p.000046: household members or to the community
p.000046: • Collecting activity or dietary information about a community
p.000046: It is important for researchers and research staff to understand whether and to what extent the research
p.000046: involves or affects third parties, and how third-party involvement might affect the study participants. Several
p.000046: examples of possible third-parties are listed in Text Box 4-5. Study planning; IRB review; and communication
p.000046: before, during, and after the study should take third- party issues into account.
p.000046:
p.000046: Text Box 4-5. Possible Third-Parties in Exposure Studies
p.000046: • Household members not enrolled in the study
p.000046: • Relatives
p.000046: • Care givers for children or elders
p.000046: • School staff
p.000046: • Employers
p.000046: • Other members of the community
p.000046: • Building managers or facility operators
p.000046: • Landlords
p.000046:
p.000046:
p.000046:
p.000046: 4.4.1 Determining Whether a Third Party Is a Human Subject
p.000046: It is up to the IRB to determine whether a third party is a human subject afforded human
p.000046: subject protections under the Common Rule. A third party would meet the Common Rule definition of
p.000046: a human subject [40 CFR 26.102(f)] if individually identifiable private information about them is collected
p.000046: (CFR, 2006). When this occurs, the informed consent of the third party must be obtained, or, if certain criteria are
p.000046: met, the IRB may determine that informed consent may be waived. It can be difficult to determine whether information
p.000046: about a third party is both individually identifiable and private. Discussions of this issue and
p.000046: recommendations for determining whether third-party information is identifiable and private have been
p.000046: submitted to the HHS Office of Human Research Protections by NIH (2001) and by the National Human
p.000046: Research Protections Advisory Committee (NHRPAC, 2002).
...
p.000048:
p.000048: NHLBI (National Heart Lung and Blood Institute) (2007). Monitoring Boards for Data and Safety (Interim Policy). Policy
p.000048: effective date: 14 May 2007. Available: http://public.nhlbi.nih.gov/ocr/home/GetPolicy.aspx?id=8 [accessed September
p.000048: 2007].
p.000048:
p.000048: NHRPAC (National Human Research Protections Advisory Committee) (2002). Clarification of the status of third parties
p.000048: when referenced by human subjects in research. Available: http://www.hhs.gov/ohrp/nhrpac/documents/third.pdf [accessed
p.000048: April 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (2002). Extramural Projects - Application Instructions (03/15/2002) - Detailed
p.000048: Application Instructions for Certificate of Confidentiality Involving Extramural Research Projects. Certificates of
p.000048: Confidentiality. Available: http://grants.nih.gov/grants/policy/coc/index.htm. [accessed April 2007]
p.000048:
p.000048: NIH (National Institutes of Health) (2001). Protection of third party information in research: Recommendations of the
p.000048: National Institutes of Health to the Office for Human Research Protections. Available:
p.000048: http://bioethics.od.nih.gov/nih_third_party_rec.html [accessed March 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (1998). NIH Guide: NIH Policy for Data and Safety Monitoring. Available:
p.000048: http://grants.nih.gov/grants/guide/notice-files/not98 084.html [accessed April 2007].
p.000048:
p.000048: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000048: Housing-Related Health Hazards Involving Children.
p.000048: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed
p.000048: June 2007].
p.000048:
p.000048:
p.000048:
p.000048:
p.000049: 49
p.000049:
p.000049: U.S. FDA (U.S. Food and Drug Administration) (2001). Draft Guidance for Clinical Trial Sponsors on the Establishment of
p.000049: Clinical Trial Data Monitoring Committees. U.S. Department of Health and Human Services, Food and Drug Administration,
p.000049: Rockville, MD. Available: http://www.fda.gov/cber/gdlns/clindatmon.pdf. [accessed April 2007].
p.000049: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000049: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000049: [accessed June 2007].
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
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p.000050: 50
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: SECTION 5
p.000050: Creating an Appropriate Relationship Between the Participant and Researcher
p.000050:
p.000050:
p.000050:
p.000050: In observational human exposure studies, the researcher and the participant routinely interact
...
p.000050: Other training, such as that provided by the National Cancer Institute
p.000050: (http://cme.cancer.gov/clinicaltrials/lear ning/humanparticipant-protections.asp) and the U.S. Department
p.000050: of Health and Human Services (http://www.hrsa.gov/humansubjects/default.htm), are available
p.000050: on-line.
p.000050:
p.000050:
p.000051: 51
p.000051:
p.000051: 5.1 Informed Consent
p.000051: In observational human exposure studies, informed consent ensures that the participant
p.000051: accurately understands the range of risks and benefits (if any) associated with participation; emphasizes
p.000051: the voluntary nature of their participation; and provides essential protections to the participant. The
p.000051: three “pillars” of the informed consent process are (1) information;
p.000051: (2) comprehension; and (3) voluntary participation, or “voluntariness” (U.S. DHEW, 1979). Informed consent
p.000051: requires “provision of information to subjects about the purpose of the research, its procedures, potential
p.000051: risks, benefits, and alternatives, so that the individual understands this information and can
p.000051: make a voluntary decision whether to enroll and continue to participate” (Emanuel et al., 2000).
p.000051: The NRC & IOM document Ethical Considerations for Research on Housing-Related Health Hazards Involving
p.000051: Children (NRC & IOM, 2005) contains a comprehensive and very useful discussion of informed consent
p.000051: procedures and requirements in Chapter 6. The IOM report, Responsible Research: A Systems Approach to Protecting
p.000051: Research Participants, also includes a thoughtful discussion of participant-investigator
p.000051: interactions and the informed consent process (IOM, 2002). CIOMS also includes recommendations for both the
p.000051: process and content of informed consent (CIOMS, 2002). Some of the important points from those
p.000051: documents are summarized in Text Box 5-1, but the reader should refer to those documents for additional
p.000051: information about this topic.
p.000051: Federal regulations governing research that is either Federally conducted or Federally funded (i.e., all human subjects
p.000051: research at NERL) are codified in the Common Rule. The regulations set forth requirements for both the content of an
p.000051: informed consent and the process for obtaining and documenting an individual’s informed consent (see Text
p.000051: Box 5-2).16 General regulatory requirements for the elements of informed consent are codified in the
p.000051: Common Rule at 40 CFR 26.116(a)(1)
...
p.000051: consent process and the consent form document. The discussion of these issues, arising from
p.000051: regulatory
p.000051:
p.000051:
p.000051: 16 An IRB may waive informed consent under some very limited conditions. See 40 CFR 26.116(c) and (d).
p.000051: requirements or identified in recent writings on ethical considerations in human subjects research, is
p.000051: grouped below, under the three pillars of informed consent:
p.000051: (1) information, (2) comprehension, and (3) voluntary participation.
p.000051:
p.000051: Text Box 5-1. Recommendations for Informed Consent In the United States and Internationally
p.000051: (1) Revitalize Informed Consent (IOM, 2002)
p.000051: Informed consent is a process, not a form. It is an on-going, interactive dialogue between research staff and research
p.000051: participants with disclosure and exchange of relevant information, including assessment of understanding.
p.000051: Ethics Review Boards should ensure that the focus of both the informed consent process and the consent forms is on
p.000051: informing and protecting participants, not the research institution.
p.000051: (2) Strengthen Process of Parental Permission and Children’s Assent if Children Are Involved in Research (NRC & IOM,
p.000051: 2005)
p.000051: The process begins with a community-based discussion and concludes with an assurance that individual parents understand
p.000051: the essential elements of the research.
p.000051: Educate parents on issues critical to informed decision making and assess their degree of understanding.
p.000051: Use informational materials in the form that is most appropriate to convey information to potential participants.
p.000051: Consult with community representatives to ensure that information is complete, clear, and understandable, and that any
p.000051: payment will not be exploitive.
p.000051: Expand the perspective about what information about risks and benefits is needed to make an informed choice.
p.000051: Ethically, it is critical to assure that participants and parents understand the crucial features of the research
p.000051: effort.
p.000051: (3) Informed Consent Is a Decision To Participate by an Informed, Competent Individual Without Undue Coercion,
p.000051: Influence, or Intimidation (CIOMS, 2002)
p.000051: Informed consent is a process that takes time and resources.
p.000051: It is not a ritual recitation of text from a form but informative communication in language that suits the individual’s
p.000051: level of understanding.
...
p.000052: (10) A statement that participation is voluntary, refusal to participate will involve no penalty, and the subject may
p.000052: discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled
p.000052: (11*) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or
p.000052: fetus, if the subject is or may become pregnant) that are currently unforeseeable
p.000052: (12*) Anticipated circumstances under which the subject's participation may be terminated by the investigator without
p.000052: regard to the subject's consent
p.000052: (13*) Any additional costs to the subject that may result from participation in the research
p.000052: (14*) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of
p.000052: participation by the subject
p.000052: (15*) A statement that significant new findings developed during the course of the research that may relate to the
p.000052: subject's willingness to continue participation will be provided to the subject.
p.000052: (16*) The approximate number of subjects in the study
p.000052: * Included if appropriate [40 CFR 26.116(b)]
p.000052:
p.000052:
p.000052:
p.000052: • The information “shall be in language understandable to the subject” (40 CFR 26.116). This may require forms
p.000052: to be written and administered in different languages during a study. For example, the National
p.000052: Children’s Study (NCS) plans to produce all consent materials in English and Spanish, with other
p.000052: translations made available as needed (NCS, 2007).
p.000052: Participants often find discussions with research staff more useful than written consent forms (p. 103, NRC & IOM,
p.000052: 2005). NCS plans to pilot test an interactive, computer-based audio/video consent tool and to compare it
p.000052: with traditional written informed consent approaches (NCS, 2007).
p.000052: • The information being discussed, including the explanation of the purpose of the research and the
p.000052: description of the study procedures, should be written or discussed at a level that the participant can
p.000052: understand.17 The National Institutes of Health recommends writing consent forms as “plain language
p.000052: documents that explain the research in an honest, straightforward way” and suggest that doing so will
p.000052: help enhance public trust (Recommendation 11, NIH, 2005).
p.000052: • The consent form should contain sufficient information to describe the study procedures, but not
p.000052: so much information that it causes confusion and results in the participant not understanding the study. There
p.000052: is not agreement on what the appropriate level of information is. IRBs do not agree on the level of
...
p.000052: to
p.000052: Ethically, “language understandable to the subject”
p.000052: goes beyond simply using the appropriate language;
p.000052:
p.000052: the researcher is compelled also to consider readability and vocabulary (e.g., avoiding jargon
p.000052: or terminology that may be clear to the researcher but which may confuse or intimidate the potential subject)
p.000052: if the information is to be understandable.
p.000052: • Information may be presented orally in addition to an appropriately written document (40 CFR 26.117).
p.000052: 17 A survey of IRBs found that their readability standards ranged from 5th- to 10th-grade level (Paasche-Orlow et al.,
p.000052: 2003). Interestingly, the same report found that, 92% of the time, the sample consent forms provided by the IRBs did
p.000052: not meet their own readability standards. The NRC & IOM report (p. 107, NRC & IOM, 2005) discusses an NCI effort to
p.000052: simplify informed consent forms by using text targeted at 8th-grade reading level. More information about the NCI
p.000052: template may be found at www.nci.nih.gov/clinicaltrials/understanding/simplification-of-informed consent-docs/page2
p.000052: (accessed September 12, 2007).
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053: participants and, if so, how and when (p. 101, NRC & IOM, 2005).
p.000053: • For studies involving children as participants, it generally is regarded as desirable that the
p.000053: informed consent process should involve both parents (assuming that there are two competent
p.000053: parents available), and that the consent of both parents be obtained, if possible. The IRB may decide
p.000053: that the permission of one parent is sufficient, but only when certain risk-benefit conditions are met.18
p.000053: • For studies involving children as participants, it is desirable for those children with sufficient capacity
p.000053: to be involved in the consent process. Moreover, it is generally accepted that the child’s assent be obtained
p.000053: whenever this is developmentally possible and otherwise appropriate. Under both the EPA Rule and the HHS
p.000053: Rule, the IRB is responsible for determining that adequate provisions have been made for soliciting the assent of the
p.000053: children when, in the judgment of the IRB, the children are capable of providing assent. Assent, however, may
p.000053: be waived in those restricted circumstances in which consent may be waived under the Common Rule. Those
p.000053: circumstances and the required IRB documentation are described in the Common Rule at 40 CFR 26.116(d).
p.000053: • The consent form should clearly state that participation is voluntary and that study
p.000053: participants may “discontinue participation at any time without any penalty or loss of benefits to which the
p.000053: subject is otherwise entitled” [40 CFR 26.116(a)(8)]. If a subject chooses to withdraw from a study, the
p.000053: consequences of their decision and the process for orderly withdrawal should be clearly
p.000053: explained [40 CFR 26.116(b)(4)].
p.000053: • The consent form should address any foreseeable potential future use of samples and data (CIOMS, 2002).
p.000053: For example, effects of environmental exposures on gene expression are potentially very important.
p.000053: Therefore, biologic specimens for DNA analysis may be obtained from participants in future studies. But, it
p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45 CFR 46.408(b)
p.000053: for all research with children. Under the EPA Rule, greater than minimal risk observational research with children that
p.000053: does not hold out the prospect of direct benefit to the child is not permitted under any circumstances. Under the HHS
p.000053: Rule, greater than minimal risk research involving children without the prospect of direct benefit is permitted in very
p.000053: limited circumstances, but the consent of both parents is required in those cases (unless one parent is deceased,
p.000053: unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and
p.000053: custody of the child).
p.000053: special concerns about the potential for discrimination, stigmatization, and impact on
p.000053: future employment or insurance. The informed consent process needs to explain what the plans may be
p.000053: for such specimens and recognize the rights of the subjects to decide about any such future use,
p.000053: including having the material destroyed. The informed consent process needs to explicitly discuss
p.000053: obtaining permission from participants on behalf of themselves and their child to obtain specimens for
p.000053: genetic analysis.
p.000053:
p.000053: 5.1.2 Comprehension
p.000053: Research participants frequently fail to understand the research protocols in which they agree to participate (NRC
p.000053: & IOM, 2005). In considering the ethical issues raised by the Grimes v. Kennedy Krieger case, the NRC & IOM
...
p.000054: or affiliated with the research study, to be available for translations.
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
p.000055: dialogue . . . involving the disclosure and exchange of relevant information” (IOM, 2002): it is not
p.000055: simply having a consent form signed. The process is most effective when the researcher spends time with
p.000055: potential participants to discuss the study and to answer questions.
p.000055:
p.000055: 5.2 Payments to Research Participants
p.000055: The decision whether to pay research participants, including the appropriate level of payment,20 is
p.000055: a complex ethical issue. Monetary or nonmonetary payments are not ethical if they constitute an
p.000055: undue inducement for participants to assume research risks that they would not otherwise accept. On the other
p.000055: hand, it may be ethically appropriate to offer reasonable payments in some research studies. Indeed,
p.000055: payment of human subjects for their participation in scientific research is a common practice in the United
p.000055: States, with a history of well over 100 years (Grady, 2005). The difficulty for researchers and IRBs is that
p.000055: there is often little clear and uniform guidance for determining what constitutes “undue inducement”
p.000055: or “reasonable” payment for any particular research study, population, and level of risk. Additional
p.000055: considerations regarding payment to participants arise when working with vulnerable populations, including
p.000055: children.
p.000055:
p.000055:
p.000055:
p.000055:
p.000055: 20 There are many terms that may be found in the literature to describe both monetary and nonmonetary payments, like
p.000055: payment, remuneration, compensation, recompense, incentive, inducement, reimbursement, and reward. Each of these words
p.000055: has its own definition, and each word also may carry specific connotations. In general, these terms refer to money or
p.000055: other items that “are often given to acknowledge the time and inconvenience of participating in research or to
p.000055: reimburse participants for any costs they incur. The term compensation is often used in the context of compensation for
p.000055: research-related injuries” (p. 112, NRC & IOM, 2005). The authors have chosen to use “payment” as the general term for
p.000055: monetary and nonmonetary items provided to research subjects for their participation in the research. They may
p.000055: occasionally refer to compensation for research-related injuries, but the text should make it clear when they do.
p.000055: 5.2.1 Types and Amounts of Payments Offered in Research Studies
p.000055: Payments have been offered in a wide variety of research studies, ranging from clinical trials
p.000055: to behavioral and social research to observational human exposure studies. Payments can take various
p.000055: forms, including monetary payments (e.g., cash, gift certificates, reimbursement for expenses),
p.000055: nonmonetary payments (e.g., gifts, valuable information), or nothing at all (e.g., for a sense of
p.000055: altruism). Grady (2005) has described payment for the participation of research subjects as serving
p.000055: from one to four purposes: (1) an incentive, (2) compensation, (3) reimbursement, or
...
p.000056: others
p.000056: (c) Provides equivalent payment for participation across communities and locations (markets)
p.000056: (d) Less risk of undue inducement across study
p.000056: (a) Different levels of payment at different locations in multicenter research or in different communities
p.000056: (b) Unequal pay for equal work may violate one’s sense of justice
p.000056:
p.000056:
p.000056: Reimbursement Actual out-of-pocket cost to
p.000056: participant related to participation, such as parking, transportation, child care, cost of food samples, etc.
p.000056: (a) Lowers barriers to participation
p.000056: (b) Reduces burden and impact of research on participants
p.000056: (a) Few disadvantages
p.000056: (b) Possible differences in costs experienced by different participants
p.000056:
p.000056:
p.000056: Reward Token of appreciation at end of study
p.000056: (a) Expresses gratitude for contribution made
p.000056: (b) Not market dependent
p.000056: (c) Avoids undue inducement
p.000056: (a) Probably no impact on recruitment
p.000056: (b) No basis for consistency
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: for differential recruitment that could result in bias in the study sample.
p.000056: Determining appropriate level of payments or incentives for participants in a research study is
p.000056: complex. “No bright line distinguishes proper and reasonable payments to parents and children
p.000056: from payments that are inappropriate” (p. 214, IOM, 2004). The ethical issue is at what level might a
p.000056: payment change from being an incentive (an encouragement) to participate and become an inducement (the
p.000056: cause or reason) for participation. Many research organizations and IRBs do not have written policies or
p.000056: guidelines
p.000056:
p.000056: regarding the determination of reasonable payment. Decisions often are made based on the level
p.000056: of discomfort and burden, costs to participants, and population characteristics. However, large
p.000056: differences in payment levels have been found even in multisite studies in which the same protocol is
p.000056: administered across all sites.
p.000056: Grady et al. (2005) performed a survey of practices for paying research participants in the United States in
p.000056: Phase 1 to 4 clinical trials and physiologic, behavioral, and other types of research. Across 467
p.000056: studies of varying complexity that included payments, the median
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: payment was $155 (mean $266, range $5 to $2,000). The basis for dollar amounts was infrequently described, with
p.000057: 19% of the payments based on time, and 12% based on the procedures. In a model of payment factors,
p.000057: studies with some prospect of therapeutic benefit, studies having at least one invasive procedure, and studies with
p.000057: greater numbers of clinic visits were significantly associated with higher dollar amounts. About 9.5%
p.000057: of the studies offered completion bonuses, and a similar percentage offered escalating payments for
p.000057: followup study visits.
p.000057:
...
p.000057: review committees, including IRBs, need to consider many factors when determining when it is appropriate to
p.000057: offer payments to research participants and the level and form of payments when they are appropriate. Review
p.000057: committees also should consider how and when information on payments is communicated to prospective study
p.000057: participants.
p.000057:
p.000057:
p.000058: 58
p.000058:
p.000058:
p.000058: Text Box 5-4. Weighing the Ethical Issues About Payments
p.000058: Concerns about Payments Reasons for Payments
p.000058: • Payments may compromise • Recognizing participant voluntary participation.
p.000058: contributions to the
p.000058: • Participants may accept risks research and knowledge they would not otherwise gained
p.000058: accept. • Providing reimbursement
p.000058: • Participants may continue in a for direct and indirect research study beyond a point
p.000058: participant costs
p.000058: they might ordinarily have • Providing reasonable withdrawn.
p.000058: payment for the time and
p.000058: • Payments may differentially effort associated with encourage research
p.000058: participation in research participation by economically • Providing incentives for disadvantaged people.
p.000058: participation in studies
p.000058: • The offer of payments may with low risk but no or few cause guardians or parents to
p.000058: direct benefits
p.000058: not act in the best interests of • It is the just and fair thing incompetent persons or children to do
p.000058: for those who bear in their care. burdens of research on
p.000058: • Persons in different behalf of society. circumstances may view the
p.000058: same amount of payment quite differently.
p.000058: • Payments may alter the composition of the study sample and potentially could compromise study integrity.
p.000058: activities is thus justified on the grounds of fairness” (p. 112, NRC & IOM, 2005).
p.000058: Similarly, the IOM Committee on Clinical Research Involving Children found that “certain types of
p.000058: payments to parents or adolescents are usually if not always acceptable, for example, reimbursement
p.000058: for reasonable expenses that are necessary for research participation. The specifics may vary, but
p.000058: examples of reasonable expenses are costs of transportation to the research site, parking, lodging, meals,
p.000058: and babysitting. Other payments are never appropriate in pediatric research, for example, paying parents
p.000058: for the use of their child in research” (pp. 225-6, IOM, 2004).21
p.000058: The IOM committee recommends establishing policies on acceptable and unacceptable types of
p.000058: payments. They also recommend that the policies disclose any recompense in a full and open
p.000058: process,22 while not overemphasizing any recompense.
p.000058: Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
p.000058: benefits, or they may be particularly vulnerable to undue influence resulting from the offer of a payment for
p.000058: research participation. In addition, payments made directly to parents or guardians could alter
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
p.000058: gestures of appreciation, investigators may also—if they minimize the potential for undue influence—act ethically to
p.000058: reduce certain barriers to research participation when they
p.000058: • reimburse reasonable expenses directly related to a child’s participation in research
p.000058: • provide reasonable, age-appropriate compensation for children based on the time involved in research that does not
p.000058: offer the prospect of direct benefit, and
p.000058: • offer evening or weekend hours, on-site child care, and other reasonable accommodations for parental work and
p.000058: family commitments.”
p.000058: 22 In recommending an open process, the IOM committee chose to reject the
p.000058: arguments from the American Academy of Pediatrics that “any token payment to children for participating in research
p.000058: should not be discussed with them until after research is completed for fear of unduly influencing their decisions
p.000058: (AAP, 2003)…. On balance, the committee agrees that it is best to mention token or other payments during the permission
p.000058: and assent processes” (p. 215, IOM, 2004).
p.000058: The IOM Recommendation 6.1 states, “Institutional review boards, research institutions, and sponsors of research that
p.000058: includes children and adolescents should adopt explicit written policies on acceptable and unacceptable types and
p.000058: amounts of payments related to research participation. These policies should specify that investigators
p.000058: • Disclose the amount, the recipient, the timing, and the purpose (e.g., an expense reimbursement or a token of
p.000058: appreciation to a child) of any payments as part of the process of seeking parents’ permission, and, as appropriate,
p.000058: children’s assent to research participation;
p.000058: • Avoid emphasis on payments or descriptions of payments as benefits of participating in research during the
p.000058: permission or assent procedures; and
p.000058: • Obtain institutional review board approval for the disclosure of information about payments in advertisements and
p.000058: in permission and assent forms and procedures.”
p.000058:
p.000058:
p.000059: 59
p.000059:
p.000059: participate in research are unacceptable. The European Union requires that clinical trials on minors
p.000059: be undertaken only if “no incentives or financial inducements are given except compensation”
p.000059: (European Parliament, 2001).
p.000059: Payment for participation of children in research also is discussed in the literature. Diekema
p.000059: (2005) emphasizes the need to ensure that payments do not distort parental decisionmaking and do not tempt
p.000059: parents to consider other issues than the welfare of their child. Similarly, Menikoff (2005) suggested that
p.000059: there need to be relatively robust protections in place to ensure that families do not change their behaviors
p.000059: to participate in a study. He suggested that these may include determining payment as a percentage of a family’s
p.000059: income and developing criteria for documenting that behaviors have not changed to be eligible for participation in a
p.000059: study. He suggested that, for a study of pesticides, potential study participants provide documentation (such as
p.000059: receipts) that they routinely have been using a commercial pesticide service. This may be difficult
p.000059: for potential participants to do if they do not save receipts, and it would exclude all potential
p.000059: participants who purchase products and apply pesticides themselves. This likely would affect the study
p.000059: objectives and generalizability of the data collected. A survey of investigators (Iltis et al., 2006) found that
p.000059: payments were made in 52% of the pediatric research studies surveyed, and that payment practices varied,
p.000059: as did the reasons for decisions regarding payments. They found a range of payment values separated
p.000059: across cash, gifts, items, vouchers, and other categories. A survey of IRBs (Weise et al., 2002) found that payment
p.000059: for participation in research was allowed by 66% of responding institutions, but that many IRBs did not have
p.000059: specific policies, and that there was considerable variability regarding the basis for decisions on
p.000059: payments in studies with children. The types of payments included money, certificates, and bonds with large
p.000059: ranges in the amounts of payments for approved pediatric research. This research shows a lack of consistency and
p.000059: the need for guidance and institutional policies that describe acceptable and unacceptable
p.000059: payments and the basis for the amount of any payments.
p.000059: The NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children
p.000059: described many of the ethical considerations, practices, and policies regarding payments (NRC & IOM, 2005)
p.000059: for research conducted in the participants’ homes, rather than in a clinical facility. The research
p.000059: setting is similar to the setting of most observational
p.000059: human exposure studies, and the committee’s commentary and recommendations are also relevant. The
p.000059: committee notes that it would be unfair to expect families to make considerable sacrifices to
p.000059: participate in a time-consuming activity designed to advance generalizable scientific knowledge,
p.000059: rather than benefit themselves directly, and that payment for reimbursement of expenses and modest payment for
p.000059: time spent in research activities is justified on the grounds of fairness. But the committee then warns that if
p.000059: payments are too high, they may distort parents’ decisions about enrolling their children. The committee also
p.000059: found that “how the payment is made may also result in undue influence. For example, if payment for a long-term
p.000059: follow-up study is made in a lump sum and only if the subjects complete the entire study, then it
p.000059: could constitute an undue influence to stay in the study. If, on the other hand, the money is paid weekly, the
p.000059: effect would not constitute an undue influence.”
p.000059: The NRC & IOM committee recognizes that the issue of payment for participation in research is
p.000059: controversial. They also discuss how “countervailing ethical guidelines” may complicate the issues even more.
p.000059: Citing Wendler et al. (2002), the NRC & IOM committee points out that payments that are trivial
p.000059: for some families may be substantial for low-income or disadvantaged families. “Yet to pay
p.000059: economically disadvantaged families less than more affluent families for participating in the research is
p.000059: unfair because it requires similar sacrifices of time and inconvenience from both” (p. 113, NRC & IOM, 2005).
p.000059: Similar ethical quandaries can arise in multisite studies with differing costs for living. If the same payment
p.000059: is used in high-cost cities as in low-cost areas, the payment may be inadequate to gain sufficient
p.000059: enrollment in the high-cost area, whereas the same dollar amount may be “coercive” in the low-cost area. The NRC & IOM
p.000059: committee notes that a similar situation can arise when a study enrolls participants from diverse
...
p.000059:
p.000059:
p.000059:
p.000059:
p.000060: 60
p.000060:
p.000060: 5.2.4 Payments in Observational Human Exposure Studies
p.000060: Observational human exposure studies most often involve minimal risks to study participants and few direct
p.000060: benefits, but may require considerable time and burden for participation. Study requirements can include multiple
p.000060: in-home visits; the burden of wearing personal air monitors for one or more 24-hour period; preparing and providing
p.000060: duplicate diet samples; collection of environmental samples inside and outside the home; completing
p.000060: questionnaires, food diaries, and time- activity diaries; and providing urine, blood, saliva, or hair
p.000060: samples. Monetary payments often have been included in these studies, with the level of payment
p.000060: related to the number of study days or visits or the specific kinds of environmental and biological
p.000060: samples and information that are collected or provided. Payment for direct participant costs has been included
p.000060: in some studies, such as a reasonable payment for providing researchers with duplicate diet samples.
p.000060: NERL scientists should review the commentary and recommendations in the literature before devising a
p.000060: payment program as part of a research protocol, especially the two recent National Academies of Science
p.000060: documents, Ethical Issues in Housing-Related Health Hazard Research Involving Children (NRC and IOM, 2005)
p.000060: and Ethical Conduct of Clinical Research Involving Children (IOM, 2004). They should seek
p.000060: guidance from EPA’s HSRRO to determine EPA’s latest policies and guidance in this regard. Input also should be sought
p.000060: from community representatives to ensure that any payment is adequate to compensate for expenses and reward
p.000060: participation, but that the payment is not so high as to constitute undue influence or coercion in the
p.000060: community. If the study includes several followup visits over a long term, NERL researchers should ensure that payment
p.000060: is made incrementally as the NRC & IOM committee suggested. NERL scientists also should adopt the IOM
p.000060: Recommendations 6.1 and 6.2, including ensuring that any payment should be for appropriate purposes
p.000060: and age-appropriate, and that the process should be open and fully disclosed, while not overly
p.000060: emphasizing payments during the recruiting or informed consent phases. The final decisions about the ethics of
p.000060: payments rest with the IRB, which will review, modify as needed, and approve the research protocol, and with the EPA
p.000060: HSRRO, who has final authority to approve, modify, or disapprove all of NERL’s human subjects research
p.000060: efforts.
p.000060: 5.3 Research Rights and Grievance Procedures
p.000060: Protecting the research rights of participants and providing independent access to information regarding
...
p.000061: the Report and Recommendations on Public Trust in Clinical Research for the NIH Director from the
p.000061: Director’s Council of Public Representatives (COPR) (NIH, 2005). Although the advice from this workshop was
p.000061: developed in the context of NIH-supported clinical research, many of the recommendations are applicable to
p.000061: observational human exposure studies and human subject research in general. A summary
p.000061: of
p.000061: recommendations from the report for enhancing public trust is provided in Appendix D. The recommendations are
p.000061: focused on the following areas.
p.000061: • Building trust through community partnerships
p.000061: • Building relationships with patients (participants) (True partnerships with patients may not be possible,
p.000061: but bidirectional relationships must be enhanced.)
p.000061: • Building partnerships with community providers
p.000061: • Building trust in scientists
p.000061: • Building trust in the (EPA) and scientific research.
p.000061:
p.000061: 5.5 Recruitment Strategies
p.000061: Many strategies are used to select and recruit people into research studies requiring human participation. The IRB is
p.000061: responsible for reviewing the selection process to ensure that it is, above all, equitable. The requirement for
p.000061: IRB review is stated in 40 CFR 26.111(a)3.
p.000061: Selection of subjects is equitable. In making this assessment, the IRB should take into account the
p.000061: purposes of the research and the setting in which the research will be conducted and should be particularly cognizant
p.000061: of the special problems of research involving vulnerable populations, such as children, prisoners,
p.000061: pregnant women, mentally disabled persons, or economically or educationally disadvantaged
p.000061: persons.
p.000061: The IRB guidebook is an excellent resource for consideration of concerns and elements for equitable
p.000061: participant selection (U.S. HHS, 1993). It states that “Defining the appropriate group of subjects
p.000061: for a research project involves a variety of factors⎯ requirements of scientific design,
p.000061: susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness.” The IRB
p.000061: guidebook raises a number of points to consider in the process for selection of human participants (see Text Box
p.000061: 5-5).
p.000061: Various participant recruitment strategies may be used depending on the type of research being performed and the
p.000061: population of interest. This section addresses the strategies and approaches for identifying and contacting people and
p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
p.000062: 1. Who will bear the burden? Who will reap the benefits?
p.000062: 2. Is there a disproportionate burden on any single group?
p.000062: 3. Is the proposed subject population required or justified?
p.000062: 4. Are there susceptible groups of people who should be excluded from the research?
p.000062: 5. Are anticipated benefits distributed fairly? Do others have a greater need to receive any of the anticipated
p.000062: benefits?
p.000062: 6. Are the research burdens distributed fairly?
p.000062: 7. Will any special physiological, psychological, or social characteristics of the subject group pose special risks
p.000062: for them?
p.000062: 8. Would it be possible to conduct the study with other, less vulnerable subjects?
p.000062: 9. Has the selection process overprotected potential subjects who are considered vulnerable (e.g., children,
p.000062: cognitively impaired, economically or educationally disadvantaged persons, patients of researchers, seriously ill
p.000062: persons), so that they are denied opportunities to participate in research?
p.000062: 10. If the subjects are susceptible to pressures, are there mechanisms to reduce the pressures or minimize their
p.000062: impact?
p.000062:
p.000062:
p.000062: Some of the common approaches for identifying and making initial contact with potential participants include, but are
p.000062: not limited to
p.000062: • direct telephone or in-person contact with a person selected through a statistical sampling process
p.000062: to obtain a representative sample of the population being studied;
p.000062: • use of print or other media advertisements, often used to recruit people in a community with specific
p.000062: characteristics;
p.000062: • advertisement or word-of-mouth contacts through community groups, civic organizations, or other types of
p.000062: organizations; and
p.000062: • recruitment at physicians’ offices, hospitals, and clinics or at churches, schools, or other
p.000062: social institutions, either in person or through the use of advertisements or study brochures.
p.000062: CABs can be consulted regarding proposed approaches for recruitment in community-based
p.000062: research. All procedures and materials for participant recruitment are reviewed and approved by the IRB prior to
p.000062: implementation. Some of the materials prepared for recruitment might include the following.
p.000062: • Recruitment scripts⎯prepared scripts used for in- person or telephone study information and recruitment
p.000062: contacts
...
p.000063: People are more likely to continue active participation in longitudinal studies when they
p.000063: believe that the research is important, and that they are making a valuable contribution, are receiving regular
p.000063: feedback, and are treated with courtesy and respect by researchers. Observational human exposure studies
p.000063: sometimes involve substantial burdens of time and effort. Over long periods, this level of burden can reduce retention.
p.000063: It may be necessary to develop novel methods that reduce participant time and effort or to focus the study
p.000063: design so that fewer study procedures are implemented at any time point. Because the time needed to analyze
p.000063: samples, verify results, and perform data analyses can be long, it may be difficult to provide timely
p.000063: feedback to participants in observational human exposure studies. Researchers might consider including
p.000063: simple measures that can provide immediate and useful information of value to participants to
p.000063: encourage continued participation. Effective use of these strategies will reduce the need for
p.000063: higher payments to encourage retention.
p.000063:
p.000063: 5.7 Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk
p.000063: Researchers and IRBs need to ensure that the procedures and materials used to recruit and retain study
p.000063: participants in observational human exposure studies do not “undermine free and informed consent by leading
p.000063: parents to expose their children to unacceptable risks. (NRC and IOM, 2005)” Payments in these
p.000063: studies should not be so high that they would cause an undue
p.000063: inducement for a participant to use a product they would not normally use or to perform an activity that they
p.000063: would not normally perform. Not only would this bias the study results but may lead to higher than
p.000063: normal levels of exposure. Alternatively, the act of studying one set of conditions or activities in an observational
p.000063: human exposure study could lead participants to assume that those conditions or activities involve substantial
p.000063: risk. In response, they subsequently may change their activities in ways that could lead to possibly higher
p.000063: risks. The potential for such unintentional outcomes is difficult for researchers to gauge but requires
p.000063: researcher caution in how information and results are conveyed. However, if the informed consent process is
p.000063: truly “an on-going, interactive dialogue . . . involving the disclosure and exchange of relevant
p.000063: information,” then such misunderstandings should be minimized.
p.000063:
p.000063: References
p.000063: AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric and Environmental Health. (2nd
p.000063: Edition). Elk Grove Village, IL: American Academy of Pediatrics.
p.000063:
p.000063: Ackerman TF (1989). An ethical framework for the practice of paying research subjects. IRB 11(4):1-4.
p.000063:
p.000063: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000063: Subjects. U.S. Code of Federal Regulations.
p.000063: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/ 40cfr26_06.html [accessed 12 June 2007].
p.000063:
p.000063: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000063: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000063: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000063:
p.000063: Diekema DS (2005) “Payments for Participation of Children in Research.” Chapter in: Kodish, E, Editor. Ethics and
p.000063: Research with Children: A Case-Based Approach. New York, NY: Oxford University Press. 143-160.
p.000063:
p.000063: Dickert N, Emanuel E, Grady C (2002). Paying research subjects: an analysis of current policies. Ann Intern Med
p.000063: 136(5):368-373.
p.000063:
p.000063: Emanuel EJ (2004). Ending concerns about undue inducement. J Law Med Ethics 32(1):100-105.
p.000063:
p.000063: Emanuel, EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000063:
p.000063:
p.000063:
p.000064: 64
p.000064:
p.000064: Erlen JA, Sauder RJ, Mellors MP (1999). Incentives in research: ethical issues. Orthop Nurs 18(2):84-87.
p.000064:
p.000064: European Parliament (2001). On the approximation of the laws, regulations, and administrative provisions of the Member
p.000064: States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products
p.000064: for human use. Directive 2001/20/EC Article 4(d) of the European Parliament and of the Council of 4 April 2001.
p.000064:
p.000064: Flory J, Emanuel E (2004). Interventions to improve research participants’ understanding in informed consent for
p.000064: research: a systematic review. JAMA 292(13):1593-1601.
p.000064:
p.000064: Fry CL, Ritter A, Baldwin S, Bowen KJ, Gardiner P, Holt T, Jenkinson R, Johnston J (2005). Paying research
p.000064: participants: a study of current practices in Australia. J Med Ethics 31:542-547.
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p.000064: Grady, C (2005) Payment of clinical research subjects. J Clin Invest 115:1681-1687.
p.000064:
p.000064: Grady C, Dickert N, Jawetz T, Gensler G, Emanuel E (2005). An analysis of U.S. practices of paying research
p.000064: participants. Contemp Clin Trials 26:365-375.
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p.000064: Iltis AS, DeVader S, Matsuo H (2006). Payments to children and adolescents enrolled in research: a pilot study.
p.000064: Pediatrics 118(4):1546-1552.
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p.000064: IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Marilyn J. Field and
p.000064: Richard E. Behrman (eds). Washington, DC: The National Academies Press.
p.000064:
p.000064: IOM (Institute of Medicine) (2002). Responsible Research: A Systems Approach to Protecting Research Participants.
p.000064: Daniel D. Federman, Kathi E. Hanna, and Laura Lyman Rodriguez (eds). Washington, DC: The National Academies Press.
p.000064:
p.000064: Menikoff J (2005). Of babies, bugs, and bombast: A look behind the crash-and-burn of the CHEERS pesticide study. Med
p.000064: Res Law Policy Rep 4(14):586-512.
p.000064:
p.000064: NCS (National Children’s Study) (2007) Research Plan, Volume 1, Version 1.1, June 20, 2007. Available:
p.000064: www.nationalchildrensstudy.gov/research/research_plan/upl oad/Research_Plan_Volume_1.pdf [accessed 12 September 2007.].
p.000064:
p.000064: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for the NIH
p.000064: Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health, Director’s
p.000064: Council of Public Representatives, January 14,
p.000064: 2005. Available: http://copr.nih.gov/reports/public_trust.asp
p.000064: [accessed 12 June 2007].
p.000064:
p.000064: NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing Research
p.000064: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000064: [accessed 16 August 2007].
p.000064:
p.000064: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000064: Housing-Related Health Hazards Involving Children.
p.000064: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000064: June 2007].
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p.000064: OMB (Office of Management and Budget). (2006a). Standards and Guidelines for Statistical Surveys. Section 2.3, Data
p.000064: Collection Methodology. http://www.whitehouse.gov/omb/inforeg/statpolicy/standard s_stat_surveys.pdf
p.000064:
p.000064: OMB (Office of Management and Budget). (2006b). Questions and Answers When Designing Surveys for Information
p.000064: Collection. Office of Information and Regulatory Affairs. January, 2006.
p.000064: http://www.whitehouse.gov/omb/inforeg/pmc_survey_guidanc e_2006.pdf
p.000064:
p.000064: Paasche-Orlow MK, Taylor HA, Brancati FL (2003). Readability standards for informed-consent forms as compared with
p.000064: actual readability. N Engl J Med 348(8):721 6.
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p.000064: Russell ML, Moralejo DG, Burgess ED. (2000). Paying research subjects: participants' perspectives. J Med Ethics
p.000064: 26(2):126-30.
p.000064:
p.000064: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979). The Belmont Report: Ethical Principles and
p.000064: Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: National Commission for the Protection
p.000064: of Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
p.000064: [accessed June 2007].
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p.000064: U.S. FDA (U.S. Food and Drug Administration) (1998). Information Sheets: Guidance for Institutional Review Boards and
p.000064: Clinical Investigators 1998 Update. U.S. Food and Drug Administration, Washington, DC. Available:
p.000064: http://www.fda.gov/oc/ohrt/irbs/toc4.html [accessed May 2007].
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p.000064: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
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p.000065: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000065: [accessed 12 June 2007].
p.000065:
p.000065: VanderWalde A (2005). Undue inducement: the only objection to payment? Am J Bioethics 5(5):25-27.
p.000065: Weise KL, Smith ML, Maschke KJ, Copeland L (2002). National practices regarding payment to research subjects for
p.000065: participating in pediatric research. Pediatrics 110(3):577-582.
p.000065:
p.000065: Wendler D, Rackoff JE, Emanuel EJ, Grady C (2002). The ethics of paying for children’s participation in research. J
p.000065: Pediatr 141(2):166-171.
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
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p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
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p.000065:
p.000065:
p.000065:
p.000065:
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p.000065:
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p.000066: 66
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: SECTION 6
p.000066: Building and Maintaining Appropriate Community and Stakeholder Relationships
p.000066:
p.000066:
p.000066:
p.000066: Community engagement promotes active community involvement in the processes that shape
p.000066: research strategies and the conduct of research studies. In developing this document, NERL held an expert panel
p.000066: workshop to identify the content and organization of this document (ERG, 2007). That panel of experts concluded that
p.000066: the need to engage the community in observational research was based on the ethical principles of (1) respect
p.000066: for persons, which manifests itself in both a respect for the individual and, through respect for the
p.000066: community, their culture; (2) fairness, resulting in efforts to assure equity in resources, burden, and benefits; and
p.000066: (3) beneficence, including “empowering the community to endure.”
p.000066: Involving the community in the research effort can improve the research both scientifically and ethically. In
p.000066: the document, Ethical Considerations for Research on Housing-Related Health Hazards Involving Children, the
p.000066: joint NRC-IOM committee found that community involvement was a “guiding theme” of their findings (NRC &
p.000066: IOM, 2005). Because the researchers were working in the homes and communities of the
p.000066: participants, they faced issues that were different from a clinical setting. They were challenged to think about the
p.000066: fundamental ethical principles in the context of the research setting and about how those ethical
p.000066: principles should be interpreted in that setting. “When researchers discuss a planned study with community
p.000066: representatives, understand their concerns and needs, and respond to them, protocols can be strengthened
p.000066: both scientifically and ethically” (p. xii, NRC & IOM, 2005). Just as was described in Section 5, where the
p.000066: informed consent process was described as needing to be “an on-going, interactive dialogue between research
p.000066: staff and research participants involving the disclosure and exchange of relevant information, discussion of that
p.000066: information, and assessment of the individual’s understanding of the
p.000066: discussion” (Recommendation 4.1, IOM, 2004), so, too, the process of community involvement should be a process
p.000066: of effective two-way communication. These NRC & IOM comments emphasize how critical
p.000066: effective, bidirectional communication is to the scientific and ethical foundation of a research study in such
p.000066: a setting.
p.000066: EPA has established a public involvement policy to “improve the content of the Agency’s decisions and enhance
p.000066: the deliberative process” (U.S. EPA, 2003) (see Text Box 6-1). The policy is focused largely on Agency decisionmaking
...
p.000068: interactions with the target communities “by helping the investigators interpret data and distribute information to
p.000068: the communities” and “developing and conducting the training” of the community members on risk reduction
p.000068: strategies. The value of the research to the TEAL target communities would have been diminished had a CAB not been
p.000068: formed to assist the researchers with specific best practices to use when engaging the tribal members and
p.000068: the appropriate tribal leadership structures.
p.000068: Another potential approach to involve the community is to use a CBPR approach, wherein the
p.000068: community is actively involved in each step of the research process, including sharing of decisionmaking
p.000068: power and resources. This will impact decisions about study design, study methods, dissemination of findings,
p.000068: and resulting actions. “Under the principles of community-based participatory research, research
p.000068: must
p.000068:
p.000068:
p.000069: 69
p.000069:
p.000069: address the concerns, needs, and priorities of the communities where it is conducted and lead to
p.000069: actions and changes that benefit the community” (p. 86, NRC & IOM, 2005). Information about CBPR approaches can
p.000069: be found online at the HHS Web sites http://www.ahrq.gov/clinic/epcsums/cbprsum.htm
p.000069: and http://www.ahrq.gov/research/cbprrole.htm.
p.000069: Israel et al. (2005a) reviewed the results of CBPR efforts at six Children’s Centers co-funded by EPA and the
p.000069: National Institute of Environment Health Sciences. They found that considerable commitment of resources and
p.000069: time are needed for the approach to be successful, and the translation of research findings into interventions
p.000069: and policies is of the utmost importance. Community partners played little role in defining the research topics
p.000069: and data analysis, but were vital to disseminating the findings to the community. Keeler et al. (2002) describe
p.000069: using CBPR methods to evaluate personal and community-level exposures to particulate matter among
p.000069: asthmatic children in Detroit. The research partnership, Community Action Against Asthma (CAAA), consisted of
p.000069: representatives from local health organizations, community environmental advocacy groups, State and local
p.000069: governmental agencies, and academia. The CAAA partnership credits community involvement as active research
p.000069: partners in the research process with the success of the project to acquire “more relevant exposure data for
p.000069: the study of children in urban neighborhoods” and to provide “immediate knowledge and understanding of the outcomes
p.000069: and results of the combined environmental health analysis to the communities” (Keeler et al., 2002). There are,
p.000069: however, several drawbacks to utilizing CBPR methods that researchers should consider before developing a
p.000069: CBPR project. CBPR is time consuming (develop partnership, establish and agree on research aims and
p.000069: objectives, disseminate results to the community using appropriate methods, and review
p.000069: manuscripts and presentations) and not conducive to situations where rapid decisions are necessary given a
p.000069: tight timeline. Weighing the research need versus the community’s desire for an intervention is the
p.000069: greatest source of tension in conducting CBPR (Israel et al.,
p.000069: 2005b).
p.000069: One additional opportunity for community input may involve participation on an IRB. IRBs are required by the
p.000069: Common Rule to have members who are sensitive to “community attitudes” [40 CFR 26.107(a)]. How they meet this
p.000069: obligation is totally at their discretion, and NERL researchers have no influence. There have been a number of
p.000069: recent articles in the literature about IRBs that have envisioned a need for more regulatory reform
p.000069: (Ledford, 2007). Ideally, the IRB should take into account the views of the community. Quinn
p.000069: (2004) argues for extending protections now reserved for individuals to groups (populations and
p.000069: communities) through CABs. Her argument is that there are “ethical issues related to research with
p.000069: communities that are distinctly different from the ethical issues related to research with individuals.”
p.000069: CAB members have to be educated on human subjects’ protections, should represent their communities
p.000069: honestly, and need to be willing to interact with researchers on complex research issues.
p.000069: Gilbert (2006) goes even further. He suggests supplementing or even replacing traditional IRBs with
p.000069: environmental health and community review boards (EHCRBs). He argues that traditional IRBs
p.000069: are inadequate for the review of community-based research because they were developed to address issues related to
p.000069: individuals involved in research projects, not communities. He proposes EHCRBs that combine
p.000069: the fundamental and ethical concept of traditional IRBs with an expanded ethical construct of dignity,
p.000069: veracity, sustainability, and justice, with added emphasis on community. He envisions that an
p.000069: EHCRB would function as an IRB with the requirements and responsibilities for review for the
p.000069: protection of human subjects, plus the additional role for review of community issues
p.000069: associated with the research project.
p.000069: Gilbert’s recommendation for EHCRBs is consistent with the recommendations of the authors of the NRC & IOM report who
p.000069: recommended that “Institutional review boards that review housing health hazards research involving
p.000069: children should ensure that those boards have the necessary expertise to conduct a complete and adequate
p.000069: review, including expertise on research involving children and community perspectives” (NRC & IOM,
p.000069: 2005).
p.000069: Involving community representatives in the IRB process is challenging for IRBs, however. One challenge could
p.000069: be the need to provide sufficient training to community members about the IRB process and the
p.000069: regulations governing IRBs. This can be significant if members sit on an IRB for a limited time to
p.000069: review specific community-based studies. In some cases, IRBs may invite community members to participate in the
p.000069: IRB process as nonvoting members to solicit the community perspective. This approach, which would be totally at the
p.000069: discretion of the IRB, might reduce the burden on the community representative by reducing
p.000069: training requirements.
p.000069:
p.000069:
p.000069:
p.000070: 70
p.000070:
p.000070: 6.2 Issues in Community Involvement
p.000070: There are a number of issues that need to be addressed in any efforts to ensure
p.000070: community involvement. The Expert Panel that was convened to advise NERL about scientific and ethical
p.000070: issues in observational human exposure studies discussed a number of challenges (ERG, 2007). The topics
p.000070: that the expert panel identified as issues are discussed below.
p.000070:
p.000070: 6.2.1 Defining “Community”
p.000070: “Community” refers to a group of people united by a shared attribute, and the attributes can be wide-ranging, such as
p.000070: geography, culture, social characteristics, values, interests, traditions, or experiences (ERG, 2007).
p.000070: Community can be defined broadly (as a system of interrelated groups operating to meet the needs of its
...
p.000075: stakeholder in the study, regardless of level of participation, does not result in actual
p.000075: or perceived conflicts of interest. This should be addressed in the plan and agreement for stakeholder involvement.
p.000075:
p.000075: References
p.000075: CDC (Centers for Disease Control and Prevention) (1997). Principles of Community Engagement. ATSDR Committee on
p.000075: Community Engagement. Available: http://www.cdc.gov/phppo/pce/ [Accessed Oct. 2007].
p.000075:
p.000075: Corburn J (2007). Community knowledge in environmental health science: co-producing policy expertise. Environ Sci
p.000075: Policy 10(2):150-161.
p.000075:
p.000075: Corburn J (2002). Environmental justice, local knowledge, and risk: the discourse of a community-based cumulative
p.000075: exposure assessment. Environ Mngt 29(4):451-466.
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p.000076: Dula A (1994). African American suspicion of the healthcare system is justified: What can we do about it? Camb Q
p.000076: Healthc Ethic 3(3):347-357.
p.000076:
p.000076: ERG (Eastern Research Group) (2007). Report on the Workshop to Discuss State-of-the-Science Approaches for
p.000076: Observational Exposure Measurement Studies. Held in Durham, North Carolina on November 28-29, 2006. Final Report:
p.000076: January 25, 2007. (PB2007-108905).
p.000076:
p.000076: Gilbert SG (2006). Supplementing the traditional institutional review board with an environmental health and community
p.000076: review board. Environ Health Perspect 114(10):1626-9.
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p.000076: IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Marilyn J. Field and
p.000076: Richard E. Behrman (eds). Washington, DC: The National Academies Press.
p.000076:
p.000076: Israel BA, Parker EA, Rowe Z, Salvatore A, Minkler M, López J, Butz A, Mosley A, Coates L, Lambert G, Potito PA,
p.000076: Brenner B, Rivera M, Romero H, Thompson B, Coronado G, Halstead S (2005a). Community-based participatory research:
p.000076: lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research. Environ Health
p.000076: Perspect 113(10):1463-71.
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p.000076: Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005b). Methods in Community-Based Participatory Research for Health. San
p.000076: Francisco, CA: Jossey-Bass.
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p.000076: Israel BA, Schulz AJ, Parker EA, Becker AB (1998). Review of community-based research: assessing partnership approaches
p.000076: to improve public health. Annu Rev Public Health 19:173-202.
p.000076:
p.000076: Juengst ET (2000). Commentary: What “community review” can and cannot do. J Law Med Ethics 28(1):52-54.
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p.000076: Keeler G, Dvonch T, Yip F, Parker E, Israel B, Marsik F, Morishita M, Barres J, Robins T, Caldwell W, Sam M (2002).
p.000076: Assessment of personal and community-level exposures to particulate matter among children with asthma in Detroit, MI,
p.000076: as part of Community Action Against Asthma. Environ Health Perspec 110(Suppl 2): 173–181.
p.000076:
p.000076: Ledford H (2007). Human Subject Research: Trial and Error.
p.000076: Nature 448(7153): 530-532.
p.000076:
p.000076: Leung MW, Yen IH, Minkler M (2004). Community-based Participatory Research: a promising approach for increasing
p.000076: epidemiology’s relevance in the 21st century. Int J Epidemiol 33(3):499-506.
p.000076:
p.000076: Minkler M, Wallerstein N (eds) (2003). Community-Based Participatory Research for Health. San Francisco, CA:
p.000076: Jossey-Bass.
p.000076: Mitchell RK, Agle BR, Wood DJ (1997). Toward a theory of stakeholder identification and salience: defining the
p.000076: principle of who and what really counts. Acad Manage Rev 22(4):853-886.
p.000076:
p.000076: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for the NIH
p.000076: Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health, Director’s
p.000076: Council of Public Representatives, January 14, 2005. Available: http://copr.nih.gov/reports/public_trust.asp
p.000076: [accessed June 2007].
p.000076:
p.000076: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000076: Housing-Related Health Hazards Involving Children.
p.000076: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000076: June 2007].
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p.000076: O’Fallon LR, Dearry A (2002). Community-based partici patory research as a tool to advance environmental health
p.000076: sciences. Environ Health Perspect 110 Suppl 2:155-9.
p.000076:
p.000076: Perkins DD, Wandersman A (1990). You’ll have to work to overcome our suspicions: the benefits and pitfalls of research
p.000076: with community organizations. Soc Policy 21(1):32-41.
p.000076:
p.000076: Quandt S, Arcury T, Pell A (2001). Something for everyone? A community and academic partnership to address farmworker
p.000076: pesticide exposure in North Carolina. Environ Health Perspect 109 Suppl 3:435-441.
p.000076:
p.000076: Quinn SC (2004). Ethics in public health research: protecting human subjects: the role of community advisory boards. Am
p.000076: J Public Health 94(6):918-22.
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p.000076: Tillman, L. (2002). Culturally sensitive research approaches: an African-American perspective. Educ Researcher
p.000076: 31(9):3-12.
p.000076:
p.000076: U.S. EPA (U.S. Environmental Protection Agency) (2003). Public Involvement Policy of the U.S. Environmental Protection
p.000076: Agency. EPA 233-B-03-022. Available: http://www.epa.gov/publicinvolvement/pdf/policy2003.pdf [Accessed 26 Sep 2007].
p.000076:
p.000076: Vega WA (1992). Theoretical and pragmatic implications of cultural diversity for community research. Am J Commun
p.000076: Psychol 20(3):375-91
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p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2000). El Superfund Hoy Día: La Estimación de Riesgos: Como Lograr la
p.000077: Participación de La Communidad. U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response.
p.000077: Washington, DC. EPA 540-K 99-005, OWSER 9200.2-26K, PB99-963230. Available:
p.000077: http://www.epa.gov/superfund/community/today/pdfs/risk fs-0203.pdf
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2001). Improved Science-Based Environmental Stakeholder Processes: A
p.000077: Commentary by the EPA Science Advisory
p.000077: Board. EPA-SAB-EC-COM-01-006. EPA Science Advisory Board. Washington, DC. Available:
p.000077: http://yosemite.epa.gov/sab/sabproduct.nsf/CEE3F362F1A1 344E8525718E004EA078/$File/eecm01006_report_appna e.pdf
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2003). Framework for Cumulative Risk Assessment. Washington, DC:
p.000077: United States Environmental Protection Agency. EPA/600/P-02/001F. Available:
p.000077: http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=54944 .
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p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2003). Framework for Assessing Risks of Environmental Exposure to
p.000077: Children. Washington, DC. Available: http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=22521.
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p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2005). Guidance on Selecting Age Groups for Monitoring and Assessing
p.000077: Childhood Exposures to Environmental Contaminants. Risk Assessment Forum, Washington, D.C. EPA/630/P-03/003F.
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p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). Considerations for Developing Alternative Health Risk
p.000077: Assessment Approaches for Addressing Multiple Chemicals, Exposures, and Effects. External Review Draft. 71 FR 16306.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). Paper on Tribal Issues Related to Tribal Traditional Lifeways,
p.000077: Risk Assessment, and Health and Well Being: Documenting What We’ve Heard. The National EPA-Tribal Science Council.
p.000077: Available: http://epa.gov/osp/tribes/tribal/TribalIssues.pdf.
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p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). EPA’s Public Involvement Policy. Available:
p.000077: http://www.epa.gov/publicinvolvement/policy2003/index.htm.
p.000077:
...
p.000081: • Do not lose your temper or get over-emotional.
p.000081: • Speak slowly and calmly; don’t raise your voice.
p.000081: • Speak clearly and concisely.
p.000081: • Get to the point; do not ramble.
p.000081: • Be kind, compassionate, and empathetic.
p.000081: • Be honest; do not play games.
p.000081: • Be assertive but tactful
p.000081:
p.000081:
p.000081: 7.2 Individuals and Groups Involved in the Communications
p.000081: An effective communication plan will identify and involve all of the individuals and relevant groups that
p.000081: should be included in the communications efforts. When conducting observational human exposure studies, this list
p.000081: may be quite long. Although researchers may desire to limit the number of individuals and groups involved to
p.000081: keep the effort as simple and focused as possible, they need to ensure that all potential stakeholders
p.000081: are identified. The communication plan should identify all groups, including community organizations
p.000081: and stakeholders, involved in a study, their roles and responsibilities in the study, how
p.000081: communications will be developed with each group, and the timing of the communications. It is likely
p.000081: that most studies will involve the individuals, community groups and stakeholders shown in Text
p.000081: Box 7-3.
p.000081:
p.000082: 82
p.000082:
p.000082:
p.000082: Text Box 7-3. Individuals and Groups Involved in Communications
p.000082: • Principal investigator—the researcher with ultimate responsibility for the study
p.000082: • Research team
p.000082: • Study participants
p.000082: • Third parties associated with study participants (e.g., spouse, children, landlords)
p.000082: • Community representatives
p.000082: • Community members
p.000082: • Governments (local, State, and Federal)
p.000082: • Study institution management
p.000082: • Study sponsors or funding organization
p.000082: • Organizations with interest in the participants, the community, or the research question
p.000082: • Stakeholders that may be impacted by the results of the study
p.000082: • The scientific community
p.000082: • Media
p.000082: • The general public
p.000082:
p.000082: The study participants are a key group involved in communications during a study and are easily identified.
p.000082: Similarly, it is generally not difficult to identify the third parties associated with the study participants,
p.000082: because these groups must be identified when considering ethical issues in the study and when developing the
p.000082: human subjects research protocol. Research teams should ensure that the communication strategy includes the
p.000082: strategy and approach for third-party communications.
p.000082: As discussed in Section 6, it is critical that community representatives are identified early in
p.000082: the scoping and planning phase of the study. It is important that researchers are informed about the community
p.000082: in which they will conduct the study and understand the unique characteristics and culture of the community and
p.000082: the potential study participants to develop effective bidirectional communications. When
p.000082: possible, researchers should identify other research organizations who have worked in the community and attempt
p.000082: to gather information from them on the nature of the community, who represents the community, and what
p.000082: communication strategies have been used previously in the community. Understanding how the community
p.000082: defines itself or thinks of itself is critical to establishing effective communications.
p.000082: Identification of all relevant stakeholder groups may be more difficult. As defined in Section 6, the term
p.000082: stakeholder is used here to identify a person or group who has a valid interest in an activity or
p.000082: decision, but who does not speak directly for the community or the participants. There may be many
p.000082: organizations who consider themselves as stakeholders that represent the
p.000082: interests of the community, the participants, or the research problem. For example, there are many
p.000082: nonprofit organizations that advocate for the protection of children’s health. When conducting an
p.000082: observational study involving children, the research team should identify those groups that could have
p.000082: an interest in the study. They need to be identified in the communication plan, and an approach needs to
p.000082: be developed for communicating with them about the study. There are many sources of information on
p.000082: potentially interested stakeholder groups. This information can be obtained from the research team based on
p.000082: similar studies, the participants, the community representatives, sponsoring organizations, and “umbrella”
p.000082: organizations for various advocacy groups. The Internet has made identification of the various stakeholder groups
p.000082: easier and is a source of information on goals of the groups and contact information. Approaches for
p.000082: communications with these and other groups on the list are discussed further in the following subsections.
p.000082: Researchers should recognize that identifying and involving all pertinent community and stakeholder
p.000082: groups in their observational human exposure studies is important for effective communications and the potential
p.000082: success of the study, but that there is the potential for the group to become so large that it becomes
p.000082: difficult to manage. Large groups not only have the potential for impeding progress on a research effort
p.000082: simply because of the logistics of the interactions within the group, but, also, because of the potential
p.000082: for conflict between the groups. It is essential, therefore, that researchers attempt to maintain stakeholder
p.000082: groups of manageable size and be prepared to deal with potential conflict within the groups. There is
p.000082: extensive literature available on conflict management, but it is outside of the scope of this document to
...
p.000085: studies should consider these factors, and communication materials should be developed with these
p.000085: factors in mind.
p.000085:
p.000085: Text Box 7-4. Activities and Materials That May Be Useful in a Communication Plan
p.000085: • Flyers
p.000085: • Web sites
p.000085: • Brochures
p.000085: • Interviews
p.000085: • Newsletters
p.000085: • Focus groups
p.000085: • Presentations
p.000085: • Direct mailings
p.000085: • Press releases
p.000085: • Questions and answers
p.000085: • Desk statements (government)
p.000085: • Abstracts
p.000085: • Study reports
p.000085: • Talking points
p.000085: • Community meetings
p.000085: • Stakeholder meetings
p.000085: • Technical presentations
p.000085: • Study participant meetings
p.000085: • Scientific meeting presentations
p.000085: • Peer-reviewed scientific journal manuscripts
p.000085: • Final reports describing the total research effort
p.000085:
p.000085: When developing communication materials, the researcher should consider the needs of the reader,
p.000085: listener, or viewer with respect to content, scope, style, and the level at which the materials are written.
p.000085: There are many sources of information on design of informational materials, such as flyers or
p.000085: brochures. For example, Alderson (1995) provides an example of the recommended content and style for information
p.000085: leaflets (that also may be flyers or brochures) for pediatric medical research. She suggests that leaflets be
p.000085: provided to parents of children who will be study participants that can be read to the children. She recommends that
p.000085: these be provided at the time that the parent is being informed of the study, prior to requesting the informed
p.000085: consent. The content of the leaflet would include the following topics.
p.000085: • Nature and purpose of the research
p.000085: • Anticipated benefits of the research
p.000085: • Risks, harms, costs, and inconvenience to the participant
p.000085: • Assurance that the participant freely can refuse to participate in or withdraw from the study
p.000085: • Details about remuneration
p.000085: • Names of the project sponsors and the researchers
p.000085: • Contact information for the researchers
p.000085: • Respect for privacy and confidentiality
p.000085: Leaflets and brochures that contain this information provide a tool for communication with study
p.000085: participants. However, these materials need to be written carefully using everyday terms that the
p.000085: average nonresearcher can understand. The brochure should be written in a friendly style that conveys the intent
p.000085: of the researcher to engage the reader as a collaborator on the study, not as a study “subject,” who will be told to do
p.000085: a series of tasks while participating in the study.
p.000085: These same leaflets and brochures can be used to inform other groups that either may be involved or
p.000085: interested in the study, such as community representatives, stakeholder organizations,
p.000085: the media, and the general public. The researcher should ensure that any brochure developed for the study includes
p.000085: accurate and complete information that is less likely to be misinterpreted by anyone who might
...
p.000089: used to provide updates on study progress and general results.
p.000089: Examples of the processes and the materials used for dissemination of information are included in case studies
p.000089: described by Israel et al. (2005) and others conducting CBPR studies.
p.000089: Overall study results generally are disseminated in peer-reviewed journal manuscripts and study reports. The
p.000089: availability of results published in manuscripts and reports has been greatly enhanced by posting them on
p.000089: Internet Web sites. For example, all EPA reports are now available electronically via EPA’s National Service
p.000089: Center for Environmental Publications Web site (http://www.epa.gov/ncepihom/).
p.000089:
p.000089: 7.8 Reporting Unanticipated Results or Observations
p.000089: The previous subsection discussed reporting of routine results from observational human exposure
p.000089: studies. The communication plan should include processes and procedures for the dissemination of
p.000089: the study results. Additionally, the communication plan needs to integrate with the data and safety
p.000089: monitoring and oversight plans for the study and include a plan for reporting unanticipated results or
p.000089: observations. Unanticipated results may include measurements of a chemical at a concentration that
p.000089: exceeds what is considered to be an “acceptable” level in environmental media or biological fluids.
p.000089: Unanticipated observations might include observation of the use of a chemical not approved for indoor
p.000089: use, storage of chemicals in inappropriate containers, storage of chemicals in places accessible by
p.000089: children, etc. Unanticipated results or observations may be directly related to the research question
p.000089: being addressed in the study (e.g., measurements of pesticide residues in a home) or
p.000089: nonstudy hazards (e.g., frayed electrical cords that may pose a hazard to young children and residences).
p.000089: Section 4 discusses issues that may affect privacy and confidentiality. Section 4.3 covers
p.000089: collateral observations of nonstudy-related hazards, including those that States may mandate must
p.000089: be reported. Section 4.5 discusses the need for data and safety monitoring and oversight, including the
p.000089: development of plans to report and react to anticipated or unanticipated adverse events or conditions.
p.000089: As part of the study implementation plan and the communication plan, researchers should develop a
p.000089: protocol for how to identify contaminant measurements and exposures of “concern” that should be reported to the
p.000089: study participant as quickly as possible because of the potential risk associated with the exposure
p.000089: (see Section 4.5, Data and Safety Monitoring and Oversight, and also Section 2.7.1, Establishing Criteria
p.000089: and Standards for Monitoring Scientific and Ethical Issues During a Study.) The plan needs to include the
p.000089: protocol for making the determination and the criteria that will be used as the threshold or “trigger” for
p.000089: reporting. The plans should describe how the results will be reported to the participants and what additional
p.000089: action will be undertaken to assist the participant in reducing their exposures. The first step in
p.000089: developing the protocol is to identify what measurement will be used to identify exposures of concern. In
p.000089: observational human exposure studies, this will generally be the chemical measurement in either environmental or
...
p.000089: environmental media may be the best exposure metric. Whatever metric is chosen, it is important that the
p.000089: chemical analyses can be performed relatively quickly to reduce such exposures as quickly as possible.
p.000089: The second, and more difficult, step in developing the reporting protocol is to determine the
p.000089: level of concern that triggers reporting of the concentration to the study participant. For some environmental
p.000089: media, such as drinking water, EPA (2007) has established maximum contaminant levels that can be used as
p.000089: triggers for reporting. For example, if the researcher measures a level of arsenic in drinking water above
p.000089: 0.010 mg/L, he or she would be expected to report the level to the study participant. For other environmental media,
p.000089: such as air, there are few applicable standards. The National Ambient Air Quality Standards might be
p.000089: used for the criteria pollutants. Guidelines for occupational exposures, such as threshold limit
p.000089: values (TLVs) and biological exposure indices (BEIs) published by the
p.000089:
p.000089:
p.000090: 90
p.000090:
p.000090: American Conference of Governmental Industrial Hygienists (ACGIH, 2008) also may be used. TLVs are not
p.000090: standards; ACGIH formulates a conclusion on the level of exposure that the typical worker can experience without
p.000090: adverse health effects. Many people would argue that the TLVs are not conservative enough for the average
p.000090: population, particularly not for vulnerable lifestages (e.g., children, the elderly) and TLVs are only for
p.000090: exposure by inhalation. WHO (2005) also publishes air quality guidelines. These types of guidelines can be used to
p.000090: advise study participants if their exposures are high relative to the guidelines. Reporting levels should
p.000090: be conservative, but not so low that reporting the level to the participant causes unwarranted concern and
p.000090: stress. For other environmental media measured in observational human exposure studies, such
p.000090: as house dust or surface wipes, the measurement results cannot be used easily to estimate exposures, and they
p.000090: are a poor metric if used alone.
p.000090: An alternative approach to comparison of measurement results against available guidelines and
p.000090: standards is the comparison of measurements in biological fluids to measurement data available from the
p.000090: National Health and Nutrition Examination Survey (NHANES). For example, results of measurements of
p.000090: chemicals or their metabolites in urine or blood can be compared to different percentiles (e.g., the
p.000090: 95th) reported in the NHANES national reports (CDC, 2005). This type of comparison shows that the participant’s
p.000090: measurements are at the high end of the distribution of the NHANES data, suggesting that action may need to be
p.000090: taken to mitigate exposures. However, researchers need to be judicious in the selection of the exposure
p.000090: metric. Biomarkers in blood and biomarkers in urine can be very different exposure metrics and may represent
...
p.000091: developing the information and approach that will be used to respond to criticism.
p.000091: There is a large volume of information available on “crisis communication” that the reader can use to
p.000091: develop a plan for anticipating and responding to criticism (e.g., FCN, 2001; ATSDR, 2007; U.S.
p.000091: HHS,
p.000091: 2002). The key is to be proactive and have a plan before any criticism is raised.
p.000091:
p.000091: 7.10 Responding to the Media, Public Inquiries, and Other Stakeholders
p.000091: Like crisis communications, the communication plan should include detailed plans for how to interact with the
p.000091: stakeholders, the media, and the public. Standard approaches have been developed for
p.000091: effective communications (e.g., the Federal Communicators Network's Communicators Guide [FCN, 2001]) with
p.000091: the media and will not be included in this document. A proactive plan, open and transparent
p.000091: communications, and easily to comprehend information will ensure effective communications with
p.000091: stakeholders and the public.
p.000091:
p.000091: References
p.000091: American Conference of Governmental Industrial Hygienists (ACGIH) (2008). TLV/BEI Resources. Available:
p.000091: http://www.acgih.org/tlv/.
p.000091:
p.000091: Alderson P (1995). Will you help us with our research? Arch Dis Child 72(6):541-42.
p.000091:
p.000091: Anderson B, Hall B (1995). Parents’ perceptions of decision making for children. J Law Med Ethics 23(1):15-9.
p.000091:
p.000091: ATSDR (Agency for Toxic Substances and Disease Registry) (2007). A Primer on Health Risk Communication Principles
p.000091: and Practices [online publication]. Available: http://www.atsdr.cdc.gov/risk/riskprimer/ [accessed 12 June 2007].
p.000091:
p.000091: CDC (Centers for Disease Control and Prevention) (2005). Third National Report on Human Exposure to Environmental
p.000091: Chemicals. National Center for Environmental Health, Atlanta, GA, NCEH Pub. No. 05 0570. Available:
p.000091: http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf [accessed 12 June 2007].
p.000091:
p.000091: Covello V, Allen F (1988). Seven Cardinal Rules of Risk Communication. OPA-87-020. U.S. Environmental Protection
p.000091: Agency, Office of Policy Analysis, Washington, DC. Distributed by the Pennsylvania Dept. of Environmental Resources.
p.000091: Available: http://www.epa.gov/stakeholders/pdf/risk.pdf [accessed 12
p.000091: June 2007].
p.000091:
p.000091: Covello VT, McCallum DB, Pavlova M (eds) (1989). Effective Risk Communication: the role and responsibility of
p.000091: Government and Non-Government Organizations. New York. NY: Plenum Press.
p.000091:
p.000091: Covello V, Minamyer S, Clayton K (2007). Effective risk and crisis communication during water security emergencies
p.000091: summary report of EPA sponsored message mapping.
p.000091: EPA/600/R-07/027. National Homeland Security Research Center, Office of Research and Development, U.S. Environmental
p.000091: Protection Agency, Washington, DC. Available: http://www.epa.gov/nhsrc/pubs/reportCrisisCom040207.pdf
p.000091:
p.000091: FCN (Federal Communicators Network) (2001). Communicators Guide For Federal, State, Regional, and Local Communicators
p.000091: by the Federal Communicators Network. Available: http://www.publicforuminstitute.org/activities/2002/fcn/co mmguid.pdf
p.000091: [accessed 12 June 2007].
p.000091:
p.000091: Fenske RA, Kissel JC, Lu C, Kalman DA, Simcox NJ, Allen EH, Keifer MC (2000) Biologically based pesticide dose
p.000091: estimates for children in an agricultural community.
p.000091: Environ Health Persp 108(6):515-20.
p.000091:
p.000091: Fernandez CV, Kodish E, Weijer C (2003). Informing study participants of research results: an ethical imperative. IRB
p.000091: 25(3):12-19.
p.000091:
p.000091: Health Canada (2006). The Strategic Risk Communications Framework. Available: http://www.riskcommunications.gc.ca
p.000091: [accessed 18
p.000091: September 2007].
p.000091:
p.000091: IOM (Institute of Medicine) (2002). Responsible Research: A Systems Approach to Protecting Research Participants.
p.000091: Daniel D. Federman, Kathi E. Hanna, and Laura Lyman
p.000091:
p.000091:
p.000092: 92
p.000092:
p.000092: Rodriguez (eds). Washington, DC: The National Academies Press.
p.000092:
p.000092: Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005). Methods in Community-Based Participatory Research for Health. San
p.000092: Francisco, CA: Jossey-Bass.
p.000092:
p.000092: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for the NIH
p.000092: Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health, Director’s
p.000092: Council of Public Representatives, January 14, 2005. Available: http://copr.nih.gov/reports/public_trust.asp
p.000092: [accessed June 2007].
p.000092:
p.000092: Parkin RT (2004). Communications with research participants and communities: foundations for best practices. J Expo
p.000092: Anal Environ Epidemiol 14(7):516-23.
p.000092:
p.000092: Peters RG, Covello VT, McCallum DB (1997). The determinants of trust and credibility in environmental risk
p.000092: communication: an empirical study. Risk Anal 17(1):43-54.
p.000092:
...
p.000097: institutions, and NERL simply would augment the pre-existing funding to expand the exposure component
p.000097: (second-party). Some other cases involve research efforts initiated by other Federal agencies with which NERL
p.000097: would collaborate and participate in directly (first-party).
p.000097: An examination of the entries in the table shows that most of the agents being studied were chemicals, often
p.000097: air pollutants or pesticides. A few of the entries indicate that other agents, for example, molds and fungi or other
p.000097: microbes, were the subject of the study. The largest number of the studies involved small numbers
p.000097: of participants and often were designed to determine whether or not a method for collecting
p.000097: exposure-related data or samples was feasible or burdensome. Most of the smaller studies used convenience samples.
p.000097: Studies, like DEARS, CTEPP, NHEXAS, and TEAM, which
p.000097: involved large numbers of participants, employed randomized or probability-based approaches
p.000097: for selecting participants.
p.000097: Table A-2 shows the types of samples that often have been collected in NERL’s observational human
p.000097: exposure studies. Some of the samples, like air concentrations or surface wipes, allow NERL staff
p.000097: to determine the concentration of the studied chemicals in the environmental media with which the participants
p.000097: may come into contact. Other items, like time activity diaries or videotaping children to measure the amount of
p.000097: hand-to-mouth activity, allow NERL researchers to understand how people may come into contact with the agent
p.000097: and to estimate the duration or frequency of a potential exposure. Still other measures, like personal
p.000097: samplers or biological samples, represent an attempt to determine a time-integrated measure of exposure. NERL
p.000097:
p.000097:
p.000098: 98
p.000098:
p.000098: staff put all of this information together to estimate an individual participant’s exposure,
p.000098: either through relatively direct measures of exposure or through algorithms that combine the
p.000098: media concentrations measurements and the activity data.
p.000098:
p.000098: References
p.000098: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000098: Subjects. U.S. Code of Federal Regulations.
p.000098: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/ 40cfr26_06.html [accessed 12 June 2007].
p.000098:
p.000098: NEAC (National Ethics Advisory Committee) (2006). Ethical Guidelines for Observational Studies: Observational research
p.000098: audits and related activities. Wellington, New
p.000098: Zealand: Ministry of Health. Available: http://www.neac.health.govt.nz/moh.nsf/indexcm/neac
p.000098: resources-publications-ethicalguidelines.
p.000098:
p.000098: U.S. EPA (U.S. Environmental Protection Agency) (1992), Guidelines for Exposure Assessment. Environmental Protection
...
p.000098: Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Medicine 4(10): e297.
p.000098: doi:10.1371/journal.pmed.0040297.
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000099: 99
p.000099:
p.000099: Table A-1. Examples of Observational Human Exposure Studies Conducted or Funded by NERL or Its Predecessor
p.000099: Organizations
p.000099: Study Date Size Type Brief Description
p.000099: NERL Role
p.000099: Total Exposure 1980-1984 400 Three-stage The TEAM study was designed to develop and
p.000099: demonstrate EPA designed and Assessment Households stratified
p.000099: methods to measure human exposure to toxic substances in run, contractor Methodology
p.000099: probability air and drinking water. The goals were to develop methods to conducted
p.000099:
p.000099: (TEAM) Studies
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: Additional TEAM Studies
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: Nonoccupationa l Pesticides Exposure Study (NOPES)
p.000099:
p.000099:
p.000099:
p.000099: Nine-Home Children’s Pilot Study
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: Particle Total Exposure Assessment Methodology (PTEAM) Study
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: National Human Activity Pattern Study (NHAPS)
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.001987: 1987
p.001987:
p.001987:
p.001987:
p.001987:
p.001987:
p.001987:
p.001987: 1986-1988
p.001987:
p.001987:
p.001987:
p.001987:
p.001987:
p.001990: 1990
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990: 1990
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990: 1992-1994
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990: 51 in LA area, 17 in NJ,
p.001990: and 75 in Baltimore
p.001990:
p.001990:
p.001990:
p.001990:
p.000259: 259
p.000259:
p.000259:
p.000259:
p.000259:
p.000259:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000178: 178
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: 9,386
p.000178: selection, cross- sectional
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Convenience sample
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Probability selection, mainly cross- sectional, partly longitudinal
p.000178:
p.000178: Convenience pilot study
p.000178: to test methodology
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Probability
p.000178:
p.000178:
...
p.000178: chemicals and to apply these methods within a probability- based sampling framework to estimate exposures and body
p.000178: burdens of urban populations in several U.S. cities. Air sampling measured personal exposure to airborne toxic
p.000178: chemicals in indoor air and in exhaled breath. Related objectives were to determine the relationships between personal,
p.000178: indoor, and outdoor, and blood, urine, and exhaled breath concentrations; determine the variability of VOC
p.000178: concentrations within a home; and determine seasonal and multiyear variability. The study was conducted in New Jersey,
p.000178: North Carolina, and North Dakota in three phases.
p.000178: A separate VOC TEAM study was carried out in Baltimore, MD: Baltimore lacks the petroleum and chemical manufacturing
p.000178: plants present in most of the previous TEAM study sites and is more representative of many U.S. cities. Focused studies
p.000178: were also conducted in New Jersey and Los Angeles to further explore the sources and factors contributing to personal
p.000178: VOC exposures identified in the earlier TEAM studies.
p.000178: First attempt to develop a methodology for measuring the potential exposure of the general population to common
p.000178: household pesticides using probability-based sampling; questionnaire data collection; and personal monitoring of air,
p.000178: drinking water, food, and dermal contact. Conducted in Jacksonville, FL, and Springfield and Chicopee, MA, to capture
p.000178: high- and low-pesticide-use areas, respectively.
p.000178: A 9-home pilot study was conducted to evaluate monitoring methods in the field that may be used to assess the potential
p.000178: exposures of children aged 6 months to 5 years to pesticides found in the home environment. Newly developed methods
p.000178: were tested for measuring pesticide residues in indoor air, carpet dust, outdoor soil, and on children's hands.
p.000178: Information also was collected on household characteristics, pesticides used and stored at the residence, and
p.000178: children's activities.
p.000178: A study of nonsmokers age 10 years and older in Riverside, CA, in which indoor, outdoor, and personal monitoring of
p.000178: integrated particle mass over 12-hour day and night periods was conducted for PM10 and PM2.5. Polycyclic aromatic
p.000178: hydrocarbon and phthalate measurements were collected indoors and outdoors at a subset of 125 homes. A separate
p.000178: monitoring site provided ongoing 12-hour measurements of ambient particles throughout the study (48 days). Reference
p.000178: PM10 and dichotomous samplers were used at this site in addition to personal and stationary monitors identical to those
p.000178: used for participant monitoring. Nighttime and daytime recall time-activity questionnaires, as well as household
p.000178: questionnaires, were administered to each selected subject and household, respectively, and meteorological and air
p.000178: exchange rate data were recorded for each monitored home.
p.000178: This survey collected 24-hour activity diaries and other questionnaire data from participants from 48 states. It was
p.000178: conducted as a next-day telephone recall interview.
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
...
p.000100: cross- is the largest, most comprehensive study of agricultural health sectional ever conducted
p.000100: in the United States. The interagency exposure study. assessment study (Pesticide Exposure Study (PES)),
p.000100: led by
p.000100: NERL, was performed to assess exposures and exposure
p.000100: classification procedures used in the epidemiological study.
p.000100: The National 1995-1998 See specifics A Federal interagency research effort
p.000100: coordinated by EPA and EPA oversaw Human in entries
p.000100: consisting of four demonstration studies using probability- general design for Exposure
p.000100: below. based sampling designs conducted in partnership
p.000100: with other the research, then Assessment
p.000100: Federal agencies (CDC, FDA, and NIST), universities, and solicited, evaluated
p.000100: Survey research
p.000100: institutions. Household environmental and personal and funded the
p.000100: (NHEXAS)— samples were collected and
p.000100: questionnaires were administered. individual studies
p.000100:
p.000100: Overview
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: NHEXAS-
p.000100: Arizona
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: NHEXAS-
p.000100: Maryland
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: NHEXAS-
p.000100: Region 5
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: Minnesota Children’s Pesticide Exposure Study (MNCPES)
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 1995-1998
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 1995-1996
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 1995-1997
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.001997: 1997
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.000179: 179
p.000179: Households
p.000179:
p.000179:
p.000179:
p.000179:
p.000080: 80
p.000080: Households
p.000080:
p.000080:
p.000080:
p.000080:
p.000080:
p.000250: 250
p.000250: Households
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: 102 Children
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: Probability, cross- sectional
p.000250:
p.000250:
p.000250:
p.000250: Probability, longitudinal
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: Probability, cross- sectional
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: Probability, cross- sectional
p.000250: Biological media, including blood and urine, also were sampled and monitored for parent contaminants or their
p.000250: metabolites.
p.000250: The studies were undertaken to evaluate total human exposure to multiple chemicals on a community and regional scale
p.000250: with the following aims: provide a baseline of the normal range of exposure to chemicals in the general population;
p.000250: identify subgroups of the general population that are likely to be highly exposed; and evaluate and improve the
p.000250: accuracy of models developed to predict exposure to chemicals.
p.000250: The NHEXAS-Arizona study sampled residences determined by a population-based probability research design for the total
p.000250: population of Arizona and measured metals, pesticides, and volatile organic compounds (VOCs). The study was conducted
p.000250: by a consortium composed of the University of Arizona, Battelle Columbus, and the Illinois Institute of Technology.
p.000250: The study sampled residences of Baltimore and four adjacent counties and measured metals, pesticides, and polycyclic
p.000250: aromatic hydrocarbons (PAHs). Data collection occurred up to 6 times over 1 year for each of the participating
p.000250: households. The study was conducted by Harvard University, Emory University, Johns Hopkins University, and Westat. The
p.000250: study investigated temporal variability in multimedia, multipollutant exposures.
p.000250: The Region 5 study was conducted in EPA's Region 5 (Ohio, Michigan, Illinois, Indiana, Wisconsin, and Minnesota), and
p.000250: included personal exposure, residential concentration, and biomarker measurements of metals and VOCs. The study was
p.000250: conducted by the Research Triangle Institute (RTI) and the Environmental and Occupational Health Sciences Institute
p.000250: (EOHSI).
p.000250: Multimedia study of children 3-13 years conducted in Minnesota to evaluate children's pesticide exposure in urban and
p.000250: rural areas. The study provides exposure, environmental, and biologic data relating to multipathway exposures of
p.000250: children for four primary pesticides (chlorpyrifos, malathion, diazinon, and atrazine), 14 secondary pesticides, and 13
p.000250: polynuclear aromatic hydrocarbons (PAHs). This study complements and extends the populations and chemicals included in
p.000250: the NHEXAS-Region 5 study.
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000101: 101
p.000101: (see below).
p.000101:
p.000101: Details of research were established by recipients.
p.000101:
p.000101:
p.000101:
p.000101: Designed and conducted by award recipient (see above).
p.000101:
p.000101:
p.000101: Designed and conducted by award recipient (see above).
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: Designed and conducted by award recipient (see above).
p.000101:
p.000101:
p.000101:
p.000101: Designed and conducted by award recipient (see above).
p.000101:
p.000101: Table A-1. (Continued)
p.000101: Study Date Size Type Brief Description
p.000101: NERL Role
p.000101: Particulate 1998-2001 200 Longitudinal A series of longitudinal studies in a
p.000101: number of U.S. cities NERL conducted Matter (PM) Individuals
p.000101: conducted by EPA or by organizations sponsored through the one panel study
p.000101:
p.000101: Panel Studies
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: Dietary Intake of Young Children (DIYC)
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: Children’s Pesticide Post- Application Exposure Study (CPPAES)
p.000101:
p.000101:
p.000101:
p.000101: Develop Risk Assessment and Define Some Risk Management Options for Exposure of Children to Toxic Mold Using
p.000101: Stachybotrys chartarum as an Example
p.000101: Children’s Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP)
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: Car-Related Occupational PM and Air Toxics Exposure to Patrolmen Study (COPP)
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: 1999-2000
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: 1999-2001
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.002000: 2000
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000: 2000-2001
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002001: 2001
p.002001: (5 to 63 per study)
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 3 Homes
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 10 Homes
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 8 cases and
p.002001: 8 controls
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.000257: 257
p.000257: Households
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience, multiday pilot study to test methodology
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Case control study
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Randomized, cross- sectional
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience, longitudinal
p.000009: National Exposure Research Laboratory (NERL). A primary goal was to determine the relationships between personal
p.000009: exposures to particles and associated gases relative to stationary outdoor monitor concentrations in high-risk
p.000009: subpopulations and to identify human activity patterns that might contribute to personal exposure. The investigators
p.000009: varied study locations, monitoring seasons, and study populations.
p.000009: Susceptible subpopulations of interest included chronic obstructive pulmonary disease (COPD) patients, individuals with
p.000009: cardiovascular disease, the elderly, asthmatics, and African Americans with hypertension. Panels of healthy individuals
p.000009: also were included. Because the elderly is the subpopulation most sensitive to health effects associated with PM
p.000009: exposures, the majority of subjects were over age 65.
p.000009: Performed in the Raleigh, NC, area in homes with children 1 to 3 years old. Homeowners reported either professional or
p.000009: self applications of diazinon. Goals of the study were to evaluate methods to measure excess dietary exposures
p.000009: resulting from food-handling activities by young children during eating and to assess whether the Children’s Dietary
p.000009: Intake Model (CDIM) accurately represents total dietary exposures of children. Study resulted in refinements of model
p.000009: parameters for transfer and activity.
p.000009: Observational measurement study of exposure to chlorpyrifos among children 2-5 years of age in urban New Jersey homes
p.000009: following crack and crevice treatment by a professional applicator. Study investigated decay of pesticide levels over
p.000009: time, transfer of pesticide from microenvironmental media to child, and factors that affect transfer. Dermal transfer
p.000009: evaluated with surface wipes, hand wipes, dermal wipes, cotton garments, and videotaping.
p.000009: Physicians at Case-Western Reserve treating children with idiopathic pulmonary hemorrhage evaluated the nature of the
p.000009: fungus found in homes of the afflicted and control children to determine if Stachybotrys was a potential factor in the
p.000009: illness. Three of the 8 cases, and none of the controls, had Stachybotrys strains that potentially were implicated.
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: The largest children’s exposure study undertaken to date. It examines aggregate exposures of children 18 months to 5
p.000009: years to pollutants commonly found in everyday environments. The major objectives were to quantify children’s aggregate
p.000009: exposures, apportion exposure pathways, and identify important exposure media. Participants were recruited from 12
p.000009: urban and rural counties in North Carolina and Ohio using a random digit dialing method. Monitoring was performed at
p.000009: both daycare centers and homes. Samples collected include food, beverages, indoor air, outdoor air, hand wipes, dust,
p.000009: soil, transferable residues, floor and surface wipes, and urine. The samples were analyzed for more than 40 pollutants,
p.000009: including insecticides, phthalate esters, phenols, polychlorinated biphenyls, and PAHs.
p.000009: Scientists monitored air pollutants inside and outside vehicles of healthy highway patrol officers in North Carolina
p.000009: while troopers were on patrol for 9-hour shifts and examined cardiovascular effects. The findings indicated that people
p.000009: driving in motor vehicles are exposed to PM2.5 and other pollutants generated from motor vehicles, and that these
p.000009: exposures appear to cause cardiovascular changes.
p.000009:
p.000009:
p.000102: 102
p.000102: with contractor support; funded and collaborated on others with Harvard School of Public Health, University. of
p.000102: Washington, and NYU.
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL designed, contractor conducted
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL funded the Environmental and Occupational Health Sciences Institute (EOHSI).
p.000102:
p.000102:
p.000102:
p.000102: NERL staff collaborated with Case-Western Reserve University by conducting lab analysis for Stachybotrys.
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL designed, contractor conducted
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: EPA designed and conducted with contractor support
p.000102:
p.000102: Table A-1. (Continued)
p.000102: Study Date Size Type Brief Description
p.000102: NERL Role
p.000102: First National 2001 168 Child care Probability- A collaborative study with the Department
p.000102: of Housing and HUD and CPSC Environmental centers based
p.000102: Urban Development (HUD) and the Consumer Product Safety study. NERL Health Survey of
p.000102: selection on Commission (CPSC) of pesticide use and young children’s collaborated
p.000102: and
p.000102: Child Care national scale (less than 6 years old)
p.000102: potential exposure to pesticides and conducted analysis
p.000102:
p.000102: Centers (CCC)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: A Pilot Study Examining Translocation Pathways Following a Granular Application of Diazinon to Residential Lawns (PET)
p.000102: Biological and Environmental Monitoring for Organo- phosphate and Pyrethroid Pesticide Exposures in Children Living in
p.000102: Jacksonville, FL (JAX)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: Exposure Assessment for Community- Acquired Legionnaires Disease
p.000102: Center for the Health Assessment of Mothers and Children of Salinas Quantitative Exposure Assessment Study (CHAMACOS)
p.000102: Feasibility of Macroactivity Approach To Assess Dermal Exposure (Daycare)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 2002
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 6 Households
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 9 Households in NERL exposure component
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 20 Children
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 9 Daycare centers
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience, multiday pilot study to test methodology for exposure measure- ments
p.000021:
p.000021:
p.000021:
p.000021: Convenience, cross- sectional
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Case-control
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience
p.000021: other pollutants in institutional childcare centers. This national study used multistage sampling with clustering.
p.000021: Indoor wipe and outdoor soil samples were analyzed for pesticides, lead, and allergens (mold/fungi). Pesticide use
p.000021: practices and application information were obtained from the commercial pest control applicators serving the centers.
p.000021: Observational pilot exposure measurement study of residential exposures after homeowner had routinely applied granular
p.000021: formulation diazinon-containing turf treatment to residential lawns. Study was performed near Raleigh, NC, and was
p.000021: preceded by a 1-home methodology feasibility study. Purpose was to evaluate methods for assessing pet-borne transfer,
p.000021: translocation and exposure pathways, and decay rates.
p.000021:
p.000021:
p.000021:
p.000021: The objectives of this investigation in Jacksonville, FL, were to
p.000021: (1) assess organophosphate (OP) and pyrethroid pesticide exposures in a group of 4- to 6-year-old children from
p.000021: Jacksonville by measuring the urine metabolite levels,
p.000021: (2) identify possible sources of these pesticides through screening measurements and pesticide inventories, and
p.000021: (3) examine the relationship between environmental and biological levels. The Duval County Health Department (DCHD)
p.000021: collected urine samples for CDC from 200 children visiting six public health clinics in Jacksonville, and collected
p.000021: environmental screening samples at approximately 25% of these children’s homes. A detailed aggregate exposure
p.000021: assessment at 9 homes was overseen by NERL and involved collection of surface wipes, transferable residues, air,
p.000021: duplicate diet, cotton garment samples, and urine samples. A time- activity diary of the children’s activities was
p.000021: included.
p.000021: Work with Veteran’s Administration hospital staff. Cases of Legionnaires Disease were evaluated for potential for
p.000021: exposure from residential drinking water taps. In about 24% of the tested cases, homes were found to have Legionella
p.000021: bacteria in water taps at home, compared to their absence in other cases and in controls
p.000021: Incidental pesticide exposure measurement study of farmworkers’ children ages 5 to 35 mo. Purpose is the evaluation of
p.000021: methods for aggregate exposure measurements and the evaluation of pathways of exposure and important factors that
p.000021: affect exposure. Measurements include pesticide distributions in microenvironments where children spend time, transfer
p.000021: of pesticides from microenvironmental media to child, and factors that affect transfer.
p.000021:
p.000021:
p.000021:
p.000021: Study identified daycare centers with previously established contracts for routine monthly pesticide applications and
p.000021: conducted screening sampling in each to evaluate the distributions of transferable pesticide residues on floor surfaces
p.000021: where children spend time. One daycare was selected for intensive measurements, and children from different age groups
p.000021: volunteered to wear full-body cotton suits for short time periods while their activities were videotaped.
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000103: 103
p.000103: of molds/fungi and helped with lead and pesticide measurements.
p.000103:
p.000103:
p.000103: EPA conducted with contractor support
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: Multiagency effort; NERL was a participant and led the 9-home exposure component.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL funded IAG with VA to conduct study.
p.000103:
p.000103:
p.000103:
p.000103: EPA grant to UC Berkeley; NERL augmented the existing research effort.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL designed, contractor conducted
p.000103:
p.000103: Table A-1. (Continued)
p.000103: Study Date Size Type Brief Description
p.000103: NERL Role
p.000103: Tampa 2002 9 Residences Convenience Pilot study on methods for measuring personal,
p.000103: indoor NERL designed, Asthmatic sample,
p.000103: pilot residential, outdoor residential, and ambient combustion- contractor
p.000103: Children's Study study to test related products, particulate
p.000103: matter, and air toxics. The study conducted
p.000103: (TACS) methods. identified microenvironmental
p.000103: factors affecting penetration of pollutants into homes and reduction of exposures to pollutants for asthmatic children
p.000103: (0-5 years of age).
p.000103:
p.000103: Pilot Study To Evaluate Data Collection Methods for Young Children’s and Household Activities
p.000103: Detroit Exposure and Aerosol Research Study (DEARS)
p.000103:
p.000103:
p.000103:
p.000103: Accelerometer Pilot Study
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: Pilot Study of Waterborne Infections
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004: 2004-2007
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002005: 2005
p.002005: 3 Homes
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.000150: 150
p.000150:
p.000150:
p.000150:
p.000150:
p.000150:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.001296: 1296
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Randomized household selection with qualification criteria; longitudinal
p.001296:
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Convenience, all volunteers from community using public water supply
p.001296: Pilot aggregate exposure study of three homes to assess burden of alternative exposure sample collection methods.
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Recruitment from seven distinct neighborhoods in Detroit required strong community relations and partnership with State
p.001296: and local organizations. This study monitored for air pollutants at the personal level and evaluates how well centrally
p.001296: located (ambient) monitors represent exposure at the residential and personal level. Sampling is for 5 days duration in
p.001296: summer and again in winter.
p.001296: Nine children <24 months old and their primary caregivers participated in this study to (a) determine if very young
p.001296: children will wear an accelerometer for relatively long periods of time and comply with the protocol for its use, (b)
p.001296: evaluate how well a caregiver can estimate the activity level of his/her infant or toddler when completing an
p.001296: exposure-oriented time-activity diary, and (c) compare accelerometer count output with caregiver-provided estimates of
p.001296: children's activity level.
p.001296: Measure antibodies in people’s saliva for antibodies to Cryptosporidium, Noroviruses, Rotaviruses, Helicobacter pylori,
p.001296: and Toxoplasma gondii before and after installation of an ultraviolet treatment system for a public water supply. Also
p.001296: served as test of methodology for detecting people’s prior exposure to infectious agents.
p.001296: NERL designed, contractor conducted
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: NERL designed and run; with contractor support and collaborators such as the University of Michigan
p.001296: NERL designed and run, with contractor support
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: EPA planned research (NERL is a collaborator), contractor conducted
p.001296:
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p.000104: 104
p.000104:
p.000104: Table A-2. Types of Samples Collected in NERL Observational Human Exposure Studies
p.000104: Samples or Data Exposure Concern and Typical Type of Analysis
p.000104: Environmental Media
p.000104: Air pollutants Air pollutants being inhaled. Collect samples from central site, outside
p.000104: residence, and inside residence to assess
p.000104: pollutants in various locales. Measure gaseous and particle-bound pollutants.
p.000104: Soil Estimate track in and subsequent dermal or inhalation contact. Analyze for
p.000104: metals, pesticides, etc.
p.000104: House dust Dust from carpets and floors that may result in dermal contact or reentrainment
p.000104: and inhalation. Analyze for pesticides, metals, and tracers of outdoor sources.
p.000104: Surface wipes Dermal contact, children’s hand to mouth, and contact with food and subsequent
p.000104: ingestion. Analyze for metals and pesticides. Examine eating and food preparation areas too.
p.000104: Transferable residues Similar to surface wipes, using a surrogate for the transfer from the surface to the
p.000104: skin.
p.000104: Duplicate diet Use to assess ingestion exposures from food. Exact duplicate of amount and items
p.000104: eaten by participant and analyzed for pesticides, metals, etc. Includes drinking water samples as part of diet or other
p.000104: beverages consumed.
p.000104: Handled food Finger foods like cheese or luncheon meets that have been prepared and processed
p.000104: identically to foods children might eat to evaluate how much pollution may be removed from surfaces and ingested with
p.000104: the food.
p.000104: Human Activity Data
p.000104: Time-activity diaries Recall diaries to account for all times and activities in a day. Information
p.000104: includes location and activities.
p.000104: Activity loggers Device used to assess the nature of a person’s activities. Portable
p.000104: nephelometers have been used to keep up with people’s activities by showing when they were near PM sources.
p.000104: Accelerometers to measure level of activity of children at play. GIS and inertial devices to try to measure locations
p.000104: as a function of time of day.
p.000104: Questionnaires Query participants about things like daily activities for themselves or their
p.000104: children; housing characteristics; participant characteristics, including occupation, diet, smoking habits, hobbies,
p.000104: etc.; and recent use of pesticides or other consumer products.
p.000104: Videotaping Use videos to measure frequency and duration of mouthing activities in children.
p.000104: Household inventories Inventory consumer products in house. Use items to ask about usage frequency and
p.000104: history.
p.000104: Researcher observations Information about open doors and windows (air exchange), heating and cooking sources,
p.000104: pets, and other activities that may lead to potential exposures may be observed.
p.000104: Personal or Biological Samples
p.000104: Urine Urinary excretion of pollutants and their contaminants give important
p.000104: information about the nature of prior exposures and their magnitude.
p.000104: Personal air monitors Individual wears samplers on his/her person while going about normal activities to
p.000104: measure pollutants in breathing zone of individual.
p.000104: Hand wipes Hand wipes remove contaminants from skin surface. Analyze for pesticides, metals,
p.000104: organic chemicals, and use values to estimate dermal exposure and hand-to-mouth ingestion of pollutants.
p.000104: Dermal surrogates Participant may wear cotton garments or socks as a collector. Clothing is analyzed
p.000104: for pesticides, metals, organic chemicals, etc. Measured contaminant quantities are used to estimate potential for
p.000104: dermal exposure.
p.000104: Saliva samples Test for antibodies to infectious agents, suggesting prior exposure and infection
p.000104: by microbial agent. Blood Some epidemiological studies that NERL scientists have
p.000104: collaborated on have collected blood samples.
p.000104:
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p.000104:
p.000105: 105
p.000105:
p.000105:
...
p.000105: a. Identify the major scientific and ethical areas/issues in the design and
p.000105: implementation of observational human exposure measurement studies that should be considered for inclusion
p.000105: in the document.
p.000105: b. Identify specific elements in each of these major areas that should be considered for inclusion in
p.000105: the document.
p.000105: c. Provide recommendations on the type and level of information that should be considered for
p.000105: inclusion in the document when describing state-of-the-science approaches, methods,
p.000105: techniques, or standards.
p.000105: d. Provide recommendations on the criteria that should be considered when evaluating and identifying
p.000105: the state-of-the-science for
p.000105: the approaches, methods, techniques, or standards.
p.000105: 2. Provide recommendations and listings of sources of information for developing the document including
p.000105: case studies where available.
p.000105: 3. Identify at least ten specific elements of the design and implementation of these studies that the
p.000105: panel considers to have the most uncertainty with regard to the “state-of-the-science,” discuss these elements, and
p.000105: provide recommendations on state-of-the-science approaches for them.
p.000105:
p.000105: The following individuals were members of the Expert Panel.
p.000105:
p.000105: Timothy Buckley (Chair)
p.000105: Division of Environmental Health Sciences School of Public Health
p.000105: Ohio State University Columbus, OH
p.000105:
p.000105: Sophie Balk
p.000105: Attending Pediatrician
p.000105: Children’s Hospital at Montefiore Professor of Clinical Pediatrics Albert Einstein College of Medicine Bronx, NY
p.000105:
p.000105: David Carpenter
p.000105: Director, Institute of Health and Environment University of Albany, SUNY
p.000105: Rensselaer, NY
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000107: 107
p.000107:
p.000107: Giselle Corbie-Smith Department of Social Medicine University of North Carolina Chapel Hill, NC
p.000107:
p.000107: Alan Fleischman
p.000107: Senior Advisor
p.000107: The New York Academy of Medicine New York, NY
p.000107:
p.000107: Natalie Freeman
p.000107: Center for Environmental and Human Toxicology Department of Physiological Sciences
p.000107: University of Florida Gainesville, FL
p.000107:
p.000107: Loretta Jones
p.000107: Healthy African American Families Los Angeles, CA
p.000107:
p.000107: Bruce Lanphear
p.000107: Professor of Pediatrics and of Environmental Health Division of General and Community Pediatrics Cincinnati Children’s
p.000107: Hospital Medical Center Cincinnati, OH
p.000107:
p.000107: Michael Lebowitz
p.000107: Arizona Health Sciences Center Colleges of Public Health and Medicine University of Arizona
p.000107: Tucson, AZ
p.000107:
p.000107: Jerry Menikoff
p.000107: Department of History and Philosophy of Medicine University of Kansas Medical Center
p.000107: Kansas City, KS
p.000107:
p.000107: Rebecca Parkin
p.000107: Associate Dean for Research and Public Health Practice Professor of Environmental and Occupational Health School of
p.000107: Public Health and Health Service
p.000107: George Washington University Medical Center Washington, DC
p.000107: Review by the EPA Human Studies Review Board and Public Comment
p.000107: The process for developing this document included the following steps after the Expert Panel Workshop.
p.000107: • A draft document was written by NERL researchers.
p.000107: • The draft document was distributed to internal EPA staff for review and comment (see Acknowledgements for the
p.000107: list of reviewers).
p.000107: • The draft document was revised to address internal reviewer comments; an external review draft
p.000107: document was prepared.
p.000107: • The availability of the external review draft document for public comment was announced in a Federal Register
p.000107: notice.
p.000107: • An EPA docket was opened, and the external review draft document was available for public comment for 45 days.
p.000107: • The external review draft document also was provided to EPA’s Human Studies Review Board (HSRB) for review
p.000107: and comment (see http://www.epa.gov/osa/hsrb/ for information on the
p.000107: HSRB).
...
p.000112: Recommendation 12: Document and publish “best practices” from efforts to reengineer the clinical research
p.000112: enterprise as soon as the NIH begins to see results, so that progress in improving public trust in medical research
p.000112: grows rapidly and steadily.
p.000112:
p.000112: Source: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for
p.000112: the NIH Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health,
p.000112: Director’s Council of Public Representatives, January 14, 2005. Available:
p.000112: http://copr.nih.gov/reports/public_trust.asp [accessed 12 June 2007].
p.000112:
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p.000113: 113
p.000113:
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p.000113:
p.000113:
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p.000113:
p.000113: Appendix E
p.000113: List of Acronyms and Abbreviations
p.000113:
p.000113:
p.000113: AAP American Academy of Pediatrics
p.000113: ACGIH American Conference of Governmental Industrial Hygienists AHS Agricultural Health
p.000113: Study
p.000113: ATSDR Agency for Toxic Substances and Disease Registry BEI biological exposure index
p.000113: CAB community advisory board
p.000113: CBPR community-based participatory research CDC Centers for Disease Control and
p.000113: Prevention CFR Code of Federal Regulations
p.000113: CIOMS Council for International Organizations of Medical Sciences
p.000113: COPR National Institutes of Health Director’s Council of Public Representatives CPSC
p.000113: Consumer Product Safety Commission
p.000113: CTEPP Children’s Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants
p.000113: DEARS Detroit Exposure and Aerosol Research Study DHEW U.S. Department of Health, Education,
p.000113: and Welfare DMOC data monitoring and oversight committee
p.000113: DNA deoxyribonucleic acid
p.000113: DSMB data safety monitoring board DSMP data and safety monitoring plan
p.000113: EHCRB environmental health and community review board EPA U.S. Environmental Protection
p.000113: Agency
p.000113: ERG Eastern Research Group
p.000113: FCN Federal Communicators Network
p.000113: FDA Food and Drug Administration
p.000113: HHS U.S. Department of Health and Human Services HSRB Human Studies Review Board
p.000113: HSRRO Human Subjects Research Review Official
p.000113: HUD U.S. Department of Housing and Urban Development ICR information collection
p.000113: request
p.000113: IOM Institute of Medicine
p.000113: IRB institutional review board
p.000113: NAS National Academy of Sciences
p.000113: NBAC National Bioethics Advisory Commission NCI National Cancer Institute
p.000113: NCS National Children’s Study
p.000113: NEI National Eye Institute
p.000113: NEJAC National Environmental Justice Advisory Council NERL National Exposure Research
p.000113: Laboratory
p.000113:
p.000113:
p.000115: 115
p.000115:
p.000115: NGO Nongovernmental organization
p.000115: NHANES National Health and Nutrition Examination Survey NHAPS National Human Activity Pattern
p.000115: Study
p.000115: NHEXAS The National Human Exposure Assessment Survey NHLBI National Heart, Lung, and Blood
p.000115: Institute
p.000115: NHRPAC National Human Research Protections Advisory Committee NIH National Institutes of
p.000115: Health
p.000115: NRC National Research Council
p.000115: OHRP Office for Human Research Protections OMB Office of Management and Budget OSMB
p.000115: observational study monitoring board PM particulate matter
p.000115: Q&As questions and answers
p.000115: QAPP quality assurance project plan
p.000115: RfD reference dose
p.000115: SEAOES Scientific and Ethical Approaches for Observational Exposure Studies TEAL Tribal
p.000115: Efforts Against Lead
p.000115: TEAM Total Exposure Assessment Methodology TLV threshold limit value
p.000115: VOC volatile organic compound
p.000115: WHO World Health Organization
p.000115:
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...
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
p.000117:
p.000118: 118
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p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118: United States Environmental Protection Agency
p.000118:
p.000118:
p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
...
Social / Elderly
Searching for indicator elderly:
(return to top)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
...
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
p.000038: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000038:
...
p.000089: chemical analyses can be performed relatively quickly to reduce such exposures as quickly as possible.
p.000089: The second, and more difficult, step in developing the reporting protocol is to determine the
p.000089: level of concern that triggers reporting of the concentration to the study participant. For some environmental
p.000089: media, such as drinking water, EPA (2007) has established maximum contaminant levels that can be used as
p.000089: triggers for reporting. For example, if the researcher measures a level of arsenic in drinking water above
p.000089: 0.010 mg/L, he or she would be expected to report the level to the study participant. For other environmental media,
p.000089: such as air, there are few applicable standards. The National Ambient Air Quality Standards might be
p.000089: used for the criteria pollutants. Guidelines for occupational exposures, such as threshold limit
p.000089: values (TLVs) and biological exposure indices (BEIs) published by the
p.000089:
p.000089:
p.000090: 90
p.000090:
p.000090: American Conference of Governmental Industrial Hygienists (ACGIH, 2008) also may be used. TLVs are not
p.000090: standards; ACGIH formulates a conclusion on the level of exposure that the typical worker can experience without
p.000090: adverse health effects. Many people would argue that the TLVs are not conservative enough for the average
p.000090: population, particularly not for vulnerable lifestages (e.g., children, the elderly) and TLVs are only for
p.000090: exposure by inhalation. WHO (2005) also publishes air quality guidelines. These types of guidelines can be used to
p.000090: advise study participants if their exposures are high relative to the guidelines. Reporting levels should
p.000090: be conservative, but not so low that reporting the level to the participant causes unwarranted concern and
p.000090: stress. For other environmental media measured in observational human exposure studies, such
p.000090: as house dust or surface wipes, the measurement results cannot be used easily to estimate exposures, and they
p.000090: are a poor metric if used alone.
p.000090: An alternative approach to comparison of measurement results against available guidelines and
p.000090: standards is the comparison of measurements in biological fluids to measurement data available from the
p.000090: National Health and Nutrition Examination Survey (NHANES). For example, results of measurements of
p.000090: chemicals or their metabolites in urine or blood can be compared to different percentiles (e.g., the
p.000090: 95th) reported in the NHANES national reports (CDC, 2005). This type of comparison shows that the participant’s
p.000090: measurements are at the high end of the distribution of the NHANES data, suggesting that action may need to be
p.000090: taken to mitigate exposures. However, researchers need to be judicious in the selection of the exposure
p.000090: metric. Biomarkers in blood and biomarkers in urine can be very different exposure metrics and may represent
p.000090: different aspects of the exposure event. A similar approach could be taken with
...
p.002001: 3 Homes
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 10 Homes
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 8 cases and
p.002001: 8 controls
p.002001:
p.002001:
p.002001:
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p.002001:
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p.002001:
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p.002001:
p.000257: 257
p.000257: Households
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p.000257:
p.000009: 9
p.000009:
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p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience, multiday pilot study to test methodology
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Case control study
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Randomized, cross- sectional
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience, longitudinal
p.000009: National Exposure Research Laboratory (NERL). A primary goal was to determine the relationships between personal
p.000009: exposures to particles and associated gases relative to stationary outdoor monitor concentrations in high-risk
p.000009: subpopulations and to identify human activity patterns that might contribute to personal exposure. The investigators
p.000009: varied study locations, monitoring seasons, and study populations.
p.000009: Susceptible subpopulations of interest included chronic obstructive pulmonary disease (COPD) patients, individuals with
p.000009: cardiovascular disease, the elderly, asthmatics, and African Americans with hypertension. Panels of healthy individuals
p.000009: also were included. Because the elderly is the subpopulation most sensitive to health effects associated with PM
p.000009: exposures, the majority of subjects were over age 65.
p.000009: Performed in the Raleigh, NC, area in homes with children 1 to 3 years old. Homeowners reported either professional or
p.000009: self applications of diazinon. Goals of the study were to evaluate methods to measure excess dietary exposures
p.000009: resulting from food-handling activities by young children during eating and to assess whether the Children’s Dietary
p.000009: Intake Model (CDIM) accurately represents total dietary exposures of children. Study resulted in refinements of model
p.000009: parameters for transfer and activity.
p.000009: Observational measurement study of exposure to chlorpyrifos among children 2-5 years of age in urban New Jersey homes
p.000009: following crack and crevice treatment by a professional applicator. Study investigated decay of pesticide levels over
p.000009: time, transfer of pesticide from microenvironmental media to child, and factors that affect transfer. Dermal transfer
p.000009: evaluated with surface wipes, hand wipes, dermal wipes, cotton garments, and videotaping.
p.000009: Physicians at Case-Western Reserve treating children with idiopathic pulmonary hemorrhage evaluated the nature of the
...
Social / Ethnicity
Searching for indicator ethnic:
(return to top)
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
...
p.000070: members) or more narrowly (as the population from which study participants are selected). For observational
p.000070: field studies, the Expert Panel from the workshop suggested the narrow definition. A narrow
p.000070: definition allows social and cultural factors to be included but excludes government agencies, industry, and
p.000070: others who do not necessarily represent the interests of the participants (ERG, 2007).
p.000070: Central to the definition of a community is a sense of “who is included and who is excluded from
p.000070: membership” (NRC & IOM, 2005). A person may be a member of a community by choice, as with voluntary
p.000070: associations, or by virtue of their innate personal characteristics, such as age, gender, race, or
p.000070: ethnicity (NRC & IOM, 2005). As a result, individuals may belong to multiple communities at any one time. When
p.000070: initiating community engagement efforts, one should be aware of these complex associations in deciding which
p.000070: individuals to work with in the targeted community.
p.000070: Quandt et al. (2001) discuss a CBPR research project, Preventing Agricultural Chemical Exposure in
p.000070: North Carolina Farmworkers, where the process of defining a community was complicated by language,
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
p.000070: sense of community was nurtured among the farmworkers collectively (O’Fallon and Dearry, 2002).
p.000070: Understanding and describing a community (CDC, 1997) involves exploring factors related to
p.000070: • people (including socioeconomics and demographics, health status, and cultural and ethnic characteristics),
p.000070: • location (geographic boundaries),
p.000070: • commonalities (including shared values, interests, and motivating forces), and
p.000070: • power relationships (including formal and informal lines of authority and influence, stakeholder relationships, and
p.000070: resource flows).
p.000070: It is important to distinguish between stakeholders and the community, but both should be engaged at some point
p.000070: in the course of a study. Stakeholders are groups or organizations that may affect, be affected by, or perceive
p.000070: themselves to be affected by a decision or activity. Stakeholders may have a direct or indirect interest in the
p.000070: “matter” of interest. They may include individuals; environmental, social, or community
p.000070: nongovernment organizations (NGOs); government entities; businesses; and industry. Stakeholders include
p.000070: business, industry, and various levels of government. A critical difference between the community and
p.000070: stakeholders is that the community has a right to speak for its own interests, but stakeholders cannot
p.000070: represent or speak for the community. Although relationships with stakeholders can, at times, be
p.000070: confrontational, stakeholders often provide useful information and expertise. When stakeholders
p.000070: and the community members overlap in particular individuals, it is important to distinguish the role in
p.000070: which the individual is acting (ERG, 2007).
p.000070:
p.000070: 6.2.2 Identifying Who Represents the Community
p.000070: To sufficiently represent the community, an individual has to have not only the right to speak for the
...
Searching for indicator ethnicity:
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p.000070: community involvement. The Expert Panel that was convened to advise NERL about scientific and ethical
p.000070: issues in observational human exposure studies discussed a number of challenges (ERG, 2007). The topics
p.000070: that the expert panel identified as issues are discussed below.
p.000070:
p.000070: 6.2.1 Defining “Community”
p.000070: “Community” refers to a group of people united by a shared attribute, and the attributes can be wide-ranging, such as
p.000070: geography, culture, social characteristics, values, interests, traditions, or experiences (ERG, 2007).
p.000070: Community can be defined broadly (as a system of interrelated groups operating to meet the needs of its
p.000070: members) or more narrowly (as the population from which study participants are selected). For observational
p.000070: field studies, the Expert Panel from the workshop suggested the narrow definition. A narrow
p.000070: definition allows social and cultural factors to be included but excludes government agencies, industry, and
p.000070: others who do not necessarily represent the interests of the participants (ERG, 2007).
p.000070: Central to the definition of a community is a sense of “who is included and who is excluded from
p.000070: membership” (NRC & IOM, 2005). A person may be a member of a community by choice, as with voluntary
p.000070: associations, or by virtue of their innate personal characteristics, such as age, gender, race, or
p.000070: ethnicity (NRC & IOM, 2005). As a result, individuals may belong to multiple communities at any one time. When
p.000070: initiating community engagement efforts, one should be aware of these complex associations in deciding which
p.000070: individuals to work with in the targeted community.
p.000070: Quandt et al. (2001) discuss a CBPR research project, Preventing Agricultural Chemical Exposure in
p.000070: North Carolina Farmworkers, where the process of defining a community was complicated by language,
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
p.000070: sense of community was nurtured among the farmworkers collectively (O’Fallon and Dearry, 2002).
p.000070: Understanding and describing a community (CDC, 1997) involves exploring factors related to
...
p.000072: 2002). The symbols, metaphors, visuals (including clothing, jewelry, and hairstyles), types of
p.000072: actors, language, and music used in communication materials all convey culture. Discussions with
p.000072: community members can assist researchers in identifying messages and images that resonate across groups or
p.000072: suggesting situations in which different messages or images are likely to work best.
p.000072: As discussed above and in Sections 5 and 7, communication materials must be tailored for each
p.000072: individual community and must be written in a language and at a reading level that will ensure comprehension.
p.000072: Many IRBs require materials to be prepared at a 5th grade reading level. Researchers should evaluate the
p.000072: reading level of all data collection instruments and study communication materials and should objectively
p.000072: measure comprehension in pretests prior to use in the study. Similarly, if translations of materials are
p.000072: required, certified translating services should be used to ensure accuracy and comprehension.
p.000072:
p.000072: 6.2.5 Recognizing and Addressing Cultural Differences
p.000072: Building and maintaining appropriate community and stakeholder relationships requires acknowledgment of the
p.000072: diversity within communities with regard to many factors, including, but not limited to, race/ethnicity,
p.000072: religious beliefs, heritage, and lifestyles. Different groups in the study area may have different
p.000072: cultural norms and practices. The researchers should take these issues into consideration as they work in the
p.000072: community. Community partners can help researchers design the study to be attentive to the increasing
p.000072: heterogeneity of community groups (Minkler and Wallerstein, 2003, Chapter 4) and to the different
p.000072: boundaries of privacy (crucial when designing sampling strategies) of different groups (Israel et al., 2005b, Chapter
p.000072: 11).
p.000072: Vega (1992) provides a thorough discussion of the theoretical and pragmatic implications of
p.000072: cultural diversity for community research and explains that researchers should interact with
p.000072: communities using methods that promote understanding and demonstrate sensitivity and competence in
p.000072: working with diverse
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073: cultures (e.g., with respect to class, gender, ethnicity, race, age, and sexual orientation). To aid in this
p.000073: process, researchers should include sufficient time in their project timeline to interact and dialogue with the
p.000073: community before the study begins to understand the cultural issues that may affect the research. Researchers and the
p.000073: results of their work are expected to promote a strengthening of the community; however, it should be recognized
p.000073: that, given the heterogeneity and the diverse views within a community, the study findings potentially may
p.000073: conflict with the desires of the community or may promote feelings of anger or distrust among members
p.000073: of the community with each other. Enlisting the services of a third-party evaluator/mediator may be
p.000073: useful for sustaining positive relations between all research participants and the community at
p.000073: large.
p.000073: The Research Triangle Park Particulate Matter Panel Study (Williams et al., 2003), a NERL investigation of PM
p.000073: and related pollutants involving African-Americans in North Carolina, demonstrated an effective strategy for using
p.000073: communication to address cultural differences between the community and research personnel. Before beginning
p.000073: the research, the study design included time and a budget for building collaborations with
p.000073: organizations having close ties with the African- American community to establish trust between
...
Social / Fetus/Neonate
Searching for indicator fetus:
(return to top)
p.000008: be 2- to 5-times higher inside homes than outside. Use of products containing organic chemicals may result in very high
p.000008: and persistent pollutant levels.
p.000008:
p.000008: EPA, States, and the Consumer Product Safety Commission worked together to influence manufacturers to voluntarily
p.000008: reduce emissions of toxic chemicals from consumer products, building materials, and furnishings, and to develop
p.000008: mitigation strategies and educational materials to teach people how to reduce their contact with chemicals indoors. As
p.000008: a result, contact with toxic chemicals indoors has been reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html).
p.000008:
p.000008:
p.000008: Formaldehyde
p.000008:
p.000008: Studies found elevated formaldehyde levels indoors and helped identify indoor sources.
p.000008:
p.000008: EPA worked with HUD, CPSC, and other agencies to limit formaldehyde in building or consumer products and to educate the
p.000008: public on how to reduce exposures (see www. epa.gov/iaq/formalde.html).
p.000008:
p.000008:
p.000008: EPA has adopted additional protections for children and pregnant or nursing mothers in Subparts B through
p.000008: D. These sections apply to all research either conducted or funded by EPA and are, therefore, directly applicable to
p.000008: NERL’s observational human exposure studies.4 Subpart B prohibits EPA from conducting or supporting research
p.000008: that involves intentional exposure of “a pregnant woman (and, thereby, her fetus), a nursing woman,
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
p.000008: from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in specified
p.000008: rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in this
p.000008: document.
p.000008: 5 The Glossary (Appendix F) lists definitions for a number of important terms; definitions that come from the
p.000008: regulatory language are identified with their specific CFR citation.
...
p.000033: populations are not targeted for risky research” [emphasis added] (Emanuel et al., 2000).
p.000033: The Common Rule requires IRBs to assure that “additional safeguards have been included in the study to protect
p.000033: the rights and welfare of these [vulnerable] subjects” [at 40 CFR 26.111(b) in CFR, 2006a]. If an
p.000033: observational human exposure study includes vulnerable research participants, it is essential that the investigators be
p.000033: cognizant of the special issues and requirements of research involving vulnerable populations. Researchers
p.000033: have to justify the involvement of vulnerable populations in the research study and
p.000033: include the appropriate safeguards for protection of their safety and welfare. The Common Rule protections are
p.000033: discussed further in the IRB guidebook (U.S. HHS, 1993). EPA regulations include not only the general
p.000033: protections for vulnerable populations found in the Common Rule (Subpart A) but also define
p.000033: additional protections for children and for pregnant or nursing women (and their fetus or nursing child)
p.000033: in Subparts B, C, and D (CFR, 2006a).
p.000033: The section begins by identifying or defining vulnerable groups and then discusses ethical issues that
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
...
p.000036: researchers should be prepared to address the issues associated with vulnerable groups in
p.000036: observational research. Furthermore, as discussed in Section 3.4, there has been increased concern in recent years that
p.000036: exclusion of vulnerable groups from research studies is not ethical. Failure to conduct research with vulnerable groups
p.000036: may deprive them of the benefits of research. NIH, for example, has a policy (NIH, 1998) with a
p.000036: goal of increasing participation of children in research.
p.000036:
p.000036: 3.3 Minimal Risk and Vulnerable Groups
p.000036: EPA has codified protections for children, pregnant or nursing women, and fetuses in Subparts B, C, and D of the EPA
p.000036: human subjects rule (40 CFR 26). Subpart B strictly prohibits research involving intentional exposure of children
p.000036: or pregnant or nursing women (and, therefore, exposure of her fetus).
p.000036: EPA’s regulations do allow for observational research involving fetuses and pregnant women (40 CFR 26
p.000036: Subpart C) or children (40 CFR 26 Subpart D) but with additional protections in place and with
p.000036: strict limitations on research that presents more than minimal
p.000036: risk (CFR, 2006a).13 When considering vulnerable groups, The Institutional Review Board Guidebook (U.S. HHS,
p.000036: 1993) states that “IRBs should therefore determine whether the proposed subject population would be more sensitive or
p.000036: vulnerable to the risks posed by the research as a result of their general condition or disabilities. If so, the
p.000036: procedures would constitute more than minimal risk for those subjects.”
p.000036: When conducting observational human exposure studies, it is recommended that researchers consult these
p.000036: regulations and guidebooks. NERL researchers also will need to ensure that all of the requirements in Subparts B, C,
p.000036: and D of the EPA Human Subjects Rule are met.
p.000036:
p.000036: 3.4 Research Involving Children
...
p.000038: Although the CIOMS guideline specifically addresses biomedical research, the ethical concepts
p.000038: behind the guidelines generally may be applicable to observational human exposure studies. EPA’s human
p.000038: subjects rule is completely consistent with the HHS rule in adding additional protections for pregnant women and
p.000038: fetuses involved in observational research (40 CFR
p.000038: 26.304 and 45 CFR 46.204). These additional protections (specified in 45 CFR 46.204 subparagraphs a
p.000038: through j) reflect the CIOMS recommendations by requiring: availability of data from previously conducted
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
...
p.000051: be recommendations as ethical “best practices.”
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: Text Box 5-2. Common Rule Requirements:
p.000052: Elements of Informed Consent
p.000052: (1) An explanation of the purposes of the research
p.000052: (2) The expected duration of the subject's participation
p.000052: (3) A description of the procedures to be followed and identification of any experimental procedures
p.000052: (4) A description of any reasonably foreseeable risks or discomforts to the subject
p.000052: (5) A description of any reasonably expected benefits to the subject or others
p.000052: (6) A disclosure of appropriate alternative procedures that might be advantageous to the subject
p.000052: (7) A description of the extent that confidentiality will be maintained
p.000052: (8) For research involving more than minimal risk, an explanation about whether compensation or medical treatments
p.000052: are available if injury occurs
p.000052: (9) An explanation of whom to contact with questions about the research or to report a research-related injury
p.000052: (10) A statement that participation is voluntary, refusal to participate will involve no penalty, and the subject may
p.000052: discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled
p.000052: (11*) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or
p.000052: fetus, if the subject is or may become pregnant) that are currently unforeseeable
p.000052: (12*) Anticipated circumstances under which the subject's participation may be terminated by the investigator without
p.000052: regard to the subject's consent
p.000052: (13*) Any additional costs to the subject that may result from participation in the research
p.000052: (14*) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of
p.000052: participation by the subject
p.000052: (15*) A statement that significant new findings developed during the course of the research that may relate to the
p.000052: subject's willingness to continue participation will be provided to the subject.
p.000052: (16*) The approximate number of subjects in the study
p.000052: * Included if appropriate [40 CFR 26.116(b)]
p.000052:
p.000052:
p.000052:
p.000052: • The information “shall be in language understandable to the subject” (40 CFR 26.116). This may require forms
p.000052: to be written and administered in different languages during a study. For example, the National
p.000052: Children’s Study (NCS) plans to produce all consent materials in English and Spanish, with other
p.000052: translations made available as needed (NCS, 2007).
p.000052: Participants often find discussions with research staff more useful than written consent forms (p. 103, NRC & IOM,
...
Searching for indicator fetuses:
(return to top)
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
...
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000012: 12
p.000012:
p.000012: address all of the relevant issues for their particular study to ensure that the specific elements of
p.000012: the study will safeguard and protect the human research subjects.
p.000012: In addition to being an information resource for NERL researchers, this document provides useful
p.000012: information for contractors and grantees funded by NERL to consider during the design and implementation of
p.000012: their exposure science research. Although not its intended audience, this document also may prove to be useful
p.000012: to other researchers, within and outside of EPA, who are involved in observational human exposure
p.000012: studies.
p.000012:
p.000012: 1.4 Process for Developing the Document
p.000012: This document was written by exposure science researchers in EPA’s NERL, with substantial input from experts
p.000012: within and outside of the Agency. Information relevant to the process and the document has been routinely
...
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
...
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
...
p.000036: If such research does not hold out the prospect of direct benefit to the child, no increase whatsoever over
p.000036: minimal risk is permitted.
p.000036: However, many observational human exposure studies are developed specifically to study the exposures of
p.000036: selected vulnerable groups to chemicals and other environmental stressors in everyday environments. So,
p.000036: researchers should be prepared to address the issues associated with vulnerable groups in
p.000036: observational research. Furthermore, as discussed in Section 3.4, there has been increased concern in recent years that
p.000036: exclusion of vulnerable groups from research studies is not ethical. Failure to conduct research with vulnerable groups
p.000036: may deprive them of the benefits of research. NIH, for example, has a policy (NIH, 1998) with a
p.000036: goal of increasing participation of children in research.
p.000036:
p.000036: 3.3 Minimal Risk and Vulnerable Groups
p.000036: EPA has codified protections for children, pregnant or nursing women, and fetuses in Subparts B, C, and D of the EPA
p.000036: human subjects rule (40 CFR 26). Subpart B strictly prohibits research involving intentional exposure of children
p.000036: or pregnant or nursing women (and, therefore, exposure of her fetus).
p.000036: EPA’s regulations do allow for observational research involving fetuses and pregnant women (40 CFR 26
p.000036: Subpart C) or children (40 CFR 26 Subpart D) but with additional protections in place and with
p.000036: strict limitations on research that presents more than minimal
p.000036: risk (CFR, 2006a).13 When considering vulnerable groups, The Institutional Review Board Guidebook (U.S. HHS,
p.000036: 1993) states that “IRBs should therefore determine whether the proposed subject population would be more sensitive or
p.000036: vulnerable to the risks posed by the research as a result of their general condition or disabilities. If so, the
p.000036: procedures would constitute more than minimal risk for those subjects.”
p.000036: When conducting observational human exposure studies, it is recommended that researchers consult these
p.000036: regulations and guidebooks. NERL researchers also will need to ensure that all of the requirements in Subparts B, C,
p.000036: and D of the EPA Human Subjects Rule are met.
p.000036:
p.000036: 3.4 Research Involving Children
p.000036: Children long have been recognized as a vulnerable group in research studies. EPA and HHS both extend special
...
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
p.000037: biomedical research because of the potential for becoming pregnant during a study. The document continues, “A
p.000037: general policy of excluding from such clinical trials women biologically capable of becoming pregnant is
p.000037: unjust in that it deprives women as a class of persons of the benefits of new knowledge derived from the
p.000037: trials.” The second relevant CIOMS guideline, number 17, asserts that, if involved in a research study,
p.000037: pregnant women should be fully informed, and included only if the
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: research benefits pregnant women and is thoroughly supported by reliable evidence in animal studies.
p.000038: Although the CIOMS guideline specifically addresses biomedical research, the ethical concepts
p.000038: behind the guidelines generally may be applicable to observational human exposure studies. EPA’s human
p.000038: subjects rule is completely consistent with the HHS rule in adding additional protections for pregnant women and
p.000038: fetuses involved in observational research (40 CFR
p.000038: 26.304 and 45 CFR 46.204). These additional protections (specified in 45 CFR 46.204 subparagraphs a
p.000038: through j) reflect the CIOMS recommendations by requiring: availability of data from previously conducted
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
...
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
p.000117:
p.000118: 118
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
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p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118:
p.000118: United States Environmental Protection Agency
p.000118:
p.000118:
p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
...
Searching for indicator neonates:
(return to top)
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
...
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
...
Social / Homeless Persons
Searching for indicator homeless:
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p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
...
Social / Incarcerated
Searching for indicator restricted:
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p.000053: informed consent process should involve both parents (assuming that there are two competent
p.000053: parents available), and that the consent of both parents be obtained, if possible. The IRB may decide
p.000053: that the permission of one parent is sufficient, but only when certain risk-benefit conditions are met.18
p.000053: • For studies involving children as participants, it is desirable for those children with sufficient capacity
p.000053: to be involved in the consent process. Moreover, it is generally accepted that the child’s assent be obtained
p.000053: whenever this is developmentally possible and otherwise appropriate. Under both the EPA Rule and the HHS
p.000053: Rule, the IRB is responsible for determining that adequate provisions have been made for soliciting the assent of the
p.000053: children when, in the judgment of the IRB, the children are capable of providing assent. Assent, however, may
p.000053: be waived in those restricted circumstances in which consent may be waived under the Common Rule. Those
p.000053: circumstances and the required IRB documentation are described in the Common Rule at 40 CFR 26.116(d).
p.000053: • The consent form should clearly state that participation is voluntary and that study
p.000053: participants may “discontinue participation at any time without any penalty or loss of benefits to which the
p.000053: subject is otherwise entitled” [40 CFR 26.116(a)(8)]. If a subject chooses to withdraw from a study, the
p.000053: consequences of their decision and the process for orderly withdrawal should be clearly
p.000053: explained [40 CFR 26.116(b)(4)].
p.000053: • The consent form should address any foreseeable potential future use of samples and data (CIOMS, 2002).
p.000053: For example, effects of environmental exposures on gene expression are potentially very important.
p.000053: Therefore, biologic specimens for DNA analysis may be obtained from participants in future studies. But, it
p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45 CFR 46.408(b)
...
p.000054: untrained persons such as co-workers usually will not meet requirements for full understanding of human subject
p.000054: protections. Researchers should make plans for trained staff or trained community members, associated
p.000054: or affiliated with the research study, to be available for translations.
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
...
Social / Infant
Searching for indicator infant:
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p.002004:
p.002004:
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002005: 2005
p.002005: 3 Homes
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.000150: 150
p.000150:
p.000150:
p.000150:
p.000150:
p.000150:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.001296: 1296
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Randomized household selection with qualification criteria; longitudinal
p.001296:
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Convenience, all volunteers from community using public water supply
p.001296: Pilot aggregate exposure study of three homes to assess burden of alternative exposure sample collection methods.
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Recruitment from seven distinct neighborhoods in Detroit required strong community relations and partnership with State
p.001296: and local organizations. This study monitored for air pollutants at the personal level and evaluates how well centrally
p.001296: located (ambient) monitors represent exposure at the residential and personal level. Sampling is for 5 days duration in
p.001296: summer and again in winter.
p.001296: Nine children <24 months old and their primary caregivers participated in this study to (a) determine if very young
p.001296: children will wear an accelerometer for relatively long periods of time and comply with the protocol for its use, (b)
p.001296: evaluate how well a caregiver can estimate the activity level of his/her infant or toddler when completing an
p.001296: exposure-oriented time-activity diary, and (c) compare accelerometer count output with caregiver-provided estimates of
p.001296: children's activity level.
p.001296: Measure antibodies in people’s saliva for antibodies to Cryptosporidium, Noroviruses, Rotaviruses, Helicobacter pylori,
p.001296: and Toxoplasma gondii before and after installation of an ultraviolet treatment system for a public water supply. Also
p.001296: served as test of methodology for detecting people’s prior exposure to infectious agents.
p.001296: NERL designed, contractor conducted
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: NERL designed and run; with contractor support and collaborators such as the University of Michigan
p.001296: NERL designed and run, with contractor support
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: EPA planned research (NERL is a collaborator), contractor conducted
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
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p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
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p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.000104: 104
p.000104:
p.000104: Table A-2. Types of Samples Collected in NERL Observational Human Exposure Studies
p.000104: Samples or Data Exposure Concern and Typical Type of Analysis
p.000104: Environmental Media
p.000104: Air pollutants Air pollutants being inhaled. Collect samples from central site, outside
p.000104: residence, and inside residence to assess
p.000104: pollutants in various locales. Measure gaseous and particle-bound pollutants.
...
Social / Laboratory Staff
Searching for indicator research staff:
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p.000042: part of a range.
p.000042: • Aggregate information across individuals; for example, only report data in cells of sufficient size
p.000042: to make individual linkages unlikely.
p.000042: • Reduce the specificity of geographic coordinate information to a level that a specific residence or other
p.000042: location can not be identified.
p.000042:
p.000042: Text Box 4-3. Approaches for Protecting Personally Identifiable Information
p.000042: • Developing procedures for safeguarding information prior to collecting the information
p.000042: • Ensuring that data or samples are anonymous by not collecting or by destroying identifying information or linkages
p.000042: • Restricting access to identifying information to only those requiring access
p.000042: • Assigning codes to participants, data, and samples rather than using identifiers
p.000042: • Physically separating identifying information and linkage files from other study information
p.000042: • Securing identifying information in locked files with limited access
p.000042: • Restricting identifying information from computers that are networked with other computers or electronic systems
p.000042: • Restricting identifying information from computers that are not kept in secure locations with limited access
p.000042: • Training research staff members on human subject protection and on information security procedures
p.000042:
p.000042:
p.000042: Another step that can help protect confidentiality is to obtain a Certificate of Confidentiality. Certificates of
p.000042: Confidentiality are issued by NIH (2002) to protect identifiable research information from forced disclosure.
p.000042: They allow the investigator and others who have access to research records to refuse to disclose identifying
p.000042: information on research participants in any civil, criminal, administrative, legislative, or other
p.000042: proceeding, whether at the Federal, State, or local level. Certificates of Confidentiality may be granted for studies
p.000042: collecting information that, if disclosed, could have adverse consequences for subjects or damage
p.000042: their financial standing, employability, insurability, or reputation. By protecting researchers and
p.000042: institutions from being
p.000042:
p.000042:
p.000043: 43
p.000043:
p.000043: compelled to disclose information that would identify research subjects, Certificates of Confidentiality
p.000043: help achieve the research objectives and promote participation in studies by assuring
p.000043: confidentiality and privacy to participants. Any research project that collects sensitive, personally identifiable
p.000043: information and that has been approved by an IRB is eligible for a certificate. Identifying information is broadly
...
p.000043: In the course of conducting an observational human exposure study, research staff may observe potentially unsafe
p.000043: conditions or situations that are unrelated to the research study. Such “collateral observations” may
p.000043: involve physical hazards in the study participant’s residential environment or evidence of situations,
p.000043: such as child abuse, that have to be reported to proper authorities. In preparing for the
p.000043: research study, it is recommended that researchers carefully plan for possible collateral observations,
p.000043: including their identification, staff training, and hazard communication and reporting. This may be a major
p.000043: element in the data and safety monitoring and oversight for the study. The informed consent process
p.000043: should reflect procedures used to manage collateral observations. Potential participants should be
p.000043: informed of situations in which confidentiality might be breached, such as statutory requirements for reporting
p.000043: abuse or imminent harm to self or others.
p.000043:
p.000043: 4.3.1 Potential Nonstudy Hazards in the Residence
p.000043: Research staff conducting observational human exposure studies often will spend time in and around
p.000043: study participant residences. In the course of visiting a residence or conducting study-related
p.000043: observations, research staff may observe potential hazards unrelated to the research being performed (see Text Box
p.000043: 4-4). Some hazards may be associated with the potential for physical injury, whereas others may be related to
p.000043: exposure to chemical or biological agents. Some situations may be potential hazards only for young children,
p.000043: whereas other conditions may present potential hazards for all residents or occupants.
p.000043: The NRC & IOM recommend that researchers should consider such foreseeable observations and
p.000043: potential hazards in advance, develop responses to the risks, and submit the proposed plans to the IRB
p.000043: for review to ensure that they are appropriate “in the context of the research and the affected community.” The NRC
p.000043:
p.000043:
p.000044: 44
p.000044:
p.000044: & IOM also advise that field staff should be trained in how to assess and respond to
p.000044: such risks (Recommendations 7.3 and 7.4, NRC & IOM, 2005). For other behaviors and risks that
p.000044: have not been specifically identified in advance, procedures should be included in the data and safety monitoring
p.000044: and oversight provisions of the study design and research protocol to address these issues. The fundamental
p.000044: ethical principle of beneficence would motivate researchers who observe serious harms to take steps to try to prevent
p.000044: those harms, even for observations that are not directly related to the study. The steps that they may take can
p.000044: range from immediate action to prevent an imminent and serious danger to statutory reporting of
p.000044: observations (see Section 4.3.2) to reporting the observation to the data and safety monitoring and oversight
...
p.000044: • Missing child-protective cabinet latches
p.000044: • Lack of window guards
p.000044: • Missing or inoperable smoke alarm
p.000044: • Housing code violations
p.000044: • Chipping or flaking paint—potential for lead exposure in older homes
p.000044: • Malfunctioning or unvented combustion appliances—potential for carbon monoxide exposure
p.000044: • Unsecured poisons or other dangerous products
p.000044: • Excessive mold growth
p.000044:
p.000044:
p.000044: 4.3.2 Collateral Observations with Mandated Reporting Requirements
p.000044: Some collateral observations may have statutory requirements for reporting to designated authorities.
p.000044: Examples of such observations include
p.000044: • observed child or elder abuse or evidence of such abuse or neglect,
p.000044: • statements or actions of intent to harm self or others, and
p.000044: • certain communicable diseases.
p.000044: Because different reporting statutes pertain in different states, it is necessary for researchers to
p.000044: learn and understand the applicable reporting requirements for the study location. In the case of abuse, it is
p.000044: also
p.000044: important to understand what actions or situations are considered abusive in a particular state. Although direct
p.000044: physical harm or violence might be obvious to a research staff member, there are other conditions of neglect that
p.000044: might be more difficult to recognize or to know when to report.
p.000044: Study participants should be made aware of statutory requirements for reporting collateral observations as part of the
p.000044: informed consent process. Researchers should include the reporting requirements in the informed
p.000044: consent form (discussed in Section 5) and should ensure that the study participant fully comprehends this
p.000044: information and the impact on their privacy and confidentiality.
p.000044:
p.000044: 4.3.3 Hazard Communication
p.000044: It is difficult for researchers to determine when and how to communicate with study participants or third
p.000044: parties about collateral observations related to potential hazards. A hazard might present such an imminent
p.000044: threat to health or safety that staff would need to communicate immediately with the participant or take
p.000044: action to mitigate the threat. In some cases, such as instances of abuse with attendant statutory reporting
p.000044: requirements, it may be necessary to breach confidentiality. More often, however, a potential hazard identified as
...
p.000045: training should be study specific and likely will include, but not be limited to
p.000045: (1) identification of actions (e.g., child abuse) that have (state-specific) statutory reporting requirements,
p.000045: (2) conditions of neglect that may adversely impact study participants or third parties,
p.000045: (3) environmental hazards and situations that may be associated with imminent harm (e.g., combustible
p.000045: materials near an open flame, unsecured firearms accessible to very young children),
p.000045: (4) policies and procedures for reporting or intervention by members of the research team, and
p.000045: (5) local and state reporting requirements.
p.000045: It is advisable that this training be developed in consultation with community representatives who can
p.000045: provide input on potential hazards and situations that may be encountered in the study community,
p.000045: local norms and attitudes about potential interventions and reporting, and local agencies available to assist on
p.000045: these types of issues. It is also especially important to consider
p.000045: staff experience and training in hazard communication. Consistency in communication is very important, and
p.000045: researchers may decide to use materials prepared by other organizations that have expertise regarding
p.000045: a particular hazard.
p.000045: Another important element of planning for field data collection and training of research staff is on hazards and
p.000045: situations that the field staff may encounter during their field work. Although the previous discussion highlights the
p.000045: need to be prepared to report potentially negligent or illegal behaviors, these same behaviors may place the
p.000045: research staff in imminent danger during the conduct of their work in residences and communities. The research team
p.000045: should develop a plan for identifying potential situations, hazards, and dangers that may place the
p.000045: research team at risk of imminent harm. This should generally involve working with
p.000045: community representatives to identify the hazards and situations that may be of concern. For example, a
p.000045: researcher’s observation of illegal drugs in a study residence may place the researcher in potential
p.000045: danger. Similarly, if studies are conducted in areas with high crime rates, researchers need to be aware of
p.000045: the potential dangers and have a plan for addressing them. In some cases, situations may arise
p.000045: because of to inadvertent actions. For example, if an area has a high rate of daytime break- ins, the presence
p.000045: of researchers in the area may trigger calls to local authorities when the researchers, who are
p.000045: strangers, are observed in the neighborhood. Feedback from the community representatives should be solicited when
p.000045: developing a plan for responding to situations such as these. Comprehensive training should be developed for
p.000045: research field staff to assist them in identifying potentially dangerous situations and in responding to
p.000045: such situations.
p.000045:
p.000045: 4.4 Third-Party Issues
...
p.000051: Common Rule at 40 CFR 26.116(a)(1)
p.000051: (8) (CFR, 2006). The regulations also prescribe the use of a written consent form and describe how informed
p.000051: consent is to be documented (at 40 CFR 26.117). The regulatory requirements for informed consent highlight a
p.000051: number of issues that a NERL researcher needs to consider in developing and administering the informed
p.000051: consent process and the consent form document. The discussion of these issues, arising from
p.000051: regulatory
p.000051:
p.000051:
p.000051: 16 An IRB may waive informed consent under some very limited conditions. See 40 CFR 26.116(c) and (d).
p.000051: requirements or identified in recent writings on ethical considerations in human subjects research, is
p.000051: grouped below, under the three pillars of informed consent:
p.000051: (1) information, (2) comprehension, and (3) voluntary participation.
p.000051:
p.000051: Text Box 5-1. Recommendations for Informed Consent In the United States and Internationally
p.000051: (1) Revitalize Informed Consent (IOM, 2002)
p.000051: Informed consent is a process, not a form. It is an on-going, interactive dialogue between research staff and research
p.000051: participants with disclosure and exchange of relevant information, including assessment of understanding.
p.000051: Ethics Review Boards should ensure that the focus of both the informed consent process and the consent forms is on
p.000051: informing and protecting participants, not the research institution.
p.000051: (2) Strengthen Process of Parental Permission and Children’s Assent if Children Are Involved in Research (NRC & IOM,
p.000051: 2005)
p.000051: The process begins with a community-based discussion and concludes with an assurance that individual parents understand
p.000051: the essential elements of the research.
p.000051: Educate parents on issues critical to informed decision making and assess their degree of understanding.
p.000051: Use informational materials in the form that is most appropriate to convey information to potential participants.
p.000051: Consult with community representatives to ensure that information is complete, clear, and understandable, and that any
p.000051: payment will not be exploitive.
p.000051: Expand the perspective about what information about risks and benefits is needed to make an informed choice.
p.000051: Ethically, it is critical to assure that participants and parents understand the crucial features of the research
p.000051: effort.
...
p.000052: fetus, if the subject is or may become pregnant) that are currently unforeseeable
p.000052: (12*) Anticipated circumstances under which the subject's participation may be terminated by the investigator without
p.000052: regard to the subject's consent
p.000052: (13*) Any additional costs to the subject that may result from participation in the research
p.000052: (14*) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of
p.000052: participation by the subject
p.000052: (15*) A statement that significant new findings developed during the course of the research that may relate to the
p.000052: subject's willingness to continue participation will be provided to the subject.
p.000052: (16*) The approximate number of subjects in the study
p.000052: * Included if appropriate [40 CFR 26.116(b)]
p.000052:
p.000052:
p.000052:
p.000052: • The information “shall be in language understandable to the subject” (40 CFR 26.116). This may require forms
p.000052: to be written and administered in different languages during a study. For example, the National
p.000052: Children’s Study (NCS) plans to produce all consent materials in English and Spanish, with other
p.000052: translations made available as needed (NCS, 2007).
p.000052: Participants often find discussions with research staff more useful than written consent forms (p. 103, NRC & IOM,
p.000052: 2005). NCS plans to pilot test an interactive, computer-based audio/video consent tool and to compare it
p.000052: with traditional written informed consent approaches (NCS, 2007).
p.000052: • The information being discussed, including the explanation of the purpose of the research and the
p.000052: description of the study procedures, should be written or discussed at a level that the participant can
p.000052: understand.17 The National Institutes of Health recommends writing consent forms as “plain language
p.000052: documents that explain the research in an honest, straightforward way” and suggest that doing so will
p.000052: help enhance public trust (Recommendation 11, NIH, 2005).
p.000052: • The consent form should contain sufficient information to describe the study procedures, but not
p.000052: so much information that it causes confusion and results in the participant not understanding the study. There
p.000052: is not agreement on what the appropriate level of information is. IRBs do not agree on the level of
p.000052: information; some require lengthy descriptions of the study, whereas others prefer concise information.
p.000052: Ultimately, the IRB dictates the language of the informed consent document, and the researcher will
...
p.000053: for such specimens and recognize the rights of the subjects to decide about any such future use,
p.000053: including having the material destroyed. The informed consent process needs to explicitly discuss
p.000053: obtaining permission from participants on behalf of themselves and their child to obtain specimens for
p.000053: genetic analysis.
p.000053:
p.000053: 5.1.2 Comprehension
p.000053: Research participants frequently fail to understand the research protocols in which they agree to participate (NRC
p.000053: & IOM, 2005). In considering the ethical issues raised by the Grimes v. Kennedy Krieger case, the NRC & IOM
p.000053: committee “realized that the crucial issue regarding consent was not what information was
p.000053: contained in the consent forms, but rather what the parents understood about the study and the hazards
p.000053: present in the home before and after the study” (p. 19, NRC & IOM, 2005). The committee laments that “IRBs
p.000053: place their attention on consent forms rather than on the process of providing and discussing information” (p.
p.000053: 103, NRC & IOM, 2005). The IOM recommends that “the informed consent process should be an on-going,
p.000053: interactive dialogue between research staff and research participants involving the disclosure and exchange of
p.000053: relevant information, discussion of that information, and assessment of the individual’s understanding of
p.000053: the discussion” (Recommendation 4.1, IOM, 2002). These comments emphasize how important true two-way
p.000053: communication is to comprehension, the second pillar in the informed consent process.
p.000053: The following items are a variety of issues concerning comprehension that NERL scientists should
p.000053: keep in mind as they develop an informed consent process in collaboration with the research team, the IRB and
p.000053: other peer reviewers, and EPA’s HSRRO. These items may be based on regulatory requirements or may simply be
p.000053: recommendations as ethical “best practices.”
p.000053: • Researchers need to assume responsibility for developing an interactive dialogue with
p.000053: participants for the exchange and discussion of relevant information as a part of the informed
p.000053: consent process, not just for conveying information. The dialogue should be ongoing, continuing throughout
p.000053: the research project (IOM, 2002).
p.000053: • The consent form and its content are only one part of the overall consent process. An equally important part
p.000053:
p.000053:
p.000054: 54
p.000054:
p.000054: is how information is conveyed to the participant outside of the written form itself.
...
p.000060: or their guardians. An ombudsman may be used in studies involving prisoners or military personnel to
p.000060: ensure that there is no coercion to participate. And the ombudsman may
p.000060:
p.000060:
p.000060:
p.000061: 61
p.000061:
p.000061: communicate problems or grievances raised by research participants to the IRB and sponsoring organization.
p.000061:
p.000061: 5.3.2 Community Advisory Board
p.000061: CABs can help ensure that participant rights are considered and addressed during the study design and can
p.000061: play an important role in monitoring the research process. Community members may choose to seek
p.000061: information about the study from the advisory panel, as an independent entity, before deciding whether to enroll.
p.000061: Representatives from such advisory boards can be included in the research team that designs the study (see
p.000061: Section 2.3). The role of CABs is more fully discussed in Section 6.
p.000061:
p.000061: 5.4 Creating a Supportive Environment for Research and Interaction
p.000061: It is recommended that researchers and institutions strive to create a supportive environment for research
p.000061: and interaction with research participants and communities. At the personal level,
p.000061: this means researchers building trust with individuals and treating them with respect. Following the IOM
p.000061: recommendations about the informed consent process⎯that it “should be an on-going, interactive dialogue between
p.000061: research staff and research participants involving the disclosure and exchange of relevant information,
p.000061: discussion of that information, and assessment of the individual’s understanding of the discussion”
p.000061: (Recommendation 4.1, IOM, 2002)⎯should go a long way in establishing a supportive environment with the
p.000061: individual participants. At the community level, engagement of the community throughout the design, conduct of the
p.000061: study, and follow- up will support trust-building and positive interactions. Developing and providing this
p.000061: kind of support can be challenging in large-scale studies, and particularly those that cross communities or are
p.000061: conducted across large geographic areas. Institutions need to recognize the need for, and value of
p.000061: creating supportive research environments by providing adequate funding because effective interaction takes
p.000061: considerable time and effort.
p.000061: Many of the factors that create a supportive environment for research participants are described in
p.000061: the Report and Recommendations on Public Trust in Clinical Research for the NIH Director from the
p.000061: Director’s Council of Public Representatives (COPR) (NIH, 2005). Although the advice from this workshop was
p.000061: developed in the context of NIH-supported clinical research, many of the recommendations are applicable to
p.000061: observational human exposure studies and human subject research in general. A summary
p.000061: of
p.000061: recommendations from the report for enhancing public trust is provided in Appendix D. The recommendations are
p.000061: focused on the following areas.
p.000061: • Building trust through community partnerships
...
p.000066: 6. Review and use input, and provide feedback to the public.
p.000066: 7. Evaluate public involvement activities .
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000067: 67
p.000067:
p.000067: 6.1 Approaches to Community Involvement
p.000067: Community involvement can take many forms. The forms of community involvement are not mutually exclusive,
p.000067: and researchers may use several approaches for seeking community involvement. The nature and extent of
p.000067: community involvement reasonably would depend on the nature of the research itself and the affected
p.000067: community. In Section 2, the authors discussed some reasons for involving the community early in the research
p.000067: planning and scoping process and the benefits that community involvement may bring to the research effort.
p.000067: “Community residents can be involved in the research process as research staff, through community
p.000067: consultation and review, membership on community advisory boards, and involvement in a community-based
p.000067: participatory research process” if that is used (p. 83, NRC & IOM, 2005). In addition, IRBs may
p.000067: seek additional community representation on the IRB panel.
p.000067: The Centers for Disease Control and Prevention (CDC) recommends nine governing principles for
p.000067: “outsiders.” To help alleviate these potential issues, researchers should ensure an equitable
p.000067: distribution of paid research work among different communities within the larger community as to not promote a
p.000067: perceived bias among community members. Additionally, when possible, researchers should make efforts
p.000067: to provide payments to community members employed as research staff through community partner
p.000067: organizations to prevent conflict of interest issues. Refer to Section 5 for further discussion on
p.000067: remuneration of community members as research participants.
p.000067:
p.000067:
p.000067: Text Box 6-2. Community Engagement Principles for Researchers
p.000067: (From CDC, 1997)
p.000067: Requirement Explanation
p.000067:
p.000067: Clarity Clear communication of the study objectives, research goals, and the populations or
p.000067: communities of interest.
p.000067:
p.000067: engaging communities in health-related research (see Text Box 6-2). Health research is a “privileged and
p.000067: empowered activity in that the researchers have special
p.000067: Knowledge of the Community
p.000067: Familiarity with the economic conditions, political structures, demographics, history, past research experiences, and
p.000067: research perceptions of the community.
p.000067:
p.000067: access to resources and sensitive information about people and, through the analysis and presentation
p.000067: of findings, are able to influence the way people think and have considerable influence on decisions regarding
p.000067: the allocation of resources” (CDC, 1997). Regardless of the approach utilized to involve the community in research,
p.000067: whether the process employs community-based participatory research (CBPR) or another community
p.000067: engagement method, researchers should guide their interactions with community members using these
p.000067: underlying principles to promote the aforementioned ethical principles of respect of persons, fairness, and
p.000067: beneficence.
p.000067: One form of community involvement is to include qualified members of the community on the research staff.
p.000067: Section 2 advocates community representatives as part of the research team. Paid research staff members from
p.000067: the community could serve as valuable consultants for protocol development and research design, including how to
p.000067: collect the data, how to recruit and retain participants, and how to interpret and disseminate the
p.000067: results. However, including paid research staff from the community may introduce a conflict of interest among
p.000067: community members: community representatives may feel a greater allegiance to the researchers providing the payment
p.000067: and be less inclined to uphold the interests of the community. In addition, the community may come to view
p.000067: the paid research staff from the community as
p.000067: Visibility Travel to the community, interact with formal
p.000067: and informal leadership, and establish relationships to build trust.
p.000067:
p.000067: Acceptance Acknowledge, without judging, the assets and deficits of the community.
p.000067:
p.000067: Partnership Balanced discussion and shared
p.000067: decisionmaking among participants concerning risks, responsibilities, expectations, benefits, and investment.
p.000067:
p.000067: Respect Value the diversity of culture, history, beliefs and opinions within the community for
p.000067: improved understanding.
p.000067:
p.000067: Asset Utilization Identify and mobilize community assets to
p.000067: improve scientific credibility of the interpretation and dissemination of results.
p.000067:
p.000067: Flexibility Anticipate changes within the community in
p.000067: regard to perceived benefits of research and stakeholder interest and additional time and resource needs.
p.000067:
p.000067: Commitment Prepare to engage the community beyond the constraints of the research projects, before and after,
p.000067: to promote longevity of the relationship for future research .
p.000067:
p.000067:
p.000067: Furthermore, institutional and community partners need to ensure that anyone involved as part of the
p.000067: research team has the requisite research and social skills. Researchers often place a greater emphasis on scientific
...
p.000116: Appendix F
p.000116: Glossary
p.000116:
p.000116:
p.000116:
p.000116: Agent. A chemical, mineralogical, biological, or physical entity that may cause deleterious effects in an organism
p.000116: after the organism is exposed to it [EPA/600/Z-92/001, May 1992].
p.000116: Assent. A child’s affirmative agreement to participate in research. Mere failure to object should not, absent
p.000116: affirmative agreement, be construed as assent [45 CFR 46.402(d)].
p.000116: Autonomy. The capability and capacity to govern oneself.
p.000116: Beneficence. The ethical obligation to maximize benefits and to minimize harms. This principle gives rise to norms
p.000116: requiring that the risks of research be reasonable in light of the expected benefits, that the research design be
p.000116: sound, and that the investigators be competent both to conduct the research and to safeguard the welfare of the
p.000116: research subjects. Beneficence further proscribes the deliberate infliction of harm on persons; this aspect of
p.000116: beneficence is sometimes expressed as a separate principle, nonmaleficence (do no harm).
p.000116: Child. A person who has not attained the age of 18 years [40 CFR 26.202(a)]
p.000116: Collateral observations. Potentially unsafe hazards, conditions, or situations unrelated to the research study that
p.000116: are observed by the research staff
p.000116: Common Rule. The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects.” It was
p.000116: adopted by more than a dozen Federal departments or agencies in 1991, with EPA adapting it in Title 40 CFR Part 26
p.000116: Subpart A.
p.000116: Community-based participatory research (CBPR). Collaborative research with a community in which the community is
p.000116: involved in all phases of the research.
p.000116: A fundamental concept is that the research aims to combine knowledge with action and to achieve social
p.000116: change to improve health outcomes and eliminate health disparities.
p.000116: Confidentiality. The keeping safe or not redisclosing by one of the parties in a confidential relationship information
p.000116: that originally was disclosed in the confidential relationship
p.000116: Environmental justice. The fair treatment and meaningful involvement of all people regardless of race, color, national
p.000116: origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations,
p.000116: and policies
p.000116: Exposure. Contact of a chemical, physical, or biological agent with the outer boundary of an organism (e.g., a
p.000116: person). Exposure is quantified as the concentration of the agent in the medium in contact integrated over the time
p.000116: duration of that contact. (The definition is taken from Guidelines for Exposure Assessment [EPA/600/Z-92/001, May
p.000116: 1992]).
p.000116: Exposure concentration. The exposure mass divided by the contact volume or the exposure mass divided by the mass of
...
Social / Linguistic Proficiency
Searching for indicator language:
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p.000052: 52
p.000052: 5.1.1. Information
p.000052: 52
p.000052: 5.1.2. Comprehension
p.000054: 54
p.000054: 5.1.3. Voluntary Participation
p.000055: 55
p.000055: 5.2. Payments to Research Participants
p.000056: 56
p.000056: 5.2.1. Types and Amounts of Payments Offered in Research Studies 56
p.000056: 5.2.2. Regulations and Guidance Regarding Payment to Research Participants 58
p.000056: 5.2.3. Payments When Children or Other Vulnerable Populations Are Involved 59
p.000056: 5.2.4. Payments in Observational Human Exposure Studies 61
p.000056: 5.3. Research Rights and Grievance Procedures
p.000061: 61
p.000061: 5.3.1. Ombudsman
p.000061: 61
p.000061: 5.3.2. Community Advisory Board
p.000062: 62
p.000062: 5.4. Creating a Supportive Environment for Research and Interaction 62
p.000062: 5.5. Recruitment Strategies
p.000062: 62
p.000062: 5.6. Retention Strategies
p.000063: 63
p.000063: 5.7. Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk 64
p.000063: 6. Building and Maintaining Appropriate Community and Stakeholder Relationships 67
p.000063: 6.1. Approaches to Community Involvement
p.000068: 68
p.000068: 6.2. Issues in Community Involvement
p.000071: 71
p.000071: 6.2.1. Defining “Community”
p.000071: 71
p.000071: 6.2.2. Identifying Who Represents the Community 71
p.000071: 6.2.3. Building Relationships and Trust
p.000072: 72
p.000072: 6.2.4. Importance of Language and Communications with the Community 73
p.000072: 6.2.5. Recognizing and Addressing Cultural Differences 73
p.000072: 6.2.6. Honesty, Power Relationships, and Partnerships 74
p.000072: 6.2.7. Building a Lasting Infrastructure
p.000074: 74
p.000074: 6.3. Community Involvement in Observational Human Exposure Studies 75
p.000074: 6.4. Identifying and Interacting with Other Stakeholders 75
p.000074: viii
p.000074:
p.000074: 7. Designing and Implementing Strategies for Effective Communication 81
p.000074: 7.1 Communication Strategy and Implementation Plan 81
p.000074: 7.2 Individuals and Groups Involved in the Communications 82
p.000074: 7.3 Communications Timetables⎯When To Communicate 83
p.000074: 7.4 Communicating at Different Levels
p.000085: 85
p.000085: 7.5 Communications Materials
p.000085: 85
p.000085: 7.6 Informing the Study Participants and Communities 87
p.000085: 7.7 Reporting Study Results to the Participant and Community 87
p.000085: 7.8 Reporting Unanticipated Results or Observations 90
p.000085: 7.9 Anticipating and Responding to Criticism
p.000091: 91
p.000091: 7.10 Responding to the Media, Public Inquiries, and Other Stakeholders 92
...
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
p.000003: range of risks associated with participation and the voluntary nature of participation, and provides
p.000003: essential protections to the participant. Recent observations by various national and international review
p.000003: committees on the appropriate level of payment to research participants are presented. This is a
p.000003: complex ethical issue, balancing the issue of fairness against the possibility of undue influence
p.000003: and the loss of free consent. Other topics include participant recruitment, retention strategies, research
p.000003: rights, and grievance procedures.
p.000003: Section 6. Building and maintaining appropriate community and stakeholder relationships: Involving
p.000003: the community in the research effort to improve the research both scientifically and ethically.
p.000003: Various approaches are discussed related to issues such as defining the community, identifying who
p.000003: represents the community, recognizing and addressing cultural differences, and the importance of language,
p.000003: power relationships, and partnerships.
p.000003: Section 7. Designing and implementing strategies for effective communication: Ongoing, interactive
p.000003: dialogue among researchers, participants, the community, stakeholders, and the public to
p.000003: establish effective communications and to foster a relationship of trust. To facilitate information dissemination
p.000003: to participants, communities, and stakeholders, this section of the document describes communication
p.000003: strategies, implementation plans, communication groups, timetables, communication materials, and other
p.000003: tools available to researchers.
p.000003: This document does not and, indeed, could not provide solutions to all scientific and ethical issues that may
p.000003: arise as observational human exposure studies are undertaken. No document could identify and address all
p.000003: potential issues in advance, nor is it possible to develop a comprehensive checklist for all such studies.
p.000003: Rather, this document attempts to present and discuss the types of ethical and scientific issues that will need
p.000003: to be considered and addressed as NERL researchers plan and implement observational human exposure studies. The
p.000003: researchers will need to work with others ― the study team, IRB members, EPA’s HSRRO, the participants
p.000003: and their community, and other stakeholders ― to identify and address all of the relevant issues
p.000003: for any particular study. The authors are confident that this document will be helpful to NERL scientists
p.000003: in their endeavors to assure that all of NERL’s observational human exposure studies will respect,
...
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
p.000008: from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in specified
p.000008: rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in this
p.000008: document.
p.000008: 5 The Glossary (Appendix F) lists definitions for a number of important terms; definitions that come from the
p.000008: regulatory language are identified with their specific CFR citation.
p.000008: about the most recent thinking and guidance on protection of human subjects.
p.000008: The Belmont Report (U.S. DHEW, 1979) is a foundational document in the development of the ethics of human
p.000008: subjects research in the United States. Because of the adverse publicity and political embarrassment arising
p.000008: from the unethical treatment of African- American men in the Tuskegee Syphilis Study, Congress passed
p.000008: the National Research Act of 1974, which called on the Department of Health, Education, and Welfare (DHEW) to
p.000008: codify its rules on human subjects research and established the National Commission for the Protection of
p.000008: Human Subjects of Biomedical and Behavioral Research. The commission was charged with identifying the
p.000008: basic ethical principles that should underlie human subjects research. The commission published the
p.000008: Belmont Report in 1979. This report established three basic principles: (1) respect for
p.000008: persons; (2) beneficence; and (3) justice, which have become the cornerstones for regulations involving
p.000008: human subjects (see Table 1-2).
...
p.000022: the researchers use information on the relevant characteristics of the population to select those
p.000022: participants who will exhibit a wide range of activity levels or potential exposure concentrations, or
p.000022: convenience sampling, where the researchers select the most accessible members of a population
p.000022: NERL’s observational human exposure studies also have routinely collected information about the
p.000022: participants’ activities by using questionnaires and surveys. Survey design is both a science and an
p.000022: art because the design of surveys is based on statistics and science, but designing a good and effective questionnaire
p.000022: is often an art that requires understanding the individuals being surveyed. Text Box 2-3 identifies some of the
p.000022: areas of art involved in designing an effective questionnaire.
p.000022: Understanding the process for selecting participants and the statistical-scientific requirements of
p.000022: questionnaire design are both components of survey sampling and design. A variety of references can provide
p.000022: the researcher with information about the issues in survey sampling and
p.000022: design. (See http://home.ubalt.edu/ntsbarsh/Business-stat/stat data/Surveys.htm and
p.000022: www.statpac.com/surveys/, for example.) But the research team must include or have access to the appropriate
p.000022: survey statistics expertise as it plans the research study.
p.000022:
p.000022: Text Box 2-3. Questionnaire Considerations
p.000022: • Questions should be simple and in a language the individual can understand.
p.000022: • Questions should be unambiguous.
p.000022: • Questions should be relevant to the study.
p.000022: • Questions should not be too personal.
p.000022: • The questionnaire should be as short as possible.
p.000022: • The questions should not be leading (e.g., internally suggestive of the answer).
p.000022: • Questions should follow a logical order.
p.000022:
p.000022:
p.000022:
p.000022: 2.2.5 Information Collection Rule
p.000022: As Federal employees, NERL researchers also must be aware of Information Collection Rule requirements. The
p.000022: Paperwork Reduction Act stipulates that every Federal agency must obtain approval from OMB before collecting
p.000022: the same or similar information from 10 or more members of the public. An Information Collection Request (ICR)
p.000022: is required if the same or similar information is being collected from 10 or more non- Federal
p.000022: respondents within a 12-month period, even if the information collection is voluntary. Generally, any
p.000022: survey, questionnaire, monitoring, reporting, or recordkeeping requirement imposed on
p.000022: non-Federal respondents by EPA will require an ICR. Information collections associated with all cooperative
p.000022: agreements funded by the EPA require an ICR. When an ICR is required, it must be approved by OMB
p.000022: before the collection begins, regardless of whether the collection of information is mandatory, voluntary,
p.000022: or required to receive a benefit. The principal investigator must prepare an ICR and submit it to the
p.000022: appropriate Office of Environmental Information Desk Officer.
...
p.000027: participants. CIOMS has developed a comprehensive list of items that they recommend for inclusion in
p.000027: a human subjects research protocol (Appendix 1, CIOMS, 2002). Many of the items that they identify are also
p.000027: useful for observational human exposure studies. (The CIOMS items can be found in Appendix C of this
p.000027: document.) The authors recommend that anyone developing a human subjects protocol for observational human
p.000027: exposure studies review and utilize the CIOMS list of topics, as appropriate. Text Box 2-5
p.000027: identifies a number of topics that should be considered in development of the human subjects research protocol.
p.000027: In addition, the authors’ experience leads them to suggest that three additional topics beyond those from
p.000027: the CIOMS (2002) document also may need to be considered in a human subjects protocol: (1) approaches to
p.000027: minimize changes in participant behavior because of participation in the study (see Section 2.3.4);
p.000027: (2) approaches to minimize therapeutic misconception (see Section 5.4.1); and (3) actions to involve
p.000027: the community in a community-based participatory research
p.000027:
p.000027: Text Box 2-5. Potential Topics in a Human Subjects Research Protocol
p.000027: 1. Title
p.000027: 2. Summary in lay language
p.000027: 3. Justification for the study
p.000027: 4. Ethical issues and proposed resolution
p.000027: 5. Summary of previous research
p.000027: 6. Affirmation of Belmont Principles and 40 CFR 26 compliance
p.000027: 7. Previous history or use of the protocol
p.000027: 8. Information on the location and demographics of research
p.000027: 9. Information on funding organization, researcher partners, and collaborators
p.000027: 10. Names, qualifications, and experience of investigators
p.000027: 11. Objectives, hypotheses, assumptions, and variables
p.000027: 12. Study design
p.000027: 13. Sample size and power and statistical analysis plan
p.000027: 14. Criteria and justification for subject selection
p.000027: 15. Justification for use of vulnerable groups, if any
p.000027: 16. Process of recruitment
p.000027: 17. Actions to involve the community in a community-based participatory research program
p.000027: 18. Description and explanation of any and all interventions
p.000027: 19. Measurements or data to be collected
p.000027: 20. Any clinical or other tests
p.000027: 21. Rules or criteria for removing subjects or terminating the study
p.000027: 22. Adverse events and unanticipated problems⎯reporting and responses
p.000027: 23. Potential benefits to subjects or others
p.000027: 24. Expected benefits of the research to the population
p.000027: 25. Informed consent process and responsibilities
p.000027: 26. Protections for the consent/assent of vulnerable participants
p.000027: 27. Efforts to minimize “therapeutic misconception”
...
p.000051: 2005)
p.000051: The process begins with a community-based discussion and concludes with an assurance that individual parents understand
p.000051: the essential elements of the research.
p.000051: Educate parents on issues critical to informed decision making and assess their degree of understanding.
p.000051: Use informational materials in the form that is most appropriate to convey information to potential participants.
p.000051: Consult with community representatives to ensure that information is complete, clear, and understandable, and that any
p.000051: payment will not be exploitive.
p.000051: Expand the perspective about what information about risks and benefits is needed to make an informed choice.
p.000051: Ethically, it is critical to assure that participants and parents understand the crucial features of the research
p.000051: effort.
p.000051: (3) Informed Consent Is a Decision To Participate by an Informed, Competent Individual Without Undue Coercion,
p.000051: Influence, or Intimidation (CIOMS, 2002)
p.000051: Informed consent is a process that takes time and resources.
p.000051: It is not a ritual recitation of text from a form but informative communication in language that suits the individual’s
p.000051: level of understanding.
p.000051: Consent is ethically obtained, considering language and cultural issues, and is documented.
p.000051: Material changes in conditions or procedures require that informed consent be renewed.
p.000051: Consent should explain how samples will be used in current research, and, if applicable, how samples may be used in
p.000051: future research.
p.000051:
p.000051:
p.000051:
p.000051: 5.1.1 Information
p.000051: Some items that researchers should keep in mind as they provide information to the study participants are
p.000051: summarized below. These items may be based on regulatory requirements or currently may
p.000051: be recommendations as ethical “best practices.”
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: Text Box 5-2. Common Rule Requirements:
p.000052: Elements of Informed Consent
p.000052: (1) An explanation of the purposes of the research
p.000052: (2) The expected duration of the subject's participation
p.000052: (3) A description of the procedures to be followed and identification of any experimental procedures
p.000052: (4) A description of any reasonably foreseeable risks or discomforts to the subject
p.000052: (5) A description of any reasonably expected benefits to the subject or others
p.000052: (6) A disclosure of appropriate alternative procedures that might be advantageous to the subject
p.000052: (7) A description of the extent that confidentiality will be maintained
p.000052: (8) For research involving more than minimal risk, an explanation about whether compensation or medical treatments
p.000052: are available if injury occurs
p.000052: (9) An explanation of whom to contact with questions about the research or to report a research-related injury
p.000052: (10) A statement that participation is voluntary, refusal to participate will involve no penalty, and the subject may
p.000052: discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled
p.000052: (11*) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or
p.000052: fetus, if the subject is or may become pregnant) that are currently unforeseeable
p.000052: (12*) Anticipated circumstances under which the subject's participation may be terminated by the investigator without
p.000052: regard to the subject's consent
p.000052: (13*) Any additional costs to the subject that may result from participation in the research
p.000052: (14*) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of
p.000052: participation by the subject
p.000052: (15*) A statement that significant new findings developed during the course of the research that may relate to the
p.000052: subject's willingness to continue participation will be provided to the subject.
p.000052: (16*) The approximate number of subjects in the study
p.000052: * Included if appropriate [40 CFR 26.116(b)]
p.000052:
p.000052:
p.000052:
p.000052: • The information “shall be in language understandable to the subject” (40 CFR 26.116). This may require forms
p.000052: to be written and administered in different languages during a study. For example, the National
p.000052: Children’s Study (NCS) plans to produce all consent materials in English and Spanish, with other
p.000052: translations made available as needed (NCS, 2007).
p.000052: Participants often find discussions with research staff more useful than written consent forms (p. 103, NRC & IOM,
p.000052: 2005). NCS plans to pilot test an interactive, computer-based audio/video consent tool and to compare it
p.000052: with traditional written informed consent approaches (NCS, 2007).
p.000052: • The information being discussed, including the explanation of the purpose of the research and the
p.000052: description of the study procedures, should be written or discussed at a level that the participant can
p.000052: understand.17 The National Institutes of Health recommends writing consent forms as “plain language
p.000052: documents that explain the research in an honest, straightforward way” and suggest that doing so will
p.000052: help enhance public trust (Recommendation 11, NIH, 2005).
p.000052: • The consent form should contain sufficient information to describe the study procedures, but not
p.000052: so much information that it causes confusion and results in the participant not understanding the study. There
p.000052: is not agreement on what the appropriate level of information is. IRBs do not agree on the level of
p.000052: information; some require lengthy descriptions of the study, whereas others prefer concise information.
p.000052: Ultimately, the IRB dictates the language of the informed consent document, and the researcher will
p.000052: need to comply. It will benefit the researcher to discuss the consent process with their IRB when they develop
p.000052: the consent form document and process (p. 108, NRC & IOM, 2005).
p.000052: • In observational human exposure studies, information about the risks of the hazards being studied needs to be
p.000052: conveyed to the participants during the consent process. Information should be provided to the study participant
p.000052: on what hazards pertinent to the topic of the study may be present in the participant’s
p.000052: environment, particularly those microenvironments being studied, what hazards will continue to exist in
p.000052: those microenvironments after the research is completed, and how those hazards may adversely
p.000052: affect the participant’s health (NRC & IOM, 2005).
p.000052: • The informed consent process should describe whether any study results will be provided
p.000052: to
p.000052: Ethically, “language understandable to the subject”
p.000052: goes beyond simply using the appropriate language;
p.000052:
p.000052: the researcher is compelled also to consider readability and vocabulary (e.g., avoiding jargon
p.000052: or terminology that may be clear to the researcher but which may confuse or intimidate the potential subject)
p.000052: if the information is to be understandable.
p.000052: • Information may be presented orally in addition to an appropriately written document (40 CFR 26.117).
p.000052: 17 A survey of IRBs found that their readability standards ranged from 5th- to 10th-grade level (Paasche-Orlow et al.,
p.000052: 2003). Interestingly, the same report found that, 92% of the time, the sample consent forms provided by the IRBs did
p.000052: not meet their own readability standards. The NRC & IOM report (p. 107, NRC & IOM, 2005) discusses an NCI effort to
p.000052: simplify informed consent forms by using text targeted at 8th-grade reading level. More information about the NCI
p.000052: template may be found at www.nci.nih.gov/clinicaltrials/understanding/simplification-of-informed consent-docs/page2
p.000052: (accessed September 12, 2007).
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053: participants and, if so, how and when (p. 101, NRC & IOM, 2005).
p.000053: • For studies involving children as participants, it generally is regarded as desirable that the
p.000053: informed consent process should involve both parents (assuming that there are two competent
...
p.000054: document (NRC & IOM, 2005).
p.000054: • The most effective way to improve comprehension is by talking one-on-one with study participants.
p.000054: “Having a study team member or a neutral educator spend more time talking one-on-one to study
p.000054: participants appears to be the most effective way of improving research participants’ understanding”
p.000054: (Flory and Emanuel, 2004).
p.000054: • The information being exchanged (e.g., explanation of the purpose of the research, description of the study
p.000054: procedures) should be written at a level that the participant can understand (NRC & IOM, 2005).
p.000054: • The researcher should describe the benefits of participation in the study [40 CFR 26.116(a)(3)], but
p.000054: should not promise any outputs or outcomes that he or she cannot deliver. Participants often misunderstand the
p.000054: purpose of the research. The researchers also should attempt to reduce the likelihood of “therapeutic
p.000054: misconception”19 or related misunderstandings in which the participant anticipates a benefit that does
p.000054: not really exist, such as reduction of the hazard in an observational study (NRC & IOM, 2005).
p.000054: • The consent procedure should include some test of the participants to demonstrate that they truly understand the
p.000054: information that is being conveyed (IOM, 2002).
p.000054: • Tools to assess comprehension have been developed, but, as described in NRC & IOM (2005), there are no standard
p.000054: mechanisms for assessing comprehension. Tests for appropriate grade-level language can be performed, but
p.000054: additional comprehension testing should be considered as well (Flory and Emanuel, 2004).
p.000054: • Researchers need to develop innovative approaches to improve comprehension. Multimedia, such as video or graphics,
p.000054: may be used but have had limited success in the past (NRC & IOM, 2005; Flory and Emanuel, 2004). NCS
p.000054: currently is developing a highly sophisticated video consent tool that may be able to
p.000054:
p.000054:
p.000054: 19 Therapeutic misconception is a term that refers to an inaccurate understanding on the part of a research participant
p.000054: that a direct therapeutic benefit will be provided by virtue of participation in a clinical trial.
p.000054: Researchers performing observational human exposure studies should be aware of the potential for misunderstandings to
p.000054: arise that are analogous to the misunderstanding represented by the therapeutic misconception. Ensuring comprehension
p.000054: of the study and its expected results is important to this issue.
p.000054: serve as a model going forward. The video presentation will include embedded questions
p.000054: to assess the participant’s understanding of the key elements of NCS and what their participation
p.000054: will involve (NCS, 2007).
p.000054: • Development of written materials with appropriate languages and comprehension levels is only part of the
p.000054: communication challenge. In communities where languages other than English are spoken, it will be
p.000054: important that the research team be able to communicate orally with participants, often in ad hoc
...
p.000070: Community can be defined broadly (as a system of interrelated groups operating to meet the needs of its
p.000070: members) or more narrowly (as the population from which study participants are selected). For observational
p.000070: field studies, the Expert Panel from the workshop suggested the narrow definition. A narrow
p.000070: definition allows social and cultural factors to be included but excludes government agencies, industry, and
p.000070: others who do not necessarily represent the interests of the participants (ERG, 2007).
p.000070: Central to the definition of a community is a sense of “who is included and who is excluded from
p.000070: membership” (NRC & IOM, 2005). A person may be a member of a community by choice, as with voluntary
p.000070: associations, or by virtue of their innate personal characteristics, such as age, gender, race, or
p.000070: ethnicity (NRC & IOM, 2005). As a result, individuals may belong to multiple communities at any one time. When
p.000070: initiating community engagement efforts, one should be aware of these complex associations in deciding which
p.000070: individuals to work with in the targeted community.
p.000070: Quandt et al. (2001) discuss a CBPR research project, Preventing Agricultural Chemical Exposure in
p.000070: North Carolina Farmworkers, where the process of defining a community was complicated by language,
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
p.000070: sense of community was nurtured among the farmworkers collectively (O’Fallon and Dearry, 2002).
p.000070: Understanding and describing a community (CDC, 1997) involves exploring factors related to
p.000070: • people (including socioeconomics and demographics, health status, and cultural and ethnic characteristics),
p.000070: • location (geographic boundaries),
p.000070: • commonalities (including shared values, interests, and motivating forces), and
p.000070: • power relationships (including formal and informal lines of authority and influence, stakeholder relationships, and
p.000070: resource flows).
...
p.000071: al. (2005).
p.000071:
p.000072: 72
p.000072:
p.000072: Development Corporation, and the Warren Conner Development Coalition for a study investigating asthma is
p.000072: available at http://depts.washington.edu/ccph/pdf_files
p.000072: /MOU10.pdf.
p.000072: Work within communities involves a considerable investment of researchers’ and residents’ time. It should be an
p.000072: ongoing, interactive exchange of information and ideas between the researchers and the community members,
p.000072: where voices are both heard and honored. Trust is fostered when all interested parties feel that they have
p.000072: influence, and that their input contributes to the community effort. The collaborations should be
p.000072: inclusive of the entire community, including those members with incompatible interests and perceptions. If
p.000072: participation, influence, and benefits are limited only to some of the partners, then distrust is likely, and
p.000072: the potential benefits of community involvement may be lost. Being inclusive can create some
p.000072: organizing challenges, but the benefit of effective community involvement “has the potential to
p.000072: lead to greater understanding of community perspectives of the risk and benefits of research, improve informed
p.000072: consent, increase study enrollment, enhance data validity and quality, and build trust for research” (NRC & IOM, 2005).
p.000072:
p.000072: 6.2.4 Importance of Language and Communications with the Community
p.000072: Even when all partners and community members are speaking the same language, some terms are not
p.000072: necessarily understood by all. Communications with participants should be reviewed by all partners to ensure
p.000072: that the language used will be appropriate for all participants. At times, one method to
p.000072: communicate research findings will not fit all community members and partners. Even among the partners,
p.000072: understanding each other’s meanings is essential, so that all partners can move forward with a common
p.000072: understanding (Israel et al., 2005b).
p.000072: Furthermore, Minkler and Wallerstein (2003) note that “research must be produced, interpreted, and
p.000072: disseminated to community members in clear, useful, and respectful language.” Researchers, and especially
p.000072: researchers in a government agency, may have their own distinct lexicon. Researchers should be careful to avoid
p.000072: acronyms, jargon, or technical terms that may obscure the meaning or intimidate participants who are
p.000072: not familiar with the terms. Communicating in “plain language” to “explain the research in an
p.000072: honest, straightforward way” will help build a strong relationship with the community and the
p.000072: participants and
p.000072: also help enhance public trust (Recommendation 11, NIH, 2005).
p.000072: Culturally sensitive communication is necessary to developing effective research partnerships with
p.000072: communities. To develop effective communications, researchers must understand key aspects of the cultures
p.000072: influencing the intended audience and build that understanding into the communication strategy (Tillman,
p.000072: 2002). The symbols, metaphors, visuals (including clothing, jewelry, and hairstyles), types of
p.000072: actors, language, and music used in communication materials all convey culture. Discussions with
p.000072: community members can assist researchers in identifying messages and images that resonate across groups or
p.000072: suggesting situations in which different messages or images are likely to work best.
p.000072: As discussed above and in Sections 5 and 7, communication materials must be tailored for each
p.000072: individual community and must be written in a language and at a reading level that will ensure comprehension.
p.000072: Many IRBs require materials to be prepared at a 5th grade reading level. Researchers should evaluate the
p.000072: reading level of all data collection instruments and study communication materials and should objectively
p.000072: measure comprehension in pretests prior to use in the study. Similarly, if translations of materials are
p.000072: required, certified translating services should be used to ensure accuracy and comprehension.
p.000072:
p.000072: 6.2.5 Recognizing and Addressing Cultural Differences
p.000072: Building and maintaining appropriate community and stakeholder relationships requires acknowledgment of the
p.000072: diversity within communities with regard to many factors, including, but not limited to, race/ethnicity,
p.000072: religious beliefs, heritage, and lifestyles. Different groups in the study area may have different
p.000072: cultural norms and practices. The researchers should take these issues into consideration as they work in the
p.000072: community. Community partners can help researchers design the study to be attentive to the increasing
p.000072: heterogeneity of community groups (Minkler and Wallerstein, 2003, Chapter 4) and to the different
p.000072: boundaries of privacy (crucial when designing sampling strategies) of different groups (Israel et al., 2005b, Chapter
p.000072: 11).
p.000072: Vega (1992) provides a thorough discussion of the theoretical and pragmatic implications of
...
p.000078: justice. (Section 3.3). Office of Environmental Justice. EPA-300/R-04-002. Available:
p.000078: http://epa.gov/compliance/resources/policies/ej/ej toolkit.pdf
p.000078:
p.000078: U.S. EPA (U.S. Environmental Protection Agency). (1995). The EPA’s Environmental Justice Strategy. Available:
p.000078: http://epa.gov/compliance/resources/policies/ej/ej_strategy_ 1995.pdf
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000079: 79
p.000079:
p.000079:
p.000079:
p.000079:
p.000079:
p.000079:
p.000079:
p.000079:
p.000079:
p.000079: SECTION 7
p.000079: Designing and Implementing Strategies for Effective Communication
p.000079:
p.000079:
p.000079:
p.000079: Successful implementation of observational human exposure studies requires effective communications between
p.000079: the researchers, study participants, community representatives, community members, stakeholders, and the
p.000079: public. The previous two sections established the need for communications that are “on-going, interactive
p.000079: dialogue…involving the disclosure and exchange of relevant information, discussion of that information, and
p.000079: assessment of the individual’s understanding of the discussion” (Recommendation 4.1, IOM, 2002). NIH
p.000079: advocates “plain language” that explains the research “in an honest, straightforward way” (Recommendation 11, NIH,
p.000079: 2005). Indeed, strong relationships can be built with participants, the community, and stakeholders only if
p.000079: there are clear and effective communications between the researchers and the community. The previous section
p.000079: illustrates, also, that effective communication is bidirectional; it involves listening as well as
p.000079: “speaking.” The ethical value of respect for persons, including respect for one another’s
p.000079: autonomy and welfare, demands that researchers, participants, community members, and stakeholders
p.000079: strive to establish effective communications and to foster a relationship of trust and respect. The researchers
p.000079: should make a commitment to effective communications and make the appropriate investment of time and
p.000079: resources to ensure that the communications are at an appropriate level and are truly effective. Researchers should
p.000079: regard communications as intrinsic to the ethical basis for the study.
p.000079: With the ethical basis for bidirectional communication assumed as a given, and the need
p.000079: for open and honest bidirectional communications having been well established in the previous
p.000079: sections that discussed relationships between the researchers and the participant (Section 5) and the
p.000079: researchers and the community (Section 6), this section discusses strategies and tools that researchers may
p.000079: find useful in developing
...
p.000081: the community, stakeholders or the media nor only a plan for reacting to “negative” feedback.
p.000081: Recognizing that the communication strategy must address the bidirectional nature of communications with the study
p.000081: participants and the community to be effective, it is important that the communication strategy and
p.000081: implementation plan be developed in collaboration with the community and other stakeholders. As discussed in
p.000081: previous sections, members of the community in which the study will be performed will provide valuable input into the
p.000081: development of the communication strategy by providing information about the community culture, norms,
p.000081: attitudes, perceptions, etc. They will provide, not only expertise about the community, but also
p.000081: experiences and lessons learned about previous communications activities in the community. It
p.000081: is important to engage community representatives and stakeholders early in the process of development of the
p.000081: communication strategy, the implementation plan, and the communication tools.
p.000081: Researchers also may find it helpful to seek guidance on how to communicate more effectively,
p.000081: especially because that is not a routine part of their training or experience. They may consult and learn from
p.000081: communications specialists in their organization. In addition, a wide variety of resources are
p.000081: available. For example, the Federal Communicators Network (FCN) (www.fcn.gov) has prepared a “communicators
p.000081: guide” that offers advice on how to communicate—in plain language, in easily digestible “chunks,” and in
p.000081: a form that will be used. They emphasize that “good communication is difficult because it
p.000081: requires a lot of effort, time, and patience” (FCN, 2001). Some tips from the guide to help federal communicators
p.000081: get their point across are listed in Text Box 7-2.
p.000081:
p.000081: Text Box 7-2. Tips for Getting Your Point Across
p.000081: • Be prepared.
p.000081: • Be confident.
p.000081: • Stay focused on your conversation and your listener.
p.000081: • Maintain eye contact with your listeners.
p.000081: • Make sure your listeners are following you by asking them for questions or feedback.
p.000081: • Do not lose your temper or get over-emotional.
p.000081: • Speak slowly and calmly; don’t raise your voice.
p.000081: • Speak clearly and concisely.
p.000081: • Get to the point; do not ramble.
p.000081: • Be kind, compassionate, and empathetic.
p.000081: • Be honest; do not play games.
p.000081: • Be assertive but tactful
p.000081:
p.000081:
p.000081: 7.2 Individuals and Groups Involved in the Communications
p.000081: An effective communication plan will identify and involve all of the individuals and relevant groups that
p.000081: should be included in the communications efforts. When conducting observational human exposure studies, this list
p.000081: may be quite long. Although researchers may desire to limit the number of individuals and groups involved to
p.000081: keep the effort as simple and focused as possible, they need to ensure that all potential stakeholders
p.000081: are identified. The communication plan should identify all groups, including community organizations
p.000081: and stakeholders, involved in a study, their roles and responsibilities in the study, how
...
p.000083: sites. In observational human exposure studies with repeated measurements over seasons or years,
p.000083: routinely meeting with participants can serve as a mechanism for providing study information to the
p.000083: participants and receiving feedback from the participants and the community about the study and their roles
p.000083: in it. Effective bidirectional communication with participants can be expected to improve their
p.000083: participation in the study (e.g., in completing surveys and collecting personal samples) and for improving
p.000083: retention in longitudinal studies. However, it is essential that the researcher recognize the implications
p.000083: of such meetings on privacy and confidentiality issues for the participants and develop
p.000083: communications to advise the participants of these issues.
p.000083: Community meetings also are effective for maintaining communications throughout a study. They
p.000083: provide the opportunity to disseminate information to
p.000083:
p.000083:
p.000084: 84
p.000084:
p.000084: community representatives and to obtain feedback. They also provide an opportune setting for news releases to
p.000084: the media to maintain or increase interest in the study.
p.000084:
p.000084: 7.4 Communicating at Different Levels
p.000084: The diversity of interested people and groups often means that communications materials should be
p.000084: developed at different levels of scientific literacy. In any case, the materials should all be written in
p.000084: “plain language” that is honest and straightforward. Stableford and Mettger (2007) state that “plain language
p.000084: embodies clear communication.” Many researchers mistakenly believe that the term means just using simple words,
p.000084: or worse, ‘‘dumbing things down.’’ It actually refers to communications that engage and are accessible to
p.000084: the intended audience.
p.000084: A 1998 Presidential memorandum required that “plain language” be used in all governmental
p.000084: communications with the public. That memorandum stated, “By using plain language, we send a
p.000084: clear message about what the Government is doing, what it requires and what services it offers. Plain language
p.000084: saves the Government and the private sector time, effort, and money.” Plain language is reader friendly and designed to
p.000084: increase the participant’s understanding of the communication material. It serves as a means by which lay
p.000084: audiences can access and understand scientific information. Researchers desiring to use plain language in
p.000084: their verbal and written communications with communities must decide on key messages to include and
p.000084: delete unnecessary descriptive, bureaucratic, or jargon-filled language. Researchers should use words that
p.000084: commonly are understood, rather than difficult abstract terms and concepts. A friendly,
p.000084: conversational tone is used to engage the lay audience, rather than a formal, scholarly tone that
p.000084: distances the community. Stableford and Mettger (2007) argue that proficiency in creating appropriate plain
p.000084: language materials is an acquired skill that requires knowledge and experience. “It is both an art and
p.000084: a science, requiring the ability to simultaneously think about the cognitive, emotional, and visual appeal of the
p.000084: piece as well as applying research- based strategies to ensure a truly easy-to-read and understand print
p.000084: material.”
p.000084: The Department of Health and Human Services (HHS) has developed a Web site that specifically
p.000084: address the issues related to “plain language” (see
p.000084: http://www.health.gov/communication/literacy/plainlang uage/PlainLanguage.htm). The site includes a list of
p.000084: references and other helpful resources.
p.000084: To maintain community engagement through the
p.000084: research process, it is critical that communications are at the appropriate level, and that materials are written at a
p.000084: reading level that is appropriate to the audience. For the nonscientist, many IRBs and other groups target
p.000084: materials to be used with participants and communities at a reading level no higher than the 8th grade to
p.000084: improve the likelihood of comprehension. In some communities, however, other factors, like primary languages other than
p.000084: English, educational disadvantages, etc., may require communications materials to be written in
p.000084: alternate languages and at different reading levels. The issue is comprehension, as was discussed in
p.000084: Section 5.1.2. Empirical testing of communication methods and content is essential to ensure
p.000084: comprehension (Health Canada, 2006).
p.000084: Researchers also should recognize that in this information age, dissemination of
p.000084: informational materials may be rapid and widespread. Therefore, even documents intended for scientific peers may
p.000084: benefit by including summary information in an executive summary or preface that a lay reader can
p.000084: understand.
p.000084:
p.000084: 7.5 Communications Materials
p.000084: Researchers need to communicate clearly with the many groups listed in Section 7.2 to develop their
...
p.000085: • Nature and purpose of the research
p.000085: • Anticipated benefits of the research
p.000085: • Risks, harms, costs, and inconvenience to the participant
p.000085: • Assurance that the participant freely can refuse to participate in or withdraw from the study
p.000085: • Details about remuneration
p.000085: • Names of the project sponsors and the researchers
p.000085: • Contact information for the researchers
p.000085: • Respect for privacy and confidentiality
p.000085: Leaflets and brochures that contain this information provide a tool for communication with study
p.000085: participants. However, these materials need to be written carefully using everyday terms that the
p.000085: average nonresearcher can understand. The brochure should be written in a friendly style that conveys the intent
p.000085: of the researcher to engage the reader as a collaborator on the study, not as a study “subject,” who will be told to do
p.000085: a series of tasks while participating in the study.
p.000085: These same leaflets and brochures can be used to inform other groups that either may be involved or
p.000085: interested in the study, such as community representatives, stakeholder organizations,
p.000085: the media, and the general public. The researcher should ensure that any brochure developed for the study includes
p.000085: accurate and complete information that is less likely to be misinterpreted by anyone who might
p.000085: pick up the brochure. Brochures and flyers that are used to announce a study or are used as recruiting tools
p.000085: should be carefully written in plain language to ensure that there is not a perception of activities that are
p.000085: unethical. For example, if flyers announcing a study state that study participants will be compensated, the flyer
p.000085: needs to ensure that the compensation is not the focus of the flyer, and that the payment does not appear to
p.000085: be excessive and coercive (see Section 5.2). Flyers announcing a study generally do not include the dollar
p.000085: amounts of payment.
p.000085: Researchers need to have similar concerns about all of the communication materials that are developed,
p.000085: regardless of the type of material, whether it is a direct mailing, a Web site, a news release, or a set of questions
p.000085: and answers (Q&As) used to respond to media or stakeholder inquiries. In developing the communication
p.000085: materials, the research staff should seek the assistance, advice, and input of people in their
p.000085: organization and community groups with experience in developing such materials. With all of these
p.000085: materials, the researchers should be concerned with how the materials could be misinterpreted, and whether
p.000085: there could be a perception that the study would not meet the highest scientific and ethical standards. In this age
p.000085: of rapid communications and increased accessibility to information, it is essential that communication materials
p.000085: are well developed, accurate, and understandable to all audiences that may read them.
p.000085: Research study Web sites are especially useful for communicating information about observational human
p.000085: exposure studies. Web sites should be developed early in
...
p.000086: disseminating study results to produce public health benefits, but there is not a consensus on when and how
p.000086: results should be reported to either communities or study participants. Although she did not identify
p.000086: well-developed guidance documents, she did identify some common themes. The first was that
p.000086: researchers are becoming aware of the importance of systematic planning of the research communications,
p.000086: planning that needs to be done early in the study.
p.000086:
p.000086:
p.000087: 87
p.000087:
p.000087: Second, organizations are recognizing the importance of communicating with communities. And, third, research
p.000087: professions are recognizing the importance of research communication and their responsibilities.
p.000087: There is a large body of literature on processes for risk communication (e.g., see Covello et al., 1989, 2007;
p.000087: U.S. HHS, 2002; ASTDR, 2007). Processes for risk communication are highly relevant to reporting results
p.000087: from observational human exposure studies, even though they may not include measurements of health outcomes or risk
p.000087: assessments.
p.000087: HHS has prepared a useful document entitled Communication in a Crisis: Risk Communication
p.000087: Guidelines for Public Officials, 2002. It is available online and in hard copy and includes a chapter
p.000087: on communicating complex, scientific, and technical information (U.S. HHS, 2002). They recommend
p.000087: using clear, nontechnical language, avoiding jargon, and putting technical terms into frames of reference
p.000087: that the public or other listeners can understand.
p.000087: Covello and Allen (1988) described seven cardinal rules for risk communication (Text Box 7-5) that are still quite
p.000087: applicable today. More recently, Covello et al. (2007) have developed a “message mapping” approach for
p.000087: risk communication. Message mapping is a process to anticipate the questions likely to be asked after an
p.000087: incident and to prepare clear and concise answers to the anticipated questions in advance. The approach builds on an
p.000087: understanding of current communications practices (e.g., short messages averaging 27 words, soundbites of around 9
p.000087: seconds, the most frequently asked questions after an incident) and typical human responses to crisis. The
p.000087: report lays out a series of steps to develop short, clear key messages to address stakeholder concerns
p.000087: in advance.
p.000087: judgment in terms of trust.” In times of crises, opinions about trustworthiness hinge largely on perceptions of
p.000087: caring and empathy, whereas competence and expertise are key factors when there is little or no stress. Figure 7-
p.000087: 1 is taken from the Covello et al. (2007) report and represents the relative importance of various
p.000087: factors in influencing whether or not people trust a speaker in times of crisis. Many of the principles and
p.000087: processes for crisis communications are applicable for communication of research results from observational human
...
p.000091:
p.000091: Fernandez CV, Kodish E, Weijer C (2003). Informing study participants of research results: an ethical imperative. IRB
p.000091: 25(3):12-19.
p.000091:
p.000091: Health Canada (2006). The Strategic Risk Communications Framework. Available: http://www.riskcommunications.gc.ca
p.000091: [accessed 18
p.000091: September 2007].
p.000091:
p.000091: IOM (Institute of Medicine) (2002). Responsible Research: A Systems Approach to Protecting Research Participants.
p.000091: Daniel D. Federman, Kathi E. Hanna, and Laura Lyman
p.000091:
p.000091:
p.000092: 92
p.000092:
p.000092: Rodriguez (eds). Washington, DC: The National Academies Press.
p.000092:
p.000092: Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005). Methods in Community-Based Participatory Research for Health. San
p.000092: Francisco, CA: Jossey-Bass.
p.000092:
p.000092: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for the NIH
p.000092: Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health, Director’s
p.000092: Council of Public Representatives, January 14, 2005. Available: http://copr.nih.gov/reports/public_trust.asp
p.000092: [accessed June 2007].
p.000092:
p.000092: Parkin RT (2004). Communications with research participants and communities: foundations for best practices. J Expo
p.000092: Anal Environ Epidemiol 14(7):516-23.
p.000092:
p.000092: Peters RG, Covello VT, McCallum DB (1997). The determinants of trust and credibility in environmental risk
p.000092: communication: an empirical study. Risk Anal 17(1):43-54.
p.000092:
p.000092: Stableford S and Mettger W (2007). Plain language: a strategic response to the health literacy challenge. J Public
p.000092: Health Pol 28:71–93.
p.000092:
p.000092: U.S. HHS (Department of Health and Human Services) (2002). Communicating in a Crisis: Risk Communication Guidelines for
p.000092: Public Officials, 2002. Available: http://www.riskcommunication.samhsa.gov/index.htm [accessed 13 June 2007].
p.000092:
p.000092: U.S. EPA (U.S. Environmental Protection Agency) (2007). Drinking Water Contaminants. Environmental Protection Agency.
p.000092: Available: http://www.epa.gov/safewater/contaminants/index.html [accessed 13 June 2007].
p.000092: Williams PR (2004) Health risk communication using comparative risk analyses. J Expo Anal Environ Epidemiol
p.000092: 14(7):498-515.
p.000092:
p.000092: World Health Organization (2005). WHO Air Quality Guidelines Global Update 2005. Available:
p.000092: http://www.euro.who.int/Document/E87950.pdf [accessed 13 June 2007].
p.000092:
p.000092: Additional Information Resources
p.000092: Reckelhoff-Dangel C, Petersen D (2007). Risk Communi- cation in Action: The Risk Communication Workbook.
p.000092: EPA/625/R-05/003. National Risk Management Research Laboratory, Office of Research and Development, U.S. Environmental
p.000092: Protection Agency, Cincinnati, OH. Available: http://www.epa.gov/nrmrl/pubs/625r05003/625r05003.pdf [accessed 18
p.000092: September 2007].
...
p.000095: researcher participation. Covert observation is said to have a “key advantage” that “the respondent or consumer is
p.000095: unaware that they are being observed, allowing their behavior to be observed naturally”
p.000095: (see http://www.asiamarketresearch.com/glossary/observatio nal-research.htm). This means that the
p.000095: subject’s behavior will be natural and uncontaminated by the researcher’s presence. On the other hand, covert
p.000095: observation may be construed to be deceitful and ethically questionable. Overt observations involve
p.000095: sampling surveys, polls, interviews, focus groups, etc. Validity of the data obtained this way may
p.000095: be shaded by people’s natural tendency to behave or respond ideally when they know they are being watched.
p.000095: Motorists routinely slow down when they think they are being observed by the police. Finally, the researcher may
p.000095: participate in the activity being observed. Ethnography is a long-term investigation of a group
p.000095: (often a culture) that is based on observations made while immersed in and, useually, participating in that
p.000095: group. “Ethnography provides a detailed exploration of group activity and may include
p.000095:
p.000095:
p.000096: 96
p.000096:
p.000096: literature about and/ or by the group.” (See
p.000096: http://writing.colostate.edu/guides/research/observe/com 3a1.cfm). One obvious problem with immersion
p.000096: techniques is that the researcher may lose his or her objectivity.
p.000096: In the common language use of the term observational research, it appears to the authors
p.000096: that some people understand the term to imply that the observations are both benign and often covert,
p.000096: that is, without interaction with the persons being studied. That is not the case in NERL’s observational human
p.000096: exposure studies. The research often takes place in and around the homes of the participants. Often, the research
p.000096: involves asking the participant to answer a questionnaire and to provide personal samples (e.g., urine,
p.000096: blood). Collection of survey information and personal urine and blood samples cannot be done covertly, and
p.000096: collecting a blood sample is not considered to be benign.
p.000096: Observational Research in NERL: NERL’s observational human exposure studies entail the
p.000096: collection of environmental or biological samples, data, and information from study participants and their
p.000096: surroundings in their everyday environments, as they go about their normal activities, for the purpose of
p.000096: quantifying the contact between the participant and the agent being studied. As such, the studies are designed
p.000096: to meet the regulatory definition of observational research in the CFR. NERL’s studies also meet the scientific
p.000096: definition of an observational study, because the variable being studied, exposure to some agent, is not controlled by
p.000096: the NERL scientists. The observations are not covert, and they may or may not be noninvasive (e.g.,
p.000096: sometimes blood samples may be collected).
p.000096: Because NERL’s observational human exposure studies meet the definition of human subjects research as set forth
...
p.000096: to sterilize the puncture site before drawing blood. But this requirement does not constitute intentional
p.000096: exposure because the research is not the study of isopropyl alcohol but of some other agent. Incidental
p.000096: exposures to chemicals like isopropyl alcohol still must be considered from a safety perspective, pass both scientific
p.000096: and ethical review, and be approved by the IRB, but such incidental exposures do not constitute intentional
p.000096: exposure.
p.000096: The second requirement is that the exposure as experienced by the subject “would not have occurred but for the
p.000096: human subject’s participation in the study.” The two primary ways in which intentional exposure studies commonly meet
p.000096: this definition are by the direct introduction of the study substance into the research environment
p.000096: under the control of the research protocol or by scripting the participants’ activities in such a way that their
p.000096: contact with the study substance is determined by the research. Although either would be sufficient to meet
p.000096: the regulatory definition, many, if not most, intentional exposure studies attempt to control both.
p.000096: Because “exposure is quantified as the concentration of the agent in the medium in contact integrated over the
p.000096: time duration of that contact,” intentional exposure studies are usually more scientifically robust if both
p.000096: the concentration of the agent and the duration of the exposure are controlled by the research.
p.000096:
p.000096:
p.000096:
p.000097: 97
p.000097:
p.000097: Observational Research: In the language of the Code of Federal Regulations, “observational research means
p.000097: any human research that does not meet the definition of research involving intentional exposure of a
p.000097: human subject” (40 CFR 26.302).
p.000097: By this definition, observational research encompasses all human research that does not meet the
p.000097: definition of intentional exposure. As a consequence, it is a broad regulatory category that includes a variety of
p.000097: research domains, including human research that does not involve the study of exposures at all. This regulatory
p.000097: definition of observational is sufficiently broad, moreover, that it encompasses study types that
p.000097: this document is not intended to address. For example, it may be possible to design an intervention study that
p.000097: does not bring about or script in any way the participants’ exposure to a substance, but rather reduces or
p.000097: mitigates it. (Consider a study to test whether professional cleaning of the carpets, floors, walls, and
p.000097: other surfaces in a home might lead to a lower exposure to a residential contaminant or a study to determine if wearing
p.000097: a particle mask would reduce an individual’s exposure to smoke from forest fires.) Such a study
p.000097: might meet the regulatory definition of observational research (Note: The final decision in regard to whether
p.000097: any EPA study meets the definition of observational research resides with the Agency’s HSRRO), but it
p.000097: would not meet the authors’ intentions regarding “observational human exposure studies” as they are defined
...
p.000108: should address in the design and implementation of observational human exposure measurement studies, with the emphasis
p.000108: on the areas requiring ethical considerations. Does each section identify the major areas and issues where ethical
p.000108: considerations should be addressed?
p.000108: 2. The document is intended to serve as a reference and resource of information that researchers can use in the design
p.000108: and implementation of observational exposure studies. For each section, are there additional sources of information
p.000108: that should be considered for inclusion?
p.000108: 3. Is the information presented accurately and clearly in each section?
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000109: 109
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109: Appendix C
p.000109: Recommended Content of a Human Subjects Protocol
p.000109:
p.000109:
p.000109:
p.000109: The Council for International Organizations of Medical Sciences (CIOMS, 2002) has developed a comprehensive list of
p.000109: items that they recommend for inclusion in a human subjects research protocol. Many of the items that they identify
p.000109: are also useful for observational human exposure studies.
p.000109:
p.000109: Items Relevant to Observational Human Exposure Studies
p.000109:
p.000109: (1) The title of the study
p.000109: (2) A summary of the proposed research in lay or nontechnical language
p.000109: (3) A clear statement of the justification for the study
p.000109: (4) The investigators’ views of the ethical issues and considerations raised by the study and,
p.000109: if appropriate, how it is proposed to deal with them
p.000109: (5) A summary of previous studies on the research problem, including unpublished studies known to the
p.000109: investigators, and information on previously published research on the topic
p.000109: (6) A statement that the principles of the Belmont Report and requirements specified in 40 CFR 26 will
p.000109: be implemented
p.000109: (7) An account of previous submissions of the protocol for ethical review and their outcomes
p.000109: (8) A brief description of the sites where the research is to be conducted, including information about the
p.000109: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000109: epidemiological information about the population to be studied
p.000109: (9) The names and addresses of the funding organization, research partners, and collaborators
p.000109: (10) The names, addresses, institutional affiliations, qualifications, and experience of the
p.000109: principal investigator and other investigators
p.000109: (11) The objectives of the study, its hypotheses or research questions, its assumptions, and
p.000109: its variables
p.000109: (12) A detailed description of the design of the study
p.000109: (13) The number of research subjects needed to achieve the study objective, and how this was determined
p.000109: statistically
p.000109: (14) The criteria for inclusion or exclusion of potential subjects and justification for the exclusion of
...
p.000111: population or of a racially or ethnically defined group of people
p.000111: (39) A statement that any proven evidence of falsification of data will be dealt with in accordance
p.000111: with the policy of the sponsor to take appropriate action against such unacceptable procedures
p.000111:
p.000111: Source: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical
p.000111: Guidelines for Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland.
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000112: 112
p.000112:
p.000112:
p.000112:
p.000112:
p.000112:
p.000112:
p.000112:
p.000112: Appendix D
p.000112: Recommendations for Enhancing Public Trust
p.000112:
p.000112:
p.000112:
p.000112: Although the Report and Recommendations on Public Trust in Clinical Research for the NIH Director from the
p.000112: Director’s Council of Public Representatives (COPR) was developed in the context of NIH-supported clinical
p.000112: research, many of the recommendations are applicable to observational human exposure studies. A summary of
p.000112: recommendations from the report is provided below.
p.000112:
p.000112: Building Trust Through Community Partnerships
p.000112: Recommendation 1: Incorporate into the NIH mission and philosophy that it values the involvement of the
p.000112: community in research and create language that expresses this value.
p.000112: Recommendation 2: Encourage change in the culture of the scientific community to ensure that medical
p.000112: research is viewed in the context of a long- term commitment to the community, not a one-time research study.
p.000112: Recommendation 3: Investigate ways to provide mechanisms that allow for follow-up health care when a clinical
p.000112: trial or treatment ends.
p.000112:
p.000112: Building Relationships with Patients (Participants) (True partnerships with patients may not be possible, but
p.000112: bidirectional relationships must be enhanced.)
p.000112: Recommendation 4: Educate and reorient the current research community to the importance of treating the
p.000112: public as a partner in the research process.
p.000112: Recommendation 5: Set the expectation across the entire research community, NIH funded research and beyond, that
p.000112: study results and outcomes should be shared with the research participants and the larger community promptly
p.000112: and consistently. This will ensure translational research.
p.000112:
p.000112: Building Partnerships with Community Providers
p.000112: Recommendation 6: Take action to interest community providers in clinical research and
p.000112: maintain their involvement.
p.000112: Recommendation 7: Provide incentives (not just financial) for primary health care providers and community
p.000112: specialists to play a role in clinical trials.
p.000112:
p.000112: Building Trust in Scientists
p.000112: Recommendation 8: Engage researchers, educators, and academic institutions in incorporating the public's
p.000112: perspective consistently at every level of training and in both the conduct of clinical research and the publication of
p.000112: findings from that research.
...
Social / Literacy
Searching for indicator literacy:
(return to top)
p.000067:
p.000067: Partnership Balanced discussion and shared
p.000067: decisionmaking among participants concerning risks, responsibilities, expectations, benefits, and investment.
p.000067:
p.000067: Respect Value the diversity of culture, history, beliefs and opinions within the community for
p.000067: improved understanding.
p.000067:
p.000067: Asset Utilization Identify and mobilize community assets to
p.000067: improve scientific credibility of the interpretation and dissemination of results.
p.000067:
p.000067: Flexibility Anticipate changes within the community in
p.000067: regard to perceived benefits of research and stakeholder interest and additional time and resource needs.
p.000067:
p.000067: Commitment Prepare to engage the community beyond the constraints of the research projects, before and after,
p.000067: to promote longevity of the relationship for future research .
p.000067:
p.000067:
p.000067: Furthermore, institutional and community partners need to ensure that anyone involved as part of the
p.000067: research team has the requisite research and social skills. Researchers often place a greater emphasis on scientific
p.000067: over social skills and may, in turn, assume that they have
p.000067:
p.000067:
p.000068: 68
p.000068:
p.000068: the necessary expertise to conduct research in community settings. Likewise, research staff from
p.000068: the community should have knowledge of research fundamentals. Education and training targeted at
p.000068: both the institutional researcher and the community researcher may, respectively, improve the competence
p.000068: of researchers to work with communities and the scientific literacy of the public.
p.000068: A recent NERL study, the Detroit Exposure and Aerosol Research Study (DEARS), included community members as
p.000068: paid members of the research team. The community researchers were instrumental in recruiting study
p.000068: participants from the seven study neighborhoods in Detroit that required multiple door-to-door visits to
p.000068: the homes of potential participants to discuss the DEARS study. The success of DEARS was dependent
p.000068: on researchers developing strong relations with community leaders and State and local organizations.
p.000068: A second approach to community involvement is to seek community consultation and review. Researchers may
p.000068: periodically meet with community residents in a process of “engagement, dialogue, and feedback” (Dula, 1994) to
p.000068: discuss research plans, research progress, and results. The objective is to seek a dialogue with
p.000068: community residents to promote co-learning and asset sharing between the researchers and the community.
p.000068: Effective communication⎯open, honest, jargon free⎯is imperative to the successful use of this approach.
p.000068: Effective communication ensures that the community has a voice in the research process for the expressed
p.000068: purpose of increasing the community’s trust and engagement in the research, the applicability of the
p.000068: research to the community’s needs, and the benefit of the research to the community. Authentic community
p.000068: consultation embraces the “experiential knowledge of the average citizen” (Leung et al., 2004). When
...
p.000083: and interest in the study. This can be aided by providing project progress reports and interim
p.000083: results to the participants and the community through community meetings, mailings, or Web
p.000083: sites. In observational human exposure studies with repeated measurements over seasons or years,
p.000083: routinely meeting with participants can serve as a mechanism for providing study information to the
p.000083: participants and receiving feedback from the participants and the community about the study and their roles
p.000083: in it. Effective bidirectional communication with participants can be expected to improve their
p.000083: participation in the study (e.g., in completing surveys and collecting personal samples) and for improving
p.000083: retention in longitudinal studies. However, it is essential that the researcher recognize the implications
p.000083: of such meetings on privacy and confidentiality issues for the participants and develop
p.000083: communications to advise the participants of these issues.
p.000083: Community meetings also are effective for maintaining communications throughout a study. They
p.000083: provide the opportunity to disseminate information to
p.000083:
p.000083:
p.000084: 84
p.000084:
p.000084: community representatives and to obtain feedback. They also provide an opportune setting for news releases to
p.000084: the media to maintain or increase interest in the study.
p.000084:
p.000084: 7.4 Communicating at Different Levels
p.000084: The diversity of interested people and groups often means that communications materials should be
p.000084: developed at different levels of scientific literacy. In any case, the materials should all be written in
p.000084: “plain language” that is honest and straightforward. Stableford and Mettger (2007) state that “plain language
p.000084: embodies clear communication.” Many researchers mistakenly believe that the term means just using simple words,
p.000084: or worse, ‘‘dumbing things down.’’ It actually refers to communications that engage and are accessible to
p.000084: the intended audience.
p.000084: A 1998 Presidential memorandum required that “plain language” be used in all governmental
p.000084: communications with the public. That memorandum stated, “By using plain language, we send a
p.000084: clear message about what the Government is doing, what it requires and what services it offers. Plain language
p.000084: saves the Government and the private sector time, effort, and money.” Plain language is reader friendly and designed to
p.000084: increase the participant’s understanding of the communication material. It serves as a means by which lay
p.000084: audiences can access and understand scientific information. Researchers desiring to use plain language in
p.000084: their verbal and written communications with communities must decide on key messages to include and
p.000084: delete unnecessary descriptive, bureaucratic, or jargon-filled language. Researchers should use words that
p.000084: commonly are understood, rather than difficult abstract terms and concepts. A friendly,
p.000084: conversational tone is used to engage the lay audience, rather than a formal, scholarly tone that
p.000084: distances the community. Stableford and Mettger (2007) argue that proficiency in creating appropriate plain
p.000084: language materials is an acquired skill that requires knowledge and experience. “It is both an art and
p.000084: a science, requiring the ability to simultaneously think about the cognitive, emotional, and visual appeal of the
p.000084: piece as well as applying research- based strategies to ensure a truly easy-to-read and understand print
p.000084: material.”
p.000084: The Department of Health and Human Services (HHS) has developed a Web site that specifically
p.000084: address the issues related to “plain language” (see
p.000084: http://www.health.gov/communication/literacy/plainlang uage/PlainLanguage.htm). The site includes a list of
p.000084: references and other helpful resources.
p.000084: To maintain community engagement through the
p.000084: research process, it is critical that communications are at the appropriate level, and that materials are written at a
p.000084: reading level that is appropriate to the audience. For the nonscientist, many IRBs and other groups target
p.000084: materials to be used with participants and communities at a reading level no higher than the 8th grade to
p.000084: improve the likelihood of comprehension. In some communities, however, other factors, like primary languages other than
p.000084: English, educational disadvantages, etc., may require communications materials to be written in
p.000084: alternate languages and at different reading levels. The issue is comprehension, as was discussed in
p.000084: Section 5.1.2. Empirical testing of communication methods and content is essential to ensure
p.000084: comprehension (Health Canada, 2006).
p.000084: Researchers also should recognize that in this information age, dissemination of
p.000084: informational materials may be rapid and widespread. Therefore, even documents intended for scientific peers may
p.000084: benefit by including summary information in an executive summary or preface that a lay reader can
p.000084: understand.
p.000084:
p.000084: 7.5 Communications Materials
p.000084: Researchers need to communicate clearly with the many groups listed in Section 7.2 to develop their
p.000084: relationship with the participants in the study, to develop their partnership with the community, to gain
...
p.000091: 25(3):12-19.
p.000091:
p.000091: Health Canada (2006). The Strategic Risk Communications Framework. Available: http://www.riskcommunications.gc.ca
p.000091: [accessed 18
p.000091: September 2007].
p.000091:
p.000091: IOM (Institute of Medicine) (2002). Responsible Research: A Systems Approach to Protecting Research Participants.
p.000091: Daniel D. Federman, Kathi E. Hanna, and Laura Lyman
p.000091:
p.000091:
p.000092: 92
p.000092:
p.000092: Rodriguez (eds). Washington, DC: The National Academies Press.
p.000092:
p.000092: Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005). Methods in Community-Based Participatory Research for Health. San
p.000092: Francisco, CA: Jossey-Bass.
p.000092:
p.000092: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for the NIH
p.000092: Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health, Director’s
p.000092: Council of Public Representatives, January 14, 2005. Available: http://copr.nih.gov/reports/public_trust.asp
p.000092: [accessed June 2007].
p.000092:
p.000092: Parkin RT (2004). Communications with research participants and communities: foundations for best practices. J Expo
p.000092: Anal Environ Epidemiol 14(7):516-23.
p.000092:
p.000092: Peters RG, Covello VT, McCallum DB (1997). The determinants of trust and credibility in environmental risk
p.000092: communication: an empirical study. Risk Anal 17(1):43-54.
p.000092:
p.000092: Stableford S and Mettger W (2007). Plain language: a strategic response to the health literacy challenge. J Public
p.000092: Health Pol 28:71–93.
p.000092:
p.000092: U.S. HHS (Department of Health and Human Services) (2002). Communicating in a Crisis: Risk Communication Guidelines for
p.000092: Public Officials, 2002. Available: http://www.riskcommunication.samhsa.gov/index.htm [accessed 13 June 2007].
p.000092:
p.000092: U.S. EPA (U.S. Environmental Protection Agency) (2007). Drinking Water Contaminants. Environmental Protection Agency.
p.000092: Available: http://www.epa.gov/safewater/contaminants/index.html [accessed 13 June 2007].
p.000092: Williams PR (2004) Health risk communication using comparative risk analyses. J Expo Anal Environ Epidemiol
p.000092: 14(7):498-515.
p.000092:
p.000092: World Health Organization (2005). WHO Air Quality Guidelines Global Update 2005. Available:
p.000092: http://www.euro.who.int/Document/E87950.pdf [accessed 13 June 2007].
p.000092:
p.000092: Additional Information Resources
p.000092: Reckelhoff-Dangel C, Petersen D (2007). Risk Communi- cation in Action: The Risk Communication Workbook.
p.000092: EPA/625/R-05/003. National Risk Management Research Laboratory, Office of Research and Development, U.S. Environmental
p.000092: Protection Agency, Cincinnati, OH. Available: http://www.epa.gov/nrmrl/pubs/625r05003/625r05003.pdf [accessed 18
p.000092: September 2007].
p.000092:
...
Social / Marital Status
Searching for indicator single:
(return to top)
p.000018: concerns about exposures in their locales. NERL’s observational human exposure studies collect data to improve
p.000018: exposure and risk assessments, to develop risk management strategies, and to substantiate informational
p.000018: and educational materials for use by EPA program offices (e.g., Office of Pollution Prevention and Toxic
p.000018: Substances, Office of Air and Radiation, Office of Children’s Health Protection).
p.000018: Emanuel et al. (2000) contend that an ethical research study must provide a worthwhile social or
p.000018: scientific value. Ideally, observational human exposure studies can provide both a scientific value and a social
p.000018: value to the participants and their community when feasible. Whenever possible, researchers should work
p.000018: with communities to develop studies that can help address community problems and maximize the
p.000018: benefit to the participants and the community, both of which also assume a burden for participation in a
p.000018: research study.
p.000018: The study problems addressed in past observational human exposure studies conducted or supported by NERL
p.000018: have varied substantially, as described in Appendix A of this document. As shown in Table A-1, NERL’s studies
p.000018: have addressed exposures to particulate matter (PM), air toxics, persistent organic chemicals, and nonpersistent
p.000018: chemicals including pesticides. The studies have examined single routes of exposure (air) and multimedia
p.000018: exposures, including dietary exposure. The studies range from small-scale pilot studies to large
p.000018: probability-based samples. They have included cross- sectional, longitudinal, and convenience samples. Table A-1
p.000018: demonstrates that many of the studies are small in scale and were intended to test a methodology to see if it may
p.000018: prove useful for a subsequent large-scale probabilistic human exposure research effort. Both
p.000018: small-scale and large-scale human exposure studies do involve human subjects. This means that the studies
p.000018: must meet both ethical standards and regulatory requirements. Regardless of the study’s scale,
p.000018: the scientific study design must be technically sound and appropriate to meet the objectives of the study. But
p.000018: the nature and objectives of the scientific inquiry will be different when the study is designed
p.000018: to test a methodology versus when the study is intended to measure a representative
p.000018: distribution of people’s exposures. Defining the study problem is a critical and fundamental first step
p.000018: in the scientific process, because it
p.000018: will establish the objectives that the research will be designed to achieve and the uses to which the research
p.000018: data will be put. The details of the scientific design of the study will naturally be strongly
p.000018: influenced by the objectives that the research is intended to meet.
p.000018:
p.000018: 2.1.2 Justifying the Study
p.000018: Justification of any human study includes both a scientific and an ethical justification. In the list of seven
...
p.000061: persons.
p.000061: The IRB guidebook is an excellent resource for consideration of concerns and elements for equitable
p.000061: participant selection (U.S. HHS, 1993). It states that “Defining the appropriate group of subjects
p.000061: for a research project involves a variety of factors⎯ requirements of scientific design,
p.000061: susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness.” The IRB
p.000061: guidebook raises a number of points to consider in the process for selection of human participants (see Text Box
p.000061: 5-5).
p.000061: Various participant recruitment strategies may be used depending on the type of research being performed and the
p.000061: population of interest. This section addresses the strategies and approaches for identifying and contacting people and
p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
p.000062: 1. Who will bear the burden? Who will reap the benefits?
p.000062: 2. Is there a disproportionate burden on any single group?
p.000062: 3. Is the proposed subject population required or justified?
p.000062: 4. Are there susceptible groups of people who should be excluded from the research?
p.000062: 5. Are anticipated benefits distributed fairly? Do others have a greater need to receive any of the anticipated
p.000062: benefits?
p.000062: 6. Are the research burdens distributed fairly?
p.000062: 7. Will any special physiological, psychological, or social characteristics of the subject group pose special risks
p.000062: for them?
p.000062: 8. Would it be possible to conduct the study with other, less vulnerable subjects?
p.000062: 9. Has the selection process overprotected potential subjects who are considered vulnerable (e.g., children,
p.000062: cognitively impaired, economically or educationally disadvantaged persons, patients of researchers, seriously ill
p.000062: persons), so that they are denied opportunities to participate in research?
p.000062: 10. If the subjects are susceptible to pressures, are there mechanisms to reduce the pressures or minimize their
p.000062: impact?
p.000062:
p.000062:
p.000062: Some of the common approaches for identifying and making initial contact with potential participants include, but are
p.000062: not limited to
p.000062: • direct telephone or in-person contact with a person selected through a statistical sampling process
p.000062: to obtain a representative sample of the population being studied;
p.000062: • use of print or other media advertisements, often used to recruit people in a community with specific
p.000062: characteristics;
...
p.000062: contacts
p.000062: • Printed materials⎯brochures, flyers, newspaper advertisements, letters, and information articles
p.000062: • Audio/visual materials⎯radio and television scripts, video segments, public service announcements
p.000062: • Internet postings⎯study announcements and information, links to study materials, links to
p.000062: related information.
p.000062: The IRB reviews all recruitment material to ensure that it does not adversely affect the informed
p.000062: consent process, is consistent with the study protocol, and is likely to result in equitable participant
p.000062: selection. IRBs will carefully consider how information regarding payment for participation is
p.000062: presented to potential participants so as not to create undue influence.
p.000062: Participant recruitment may be performed directly by the researcher or staff members of the researcher’s
p.000062: organization, or other individuals or organizations may be asked to recruit or make initial informational
p.000062: contacts with potential participants. All persons involved in recruiting must adhere to the procedures
p.000062: and materials approved by the IRB. It is recommended that sponsoring organizations should not pay recruiters
p.000062: on a per- individual basis to minimize the likelihood that individual recruiters will put undue
p.000062: pressure on potential participants to enroll.
p.000062:
p.000062: 5.6 Retention Strategies
p.000062: Some observational human exposure studies require only a single visit or a single set of visits with a
p.000062: participant over a relatively short time period (e.g., 24 hours or 1 week). Other studies may involve
p.000062: repeated interaction with participants over longer periods of time. Longitudinal study designs require retention
p.000062: strategies that ensure that adequate sample sizes are maintained for meeting study objectives. It is
p.000062: recommended that researchers and IRBs evaluate the level of burden in longitudinal studies and ensure
p.000062: that retention strategies are not likely to create conditions of coercion or undue influence.
p.000062: Some of the common strategies for maintaining high retention rates in longitudinal studies are listed in Text
p.000062: Box 5-6.
p.000062:
p.000062: Text Box 5-6. Common Strategies for Maintaining High Retention Rates in Longitudinal Studies
p.000062: • Developing and maintaining a strong study identity
p.000062: • Building participant trust
p.000062: • Communicating regularly with participants
p.000062: • Providing feedback that is of use to participants
p.000062: • Maintaining confidentiality
p.000062: • Incorporating active participant tracking mechanisms
p.000062: • Maintaining reasonable levels of burden
p.000062: • Providing periodic tokens of appreciation
p.000062: • Providing reasonable levels of payment at each time point, sometimes including escalating payments or a higher
p.000062: final payment for completion of all study activities
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000063: 63
p.000063:
p.000063: It is important that strategies that use payments to encourage retention should be carefully
...
Social / Mothers
Searching for indicator mothers:
(return to top)
p.000008: concentrations are a key determinant of the longitudinal variation in personal exposure.” (NRC, 2004). These results
p.000008: have been instrumental in support of the National Ambient Air Quality Standard for PM (U.S. EPA, 1999).
p.000008:
p.000008:
p.000008: Volatile Organic Compounds (VOCs)
p.000008:
p.000008: EPA's Total Exposure Assessment Methodology (TEAM) studies found levels of about a dozen common organic pollutants to
p.000008: be 2- to 5-times higher inside homes than outside. Use of products containing organic chemicals may result in very high
p.000008: and persistent pollutant levels.
p.000008:
p.000008: EPA, States, and the Consumer Product Safety Commission worked together to influence manufacturers to voluntarily
p.000008: reduce emissions of toxic chemicals from consumer products, building materials, and furnishings, and to develop
p.000008: mitigation strategies and educational materials to teach people how to reduce their contact with chemicals indoors. As
p.000008: a result, contact with toxic chemicals indoors has been reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html).
p.000008:
p.000008:
p.000008: Formaldehyde
p.000008:
p.000008: Studies found elevated formaldehyde levels indoors and helped identify indoor sources.
p.000008:
p.000008: EPA worked with HUD, CPSC, and other agencies to limit formaldehyde in building or consumer products and to educate the
p.000008: public on how to reduce exposures (see www. epa.gov/iaq/formalde.html).
p.000008:
p.000008:
p.000008: EPA has adopted additional protections for children and pregnant or nursing mothers in Subparts B through
p.000008: D. These sections apply to all research either conducted or funded by EPA and are, therefore, directly applicable to
p.000008: NERL’s observational human exposure studies.4 Subpart B prohibits EPA from conducting or supporting research
p.000008: that involves intentional exposure of “a pregnant woman (and, thereby, her fetus), a nursing woman,
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
...
p.000102:
p.000102:
p.000102:
p.000102: NERL designed, contractor conducted
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: EPA designed and conducted with contractor support
p.000102:
p.000102: Table A-1. (Continued)
p.000102: Study Date Size Type Brief Description
p.000102: NERL Role
p.000102: First National 2001 168 Child care Probability- A collaborative study with the Department
p.000102: of Housing and HUD and CPSC Environmental centers based
p.000102: Urban Development (HUD) and the Consumer Product Safety study. NERL Health Survey of
p.000102: selection on Commission (CPSC) of pesticide use and young children’s collaborated
p.000102: and
p.000102: Child Care national scale (less than 6 years old)
p.000102: potential exposure to pesticides and conducted analysis
p.000102:
p.000102: Centers (CCC)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: A Pilot Study Examining Translocation Pathways Following a Granular Application of Diazinon to Residential Lawns (PET)
p.000102: Biological and Environmental Monitoring for Organo- phosphate and Pyrethroid Pesticide Exposures in Children Living in
p.000102: Jacksonville, FL (JAX)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: Exposure Assessment for Community- Acquired Legionnaires Disease
p.000102: Center for the Health Assessment of Mothers and Children of Salinas Quantitative Exposure Assessment Study (CHAMACOS)
p.000102: Feasibility of Macroactivity Approach To Assess Dermal Exposure (Daycare)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 2002
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 6 Households
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 9 Households in NERL exposure component
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 20 Children
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 9 Daycare centers
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience, multiday pilot study to test methodology for exposure measure- ments
p.000021:
p.000021:
p.000021:
p.000021: Convenience, cross- sectional
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Case-control
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
...
Social / Occupation
Searching for indicator job:
(return to top)
p.000086: understand the key elements of the research. The most effective way to improve comprehension is by talking
p.000086: one-on-one with study participants.
p.000086: To accomplish that, the researchers need to make a commitment to communicating with both the study
p.000086: participants and the community to inform them of the study and provide training as appropriate. This can
p.000086: require a substantial investment of time and resources, but it is critical to the success of the study.
p.000086: Working with study participants to inform them about the study and the scientific basis of the study will have
p.000086: many benefits. The more educated the participant is about the purpose of the study and the activities to be
p.000086: performed during the study, the more likely the participant will be to develop a beneficial
p.000086: researcher- participant relationship. By taking the time to inform the participant, the researcher demonstrates
p.000086: his or her commitment to the participant and conveys the importance or value of their
p.000086: participation in the study. If the researcher-participant relationship is well developed, the participant will have
p.000086: a higher level of trust in the researcher and will be likely to have more interest in the study and a positive
p.000086: outcome. If such a relationship is
p.000086: developed and the participant is informed about the study goals, the participant will take part more
p.000086: readily and effectively in the specific study activities. For example, a study participant who
p.000086: understands why time/activity information is critical to understanding exposure is likely to do a
p.000086: better job completing a time/activity log than a participant with no interest in the outcome of the study.
p.000086: In addition, an informed participant may have good suggestions for improving the study and the interactions
p.000086: with the participants and the community that the researchers should listen to and adopt. Developing the
p.000086: researcher-participant relationship and informing the participants also should improve retention in
p.000086: longitudinal, repeated measures studies because the participant feels that he or she is
p.000086: collaborating with the researcher and is not merely a study “subject.”
p.000086: Similarly, providing information on the research study to the community should provide significant
p.000086: benefits in terms of support to the research team and working with the team to facilitate the study in
p.000086: their community to address both the scientific issues and the community’s concerns. If community leaders understand
p.000086: the research problem, the study goals, and the study activities, they can more effectively articulate
p.000086: the community’s concerns to the researchers and integrate those issues into the study design. This will
p.000086: enhance their work with the research team during the design phase and will enable them to more
p.000086: effectively advise and assist during the implementation of the study.
p.000086:
p.000086: 7.7 Reporting Study Results to the Participant and Community
p.000086: Researchers need to develop the approach for reporting results to the participants,
p.000086: community, stakeholders, media, and others during the initial planning of the study. There are not
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Searching for indicator occupation:
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p.000007: human exposure studies that have been conducted over the past decade, and the reader is referred to the Journal
p.000007: of Exposure Science and Environmental Epidemiology and to Environmental Health Perspectives for examples of the
p.000007: objectives, designs, and results of these studies.
p.000007: NERL researchers have conducted and relied on observational human exposure studies for more than three
p.000007: decades. Examples of studies conducted or funded by NERL are listed in Appendix A, Table A-1. Common goals in those
p.000007: studies included those that follow.
p.000007: • Identify which chemicals or other stressors that people are exposed to during their normal activities in the
p.000007: environments that they occupy.
p.000007: • Measure the concentrations of the chemicals to which people are exposed.
p.000007: • Identify the most important routes and pathways of exposure.
p.000007: • Identify the factors that impact people’s exposures (i.e., determine the when, why, how, and how much
p.000007: that people are exposed to chemicals in the environment).
p.000007: These studies involve many different types of data collection efforts and typically include
p.000007: observations,
p.000007: measurements, and information on the following items.
p.000007: • Chemical concentrations in environmental media (air, water, soil, floor dust, and dust on surfaces)
p.000007: • Chemical concentrations in the diet (food and beverages).
p.000007: • Biomonitoring (measurements of biomarkers of exposure in urine, blood, and saliva)
p.000007: • Time, location, and activity information
p.000007: • Information on personal activities, product use, diet, occupation, and other factors that may
p.000007: impact exposure
p.000007: • Information on the characteristics of the environments that study participants occupy (homes, schools,
p.000007: offices, public access buildings, etc.)
p.000007: The information obtained in observational human exposure studies is used to better understand people’s
p.000007: contact with chemicals in the environment and to improve exposure assessments and risk assessments.
p.000007: This information is also essential for developing risk mitigation strategies and for developing
p.000007: educational materials and programs for reducing exposures and risks to chemicals or other stressors in the
p.000007: environment (see Table 1-1).
p.000007:
p.000007: 1.2 Ethical Issues in Observational Human Exposure Studies
p.000007: By definition, observational human exposure studies involve human subjects. Whenever their research
p.000007: involves human subjects, EPA researchers are required to ensure the protection of the study participants
p.000007: by complying with the Agency’s human subjects rules as set forth in 40 CFR 26.
p.000007: The Common Rule (Subpart A of the rules) represents basic regulatory actions (common to more than
p.000007: a dozen Federal departments or agencies) that are intended to ensure the protection of all human subjects. The
...
p.000104: ingestion. Analyze for metals and pesticides. Examine eating and food preparation areas too.
p.000104: Transferable residues Similar to surface wipes, using a surrogate for the transfer from the surface to the
p.000104: skin.
p.000104: Duplicate diet Use to assess ingestion exposures from food. Exact duplicate of amount and items
p.000104: eaten by participant and analyzed for pesticides, metals, etc. Includes drinking water samples as part of diet or other
p.000104: beverages consumed.
p.000104: Handled food Finger foods like cheese or luncheon meets that have been prepared and processed
p.000104: identically to foods children might eat to evaluate how much pollution may be removed from surfaces and ingested with
p.000104: the food.
p.000104: Human Activity Data
p.000104: Time-activity diaries Recall diaries to account for all times and activities in a day. Information
p.000104: includes location and activities.
p.000104: Activity loggers Device used to assess the nature of a person’s activities. Portable
p.000104: nephelometers have been used to keep up with people’s activities by showing when they were near PM sources.
p.000104: Accelerometers to measure level of activity of children at play. GIS and inertial devices to try to measure locations
p.000104: as a function of time of day.
p.000104: Questionnaires Query participants about things like daily activities for themselves or their
p.000104: children; housing characteristics; participant characteristics, including occupation, diet, smoking habits, hobbies,
p.000104: etc.; and recent use of pesticides or other consumer products.
p.000104: Videotaping Use videos to measure frequency and duration of mouthing activities in children.
p.000104: Household inventories Inventory consumer products in house. Use items to ask about usage frequency and
p.000104: history.
p.000104: Researcher observations Information about open doors and windows (air exchange), heating and cooking sources,
p.000104: pets, and other activities that may lead to potential exposures may be observed.
p.000104: Personal or Biological Samples
p.000104: Urine Urinary excretion of pollutants and their contaminants give important
p.000104: information about the nature of prior exposures and their magnitude.
p.000104: Personal air monitors Individual wears samplers on his/her person while going about normal activities to
p.000104: measure pollutants in breathing zone of individual.
p.000104: Hand wipes Hand wipes remove contaminants from skin surface. Analyze for pesticides, metals,
p.000104: organic chemicals, and use values to estimate dermal exposure and hand-to-mouth ingestion of pollutants.
p.000104: Dermal surrogates Participant may wear cotton garments or socks as a collector. Clothing is analyzed
p.000104: for pesticides, metals, organic chemicals, etc. Measured contaminant quantities are used to estimate potential for
p.000104: dermal exposure.
p.000104: Saliva samples Test for antibodies to infectious agents, suggesting prior exposure and infection
p.000104: by microbial agent. Blood Some epidemiological studies that NERL scientists have
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Social / Police Officer
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p.000022: • Questions should be unambiguous.
p.000022: • Questions should be relevant to the study.
p.000022: • Questions should not be too personal.
p.000022: • The questionnaire should be as short as possible.
p.000022: • The questions should not be leading (e.g., internally suggestive of the answer).
p.000022: • Questions should follow a logical order.
p.000022:
p.000022:
p.000022:
p.000022: 2.2.5 Information Collection Rule
p.000022: As Federal employees, NERL researchers also must be aware of Information Collection Rule requirements. The
p.000022: Paperwork Reduction Act stipulates that every Federal agency must obtain approval from OMB before collecting
p.000022: the same or similar information from 10 or more members of the public. An Information Collection Request (ICR)
p.000022: is required if the same or similar information is being collected from 10 or more non- Federal
p.000022: respondents within a 12-month period, even if the information collection is voluntary. Generally, any
p.000022: survey, questionnaire, monitoring, reporting, or recordkeeping requirement imposed on
p.000022: non-Federal respondents by EPA will require an ICR. Information collections associated with all cooperative
p.000022: agreements funded by the EPA require an ICR. When an ICR is required, it must be approved by OMB
p.000022: before the collection begins, regardless of whether the collection of information is mandatory, voluntary,
p.000022: or required to receive a benefit. The principal investigator must prepare an ICR and submit it to the
p.000022: appropriate Office of Environmental Information Desk Officer.
p.000022: An ICR
p.000022: • describes the information to be collected,
p.000022: • provides justification for why the information is needed, and
p.000022: • estimates the time and cost for the public to answer the request.
p.000022: Information about ICRs and their requirements is available to NERL and other EPA staff members at
p.000022: http://intranet.epa.gov/icrintra/index.html.
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023: 2.2.6 Quality Assurance Project Plan
p.000023: Data of unknown or uncertain quality can undermine the scientific integrity of a study and render an otherwise sound
p.000023: study invalid. NERL scientists must be diligent in the implementation of the procedures and processes specified
p.000023: in a well-developed quality assurance project plan (QAPP). A discussion of quality assurance
p.000023: programs and QAPPs is outside of the scope of this document. There are many good references on the topic,
p.000023: including the EPA Web site, www.epa.gov/quality/.
p.000023:
p.000023: 2.2.7 The Study Design Document
p.000023: The study design document should contain sufficient detail to allow independent review and assessment of the scientific
p.000023: soundness of the study and the approaches that will be followed to ensure that the study meets the highest
p.000023: scientific and ethical standards. The research team can meet regularly to specifically evaluate the plan. It
p.000023: should be noted that a study design is not the same as an implementation plan. The latter includes an even
p.000023: greater level of detail describing how the study will be performed and includes protocols and
p.000023: operating procedures. Text Box 2-4 lists a number of elements that may be appropriate to include in a study design.
p.000023:
p.000023: 2.3 Ethical Issues in Ensuring Fair Subject Selection
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p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
...
p.000095: research, data selection to exclude confounding factors) can sometimes influence the range of values over which a
p.000095: variable may be observed. For example, NERL’s observational human exposure studies to understand exposure to PM
p.000095: (see www.epa.gov/heasd/sources/projects_completed/pm_pa nel_studies.htm and www.epa.gov/heasd/sources/project
p.000095: s/a3a_understanding_airshed_sources.htm) have traditionally excluded homes with smokers from the
p.000095: study population to avoid cigarette smoke as a confounding factor in the studies.
p.000095: Observational Studies in Market Research, Ethnography, and the Common Vernacular:
p.000095: Observational market research can involve covert observation, overt observation, or
p.000095: researcher participation. Covert observation is said to have a “key advantage” that “the respondent or consumer is
p.000095: unaware that they are being observed, allowing their behavior to be observed naturally”
p.000095: (see http://www.asiamarketresearch.com/glossary/observatio nal-research.htm). This means that the
p.000095: subject’s behavior will be natural and uncontaminated by the researcher’s presence. On the other hand, covert
p.000095: observation may be construed to be deceitful and ethically questionable. Overt observations involve
p.000095: sampling surveys, polls, interviews, focus groups, etc. Validity of the data obtained this way may
p.000095: be shaded by people’s natural tendency to behave or respond ideally when they know they are being watched.
p.000095: Motorists routinely slow down when they think they are being observed by the police. Finally, the researcher may
p.000095: participate in the activity being observed. Ethnography is a long-term investigation of a group
p.000095: (often a culture) that is based on observations made while immersed in and, useually, participating in that
p.000095: group. “Ethnography provides a detailed exploration of group activity and may include
p.000095:
p.000095:
p.000096: 96
p.000096:
p.000096: literature about and/ or by the group.” (See
p.000096: http://writing.colostate.edu/guides/research/observe/com 3a1.cfm). One obvious problem with immersion
p.000096: techniques is that the researcher may lose his or her objectivity.
p.000096: In the common language use of the term observational research, it appears to the authors
p.000096: that some people understand the term to imply that the observations are both benign and often covert,
p.000096: that is, without interaction with the persons being studied. That is not the case in NERL’s observational human
p.000096: exposure studies. The research often takes place in and around the homes of the participants. Often, the research
p.000096: involves asking the participant to answer a questionnaire and to provide personal samples (e.g., urine,
p.000096: blood). Collection of survey information and personal urine and blood samples cannot be done covertly, and
p.000096: collecting a blood sample is not considered to be benign.
p.000096: Observational Research in NERL: NERL’s observational human exposure studies entail the
p.000096: collection of environmental or biological samples, data, and information from study participants and their
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Social / Presence of Coercion
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p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
p.000055: dialogue . . . involving the disclosure and exchange of relevant information” (IOM, 2002): it is not
p.000055: simply having a consent form signed. The process is most effective when the researcher spends time with
p.000055: potential participants to discuss the study and to answer questions.
p.000055:
p.000055: 5.2 Payments to Research Participants
p.000055: The decision whether to pay research participants, including the appropriate level of payment,20 is
p.000055: a complex ethical issue. Monetary or nonmonetary payments are not ethical if they constitute an
p.000055: undue inducement for participants to assume research risks that they would not otherwise accept. On the other
p.000055: hand, it may be ethically appropriate to offer reasonable payments in some research studies. Indeed,
p.000055: payment of human subjects for their participation in scientific research is a common practice in the United
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Social / Property Ownership
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p.000009: the subject and to society
p.000009: Review of the design of the research trial, its proposed subject population, and risk-benefit ratio by individuals
p.000009: unaffiliated with the research
p.000009: Provision of information to subjects about the purpose of the research and its procedures, potential risks, benefits,
p.000009: and alternatives, so that the individual understands this information and can make a voluntary decision whether to
p.000009: enroll and continue to participate
p.000009: Respect for subjects by
p.000009: • permitting withdrawal from the research,
p.000009: • protecting privacy through confidentiality,
p.000009: • informing subjects of newly discovered risks or benefits,
p.000009: • informing subjects of results of the research, and
p.000009: • maintaining welfare of subjects.
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: Collectively, these documents have reaffirmed the basic ethical principles asserted in the Belmont Report
p.000010: and have attempted, in some cases, to expand scientific and ethical reasoning and understanding to define
p.000010: approaches for dealing with additional elements of human subjects research. These additional
p.000010: elements, which often have been identified because of specific incidents or case studies, include issues
p.000010: such as those described below.
p.000010: • Payment to participants⎯How much is adequate and fair, without being an undue inducement?
p.000010: • Non-study hazards⎯What is the researcher’s responsibility to identify hazards in the home that are
p.000010: not part of the study?
p.000010: • Third-party issues⎯Are there people other than the participant who may be impacted during the study and by the
p.000010: study results? If so, what needs to be done to protect their interests and to respect them as persons?
p.000010: • Community involvement⎯How should the community be involved in the design
p.000010: and implementation of studies?
p.000010: These documents, together with EPA’s regulatory requirements for the protection of human subjects, serve as
p.000010: important references for the subsequent sections of this document (see Table 1-4).
p.000010:
p.000010: 1.3 Purpose of This Document
p.000010: This document is meant to serve as a resource of current scientific and ethical information for
p.000010: NERL researchers as they develop and conduct observational human exposure studies. The increased
p.000010: scrutiny of research studies involving human participants makes it imperative that researchers ensure that
p.000010: their research protocols for protection of human subjects in observational human exposure studies
p.000010: incorporate the most up-to-date ethical approaches. Protocols for protecting study participants in
p.000010: research studies have been developed by experts in both academia and various Federal agencies and adopted
p.000010: by the research community because they ensure that observational research meets the highest
...
p.000022: required a large number of randomly-selected participants. Randomized selection is recognized
p.000022: as a valid statistical method to get a sample that is representative of the larger population
p.000022: from which the participants were selected. Pilot studies performed to evaluate a method or to estimate
p.000022: the likely range of exposure concentrations often have employed either purposeful sampling, where
p.000022: the researchers use information on the relevant characteristics of the population to select those
p.000022: participants who will exhibit a wide range of activity levels or potential exposure concentrations, or
p.000022: convenience sampling, where the researchers select the most accessible members of a population
p.000022: NERL’s observational human exposure studies also have routinely collected information about the
p.000022: participants’ activities by using questionnaires and surveys. Survey design is both a science and an
p.000022: art because the design of surveys is based on statistics and science, but designing a good and effective questionnaire
p.000022: is often an art that requires understanding the individuals being surveyed. Text Box 2-3 identifies some of the
p.000022: areas of art involved in designing an effective questionnaire.
p.000022: Understanding the process for selecting participants and the statistical-scientific requirements of
p.000022: questionnaire design are both components of survey sampling and design. A variety of references can provide
p.000022: the researcher with information about the issues in survey sampling and
p.000022: design. (See http://home.ubalt.edu/ntsbarsh/Business-stat/stat data/Surveys.htm and
p.000022: www.statpac.com/surveys/, for example.) But the research team must include or have access to the appropriate
p.000022: survey statistics expertise as it plans the research study.
p.000022:
p.000022: Text Box 2-3. Questionnaire Considerations
p.000022: • Questions should be simple and in a language the individual can understand.
p.000022: • Questions should be unambiguous.
p.000022: • Questions should be relevant to the study.
p.000022: • Questions should not be too personal.
p.000022: • The questionnaire should be as short as possible.
p.000022: • The questions should not be leading (e.g., internally suggestive of the answer).
p.000022: • Questions should follow a logical order.
p.000022:
p.000022:
p.000022:
p.000022: 2.2.5 Information Collection Rule
p.000022: As Federal employees, NERL researchers also must be aware of Information Collection Rule requirements. The
p.000022: Paperwork Reduction Act stipulates that every Federal agency must obtain approval from OMB before collecting
p.000022: the same or similar information from 10 or more members of the public. An Information Collection Request (ICR)
p.000022: is required if the same or similar information is being collected from 10 or more non- Federal
p.000022: respondents within a 12-month period, even if the information collection is voluntary. Generally, any
p.000022: survey, questionnaire, monitoring, reporting, or recordkeeping requirement imposed on
p.000022: non-Federal respondents by EPA will require an ICR. Information collections associated with all cooperative
...
p.000024: stringent requirements for working with these groups.
p.000024:
p.000024: 2.4 Ensuring a Favorable Risk-Benefit Ratio
p.000024: 2.4.1 Designing in Benefits for the Participants
p.000024: Study designs vary depending on the objectives of the study, existing knowledge on the research question, and
p.000024: the hazard being studied (NRC & IOM, 2005). Recent ethical discussions about study designs in human subjects
p.000024: research (cf., Recommendation 7.1, p. 143, NRC & IOM [2005] and Emanuel et al. [2000]) support the development
p.000024: of innovative study designs to maximize the benefit9 to the study participants, as well as to
p.000024: the community and the greater society beyond. Observational human exposure studies generally collect data that
p.000024: contribute to generalizable knowledge that will benefit the community and society as a whole, but they often do not
p.000024: provide obvious direct benefit to study participants. Therefore, it is important to include elements
p.000024: in the study design that can offer benefits to the participants wherever possible. This is not always
p.000024: straightforward, but one way that participants, as well as communities, can benefit from these studies is
p.000024: by incorporating strong educational components into the conduct of the research. For example, brochures, videos,
p.000024: and other materials that educate study participants on safety around the home or on how to reduce their
p.000024: exposure to chemicals can be distributed during the study. EPA’s program offices, including the Office of
p.000024: Children’s Health Protection, the Office of Pollution Prevention and Toxics, the Office of Pesticide Programs,
p.000024: the Office of Drinking Water, and others have Web sites with substantial amounts of informational
p.000024: and educational materials available that could be distributed to study participants. Other organizations, such as
p.000024: the American Lung Association, the American Cancer Society, the American Academy of Pediatrics (AAP),
p.000024: and various environmental groups, have materials of which study participants may not be aware that could be used
p.000024: as educational materials when relevant.
p.000024: In addition, approaches that provide direct benefits to study participants will need to be tailored to
p.000024: the particular study population and community. Feedback from potential participants in focus groups and
p.000024: input from community representatives may be useful in identifying these approaches.
p.000024:
p.000024:
p.000024:
p.000024: 9 Payment to participants is never considered a benefit of a study.
p.000024: 2.4.2 Assessing Benefits and Risks of Study Participation
p.000024: For all research involving human participants, the Common Rule requires researchers to ensure that
p.000024: potential risks “are reasonable in relation to the anticipated benefits,” and that risks are
...
p.000029: The goal of observational human exposure studies is to collect information on people’s exposures to
p.000029: chemicals in their real-world environment as they carry on their normal daily activities. Researchers who
p.000029: conduct these studies, however, recognize that participation in a study may affect behavior. This cannot
p.000029: always be avoided, as simply agreeing to participate in a study may impact the participant’s activities and
p.000029: schedules. For example, this occurs when technicians visit homes to collect samples or when participants
p.000029: are asked to collect samples (e.g., food, urine), or to complete surveys, activity logs, or
p.000029: questionnaires. These types of changes in behavior may or may not affect the outcome of the study.
p.000029: Some changes in behavior can affect the study outcome. The Hawthorne Effect is a well-recognized
p.000029: phenomenon. It is an effect on an outcome variable caused by the fact that the participants of the study know
p.000029: they are participating in the study. The Hawthorne Effect originally referred to the increase in worker productivity
p.000029: observed when a worker is singled out and made to feel important; the increased productivity was not related to the
p.000029: environmental factors that were being studied. The effect was described based on a series of industrial
p.000029: productivity studies from 1927 to 1932. Similarly, some changes in participant behaviors may change the
p.000029: observations, measurements, and conclusions from observational human exposure studies. For
p.000029: example, participants may do more cleaning in their home because they do not want the researchers to think they are
p.000029: poor housekeepers; this could affect the measurement of environmental concentrations in the home. In a
p.000029: study of chemicals from consumer products, participants may think that because the researchers are
p.000029: studying the products, the products must be harmful. Therefore, study participants may elect not to use the products
p.000029: during the study in the same manner as they would normally. Alternatively, prospective participants may
p.000029: choose to use more of the household product to qualify for the
p.000029: study. As a result, the participant’s exposure to the chemicals could be either more or less than “normal.”
p.000029: Any change in a participant’s behavior that is related to the research question being addressed in the study
p.000029: may impact the study results. Researchers should try to anticipate how a study may impact participant behaviors and
p.000029: ensure that the study design and implementation protocols do not cause changes in behavior that may cause
p.000029: harm to a participant during a study. A number of study elements with the potential to influence
p.000029: participants’ behavior are listed in Text Box 2-6.
p.000029:
p.000029: Text Box 2-6. Study Elements That Could Affect People’s Behavior
p.000029: • Eligibility criteria
p.000029: • Recruiting approach and materials
p.000029: • Enrollment approach
p.000029: • Payments
p.000029: • Retention strategy
p.000029: • Types of measurements made and data collected
p.000029: • Protocols for data collection
p.000029: • Protocols for visits to homes
p.000029: • Interactions with participants
p.000029: • Communications
p.000029:
p.000029:
p.000029: It is very difficult to predict in advance how these elements may be interpreted and acted on by
...
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
...
p.000039: June 2007].
p.000039:
p.000039: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000039: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000039: [accessed 12 June 2007].
p.000039:
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p.000040: 40
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p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040: SECTION 4
p.000040: Privacy, Confidentiality, and Other Concerns Related to Observational Human Exposure Studies
p.000040:
p.000040:
p.000040:
p.000040: Observational human exposure studies are designed to describe people’s contact with pollutants as they go about
p.000040: their everyday lives. Of necessity then, these studies take place in the locations that participants often
p.000040: consider to be personal and private. Clinical research studies generally are conducted in a research
p.000040: facility, a clinic, a hospital, or some other institutional or medical setting. Survey research may be conducted by
p.000040: mail, over the phone, or in another “neutral” setting. But, observational human exposure studies are
p.000040: conducted in the participants’ “personal” environment⎯their home, daycare center, school, vehicle,
p.000040: workplace, or other environments that people occupy during their routine daily activities. This difference
p.000040: in the research setting means that researchers involved in observational human exposure studies have an
p.000040: even greater challenge in meeting the ethical obligation to respect the privacy of the participants.
p.000040: When exposure science researchers like those at NERL enter a home to carry out their studies, the
p.000040: “expectations and constraints may be strikingly different than when research is carried out in a medical
p.000040: setting” (p. 64, NRC & IOM, 2005). The legal precept of freedom from unreasonable search and
p.000040: seizure and the historic and deeply rooted principle that “a man’s home is his castle” contribute to a belief in the
p.000040: “sanctity of the home” (see the discussion on pp. 62-66, NRC & IOM, 2005).
p.000040: The joint NRC and IOM report Ethical Considerations for Research on Housing-Related Health
p.000040: Hazards Involving Children discusses the ethical issues associated with entering a participant’s home to conduct
p.000040: research and explores the researchers’ responsibilities that derive from conducting research in people’s homes
p.000040: (NRC & IOM, 2005). These housing-related discussions are particularly relevant to observational human
p.000040: exposure studies, which often include environmental and
p.000040: biological measurements in people’s homes or personal locations. Many of the topics identified in that report are
p.000040: discussed in this section (Text Box 4-1).
p.000040:
p.000040:
p.000040: Text Box 4-1. Topics in Section 4
p.000040: Privacy Issues Confidentiality
p.000040: Confidentiality of Information Confidentiality of Participation
p.000040: Collateral Observations
p.000040: Potential Nonstudy Hazards in the Residence Collateral Observations with Mandated Reporting
p.000040: Requirements
p.000040: Hazard Communication Planning and Staff Training
p.000040: Third-Party Issues
p.000040: Determining Whether a Third Party is a Human Subject Informing Third Parties of Research Activities Research Results
p.000040: and Third Parties
p.000040: Data and Safety Monitoring and Oversight
p.000040:
p.000040:
p.000040:
p.000040: 4.1 Privacy Issues
p.000040: Privacy refers to an expectation that a person is free from intrusion into personal matters and is free from the
p.000040: presence or view of others. The Institutional Review Board Guidebook defines privacy as “control over the
p.000040: extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with
p.000040: others” (U.S. HHS, 1993). Beauchamp and Childress find that the right to privacy is based on the principle of
p.000040: respect for autonomy. “We often respect persons by respecting their autonomous wishes not to be observed, touched, or
p.000040: intruded upon…. A loss of privacy occurs if others use any of several forms of access, including intervening in zones
p.000040: of secrecy, anonymity, seclusion, or solitude” (pp. 295-296, Beauchamp and Childress, 2001).
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041: Although research participants may agree to allow researchers to enter their home or other zone of personal space
p.000041: to conduct their research measurements, they have not abrogated their right to privacy. “When individuals
p.000041: voluntarily grant others some form of access to themselves, their act is an exercise of the
p.000041: right to privacy, not a waiver of that right” (p. 297, Beauchamp and Childress, 2001). Researchers should remember
p.000041: that they are guests in the homes for a specific purpose. “When people visit a home, there are social
p.000041: expectations about what is acceptable behavior. People who are invited into a home are expected to be
p.000041: sensitive to and respectful of the host’s customs and values” (p. 65, NRC & IOM, 2005).
p.000041: By their very nature, observational human exposure studies encroach on the privacy of a research participant. Entry in
p.000041: a participant’s home (or other personal zones) does represent a loss of privacy, but researchers should be
p.000041: careful to ensure that their presence does not become a violation of the individual’s right to privacy. The
p.000041: relationship between the researcher and the participant may be complicated, and there may be conflicts between
p.000041: the researcher’s role and their ethical obligations (NRC & IOM, 2005). In entering a participant’s
p.000041: personal space, it may be difficult, or impossible, to avoid making observations unrelated to the research question,
p.000041: thereby further intruding on the participant’s personal privacy. Indeed, there may be ethical and legal
p.000041: obligations for the researchers to respond to those observations. Beauchamp and Childress suggest that “policies
p.000041: carefully specify the conditions of access that will and will not count as a loss of privacy or a violation of
p.000041: the right to privacy. The policy should accurately define the zones that are considered private and
p.000041: not to be invaded, and should also identify interests that legitimately may be balanced against privacy
p.000041: interests” (Beauchamp and Childress, 2001).
p.000041: Observational human exposure studies also may infringe on the privacy of other individuals, for example,
p.000041: other members of the participant’s family or household. Researchers should strive to minimize the intrusion and loss
p.000041: of privacy and to show respect for the privacy of study participants and third parties at all times (see Text
p.000041: Box 4-2 for a list of relevant privacy issues). It is incumbent on the researcher to recognize privacy issues
p.000041: in the design and implementation of the research study. The NRC & IOM report suggests that researchers
p.000041: anticipate the ethical issues that arise from conducting research in a person’s home, and that they take steps
p.000041: to correct them (1) by thinking through the issues as part of the study design; (2) by discussing the issues during the
p.000041: informed consent process; and (3) by ensuring that the frontline staff that enter a
p.000041: participant’s home “understand their role as members of the research team, how that role differs from the role of
p.000041: neighbor or friend, and how they should respond when they make observations that are not part
p.000041: of the protocol” (p. 66, NRC & IOM, 2005).
p.000041:
p.000041: Text Box 4-2. Privacy Issues
p.000041: • Researchers should develop an anticipatory plan for how to deal with privacy issues during the study. The plan
p.000041: should include a list of potential observations that could be of concern and a plan for how they will be handled.
p.000041: • The plan needs to address both the legal and ethical obligations of the researcher in response to situations where
p.000041: privacy is compromised.
p.000041: • Privacy issues will vary depending on the culture of the population being studied. What one individual or group
p.000041: may find as an invasion of privacy, another group may not have a concern about.
p.000041: • Privacy issues involve individual participants and may extend to third parties, including the community.
p.000041: • Researchers may find a meeting with community representatives to learn about the community residents and potential
p.000041: privacy issues to be helpful. Community representatives can help the researcher identify potential privacy issues and
p.000041: offer advice on how to address them.
p.000041: • Researchers may wish to respect the privacy of occupants sharing the study participant’s household or other study
p.000041: locations by providing advance notification of study visits and by giving them the opportunity not to be present during
p.000041: those visits.
p.000041: • Field staff should be trained on how to minimize breaches of privacy and how to handle privacy issues.
...
p.000043: In some types of research, the knowledge that a person is participating in a particular research study
p.000043: could, potentially, put the participant at risk for harm or distress. This topic is discussed in The
p.000043: Institutional Review Board Guidebook, with special emphasis on behavioral and social research that deals
p.000043: with sensitive topics (U.S. HHS, 1993). The guidebook describes the need for additional safeguards to
p.000043: protect and prevent disclosure of the identity of participants, including the use of Certificates of
p.000043: Confidentiality for sensitive matters.
p.000043: Observational human exposure studies often pose particular challenges with regard to limiting
p.000043: dissemination of the knowledge of an individual’s participation in the study. Visiting the
p.000043: research participant’s residence to collect samples or to make observations will necessitate informing
p.000043: other family members or occupants about the visit and study procedures. Research participants may be
p.000043: asked to wear personal monitors over time periods ranging from a day to a week or more. Wearing these devices
p.000043: in public places, schools, or workplaces may identify them as a study participant or generate questions
p.000043: regarding the activity. Field staff visits to the participant’s home or setting up outdoor sample collection
p.000043: devices around the home also might disclose their participation. And, in some cases, third parties outside of
p.000043: the home have to be asked for permission or be informed that monitoring activities are taking place.
p.000043: Researchers and IRBs should consider whether knowledge of an individual’s participation by others might
p.000043: create potential for harm or distress in an observational human exposure study. Such risks might
p.000043: be limited to possible discomfort in attracting unwanted
p.000043: attention; this may be particularly true for adolescents. However, in some cases, the potential risks
p.000043: could be greater, for example, in cases where participation could provoke an adverse reaction from a
p.000043: landlord or employer. Oftentimes study protocols can be structured to minimize these potential risks. Through the
p.000043: informed consent process, prospective participants should be made aware of the limits of the researcher’s ability to
p.000043: protect knowledge of their participation in the study and of the possible risks of disclosure.
p.000043:
p.000043: 4.3 Collateral Observations
p.000043: In the course of conducting an observational human exposure study, research staff may observe potentially unsafe
p.000043: conditions or situations that are unrelated to the research study. Such “collateral observations” may
p.000043: involve physical hazards in the study participant’s residential environment or evidence of situations,
p.000043: such as child abuse, that have to be reported to proper authorities. In preparing for the
...
p.000044: communication of environmental health risks (AAP, 2003). Researchers likely will benefit from including
p.000044: community members on the research team in developing the study design and research protocol or from
p.000044: consultation with community boards regarding identification of hazards and hazard communication.
p.000044:
p.000044:
p.000045: 45
p.000045:
p.000045: It is important that any advice that the researcher might provide to study participants regarding hazard
p.000045: mitigation should be carefully considered. Considerations in recommending an action may include
p.000045: whether the mitigation approach has been shown to be effective, whether the study participant can
p.000045: understand and effectively implement the action, and whether unintended adverse consequences might
p.000045: result from taking an action. In some cases, it may be reasonable to refer the participant to another
p.000045: organization that can provide expert advice or assistance.
p.000045:
p.000045: 4.3.4 Planning and Staff Training
p.000045: As part of the study planning process and protocol development, it is important that researchers
p.000045: be cognizant of the kinds of collateral observations that might occur in the implementation of the study
p.000045: protocol and to develop plans as to how such observations would be handled. Researchers may choose to
p.000045: include a systematic approach in hazard identification, such as using a home-hazard checklist that becomes an
p.000045: ancillary part of the study protocol. Alternatively, collateral observations could be handled on a
p.000045: case-by-case basis.
p.000045: Staff experience and training is a critical consideration for managing collateral observations. Staff
p.000045: members that visit study participant residences may not have expertise or experience in identifying many of the
p.000045: potential hazards without adequate training. All staff involved in a study, particularly those responsible
p.000045: for field data collection, should be trained on identification and reporting of collateral observations. This
p.000045: training should be study specific and likely will include, but not be limited to
p.000045: (1) identification of actions (e.g., child abuse) that have (state-specific) statutory reporting requirements,
p.000045: (2) conditions of neglect that may adversely impact study participants or third parties,
p.000045: (3) environmental hazards and situations that may be associated with imminent harm (e.g., combustible
p.000045: materials near an open flame, unsecured firearms accessible to very young children),
p.000045: (4) policies and procedures for reporting or intervention by members of the research team, and
p.000045: (5) local and state reporting requirements.
p.000045: It is advisable that this training be developed in consultation with community representatives who can
p.000045: provide input on potential hazards and situations that may be encountered in the study community,
...
p.000046: a human subject [40 CFR 26.102(f)] if individually identifiable private information about them is collected
p.000046: (CFR, 2006). When this occurs, the informed consent of the third party must be obtained, or, if certain criteria are
p.000046: met, the IRB may determine that informed consent may be waived. It can be difficult to determine whether information
p.000046: about a third party is both individually identifiable and private. Discussions of this issue and
p.000046: recommendations for determining whether third-party information is identifiable and private have been
p.000046: submitted to the HHS Office of Human Research Protections by NIH (2001) and by the National Human
p.000046: Research Protections Advisory Committee (NHRPAC, 2002).
p.000046: Whether or not a third party is determined to be a human subject, the researcher should treat
p.000046: research
p.000046: information about a third party as confidential.
p.000046:
p.000046: 4.4.2 Informing Third Parties of Research Activities
p.000046: Obtaining permission from or informing third parties of certain types of activities may be needed in some
p.000046: observational human exposure studies. For example, household members living with a study participant need to
p.000046: be informed about home study visits and residential sample collection activities. Study activities that
p.000046: occur outside of the participant’s home or yard may require informing or gaining permission from third
p.000046: parties. A study may include collection of environmental samples (i.e., ambient air, dust, soil) from outdoor
p.000046: common areas of multifamily housing where the study participant lives. Issues regarding privacy, permission, and
p.000046: payments for third parties in housing-related studies have been discussed in the NRC & IOM (2005) report.
p.000046: Observational human exposure studies also may include cases when study participants are asked
p.000046: to collect personal samples (i.e., wearing a personal air monitor) over a time period that includes time
p.000046: they spend in a school, day care, or workplace. Such monitoring might require informing or
p.000046: gaining permission from an organization’s staff or an employer. In each case, the researcher and IRB have to
p.000046: consider whether obtaining permission from or informing a third party is appropriate and, if so, to define the
p.000046: procedures for doing so. The researcher and IRB have to also consider the potential impact of third-party
p.000046: knowledge of research activities on confidentiality and risk for the study participant and have to ensure that it is
p.000046: clearly and fully explained in the informed consent process.
p.000046:
p.000046: 4.4.3 Research Results and Third Parties
p.000046: Prior to initiating a research study, researchers should consider whether research results may
...
p.000047: the research. Even though most observational human exposure studies are considered low-risk, there is often a need to
p.000047: determine whether appropriate threshold values for biological or environmental levels of chemicals exist or can be
p.000047: determined that, if the threshold value is exceeded, it would trigger reporting or other actions. The safety of
p.000047: measurement procedures and equipment also has to be considered. Unanticipated adverse events also may be
p.000047: encountered in observational research. Participant consent and understanding of the research effort,
p.000047: participant recruitment, participant retention, and data accuracy and quality should all be monitored to ensure
p.000047: the scientific integrity of research results.
p.000047: The authors already have discussed (Section 2.8) the needs (1) to establish, in advance, criteria and standards for
p.000047: monitoring the research program in regard to both scientific and ethical issues; (2) to establish who
p.000047: will monitor and oversee the research progress (the monitoring and oversight authority, be it
p.000047: an individual, team, or review committee); and (3) to establish the roles, responsibilities, and authorities
p.000047: of the researchers and of the monitoring and oversight authority. The planning also should include steps
p.000047: to meet the IOM recommendations that researchers should “anticipate risks and behaviors that may be
p.000047: observed in the home… [and] develop anticipatory plans that specify how to assess and respond to risks when they
p.000047: are identified, and educate their staffs about the plan” (Recommendation 7.3, p. 144, NRC & IOM, 2005).
p.000047: Once the procedures and organization for monitoring and oversight of the observational study are approved by the IRB,
p.000047: it is the responsibility of the researchers and of the monitoring and oversight authority to ensure that the planned
p.000047: actions are implemented. Implementation of the monitoring and oversight function may include the following
p.000047: items.
p.000047: • Ensuring that procedures for identifying, reporting, and responding to anticipated or unanticipated adverse
p.000047: events and safety issues are in place and are being followed
p.000047:
p.000047:
p.000048: 48
p.000048:
p.000048: • Assessing and responding to risks when they are identified
p.000048: • Evaluating the performance and knowledge of the staff regarding identification of potential risks and the
p.000048: actions they should take
p.000048: • Implementing procedures for monitoring the informed consent process, participant behaviors, participant
p.000048: recruitment, participant retention, procedures to protect privacy and confidentiality, and other
p.000048: human requirements for adherence to the research protocol and compliance with ethical standards and with EPA’s
p.000048: human subjects rules
p.000048: • Ensuring that measurements and samples are collected as planned, and that data are reported on a timely basis
p.000048: • Evaluating whether the observed measurements exceed the pre-established threshold values and, if so,
...
p.000048: Press.
p.000048:
p.000048: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I⎯Environmental Protection Agency Part 26 Protection of Human
p.000048: Subjects. U.S. Code of Federal Regulations.
p.000048: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed August 2007].
p.000048:
p.000048: CIOMS (Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000048: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000048: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed June 2007].
p.000048: Emanuel, EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000048:
p.000048: NCI (National Cancer Institute) (2001). Essential Elements of a Data and Safety Monitoring Plan for Clinical Trials
p.000048: Funded by the National Cancer Institute. Available: http://www3.cancer.gov/rrp/dsm_ess.html [accessed April 2007].
p.000048:
p.000048: NEI (National Eye Institute) (2001). National Eye Institute Guidelines for Data Monitoring and Oversight of
p.000048: Observational Studies. Available: http://www.nei.nih.gov/funding/datastudies.asp [accessed April 2007].
p.000048:
p.000048: NHLBI (National Heart Lung and Blood Institute) (2007). Monitoring Boards for Data and Safety (Interim Policy). Policy
p.000048: effective date: 14 May 2007. Available: http://public.nhlbi.nih.gov/ocr/home/GetPolicy.aspx?id=8 [accessed September
p.000048: 2007].
p.000048:
p.000048: NHRPAC (National Human Research Protections Advisory Committee) (2002). Clarification of the status of third parties
p.000048: when referenced by human subjects in research. Available: http://www.hhs.gov/ohrp/nhrpac/documents/third.pdf [accessed
p.000048: April 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (2002). Extramural Projects - Application Instructions (03/15/2002) - Detailed
p.000048: Application Instructions for Certificate of Confidentiality Involving Extramural Research Projects. Certificates of
p.000048: Confidentiality. Available: http://grants.nih.gov/grants/policy/coc/index.htm. [accessed April 2007]
p.000048:
p.000048: NIH (National Institutes of Health) (2001). Protection of third party information in research: Recommendations of the
p.000048: National Institutes of Health to the Office for Human Research Protections. Available:
p.000048: http://bioethics.od.nih.gov/nih_third_party_rec.html [accessed March 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (1998). NIH Guide: NIH Policy for Data and Safety Monitoring. Available:
p.000048: http://grants.nih.gov/grants/guide/notice-files/not98 084.html [accessed April 2007].
p.000048:
p.000048: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000048: Housing-Related Health Hazards Involving Children.
p.000048: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed
p.000048: June 2007].
p.000048:
p.000048:
p.000048:
p.000048:
p.000049: 49
p.000049:
p.000049: U.S. FDA (U.S. Food and Drug Administration) (2001). Draft Guidance for Clinical Trial Sponsors on the Establishment of
p.000049: Clinical Trial Data Monitoring Committees. U.S. Department of Health and Human Services, Food and Drug Administration,
p.000049: Rockville, MD. Available: http://www.fda.gov/cber/gdlns/clindatmon.pdf. [accessed April 2007].
p.000049: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000049: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000049: [accessed June 2007].
p.000049:
p.000049:
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p.000050: 50
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p.000050:
p.000050:
p.000050:
p.000050: SECTION 5
p.000050: Creating an Appropriate Relationship Between the Participant and Researcher
p.000050:
p.000050:
p.000050:
p.000050: In observational human exposure studies, the researcher and the participant routinely interact
p.000050: with each other, often in the participant’s home or other private setting and often repeatedly over a
p.000050: number of days. The nature and setting of the interactions mean that exposure researchers should give special
p.000050: consideration to the many scientific and ethical issues that shape the relationship between participants and
p.000050: the researchers. In these studies, it is recommended that a strong relationship, built on
p.000050: openness and trust, should be developed between the researcher and participant. The nature of that
p.000050: relationship and the ethical principles underpinning an appropriate relationship are the focuses of this section of
p.000050: the document.
p.000050: This relationship should be established on the ethical values of respect for the participant’s autonomy and
p.000050: respect for their welfare. Emanuel and his co-authors find that these two ethical values translate into
p.000050: specific responsibilities for an ethical researcher in regard to informed consent and respect for potential and
p.000050: enrolled subjects (Emanuel et al., 2000). They describe the ethical principles for these responsible actions thusly,
p.000050: “Respect for potential and enrolled subjects is justified by multiple principles including beneficence,
p.000050: nonmaleficence, and respect for persons. Permitting subjects to withdraw and providing them additional information
p.000050: learned from the research are key aspects of respecting subject autonomy. Protecting confidentiality and monitoring
p.000050: well-being are motivated by respect for persons, beneficence, and nonmaleficence.” Section 4 already has
...
p.000053: custody of the child).
p.000053: special concerns about the potential for discrimination, stigmatization, and impact on
p.000053: future employment or insurance. The informed consent process needs to explain what the plans may be
p.000053: for such specimens and recognize the rights of the subjects to decide about any such future use,
p.000053: including having the material destroyed. The informed consent process needs to explicitly discuss
p.000053: obtaining permission from participants on behalf of themselves and their child to obtain specimens for
p.000053: genetic analysis.
p.000053:
p.000053: 5.1.2 Comprehension
p.000053: Research participants frequently fail to understand the research protocols in which they agree to participate (NRC
p.000053: & IOM, 2005). In considering the ethical issues raised by the Grimes v. Kennedy Krieger case, the NRC & IOM
p.000053: committee “realized that the crucial issue regarding consent was not what information was
p.000053: contained in the consent forms, but rather what the parents understood about the study and the hazards
p.000053: present in the home before and after the study” (p. 19, NRC & IOM, 2005). The committee laments that “IRBs
p.000053: place their attention on consent forms rather than on the process of providing and discussing information” (p.
p.000053: 103, NRC & IOM, 2005). The IOM recommends that “the informed consent process should be an on-going,
p.000053: interactive dialogue between research staff and research participants involving the disclosure and exchange of
p.000053: relevant information, discussion of that information, and assessment of the individual’s understanding of
p.000053: the discussion” (Recommendation 4.1, IOM, 2002). These comments emphasize how important true two-way
p.000053: communication is to comprehension, the second pillar in the informed consent process.
p.000053: The following items are a variety of issues concerning comprehension that NERL scientists should
p.000053: keep in mind as they develop an informed consent process in collaboration with the research team, the IRB and
p.000053: other peer reviewers, and EPA’s HSRRO. These items may be based on regulatory requirements or may simply be
p.000053: recommendations as ethical “best practices.”
p.000053: • Researchers need to assume responsibility for developing an interactive dialogue with
p.000053: participants for the exchange and discussion of relevant information as a part of the informed
...
p.000059: unfair because it requires similar sacrifices of time and inconvenience from both” (p. 113, NRC & IOM, 2005).
p.000059: Similar ethical quandaries can arise in multisite studies with differing costs for living. If the same payment
p.000059: is used in high-cost cities as in low-cost areas, the payment may be inadequate to gain sufficient
p.000059: enrollment in the high-cost area, whereas the same dollar amount may be “coercive” in the low-cost area. The NRC & IOM
p.000059: committee notes that a similar situation can arise when a study enrolls participants from diverse
p.000059: socioeconomic backgrounds. There are social justice concerns that poorer people might incur a disproportionate
p.000059: share of research risk and burden if payments induce unequal participation rates in the population. Decisions
p.000059: regarding payment for research participation will require careful consideration by IRBs when economically
p.000059: disadvantaged people may be enrolled. Community advisory boards (CABs) can be very important in helping
p.000059: researchers and IRBs determine what is appropriate with regard to payments within their community.
p.000059:
p.000059:
p.000059:
p.000059:
p.000060: 60
p.000060:
p.000060: 5.2.4 Payments in Observational Human Exposure Studies
p.000060: Observational human exposure studies most often involve minimal risks to study participants and few direct
p.000060: benefits, but may require considerable time and burden for participation. Study requirements can include multiple
p.000060: in-home visits; the burden of wearing personal air monitors for one or more 24-hour period; preparing and providing
p.000060: duplicate diet samples; collection of environmental samples inside and outside the home; completing
p.000060: questionnaires, food diaries, and time- activity diaries; and providing urine, blood, saliva, or hair
p.000060: samples. Monetary payments often have been included in these studies, with the level of payment
p.000060: related to the number of study days or visits or the specific kinds of environmental and biological
p.000060: samples and information that are collected or provided. Payment for direct participant costs has been included
p.000060: in some studies, such as a reasonable payment for providing researchers with duplicate diet samples.
p.000060: NERL scientists should review the commentary and recommendations in the literature before devising a
p.000060: payment program as part of a research protocol, especially the two recent National Academies of Science
p.000060: documents, Ethical Issues in Housing-Related Health Hazard Research Involving Children (NRC and IOM, 2005)
p.000060: and Ethical Conduct of Clinical Research Involving Children (IOM, 2004). They should seek
p.000060: guidance from EPA’s HSRRO to determine EPA’s latest policies and guidance in this regard. Input also should be sought
p.000060: from community representatives to ensure that any payment is adequate to compensate for expenses and reward
p.000060: participation, but that the payment is not so high as to constitute undue influence or coercion in the
p.000060: community. If the study includes several followup visits over a long term, NERL researchers should ensure that payment
...
p.000089: Overall study results generally are disseminated in peer-reviewed journal manuscripts and study reports. The
p.000089: availability of results published in manuscripts and reports has been greatly enhanced by posting them on
p.000089: Internet Web sites. For example, all EPA reports are now available electronically via EPA’s National Service
p.000089: Center for Environmental Publications Web site (http://www.epa.gov/ncepihom/).
p.000089:
p.000089: 7.8 Reporting Unanticipated Results or Observations
p.000089: The previous subsection discussed reporting of routine results from observational human exposure
p.000089: studies. The communication plan should include processes and procedures for the dissemination of
p.000089: the study results. Additionally, the communication plan needs to integrate with the data and safety
p.000089: monitoring and oversight plans for the study and include a plan for reporting unanticipated results or
p.000089: observations. Unanticipated results may include measurements of a chemical at a concentration that
p.000089: exceeds what is considered to be an “acceptable” level in environmental media or biological fluids.
p.000089: Unanticipated observations might include observation of the use of a chemical not approved for indoor
p.000089: use, storage of chemicals in inappropriate containers, storage of chemicals in places accessible by
p.000089: children, etc. Unanticipated results or observations may be directly related to the research question
p.000089: being addressed in the study (e.g., measurements of pesticide residues in a home) or
p.000089: nonstudy hazards (e.g., frayed electrical cords that may pose a hazard to young children and residences).
p.000089: Section 4 discusses issues that may affect privacy and confidentiality. Section 4.3 covers
p.000089: collateral observations of nonstudy-related hazards, including those that States may mandate must
p.000089: be reported. Section 4.5 discusses the need for data and safety monitoring and oversight, including the
p.000089: development of plans to report and react to anticipated or unanticipated adverse events or conditions.
p.000089: As part of the study implementation plan and the communication plan, researchers should develop a
p.000089: protocol for how to identify contaminant measurements and exposures of “concern” that should be reported to the
p.000089: study participant as quickly as possible because of the potential risk associated with the exposure
p.000089: (see Section 4.5, Data and Safety Monitoring and Oversight, and also Section 2.7.1, Establishing Criteria
p.000089: and Standards for Monitoring Scientific and Ethical Issues During a Study.) The plan needs to include the
p.000089: protocol for making the determination and the criteria that will be used as the threshold or “trigger” for
p.000089: reporting. The plans should describe how the results will be reported to the participants and what additional
p.000089: action will be undertaken to assist the participant in reducing their exposures. The first step in
...
p.000096: Because “exposure is quantified as the concentration of the agent in the medium in contact integrated over the
p.000096: time duration of that contact,” intentional exposure studies are usually more scientifically robust if both
p.000096: the concentration of the agent and the duration of the exposure are controlled by the research.
p.000096:
p.000096:
p.000096:
p.000097: 97
p.000097:
p.000097: Observational Research: In the language of the Code of Federal Regulations, “observational research means
p.000097: any human research that does not meet the definition of research involving intentional exposure of a
p.000097: human subject” (40 CFR 26.302).
p.000097: By this definition, observational research encompasses all human research that does not meet the
p.000097: definition of intentional exposure. As a consequence, it is a broad regulatory category that includes a variety of
p.000097: research domains, including human research that does not involve the study of exposures at all. This regulatory
p.000097: definition of observational is sufficiently broad, moreover, that it encompasses study types that
p.000097: this document is not intended to address. For example, it may be possible to design an intervention study that
p.000097: does not bring about or script in any way the participants’ exposure to a substance, but rather reduces or
p.000097: mitigates it. (Consider a study to test whether professional cleaning of the carpets, floors, walls, and
p.000097: other surfaces in a home might lead to a lower exposure to a residential contaminant or a study to determine if wearing
p.000097: a particle mask would reduce an individual’s exposure to smoke from forest fires.) Such a study
p.000097: might meet the regulatory definition of observational research (Note: The final decision in regard to whether
p.000097: any EPA study meets the definition of observational research resides with the Agency’s HSRRO), but it
p.000097: would not meet the authors’ intentions regarding “observational human exposure studies” as they are defined
p.000097: in this document. An intervention study, such as described in these two examples, does not involve
p.000097: observing people’s exposures in their everyday environments, as they go about their normal activities. In
p.000097: an intervention study, either the participant’s environment (cleaning of the household surfaces) or their
p.000097: behavior (wearing a particle mask) has been manipulated by the researcher. Secondly, the objective of these
p.000097: studies is not to understand exposures in everyday environments but would use changes in exposure
p.000097: to test the effectiveness of an intervention strategy. Such a study is not addressed in this document.
p.000097: Observational human exposure studies, as used by the authors of this document, generally meet the
p.000097: regulatory definition of observational research. But, not all studies meeting the CFR definition of
p.000097: observational research would be considered by the authors to be observational human exposure studies.
p.000097:
p.000097: Examples of NERL Observational Human Exposure Studies
p.000097: NERL and its predecessor organizations have
...
p.000098:
p.000098: Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, et al. (2007). Strengthening the Report of Observation
p.000098: Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Medicine 4(10): e297.
p.000098: doi:10.1371/journal.pmed.0040297.
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000099: 99
p.000099:
p.000099: Table A-1. Examples of Observational Human Exposure Studies Conducted or Funded by NERL or Its Predecessor
p.000099: Organizations
p.000099: Study Date Size Type Brief Description
p.000099: NERL Role
p.000099: Total Exposure 1980-1984 400 Three-stage The TEAM study was designed to develop and
p.000099: demonstrate EPA designed and Assessment Households stratified
p.000099: methods to measure human exposure to toxic substances in run, contractor Methodology
p.000099: probability air and drinking water. The goals were to develop methods to conducted
p.000099:
p.000099: (TEAM) Studies
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: Additional TEAM Studies
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: Nonoccupationa l Pesticides Exposure Study (NOPES)
p.000099:
p.000099:
p.000099:
p.000099: Nine-Home Children’s Pilot Study
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: Particle Total Exposure Assessment Methodology (PTEAM) Study
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: National Human Activity Pattern Study (NHAPS)
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.001987: 1987
p.001987:
p.001987:
p.001987:
p.001987:
p.001987:
p.001987:
p.001987: 1986-1988
p.001987:
p.001987:
p.001987:
p.001987:
p.001987:
p.001990: 1990
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990: 1990
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990: 1992-1994
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990: 51 in LA area, 17 in NJ,
p.001990: and 75 in Baltimore
p.001990:
p.001990:
p.001990:
p.001990:
p.000259: 259
p.000259:
p.000259:
p.000259:
p.000259:
p.000259:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000178: 178
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: 9,386
p.000178: selection, cross- sectional
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Convenience sample
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Probability selection, mainly cross- sectional, partly longitudinal
p.000178:
p.000178: Convenience pilot study
p.000178: to test methodology
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Probability
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Probability (national random dialing)
p.000178: measure individual total exposure (from air, food, and water) and the resulting body burden of toxic and carcinogenic
p.000178: chemicals and to apply these methods within a probability- based sampling framework to estimate exposures and body
p.000178: burdens of urban populations in several U.S. cities. Air sampling measured personal exposure to airborne toxic
p.000178: chemicals in indoor air and in exhaled breath. Related objectives were to determine the relationships between personal,
p.000178: indoor, and outdoor, and blood, urine, and exhaled breath concentrations; determine the variability of VOC
p.000178: concentrations within a home; and determine seasonal and multiyear variability. The study was conducted in New Jersey,
p.000178: North Carolina, and North Dakota in three phases.
p.000178: A separate VOC TEAM study was carried out in Baltimore, MD: Baltimore lacks the petroleum and chemical manufacturing
p.000178: plants present in most of the previous TEAM study sites and is more representative of many U.S. cities. Focused studies
p.000178: were also conducted in New Jersey and Los Angeles to further explore the sources and factors contributing to personal
p.000178: VOC exposures identified in the earlier TEAM studies.
p.000178: First attempt to develop a methodology for measuring the potential exposure of the general population to common
p.000178: household pesticides using probability-based sampling; questionnaire data collection; and personal monitoring of air,
p.000178: drinking water, food, and dermal contact. Conducted in Jacksonville, FL, and Springfield and Chicopee, MA, to capture
p.000178: high- and low-pesticide-use areas, respectively.
p.000178: A 9-home pilot study was conducted to evaluate monitoring methods in the field that may be used to assess the potential
p.000178: exposures of children aged 6 months to 5 years to pesticides found in the home environment. Newly developed methods
p.000178: were tested for measuring pesticide residues in indoor air, carpet dust, outdoor soil, and on children's hands.
p.000178: Information also was collected on household characteristics, pesticides used and stored at the residence, and
p.000178: children's activities.
p.000178: A study of nonsmokers age 10 years and older in Riverside, CA, in which indoor, outdoor, and personal monitoring of
p.000178: integrated particle mass over 12-hour day and night periods was conducted for PM10 and PM2.5. Polycyclic aromatic
p.000178: hydrocarbon and phthalate measurements were collected indoors and outdoors at a subset of 125 homes. A separate
p.000178: monitoring site provided ongoing 12-hour measurements of ambient particles throughout the study (48 days). Reference
p.000178: PM10 and dichotomous samplers were used at this site in addition to personal and stationary monitors identical to those
p.000178: used for participant monitoring. Nighttime and daytime recall time-activity questionnaires, as well as household
p.000178: questionnaires, were administered to each selected subject and household, respectively, and meteorological and air
p.000178: exchange rate data were recorded for each monitored home.
p.000178: This survey collected 24-hour activity diaries and other questionnaire data from participants from 48 states. It was
p.000178: conducted as a next-day telephone recall interview.
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000100: 100
p.000100:
p.000100: Table A-1. (Continued)
p.000100: Study Date Size Type Brief Description
p.000100: NERL Role
p.000100: Agricultural 1993- 84 applicators AHS survey A large-scale, long-term ongoing study of
p.000100: Iowa and North Collaboration with Health Study present; and a subset is a
p.000100: Carolina pesticide applicators and farm families. This other agencies; (AHS)
p.000100: PES 1999- of family longitudinal collaborative effort involving the National Cancer Institute
p.000100: NERL led a
p.000100: 2003 members in study of (NCI), the National Institute of Environmental Health Sciences
p.000100: contractor-
...
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 9 Households in NERL exposure component
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 20 Children
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 9 Daycare centers
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience, multiday pilot study to test methodology for exposure measure- ments
p.000021:
p.000021:
p.000021:
p.000021: Convenience, cross- sectional
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Case-control
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience
p.000021: other pollutants in institutional childcare centers. This national study used multistage sampling with clustering.
p.000021: Indoor wipe and outdoor soil samples were analyzed for pesticides, lead, and allergens (mold/fungi). Pesticide use
p.000021: practices and application information were obtained from the commercial pest control applicators serving the centers.
p.000021: Observational pilot exposure measurement study of residential exposures after homeowner had routinely applied granular
p.000021: formulation diazinon-containing turf treatment to residential lawns. Study was performed near Raleigh, NC, and was
p.000021: preceded by a 1-home methodology feasibility study. Purpose was to evaluate methods for assessing pet-borne transfer,
p.000021: translocation and exposure pathways, and decay rates.
p.000021:
p.000021:
p.000021:
p.000021: The objectives of this investigation in Jacksonville, FL, were to
p.000021: (1) assess organophosphate (OP) and pyrethroid pesticide exposures in a group of 4- to 6-year-old children from
p.000021: Jacksonville by measuring the urine metabolite levels,
p.000021: (2) identify possible sources of these pesticides through screening measurements and pesticide inventories, and
p.000021: (3) examine the relationship between environmental and biological levels. The Duval County Health Department (DCHD)
p.000021: collected urine samples for CDC from 200 children visiting six public health clinics in Jacksonville, and collected
p.000021: environmental screening samples at approximately 25% of these children’s homes. A detailed aggregate exposure
p.000021: assessment at 9 homes was overseen by NERL and involved collection of surface wipes, transferable residues, air,
p.000021: duplicate diet, cotton garment samples, and urine samples. A time- activity diary of the children’s activities was
p.000021: included.
p.000021: Work with Veteran’s Administration hospital staff. Cases of Legionnaires Disease were evaluated for potential for
p.000021: exposure from residential drinking water taps. In about 24% of the tested cases, homes were found to have Legionella
p.000021: bacteria in water taps at home, compared to their absence in other cases and in controls
p.000021: Incidental pesticide exposure measurement study of farmworkers’ children ages 5 to 35 mo. Purpose is the evaluation of
p.000021: methods for aggregate exposure measurements and the evaluation of pathways of exposure and important factors that
p.000021: affect exposure. Measurements include pesticide distributions in microenvironments where children spend time, transfer
p.000021: of pesticides from microenvironmental media to child, and factors that affect transfer.
p.000021:
p.000021:
p.000021:
p.000021: Study identified daycare centers with previously established contracts for routine monthly pesticide applications and
p.000021: conducted screening sampling in each to evaluate the distributions of transferable pesticide residues on floor surfaces
p.000021: where children spend time. One daycare was selected for intensive measurements, and children from different age groups
p.000021: volunteered to wear full-body cotton suits for short time periods while their activities were videotaped.
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000103: 103
p.000103: of molds/fungi and helped with lead and pesticide measurements.
p.000103:
p.000103:
p.000103: EPA conducted with contractor support
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: Multiagency effort; NERL was a participant and led the 9-home exposure component.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL funded IAG with VA to conduct study.
p.000103:
p.000103:
p.000103:
p.000103: EPA grant to UC Berkeley; NERL augmented the existing research effort.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL designed, contractor conducted
p.000103:
p.000103: Table A-1. (Continued)
p.000103: Study Date Size Type Brief Description
p.000103: NERL Role
p.000103: Tampa 2002 9 Residences Convenience Pilot study on methods for measuring personal,
p.000103: indoor NERL designed, Asthmatic sample,
p.000103: pilot residential, outdoor residential, and ambient combustion- contractor
p.000103: Children's Study study to test related products, particulate
p.000103: matter, and air toxics. The study conducted
p.000103: (TACS) methods. identified microenvironmental
p.000103: factors affecting penetration of pollutants into homes and reduction of exposures to pollutants for asthmatic children
p.000103: (0-5 years of age).
p.000103:
p.000103: Pilot Study To Evaluate Data Collection Methods for Young Children’s and Household Activities
p.000103: Detroit Exposure and Aerosol Research Study (DEARS)
p.000103:
p.000103:
p.000103:
p.000103: Accelerometer Pilot Study
p.000103:
p.000103:
p.000103:
...
Searching for indicator homeowner:
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p.002002: 2002
p.002002:
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p.002002:
p.002002: 6 Households
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 9 Households in NERL exposure component
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 20 Children
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 9 Daycare centers
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience, multiday pilot study to test methodology for exposure measure- ments
p.000021:
p.000021:
p.000021:
p.000021: Convenience, cross- sectional
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Case-control
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience
p.000021: other pollutants in institutional childcare centers. This national study used multistage sampling with clustering.
p.000021: Indoor wipe and outdoor soil samples were analyzed for pesticides, lead, and allergens (mold/fungi). Pesticide use
p.000021: practices and application information were obtained from the commercial pest control applicators serving the centers.
p.000021: Observational pilot exposure measurement study of residential exposures after homeowner had routinely applied granular
p.000021: formulation diazinon-containing turf treatment to residential lawns. Study was performed near Raleigh, NC, and was
p.000021: preceded by a 1-home methodology feasibility study. Purpose was to evaluate methods for assessing pet-borne transfer,
p.000021: translocation and exposure pathways, and decay rates.
p.000021:
p.000021:
p.000021:
p.000021: The objectives of this investigation in Jacksonville, FL, were to
p.000021: (1) assess organophosphate (OP) and pyrethroid pesticide exposures in a group of 4- to 6-year-old children from
p.000021: Jacksonville by measuring the urine metabolite levels,
p.000021: (2) identify possible sources of these pesticides through screening measurements and pesticide inventories, and
p.000021: (3) examine the relationship between environmental and biological levels. The Duval County Health Department (DCHD)
p.000021: collected urine samples for CDC from 200 children visiting six public health clinics in Jacksonville, and collected
p.000021: environmental screening samples at approximately 25% of these children’s homes. A detailed aggregate exposure
p.000021: assessment at 9 homes was overseen by NERL and involved collection of surface wipes, transferable residues, air,
p.000021: duplicate diet, cotton garment samples, and urine samples. A time- activity diary of the children’s activities was
p.000021: included.
p.000021: Work with Veteran’s Administration hospital staff. Cases of Legionnaires Disease were evaluated for potential for
...
Social / Racial Minority
Searching for indicator minority:
(return to top)
p.000001: implementation. As shown in the text box below, the planning process involves the initial identification of the
p.000001: research question and justification of the research effort during the problem conceptualization phase. If human
p.000001: subjects research is justified for the study, the scientific and ethical approaches are described in the study
p.000001: design and the human subjects research protocol. The basic elements that should be included in the
p.000001: study design and in the human subjects research protocol are described, and researchers are advised to consider
p.000001: alternative and innovative study designs that maximize the benefits to the study participants and their
p.000001: community. Information is provided on both scientific peer review and ethical review, and the integration
p.000001: of the two. Mandated procedures for review by external peers, by Institutional Review Boards (IRBs),
p.000001: and by the EPA Human Subjects Research Review Official (HSRRO) are detailed.
p.000001:
p.000001: to the authors as they have developed this document. Those references are listed in Table 1-4,
p.000001: which is replicated below.
p.000001: The authors also have relied extensively on the
p.000001: Problem Conceptualization
p.000001:
p.000001: Planning
p.000001: Define & Justify the Study
p.000001:
p.000001: advice of an expert panel that convened in November 2006 to provide advice and guidance about the structure and
p.000001: content of this document. The Expert Panel consisted of 11 nationally recognized authorities from
p.000001: diverse fields ― exposure science, environmental health, bioethics, epidemiology, community-based research, law,
p.000001: research in minority communities, public health, toxicology, pediatrics, and children’s environmental
p.000001: health.
p.000001: The Expert Panel Workshop resulted in suggestions
p.000001: & Scoping
p.000001:
p.000001:
p.000001: Independent Review
p.000001:
p.000001:
p.000001: Agency HSRRO
p.000001: Review
p.000001: Develop Study Design
p.000001:
p.000001:
p.000001: Peer Review
p.000001: Scientific & Ethical Review
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: HSRRO
p.000001: Review
p.000001: Develop Human Subjects Protocol
p.000001:
p.000001:
p.000001: IRB Review
p.000001: Ethical & Scientific Review
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Disapprove No Study
p.000001:
p.000001: for both the structure and the content of this document (ERG, 2007). Following the advice of the Expert Panel,
p.000001:
p.000001: Implement Study
p.000001: Approve Conduct Study
p.000001:
p.000001: this document is organized in seven sections.
p.000001: & Monitor Progress
p.000001: Criteria OK
p.000001: Continue Study
p.000001: Implement
p.000001: & Monitor
p.000001: Criteria Exceeded
p.000001: Terminate Study
p.000001:
p.000001:
p.000001: 1 See, for example, the writings of Beauchamp and Childress in Principles of Biomedical Ethics (Beauchamp and
p.000001: Childress, 2001) and the discussion of “What Makes Clinical Research Ethical?” by Emanuel, Wendler, and Grady (Emanuel
p.000001: et al., 2000).
p.000001: Stages in the Development of a NERL Observational Human Exposure Study
p.000001:
p.000002: 2
p.000002:
p.000002:
p.000002: Table 1-4. Important References in Developing This Document:
...
p.002008:
p.002008:
p.000012: 12
p.000012:
p.000012: address all of the relevant issues for their particular study to ensure that the specific elements of
p.000012: the study will safeguard and protect the human research subjects.
p.000012: In addition to being an information resource for NERL researchers, this document provides useful
p.000012: information for contractors and grantees funded by NERL to consider during the design and implementation of
p.000012: their exposure science research. Although not its intended audience, this document also may prove to be useful
p.000012: to other researchers, within and outside of EPA, who are involved in observational human exposure
p.000012: studies.
p.000012:
p.000012: 1.4 Process for Developing the Document
p.000012: This document was written by exposure science researchers in EPA’s NERL, with substantial input from experts
p.000012: within and outside of the Agency. Information relevant to the process and the document has been routinely
p.000012: posted on the EPA Web site at http://www.epa.gov/nerl/sots.
p.000012: NERL staff began this work by hosting a series of stakeholder meetings in the summer of 2006 to seek
p.000012: input on the content and format of the document. In November 2006, NERL convened an expert panel to
p.000012: provide its advice and guidance about the scope and content of this document. The Expert Panel consisted of
p.000012: 11 nationally recognized authorities in diverse fields: exposure science, environmental health,
p.000012: bioethics, epidemiology law, community-based research, research in minority communities, public health,
p.000012: toxicology, pediatrics, children’s environmental health, etc. Details about the Expert Panel and the workshop can
p.000012: be found in Appendix B. The summary report from the Expert Panel may be accessed
p.000012: online at http://www.epa.gov/nerl/sots/workshop-report.pdf.
p.000012: The structure and content of the current report follow the recommendations of the Expert
p.000012: Panel. Specifically, the Expert Panel recommended that this document should include the following six major
p.000012: topic areas:
p.000012: (1) elements to be considered in study conceptualization,
p.000012: (2) ensuring protection of vulnerable groups,
p.000012: (3) addressing privacy and other concerns related to observational human exposure studies,
p.000012: (4) creating an appropriate relationship between the participant and investigator,
p.000012: (5) building and maintaining appropriate community and stakeholder relationships, and
p.000012: (6) designing and implementing strategies for effective communication.
p.000012: These recommendations include pragmatic steps that NERL scientists can undertake during the development and
p.000012: implementation of observational human exposure studies. Note that each step may require consideration and
p.000012: application of multiple ethical and scientific principles, and the same ethical principle may
p.000012: be fundamental to several of the topic areas. As a result, the same ethical principle may be discussed in
p.000012: several sections throughout this document.
...
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
p.000035: broader definition of vulnerability as it relates to education, economics, social status, and other factors. As
...
Searching for indicator race:
(return to top)
p.000070: community involvement. The Expert Panel that was convened to advise NERL about scientific and ethical
p.000070: issues in observational human exposure studies discussed a number of challenges (ERG, 2007). The topics
p.000070: that the expert panel identified as issues are discussed below.
p.000070:
p.000070: 6.2.1 Defining “Community”
p.000070: “Community” refers to a group of people united by a shared attribute, and the attributes can be wide-ranging, such as
p.000070: geography, culture, social characteristics, values, interests, traditions, or experiences (ERG, 2007).
p.000070: Community can be defined broadly (as a system of interrelated groups operating to meet the needs of its
p.000070: members) or more narrowly (as the population from which study participants are selected). For observational
p.000070: field studies, the Expert Panel from the workshop suggested the narrow definition. A narrow
p.000070: definition allows social and cultural factors to be included but excludes government agencies, industry, and
p.000070: others who do not necessarily represent the interests of the participants (ERG, 2007).
p.000070: Central to the definition of a community is a sense of “who is included and who is excluded from
p.000070: membership” (NRC & IOM, 2005). A person may be a member of a community by choice, as with voluntary
p.000070: associations, or by virtue of their innate personal characteristics, such as age, gender, race, or
p.000070: ethnicity (NRC & IOM, 2005). As a result, individuals may belong to multiple communities at any one time. When
p.000070: initiating community engagement efforts, one should be aware of these complex associations in deciding which
p.000070: individuals to work with in the targeted community.
p.000070: Quandt et al. (2001) discuss a CBPR research project, Preventing Agricultural Chemical Exposure in
p.000070: North Carolina Farmworkers, where the process of defining a community was complicated by language,
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
p.000070: sense of community was nurtured among the farmworkers collectively (O’Fallon and Dearry, 2002).
...
p.000072: influencing the intended audience and build that understanding into the communication strategy (Tillman,
p.000072: 2002). The symbols, metaphors, visuals (including clothing, jewelry, and hairstyles), types of
p.000072: actors, language, and music used in communication materials all convey culture. Discussions with
p.000072: community members can assist researchers in identifying messages and images that resonate across groups or
p.000072: suggesting situations in which different messages or images are likely to work best.
p.000072: As discussed above and in Sections 5 and 7, communication materials must be tailored for each
p.000072: individual community and must be written in a language and at a reading level that will ensure comprehension.
p.000072: Many IRBs require materials to be prepared at a 5th grade reading level. Researchers should evaluate the
p.000072: reading level of all data collection instruments and study communication materials and should objectively
p.000072: measure comprehension in pretests prior to use in the study. Similarly, if translations of materials are
p.000072: required, certified translating services should be used to ensure accuracy and comprehension.
p.000072:
p.000072: 6.2.5 Recognizing and Addressing Cultural Differences
p.000072: Building and maintaining appropriate community and stakeholder relationships requires acknowledgment of the
p.000072: diversity within communities with regard to many factors, including, but not limited to, race/ethnicity,
p.000072: religious beliefs, heritage, and lifestyles. Different groups in the study area may have different
p.000072: cultural norms and practices. The researchers should take these issues into consideration as they work in the
p.000072: community. Community partners can help researchers design the study to be attentive to the increasing
p.000072: heterogeneity of community groups (Minkler and Wallerstein, 2003, Chapter 4) and to the different
p.000072: boundaries of privacy (crucial when designing sampling strategies) of different groups (Israel et al., 2005b, Chapter
p.000072: 11).
p.000072: Vega (1992) provides a thorough discussion of the theoretical and pragmatic implications of
p.000072: cultural diversity for community research and explains that researchers should interact with
p.000072: communities using methods that promote understanding and demonstrate sensitivity and competence in
p.000072: working with diverse
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073: cultures (e.g., with respect to class, gender, ethnicity, race, age, and sexual orientation). To aid in this
p.000073: process, researchers should include sufficient time in their project timeline to interact and dialogue with the
p.000073: community before the study begins to understand the cultural issues that may affect the research. Researchers and the
p.000073: results of their work are expected to promote a strengthening of the community; however, it should be recognized
p.000073: that, given the heterogeneity and the diverse views within a community, the study findings potentially may
p.000073: conflict with the desires of the community or may promote feelings of anger or distrust among members
p.000073: of the community with each other. Enlisting the services of a third-party evaluator/mediator may be
p.000073: useful for sustaining positive relations between all research participants and the community at
p.000073: large.
p.000073: The Research Triangle Park Particulate Matter Panel Study (Williams et al., 2003), a NERL investigation of PM
p.000073: and related pollutants involving African-Americans in North Carolina, demonstrated an effective strategy for using
p.000073: communication to address cultural differences between the community and research personnel. Before beginning
p.000073: the research, the study design included time and a budget for building collaborations with
p.000073: organizations having close ties with the African- American community to establish trust between
p.000073: the community and research team. Using input from the community partner organizations, the
...
p.000116: beneficence is sometimes expressed as a separate principle, nonmaleficence (do no harm).
p.000116: Child. A person who has not attained the age of 18 years [40 CFR 26.202(a)]
p.000116: Collateral observations. Potentially unsafe hazards, conditions, or situations unrelated to the research study that
p.000116: are observed by the research staff
p.000116: Common Rule. The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects.” It was
p.000116: adopted by more than a dozen Federal departments or agencies in 1991, with EPA adapting it in Title 40 CFR Part 26
p.000116: Subpart A.
p.000116: Community-based participatory research (CBPR). Collaborative research with a community in which the community is
p.000116: involved in all phases of the research.
p.000116: A fundamental concept is that the research aims to combine knowledge with action and to achieve social
p.000116: change to improve health outcomes and eliminate health disparities.
p.000116: Confidentiality. The keeping safe or not redisclosing by one of the parties in a confidential relationship information
p.000116: that originally was disclosed in the confidential relationship
p.000116: Environmental justice. The fair treatment and meaningful involvement of all people regardless of race, color, national
p.000116: origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations,
p.000116: and policies
p.000116: Exposure. Contact of a chemical, physical, or biological agent with the outer boundary of an organism (e.g., a
p.000116: person). Exposure is quantified as the concentration of the agent in the medium in contact integrated over the time
p.000116: duration of that contact. (The definition is taken from Guidelines for Exposure Assessment [EPA/600/Z-92/001, May
p.000116: 1992]).
p.000116: Exposure concentration. The exposure mass divided by the contact volume or the exposure mass divided by the mass of
p.000116: contact volume depending on the medium
p.000116: Exposure duration. The length of time over which continuous or intermittent contacts occur between an agent and a
p.000116: target. For example, if an individual is in contact with an agent for 10 minutes per day for 300 days over a 1-year
p.000116: time period, the exposure duration is 1 year.
p.000116: Exposure event. The occurrence of continuous contact between an agent and a target
p.000116: Exposure pathway. The course an agent takes from the source to the target
p.000116: Exposure route. The way an agent enters a target after contact (e.g., by ingestion, inhalation, or dermal absorption)
p.000116:
p.000116:
p.000117: 117
p.000117:
p.000117: Human subject. A living individual about whom an investigator (whether professional or student) conducting research
p.000117: obtains: (1) data through intervention or interaction with the individual, or (2) identifiable private information [40
p.000117: CFR 26.102(f)]
p.000117: Informed consent. A potential participant’s autonomous authorization to participate in the research.
...
Searching for indicator racial:
(return to top)
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
p.000035: broader definition of vulnerability as it relates to education, economics, social status, and other factors. As
...
p.000070: members) or more narrowly (as the population from which study participants are selected). For observational
p.000070: field studies, the Expert Panel from the workshop suggested the narrow definition. A narrow
p.000070: definition allows social and cultural factors to be included but excludes government agencies, industry, and
p.000070: others who do not necessarily represent the interests of the participants (ERG, 2007).
p.000070: Central to the definition of a community is a sense of “who is included and who is excluded from
p.000070: membership” (NRC & IOM, 2005). A person may be a member of a community by choice, as with voluntary
p.000070: associations, or by virtue of their innate personal characteristics, such as age, gender, race, or
p.000070: ethnicity (NRC & IOM, 2005). As a result, individuals may belong to multiple communities at any one time. When
p.000070: initiating community engagement efforts, one should be aware of these complex associations in deciding which
p.000070: individuals to work with in the targeted community.
p.000070: Quandt et al. (2001) discuss a CBPR research project, Preventing Agricultural Chemical Exposure in
p.000070: North Carolina Farmworkers, where the process of defining a community was complicated by language,
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
p.000070: sense of community was nurtured among the farmworkers collectively (O’Fallon and Dearry, 2002).
p.000070: Understanding and describing a community (CDC, 1997) involves exploring factors related to
p.000070: • people (including socioeconomics and demographics, health status, and cultural and ethnic characteristics),
p.000070: • location (geographic boundaries),
p.000070: • commonalities (including shared values, interests, and motivating forces), and
p.000070: • power relationships (including formal and informal lines of authority and influence, stakeholder relationships, and
p.000070: resource flows).
p.000070: It is important to distinguish between stakeholders and the community, but both should be engaged at some point
...
Social / Religion
Searching for indicator belief:
(return to top)
p.000040:
p.000040:
p.000040:
p.000040: Observational human exposure studies are designed to describe people’s contact with pollutants as they go about
p.000040: their everyday lives. Of necessity then, these studies take place in the locations that participants often
p.000040: consider to be personal and private. Clinical research studies generally are conducted in a research
p.000040: facility, a clinic, a hospital, or some other institutional or medical setting. Survey research may be conducted by
p.000040: mail, over the phone, or in another “neutral” setting. But, observational human exposure studies are
p.000040: conducted in the participants’ “personal” environment⎯their home, daycare center, school, vehicle,
p.000040: workplace, or other environments that people occupy during their routine daily activities. This difference
p.000040: in the research setting means that researchers involved in observational human exposure studies have an
p.000040: even greater challenge in meeting the ethical obligation to respect the privacy of the participants.
p.000040: When exposure science researchers like those at NERL enter a home to carry out their studies, the
p.000040: “expectations and constraints may be strikingly different than when research is carried out in a medical
p.000040: setting” (p. 64, NRC & IOM, 2005). The legal precept of freedom from unreasonable search and
p.000040: seizure and the historic and deeply rooted principle that “a man’s home is his castle” contribute to a belief in the
p.000040: “sanctity of the home” (see the discussion on pp. 62-66, NRC & IOM, 2005).
p.000040: The joint NRC and IOM report Ethical Considerations for Research on Housing-Related Health
p.000040: Hazards Involving Children discusses the ethical issues associated with entering a participant’s home to conduct
p.000040: research and explores the researchers’ responsibilities that derive from conducting research in people’s homes
p.000040: (NRC & IOM, 2005). These housing-related discussions are particularly relevant to observational human
p.000040: exposure studies, which often include environmental and
p.000040: biological measurements in people’s homes or personal locations. Many of the topics identified in that report are
p.000040: discussed in this section (Text Box 4-1).
p.000040:
p.000040:
p.000040: Text Box 4-1. Topics in Section 4
p.000040: Privacy Issues Confidentiality
p.000040: Confidentiality of Information Confidentiality of Participation
p.000040: Collateral Observations
p.000040: Potential Nonstudy Hazards in the Residence Collateral Observations with Mandated Reporting
p.000040: Requirements
p.000040: Hazard Communication Planning and Staff Training
p.000040: Third-Party Issues
p.000040: Determining Whether a Third Party is a Human Subject Informing Third Parties of Research Activities Research Results
p.000040: and Third Parties
p.000040: Data and Safety Monitoring and Oversight
p.000040:
p.000040:
p.000040:
p.000040: 4.1 Privacy Issues
...
Searching for indicator religious:
(return to top)
p.000070: community’s interests (a right afforded by legitimate membership in the group) but also should be able
p.000070: to describe those interests on behalf of the community. Identifying those who represent the community is
p.000070: not simply a matter of identifying the most vocal activists because those individuals do not necessarily
p.000070: represent the interests of the entire community. In fact, several individuals may be necessary to adequately
p.000070: represent the diversity of viewpoints within a community; in such cases, a CAB may be appropriate (ERG, 2007).
p.000070: One of the researcher’s first steps should be asking the potential participants from the community who they see
p.000070: as a
p.000070:
p.000070:
p.000071: 71
p.000071:
p.000071: legitimate representative (i.e., someone who can speak for them). Corburn cites an example of a locale
p.000071: in Brooklyn, NY, that contained individuals with widely different backgrounds. It was impossible to
p.000071: identify appropriate spokespeople, or even to define the nature of the community, without talking with
p.000071: community members (Corburn, 2007).
p.000071: The NRC & IOM (2005) Report also discusses the issue of who can represent the identified community. Some
p.000071: communities may have a formal governmental structure and a recognized political authority (e.g.,
p.000071: Native American tribes). Other communities may have clearly identifiable leaders (e.g., religious communities),
p.000071: whereas still other communities have no formal leadership structure at all. Whether there is a
p.000071: legitimate political authority or some other hierarchal leadership structure, the goal is to seek community input
p.000071: as to who best represents the interests of the community with regard to the proposed research project,
p.000071: rather than selecting those who are favorable to the research project. The NRC & IOM report cautions against
p.000071: the ethically questionable practice of seeking out population spokespeople and research participants
p.000071: whose positive response to a research plan can be predicted in advance and refers the reader to an article on this
p.000071: topic by Juengst (2000).
p.000071: With multiple sources of leadership and authority in many communities, careful consideration should be given
p.000071: to what aspect of the community a particular person will represent, and what efforts may be needed to ensure
p.000071: that the entire range of views in a community are obtained. Researchers should consider reaching out to multiple
p.000071: organizations such as churches, social service agencies, community-based organizations, and tenant and
p.000071: other community advocacy groups.
p.000071:
p.000071: 6.2.3 Building Relationships and Trust
p.000071: A key first step in developing trust is to establish a relationship with the community before the study. Trust must be
p.000071: built; it cannot be assumed. This relationship involves not only listening to community input but
...
p.000072: 2002). The symbols, metaphors, visuals (including clothing, jewelry, and hairstyles), types of
p.000072: actors, language, and music used in communication materials all convey culture. Discussions with
p.000072: community members can assist researchers in identifying messages and images that resonate across groups or
p.000072: suggesting situations in which different messages or images are likely to work best.
p.000072: As discussed above and in Sections 5 and 7, communication materials must be tailored for each
p.000072: individual community and must be written in a language and at a reading level that will ensure comprehension.
p.000072: Many IRBs require materials to be prepared at a 5th grade reading level. Researchers should evaluate the
p.000072: reading level of all data collection instruments and study communication materials and should objectively
p.000072: measure comprehension in pretests prior to use in the study. Similarly, if translations of materials are
p.000072: required, certified translating services should be used to ensure accuracy and comprehension.
p.000072:
p.000072: 6.2.5 Recognizing and Addressing Cultural Differences
p.000072: Building and maintaining appropriate community and stakeholder relationships requires acknowledgment of the
p.000072: diversity within communities with regard to many factors, including, but not limited to, race/ethnicity,
p.000072: religious beliefs, heritage, and lifestyles. Different groups in the study area may have different
p.000072: cultural norms and practices. The researchers should take these issues into consideration as they work in the
p.000072: community. Community partners can help researchers design the study to be attentive to the increasing
p.000072: heterogeneity of community groups (Minkler and Wallerstein, 2003, Chapter 4) and to the different
p.000072: boundaries of privacy (crucial when designing sampling strategies) of different groups (Israel et al., 2005b, Chapter
p.000072: 11).
p.000072: Vega (1992) provides a thorough discussion of the theoretical and pragmatic implications of
p.000072: cultural diversity for community research and explains that researchers should interact with
p.000072: communities using methods that promote understanding and demonstrate sensitivity and competence in
p.000072: working with diverse
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073: cultures (e.g., with respect to class, gender, ethnicity, race, age, and sexual orientation). To aid in this
p.000073: process, researchers should include sufficient time in their project timeline to interact and dialogue with the
p.000073: community before the study begins to understand the cultural issues that may affect the research. Researchers and the
...
Social / Soldier
Searching for indicator armed forces:
(return to top)
Searching for indicator military:
(return to top)
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
p.000055: dialogue . . . involving the disclosure and exchange of relevant information” (IOM, 2002): it is not
p.000055: simply having a consent form signed. The process is most effective when the researcher spends time with
p.000055: potential participants to discuss the study and to answer questions.
p.000055:
p.000055: 5.2 Payments to Research Participants
p.000055: The decision whether to pay research participants, including the appropriate level of payment,20 is
...
p.000060: could be addressed to the IRB, an ombudsman, an ethics committee, or other knowledgeable
p.000060: administrative body. Consent documents are expected to have at least two names with appropriate
p.000060: telephone contact information⎯one that can provide information regarding the research and
p.000060: another that can provide information regarding their rights as research participants. Grievance
p.000060: procedures should be structured so that grievances reach the approving IRBs and sponsoring
p.000060: organizations.
p.000060:
p.000060: 5.3.1 Ombudsman
p.000060: An ombudsman is a neutral independent advocate for research participants (and their families or guardians, where
p.000060: applicable). Institutions and IRBs may recommend or require the use of an ombudsman in
p.000060: certain types of research studies, particularly those seeking to study vulnerable populations.
p.000060: Ombudsmen can fill several roles as participant advocates. They may be an independent source of information
p.000060: regarding the study. They may be present during the informed consent process to ensure that risks, benefits,
p.000060: and study requirements are communicated correctly and understood by potential participants
p.000060: or their guardians. An ombudsman may be used in studies involving prisoners or military personnel to
p.000060: ensure that there is no coercion to participate. And the ombudsman may
p.000060:
p.000060:
p.000060:
p.000061: 61
p.000061:
p.000061: communicate problems or grievances raised by research participants to the IRB and sponsoring organization.
p.000061:
p.000061: 5.3.2 Community Advisory Board
p.000061: CABs can help ensure that participant rights are considered and addressed during the study design and can
p.000061: play an important role in monitoring the research process. Community members may choose to seek
p.000061: information about the study from the advisory panel, as an independent entity, before deciding whether to enroll.
p.000061: Representatives from such advisory boards can be included in the research team that designs the study (see
p.000061: Section 2.3). The role of CABs is more fully discussed in Section 6.
p.000061:
p.000061: 5.4 Creating a Supportive Environment for Research and Interaction
p.000061: It is recommended that researchers and institutions strive to create a supportive environment for research
p.000061: and interaction with research participants and communities. At the personal level,
p.000061: this means researchers building trust with individuals and treating them with respect. Following the IOM
p.000061: recommendations about the informed consent process⎯that it “should be an on-going, interactive dialogue between
p.000061: research staff and research participants involving the disclosure and exchange of relevant information,
p.000061: discussion of that information, and assessment of the individual’s understanding of the discussion”
...
Social / Student
Searching for indicator student:
(return to top)
p.000054: situations. Research protocols should address how translations will be accomplished. The use of
p.000054: untrained persons such as co-workers usually will not meet requirements for full understanding of human subject
p.000054: protections. Researchers should make plans for trained staff or trained community members, associated
p.000054: or affiliated with the research study, to be available for translations.
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
...
p.000116: that originally was disclosed in the confidential relationship
p.000116: Environmental justice. The fair treatment and meaningful involvement of all people regardless of race, color, national
p.000116: origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations,
p.000116: and policies
p.000116: Exposure. Contact of a chemical, physical, or biological agent with the outer boundary of an organism (e.g., a
p.000116: person). Exposure is quantified as the concentration of the agent in the medium in contact integrated over the time
p.000116: duration of that contact. (The definition is taken from Guidelines for Exposure Assessment [EPA/600/Z-92/001, May
p.000116: 1992]).
p.000116: Exposure concentration. The exposure mass divided by the contact volume or the exposure mass divided by the mass of
p.000116: contact volume depending on the medium
p.000116: Exposure duration. The length of time over which continuous or intermittent contacts occur between an agent and a
p.000116: target. For example, if an individual is in contact with an agent for 10 minutes per day for 300 days over a 1-year
p.000116: time period, the exposure duration is 1 year.
p.000116: Exposure event. The occurrence of continuous contact between an agent and a target
p.000116: Exposure pathway. The course an agent takes from the source to the target
p.000116: Exposure route. The way an agent enters a target after contact (e.g., by ingestion, inhalation, or dermal absorption)
p.000116:
p.000116:
p.000117: 117
p.000117:
p.000117: Human subject. A living individual about whom an investigator (whether professional or student) conducting research
p.000117: obtains: (1) data through intervention or interaction with the individual, or (2) identifiable private information [40
p.000117: CFR 26.102(f)]
p.000117: Informed consent. A potential participant’s autonomous authorization to participate in the research.
p.000117: The three pillars of valid informed consent are
p.000117: (1) information, (2) comprehension, and (3) voluntary participation.
p.000117: Institutional review board (IRB). An IRB established in accord with and for the purposes expressed in EPA’s Policy for
p.000117: Protection of Subjects in Human Research conducted and supported by EPA [40 CFR 26.102(g)]
p.000117: Justice. The ethical obligation to treat each person in accordance with what is due to him or her. In the ethics of
p.000117: research involving human subjects, the principle refers primarily to distributive justice, which requires the equitable
p.000117: distribution of both the burdens and the benefits of participation in research. Differences in distribution of burdens
p.000117: and benefits are justifiable only if they are based on morally relevant distinctions among persons.
p.000117: Minimal risk. The probability and magnitude of harm or discomfort anticipated in the research are not greater in and
p.000117: of themselves than those ordinarily encountered in daily life or during the performance of routine physical or
p.000117: psychological examinations or tests [40 CFR 26.102(i)].
...
Social / Threat of Stigma
Searching for indicator threat:
(return to top)
p.000044: • certain communicable diseases.
p.000044: Because different reporting statutes pertain in different states, it is necessary for researchers to
p.000044: learn and understand the applicable reporting requirements for the study location. In the case of abuse, it is
p.000044: also
p.000044: important to understand what actions or situations are considered abusive in a particular state. Although direct
p.000044: physical harm or violence might be obvious to a research staff member, there are other conditions of neglect that
p.000044: might be more difficult to recognize or to know when to report.
p.000044: Study participants should be made aware of statutory requirements for reporting collateral observations as part of the
p.000044: informed consent process. Researchers should include the reporting requirements in the informed
p.000044: consent form (discussed in Section 5) and should ensure that the study participant fully comprehends this
p.000044: information and the impact on their privacy and confidentiality.
p.000044:
p.000044: 4.3.3 Hazard Communication
p.000044: It is difficult for researchers to determine when and how to communicate with study participants or third
p.000044: parties about collateral observations related to potential hazards. A hazard might present such an imminent
p.000044: threat to health or safety that staff would need to communicate immediately with the participant or take
p.000044: action to mitigate the threat. In some cases, such as instances of abuse with attendant statutory reporting
p.000044: requirements, it may be necessary to breach confidentiality. More often, however, a potential hazard identified as
p.000044: a result of collateral observation may not be an imminent threat or pose a potential risk that is situation
p.000044: dependent or is related to third parties. A number of considerations in hazard communication come
p.000044: into play regarding confidentiality, privacy, the ability of the researcher to provide accurate and
p.000044: effective information regarding the hazard and hazard mitigation, and the ability of the study participant or others
p.000044: to effectively mitigate the hazard without unintended adverse consequences. The National Academy of Sciences
p.000044: Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children, Youth, and
p.000044: Families discussed many of these issues in depth (NRC & IOM, 2005).
p.000044: Different communities, cultures, or demographic groups can have different risk perceptions, which may
p.000044: affect how collateral observations are assessed and reported from one study location to the next. The AAP
p.000044: Committee on Environmental Health has prepared information regarding perception, identification, and
p.000044: communication of environmental health risks (AAP, 2003). Researchers likely will benefit from including
...
Searching for indicator stigmatization:
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p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45 CFR 46.408(b)
p.000053: for all research with children. Under the EPA Rule, greater than minimal risk observational research with children that
p.000053: does not hold out the prospect of direct benefit to the child is not permitted under any circumstances. Under the HHS
p.000053: Rule, greater than minimal risk research involving children without the prospect of direct benefit is permitted in very
p.000053: limited circumstances, but the consent of both parents is required in those cases (unless one parent is deceased,
p.000053: unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and
p.000053: custody of the child).
p.000053: special concerns about the potential for discrimination, stigmatization, and impact on
p.000053: future employment or insurance. The informed consent process needs to explain what the plans may be
p.000053: for such specimens and recognize the rights of the subjects to decide about any such future use,
p.000053: including having the material destroyed. The informed consent process needs to explicitly discuss
p.000053: obtaining permission from participants on behalf of themselves and their child to obtain specimens for
p.000053: genetic analysis.
p.000053:
p.000053: 5.1.2 Comprehension
p.000053: Research participants frequently fail to understand the research protocols in which they agree to participate (NRC
p.000053: & IOM, 2005). In considering the ethical issues raised by the Grimes v. Kennedy Krieger case, the NRC & IOM
p.000053: committee “realized that the crucial issue regarding consent was not what information was
p.000053: contained in the consent forms, but rather what the parents understood about the study and the hazards
p.000053: present in the home before and after the study” (p. 19, NRC & IOM, 2005). The committee laments that “IRBs
p.000053: place their attention on consent forms rather than on the process of providing and discussing information” (p.
...
Searching for indicator stigmatized:
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p.000009: the subject population, and the risk-benefit ratio. The principle of respect for subjects also includes
p.000009: additional emphasis on the welfare of the subjects.
p.000009: More recently, there has been increased scrutiny and discussions of the ethics of research involving human
p.000009: participants,6 and a number of respected institutions have
p.000009:
p.000009:
p.000009: 6 The term “human participants” often is used in this document. It denotes the importance of the study participant
p.000009: being actively engaged in a partnership with the researchers to address the objectives and goals of the study. The term
p.000009: should be considered to be synonymous with the term “human subject” as used in the Common Rule and in documents used to
p.000009: describe regulatory requirements for studies involving human subjects.
p.000009: Social or scientific value
p.000009:
p.000009: Scientific validity
p.000009:
p.000009:
p.000009: Fair subject selection
p.000009:
p.000009:
p.000009: Favorable risk- benefit ratio
p.000009:
p.000009:
p.000009: Independent review
p.000009:
p.000009:
p.000009:
p.000009: Informed consent
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Respect for potential and enrolled subjects
p.000009: that will improve health and well-being or increase knowledge
p.000009: Use of accepted scientific principles and methods, including statistical techniques, to produce reliable and valid data
p.000009: Selection of subjects so that stigmatized and vulnerable individuals are not targeted for risky research, and the rich
p.000009: and socially powerful are not favored for potentially beneficial research
p.000009: Minimization of risks; enhancement of potential benefits and risks to the subject are proportionate to the benefits to
p.000009: the subject and to society
p.000009: Review of the design of the research trial, its proposed subject population, and risk-benefit ratio by individuals
p.000009: unaffiliated with the research
p.000009: Provision of information to subjects about the purpose of the research and its procedures, potential risks, benefits,
p.000009: and alternatives, so that the individual understands this information and can make a voluntary decision whether to
p.000009: enroll and continue to participate
p.000009: Respect for subjects by
p.000009: • permitting withdrawal from the research,
p.000009: • protecting privacy through confidentiality,
p.000009: • informing subjects of newly discovered risks or benefits,
p.000009: • informing subjects of results of the research, and
p.000009: • maintaining welfare of subjects.
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: Collectively, these documents have reaffirmed the basic ethical principles asserted in the Belmont Report
p.000010: and have attempted, in some cases, to expand scientific and ethical reasoning and understanding to define
p.000010: approaches for dealing with additional elements of human subjects research. These additional
p.000010: elements, which often have been identified because of specific incidents or case studies, include issues
...
p.000015: human subjects research protocol undergo evaluation by the Agency’s Human Subjects Research Review Official
p.000015: (HSRRO). The HSRRO, located in the EPA Office of the Science Advisor, ensures that Agency studies comply with
p.000015: the Common Rule and all directives of 40 CFR 26 providing guidance and principles to govern Federal agency
p.000015: sponsored human subject research.. Only after HSRRO approval can any research actually begin. As the NERL study
p.000015: is implemented, project data and concerns of the participants will be monitored on a continuing basis and
p.000015: compared with previously established standards and
p.000015:
p.000015:
p.000017: 17
p.000017:
p.000017:
p.000017: Table 2.1. Seven Requirements for Determining Whether a Research Trial is Ethical
p.000017: From Emanuel, Wendler, and Grady (2000)
p.000017: Requirement Explanation
p.000017: Topics in this Section
p.000017:
p.000017:
p.000017: Social or scientific value
p.000017:
p.000017: Evaluation of a treatment, intervention, or theory that will improve health and well-being or increase knowledge
p.000017:
p.000017: Defining the study problem Justifying the study Identifying a research team
p.000017:
p.000017:
p.000017: Scientific validity
p.000017:
p.000017: Use of accepted scientific principles and methods, including statistical techniques, to produce reliable and valid data
p.000017:
p.000017: Study design Feasibility
p.000017: Sample size determination Representativeness of the sample Information collection rule
p.000017: Quality assurance Study design document
p.000017:
p.000017:
p.000017: Fair subject selection
p.000017:
p.000017: Selection of subjects so that stigmatized and vulnerable individuals are not targeted for risky research, and the rich
p.000017: and socially powerful are not favored for potentially beneficial research
p.000017:
p.000017: Ethical issues in fair subject selection
p.000017:
p.000017:
p.000017: Favorable risk- benefit ratio
p.000017:
p.000017: Minimization of risks; enhancement of potential benefits and risks to the subject are proportionate to the benefits to
p.000017: the subject and to society
p.000017:
p.000017: Designing in benefits for participants
p.000017: Assessing benefits and risks of study participation
p.000017:
p.000017:
p.000017: Independent review
p.000017:
p.000017: Review of the design of the research trial, its proposed subject population, and risk-benefit ratio by individuals
p.000017: unaffiliated with the research
p.000017:
p.000017: Scientific peer review Conflicts of interest
p.000017: Developing the protocol for ethical review Ethical review
p.000017: EPA review of scientific and ethical issues
p.000017:
p.000017:
p.000017: Informed consent
p.000017:
p.000017: Provision of information to subjects about the purpose of the research, its procedures, potential risks, benefits, and
p.000017: alternatives, so that the individual understands this information and can make a voluntary decision whether to enroll
p.000017: and continue to participate
p.000017:
p.000017: Informed consent
p.000017: Ensuring that participant behaviors are not adversely changed
p.000017:
p.000017:
p.000017: Respect for potential and enrolled subjects
p.000017:
p.000017: Respect for subjects by
...
Social / Threat of Violence
Searching for indicator violence:
(return to top)
p.000044: • Uncovered electrical outlets
p.000044: • Unprotected stairways
p.000044: • Missing child-protective cabinet latches
p.000044: • Lack of window guards
p.000044: • Missing or inoperable smoke alarm
p.000044: • Housing code violations
p.000044: • Chipping or flaking paint—potential for lead exposure in older homes
p.000044: • Malfunctioning or unvented combustion appliances—potential for carbon monoxide exposure
p.000044: • Unsecured poisons or other dangerous products
p.000044: • Excessive mold growth
p.000044:
p.000044:
p.000044: 4.3.2 Collateral Observations with Mandated Reporting Requirements
p.000044: Some collateral observations may have statutory requirements for reporting to designated authorities.
p.000044: Examples of such observations include
p.000044: • observed child or elder abuse or evidence of such abuse or neglect,
p.000044: • statements or actions of intent to harm self or others, and
p.000044: • certain communicable diseases.
p.000044: Because different reporting statutes pertain in different states, it is necessary for researchers to
p.000044: learn and understand the applicable reporting requirements for the study location. In the case of abuse, it is
p.000044: also
p.000044: important to understand what actions or situations are considered abusive in a particular state. Although direct
p.000044: physical harm or violence might be obvious to a research staff member, there are other conditions of neglect that
p.000044: might be more difficult to recognize or to know when to report.
p.000044: Study participants should be made aware of statutory requirements for reporting collateral observations as part of the
p.000044: informed consent process. Researchers should include the reporting requirements in the informed
p.000044: consent form (discussed in Section 5) and should ensure that the study participant fully comprehends this
p.000044: information and the impact on their privacy and confidentiality.
p.000044:
p.000044: 4.3.3 Hazard Communication
p.000044: It is difficult for researchers to determine when and how to communicate with study participants or third
p.000044: parties about collateral observations related to potential hazards. A hazard might present such an imminent
p.000044: threat to health or safety that staff would need to communicate immediately with the participant or take
p.000044: action to mitigate the threat. In some cases, such as instances of abuse with attendant statutory reporting
p.000044: requirements, it may be necessary to breach confidentiality. More often, however, a potential hazard identified as
...
Social / Trade Union Membership
Searching for indicator union:
(return to top)
p.000058: arguments from the American Academy of Pediatrics that “any token payment to children for participating in research
p.000058: should not be discussed with them until after research is completed for fear of unduly influencing their decisions
p.000058: (AAP, 2003)…. On balance, the committee agrees that it is best to mention token or other payments during the permission
p.000058: and assent processes” (p. 215, IOM, 2004).
p.000058: The IOM Recommendation 6.1 states, “Institutional review boards, research institutions, and sponsors of research that
p.000058: includes children and adolescents should adopt explicit written policies on acceptable and unacceptable types and
p.000058: amounts of payments related to research participation. These policies should specify that investigators
p.000058: • Disclose the amount, the recipient, the timing, and the purpose (e.g., an expense reimbursement or a token of
p.000058: appreciation to a child) of any payments as part of the process of seeking parents’ permission, and, as appropriate,
p.000058: children’s assent to research participation;
p.000058: • Avoid emphasis on payments or descriptions of payments as benefits of participating in research during the
p.000058: permission or assent procedures; and
p.000058: • Obtain institutional review board approval for the disclosure of information about payments in advertisements and
p.000058: in permission and assent forms and procedures.”
p.000058:
p.000058:
p.000059: 59
p.000059:
p.000059: participate in research are unacceptable. The European Union requires that clinical trials on minors
p.000059: be undertaken only if “no incentives or financial inducements are given except compensation”
p.000059: (European Parliament, 2001).
p.000059: Payment for participation of children in research also is discussed in the literature. Diekema
p.000059: (2005) emphasizes the need to ensure that payments do not distort parental decisionmaking and do not tempt
p.000059: parents to consider other issues than the welfare of their child. Similarly, Menikoff (2005) suggested that
p.000059: there need to be relatively robust protections in place to ensure that families do not change their behaviors
p.000059: to participate in a study. He suggested that these may include determining payment as a percentage of a family’s
p.000059: income and developing criteria for documenting that behaviors have not changed to be eligible for participation in a
p.000059: study. He suggested that, for a study of pesticides, potential study participants provide documentation (such as
p.000059: receipts) that they routinely have been using a commercial pesticide service. This may be difficult
p.000059: for potential participants to do if they do not save receipts, and it would exclude all potential
p.000059: participants who purchase products and apply pesticides themselves. This likely would affect the study
p.000059: objectives and generalizability of the data collected. A survey of investigators (Iltis et al., 2006) found that
...
Social / Unemployment
Searching for indicator unemployed:
(return to top)
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
...
Social / Victim of Abuse
Searching for indicator abuse:
(return to top)
p.000042: may sometimes lead to the indirect identification of the individual. Certain combinations of
p.000042: demographic information, for example, may make it relatively simple
p.000042:
p.000042:
p.000042: 14 Beauchamp and Childress (2001) discuss when one may be ethically justified in infringing on an individual’s privacy
p.000042: and confidentiality⎯for example, because of risks to others evidenced by biomarkers of infectious disease. They also
p.000042: discuss similar ethical issues that may arise in regard to genetic data. CIOMS (2002) Guideline 18 provides suggestions
p.000042: for safeguarding or disclosing genetic information. If exposure scientists collaborate with medical researchers or
p.000042: epidemiologists and obtain such information, they need to be cognizant of the relevant ethical issues and of the CIOMS
p.000042: guidelines.
p.000042: 15 Guideline 18 states, “The investigator must establish secure safeguards of
p.000042: the confidentiality of subjects’ research data. Subjects should be told the limits, legal or other, to the
p.000042: investigators’ ability to safeguard confidentiality and the possible consequences of breaches of confidentiality.”
p.000042: Additional CIOMS commentary on the confidentiality guideline states, “Prospective subjects should be informed of limits
p.000042: to the ability of researchers to ensure strict confidentiality and of the foreseeable adverse social consequences of
p.000042: breaches of confidentiality. Some jurisdictions require the reporting to appropriate agencies of, for instance, certain
p.000042: communicable diseases or evidence of child abuse or neglect. These and similar limits to the ability
p.000042: to maintain confidentiality should be anticipated and disclosed to prospective subjects.”
p.000042: to identify an individual. Precise geographic location information may be sufficient to pinpoint a
p.000042: residence. Researchers may use several strategies to reduce the likelihood of indirect identification when
p.000042: study results are reported (see, also, Text Box 4-3).
p.000042: • Redact from publications, reports, or public data sets information that might be used to indirectly identify a
p.000042: research participant.
p.000042: • Generalize exact information; for example, replace birth date with age or year of birth or classify age as
p.000042: part of a range.
p.000042: • Aggregate information across individuals; for example, only report data in cells of sufficient size
p.000042: to make individual linkages unlikely.
p.000042: • Reduce the specificity of geographic coordinate information to a level that a specific residence or other
p.000042: location can not be identified.
p.000042:
p.000042: Text Box 4-3. Approaches for Protecting Personally Identifiable Information
p.000042: • Developing procedures for safeguarding information prior to collecting the information
p.000042: • Ensuring that data or samples are anonymous by not collecting or by destroying identifying information or linkages
p.000042: • Restricting access to identifying information to only those requiring access
p.000042: • Assigning codes to participants, data, and samples rather than using identifiers
...
p.000043: the home have to be asked for permission or be informed that monitoring activities are taking place.
p.000043: Researchers and IRBs should consider whether knowledge of an individual’s participation by others might
p.000043: create potential for harm or distress in an observational human exposure study. Such risks might
p.000043: be limited to possible discomfort in attracting unwanted
p.000043: attention; this may be particularly true for adolescents. However, in some cases, the potential risks
p.000043: could be greater, for example, in cases where participation could provoke an adverse reaction from a
p.000043: landlord or employer. Oftentimes study protocols can be structured to minimize these potential risks. Through the
p.000043: informed consent process, prospective participants should be made aware of the limits of the researcher’s ability to
p.000043: protect knowledge of their participation in the study and of the possible risks of disclosure.
p.000043:
p.000043: 4.3 Collateral Observations
p.000043: In the course of conducting an observational human exposure study, research staff may observe potentially unsafe
p.000043: conditions or situations that are unrelated to the research study. Such “collateral observations” may
p.000043: involve physical hazards in the study participant’s residential environment or evidence of situations,
p.000043: such as child abuse, that have to be reported to proper authorities. In preparing for the
p.000043: research study, it is recommended that researchers carefully plan for possible collateral observations,
p.000043: including their identification, staff training, and hazard communication and reporting. This may be a major
p.000043: element in the data and safety monitoring and oversight for the study. The informed consent process
p.000043: should reflect procedures used to manage collateral observations. Potential participants should be
p.000043: informed of situations in which confidentiality might be breached, such as statutory requirements for reporting
p.000043: abuse or imminent harm to self or others.
p.000043:
p.000043: 4.3.1 Potential Nonstudy Hazards in the Residence
p.000043: Research staff conducting observational human exposure studies often will spend time in and around
p.000043: study participant residences. In the course of visiting a residence or conducting study-related
p.000043: observations, research staff may observe potential hazards unrelated to the research being performed (see Text Box
p.000043: 4-4). Some hazards may be associated with the potential for physical injury, whereas others may be related to
p.000043: exposure to chemical or biological agents. Some situations may be potential hazards only for young children,
p.000043: whereas other conditions may present potential hazards for all residents or occupants.
p.000043: The NRC & IOM recommend that researchers should consider such foreseeable observations and
p.000043: potential hazards in advance, develop responses to the risks, and submit the proposed plans to the IRB
p.000043: for review to ensure that they are appropriate “in the context of the research and the affected community.” The NRC
p.000043:
p.000043:
p.000044: 44
p.000044:
p.000044: & IOM also advise that field staff should be trained in how to assess and respond to
p.000044: such risks (Recommendations 7.3 and 7.4, NRC & IOM, 2005). For other behaviors and risks that
p.000044: have not been specifically identified in advance, procedures should be included in the data and safety monitoring
p.000044: and oversight provisions of the study design and research protocol to address these issues. The fundamental
...
p.000044: those harms, even for observations that are not directly related to the study. The steps that they may take can
p.000044: range from immediate action to prevent an imminent and serious danger to statutory reporting of
p.000044: observations (see Section 4.3.2) to reporting the observation to the data and safety monitoring and oversight
p.000044: authority for advice on how to respond (see Section 4.5). (The reader is also referred to pages 59-61 and 134-144 of
p.000044: the NRC & IOM [2005] report for a more thorough discussion of researchers’ responsibilities in such
p.000044: cases.)
p.000044:
p.000044: Text Box 4-4. Potential Hazards that Might Be Encountered in a Residential Environment
p.000044: • Unsecured firearm
p.000044: • Uncovered electrical outlets
p.000044: • Unprotected stairways
p.000044: • Missing child-protective cabinet latches
p.000044: • Lack of window guards
p.000044: • Missing or inoperable smoke alarm
p.000044: • Housing code violations
p.000044: • Chipping or flaking paint—potential for lead exposure in older homes
p.000044: • Malfunctioning or unvented combustion appliances—potential for carbon monoxide exposure
p.000044: • Unsecured poisons or other dangerous products
p.000044: • Excessive mold growth
p.000044:
p.000044:
p.000044: 4.3.2 Collateral Observations with Mandated Reporting Requirements
p.000044: Some collateral observations may have statutory requirements for reporting to designated authorities.
p.000044: Examples of such observations include
p.000044: • observed child or elder abuse or evidence of such abuse or neglect,
p.000044: • statements or actions of intent to harm self or others, and
p.000044: • certain communicable diseases.
p.000044: Because different reporting statutes pertain in different states, it is necessary for researchers to
p.000044: learn and understand the applicable reporting requirements for the study location. In the case of abuse, it is
p.000044: also
p.000044: important to understand what actions or situations are considered abusive in a particular state. Although direct
p.000044: physical harm or violence might be obvious to a research staff member, there are other conditions of neglect that
p.000044: might be more difficult to recognize or to know when to report.
p.000044: Study participants should be made aware of statutory requirements for reporting collateral observations as part of the
p.000044: informed consent process. Researchers should include the reporting requirements in the informed
p.000044: consent form (discussed in Section 5) and should ensure that the study participant fully comprehends this
p.000044: information and the impact on their privacy and confidentiality.
p.000044:
p.000044: 4.3.3 Hazard Communication
p.000044: It is difficult for researchers to determine when and how to communicate with study participants or third
p.000044: parties about collateral observations related to potential hazards. A hazard might present such an imminent
p.000044: threat to health or safety that staff would need to communicate immediately with the participant or take
p.000044: action to mitigate the threat. In some cases, such as instances of abuse with attendant statutory reporting
p.000044: requirements, it may be necessary to breach confidentiality. More often, however, a potential hazard identified as
p.000044: a result of collateral observation may not be an imminent threat or pose a potential risk that is situation
p.000044: dependent or is related to third parties. A number of considerations in hazard communication come
p.000044: into play regarding confidentiality, privacy, the ability of the researcher to provide accurate and
p.000044: effective information regarding the hazard and hazard mitigation, and the ability of the study participant or others
p.000044: to effectively mitigate the hazard without unintended adverse consequences. The National Academy of Sciences
p.000044: Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children, Youth, and
p.000044: Families discussed many of these issues in depth (NRC & IOM, 2005).
p.000044: Different communities, cultures, or demographic groups can have different risk perceptions, which may
p.000044: affect how collateral observations are assessed and reported from one study location to the next. The AAP
...
p.000045: result from taking an action. In some cases, it may be reasonable to refer the participant to another
p.000045: organization that can provide expert advice or assistance.
p.000045:
p.000045: 4.3.4 Planning and Staff Training
p.000045: As part of the study planning process and protocol development, it is important that researchers
p.000045: be cognizant of the kinds of collateral observations that might occur in the implementation of the study
p.000045: protocol and to develop plans as to how such observations would be handled. Researchers may choose to
p.000045: include a systematic approach in hazard identification, such as using a home-hazard checklist that becomes an
p.000045: ancillary part of the study protocol. Alternatively, collateral observations could be handled on a
p.000045: case-by-case basis.
p.000045: Staff experience and training is a critical consideration for managing collateral observations. Staff
p.000045: members that visit study participant residences may not have expertise or experience in identifying many of the
p.000045: potential hazards without adequate training. All staff involved in a study, particularly those responsible
p.000045: for field data collection, should be trained on identification and reporting of collateral observations. This
p.000045: training should be study specific and likely will include, but not be limited to
p.000045: (1) identification of actions (e.g., child abuse) that have (state-specific) statutory reporting requirements,
p.000045: (2) conditions of neglect that may adversely impact study participants or third parties,
p.000045: (3) environmental hazards and situations that may be associated with imminent harm (e.g., combustible
p.000045: materials near an open flame, unsecured firearms accessible to very young children),
p.000045: (4) policies and procedures for reporting or intervention by members of the research team, and
p.000045: (5) local and state reporting requirements.
p.000045: It is advisable that this training be developed in consultation with community representatives who can
p.000045: provide input on potential hazards and situations that may be encountered in the study community,
p.000045: local norms and attitudes about potential interventions and reporting, and local agencies available to assist on
p.000045: these types of issues. It is also especially important to consider
p.000045: staff experience and training in hazard communication. Consistency in communication is very important, and
p.000045: researchers may decide to use materials prepared by other organizations that have expertise regarding
p.000045: a particular hazard.
p.000045: Another important element of planning for field data collection and training of research staff is on hazards and
p.000045: situations that the field staff may encounter during their field work. Although the previous discussion highlights the
...
p.000071: as to who best represents the interests of the community with regard to the proposed research project,
p.000071: rather than selecting those who are favorable to the research project. The NRC & IOM report cautions against
p.000071: the ethically questionable practice of seeking out population spokespeople and research participants
p.000071: whose positive response to a research plan can be predicted in advance and refers the reader to an article on this
p.000071: topic by Juengst (2000).
p.000071: With multiple sources of leadership and authority in many communities, careful consideration should be given
p.000071: to what aspect of the community a particular person will represent, and what efforts may be needed to ensure
p.000071: that the entire range of views in a community are obtained. Researchers should consider reaching out to multiple
p.000071: organizations such as churches, social service agencies, community-based organizations, and tenant and
p.000071: other community advocacy groups.
p.000071:
p.000071: 6.2.3 Building Relationships and Trust
p.000071: A key first step in developing trust is to establish a relationship with the community before the study. Trust must be
p.000071: built; it cannot be assumed. This relationship involves not only listening to community input but
p.000071: actually taking it into consideration (ERG, 2007). A long history of research with no direct benefits and
p.000071: no feedback of results to the community, however, has contributed to a general mistrust of
p.000071: researchers by community members (Israel et al., 1998). Moreover, the recurring abuse of trust in communities is a
p.000071: reality that researchers should be aware of when attempting to build a long-term relationship (Minkler and
p.000071: Wallerstein, 2003). Past ethical failures have created distrust among some communities and have produced great
p.000071: challenges
p.000071: for current community organizers. Although it may seem self-evident, researchers need to remember that ethical
p.000071: action, during all phases of the research, is necessary for developing and maintaining the trust of communities
p.000071: (Perkins and Wandersman, 1990; CDC, 1997).
p.000071: Developing trust is a difficult and time-consuming process. Israel et al. (2005b) suggest a number of ways
p.000071: partners can gain each other’s trust. First, partners can show respect by seriously considering the ideas
p.000071: and opinions of others. Second, trustworthiness can be demonstrated by following through with those
p.000071: things that each partner commits to. Third, partners have to respect confidentiality. Fourth, they
p.000071: recommend attending to each other’s interests and needs by participating in activities beyond the
p.000071: specific work of the partnership.23 A history of prior positive working relationships is also beneficial
p.000071: (Israel et al., 1998).
p.000071: Trust cannot be separated from respect. Potential participants need to see researchers fostering respect for
p.000071: community members and leaders to gain trust. For example, meeting with key community leaders
p.000071: and groups in their surroundings helps to build trust for a true partnership. Such meetings provide
...
p.000117: intellectually) with others
p.000117: Research. A systematic investigation, including research development, testing, and evaluation, designed to develop or
p.000117: contribute to generalizable knowledge
p.000117: Research involving intentional exposure of a human subject. A study of a substance in which the exposure to the
p.000117: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
...
Social / Women
Searching for indicator women:
(return to top)
p.000025: 25
p.000025: 2.4.1. Designing in Benefits for the Participants
p.000025: 25
p.000025: 2.4.2. Assessing Benefits and Risks of Study Participation 25
p.000025: 2.5. Independent Scientific and Ethical Review
p.000026: 26
p.000026: 2.5.1. Scientific Peer Review
p.000027: 27
p.000027: 2.5.2. Conflicts of Interest
p.000027: 27
p.000027: 2.5.3. Develop the Human Subjects Protocol for Institutional Review Board Review 28
p.000027: 2.5.4. Ethical Review
p.000029: 29
p.000029: 2.5.5. Internal U.S. EPA Review of Scientific and Ethical Issues 29
p.000029: 2.6. Informed Consent
p.000029: 29
p.000029: 2.7. Ensuring That Participant Behaviors Are Not Changed Adversely Because of
p.000029: Being in the Study
p.000030: 30
p.000030: 2.8. Criteria and Standards for Monitoring Scientific and Ethical Issues 30
p.000030: 3. Ensuring Protection of Vulnerable Groups
p.000035: 35
p.000035: 3.1. Identification of Vulnerable Groups
p.000035: 35
p.000035: vii
p.000035:
p.000035: 3.2. Justification for Involving Vulnerable Persons in Observational Research 36
p.000035: 3.3. Minimal Risk and Vulnerable Groups
p.000037: 37
p.000037: 3.4. Research Involving Children
p.000037: 37
p.000037: 3.5. Women as Research Subjects
p.000038: 38
p.000038: 3.6. Other Potentially Vulnerable Groups
p.000039: 39
p.000039: 4. Privacy, Confidentiality, and Other Concerns Related to Observational
p.000039: Human Exposure Studies
p.000041: 41
p.000041: 4.1. Privacy Issues
p.000041: 41
p.000041: 4.2. Confidentiality
p.000042: 42
p.000042: 4.2.1. Confidentiality of Information
p.000043: 43
p.000043: 4.2.2. Confidentiality of Participation
p.000044: 44
p.000044: 4.3. Collateral Observations
p.000044: 44
p.000044: 4.3.1. Potential Nonstudy Hazards in the Residence 44
p.000044: 4.3.2. Collateral Observations with Mandated Reporting Requirements 45
p.000044: 4.3.3. Hazard Communication
p.000045: 45
p.000045: 4.3.4. Planning and Staff Training
p.000046: 46
p.000046: 4.4. Third-Party Issues
p.000046: 46
p.000046: 4.4.1. Determining Whether a Third Party Is a Human Subject 47
p.000046: 4.4.2. Informing Third Parties of Research Activities 47
p.000046: 4.4.3. Research Results and Third Parties
p.000047: 47
p.000047: 4.5. Data and Safety Monitoring and Oversight
p.000048: 48
p.000048: 5. Creating an Appropriate Relationship Between the Participant and Researcher 51
p.000048: 5.1. Informed Consent
p.000052: 52
p.000052: 5.1.1. Information
p.000052: 52
p.000052: 5.1.2. Comprehension
p.000054: 54
p.000054: 5.1.3. Voluntary Participation
p.000055: 55
...
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
p.000003: range of risks associated with participation and the voluntary nature of participation, and provides
...
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000012: 12
p.000012:
p.000012: address all of the relevant issues for their particular study to ensure that the specific elements of
p.000012: the study will safeguard and protect the human research subjects.
p.000012: In addition to being an information resource for NERL researchers, this document provides useful
p.000012: information for contractors and grantees funded by NERL to consider during the design and implementation of
p.000012: their exposure science research. Although not its intended audience, this document also may prove to be useful
p.000012: to other researchers, within and outside of EPA, who are involved in observational human exposure
p.000012: studies.
p.000012:
p.000012: 1.4 Process for Developing the Document
p.000012: This document was written by exposure science researchers in EPA’s NERL, with substantial input from experts
...
p.000033: populations are not targeted for risky research” [emphasis added] (Emanuel et al., 2000).
p.000033: The Common Rule requires IRBs to assure that “additional safeguards have been included in the study to protect
p.000033: the rights and welfare of these [vulnerable] subjects” [at 40 CFR 26.111(b) in CFR, 2006a]. If an
p.000033: observational human exposure study includes vulnerable research participants, it is essential that the investigators be
p.000033: cognizant of the special issues and requirements of research involving vulnerable populations. Researchers
p.000033: have to justify the involvement of vulnerable populations in the research study and
p.000033: include the appropriate safeguards for protection of their safety and welfare. The Common Rule protections are
p.000033: discussed further in the IRB guidebook (U.S. HHS, 1993). EPA regulations include not only the general
p.000033: protections for vulnerable populations found in the Common Rule (Subpart A) but also define
p.000033: additional protections for children and for pregnant or nursing women (and their fetus or nursing child)
p.000033: in Subparts B, C, and D (CFR, 2006a).
p.000033: The section begins by identifying or defining vulnerable groups and then discusses ethical issues that
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
...
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
...
p.000036: If such research does not hold out the prospect of direct benefit to the child, no increase whatsoever over
p.000036: minimal risk is permitted.
p.000036: However, many observational human exposure studies are developed specifically to study the exposures of
p.000036: selected vulnerable groups to chemicals and other environmental stressors in everyday environments. So,
p.000036: researchers should be prepared to address the issues associated with vulnerable groups in
p.000036: observational research. Furthermore, as discussed in Section 3.4, there has been increased concern in recent years that
p.000036: exclusion of vulnerable groups from research studies is not ethical. Failure to conduct research with vulnerable groups
p.000036: may deprive them of the benefits of research. NIH, for example, has a policy (NIH, 1998) with a
p.000036: goal of increasing participation of children in research.
p.000036:
p.000036: 3.3 Minimal Risk and Vulnerable Groups
p.000036: EPA has codified protections for children, pregnant or nursing women, and fetuses in Subparts B, C, and D of the EPA
p.000036: human subjects rule (40 CFR 26). Subpart B strictly prohibits research involving intentional exposure of children
p.000036: or pregnant or nursing women (and, therefore, exposure of her fetus).
p.000036: EPA’s regulations do allow for observational research involving fetuses and pregnant women (40 CFR 26
p.000036: Subpart C) or children (40 CFR 26 Subpart D) but with additional protections in place and with
p.000036: strict limitations on research that presents more than minimal
p.000036: risk (CFR, 2006a).13 When considering vulnerable groups, The Institutional Review Board Guidebook (U.S. HHS,
p.000036: 1993) states that “IRBs should therefore determine whether the proposed subject population would be more sensitive or
p.000036: vulnerable to the risks posed by the research as a result of their general condition or disabilities. If so, the
p.000036: procedures would constitute more than minimal risk for those subjects.”
p.000036: When conducting observational human exposure studies, it is recommended that researchers consult these
p.000036: regulations and guidebooks. NERL researchers also will need to ensure that all of the requirements in Subparts B, C,
p.000036: and D of the EPA Human Subjects Rule are met.
p.000036:
p.000036: 3.4 Research Involving Children
p.000036: Children long have been recognized as a vulnerable group in research studies. EPA and HHS both extend special
p.000036: protections to children (CFR, 2006a,b). There are many books, reports, and research manuscripts that
...
p.000037: children (40 CFR 26.404) (i.e., the kinds of observational human exposure studies that NERL exposure research
p.000037: is likely to entail) focuses on obtaining assent of the children and permission of their parents or guardians. But the
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
p.000037: biomedical research because of the potential for becoming pregnant during a study. The document continues, “A
p.000037: general policy of excluding from such clinical trials women biologically capable of becoming pregnant is
p.000037: unjust in that it deprives women as a class of persons of the benefits of new knowledge derived from the
p.000037: trials.” The second relevant CIOMS guideline, number 17, asserts that, if involved in a research study,
p.000037: pregnant women should be fully informed, and included only if the
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: research benefits pregnant women and is thoroughly supported by reliable evidence in animal studies.
p.000038: Although the CIOMS guideline specifically addresses biomedical research, the ethical concepts
p.000038: behind the guidelines generally may be applicable to observational human exposure studies. EPA’s human
p.000038: subjects rule is completely consistent with the HHS rule in adding additional protections for pregnant women and
p.000038: fetuses involved in observational research (40 CFR
p.000038: 26.304 and 45 CFR 46.204). These additional protections (specified in 45 CFR 46.204 subparagraphs a
p.000038: through j) reflect the CIOMS recommendations by requiring: availability of data from previously conducted
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
...
p.000061: developed in the context of NIH-supported clinical research, many of the recommendations are applicable to
p.000061: observational human exposure studies and human subject research in general. A summary
p.000061: of
p.000061: recommendations from the report for enhancing public trust is provided in Appendix D. The recommendations are
p.000061: focused on the following areas.
p.000061: • Building trust through community partnerships
p.000061: • Building relationships with patients (participants) (True partnerships with patients may not be possible,
p.000061: but bidirectional relationships must be enhanced.)
p.000061: • Building partnerships with community providers
p.000061: • Building trust in scientists
p.000061: • Building trust in the (EPA) and scientific research.
p.000061:
p.000061: 5.5 Recruitment Strategies
p.000061: Many strategies are used to select and recruit people into research studies requiring human participation. The IRB is
p.000061: responsible for reviewing the selection process to ensure that it is, above all, equitable. The requirement for
p.000061: IRB review is stated in 40 CFR 26.111(a)3.
p.000061: Selection of subjects is equitable. In making this assessment, the IRB should take into account the
p.000061: purposes of the research and the setting in which the research will be conducted and should be particularly cognizant
p.000061: of the special problems of research involving vulnerable populations, such as children, prisoners,
p.000061: pregnant women, mentally disabled persons, or economically or educationally disadvantaged
p.000061: persons.
p.000061: The IRB guidebook is an excellent resource for consideration of concerns and elements for equitable
p.000061: participant selection (U.S. HHS, 1993). It states that “Defining the appropriate group of subjects
p.000061: for a research project involves a variety of factors⎯ requirements of scientific design,
p.000061: susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness.” The IRB
p.000061: guidebook raises a number of points to consider in the process for selection of human participants (see Text Box
p.000061: 5-5).
p.000061: Various participant recruitment strategies may be used depending on the type of research being performed and the
p.000061: population of interest. This section addresses the strategies and approaches for identifying and contacting people and
p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
p.000062: 1. Who will bear the burden? Who will reap the benefits?
...
p.000095: outcome measure. Consider the intervention study examples cited in the section on regulatory
p.000095: distinctions below (cleaning a house to reduce exposure in the residence and wearing a particle mask to reduce
p.000095: exposure to smoke from forest fires). In those cases, participants would be assigned either to receive the
p.000095: intervention (treatment) or not (the control group). The outcomes (exposures) would be measured and compared
p.000095: between the two groups to assess the effectiveness of the intervention. Similarly, drug trials would randomly
p.000095: assign participants to receive either a test medication or a placebo. The medical outcome (e.g., pain
p.000095: relief, blood pressure, cholesterol levels in blood) would then be measured for all participants,
p.000095: and the outcomes compared between the treated group (getting the test medication) and the control
p.000095: group (receiving the placebo).
p.000095: Controlled studies are often desirable in science because, when properly designed, they provide
p.000095: unambiguous estimates of the impact of unique variables on the outcome (even if the impact of one variable could
p.000095: normally be overwhelmed by other factors) and eliminate the need for alternate explanations of
p.000095: the experimental results (because other factors are held constant). However, controlled studies are
p.000095: not always possible. They may be unethical (e.g., to “treat” a group of women with abortions to test if there
p.000095: is a linkage between having had an abortion and breast cancer), impractical (e.g., to follow a cohort large
p.000095: enough to yield statistically significant results in a test of rare side effects to a medication), or just
p.000095: impossible to accomplish (e.g., to measure nutritional levels of a population in the middle of a war zone).
p.000095: As a consequence, much medical research is observational in the scientific sense being considered
p.000095: here. Public health data represent observations of health outcomes, but the factors that may have led
p.000095: to or influenced those outcomes are not under the control of any researcher. Observational techniques long
p.000095: have been
p.000095: used in medical studies to infer information about the impacts of certain factors on health
p.000095: outcomes. Commonly used techniques include cohort studies, case- control studies, cross-sectional studies, case
p.000095: reports, case series, and descriptive studies (NEAC, 2006; Vandenbroucke et al., 2007).
p.000095: Observational human exposure studies as used in this document are considered to be observational from a
p.000095: scientific study design perspective because the variables leading to exposure are not controlled by the researchers.
p.000095: Most of the observational human exposure studies conducted by NERL to date have been cross-sectional
p.000095: studies (sometimes repeated several times). While a particular variable may not be controlled by
p.000095: the researcher, the study design (e.g., selection of the population to be studied, location of the
...
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
p.000117:
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p.000118:
p.000118: United States Environmental Protection Agency
p.000118:
p.000118:
p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
...
Social / Youth/Minors
Searching for indicator minor:
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p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
p.000058: benefits, or they may be particularly vulnerable to undue influence resulting from the offer of a payment for
p.000058: research participation. In addition, payments made directly to parents or guardians could alter
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
p.000058: gestures of appreciation, investigators may also—if they minimize the potential for undue influence—act ethically to
p.000058: reduce certain barriers to research participation when they
p.000058: • reimburse reasonable expenses directly related to a child’s participation in research
p.000058: • provide reasonable, age-appropriate compensation for children based on the time involved in research that does not
p.000058: offer the prospect of direct benefit, and
...
Searching for indicator youth:
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p.000044: threat to health or safety that staff would need to communicate immediately with the participant or take
p.000044: action to mitigate the threat. In some cases, such as instances of abuse with attendant statutory reporting
p.000044: requirements, it may be necessary to breach confidentiality. More often, however, a potential hazard identified as
p.000044: a result of collateral observation may not be an imminent threat or pose a potential risk that is situation
p.000044: dependent or is related to third parties. A number of considerations in hazard communication come
p.000044: into play regarding confidentiality, privacy, the ability of the researcher to provide accurate and
p.000044: effective information regarding the hazard and hazard mitigation, and the ability of the study participant or others
p.000044: to effectively mitigate the hazard without unintended adverse consequences. The National Academy of Sciences
p.000044: Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children, Youth, and
p.000044: Families discussed many of these issues in depth (NRC & IOM, 2005).
p.000044: Different communities, cultures, or demographic groups can have different risk perceptions, which may
p.000044: affect how collateral observations are assessed and reported from one study location to the next. The AAP
p.000044: Committee on Environmental Health has prepared information regarding perception, identification, and
p.000044: communication of environmental health risks (AAP, 2003). Researchers likely will benefit from including
p.000044: community members on the research team in developing the study design and research protocol or from
p.000044: consultation with community boards regarding identification of hazards and hazard communication.
p.000044:
p.000044:
p.000045: 45
p.000045:
p.000045: It is important that any advice that the researcher might provide to study participants regarding hazard
p.000045: mitigation should be carefully considered. Considerations in recommending an action may include
p.000045: whether the mitigation approach has been shown to be effective, whether the study participant can
p.000045: understand and effectively implement the action, and whether unintended adverse consequences might
p.000045: result from taking an action. In some cases, it may be reasonable to refer the participant to another
p.000045: organization that can provide expert advice or assistance.
p.000045:
p.000045: 4.3.4 Planning and Staff Training
...
Social / education
Searching for indicator education:
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p.000003: http://www.cioms.ch/080221feb_2008.pdf [accessed 25
p.000003: April 2008].
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000003: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000003:
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000004: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000004:
p.000004: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
p.000004:
p.000004: ERG (Eastern Research Group) (2007). Report on the Workshop to Discuss State-of-the-Science Approaches for
p.000004: Observational Exposure Measurement Studies. Held in Durham, North Carolina on November 28-29, 2006. Final Report:
p.000004: January 25, 2007. (PB2007-108905).
p.000004:
p.000004: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000004: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000004: [accessed 12 June 2007].
p.000004:
p.000004: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000004: Housing-Related Health Hazards Involving Children.
p.000004: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000004: June 2007].
p.000004: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
p.000004: Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of Human Subjects
p.000004: of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 12 June
p.000004: 2007].
p.000004:
p.000004: U.S. EPA (U.S. Environmental Protection Agency) (2000) Comments on the Use of Data from the Testing of Human Subjects:
p.000004: A Report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. United States Environmental Protection
p.000004: Agency, Science Advisory Board, EPA-SAB-EC-00-017. Available: http://yosemite.epa.gov/sab/SABPRODUCT.NSF/E3AE0F3
p.000004: 0D7430436852571A7005325E8/$File/ec0017.pdf [accessed 12 June 2007].
p.000004:
p.000004: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000004: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000004: [accessed 12 June 2007].
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005:
p.000005:
...
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
p.000008: from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in specified
p.000008: rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in this
p.000008: document.
p.000008: 5 The Glossary (Appendix F) lists definitions for a number of important terms; definitions that come from the
p.000008: regulatory language are identified with their specific CFR citation.
p.000008: about the most recent thinking and guidance on protection of human subjects.
p.000008: The Belmont Report (U.S. DHEW, 1979) is a foundational document in the development of the ethics of human
p.000008: subjects research in the United States. Because of the adverse publicity and political embarrassment arising
p.000008: from the unethical treatment of African- American men in the Tuskegee Syphilis Study, Congress passed
p.000008: the National Research Act of 1974, which called on the Department of Health, Education, and Welfare (DHEW) to
p.000008: codify its rules on human subjects research and established the National Commission for the Protection of
p.000008: Human Subjects of Biomedical and Behavioral Research. The commission was charged with identifying the
p.000008: basic ethical principles that should underlie human subjects research. The commission published the
p.000008: Belmont Report in 1979. This report established three basic principles: (1) respect for
p.000008: persons; (2) beneficence; and (3) justice, which have become the cornerstones for regulations involving
p.000008: human subjects (see Table 1-2).
p.000008: In 1981, the Department of Health and Human Services (HHS) issued regulations based on the Belmont Report. Ten
p.000008: years later, the core HHS regulations (Subpart A) were adopted by almost all of the Federal
p.000008: departments and agencies that conducted or sponsored human subjects research as the “Common Rule.”
p.000008: Since 1991, ethical thought and regulatory processes for the protection of human subjects have continued to
p.000008: evolve and grow. For example, many ethicists expand the elements contained in the principle of
p.000008: beneficence from the Belmont Report into two principles:
...
p.000013: Biomedical Research Involving Human Subjects.
p.000013: Geneva, Switzerland: CIOMS. Available: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000013:
p.000013: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000013:
p.000013: NEAC (National Ethics Advisory Committee) (2006). Ethical Guidelines for Observational Studies: Observational research
p.000013: audits and related activities. Wellington, New Zealand: Ministry of Health. Available:
p.000013: http://www.neac.health.govt.nz/moh.nsf/indexcm/neac resources-publications-ethicalguidelines.
p.000013:
p.000013: NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing Research
p.000013: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000013: [accessed 16 August 2007].
p.000013:
p.000013: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000013: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000013: [accessed 12 June 2007].
p.000013:
p.000013: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000013: Housing-Related Health Hazards Involving Children.
p.000013: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000013: June 2007].
p.000013:
p.000013: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
p.000013: Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of Human Subjects
p.000013: of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 12 June
p.000013: 2007].
p.000013:
p.000013: U.S. EPA (U.S. Environmental Protection Agency) (1999). Air Quality Criteria for Particulate Matter. Environmental
p.000013: Protection Agency, National Center for Environmental
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014: Assessment, Office of Research and Development. EPA/600/P-99/002.
p.000014:
p.000014: U.S. EPA (U.S. Environmental Protection Agency) (1992). Guidelines for Exposure Assessment. Environmental Protection
p.000014: Agency, Risk Assessment Forum. EPA/600/Z 92/001. Available: http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_
p.000014: id=429103 [accessed 15 April 2008].
p.000014:
p.000014: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000014: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000014: [accessed 12 June 2007].
p.000014:
...
p.000018: considered in justifying an observational human exposure study. As discussed below, a critical element to
p.000018: support justification of both the scientific and ethical elements of a study is the use of independent scientific and
p.000018: ethical peer review.
p.000018:
p.000018:
p.000018:
p.000018: 7 Guideline 1 states “research can be ethically justifiable only if it is carried out in ways that respect and
p.000018: protect, and are fair to, the subjects of that research and are morally acceptable within the communities in which the
p.000018: research is carried out. Moreover, because scientifically invalid research is unethical in that it exposes research
p.000018: subjects to risks without possible benefit, investigators and sponsors must ensure that proposed studies involving
p.000018: human subjects conform to generally accepted scientific principles and are based on adequate knowledge of the pertinent
p.000018: scientific literature.” The commentary on the guideline goes on to say, “Among the essential features of ethically
p.000018: justified research involving human subjects, including research with identifiable human tissue or data, are that the
p.000018: research offers a means of developing information not otherwise obtainable, that the design of the research is
p.000018: scientifically sound, and that the investigators and other research personnel are competent. The methods to be used
p.000018: should be appropriate to the objectives of the research and the field of study. Investigators and sponsors must also
p.000018: ensure that all who participate in the conduct of the research are qualified by virtue of their education and
p.000018: experience to perform competently in their roles. These considerations should be adequately reflected in the research
p.000018: protocol submitted for review and clearance to scientific and ethical review committees.”
p.000018:
p.000018:
p.000019: 19
p.000019:
p.000019:
p.000019: Text Box 2-1. Elements to be Considered in Justifying a Study
p.000019: • The research problem and questions to be addressed in the study
p.000019: • The objectives of the study or the hypotheses to be tested
p.000019: • A discussion of why human participants are required for the study, including a discussion of alternative designs
p.000019: that were considered
p.000019: • Available information on the need for the study (i.e., it is not redundant and the research question has not been
p.000019: already answered)
p.000019: • Available information from the scientific literature demonstrating the relevance of the proposed study
p.000019: • A discussion of the general technical approach and scientific soundness of the approach
p.000019: • An assessment of the needed competencies and qualifications of all personnel involved in conducting the research
p.000019: • The likelihood of success in meeting the study goals and objectives (including an evaluation of the accuracy,
p.000019: precision, and quality assurance of the data needed to attain the study goals and objectives)
p.000019: • Justification for the investment of time and money
p.000019:
p.000019:
p.000019: 2.1.3 Identifying a Research Team To Plan and Implement the Study
p.000019: Once the study problem has been defined and justified, the next step in developing the research study is
p.000019: to form the research team. The team should be diverse, including the technical experts (e.g.,
...
p.000031:
p.000031: Gilbert, SG (2006). Supplementing the traditional institutional review board with an environmental health and community
p.000031: review board. Environmental Health Perspectives 114(10): 1626-1629.
p.000031:
p.000031: Kraemer HC, Thiemann S (1987). How Many Subjects? Statistical Power Analysis in Research. Newbury Park, CA: Sage
p.000031: Publications.
p.000031:
p.000031: Lenth RV (2001). Some practical guidelines for effective sample size determination. American Statistician 55(3):
p.000031: 187-193. Available:
p.000031: http://www.stat.uiowa.edu/techrep/tr303.pdf [accessed 13
p.000031: June 2007].
p.000031:
p.000031: NRC (National Research Council) (2003). Protecting Participants and Facilitating Social and Behavioral Sciences
p.000031: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000031: [accessed 12 June 2007].
p.000031:
p.000031: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000031: Housing-Related Health Hazards Involving Children.
p.000031: Washington, DC: The National Academies Press. Available:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12 June 2007].
p.000032:
p.000032: OHRP (Office for Human Research Protections) (2007). U.S. Department of Health and Human Services [Online].
p.000032: Available: http://www.hhs.gov/ohrp/ [accessed 13 June 2007].
p.000032:
p.000032: Resnik DB, Wing S (2007). Lessons learned from the Children's Environmental Exposure Research Study. Am J Public Health
p.000032: 97(3): 414-8.
p.000032:
p.000032: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979). The Belmont Report: Ethical Principles and
p.000032: Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: National Commission for the Protection
p.000032: of Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
p.000032: [accessed June 2007].
p.000032: U.S. EPA (U.S. Environmental Protection Agency) (2000). Comments on the use of data from the testing of human subjects:
p.000032: A report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. Environmental Protection Agency,
p.000032: Science Advisory Board. EPA-SAB-EC-00-017. Available: http://www.epa.gov/scipoly/sap/meetings/1999/november/e c0017.pdf
p.000032: [accessed 16 April 2008].
p.000032:
p.000032: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000032: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000032: [accessed 12 June 2007].
p.000032:
p.000032: Van Belle G, Fisher L (2004). Biostatistics: A Methodology for the Health Sciences (2nd Edition) Hoboken, NJ: John
p.000032: Wiley & Sons.
p.000032:
p.000032: Wackerly DD, Mendenhall W, Scheaffer RL (2001). Mathematical Statistics with Applications (6th Edition). Pacific Grove,
p.000032: CA: Duxbury Press.
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
...
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
...
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
p.000035: broader definition of vulnerability as it relates to education, economics, social status, and other factors. As
p.000035: shown in Text Boxes 3-1 and 3-2 and described above, the concept of vulnerability is broader than that
p.000035: presented in the Common Rule. It is not adequate to simply check the list in Text Box 3-1 to identify if a potentially
p.000035: vulnerable group is included in an observational study. The researchers should assess the potential
p.000035: vulnerability of a study population within the study by evaluating the characteristics (e.g., socioeconomic
p.000035: status) of the study population within the context of the study by considering the various design elements of the
p.000035: study, as discussed in Section 2.
p.000035: 12 In the commentary on Guideline 13 in CIOMS (2002), the committee states that the central problem presented by plans
p.000035: to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
...
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
p.000038: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle A Department of Health and Human Services Part 46 Protection
p.000038: of Human Subjects. U.S. Code of Federal Regulations. Available:
p.000038: http://www.access.gpo.gov/nara/cfr/waisidx_06/45cfr46_06.ht ml [accessed 13 June 2007].
p.000038:
p.000038: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000038: Biomedical Research Involving Human Subjects.
p.000038: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000038:
p.000038: Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry MR, Rigas ML, Zartarian VG, Freeman NCG (2000).
p.000038: Children’s exposure assessment: a review of factors influencing children’s exposure, and the data available to
p.000038: characterize and assess that exposure. Environ Health Perspect 108(6): 475-486.
p.000038:
p.000038: Emanuel EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000038:
p.000038: IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Washington, DC: The
p.000038: National Academies Press. Available: http://www.nap.edu/catalog.php?record_id=10958 [accessed 16 April 2008].
p.000038:
p.000038: Kodish E (Ed.) (2005). Ethics and Research with Children: A Case-Based Approach. New York: Oxford University Press.
p.000038:
p.000038: NBAC (National Bioethics Advisory Commission) (2001). Ethical and Policy Issues in Research Involving Human
p.000038: Participants, Volume I: Report and Recommendations of the National Bioethics Advisory Commission. Bethesda, MD:
p.000038: National Bioethics Advisory Commission. Available: http://www.bioethics.gov/reports/past_commissions/nbac_h
p.000038: uman_part.pdf [accessed 3 September 2007].
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000039: 39
p.000039:
p.000039: NIH (National Institutes of Health) (2002) Human Participant Protections Education for Research Teams [online
p.000039: tutorial].
p.000039:
p.000039: NIH (National Institutes of Health) (1998). NIH Policy and Guidelines on The Inclusion of Children as Participants in
p.000039: Research Involving Human Subjects. Available: http://grants.nih.gov/grants/guide/notice-files/not98 024.html [accessed
p.000039: 13 June 2007].
p.000039:
p.000039: NRC (National Research Council) (2003). Protecting Participants and Facilitating Social and Behavioral Sciences
p.000039: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000039: [accessed 12 June 2007].
p.000039: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000039: Housing-Related Health Hazards Involving Children.
p.000039: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000039: June 2007].
p.000039:
p.000039: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000039: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000039: [accessed 12 June 2007].
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000040:
p.000040:
p.000040:
...
p.000050: Good, two- way communications are critical for the development and nourishment of an appropriate
p.000050: researcher-participant relationship. Although those two topics are the subject of the next sections of this document,
p.000050: elements from those topics unavoidably will color the discussions in this section as well.
p.000050: Researcher training is a key component for conducting research that incorporates human
p.000050: subject protections and fosters appropriate researcher-participant relationships. Most organizations require basic
p.000050: human subjects training on the essential elements for processes and procedures for research with human subjects. More
p.000050: in-depth training will improve researcher understanding in areas of the informed consent process, observational
p.000050: techniques, community-based research, and other topic areas. Such training will benefit principal
p.000050: investigators throughout the research study from the design stage through communication of research results.
p.000050: Training is also important for staff that will work directly or indirectly with research participants
p.000050: or their samples and data. This document can be used as both a training tool for researchers as well as a
p.000050: resource for designing training courses. There are a number of sources of training on human
p.000050: subjects protection. The Collaborative Institutional Training Initiative (CITI,
p.000050: http://www.citiprogram.org/) is a subscription service providing research ethics education to many institutions.
p.000050: Other training, such as that provided by the National Cancer Institute
p.000050: (http://cme.cancer.gov/clinicaltrials/lear ning/humanparticipant-protections.asp) and the U.S. Department
p.000050: of Health and Human Services (http://www.hrsa.gov/humansubjects/default.htm), are available
p.000050: on-line.
p.000050:
p.000050:
p.000051: 51
p.000051:
p.000051: 5.1 Informed Consent
p.000051: In observational human exposure studies, informed consent ensures that the participant
p.000051: accurately understands the range of risks and benefits (if any) associated with participation; emphasizes
p.000051: the voluntary nature of their participation; and provides essential protections to the participant. The
p.000051: three “pillars” of the informed consent process are (1) information;
p.000051: (2) comprehension; and (3) voluntary participation, or “voluntariness” (U.S. DHEW, 1979). Informed consent
p.000051: requires “provision of information to subjects about the purpose of the research, its procedures, potential
p.000051: risks, benefits, and alternatives, so that the individual understands this information and can
p.000051: make a voluntary decision whether to enroll and continue to participate” (Emanuel et al., 2000).
p.000051: The NRC & IOM document Ethical Considerations for Research on Housing-Related Health Hazards Involving
...
p.000064: 2005. Available: http://copr.nih.gov/reports/public_trust.asp
p.000064: [accessed 12 June 2007].
p.000064:
p.000064: NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing Research
p.000064: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000064: [accessed 16 August 2007].
p.000064:
p.000064: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000064: Housing-Related Health Hazards Involving Children.
p.000064: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000064: June 2007].
p.000064:
p.000064: OMB (Office of Management and Budget). (2006a). Standards and Guidelines for Statistical Surveys. Section 2.3, Data
p.000064: Collection Methodology. http://www.whitehouse.gov/omb/inforeg/statpolicy/standard s_stat_surveys.pdf
p.000064:
p.000064: OMB (Office of Management and Budget). (2006b). Questions and Answers When Designing Surveys for Information
p.000064: Collection. Office of Information and Regulatory Affairs. January, 2006.
p.000064: http://www.whitehouse.gov/omb/inforeg/pmc_survey_guidanc e_2006.pdf
p.000064:
p.000064: Paasche-Orlow MK, Taylor HA, Brancati FL (2003). Readability standards for informed-consent forms as compared with
p.000064: actual readability. N Engl J Med 348(8):721 6.
p.000064:
p.000064: Russell ML, Moralejo DG, Burgess ED. (2000). Paying research subjects: participants' perspectives. J Med Ethics
p.000064: 26(2):126-30.
p.000064:
p.000064: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979). The Belmont Report: Ethical Principles and
p.000064: Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: National Commission for the Protection
p.000064: of Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
p.000064: [accessed June 2007].
p.000064:
p.000064: U.S. FDA (U.S. Food and Drug Administration) (1998). Information Sheets: Guidance for Institutional Review Boards and
p.000064: Clinical Investigators 1998 Update. U.S. Food and Drug Administration, Washington, DC. Available:
p.000064: http://www.fda.gov/oc/ohrt/irbs/toc4.html [accessed May 2007].
p.000064:
p.000064: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000064:
p.000064:
p.000065: 65
p.000065:
p.000065: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000065: [accessed 12 June 2007].
p.000065:
p.000065: VanderWalde A (2005). Undue inducement: the only objection to payment? Am J Bioethics 5(5):25-27.
p.000065: Weise KL, Smith ML, Maschke KJ, Copeland L (2002). National practices regarding payment to research subjects for
p.000065: participating in pediatric research. Pediatrics 110(3):577-582.
p.000065:
...
p.000067: Visibility Travel to the community, interact with formal
p.000067: and informal leadership, and establish relationships to build trust.
p.000067:
p.000067: Acceptance Acknowledge, without judging, the assets and deficits of the community.
p.000067:
p.000067: Partnership Balanced discussion and shared
p.000067: decisionmaking among participants concerning risks, responsibilities, expectations, benefits, and investment.
p.000067:
p.000067: Respect Value the diversity of culture, history, beliefs and opinions within the community for
p.000067: improved understanding.
p.000067:
p.000067: Asset Utilization Identify and mobilize community assets to
p.000067: improve scientific credibility of the interpretation and dissemination of results.
p.000067:
p.000067: Flexibility Anticipate changes within the community in
p.000067: regard to perceived benefits of research and stakeholder interest and additional time and resource needs.
p.000067:
p.000067: Commitment Prepare to engage the community beyond the constraints of the research projects, before and after,
p.000067: to promote longevity of the relationship for future research .
p.000067:
p.000067:
p.000067: Furthermore, institutional and community partners need to ensure that anyone involved as part of the
p.000067: research team has the requisite research and social skills. Researchers often place a greater emphasis on scientific
p.000067: over social skills and may, in turn, assume that they have
p.000067:
p.000067:
p.000068: 68
p.000068:
p.000068: the necessary expertise to conduct research in community settings. Likewise, research staff from
p.000068: the community should have knowledge of research fundamentals. Education and training targeted at
p.000068: both the institutional researcher and the community researcher may, respectively, improve the competence
p.000068: of researchers to work with communities and the scientific literacy of the public.
p.000068: A recent NERL study, the Detroit Exposure and Aerosol Research Study (DEARS), included community members as
p.000068: paid members of the research team. The community researchers were instrumental in recruiting study
p.000068: participants from the seven study neighborhoods in Detroit that required multiple door-to-door visits to
p.000068: the homes of potential participants to discuss the DEARS study. The success of DEARS was dependent
p.000068: on researchers developing strong relations with community leaders and State and local organizations.
p.000068: A second approach to community involvement is to seek community consultation and review. Researchers may
p.000068: periodically meet with community residents in a process of “engagement, dialogue, and feedback” (Dula, 1994) to
p.000068: discuss research plans, research progress, and results. The objective is to seek a dialogue with
p.000068: community residents to promote co-learning and asset sharing between the researchers and the community.
p.000068: Effective communication⎯open, honest, jargon free⎯is imperative to the successful use of this approach.
p.000068: Effective communication ensures that the community has a voice in the research process for the expressed
p.000068: purpose of increasing the community’s trust and engagement in the research, the applicability of the
...
p.000079: because that is the aspect of communication most under the control of the researchers. Nonetheless, effective
p.000079: communications will be bidirectional and involve effective listening. Researchers should keep in mind that it
p.000079: is as important to listen to the participants, community, and other stakeholders as it is for the researchers
p.000079: to provide them with information using the approaches described in this section.
p.000079:
p.000079: 7.1 Communication Strategy and Implementation Plan
p.000079: Fundamental to achieving effective communications are a communications strategy and implementation plan. In general,
p.000079: the goal of the communication strategy and plan is to clearly define how effective bidirectional
p.000079: communications will be achieved in the study. Specific goals should be developed based on the specifics of the study
p.000079: design, the study population, the community, and the stakeholders. The plan will describe who will be involved
p.000079: in the communications, what communications are required, and how the communications will be
p.000079: performed. The communication strategy and implementation plan should be developed early in
p.000079: the planning stages of a study. The communication plan, however, needs to be dynamic, with revisions
p.000079: and updates occurring throughout the study and in collaboration with the community and
p.000079: stakeholders.
p.000079: Text Box 7-1 lists elements that should be included in a communication plan. The communication strategy should be
p.000079: developed based on the goals of the study and an understanding of the background, education, attitudes,
p.000079: and opinions of the stakeholders and the community that will be involved in the many different
p.000079: aspects of the study from the initial conceptualization to the final reporting of the study results.
p.000079:
p.000079:
p.000081: 81
p.000081:
p.000081:
p.000081: Text Box 7-1. Elements in a Communication Plan
p.000081: • Background information description (overview) of the study, relevant historical background information, statement
p.000081: of communication needs, and identification of communication opportunities and issues
p.000081: • Purpose and goals of the communication strategy
p.000081: • List of individuals and groups involved in the communications, plus relevant demographics and other information to
p.000081: profile the groups
p.000081: • Strategy and approach for achieving the goals, including a statement of the primary message to be conveyed and
p.000081: descriptions of the communication channels
p.000081: • Activities and materials to achieve the goals of specific elements of the plan to be performed
p.000081: • Timetable
p.000081: • Roles and responsibilities
p.000081: • Resources needed (budget)
p.000081: • Measures of effectiveness
p.000081:
p.000081: Careful planning is required to develop a communication plan that will be effective. The research
p.000081: team has to invest the time and resources necessary to develop and implement the plan. They also
p.000081: should recognize that the communication plan is essential for conducting the study and is just as important as
p.000081: the study design, human subjects research protocol, or QAPP. The observational study, if properly justified as
p.000081: described earlier, provides a social and scientific value and brings benefit to society (and perhaps the
...
p.000084: English, educational disadvantages, etc., may require communications materials to be written in
p.000084: alternate languages and at different reading levels. The issue is comprehension, as was discussed in
p.000084: Section 5.1.2. Empirical testing of communication methods and content is essential to ensure
p.000084: comprehension (Health Canada, 2006).
p.000084: Researchers also should recognize that in this information age, dissemination of
p.000084: informational materials may be rapid and widespread. Therefore, even documents intended for scientific peers may
p.000084: benefit by including summary information in an executive summary or preface that a lay reader can
p.000084: understand.
p.000084:
p.000084: 7.5 Communications Materials
p.000084: Researchers need to communicate clearly with the many groups listed in Section 7.2 to develop their
p.000084: relationship with the participants in the study, to develop their partnership with the community, to gain
p.000084: support from stakeholders, and to inform the public. To achieve the multiple purposes of communications
p.000084: during a research study and to communicate with many diverse groups, a variety of communications materials may
p.000084: need to be developed. Different materials have different purposes and different types of
p.000084: information to be communicated. Because of diversity in interested individuals and groups with
p.000084: respect to education, cultures, information needs, etc., the format and content of communication materials
p.000084: likely will need to be diverse. Text Box 7-4 list activities and materials that may be helpful in
p.000084: facilitating communications.
p.000084: By definition, communication is an exchange of information. This has to be the primary goal of
p.000084: communication activities. The accuracy and completeness of the information transferred is
p.000084: important. There are many different ways to communicate, the effectiveness of which varies substantially.
p.000084: The way in which the information is conveyed is as important as the information itself. Effective communication
p.000084: should promote trust and credibility. Peters et al. (1997) found that three determinants, namely, (1)
p.000084: knowledge and expertise, (2) openness and honesty, and (3) concern and care, were important factors determining
p.000084: perceptions of
p.000084:
p.000084:
p.000085: 85
p.000085:
p.000085: trust and credibility. Therefore, the approach to communication in observational human exposure
p.000085: studies should consider these factors, and communication materials should be developed with these
p.000085: factors in mind.
p.000085:
p.000085: Text Box 7-4. Activities and Materials That May Be Useful in a Communication Plan
p.000085: • Flyers
p.000085: • Web sites
p.000085: • Brochures
p.000085: • Interviews
p.000085: • Newsletters
p.000085: • Focus groups
p.000085: • Presentations
p.000085: • Direct mailings
p.000085: • Press releases
p.000085: • Questions and answers
p.000085: • Desk statements (government)
p.000085: • Abstracts
p.000085: • Study reports
p.000085: • Talking points
p.000085: • Community meetings
p.000085: • Stakeholder meetings
...
p.000112: Recommendation 5: Set the expectation across the entire research community, NIH funded research and beyond, that
p.000112: study results and outcomes should be shared with the research participants and the larger community promptly
p.000112: and consistently. This will ensure translational research.
p.000112:
p.000112: Building Partnerships with Community Providers
p.000112: Recommendation 6: Take action to interest community providers in clinical research and
p.000112: maintain their involvement.
p.000112: Recommendation 7: Provide incentives (not just financial) for primary health care providers and community
p.000112: specialists to play a role in clinical trials.
p.000112:
p.000112: Building Trust in Scientists
p.000112: Recommendation 8: Engage researchers, educators, and academic institutions in incorporating the public's
p.000112: perspective consistently at every level of training and in both the conduct of clinical research and the publication of
p.000112: findings from that research.
p.000112: Recommendation 9: Focus on educational strategies to help patients and communities better understand
p.000112: clinical research. This will help scientists because educating the public will empower and prepare
p.000112: individuals to be informed partners in the clinical research process. An informed and trusting public will
p.000112: enhance research participation.
p.000112:
p.000112: Building Trust in the NIH and Scientific Research
p.000112: Recommendation 10: Continue to develop and fund efforts to build a national identity for the NIH based
p.000112: on what NIH does best—research and education—as a basis for enhancing public trust in clinical
p.000112: research.
p.000112: Recommendation 11: Review the role and impact of Institutional Review Boards and other patient protections
p.000112: in the clinical research process because the public views these protections as less effective than they
p.000112: should be.
p.000112: Recommendation 12: Document and publish “best practices” from efforts to reengineer the clinical research
p.000112: enterprise as soon as the NIH begins to see results, so that progress in improving public trust in medical research
p.000112: grows rapidly and steadily.
p.000112:
p.000112: Source: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for
p.000112: the NIH Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health,
p.000112: Director’s Council of Public Representatives, January 14, 2005. Available:
p.000112: http://copr.nih.gov/reports/public_trust.asp [accessed 12 June 2007].
p.000112:
p.000112:
p.000112:
p.000113: 113
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113: Appendix E
p.000113: List of Acronyms and Abbreviations
p.000113:
p.000113:
p.000113: AAP American Academy of Pediatrics
p.000113: ACGIH American Conference of Governmental Industrial Hygienists AHS Agricultural Health
p.000113: Study
p.000113: ATSDR Agency for Toxic Substances and Disease Registry BEI biological exposure index
p.000113: CAB community advisory board
p.000113: CBPR community-based participatory research CDC Centers for Disease Control and
p.000113: Prevention CFR Code of Federal Regulations
p.000113: CIOMS Council for International Organizations of Medical Sciences
p.000113: COPR National Institutes of Health Director’s Council of Public Representatives CPSC
p.000113: Consumer Product Safety Commission
p.000113: CTEPP Children’s Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants
p.000113: DEARS Detroit Exposure and Aerosol Research Study DHEW U.S. Department of Health, Education,
p.000113: and Welfare DMOC data monitoring and oversight committee
p.000113: DNA deoxyribonucleic acid
p.000113: DSMB data safety monitoring board DSMP data and safety monitoring plan
p.000113: EHCRB environmental health and community review board EPA U.S. Environmental Protection
p.000113: Agency
p.000113: ERG Eastern Research Group
p.000113: FCN Federal Communicators Network
p.000113: FDA Food and Drug Administration
p.000113: HHS U.S. Department of Health and Human Services HSRB Human Studies Review Board
p.000113: HSRRO Human Subjects Research Review Official
p.000113: HUD U.S. Department of Housing and Urban Development ICR information collection
p.000113: request
p.000113: IOM Institute of Medicine
p.000113: IRB institutional review board
p.000113: NAS National Academy of Sciences
p.000113: NBAC National Bioethics Advisory Commission NCI National Cancer Institute
p.000113: NCS National Children’s Study
p.000113: NEI National Eye Institute
p.000113: NEJAC National Environmental Justice Advisory Council NERL National Exposure Research
p.000113: Laboratory
p.000113:
p.000113:
p.000115: 115
p.000115:
p.000115: NGO Nongovernmental organization
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p.000007: • Identify the factors that impact people’s exposures (i.e., determine the when, why, how, and how much
p.000007: that people are exposed to chemicals in the environment).
p.000007: These studies involve many different types of data collection efforts and typically include
p.000007: observations,
p.000007: measurements, and information on the following items.
p.000007: • Chemical concentrations in environmental media (air, water, soil, floor dust, and dust on surfaces)
p.000007: • Chemical concentrations in the diet (food and beverages).
p.000007: • Biomonitoring (measurements of biomarkers of exposure in urine, blood, and saliva)
p.000007: • Time, location, and activity information
p.000007: • Information on personal activities, product use, diet, occupation, and other factors that may
p.000007: impact exposure
p.000007: • Information on the characteristics of the environments that study participants occupy (homes, schools,
p.000007: offices, public access buildings, etc.)
p.000007: The information obtained in observational human exposure studies is used to better understand people’s
p.000007: contact with chemicals in the environment and to improve exposure assessments and risk assessments.
p.000007: This information is also essential for developing risk mitigation strategies and for developing
p.000007: educational materials and programs for reducing exposures and risks to chemicals or other stressors in the
p.000007: environment (see Table 1-1).
p.000007:
p.000007: 1.2 Ethical Issues in Observational Human Exposure Studies
p.000007: By definition, observational human exposure studies involve human subjects. Whenever their research
p.000007: involves human subjects, EPA researchers are required to ensure the protection of the study participants
p.000007: by complying with the Agency’s human subjects rules as set forth in 40 CFR 26.
p.000007: The Common Rule (Subpart A of the rules) represents basic regulatory actions (common to more than
p.000007: a dozen Federal departments or agencies) that are intended to ensure the protection of all human subjects. The
p.000007: central requirements of the Common Rule are twofold:
p.000007: (1) that people who participate as subjects in covered research are selected equitably and give
p.000007: their fully informed, fully voluntary written consent; and
p.000007: (2) that proposed research be reviewed by an independent oversight group referred to
p.000007: as an institutional review board (IRB) and approved only if risks to subjects have been minimized, and
p.000007: risks are reasonable in relation to anticipated benefits, if any, to the subjects and to the importance of the
p.000007: knowledge that may realistically be expected to result.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008: Table 1-1. Examples of the Impact of Observational Human Exposure Studies on Pollution Levels and Regulatory Actions
p.000008: Pollutant Observational Study Result
p.000008: Impact/Action/Result
p.000008:
p.000008: Particulate Matter (PM)
p.000008: Observational panel studies demonstrated the appropriateness of ambient measurement of fine particles as a surrogate
p.000008: for a population’s longitudinal exposure to fine PM.
p.000008: Resolved questions in NAS review of PM science and provided a “generally consistent finding that ambient particle
p.000008: concentrations are a key determinant of the longitudinal variation in personal exposure.” (NRC, 2004). These results
p.000008: have been instrumental in support of the National Ambient Air Quality Standard for PM (U.S. EPA, 1999).
p.000008:
p.000008:
p.000008: Volatile Organic Compounds (VOCs)
p.000008:
p.000008: EPA's Total Exposure Assessment Methodology (TEAM) studies found levels of about a dozen common organic pollutants to
p.000008: be 2- to 5-times higher inside homes than outside. Use of products containing organic chemicals may result in very high
p.000008: and persistent pollutant levels.
p.000008:
p.000008: EPA, States, and the Consumer Product Safety Commission worked together to influence manufacturers to voluntarily
p.000008: reduce emissions of toxic chemicals from consumer products, building materials, and furnishings, and to develop
p.000008: mitigation strategies and educational materials to teach people how to reduce their contact with chemicals indoors. As
p.000008: a result, contact with toxic chemicals indoors has been reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html).
p.000008:
p.000008:
p.000008: Formaldehyde
p.000008:
p.000008: Studies found elevated formaldehyde levels indoors and helped identify indoor sources.
p.000008:
p.000008: EPA worked with HUD, CPSC, and other agencies to limit formaldehyde in building or consumer products and to educate the
p.000008: public on how to reduce exposures (see www. epa.gov/iaq/formalde.html).
p.000008:
p.000008:
p.000008: EPA has adopted additional protections for children and pregnant or nursing mothers in Subparts B through
p.000008: D. These sections apply to all research either conducted or funded by EPA and are, therefore, directly applicable to
p.000008: NERL’s observational human exposure studies.4 Subpart B prohibits EPA from conducting or supporting research
p.000008: that involves intentional exposure of “a pregnant woman (and, thereby, her fetus), a nursing woman,
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
...
p.000017: meet the Agency’s need.
p.000017:
p.000017: 2.1.1 Defining the Study Problem
p.000017: Observational studies historically have been performed for many different purposes and in many
p.000017: different fields of research—social behavioral, economic, biological, medical, epidemiological,
p.000017: and exposure science. NERL has used observational human exposure studies to understand how people come into
p.000017: contact with pollutants in their everyday lives, with the ultimate goal of protecting public health. NERL’s
p.000017: exposure research program addresses critical science needs directly related to Agency goals for protection of
p.000017: human health. The research program is driven by key exposure science questions that may be generated from a
p.000017: number of different sources, including legislative mandates (e.g., the Food Quality Protection
p.000017: Act, the
p.000017:
p.000017:
p.000018: 18
p.000018:
p.000018: Clean Air Act, the Safe Drinking Water Act), program offices or research planning groups in the
p.000018: Agency, scientific peers and researchers, or collaborators. Communities also may identify
p.000018: concerns about exposures in their locales. NERL’s observational human exposure studies collect data to improve
p.000018: exposure and risk assessments, to develop risk management strategies, and to substantiate informational
p.000018: and educational materials for use by EPA program offices (e.g., Office of Pollution Prevention and Toxic
p.000018: Substances, Office of Air and Radiation, Office of Children’s Health Protection).
p.000018: Emanuel et al. (2000) contend that an ethical research study must provide a worthwhile social or
p.000018: scientific value. Ideally, observational human exposure studies can provide both a scientific value and a social
p.000018: value to the participants and their community when feasible. Whenever possible, researchers should work
p.000018: with communities to develop studies that can help address community problems and maximize the
p.000018: benefit to the participants and the community, both of which also assume a burden for participation in a
p.000018: research study.
p.000018: The study problems addressed in past observational human exposure studies conducted or supported by NERL
p.000018: have varied substantially, as described in Appendix A of this document. As shown in Table A-1, NERL’s studies
p.000018: have addressed exposures to particulate matter (PM), air toxics, persistent organic chemicals, and nonpersistent
p.000018: chemicals including pesticides. The studies have examined single routes of exposure (air) and multimedia
p.000018: exposures, including dietary exposure. The studies range from small-scale pilot studies to large
p.000018: probability-based samples. They have included cross- sectional, longitudinal, and convenience samples. Table A-1
p.000018: demonstrates that many of the studies are small in scale and were intended to test a methodology to see if it may
...
p.000023: research studies that will,
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024: of necessity, include vulnerable groups to address the study hypotheses or objectives simply to avoid the more
p.000024: stringent requirements for working with these groups.
p.000024:
p.000024: 2.4 Ensuring a Favorable Risk-Benefit Ratio
p.000024: 2.4.1 Designing in Benefits for the Participants
p.000024: Study designs vary depending on the objectives of the study, existing knowledge on the research question, and
p.000024: the hazard being studied (NRC & IOM, 2005). Recent ethical discussions about study designs in human subjects
p.000024: research (cf., Recommendation 7.1, p. 143, NRC & IOM [2005] and Emanuel et al. [2000]) support the development
p.000024: of innovative study designs to maximize the benefit9 to the study participants, as well as to
p.000024: the community and the greater society beyond. Observational human exposure studies generally collect data that
p.000024: contribute to generalizable knowledge that will benefit the community and society as a whole, but they often do not
p.000024: provide obvious direct benefit to study participants. Therefore, it is important to include elements
p.000024: in the study design that can offer benefits to the participants wherever possible. This is not always
p.000024: straightforward, but one way that participants, as well as communities, can benefit from these studies is
p.000024: by incorporating strong educational components into the conduct of the research. For example, brochures, videos,
p.000024: and other materials that educate study participants on safety around the home or on how to reduce their
p.000024: exposure to chemicals can be distributed during the study. EPA’s program offices, including the Office of
p.000024: Children’s Health Protection, the Office of Pollution Prevention and Toxics, the Office of Pesticide Programs,
p.000024: the Office of Drinking Water, and others have Web sites with substantial amounts of informational
p.000024: and educational materials available that could be distributed to study participants. Other organizations, such as
p.000024: the American Lung Association, the American Cancer Society, the American Academy of Pediatrics (AAP),
p.000024: and various environmental groups, have materials of which study participants may not be aware that could be used
p.000024: as educational materials when relevant.
p.000024: In addition, approaches that provide direct benefits to study participants will need to be tailored to
p.000024: the particular study population and community. Feedback from potential participants in focus groups and
p.000024: input from community representatives may be useful in identifying these approaches.
p.000024:
p.000024:
p.000024:
p.000024: 9 Payment to participants is never considered a benefit of a study.
p.000024: 2.4.2 Assessing Benefits and Risks of Study Participation
p.000024: For all research involving human participants, the Common Rule requires researchers to ensure that
p.000024: potential risks “are reasonable in relation to the anticipated benefits,” and that risks are
p.000024: minimized (40 CFR 26.111). It is most useful if the assessment of benefits and risks is begun early in
p.000024: the scoping and planning phase of a study.
p.000024: Unlike some biomedical research that involves the study of interventions or procedures that hold out the
p.000024: prospect of direct diagnostic, therapeutic, or preventative benefit for the study participants, observational
p.000024: human exposure studies often do not have a similar prospect of direct benefit to the participant. Therefore, the
p.000024: risk- benefit balance is based on the balance between the risks to the participants and the expected benefits to
p.000024: society (generalizable knowledge). The risks to participants must be reasonable [40 CFR 26.111(a)(2)] in
p.000024: relation to the importance of the knowledge gained. This assessment of the risk-benefit balance,
...
p.000084: conversational tone is used to engage the lay audience, rather than a formal, scholarly tone that
p.000084: distances the community. Stableford and Mettger (2007) argue that proficiency in creating appropriate plain
p.000084: language materials is an acquired skill that requires knowledge and experience. “It is both an art and
p.000084: a science, requiring the ability to simultaneously think about the cognitive, emotional, and visual appeal of the
p.000084: piece as well as applying research- based strategies to ensure a truly easy-to-read and understand print
p.000084: material.”
p.000084: The Department of Health and Human Services (HHS) has developed a Web site that specifically
p.000084: address the issues related to “plain language” (see
p.000084: http://www.health.gov/communication/literacy/plainlang uage/PlainLanguage.htm). The site includes a list of
p.000084: references and other helpful resources.
p.000084: To maintain community engagement through the
p.000084: research process, it is critical that communications are at the appropriate level, and that materials are written at a
p.000084: reading level that is appropriate to the audience. For the nonscientist, many IRBs and other groups target
p.000084: materials to be used with participants and communities at a reading level no higher than the 8th grade to
p.000084: improve the likelihood of comprehension. In some communities, however, other factors, like primary languages other than
p.000084: English, educational disadvantages, etc., may require communications materials to be written in
p.000084: alternate languages and at different reading levels. The issue is comprehension, as was discussed in
p.000084: Section 5.1.2. Empirical testing of communication methods and content is essential to ensure
p.000084: comprehension (Health Canada, 2006).
p.000084: Researchers also should recognize that in this information age, dissemination of
p.000084: informational materials may be rapid and widespread. Therefore, even documents intended for scientific peers may
p.000084: benefit by including summary information in an executive summary or preface that a lay reader can
p.000084: understand.
p.000084:
p.000084: 7.5 Communications Materials
p.000084: Researchers need to communicate clearly with the many groups listed in Section 7.2 to develop their
p.000084: relationship with the participants in the study, to develop their partnership with the community, to gain
p.000084: support from stakeholders, and to inform the public. To achieve the multiple purposes of communications
p.000084: during a research study and to communicate with many diverse groups, a variety of communications materials may
p.000084: need to be developed. Different materials have different purposes and different types of
p.000084: information to be communicated. Because of diversity in interested individuals and groups with
p.000084: respect to education, cultures, information needs, etc., the format and content of communication materials
...
p.000112: research is viewed in the context of a long- term commitment to the community, not a one-time research study.
p.000112: Recommendation 3: Investigate ways to provide mechanisms that allow for follow-up health care when a clinical
p.000112: trial or treatment ends.
p.000112:
p.000112: Building Relationships with Patients (Participants) (True partnerships with patients may not be possible, but
p.000112: bidirectional relationships must be enhanced.)
p.000112: Recommendation 4: Educate and reorient the current research community to the importance of treating the
p.000112: public as a partner in the research process.
p.000112: Recommendation 5: Set the expectation across the entire research community, NIH funded research and beyond, that
p.000112: study results and outcomes should be shared with the research participants and the larger community promptly
p.000112: and consistently. This will ensure translational research.
p.000112:
p.000112: Building Partnerships with Community Providers
p.000112: Recommendation 6: Take action to interest community providers in clinical research and
p.000112: maintain their involvement.
p.000112: Recommendation 7: Provide incentives (not just financial) for primary health care providers and community
p.000112: specialists to play a role in clinical trials.
p.000112:
p.000112: Building Trust in Scientists
p.000112: Recommendation 8: Engage researchers, educators, and academic institutions in incorporating the public's
p.000112: perspective consistently at every level of training and in both the conduct of clinical research and the publication of
p.000112: findings from that research.
p.000112: Recommendation 9: Focus on educational strategies to help patients and communities better understand
p.000112: clinical research. This will help scientists because educating the public will empower and prepare
p.000112: individuals to be informed partners in the clinical research process. An informed and trusting public will
p.000112: enhance research participation.
p.000112:
p.000112: Building Trust in the NIH and Scientific Research
p.000112: Recommendation 10: Continue to develop and fund efforts to build a national identity for the NIH based
p.000112: on what NIH does best—research and education—as a basis for enhancing public trust in clinical
p.000112: research.
p.000112: Recommendation 11: Review the role and impact of Institutional Review Boards and other patient protections
p.000112: in the clinical research process because the public views these protections as less effective than they
p.000112: should be.
p.000112: Recommendation 12: Document and publish “best practices” from efforts to reengineer the clinical research
p.000112: enterprise as soon as the NIH begins to see results, so that progress in improving public trust in medical research
p.000112: grows rapidly and steadily.
p.000112:
p.000112: Source: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for
p.000112: the NIH Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health,
p.000112: Director’s Council of Public Representatives, January 14, 2005. Available:
p.000112: http://copr.nih.gov/reports/public_trust.asp [accessed 12 June 2007].
p.000112:
p.000112:
p.000112:
p.000113: 113
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
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Social / embryo
Searching for indicator embryo:
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p.000051: summarized below. These items may be based on regulatory requirements or currently may
p.000051: be recommendations as ethical “best practices.”
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: Text Box 5-2. Common Rule Requirements:
p.000052: Elements of Informed Consent
p.000052: (1) An explanation of the purposes of the research
p.000052: (2) The expected duration of the subject's participation
p.000052: (3) A description of the procedures to be followed and identification of any experimental procedures
p.000052: (4) A description of any reasonably foreseeable risks or discomforts to the subject
p.000052: (5) A description of any reasonably expected benefits to the subject or others
p.000052: (6) A disclosure of appropriate alternative procedures that might be advantageous to the subject
p.000052: (7) A description of the extent that confidentiality will be maintained
p.000052: (8) For research involving more than minimal risk, an explanation about whether compensation or medical treatments
p.000052: are available if injury occurs
p.000052: (9) An explanation of whom to contact with questions about the research or to report a research-related injury
p.000052: (10) A statement that participation is voluntary, refusal to participate will involve no penalty, and the subject may
p.000052: discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled
p.000052: (11*) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or
p.000052: fetus, if the subject is or may become pregnant) that are currently unforeseeable
p.000052: (12*) Anticipated circumstances under which the subject's participation may be terminated by the investigator without
p.000052: regard to the subject's consent
p.000052: (13*) Any additional costs to the subject that may result from participation in the research
p.000052: (14*) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of
p.000052: participation by the subject
p.000052: (15*) A statement that significant new findings developed during the course of the research that may relate to the
p.000052: subject's willingness to continue participation will be provided to the subject.
p.000052: (16*) The approximate number of subjects in the study
p.000052: * Included if appropriate [40 CFR 26.116(b)]
p.000052:
p.000052:
p.000052:
p.000052: • The information “shall be in language understandable to the subject” (40 CFR 26.116). This may require forms
p.000052: to be written and administered in different languages during a study. For example, the National
p.000052: Children’s Study (NCS) plans to produce all consent materials in English and Spanish, with other
p.000052: translations made available as needed (NCS, 2007).
p.000052: Participants often find discussions with research staff more useful than written consent forms (p. 103, NRC & IOM,
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Social / employees
Searching for indicator employees:
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p.000001: research, but the document is not meant to represent an official Agency “guidance document” and should not be used for
p.000001: that purpose.
p.000001: Observational human exposure studies involve the collection of information about individuals and the environment around
p.000001: them. NERL scientists and managers take the protection of human subjects who participate in these studies very
p.000001: seriously. The steps needed to ensure protection of the human subjects are often complex, and the specific
p.000001: actions will vary depending on the objectives of the study and details about the participants.
p.000001: This document does not provide solutions to all scientific and ethical issues that may arise as such studies are
p.000001: undertaken. That is, it is not possible to identify or address all potential issues in advance or to develop a
p.000001: comprehensive checklist for all such studies. Rather, this document attempts to present and discuss the types
p.000001: of issues that will need to be considered and addressed as NERL researchers plan and implement observational human
p.000001: exposure studies. The researchers will need to work with others⎯the study team, institutional review board
p.000001: members, EPA’s Human Subjects Research Review Official, the participants and their community, and other
p.000001: stakeholders⎯to identify and address all of the relevant issues for their particular study in order to ensure that the
p.000001: specific elements of the study will respect, safeguard, and protect the human research subjects.
p.000001: As EPA employees, NERL scientists face both regulatory and moral obligations to ensure the protection of the
p.000001: human subjects participating in observational research. The regulatory requirements are set forth in
p.000001: EPA’s human subjects regulations (40 CFR 26). NERL scientists are resolved to meet both the “letter” of the law as set
p.000001: forth in the regulations and also the “spirit” that derives from the most up-to-date thinking and consensus on
p.000001: these sensitive issues. This document provides information on regulatory requirements and the state of
p.000001: the science for a number of issues associated with observational human exposure studies to help NERL scientists meet
p.000001: their goal of conducting these studies based on the most up-to-date and sound science and the highest ethical
p.000001: standards.
p.000001: To gather information for the scientific and ethical approaches for observational human exposure studies,
p.000001: NERL convened an expert panel workshop on November 28 and 29, 2006, to discuss the state of the science. The 11-member
p.000001: panel discussed their ideas for the content of this document and the state of the science for various elements
p.000001: of observational human exposure studies. The panel agreed that the document planned by EPA should
p.000001: include the following six major topic areas:
p.000001: (1) identifying elements to be considered in study conceptualization,
p.000001: (2) ensuring protection of vulnerable groups,
p.000001: (3) addressing privacy and other concerns related to observational human exposure studies,
...
p.000117: protection of the human subjects throughout the study. Such studies are often complex, and the specific actions
p.000117: will vary depending on the objectives of the study, the details of the study design and human subjects
p.000117: research protocol, and the details about the participants and the communities in which they live. To
p.000117: ensure that the actions of NERL researchers will properly respect, safeguard, and protect the rights
p.000117: and welfare of the participants in their research, NERL scientists need to be knowledgeable about the scientific
p.000117: and ethical issues that may arise as they plan and conduct their research, and they also need to be diligent
p.000117: in the application of the most up-to-date and sound scientific approaches and of the highest ethical standards to their
p.000117: research.
p.000117: This document, therefore, was prepared by NERL scientists as a resource and reference for EPA’s NERL
p.000117: scientists as they develop and implement observational human exposure studies. The authors recognize that this
p.000117: document also may prove to be useful to others involved in exposure science research, but that this document
p.000117: does not meet the definition of an official Agency “guidance document” (it does not set forth “a policy on a
p.000117: statutory, regulatory or technical issue or an interpretation of a statutory or regulatory
p.000117: issue”) and should not be used for that purpose.
p.000117: As EPA employees, NERL scientists face both regulatory and moral and ethical obligations to ensure
p.000117: the protection of the human subjects participating in their observational research. The
p.000117: regulatory requirements are set forth in EPA’s human subjects regulations (40 CFR 26). The moral
p.000117: obligations derive from the ethical principles of biomedical ethics. NERL scientists and managers are
p.000117: resolved to meet both the “letter” of the law as set forth in the regulations and also the “spirit” that
p.000117: derives from the most up-to-date thinking and consensus on these sensitive issues.
p.000117: This document provides information on regulatory requirements and ethical issues to consider when
p.000117: performing human subjects research. Knowledge about these requirements and issues will help NERL scientists meet
p.000117: their goal of conducting observational human exposure studies based on the most up-to-date and sound science
p.000117: and the highest ethical scientific standards.
p.000117: The ethical and moral issues associated with human subjects research has long been the subject of a great deal
p.000117: of thought and discussion, both in the United States and abroad. Issues in biomedical ethics continue to be
p.000117: discussed and debated in today’s headlines. Spurred by the atrocities of World War II concentration camps and by
p.000117: the disclosure of unethical treatment of undereducated African-American men and
...
p.000022: art because the design of surveys is based on statistics and science, but designing a good and effective questionnaire
p.000022: is often an art that requires understanding the individuals being surveyed. Text Box 2-3 identifies some of the
p.000022: areas of art involved in designing an effective questionnaire.
p.000022: Understanding the process for selecting participants and the statistical-scientific requirements of
p.000022: questionnaire design are both components of survey sampling and design. A variety of references can provide
p.000022: the researcher with information about the issues in survey sampling and
p.000022: design. (See http://home.ubalt.edu/ntsbarsh/Business-stat/stat data/Surveys.htm and
p.000022: www.statpac.com/surveys/, for example.) But the research team must include or have access to the appropriate
p.000022: survey statistics expertise as it plans the research study.
p.000022:
p.000022: Text Box 2-3. Questionnaire Considerations
p.000022: • Questions should be simple and in a language the individual can understand.
p.000022: • Questions should be unambiguous.
p.000022: • Questions should be relevant to the study.
p.000022: • Questions should not be too personal.
p.000022: • The questionnaire should be as short as possible.
p.000022: • The questions should not be leading (e.g., internally suggestive of the answer).
p.000022: • Questions should follow a logical order.
p.000022:
p.000022:
p.000022:
p.000022: 2.2.5 Information Collection Rule
p.000022: As Federal employees, NERL researchers also must be aware of Information Collection Rule requirements. The
p.000022: Paperwork Reduction Act stipulates that every Federal agency must obtain approval from OMB before collecting
p.000022: the same or similar information from 10 or more members of the public. An Information Collection Request (ICR)
p.000022: is required if the same or similar information is being collected from 10 or more non- Federal
p.000022: respondents within a 12-month period, even if the information collection is voluntary. Generally, any
p.000022: survey, questionnaire, monitoring, reporting, or recordkeeping requirement imposed on
p.000022: non-Federal respondents by EPA will require an ICR. Information collections associated with all cooperative
p.000022: agreements funded by the EPA require an ICR. When an ICR is required, it must be approved by OMB
p.000022: before the collection begins, regardless of whether the collection of information is mandatory, voluntary,
p.000022: or required to receive a benefit. The principal investigator must prepare an ICR and submit it to the
p.000022: appropriate Office of Environmental Information Desk Officer.
p.000022: An ICR
p.000022: • describes the information to be collected,
p.000022: • provides justification for why the information is needed, and
p.000022: • estimates the time and cost for the public to answer the request.
p.000022: Information about ICRs and their requirements is available to NERL and other EPA staff members at
p.000022: http://intranet.epa.gov/icrintra/index.html.
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023: 2.2.6 Quality Assurance Project Plan
...
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
...
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
...
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
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p.000117:
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p.000118:
p.000118: United States Environmental Protection Agency
p.000118:
p.000118:
p.000118:
p.000118: Office of Research and Development (810R) Washington, DC 20460
p.000118:
p.000118: Official Business Penalty for Private Use
p.000118: $300
p.000118: PRESORTED STANDARD POSTAGE & FEES PAID EPA
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Social / gender
Searching for indicator gender:
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p.000070: 6.2 Issues in Community Involvement
p.000070: There are a number of issues that need to be addressed in any efforts to ensure
p.000070: community involvement. The Expert Panel that was convened to advise NERL about scientific and ethical
p.000070: issues in observational human exposure studies discussed a number of challenges (ERG, 2007). The topics
p.000070: that the expert panel identified as issues are discussed below.
p.000070:
p.000070: 6.2.1 Defining “Community”
p.000070: “Community” refers to a group of people united by a shared attribute, and the attributes can be wide-ranging, such as
p.000070: geography, culture, social characteristics, values, interests, traditions, or experiences (ERG, 2007).
p.000070: Community can be defined broadly (as a system of interrelated groups operating to meet the needs of its
p.000070: members) or more narrowly (as the population from which study participants are selected). For observational
p.000070: field studies, the Expert Panel from the workshop suggested the narrow definition. A narrow
p.000070: definition allows social and cultural factors to be included but excludes government agencies, industry, and
p.000070: others who do not necessarily represent the interests of the participants (ERG, 2007).
p.000070: Central to the definition of a community is a sense of “who is included and who is excluded from
p.000070: membership” (NRC & IOM, 2005). A person may be a member of a community by choice, as with voluntary
p.000070: associations, or by virtue of their innate personal characteristics, such as age, gender, race, or
p.000070: ethnicity (NRC & IOM, 2005). As a result, individuals may belong to multiple communities at any one time. When
p.000070: initiating community engagement efforts, one should be aware of these complex associations in deciding which
p.000070: individuals to work with in the targeted community.
p.000070: Quandt et al. (2001) discuss a CBPR research project, Preventing Agricultural Chemical Exposure in
p.000070: North Carolina Farmworkers, where the process of defining a community was complicated by language,
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
p.000070: sense of community was nurtured among the farmworkers collectively (O’Fallon and Dearry, 2002).
...
p.000072:
p.000072: 6.2.5 Recognizing and Addressing Cultural Differences
p.000072: Building and maintaining appropriate community and stakeholder relationships requires acknowledgment of the
p.000072: diversity within communities with regard to many factors, including, but not limited to, race/ethnicity,
p.000072: religious beliefs, heritage, and lifestyles. Different groups in the study area may have different
p.000072: cultural norms and practices. The researchers should take these issues into consideration as they work in the
p.000072: community. Community partners can help researchers design the study to be attentive to the increasing
p.000072: heterogeneity of community groups (Minkler and Wallerstein, 2003, Chapter 4) and to the different
p.000072: boundaries of privacy (crucial when designing sampling strategies) of different groups (Israel et al., 2005b, Chapter
p.000072: 11).
p.000072: Vega (1992) provides a thorough discussion of the theoretical and pragmatic implications of
p.000072: cultural diversity for community research and explains that researchers should interact with
p.000072: communities using methods that promote understanding and demonstrate sensitivity and competence in
p.000072: working with diverse
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073: cultures (e.g., with respect to class, gender, ethnicity, race, age, and sexual orientation). To aid in this
p.000073: process, researchers should include sufficient time in their project timeline to interact and dialogue with the
p.000073: community before the study begins to understand the cultural issues that may affect the research. Researchers and the
p.000073: results of their work are expected to promote a strengthening of the community; however, it should be recognized
p.000073: that, given the heterogeneity and the diverse views within a community, the study findings potentially may
p.000073: conflict with the desires of the community or may promote feelings of anger or distrust among members
p.000073: of the community with each other. Enlisting the services of a third-party evaluator/mediator may be
p.000073: useful for sustaining positive relations between all research participants and the community at
p.000073: large.
p.000073: The Research Triangle Park Particulate Matter Panel Study (Williams et al., 2003), a NERL investigation of PM
p.000073: and related pollutants involving African-Americans in North Carolina, demonstrated an effective strategy for using
p.000073: communication to address cultural differences between the community and research personnel. Before beginning
p.000073: the research, the study design included time and a budget for building collaborations with
p.000073: organizations having close ties with the African- American community to establish trust between
...
Social / parents
Searching for indicator parent:
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p.000036: and D of the EPA Human Subjects Rule are met.
p.000036:
p.000036: 3.4 Research Involving Children
p.000036: Children long have been recognized as a vulnerable group in research studies. EPA and HHS both extend special
p.000036: protections to children (CFR, 2006a,b). There are many books, reports, and research manuscripts that
p.000036: specifically address issues associated with research involving children (e.g., NRC & IOM, 2005; IOM,
p.000036: 2004; Kodish, 2005; NRC, 2003; AAP, 2003).
p.000036: CIOMS has drafted guidelines for including children in biomedical research (Guideline 14, CIOMS, 2002). The
p.000036: guidelines require an investigator to provide the assurances shown in Text Box 3-3 before undertaking
p.000036: research involving children.
p.000036:
p.000036: Text Box 3-3. Assurances Required by CIOMS Before Research Involving Children May Begin
p.000036: • the research might not equally well be carried out with adults;
p.000036: • the purpose of the research is to obtain knowledge relevant to the health needs of children;
p.000036: • a parent or legal representative of each child has given permission;
p.000036: • the agreement (assent) of each child has been obtained to the extent of the child’s capabilities; and
p.000036: • a child’s refusal to participate or continue in the research will be respected.
p.000036:
p.000036:
p.000036: The participation of children in some observational human exposure studies is critical to
p.000036: characterizing children’s exposures to chemicals in the environment. It is well recognized that children are not
p.000036: “little adults,”
p.000036: and that their
p.000036: exposures to chemicals differ (and, in
p.000036:
p.000036:
p.000036: with routine medical or psychological examination of such persons unless an ethical review committee authorizes a
p.000036: slight increase over this level of risk (Guideline 9); and,
p.000036: • when the prospective subjects are either incompetent or otherwise substantially unable to give informed consent,
p.000036: their agreement will be supplemented by the permission of their legal guardians or other appropriate representatives.
p.000036:
p.000036:
p.000036: 13 Minimal risk is defined at 40 CFR 26.102(i) and again at 40 CFR 26.402(g). It “means that the probability and
...
p.000052: 17 A survey of IRBs found that their readability standards ranged from 5th- to 10th-grade level (Paasche-Orlow et al.,
p.000052: 2003). Interestingly, the same report found that, 92% of the time, the sample consent forms provided by the IRBs did
p.000052: not meet their own readability standards. The NRC & IOM report (p. 107, NRC & IOM, 2005) discusses an NCI effort to
p.000052: simplify informed consent forms by using text targeted at 8th-grade reading level. More information about the NCI
p.000052: template may be found at www.nci.nih.gov/clinicaltrials/understanding/simplification-of-informed consent-docs/page2
p.000052: (accessed September 12, 2007).
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053: participants and, if so, how and when (p. 101, NRC & IOM, 2005).
p.000053: • For studies involving children as participants, it generally is regarded as desirable that the
p.000053: informed consent process should involve both parents (assuming that there are two competent
p.000053: parents available), and that the consent of both parents be obtained, if possible. The IRB may decide
p.000053: that the permission of one parent is sufficient, but only when certain risk-benefit conditions are met.18
p.000053: • For studies involving children as participants, it is desirable for those children with sufficient capacity
p.000053: to be involved in the consent process. Moreover, it is generally accepted that the child’s assent be obtained
p.000053: whenever this is developmentally possible and otherwise appropriate. Under both the EPA Rule and the HHS
p.000053: Rule, the IRB is responsible for determining that adequate provisions have been made for soliciting the assent of the
p.000053: children when, in the judgment of the IRB, the children are capable of providing assent. Assent, however, may
p.000053: be waived in those restricted circumstances in which consent may be waived under the Common Rule. Those
p.000053: circumstances and the required IRB documentation are described in the Common Rule at 40 CFR 26.116(d).
p.000053: • The consent form should clearly state that participation is voluntary and that study
p.000053: participants may “discontinue participation at any time without any penalty or loss of benefits to which the
...
p.000053: For example, effects of environmental exposures on gene expression are potentially very important.
p.000053: Therefore, biologic specimens for DNA analysis may be obtained from participants in future studies. But, it
p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45 CFR 46.408(b)
p.000053: for all research with children. Under the EPA Rule, greater than minimal risk observational research with children that
p.000053: does not hold out the prospect of direct benefit to the child is not permitted under any circumstances. Under the HHS
p.000053: Rule, greater than minimal risk research involving children without the prospect of direct benefit is permitted in very
p.000053: limited circumstances, but the consent of both parents is required in those cases (unless one parent is deceased,
p.000053: unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and
p.000053: custody of the child).
p.000053: special concerns about the potential for discrimination, stigmatization, and impact on
p.000053: future employment or insurance. The informed consent process needs to explain what the plans may be
p.000053: for such specimens and recognize the rights of the subjects to decide about any such future use,
p.000053: including having the material destroyed. The informed consent process needs to explicitly discuss
p.000053: obtaining permission from participants on behalf of themselves and their child to obtain specimens for
p.000053: genetic analysis.
p.000053:
p.000053: 5.1.2 Comprehension
p.000053: Research participants frequently fail to understand the research protocols in which they agree to participate (NRC
p.000053: & IOM, 2005). In considering the ethical issues raised by the Grimes v. Kennedy Krieger case, the NRC & IOM
p.000053: committee “realized that the crucial issue regarding consent was not what information was
p.000053: contained in the consent forms, but rather what the parents understood about the study and the hazards
...
p.000085: • Flyers
p.000085: • Web sites
p.000085: • Brochures
p.000085: • Interviews
p.000085: • Newsletters
p.000085: • Focus groups
p.000085: • Presentations
p.000085: • Direct mailings
p.000085: • Press releases
p.000085: • Questions and answers
p.000085: • Desk statements (government)
p.000085: • Abstracts
p.000085: • Study reports
p.000085: • Talking points
p.000085: • Community meetings
p.000085: • Stakeholder meetings
p.000085: • Technical presentations
p.000085: • Study participant meetings
p.000085: • Scientific meeting presentations
p.000085: • Peer-reviewed scientific journal manuscripts
p.000085: • Final reports describing the total research effort
p.000085:
p.000085: When developing communication materials, the researcher should consider the needs of the reader,
p.000085: listener, or viewer with respect to content, scope, style, and the level at which the materials are written.
p.000085: There are many sources of information on design of informational materials, such as flyers or
p.000085: brochures. For example, Alderson (1995) provides an example of the recommended content and style for information
p.000085: leaflets (that also may be flyers or brochures) for pediatric medical research. She suggests that leaflets be
p.000085: provided to parents of children who will be study participants that can be read to the children. She recommends that
p.000085: these be provided at the time that the parent is being informed of the study, prior to requesting the informed
p.000085: consent. The content of the leaflet would include the following topics.
p.000085: • Nature and purpose of the research
p.000085: • Anticipated benefits of the research
p.000085: • Risks, harms, costs, and inconvenience to the participant
p.000085: • Assurance that the participant freely can refuse to participate in or withdraw from the study
p.000085: • Details about remuneration
p.000085: • Names of the project sponsors and the researchers
p.000085: • Contact information for the researchers
p.000085: • Respect for privacy and confidentiality
p.000085: Leaflets and brochures that contain this information provide a tool for communication with study
p.000085: participants. However, these materials need to be written carefully using everyday terms that the
p.000085: average nonresearcher can understand. The brochure should be written in a friendly style that conveys the intent
p.000085: of the researcher to engage the reader as a collaborator on the study, not as a study “subject,” who will be told to do
p.000085: a series of tasks while participating in the study.
p.000085: These same leaflets and brochures can be used to inform other groups that either may be involved or
p.000085: interested in the study, such as community representatives, stakeholder organizations,
p.000085: the media, and the general public. The researcher should ensure that any brochure developed for the study includes
p.000085: accurate and complete information that is less likely to be misinterpreted by anyone who might
p.000085: pick up the brochure. Brochures and flyers that are used to announce a study or are used as recruiting tools
...
p.000100: questionnaires were administered. individual studies
p.000100:
p.000100: Overview
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: NHEXAS-
p.000100: Arizona
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: NHEXAS-
p.000100: Maryland
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: NHEXAS-
p.000100: Region 5
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: Minnesota Children’s Pesticide Exposure Study (MNCPES)
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 1995-1998
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 1995-1996
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 1995-1997
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.001997: 1997
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.000179: 179
p.000179: Households
p.000179:
p.000179:
p.000179:
p.000179:
p.000080: 80
p.000080: Households
p.000080:
p.000080:
p.000080:
p.000080:
p.000080:
p.000250: 250
p.000250: Households
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: 102 Children
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: Probability, cross- sectional
p.000250:
p.000250:
p.000250:
p.000250: Probability, longitudinal
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: Probability, cross- sectional
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: Probability, cross- sectional
p.000250: Biological media, including blood and urine, also were sampled and monitored for parent contaminants or their
p.000250: metabolites.
p.000250: The studies were undertaken to evaluate total human exposure to multiple chemicals on a community and regional scale
p.000250: with the following aims: provide a baseline of the normal range of exposure to chemicals in the general population;
p.000250: identify subgroups of the general population that are likely to be highly exposed; and evaluate and improve the
p.000250: accuracy of models developed to predict exposure to chemicals.
p.000250: The NHEXAS-Arizona study sampled residences determined by a population-based probability research design for the total
p.000250: population of Arizona and measured metals, pesticides, and volatile organic compounds (VOCs). The study was conducted
p.000250: by a consortium composed of the University of Arizona, Battelle Columbus, and the Illinois Institute of Technology.
p.000250: The study sampled residences of Baltimore and four adjacent counties and measured metals, pesticides, and polycyclic
p.000250: aromatic hydrocarbons (PAHs). Data collection occurred up to 6 times over 1 year for each of the participating
p.000250: households. The study was conducted by Harvard University, Emory University, Johns Hopkins University, and Westat. The
p.000250: study investigated temporal variability in multimedia, multipollutant exposures.
p.000250: The Region 5 study was conducted in EPA's Region 5 (Ohio, Michigan, Illinois, Indiana, Wisconsin, and Minnesota), and
p.000250: included personal exposure, residential concentration, and biomarker measurements of metals and VOCs. The study was
p.000250: conducted by the Research Triangle Institute (RTI) and the Environmental and Occupational Health Sciences Institute
p.000250: (EOHSI).
...
p.000109: (19) If applicable, clinical and other tests involving the study participants that are to be carried out
p.000109: (20) The rules or criteria according to which subjects may be removed from the study or the study may be
p.000109: terminated
p.000109: (21) The methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000109: complications
p.000109: (22) The potential benefits of the research to subjects and to others
p.000109: (23) The expected benefits of the research to the population, including new knowledge that the study
p.000109: might generate
p.000109:
p.000109:
p.000109:
p.000111: 111
p.000111:
p.000111: (24) The means proposed to obtain individual informed consent and the procedure planned to communicate information to
p.000111: prospective subjects, including the name and position of the person responsible for obtaining consent
p.000111: (25) When a prospective subject is not capable of informed consent, satisfactory assurance
p.000111: that permission will be obtained from a duly authorized person, or, in the case of a child who is sufficiently mature
p.000111: to understand the implications of informed consent but has not reached the legal age of consent,
p.000111: that knowing agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian
p.000111: or other duly authorized representative.
p.000111: (26) An account of any economic or other compensation or incentives to prospective subjects to participate, such as
p.000111: offers of cash payments, gifts, or free services or facilities, and of any financial
p.000111: obligations assumed by the subjects, such as payment for medical services
p.000111: (27) The plans and procedures and the persons responsible for communicating to
p.000111: subjects information arising from the study (on harm or benefit, for example) or from other research on the same
p.000111: topic that could affect subjects’ willingness to continue in the study
p.000111: (28) The plans to inform subjects about the results of the study
p.000111: (29) The provisions for protecting the confidentiality of personal data and respecting the privacy of subjects,
p.000111: including the precautions that are in place to prevent disclosure of the results of a
p.000111: subject’s genetic tests to immediate family relatives without the consent of the subject
p.000111: (30) Information about how the code, if any, for the subjects’ identity is established; where it will be
p.000111: kept; and when, how, and by whom it can be broken in the event of an emergency
p.000111: (31) Any foreseen further uses of personal data or biological materials
p.000111: (32) A description of the plans for statistical analysis of the study, including plans for interim analyses, if
p.000111: any, and criteria for prematurely terminating the study if necessary
...
Searching for indicator parents:
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p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
...
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
...
p.000037: risks and harm are minimized. The perception of risks and benefits, both by
p.000037: the individual and by the family or community, may influence the risk-benefit determination. It may prove
p.000037: useful for the research team to consult with other experienced researchers who have conducted
p.000037: similar studies and with members of the IRB to ensure that the information included in the human subjects
p.000037: research protocol is adequate for the IRB’s review.
p.000037: It is recommended that researchers consider all of the potential issues associated with involvement
p.000037: of children in their studies in developing the study design and research protocols, including the role of the
p.000037: family. EPA’s human subjects rule for observational research not involving greater than minimal risk to
p.000037: children (40 CFR 26.404) (i.e., the kinds of observational human exposure studies that NERL exposure research
p.000037: is likely to entail) focuses on obtaining assent of the children and permission of their parents or guardians. But the
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
p.000037: biomedical research because of the potential for becoming pregnant during a study. The document continues, “A
p.000037: general policy of excluding from such clinical trials women biologically capable of becoming pregnant is
...
p.000051: 16 An IRB may waive informed consent under some very limited conditions. See 40 CFR 26.116(c) and (d).
p.000051: requirements or identified in recent writings on ethical considerations in human subjects research, is
p.000051: grouped below, under the three pillars of informed consent:
p.000051: (1) information, (2) comprehension, and (3) voluntary participation.
p.000051:
p.000051: Text Box 5-1. Recommendations for Informed Consent In the United States and Internationally
p.000051: (1) Revitalize Informed Consent (IOM, 2002)
p.000051: Informed consent is a process, not a form. It is an on-going, interactive dialogue between research staff and research
p.000051: participants with disclosure and exchange of relevant information, including assessment of understanding.
p.000051: Ethics Review Boards should ensure that the focus of both the informed consent process and the consent forms is on
p.000051: informing and protecting participants, not the research institution.
p.000051: (2) Strengthen Process of Parental Permission and Children’s Assent if Children Are Involved in Research (NRC & IOM,
p.000051: 2005)
p.000051: The process begins with a community-based discussion and concludes with an assurance that individual parents understand
p.000051: the essential elements of the research.
p.000051: Educate parents on issues critical to informed decision making and assess their degree of understanding.
p.000051: Use informational materials in the form that is most appropriate to convey information to potential participants.
p.000051: Consult with community representatives to ensure that information is complete, clear, and understandable, and that any
p.000051: payment will not be exploitive.
p.000051: Expand the perspective about what information about risks and benefits is needed to make an informed choice.
p.000051: Ethically, it is critical to assure that participants and parents understand the crucial features of the research
p.000051: effort.
p.000051: (3) Informed Consent Is a Decision To Participate by an Informed, Competent Individual Without Undue Coercion,
p.000051: Influence, or Intimidation (CIOMS, 2002)
p.000051: Informed consent is a process that takes time and resources.
p.000051: It is not a ritual recitation of text from a form but informative communication in language that suits the individual’s
p.000051: level of understanding.
p.000051: Consent is ethically obtained, considering language and cultural issues, and is documented.
p.000051: Material changes in conditions or procedures require that informed consent be renewed.
p.000051: Consent should explain how samples will be used in current research, and, if applicable, how samples may be used in
p.000051: future research.
p.000051:
p.000051:
p.000051:
p.000051: 5.1.1 Information
p.000051: Some items that researchers should keep in mind as they provide information to the study participants are
p.000051: summarized below. These items may be based on regulatory requirements or currently may
p.000051: be recommendations as ethical “best practices.”
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
...
p.000052: goes beyond simply using the appropriate language;
p.000052:
p.000052: the researcher is compelled also to consider readability and vocabulary (e.g., avoiding jargon
p.000052: or terminology that may be clear to the researcher but which may confuse or intimidate the potential subject)
p.000052: if the information is to be understandable.
p.000052: • Information may be presented orally in addition to an appropriately written document (40 CFR 26.117).
p.000052: 17 A survey of IRBs found that their readability standards ranged from 5th- to 10th-grade level (Paasche-Orlow et al.,
p.000052: 2003). Interestingly, the same report found that, 92% of the time, the sample consent forms provided by the IRBs did
p.000052: not meet their own readability standards. The NRC & IOM report (p. 107, NRC & IOM, 2005) discusses an NCI effort to
p.000052: simplify informed consent forms by using text targeted at 8th-grade reading level. More information about the NCI
p.000052: template may be found at www.nci.nih.gov/clinicaltrials/understanding/simplification-of-informed consent-docs/page2
p.000052: (accessed September 12, 2007).
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053: participants and, if so, how and when (p. 101, NRC & IOM, 2005).
p.000053: • For studies involving children as participants, it generally is regarded as desirable that the
p.000053: informed consent process should involve both parents (assuming that there are two competent
p.000053: parents available), and that the consent of both parents be obtained, if possible. The IRB may decide
p.000053: that the permission of one parent is sufficient, but only when certain risk-benefit conditions are met.18
p.000053: • For studies involving children as participants, it is desirable for those children with sufficient capacity
p.000053: to be involved in the consent process. Moreover, it is generally accepted that the child’s assent be obtained
p.000053: whenever this is developmentally possible and otherwise appropriate. Under both the EPA Rule and the HHS
p.000053: Rule, the IRB is responsible for determining that adequate provisions have been made for soliciting the assent of the
p.000053: children when, in the judgment of the IRB, the children are capable of providing assent. Assent, however, may
p.000053: be waived in those restricted circumstances in which consent may be waived under the Common Rule. Those
p.000053: circumstances and the required IRB documentation are described in the Common Rule at 40 CFR 26.116(d).
...
p.000053: explained [40 CFR 26.116(b)(4)].
p.000053: • The consent form should address any foreseeable potential future use of samples and data (CIOMS, 2002).
p.000053: For example, effects of environmental exposures on gene expression are potentially very important.
p.000053: Therefore, biologic specimens for DNA analysis may be obtained from participants in future studies. But, it
p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45 CFR 46.408(b)
p.000053: for all research with children. Under the EPA Rule, greater than minimal risk observational research with children that
p.000053: does not hold out the prospect of direct benefit to the child is not permitted under any circumstances. Under the HHS
p.000053: Rule, greater than minimal risk research involving children without the prospect of direct benefit is permitted in very
p.000053: limited circumstances, but the consent of both parents is required in those cases (unless one parent is deceased,
p.000053: unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and
p.000053: custody of the child).
p.000053: special concerns about the potential for discrimination, stigmatization, and impact on
p.000053: future employment or insurance. The informed consent process needs to explain what the plans may be
p.000053: for such specimens and recognize the rights of the subjects to decide about any such future use,
p.000053: including having the material destroyed. The informed consent process needs to explicitly discuss
p.000053: obtaining permission from participants on behalf of themselves and their child to obtain specimens for
p.000053: genetic analysis.
p.000053:
p.000053: 5.1.2 Comprehension
p.000053: Research participants frequently fail to understand the research protocols in which they agree to participate (NRC
p.000053: & IOM, 2005). In considering the ethical issues raised by the Grimes v. Kennedy Krieger case, the NRC & IOM
p.000053: committee “realized that the crucial issue regarding consent was not what information was
p.000053: contained in the consent forms, but rather what the parents understood about the study and the hazards
p.000053: present in the home before and after the study” (p. 19, NRC & IOM, 2005). The committee laments that “IRBs
p.000053: place their attention on consent forms rather than on the process of providing and discussing information” (p.
p.000053: 103, NRC & IOM, 2005). The IOM recommends that “the informed consent process should be an on-going,
p.000053: interactive dialogue between research staff and research participants involving the disclosure and exchange of
p.000053: relevant information, discussion of that information, and assessment of the individual’s understanding of
p.000053: the discussion” (Recommendation 4.1, IOM, 2002). These comments emphasize how important true two-way
p.000053: communication is to comprehension, the second pillar in the informed consent process.
p.000053: The following items are a variety of issues concerning comprehension that NERL scientists should
p.000053: keep in mind as they develop an informed consent process in collaboration with the research team, the IRB and
p.000053: other peer reviewers, and EPA’s HSRRO. These items may be based on regulatory requirements or may simply be
p.000053: recommendations as ethical “best practices.”
p.000053: • Researchers need to assume responsibility for developing an interactive dialogue with
...
p.000056: (b) Decreases potential that payment would be undue inducement in some communities or locations and insufficient in
p.000056: others
p.000056: (c) Provides equivalent payment for participation across communities and locations (markets)
p.000056: (d) Less risk of undue inducement across study
p.000056: (a) Different levels of payment at different locations in multicenter research or in different communities
p.000056: (b) Unequal pay for equal work may violate one’s sense of justice
p.000056:
p.000056:
p.000056: Reimbursement Actual out-of-pocket cost to
p.000056: participant related to participation, such as parking, transportation, child care, cost of food samples, etc.
p.000056: (a) Lowers barriers to participation
p.000056: (b) Reduces burden and impact of research on participants
p.000056: (a) Few disadvantages
p.000056: (b) Possible differences in costs experienced by different participants
p.000056:
p.000056:
p.000056: Reward Token of appreciation at end of study
p.000056: (a) Expresses gratitude for contribution made
p.000056: (b) Not market dependent
p.000056: (c) Avoids undue inducement
p.000056: (a) Probably no impact on recruitment
p.000056: (b) No basis for consistency
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: for differential recruitment that could result in bias in the study sample.
p.000056: Determining appropriate level of payments or incentives for participants in a research study is
p.000056: complex. “No bright line distinguishes proper and reasonable payments to parents and children
p.000056: from payments that are inappropriate” (p. 214, IOM, 2004). The ethical issue is at what level might a
p.000056: payment change from being an incentive (an encouragement) to participate and become an inducement (the
p.000056: cause or reason) for participation. Many research organizations and IRBs do not have written policies or
p.000056: guidelines
p.000056:
p.000056: regarding the determination of reasonable payment. Decisions often are made based on the level
p.000056: of discomfort and burden, costs to participants, and population characteristics. However, large
p.000056: differences in payment levels have been found even in multisite studies in which the same protocol is
p.000056: administered across all sites.
p.000056: Grady et al. (2005) performed a survey of practices for paying research participants in the United States in
p.000056: Phase 1 to 4 clinical trials and physiologic, behavioral, and other types of research. Across 467
p.000056: studies of varying complexity that included payments, the median
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: payment was $155 (mean $266, range $5 to $2,000). The basis for dollar amounts was infrequently described, with
p.000057: 19% of the payments based on time, and 12% based on the procedures. In a model of payment factors,
p.000057: studies with some prospect of therapeutic benefit, studies having at least one invasive procedure, and studies with
p.000057: greater numbers of clinic visits were significantly associated with higher dollar amounts. About 9.5%
p.000057: of the studies offered completion bonuses, and a similar percentage offered escalating payments for
p.000057: followup study visits.
p.000057:
...
p.000057: review committees, including IRBs, need to consider many factors when determining when it is appropriate to
p.000057: offer payments to research participants and the level and form of payments when they are appropriate. Review
p.000057: committees also should consider how and when information on payments is communicated to prospective study
p.000057: participants.
p.000057:
p.000057:
p.000058: 58
p.000058:
p.000058:
p.000058: Text Box 5-4. Weighing the Ethical Issues About Payments
p.000058: Concerns about Payments Reasons for Payments
p.000058: • Payments may compromise • Recognizing participant voluntary participation.
p.000058: contributions to the
p.000058: • Participants may accept risks research and knowledge they would not otherwise gained
p.000058: accept. • Providing reimbursement
p.000058: • Participants may continue in a for direct and indirect research study beyond a point
p.000058: participant costs
p.000058: they might ordinarily have • Providing reasonable withdrawn.
p.000058: payment for the time and
p.000058: • Payments may differentially effort associated with encourage research
p.000058: participation in research participation by economically • Providing incentives for disadvantaged people.
p.000058: participation in studies
p.000058: • The offer of payments may with low risk but no or few cause guardians or parents to
p.000058: direct benefits
p.000058: not act in the best interests of • It is the just and fair thing incompetent persons or children to do
p.000058: for those who bear in their care. burdens of research on
p.000058: • Persons in different behalf of society. circumstances may view the
p.000058: same amount of payment quite differently.
p.000058: • Payments may alter the composition of the study sample and potentially could compromise study integrity.
p.000058: activities is thus justified on the grounds of fairness” (p. 112, NRC & IOM, 2005).
p.000058: Similarly, the IOM Committee on Clinical Research Involving Children found that “certain types of
p.000058: payments to parents or adolescents are usually if not always acceptable, for example, reimbursement
p.000058: for reasonable expenses that are necessary for research participation. The specifics may vary, but
p.000058: examples of reasonable expenses are costs of transportation to the research site, parking, lodging, meals,
p.000058: and babysitting. Other payments are never appropriate in pediatric research, for example, paying parents
p.000058: for the use of their child in research” (pp. 225-6, IOM, 2004).21
p.000058: The IOM committee recommends establishing policies on acceptable and unacceptable types of
p.000058: payments. They also recommend that the policies disclose any recompense in a full and open
p.000058: process,22 while not overemphasizing any recompense.
p.000058: Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
p.000058: benefits, or they may be particularly vulnerable to undue influence resulting from the offer of a payment for
p.000058: research participation. In addition, payments made directly to parents or guardians could alter
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
p.000058: gestures of appreciation, investigators may also—if they minimize the potential for undue influence—act ethically to
p.000058: reduce certain barriers to research participation when they
p.000058: • reimburse reasonable expenses directly related to a child’s participation in research
p.000058: • provide reasonable, age-appropriate compensation for children based on the time involved in research that does not
p.000058: offer the prospect of direct benefit, and
p.000058: • offer evening or weekend hours, on-site child care, and other reasonable accommodations for parental work and
p.000058: family commitments.”
p.000058: 22 In recommending an open process, the IOM committee chose to reject the
p.000058: arguments from the American Academy of Pediatrics that “any token payment to children for participating in research
p.000058: should not be discussed with them until after research is completed for fear of unduly influencing their decisions
p.000058: (AAP, 2003)…. On balance, the committee agrees that it is best to mention token or other payments during the permission
p.000058: and assent processes” (p. 215, IOM, 2004).
p.000058: The IOM Recommendation 6.1 states, “Institutional review boards, research institutions, and sponsors of research that
p.000058: includes children and adolescents should adopt explicit written policies on acceptable and unacceptable types and
p.000058: amounts of payments related to research participation. These policies should specify that investigators
p.000058: • Disclose the amount, the recipient, the timing, and the purpose (e.g., an expense reimbursement or a token of
p.000058: appreciation to a child) of any payments as part of the process of seeking parents’ permission, and, as appropriate,
p.000058: children’s assent to research participation;
p.000058: • Avoid emphasis on payments or descriptions of payments as benefits of participating in research during the
p.000058: permission or assent procedures; and
p.000058: • Obtain institutional review board approval for the disclosure of information about payments in advertisements and
p.000058: in permission and assent forms and procedures.”
p.000058:
p.000058:
p.000059: 59
p.000059:
p.000059: participate in research are unacceptable. The European Union requires that clinical trials on minors
p.000059: be undertaken only if “no incentives or financial inducements are given except compensation”
p.000059: (European Parliament, 2001).
p.000059: Payment for participation of children in research also is discussed in the literature. Diekema
p.000059: (2005) emphasizes the need to ensure that payments do not distort parental decisionmaking and do not tempt
p.000059: parents to consider other issues than the welfare of their child. Similarly, Menikoff (2005) suggested that
p.000059: there need to be relatively robust protections in place to ensure that families do not change their behaviors
p.000059: to participate in a study. He suggested that these may include determining payment as a percentage of a family’s
p.000059: income and developing criteria for documenting that behaviors have not changed to be eligible for participation in a
p.000059: study. He suggested that, for a study of pesticides, potential study participants provide documentation (such as
p.000059: receipts) that they routinely have been using a commercial pesticide service. This may be difficult
p.000059: for potential participants to do if they do not save receipts, and it would exclude all potential
p.000059: participants who purchase products and apply pesticides themselves. This likely would affect the study
p.000059: objectives and generalizability of the data collected. A survey of investigators (Iltis et al., 2006) found that
p.000059: payments were made in 52% of the pediatric research studies surveyed, and that payment practices varied,
p.000059: as did the reasons for decisions regarding payments. They found a range of payment values separated
p.000059: across cash, gifts, items, vouchers, and other categories. A survey of IRBs (Weise et al., 2002) found that payment
p.000059: for participation in research was allowed by 66% of responding institutions, but that many IRBs did not have
p.000059: specific policies, and that there was considerable variability regarding the basis for decisions on
p.000059: payments in studies with children. The types of payments included money, certificates, and bonds with large
p.000059: ranges in the amounts of payments for approved pediatric research. This research shows a lack of consistency and
p.000059: the need for guidance and institutional policies that describe acceptable and unacceptable
p.000059: payments and the basis for the amount of any payments.
p.000059: The NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children
p.000059: described many of the ethical considerations, practices, and policies regarding payments (NRC & IOM, 2005)
p.000059: for research conducted in the participants’ homes, rather than in a clinical facility. The research
p.000059: setting is similar to the setting of most observational
p.000059: human exposure studies, and the committee’s commentary and recommendations are also relevant. The
p.000059: committee notes that it would be unfair to expect families to make considerable sacrifices to
p.000059: participate in a time-consuming activity designed to advance generalizable scientific knowledge,
p.000059: rather than benefit themselves directly, and that payment for reimbursement of expenses and modest payment for
p.000059: time spent in research activities is justified on the grounds of fairness. But the committee then warns that if
p.000059: payments are too high, they may distort parents’ decisions about enrolling their children. The committee also
p.000059: found that “how the payment is made may also result in undue influence. For example, if payment for a long-term
p.000059: follow-up study is made in a lump sum and only if the subjects complete the entire study, then it
p.000059: could constitute an undue influence to stay in the study. If, on the other hand, the money is paid weekly, the
p.000059: effect would not constitute an undue influence.”
p.000059: The NRC & IOM committee recognizes that the issue of payment for participation in research is
p.000059: controversial. They also discuss how “countervailing ethical guidelines” may complicate the issues even more.
p.000059: Citing Wendler et al. (2002), the NRC & IOM committee points out that payments that are trivial
p.000059: for some families may be substantial for low-income or disadvantaged families. “Yet to pay
p.000059: economically disadvantaged families less than more affluent families for participating in the research is
p.000059: unfair because it requires similar sacrifices of time and inconvenience from both” (p. 113, NRC & IOM, 2005).
p.000059: Similar ethical quandaries can arise in multisite studies with differing costs for living. If the same payment
p.000059: is used in high-cost cities as in low-cost areas, the payment may be inadequate to gain sufficient
p.000059: enrollment in the high-cost area, whereas the same dollar amount may be “coercive” in the low-cost area. The NRC & IOM
...
p.000063: discussion about payment issues in long-term studies in Section 5.2.3.)
p.000063: People are more likely to continue active participation in longitudinal studies when they
p.000063: believe that the research is important, and that they are making a valuable contribution, are receiving regular
p.000063: feedback, and are treated with courtesy and respect by researchers. Observational human exposure studies
p.000063: sometimes involve substantial burdens of time and effort. Over long periods, this level of burden can reduce retention.
p.000063: It may be necessary to develop novel methods that reduce participant time and effort or to focus the study
p.000063: design so that fewer study procedures are implemented at any time point. Because the time needed to analyze
p.000063: samples, verify results, and perform data analyses can be long, it may be difficult to provide timely
p.000063: feedback to participants in observational human exposure studies. Researchers might consider including
p.000063: simple measures that can provide immediate and useful information of value to participants to
p.000063: encourage continued participation. Effective use of these strategies will reduce the need for
p.000063: higher payments to encourage retention.
p.000063:
p.000063: 5.7 Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk
p.000063: Researchers and IRBs need to ensure that the procedures and materials used to recruit and retain study
p.000063: participants in observational human exposure studies do not “undermine free and informed consent by leading
p.000063: parents to expose their children to unacceptable risks. (NRC and IOM, 2005)” Payments in these
p.000063: studies should not be so high that they would cause an undue
p.000063: inducement for a participant to use a product they would not normally use or to perform an activity that they
p.000063: would not normally perform. Not only would this bias the study results but may lead to higher than
p.000063: normal levels of exposure. Alternatively, the act of studying one set of conditions or activities in an observational
p.000063: human exposure study could lead participants to assume that those conditions or activities involve substantial
p.000063: risk. In response, they subsequently may change their activities in ways that could lead to possibly higher
p.000063: risks. The potential for such unintentional outcomes is difficult for researchers to gauge but requires
p.000063: researcher caution in how information and results are conveyed. However, if the informed consent process is
p.000063: truly “an on-going, interactive dialogue . . . involving the disclosure and exchange of relevant
p.000063: information,” then such misunderstandings should be minimized.
p.000063:
p.000063: References
p.000063: AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric and Environmental Health. (2nd
p.000063: Edition). Elk Grove Village, IL: American Academy of Pediatrics.
p.000063:
p.000063: Ackerman TF (1989). An ethical framework for the practice of paying research subjects. IRB 11(4):1-4.
p.000063:
...
p.000084:
p.000085: 85
p.000085:
p.000085: trust and credibility. Therefore, the approach to communication in observational human exposure
p.000085: studies should consider these factors, and communication materials should be developed with these
p.000085: factors in mind.
p.000085:
p.000085: Text Box 7-4. Activities and Materials That May Be Useful in a Communication Plan
p.000085: • Flyers
p.000085: • Web sites
p.000085: • Brochures
p.000085: • Interviews
p.000085: • Newsletters
p.000085: • Focus groups
p.000085: • Presentations
p.000085: • Direct mailings
p.000085: • Press releases
p.000085: • Questions and answers
p.000085: • Desk statements (government)
p.000085: • Abstracts
p.000085: • Study reports
p.000085: • Talking points
p.000085: • Community meetings
p.000085: • Stakeholder meetings
p.000085: • Technical presentations
p.000085: • Study participant meetings
p.000085: • Scientific meeting presentations
p.000085: • Peer-reviewed scientific journal manuscripts
p.000085: • Final reports describing the total research effort
p.000085:
p.000085: When developing communication materials, the researcher should consider the needs of the reader,
p.000085: listener, or viewer with respect to content, scope, style, and the level at which the materials are written.
p.000085: There are many sources of information on design of informational materials, such as flyers or
p.000085: brochures. For example, Alderson (1995) provides an example of the recommended content and style for information
p.000085: leaflets (that also may be flyers or brochures) for pediatric medical research. She suggests that leaflets be
p.000085: provided to parents of children who will be study participants that can be read to the children. She recommends that
p.000085: these be provided at the time that the parent is being informed of the study, prior to requesting the informed
p.000085: consent. The content of the leaflet would include the following topics.
p.000085: • Nature and purpose of the research
p.000085: • Anticipated benefits of the research
p.000085: • Risks, harms, costs, and inconvenience to the participant
p.000085: • Assurance that the participant freely can refuse to participate in or withdraw from the study
p.000085: • Details about remuneration
p.000085: • Names of the project sponsors and the researchers
p.000085: • Contact information for the researchers
p.000085: • Respect for privacy and confidentiality
p.000085: Leaflets and brochures that contain this information provide a tool for communication with study
p.000085: participants. However, these materials need to be written carefully using everyday terms that the
p.000085: average nonresearcher can understand. The brochure should be written in a friendly style that conveys the intent
p.000085: of the researcher to engage the reader as a collaborator on the study, not as a study “subject,” who will be told to do
p.000085: a series of tasks while participating in the study.
p.000085: These same leaflets and brochures can be used to inform other groups that either may be involved or
p.000085: interested in the study, such as community representatives, stakeholder organizations,
...
p.000091: and honesty, and concern and care (Peters et al., 1997). These factors are important to consider in
p.000091: developing the information and approach that will be used to respond to criticism.
p.000091: There is a large volume of information available on “crisis communication” that the reader can use to
p.000091: develop a plan for anticipating and responding to criticism (e.g., FCN, 2001; ATSDR, 2007; U.S.
p.000091: HHS,
p.000091: 2002). The key is to be proactive and have a plan before any criticism is raised.
p.000091:
p.000091: 7.10 Responding to the Media, Public Inquiries, and Other Stakeholders
p.000091: Like crisis communications, the communication plan should include detailed plans for how to interact with the
p.000091: stakeholders, the media, and the public. Standard approaches have been developed for
p.000091: effective communications (e.g., the Federal Communicators Network's Communicators Guide [FCN, 2001]) with
p.000091: the media and will not be included in this document. A proactive plan, open and transparent
p.000091: communications, and easily to comprehend information will ensure effective communications with
p.000091: stakeholders and the public.
p.000091:
p.000091: References
p.000091: American Conference of Governmental Industrial Hygienists (ACGIH) (2008). TLV/BEI Resources. Available:
p.000091: http://www.acgih.org/tlv/.
p.000091:
p.000091: Alderson P (1995). Will you help us with our research? Arch Dis Child 72(6):541-42.
p.000091:
p.000091: Anderson B, Hall B (1995). Parents’ perceptions of decision making for children. J Law Med Ethics 23(1):15-9.
p.000091:
p.000091: ATSDR (Agency for Toxic Substances and Disease Registry) (2007). A Primer on Health Risk Communication Principles
p.000091: and Practices [online publication]. Available: http://www.atsdr.cdc.gov/risk/riskprimer/ [accessed 12 June 2007].
p.000091:
p.000091: CDC (Centers for Disease Control and Prevention) (2005). Third National Report on Human Exposure to Environmental
p.000091: Chemicals. National Center for Environmental Health, Atlanta, GA, NCEH Pub. No. 05 0570. Available:
p.000091: http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf [accessed 12 June 2007].
p.000091:
p.000091: Covello V, Allen F (1988). Seven Cardinal Rules of Risk Communication. OPA-87-020. U.S. Environmental Protection
p.000091: Agency, Office of Policy Analysis, Washington, DC. Distributed by the Pennsylvania Dept. of Environmental Resources.
p.000091: Available: http://www.epa.gov/stakeholders/pdf/risk.pdf [accessed 12
p.000091: June 2007].
p.000091:
p.000091: Covello VT, McCallum DB, Pavlova M (eds) (1989). Effective Risk Communication: the role and responsibility of
p.000091: Government and Non-Government Organizations. New York. NY: Plenum Press.
p.000091:
p.000091: Covello V, Minamyer S, Clayton K (2007). Effective risk and crisis communication during water security emergencies
...
Social / philosophical differences/differences of opinion
Searching for indicator opinion:
(return to top)
p.000090: back-calculation of doses from urinary metabolite concentrations using few assumptions and is
p.000090: consistent with current pesticide regulatory procedures for risk assessment. When using this approach, the
p.000090: research team will need to determine how conservative the reporting level should be, as there are no guidelines
p.000090: available for using this approach. If the concentrations of a metabolite measured in a study participants’
p.000090: urine level are indicative of elevated exposures (i.e., above the reporting level), the
p.000090: researchers would be expected to report the information to the participants and provide information or local
p.000090: contacts that could assist in helping the participants identify sources of exposure and reduce their exposures.
p.000090: Although this would seem to be a reasonable approach for some classes of chemicals, the authors are not aware
p.000090: of reports of the use of this approach in the scientific literature.
p.000090:
p.000090: 7.9 Anticipating and Responding to Criticism
p.000090: As discussed in other parts of this document, in spite of researchers best intentions, there may be situations
p.000090: that arise in which people’s perceptions of the study design or implementation plan are not accurate, or their
p.000090: opinions and beliefs about the ethical issues associated with a study may not be in agreement with those of the
p.000090: research team and others involved in the study (e.g., the peer review panel, the IRB). Just as it is
p.000090: not unreasonable to expect differences in opinion on scientific approaches to an observational study, it is
p.000090: not unreasonable to expect differences of opinion on ethical approaches. The researchers, therefore, should
p.000090: be prepared to respond to criticism. The implementation plan and the communication plan should address
p.000090: how the research team should anticipate study elements that may be criticized. During study
p.000090: conceptualization, the research team should develop a list of potentially controversial study
p.000090: elements (many of which are discussed in this document). For each study element, the research team should
p.000090: describe how the ethical approaches to the study element were evaluated and selected. Both the
p.000090: process and the rationale for selection of a particular approach should be documented. At each step in the study
p.000090: planning and review process, the research team should document discussions related to
p.000090:
p.000090:
p.000091: 91
p.000091:
p.000091: the specific element, considerations that were made, actions taken, and justification for the actions.
p.000091: Input from research team members, internal reviewers, external reviewers, community members, and
p.000091: others involved in the study should be documented for these controversial study elements. Similarly, for
p.000091: potentially controversial study elements, the review and actions by the IRB should be documented. All of this
p.000091: information should be compiled for potential use to prepare a set of Q&As that can be used by the
p.000091: research team and sponsoring organization to respond to criticism. When responding to criticism, establishing
p.000091: trust and credibility are essential, as discussed previously. The public’s perception of trust and
...
Searching for indicator philosophy:
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p.000105: provide recommendations on state-of-the-science approaches for them.
p.000105:
p.000105: The following individuals were members of the Expert Panel.
p.000105:
p.000105: Timothy Buckley (Chair)
p.000105: Division of Environmental Health Sciences School of Public Health
p.000105: Ohio State University Columbus, OH
p.000105:
p.000105: Sophie Balk
p.000105: Attending Pediatrician
p.000105: Children’s Hospital at Montefiore Professor of Clinical Pediatrics Albert Einstein College of Medicine Bronx, NY
p.000105:
p.000105: David Carpenter
p.000105: Director, Institute of Health and Environment University of Albany, SUNY
p.000105: Rensselaer, NY
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000107: 107
p.000107:
p.000107: Giselle Corbie-Smith Department of Social Medicine University of North Carolina Chapel Hill, NC
p.000107:
p.000107: Alan Fleischman
p.000107: Senior Advisor
p.000107: The New York Academy of Medicine New York, NY
p.000107:
p.000107: Natalie Freeman
p.000107: Center for Environmental and Human Toxicology Department of Physiological Sciences
p.000107: University of Florida Gainesville, FL
p.000107:
p.000107: Loretta Jones
p.000107: Healthy African American Families Los Angeles, CA
p.000107:
p.000107: Bruce Lanphear
p.000107: Professor of Pediatrics and of Environmental Health Division of General and Community Pediatrics Cincinnati Children’s
p.000107: Hospital Medical Center Cincinnati, OH
p.000107:
p.000107: Michael Lebowitz
p.000107: Arizona Health Sciences Center Colleges of Public Health and Medicine University of Arizona
p.000107: Tucson, AZ
p.000107:
p.000107: Jerry Menikoff
p.000107: Department of History and Philosophy of Medicine University of Kansas Medical Center
p.000107: Kansas City, KS
p.000107:
p.000107: Rebecca Parkin
p.000107: Associate Dean for Research and Public Health Practice Professor of Environmental and Occupational Health School of
p.000107: Public Health and Health Service
p.000107: George Washington University Medical Center Washington, DC
p.000107: Review by the EPA Human Studies Review Board and Public Comment
p.000107: The process for developing this document included the following steps after the Expert Panel Workshop.
p.000107: • A draft document was written by NERL researchers.
p.000107: • The draft document was distributed to internal EPA staff for review and comment (see Acknowledgements for the
p.000107: list of reviewers).
p.000107: • The draft document was revised to address internal reviewer comments; an external review draft
p.000107: document was prepared.
p.000107: • The availability of the external review draft document for public comment was announced in a Federal Register
p.000107: notice.
p.000107: • An EPA docket was opened, and the external review draft document was available for public comment for 45 days.
p.000107: • The external review draft document also was provided to EPA’s Human Studies Review Board (HSRB) for review
p.000107: and comment (see http://www.epa.gov/osa/hsrb/ for information on the
p.000107: HSRB).
p.000107: • The review by HSRB was announced in a Federal Register notice.
p.000107: • HSRB met October 21-24, 2007, and discussed the document during the meeting.
p.000107: • HSRB provided EPA with comments on the document in their final report of the October meeting.
p.000107:
p.000107: The charge to the HSRB for the SEAOES document review was that shown just below.
p.000107:
...
p.000111: (38) The circumstances in which it might be considered inappropriate to publish findings, such as when the findings
p.000111: of any study may present risks to or stigmatize the interests of a community or
p.000111: population or of a racially or ethnically defined group of people
p.000111: (39) A statement that any proven evidence of falsification of data will be dealt with in accordance
p.000111: with the policy of the sponsor to take appropriate action against such unacceptable procedures
p.000111:
p.000111: Source: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical
p.000111: Guidelines for Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland.
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000112: 112
p.000112:
p.000112:
p.000112:
p.000112:
p.000112:
p.000112:
p.000112:
p.000112: Appendix D
p.000112: Recommendations for Enhancing Public Trust
p.000112:
p.000112:
p.000112:
p.000112: Although the Report and Recommendations on Public Trust in Clinical Research for the NIH Director from the
p.000112: Director’s Council of Public Representatives (COPR) was developed in the context of NIH-supported clinical
p.000112: research, many of the recommendations are applicable to observational human exposure studies. A summary of
p.000112: recommendations from the report is provided below.
p.000112:
p.000112: Building Trust Through Community Partnerships
p.000112: Recommendation 1: Incorporate into the NIH mission and philosophy that it values the involvement of the
p.000112: community in research and create language that expresses this value.
p.000112: Recommendation 2: Encourage change in the culture of the scientific community to ensure that medical
p.000112: research is viewed in the context of a long- term commitment to the community, not a one-time research study.
p.000112: Recommendation 3: Investigate ways to provide mechanisms that allow for follow-up health care when a clinical
p.000112: trial or treatment ends.
p.000112:
p.000112: Building Relationships with Patients (Participants) (True partnerships with patients may not be possible, but
p.000112: bidirectional relationships must be enhanced.)
p.000112: Recommendation 4: Educate and reorient the current research community to the importance of treating the
p.000112: public as a partner in the research process.
p.000112: Recommendation 5: Set the expectation across the entire research community, NIH funded research and beyond, that
p.000112: study results and outcomes should be shared with the research participants and the larger community promptly
p.000112: and consistently. This will ensure translational research.
p.000112:
p.000112: Building Partnerships with Community Providers
p.000112: Recommendation 6: Take action to interest community providers in clinical research and
p.000112: maintain their involvement.
p.000112: Recommendation 7: Provide incentives (not just financial) for primary health care providers and community
p.000112: specialists to play a role in clinical trials.
p.000112:
p.000112: Building Trust in Scientists
p.000112: Recommendation 8: Engage researchers, educators, and academic institutions in incorporating the public's
...
Economic / Economic/Poverty
Searching for indicator poor:
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p.000024: in safe, healthy environments. In its discussion of the perception of risks and benefits, the NRC & IOM (2005) report
p.000024: on housing health hazards in children notes that the children participating in these studies may be at
p.000024: risk for physical harms or adverse health outcomes because they live in housing (or otherwise occupy
p.000024: environments) with health hazards. However, such risks are not introduced by the research but, rather, would be present
p.000024: whether or not the children were involved in a research study. As a consequence, the study still
p.000024: would meet the regulatory criteria for minimal risk as long as the research itself introduced no risks over
p.000024: and above those minimal risks
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025: experienced by normal children living in safe healthy environments.
p.000025: However, the existence of greater than minimal background risks that are not introduced by the research,
p.000025: nonetheless, raises additional ethical considerations. The joint NRC & IOM Committee on Research on Housing- Related
p.000025: Health Hazards Involving Children discussed the ethical arguments that arise when scientists conduct research that
p.000025: observes children in poor-quality housing. They point out that a researcher’s first duty of beneficence
p.000025: under the Common Rule requires that the risks of the research actions be proportionate to
p.000025: [“reasonable in relation to”; 40 CFR 26.111(a)(2)] the benefits of the research, and that the risks be
p.000025: minimized. They acknowledge, however, that some have argued that the “best interests of the child” also obligates
p.000025: researchers to “rescue” children from harm and to provide better living conditions. They conclude that,
p.000025: properly applied, the ethical principle of beneficence does indeed direct researchers who observe serious harms
p.000025: to child subjects to take steps to try to prevent the harms. However, they also argue that the researcher’s duty does
p.000025: not extend to “personally and directly prevent harm by removing the child from the harmful environment” (p.
p.000025: 60, NRC & IOM, 2005). They conclude instead that “it is unrealistic and unfair to hold individual research
p.000025: investigators responsible for ameliorating the social circumstances that they study” and that “a nuanced
p.000025: balancing of the benefits and risks of research” is an ethically sound approach that is firmly established in
p.000025: Federal regulations (p. 60, NRC & IOM, 2005). Balancing the ethical obligation to mitigate risks or
p.000025: harms observed during research with the reasonable limits on an investigator’s moral responsibility for
...
p.000029: chemicals in their real-world environment as they carry on their normal daily activities. Researchers who
p.000029: conduct these studies, however, recognize that participation in a study may affect behavior. This cannot
p.000029: always be avoided, as simply agreeing to participate in a study may impact the participant’s activities and
p.000029: schedules. For example, this occurs when technicians visit homes to collect samples or when participants
p.000029: are asked to collect samples (e.g., food, urine), or to complete surveys, activity logs, or
p.000029: questionnaires. These types of changes in behavior may or may not affect the outcome of the study.
p.000029: Some changes in behavior can affect the study outcome. The Hawthorne Effect is a well-recognized
p.000029: phenomenon. It is an effect on an outcome variable caused by the fact that the participants of the study know
p.000029: they are participating in the study. The Hawthorne Effect originally referred to the increase in worker productivity
p.000029: observed when a worker is singled out and made to feel important; the increased productivity was not related to the
p.000029: environmental factors that were being studied. The effect was described based on a series of industrial
p.000029: productivity studies from 1927 to 1932. Similarly, some changes in participant behaviors may change the
p.000029: observations, measurements, and conclusions from observational human exposure studies. For
p.000029: example, participants may do more cleaning in their home because they do not want the researchers to think they are
p.000029: poor housekeepers; this could affect the measurement of environmental concentrations in the home. In a
p.000029: study of chemicals from consumer products, participants may think that because the researchers are
p.000029: studying the products, the products must be harmful. Therefore, study participants may elect not to use the products
p.000029: during the study in the same manner as they would normally. Alternatively, prospective participants may
p.000029: choose to use more of the household product to qualify for the
p.000029: study. As a result, the participant’s exposure to the chemicals could be either more or less than “normal.”
p.000029: Any change in a participant’s behavior that is related to the research question being addressed in the study
p.000029: may impact the study results. Researchers should try to anticipate how a study may impact participant behaviors and
p.000029: ensure that the study design and implementation protocols do not cause changes in behavior that may cause
p.000029: harm to a participant during a study. A number of study elements with the potential to influence
p.000029: participants’ behavior are listed in Text Box 2-6.
p.000029:
p.000029: Text Box 2-6. Study Elements That Could Affect People’s Behavior
p.000029: • Eligibility criteria
p.000029: • Recruiting approach and materials
p.000029: • Enrollment approach
p.000029: • Payments
p.000029: • Retention strategy
p.000029: • Types of measurements made and data collected
p.000029: • Protocols for data collection
p.000029: • Protocols for visits to homes
p.000029: • Interactions with participants
p.000029: • Communications
p.000029:
...
p.000030: results can be evaluated, and these criteria and standards need to be incorporated into the study
p.000030: design, the human subjects research protocol, and the QAPP.
p.000030: In developing an approach to monitor scientific and ethical issues during the study, the research team may
p.000030: choose to
p.000030: • identify the individual, team, advisory committee, or
p.000030: data safety monitoring board (DSMB) responsible for monitoring the progress and results of the study;
p.000030: • develop roles and responsibilities;
p.000030: • develop a schedule and timeline for the activities to be conducted;
p.000030: • develop goals for interim data analysis and prepare an analysis plan;
p.000030: • identify what data will be analyzed, how it will be processed and validated, and who will perform
p.000030: the analyses;
p.000030: • develop a plan for reporting interim results to the research team;
p.000030: • develop standards for reporting scientific and ethical issues to the research team; or
p.000030: • develop criteria for evaluating scientific and ethical issues that arise during the study.
p.000030: In a well-designed observational study for which the research team has adequately prepared, it is unlikely that there
p.000030: will be scientific issues requiring that the study be stopped. Nonetheless, it is important for criteria to be
p.000030: established for when the study needs to be changed or terminated. An example might be the
p.000030: participant retention rate. In a study with repeated measurements, a certain sample size is required to obtain
p.000030: statistically significant results. If the retention rate is poor, and too many participants drop out of
p.000030: the study, it may not be possible to meet the study objectives, and early termination of the
p.000030: study may be warranted (see Text Box 2-7 for issues that warrant early termination). However, it is
p.000030: anticipated that the study design would include contingency planning (for example, related to replacement).
p.000030: Developing criteria for study elements that may have associated ethical concerns as a study progresses will no doubt be
p.000030: more difficult than reviewing the measurement data. Nonetheless, assuring the ethical safety of the participants
p.000030: is critically important. There are no standard formulas for dealing with ethical concerns. For example, if the
p.000030: privacy of a number of study participants is compromised by a technician conducting the
p.000030: measurements in their homes, what criteria should be used to evaluate the severity of the issues? How
p.000030: many landlord-participant problems are too many before the study needs to be changed to exclude
p.000030: participants who rent their dwellings? Despite the challenges, the team of people involved in the data and
p.000030: safety monitoring and oversight effort should work diligently, with input from the community, to establish
p.000030: open and continuing channels of communication with participants, the community, and stakeholders –
p.000030: with the goal of ensuring that their involvement in the research effort is, and
p.000030:
p.000030:
p.000031: 31
p.000031:
p.000031: remains to be, based on the three pillars of informed consent: (1) that the parties are fully informed of all
p.000031: of the relevant and useful information, (2) that the information is understood by the parties, and (3)
p.000031: that all parties continue to participate voluntarily. With diligent effort to continue an open dialogue with the
p.000031: involved parties – combined with thoughtful review and oversight of the technical study results and procedures
p.000031: – the monitoring and oversight team can ensure that participants are free to withdraw from the
p.000031: research at any time; are fully informed about the technical study results; understand any new
p.000031: information about relevant risks and benefits; and that the privacy and confidentiality of
p.000031: the subjects is properly protected. Through these efforts, the monitoring and oversight team will ensure that
p.000031: the welfare of the research subjects remains a focus of the study effort.
p.000031:
p.000031: Text Box 2-7. Examples of Issues That May Cause a Study To Be Stopped Early
p.000031: • Participant recruiting and enrollment⎯low response rates, disproportionate enrollment of select groups, problems
p.000031: associated with advertising, inadequate selection criteria
p.000031: • Informed consent⎯difficulties with the process and materials, poor comprehension
p.000031: • Participation⎯poor response to questionnaires, poor compliance with researcher requests in data collection
p.000031: activities
p.000031: • Burden⎯higher than predicted
p.000031: • Changes in participant behaviors⎯potential changes because of participation in the study
p.000031: • Grievances⎯participant issues
p.000031: • Retention⎯high dropout rates
p.000031: • Community issues⎯poor interactions, lack of support
p.000031: • Third-party issues⎯problems with landlords, spouses, or others
p.000031: • Collateral observations⎯identification of nonstudy hazards, difficulty reporting
p.000031: • Unanticipated results⎯high contaminant concentrations measured, unexpected results
p.000031: • New data indicating that participation in the study (or observations measured in the study) represent a risk to
p.000031: participants or others
p.000031:
p.000031:
p.000031:
p.000031: References
p.000031: Castelloe, JM (2000). Sample size computations and power analysis with the SAS system. Paper 265-25 in Proceedings of
p.000031: the 25th Annual SAS Users Group International Conference. Cary, NC: SAS Institute, Inc. Available:
p.000031: http://support.sas.com/rnd/app/papers/powersamplesize.pdf [accessed 16 April 2008].
p.000031:
p.000031: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of
p.000031: Human Subjects. U.S. Code of Federal Regulations. Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/
p.000031: 40cfr26_06.html [accessed 12 June 2007].
p.000031:
p.000031: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000031: Biomedical Research Involving Human Subjects.
p.000031: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000031:
...
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
...
p.000057: considered a benefit, it is a recruitment incentive.” FDA expects payments to accrue as the study progresses and not
p.000057: to be contingent on completing the study, although a “small proportion as an incentive for
p.000057: completion of the study is acceptable.” The guidance is concerned with the issue of coercion or undue influence, and
p.000057: it recognizes the IRB as the responsible party for deciding what is or is not acceptable.
p.000057: The U.S. Office of Management and Budget (OMB) develops standards and guidelines for statistical surveys performed by
p.000057: the Federal government. Under Guideline 2.3.2, OMB states that, while incentives are not typically used in Federal
p.000057: surveys, agencies may consider use of respondent incentives if they believe incentives would be necessary
p.000057: to use for a particular survey to achieve data of sufficient quality for their intended use (OMB,
p.000057: 2006a). OMB requires that agencies provide a justification for giving incentives to respondents.
p.000057: Some
p.000057: of the factors cited by OMB to be addressed include those particularly relevant to observational
p.000057: human exposure studies, including unusual reporting burdens (keeping data logs for extended periods,
p.000057: coordinating study team visits, participating in a medical examination, etc.), complex study designs (such as
p.000057: studies requiring ongoing participation of respondents), and past experience, especially when there is
p.000057: evidence of attrition or poor response rates (OMB, 2006b). Although OMB primarily considers incentives with
p.000057: regard to survey response rates and data quality, researchers need to consider payments to
p.000057: participants, including participation incentives, in the broader context discussed in this section.
p.000057: CIOMS also provides guidance and commentary on this issue in the International Ethical Guidelines for Biomedical
p.000057: Research Involving Human Subjects (2002). Guideline 7 and the associated commentary emphasize that payments to
p.000057: subjects for expenses incurred because of their participating in a research study are legitimate. The guideline
p.000057: also allows payment for inconvenience and time spent, so long as the payments or other direct benefits are not
p.000057: “so extensive as to induce prospective subjects to consent to participate in research against their better
p.000057: judgment.”
p.000057: The approaches of HHS, FDA, and CIOMS above are consistent in not considering payments to be a benefit
p.000057: to research participants when considering risks versus benefits. All of the guidelines recognize the
p.000057: legitimacy of some recompense, but they all are concerned with the issue of undue influence. “Payments or
p.000057: rewards that undermine a person’s capacity to exercise free choice invalidate consent” (CIOMS, 2002), and
...
p.000089: 0.010 mg/L, he or she would be expected to report the level to the study participant. For other environmental media,
p.000089: such as air, there are few applicable standards. The National Ambient Air Quality Standards might be
p.000089: used for the criteria pollutants. Guidelines for occupational exposures, such as threshold limit
p.000089: values (TLVs) and biological exposure indices (BEIs) published by the
p.000089:
p.000089:
p.000090: 90
p.000090:
p.000090: American Conference of Governmental Industrial Hygienists (ACGIH, 2008) also may be used. TLVs are not
p.000090: standards; ACGIH formulates a conclusion on the level of exposure that the typical worker can experience without
p.000090: adverse health effects. Many people would argue that the TLVs are not conservative enough for the average
p.000090: population, particularly not for vulnerable lifestages (e.g., children, the elderly) and TLVs are only for
p.000090: exposure by inhalation. WHO (2005) also publishes air quality guidelines. These types of guidelines can be used to
p.000090: advise study participants if their exposures are high relative to the guidelines. Reporting levels should
p.000090: be conservative, but not so low that reporting the level to the participant causes unwarranted concern and
p.000090: stress. For other environmental media measured in observational human exposure studies, such
p.000090: as house dust or surface wipes, the measurement results cannot be used easily to estimate exposures, and they
p.000090: are a poor metric if used alone.
p.000090: An alternative approach to comparison of measurement results against available guidelines and
p.000090: standards is the comparison of measurements in biological fluids to measurement data available from the
p.000090: National Health and Nutrition Examination Survey (NHANES). For example, results of measurements of
p.000090: chemicals or their metabolites in urine or blood can be compared to different percentiles (e.g., the
p.000090: 95th) reported in the NHANES national reports (CDC, 2005). This type of comparison shows that the participant’s
p.000090: measurements are at the high end of the distribution of the NHANES data, suggesting that action may need to be
p.000090: taken to mitigate exposures. However, researchers need to be judicious in the selection of the exposure
p.000090: metric. Biomarkers in blood and biomarkers in urine can be very different exposure metrics and may represent
p.000090: different aspects of the exposure event. A similar approach could be taken with
p.000090: measurements of chemicals in environmental media if there are sufficiently large databases
p.000090: available for comparison. For many chemicals and many media such databases are not available. In some NERL
p.000090: studies, one comparison approach that has been used is to compare an individual’s environmental
p.000090: media measurements to the 50th, 75th, or 95th percentile concentrations for the entire study population,
p.000090: so that the participant can evaluate his or her measurement results relative to those of the other study
p.000090: participants.
p.000090: A more complex approach than using simple data comparisons is to calculate a reporting level defined as a
...
Searching for indicator low-income:
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p.000059: committee notes that it would be unfair to expect families to make considerable sacrifices to
p.000059: participate in a time-consuming activity designed to advance generalizable scientific knowledge,
p.000059: rather than benefit themselves directly, and that payment for reimbursement of expenses and modest payment for
p.000059: time spent in research activities is justified on the grounds of fairness. But the committee then warns that if
p.000059: payments are too high, they may distort parents’ decisions about enrolling their children. The committee also
p.000059: found that “how the payment is made may also result in undue influence. For example, if payment for a long-term
p.000059: follow-up study is made in a lump sum and only if the subjects complete the entire study, then it
p.000059: could constitute an undue influence to stay in the study. If, on the other hand, the money is paid weekly, the
p.000059: effect would not constitute an undue influence.”
p.000059: The NRC & IOM committee recognizes that the issue of payment for participation in research is
p.000059: controversial. They also discuss how “countervailing ethical guidelines” may complicate the issues even more.
p.000059: Citing Wendler et al. (2002), the NRC & IOM committee points out that payments that are trivial
p.000059: for some families may be substantial for low-income or disadvantaged families. “Yet to pay
p.000059: economically disadvantaged families less than more affluent families for participating in the research is
p.000059: unfair because it requires similar sacrifices of time and inconvenience from both” (p. 113, NRC & IOM, 2005).
p.000059: Similar ethical quandaries can arise in multisite studies with differing costs for living. If the same payment
p.000059: is used in high-cost cities as in low-cost areas, the payment may be inadequate to gain sufficient
p.000059: enrollment in the high-cost area, whereas the same dollar amount may be “coercive” in the low-cost area. The NRC & IOM
p.000059: committee notes that a similar situation can arise when a study enrolls participants from diverse
p.000059: socioeconomic backgrounds. There are social justice concerns that poorer people might incur a disproportionate
p.000059: share of research risk and burden if payments induce unequal participation rates in the population. Decisions
p.000059: regarding payment for research participation will require careful consideration by IRBs when economically
p.000059: disadvantaged people may be enrolled. Community advisory boards (CABs) can be very important in helping
p.000059: researchers and IRBs determine what is appropriate with regard to payments within their community.
p.000059:
p.000059:
p.000059:
p.000059:
p.000060: 60
p.000060:
p.000060: 5.2.4 Payments in Observational Human Exposure Studies
p.000060: Observational human exposure studies most often involve minimal risks to study participants and few direct
p.000060: benefits, but may require considerable time and burden for participation. Study requirements can include multiple
...
Searching for indicator social status:
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p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
p.000035: broader definition of vulnerability as it relates to education, economics, social status, and other factors. As
p.000035: shown in Text Boxes 3-1 and 3-2 and described above, the concept of vulnerability is broader than that
p.000035: presented in the Common Rule. It is not adequate to simply check the list in Text Box 3-1 to identify if a potentially
p.000035: vulnerable group is included in an observational study. The researchers should assess the potential
p.000035: vulnerability of a study population within the study by evaluating the characteristics (e.g., socioeconomic
p.000035: status) of the study population within the context of the study by considering the various design elements of the
p.000035: study, as discussed in Section 2.
p.000035: 12 In the commentary on Guideline 13 in CIOMS (2002), the committee states that the central problem presented by plans
p.000035: to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
...
General/Other / Dependent
Searching for indicator dependent:
(return to top)
p.000044: Study participants should be made aware of statutory requirements for reporting collateral observations as part of the
p.000044: informed consent process. Researchers should include the reporting requirements in the informed
p.000044: consent form (discussed in Section 5) and should ensure that the study participant fully comprehends this
p.000044: information and the impact on their privacy and confidentiality.
p.000044:
p.000044: 4.3.3 Hazard Communication
p.000044: It is difficult for researchers to determine when and how to communicate with study participants or third
p.000044: parties about collateral observations related to potential hazards. A hazard might present such an imminent
p.000044: threat to health or safety that staff would need to communicate immediately with the participant or take
p.000044: action to mitigate the threat. In some cases, such as instances of abuse with attendant statutory reporting
p.000044: requirements, it may be necessary to breach confidentiality. More often, however, a potential hazard identified as
p.000044: a result of collateral observation may not be an imminent threat or pose a potential risk that is situation
p.000044: dependent or is related to third parties. A number of considerations in hazard communication come
p.000044: into play regarding confidentiality, privacy, the ability of the researcher to provide accurate and
p.000044: effective information regarding the hazard and hazard mitigation, and the ability of the study participant or others
p.000044: to effectively mitigate the hazard without unintended adverse consequences. The National Academy of Sciences
p.000044: Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children, Youth, and
p.000044: Families discussed many of these issues in depth (NRC & IOM, 2005).
p.000044: Different communities, cultures, or demographic groups can have different risk perceptions, which may
p.000044: affect how collateral observations are assessed and reported from one study location to the next. The AAP
p.000044: Committee on Environmental Health has prepared information regarding perception, identification, and
p.000044: communication of environmental health risks (AAP, 2003). Researchers likely will benefit from including
p.000044: community members on the research team in developing the study design and research protocol or from
...
p.000054: will involve (NCS, 2007).
p.000054: • Development of written materials with appropriate languages and comprehension levels is only part of the
p.000054: communication challenge. In communities where languages other than English are spoken, it will be
p.000054: important that the research team be able to communicate orally with participants, often in ad hoc
p.000054: situations. Research protocols should address how translations will be accomplished. The use of
p.000054: untrained persons such as co-workers usually will not meet requirements for full understanding of human subject
p.000054: protections. Researchers should make plans for trained staff or trained community members, associated
p.000054: or affiliated with the research study, to be available for translations.
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
...
p.000056: (a) May have little impact on recruitment
p.000056: (b) Might undercompensate some subjects in relation to regular wage and preferentially attract others
p.000056:
p.000056:
p.000056: Provide “wage” for time and effort; base level of payment on some small fraction of participant’s or the community’s
p.000056: income, or on an appropriate hourly rate for the location, or on community-input about the appropriate level of payment
p.000056: (a) Recognizes contributions of participants
p.000056: (b) Decreases potential that payment would be undue inducement in some communities or locations and insufficient in
p.000056: others
p.000056: (c) Provides equivalent payment for participation across communities and locations (markets)
p.000056: (d) Less risk of undue inducement across study
p.000056: (a) Different levels of payment at different locations in multicenter research or in different communities
p.000056: (b) Unequal pay for equal work may violate one’s sense of justice
p.000056:
p.000056:
p.000056: Reimbursement Actual out-of-pocket cost to
p.000056: participant related to participation, such as parking, transportation, child care, cost of food samples, etc.
p.000056: (a) Lowers barriers to participation
p.000056: (b) Reduces burden and impact of research on participants
p.000056: (a) Few disadvantages
p.000056: (b) Possible differences in costs experienced by different participants
p.000056:
p.000056:
p.000056: Reward Token of appreciation at end of study
p.000056: (a) Expresses gratitude for contribution made
p.000056: (b) Not market dependent
p.000056: (c) Avoids undue inducement
p.000056: (a) Probably no impact on recruitment
p.000056: (b) No basis for consistency
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: for differential recruitment that could result in bias in the study sample.
p.000056: Determining appropriate level of payments or incentives for participants in a research study is
p.000056: complex. “No bright line distinguishes proper and reasonable payments to parents and children
p.000056: from payments that are inappropriate” (p. 214, IOM, 2004). The ethical issue is at what level might a
p.000056: payment change from being an incentive (an encouragement) to participate and become an inducement (the
p.000056: cause or reason) for participation. Many research organizations and IRBs do not have written policies or
p.000056: guidelines
p.000056:
p.000056: regarding the determination of reasonable payment. Decisions often are made based on the level
p.000056: of discomfort and burden, costs to participants, and population characteristics. However, large
p.000056: differences in payment levels have been found even in multisite studies in which the same protocol is
p.000056: administered across all sites.
p.000056: Grady et al. (2005) performed a survey of practices for paying research participants in the United States in
p.000056: Phase 1 to 4 clinical trials and physiologic, behavioral, and other types of research. Across 467
p.000056: studies of varying complexity that included payments, the median
p.000056:
p.000056:
p.000057: 57
p.000057:
...
p.000067: Flexibility Anticipate changes within the community in
p.000067: regard to perceived benefits of research and stakeholder interest and additional time and resource needs.
p.000067:
p.000067: Commitment Prepare to engage the community beyond the constraints of the research projects, before and after,
p.000067: to promote longevity of the relationship for future research .
p.000067:
p.000067:
p.000067: Furthermore, institutional and community partners need to ensure that anyone involved as part of the
p.000067: research team has the requisite research and social skills. Researchers often place a greater emphasis on scientific
p.000067: over social skills and may, in turn, assume that they have
p.000067:
p.000067:
p.000068: 68
p.000068:
p.000068: the necessary expertise to conduct research in community settings. Likewise, research staff from
p.000068: the community should have knowledge of research fundamentals. Education and training targeted at
p.000068: both the institutional researcher and the community researcher may, respectively, improve the competence
p.000068: of researchers to work with communities and the scientific literacy of the public.
p.000068: A recent NERL study, the Detroit Exposure and Aerosol Research Study (DEARS), included community members as
p.000068: paid members of the research team. The community researchers were instrumental in recruiting study
p.000068: participants from the seven study neighborhoods in Detroit that required multiple door-to-door visits to
p.000068: the homes of potential participants to discuss the DEARS study. The success of DEARS was dependent
p.000068: on researchers developing strong relations with community leaders and State and local organizations.
p.000068: A second approach to community involvement is to seek community consultation and review. Researchers may
p.000068: periodically meet with community residents in a process of “engagement, dialogue, and feedback” (Dula, 1994) to
p.000068: discuss research plans, research progress, and results. The objective is to seek a dialogue with
p.000068: community residents to promote co-learning and asset sharing between the researchers and the community.
p.000068: Effective communication⎯open, honest, jargon free⎯is imperative to the successful use of this approach.
p.000068: Effective communication ensures that the community has a voice in the research process for the expressed
p.000068: purpose of increasing the community’s trust and engagement in the research, the applicability of the
p.000068: research to the community’s needs, and the benefit of the research to the community. Authentic community
p.000068: consultation embraces the “experiential knowledge of the average citizen” (Leung et al., 2004). When
p.000068: developing research budgets and timescales, researchers who plan to incorporate community consultation and review
p.000068: in the research process should take into account the additional expenses and time necessary for
p.000068: community marketing efforts and travel.
p.000068: Corburn (2002) describes a successful community participation in an EPA exposure assessment in
...
p.000117: Observational research. Any human research that does not meet the definition of research involving intentional
p.000117: exposure of a human subject [40 CFR 26.302]
p.000117: Privacy. Control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or
p.000117: intellectually) with others
p.000117: Research. A systematic investigation, including research development, testing, and evaluation, designed to develop or
p.000117: contribute to generalizable knowledge
p.000117: Research involving intentional exposure of a human subject. A study of a substance in which the exposure to the
p.000117: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
...
General/Other / Diminished Autonomy
Searching for indicator diminished:
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p.000008: Since 1991, ethical thought and regulatory processes for the protection of human subjects have continued to
p.000008: evolve and grow. For example, many ethicists expand the elements contained in the principle of
p.000008: beneficence from the Belmont Report into two principles:
p.000008: (1) beneficence, meaning to prevent or remove harm and
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: to maximize the possible benefits; and
p.000009: (2) nonmaleficence, meaning not to inflict harm (Beauchamp and Childress, 2001).
p.000009:
p.000009: Table 1-2. The Belmont Report— Principles and Recommendations
p.000009:
p.000009: Ethical Principle Regulatory Manifestation
p.000009: addressed many important scientific and ethical issues on this topic, including the National Research
p.000009: Council (NRC) in its report, Protecting Participants and Facilitating Social and Behavioral Sciences
p.000009: Research (NRC, 2003), a joint NRC and Institute of Medicine (NRC & IOM, 2005) committee in the report on
p.000009: Ethical Considerations for Research on Housing-Related Health Hazards Involving Children; the Council
p.000009: for
p.000009:
p.000009: Respect for Persons
p.000009: • Individuals should be treated as autonomous agents.
p.000009: • Persons with diminished autonomy are entitled to protection.
p.000009:
p.000009: Beneficence
p.000009: • Human subjects should not be harmed.
p.000009: • Research should maximize possible benefits and minimize possible harms.
p.000009: Justice
p.000009: • The benefits and risks of research must be distributed fairly.
p.000009: Informed Consent
p.000009: • Subjects must be given the opportunity to choose what will or will not happen to them
p.000009: • The consent process must include
p.000009: (1) information,
p.000009: (2) comprehension, and
p.000009: (3) voluntariness
p.000009: Assessment of Risks and Benefits
p.000009: • The nature and scope of risks and benefits must be assessed in a systematic manner.
p.000009:
p.000009:
p.000009: Selection of Subjects
p.000009: • There must be fair procedures and outcomes in the selection of research subjects.
p.000009: International Organizations of Medical Sciences (CIOMS) under the World Health Organization in
p.000009: its International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002) and
p.000009: in the International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008); and
p.000009: the National Ethics Advisory Committee of New Zealand in the Ethical Guidelines for Observational Studies:
...
p.000068: explain the study to potential participants. CABs should be sufficiently large to ensure a diversity of
p.000068: community views, perspectives, and attitudes. Representatives from the board may be selected for
p.000068: participation on the research team. In Section 5, it was noted by the authors that such a board could function
p.000068: as an oversight committee in case of any participant grievances. According to Quinn (2004), the
p.000068: success of CABs “lies in the ability of the researchers and CABs to form a true partnership, enabling their different
p.000068: voices to be heard equally.” Creating a CAB may be perceived as “window dressing” and, in fact, harm relationships with
p.000068: the community if researchers are not truly open to working with the CAB.
p.000068: O’Fallon and Dearry (2002) describe how the Tribal Efforts Against Lead (TEAL) partnership collaborated with EPA
p.000068: to clean up and minimize exposure to toxins from a Superfund site in Ottowa County, OK. The TEAL project
p.000068: utilized the services of a CAB, which included representatives from several local tribes, to ensure that
p.000068: the research would be responsive to the needs and concerns of the tribal residents. The CAB facilitated the researchers
p.000068: interactions with the target communities “by helping the investigators interpret data and distribute information to
p.000068: the communities” and “developing and conducting the training” of the community members on risk reduction
p.000068: strategies. The value of the research to the TEAL target communities would have been diminished had a CAB not been
p.000068: formed to assist the researchers with specific best practices to use when engaging the tribal members and
p.000068: the appropriate tribal leadership structures.
p.000068: Another potential approach to involve the community is to use a CBPR approach, wherein the
p.000068: community is actively involved in each step of the research process, including sharing of decisionmaking
p.000068: power and resources. This will impact decisions about study design, study methods, dissemination of findings,
p.000068: and resulting actions. “Under the principles of community-based participatory research, research
p.000068: must
p.000068:
p.000068:
p.000069: 69
p.000069:
p.000069: address the concerns, needs, and priorities of the communities where it is conducted and lead to
p.000069: actions and changes that benefit the community” (p. 86, NRC & IOM, 2005). Information about CBPR approaches can
p.000069: be found online at the HHS Web sites http://www.ahrq.gov/clinic/epcsums/cbprsum.htm
p.000069: and http://www.ahrq.gov/research/cbprrole.htm.
p.000069: Israel et al. (2005a) reviewed the results of CBPR efforts at six Children’s Centers co-funded by EPA and the
p.000069: National Institute of Environment Health Sciences. They found that considerable commitment of resources and
p.000069: time are needed for the approach to be successful, and the translation of research findings into interventions
p.000069: and policies is of the utmost importance. Community partners played little role in defining the research topics
p.000069: and data analysis, but were vital to disseminating the findings to the community. Keeler et al. (2002) describe
...
p.000117: of the factors being studied, and there is no attempt by the researcher to affect the outcome.
p.000117: Observational research. Any human research that does not meet the definition of research involving intentional
p.000117: exposure of a human subject [40 CFR 26.302]
p.000117: Privacy. Control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or
p.000117: intellectually) with others
p.000117: Research. A systematic investigation, including research development, testing, and evaluation, designed to develop or
p.000117: contribute to generalizable knowledge
p.000117: Research involving intentional exposure of a human subject. A study of a substance in which the exposure to the
p.000117: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
...
General/Other / Impaired Autonomy
Searching for indicator autonomy:
(return to top)
p.001991: than a dozen Federal departments or agencies in 1991. Each agency incorporated the policy into its own Code of Federal
p.001991: Regulations (CFR), with EPA adapting it in Title 40 CFR Part 26, Subpart A.
p.001991:
p.001991:
p.001993: 1993
p.001993:
p.001993: The Institutional Review Board Guidebook (U.S. HHS, 1993)
p.001993:
p.001993: The document is intended as a resource and a reference document for IRB members, researchers, and institutional
p.001993: administrators. It is not designed to tell IRBs whether or not specific protocols should be approved; rather, the
p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
p.002000: What Makes Clinical Research Ethical? (Emanuel et al., 2000)
p.002000:
p.002000: This journal article lays out seven areas of concern that need to be addressed if clinical research is deemed to be
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
...
p.000006: and (2) the human activities that bring people into contact with the media containing the chemicals.3 This
p.000006: document addresses issues associated with observational human exposure studies that are conducted by the
p.000006: National Exposure Research Laboratory (NERL) of the U.S. Environmental Protection Agency (EPA) in an effort
p.000006: to understand and characterize the exposures that people encounter as they go about their daily lives.
p.000006: Because observational human exposure studies involve human participants, they are complex in their
p.000006: design and implementation. As in all research involving human participants, observational human exposure
p.000006: studies carry both regulatory obligations for the protection of human subjects (40 CFR 26) and
p.000006: ethical obligations to the study participants: namely, to respect
p.000006:
p.000006:
p.000006: 2 Exposure, as it is used throughout this document, is a technical term that is defined as the “contact of a chemical,
p.000006: physical, or biological agent with the outer boundary of an organism [e.g., a person]. Exposure is quantified as the
p.000006: concentration of the agent in the medium in contact integrated over the time duration of that contact.” (The definition
p.000006: is taken from Guidelines for Exposure Assessment [EPA/600/Z-92/001, May 1992]). See the Glossary for more information
p.000006: and the definition of additional terms.
p.000006: 3 The term “chemical” is used in this document as a surrogate term for all stressors, including chemical, physical, or
p.000006: biological agents.
p.000006: their autonomy, to not inflict harm (nonmaleficence), to avoid harm and to maximize their benefits (beneficence), and
p.000006: to treat all participants fairly (justice) (See, for example, Principles of Biomedical Ethics, Beauchamp
p.000006: and Childress, 2001). Ethical obligations have to be carefully considered as they relate to the
p.000006: scientific elements of these studies. Therefore, it is important that researchers recognize and understand these
p.000006: obligations and use the most up-to-date scientific and ethical approaches in the design and
p.000006: implementation of observational human exposure studies.
p.000006:
p.000006: 1.1 Observational Human Exposure Studies As we are using the term in this document, “observational
p.000006: human exposure studies” are studies that involve the collection of environmental samples, data, and
p.000006: information from study participants in their everyday environments as they go about their normal
p.000006: activities. These are studies where the NERL researchers do not intentionally try to control the study variables or
p.000006: outcomes, but instead merely observe both the variables and the outcomes. They involve neither the deliberate
p.000006: exposure of participants nor the control of environmental conditions in a way that impacts the
p.000006: participants’ naturally occurring exposures. This scientifically based definition needs to be distinguished
p.000006: at the outset from the broader regulatory term “observational” so that the scope and limits of this
...
p.000008: Since 1991, ethical thought and regulatory processes for the protection of human subjects have continued to
p.000008: evolve and grow. For example, many ethicists expand the elements contained in the principle of
p.000008: beneficence from the Belmont Report into two principles:
p.000008: (1) beneficence, meaning to prevent or remove harm and
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: to maximize the possible benefits; and
p.000009: (2) nonmaleficence, meaning not to inflict harm (Beauchamp and Childress, 2001).
p.000009:
p.000009: Table 1-2. The Belmont Report— Principles and Recommendations
p.000009:
p.000009: Ethical Principle Regulatory Manifestation
p.000009: addressed many important scientific and ethical issues on this topic, including the National Research
p.000009: Council (NRC) in its report, Protecting Participants and Facilitating Social and Behavioral Sciences
p.000009: Research (NRC, 2003), a joint NRC and Institute of Medicine (NRC & IOM, 2005) committee in the report on
p.000009: Ethical Considerations for Research on Housing-Related Health Hazards Involving Children; the Council
p.000009: for
p.000009:
p.000009: Respect for Persons
p.000009: • Individuals should be treated as autonomous agents.
p.000009: • Persons with diminished autonomy are entitled to protection.
p.000009:
p.000009: Beneficence
p.000009: • Human subjects should not be harmed.
p.000009: • Research should maximize possible benefits and minimize possible harms.
p.000009: Justice
p.000009: • The benefits and risks of research must be distributed fairly.
p.000009: Informed Consent
p.000009: • Subjects must be given the opportunity to choose what will or will not happen to them
p.000009: • The consent process must include
p.000009: (1) information,
p.000009: (2) comprehension, and
p.000009: (3) voluntariness
p.000009: Assessment of Risks and Benefits
p.000009: • The nature and scope of risks and benefits must be assessed in a systematic manner.
p.000009:
p.000009:
p.000009: Selection of Subjects
p.000009: • There must be fair procedures and outcomes in the selection of research subjects.
p.000009: International Organizations of Medical Sciences (CIOMS) under the World Health Organization in
p.000009: its International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002) and
p.000009: in the International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008); and
p.000009: the National Ethics Advisory Committee of New Zealand in the Ethical Guidelines for Observational Studies:
p.000009: Observational Research, Audits and Related Activities (NEAC, 2006).
p.000009:
p.000009:
...
p.001991: than a dozen Federal departments or agencies in 1991. Each agency incorporated the policy into its own Code of Federal
p.001991: Regulations (CFR), with EPA adapting it in Title 40 CFR Part 26, Subpart A.
p.001991:
p.001991:
p.001993: 1993
p.001993:
p.001993: The Institutional Review Board Guidebook (U.S. HHS, 1993)
p.001993:
p.001993: The document is intended as a resource and a reference document for IRB members, researchers, and institutional
p.001993: administrators. It is not designed to tell IRBs whether or not specific protocols should be approved; rather, the
p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
p.002000: What Makes Clinical Research Ethical? (Emanuel et al., 2000)
p.002000:
p.002000: This journal article lays out seven areas of concern that need to be addressed if clinical research is deemed to be
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
...
p.000026: affected parties, participation in affected advocacy groups, collaborations or relationships with
p.000026: experts on the IRB or other independent review committees, institutional conflicts for any contractors
p.000026: who may be involved, or a wide range of other situations.
p.000026: Any situations that constitute actual conflicts of interest and all potential or apparent conflicts of interest
p.000026: must be reported to the IRB for their review and resolution. The CIOMS (2002) guidelines for
p.000026: research protocols involving human subjects specify that all sponsors of the research be identified,
p.000026: and that the protocol include actions to disclose and address potential conflicts of interest. Concerns about
p.000026: conflicts of interest also need to be identified and discussed with the researchers, community, and
p.000026: other stakeholders to make a determination of the existence of conflicts, and how they should be avoided or
p.000026: handled.
p.000026: Even if actual conflicts of interest do not exist, researchers should recognize that there can be perceived
p.000026: conflicts of interest that can be just as damaging as real conflicts of interest. Perceptions by
p.000026: participants, community members and representatives, stakeholder groups, and the public may be substantially
p.000026: different from the reality of the situation. This is especially likely to occur when external sources, such as
p.000026: industry, are
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027: involved in funding research. Even though researchers may develop agreements with funding organizations that
p.000027: ensure researcher autonomy, a perception may exist that the funding organization will bias the study (Resnik and Wing,
p.000027: 2007). Concerns about perceived conflicts of interest should be discussed with the IRB and other relevant
p.000027: review committees, in addition to the researchers, the community, and other stakeholders. The IRB must
p.000027: be made aware of any circumstances that may give rise to actual conflicts of interest or to the
p.000027: appearance or perception of a conflict of interest. The IRB’s recommendations about how to resolve any such
p.000027: conflicts must be strictly adhered to by NERL researchers.
p.000027:
p.000027: 2.5.3 Develop the Human Subjects Protocol for IRB Review
p.000027: IRBs may have specific format requirements for their human subject research protocols. Traditionally, the human
p.000027: subjects research protocols for research conducted or funded by NERL have included
p.000027: descriptions of the project, including title and description of the research; the duration of the project; the
p.000027: type of data to be collected; the objectives of the study; the number of samples; a description of the
p.000027: participants and participant recruitment procedures; the informed consent procedures and forms; estimates of
p.000027: participant risk and burden, an assessment of benefits and the risk-benefit ratio; and actions to protect the
p.000027: participants. CIOMS has developed a comprehensive list of items that they recommend for inclusion in
...
p.000040: (NRC & IOM, 2005). These housing-related discussions are particularly relevant to observational human
p.000040: exposure studies, which often include environmental and
p.000040: biological measurements in people’s homes or personal locations. Many of the topics identified in that report are
p.000040: discussed in this section (Text Box 4-1).
p.000040:
p.000040:
p.000040: Text Box 4-1. Topics in Section 4
p.000040: Privacy Issues Confidentiality
p.000040: Confidentiality of Information Confidentiality of Participation
p.000040: Collateral Observations
p.000040: Potential Nonstudy Hazards in the Residence Collateral Observations with Mandated Reporting
p.000040: Requirements
p.000040: Hazard Communication Planning and Staff Training
p.000040: Third-Party Issues
p.000040: Determining Whether a Third Party is a Human Subject Informing Third Parties of Research Activities Research Results
p.000040: and Third Parties
p.000040: Data and Safety Monitoring and Oversight
p.000040:
p.000040:
p.000040:
p.000040: 4.1 Privacy Issues
p.000040: Privacy refers to an expectation that a person is free from intrusion into personal matters and is free from the
p.000040: presence or view of others. The Institutional Review Board Guidebook defines privacy as “control over the
p.000040: extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with
p.000040: others” (U.S. HHS, 1993). Beauchamp and Childress find that the right to privacy is based on the principle of
p.000040: respect for autonomy. “We often respect persons by respecting their autonomous wishes not to be observed, touched, or
p.000040: intruded upon…. A loss of privacy occurs if others use any of several forms of access, including intervening in zones
p.000040: of secrecy, anonymity, seclusion, or solitude” (pp. 295-296, Beauchamp and Childress, 2001).
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041: Although research participants may agree to allow researchers to enter their home or other zone of personal space
p.000041: to conduct their research measurements, they have not abrogated their right to privacy. “When individuals
p.000041: voluntarily grant others some form of access to themselves, their act is an exercise of the
p.000041: right to privacy, not a waiver of that right” (p. 297, Beauchamp and Childress, 2001). Researchers should remember
p.000041: that they are guests in the homes for a specific purpose. “When people visit a home, there are social
p.000041: expectations about what is acceptable behavior. People who are invited into a home are expected to be
p.000041: sensitive to and respectful of the host’s customs and values” (p. 65, NRC & IOM, 2005).
p.000041: By their very nature, observational human exposure studies encroach on the privacy of a research participant. Entry in
p.000041: a participant’s home (or other personal zones) does represent a loss of privacy, but researchers should be
...
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p.000050: 50
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050:
p.000050: SECTION 5
p.000050: Creating an Appropriate Relationship Between the Participant and Researcher
p.000050:
p.000050:
p.000050:
p.000050: In observational human exposure studies, the researcher and the participant routinely interact
p.000050: with each other, often in the participant’s home or other private setting and often repeatedly over a
p.000050: number of days. The nature and setting of the interactions mean that exposure researchers should give special
p.000050: consideration to the many scientific and ethical issues that shape the relationship between participants and
p.000050: the researchers. In these studies, it is recommended that a strong relationship, built on
p.000050: openness and trust, should be developed between the researcher and participant. The nature of that
p.000050: relationship and the ethical principles underpinning an appropriate relationship are the focuses of this section of
p.000050: the document.
p.000050: This relationship should be established on the ethical values of respect for the participant’s autonomy and
p.000050: respect for their welfare. Emanuel and his co-authors find that these two ethical values translate into
p.000050: specific responsibilities for an ethical researcher in regard to informed consent and respect for potential and
p.000050: enrolled subjects (Emanuel et al., 2000). They describe the ethical principles for these responsible actions thusly,
p.000050: “Respect for potential and enrolled subjects is justified by multiple principles including beneficence,
p.000050: nonmaleficence, and respect for persons. Permitting subjects to withdraw and providing them additional information
p.000050: learned from the research are key aspects of respecting subject autonomy. Protecting confidentiality and monitoring
p.000050: well-being are motivated by respect for persons, beneficence, and nonmaleficence.” Section 4 already has
p.000050: described some of the particular concerns regarding privacy, confidentiality, and other issues
p.000050: related to observational human exposure studies. This section further describes elements of the relationship
p.000050: between researchers and participants that are important to consider and address during design and
p.000050: implementation of a study.
p.000050: Of course, the relationship between the researchers
p.000050: and the individual participants does not exist in isolation. The researcher-participant relationship may influence
p.000050: and be influenced by the relationship with the community in which the participant lives.
p.000050: Good, two- way communications are critical for the development and nourishment of an appropriate
p.000050: researcher-participant relationship. Although those two topics are the subject of the next sections of this document,
p.000050: elements from those topics unavoidably will color the discussions in this section as well.
p.000050: Researcher training is a key component for conducting research that incorporates human
p.000050: subject protections and fosters appropriate researcher-participant relationships. Most organizations require basic
p.000050: human subjects training on the essential elements for processes and procedures for research with human subjects. More
p.000050: in-depth training will improve researcher understanding in areas of the informed consent process, observational
...
p.000078: http://epa.gov/compliance/resources/policies/ej/ej_strategy_ 1995.pdf
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
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p.000079:
p.000079:
p.000079:
p.000079:
p.000079:
p.000079: SECTION 7
p.000079: Designing and Implementing Strategies for Effective Communication
p.000079:
p.000079:
p.000079:
p.000079: Successful implementation of observational human exposure studies requires effective communications between
p.000079: the researchers, study participants, community representatives, community members, stakeholders, and the
p.000079: public. The previous two sections established the need for communications that are “on-going, interactive
p.000079: dialogue…involving the disclosure and exchange of relevant information, discussion of that information, and
p.000079: assessment of the individual’s understanding of the discussion” (Recommendation 4.1, IOM, 2002). NIH
p.000079: advocates “plain language” that explains the research “in an honest, straightforward way” (Recommendation 11, NIH,
p.000079: 2005). Indeed, strong relationships can be built with participants, the community, and stakeholders only if
p.000079: there are clear and effective communications between the researchers and the community. The previous section
p.000079: illustrates, also, that effective communication is bidirectional; it involves listening as well as
p.000079: “speaking.” The ethical value of respect for persons, including respect for one another’s
p.000079: autonomy and welfare, demands that researchers, participants, community members, and stakeholders
p.000079: strive to establish effective communications and to foster a relationship of trust and respect. The researchers
p.000079: should make a commitment to effective communications and make the appropriate investment of time and
p.000079: resources to ensure that the communications are at an appropriate level and are truly effective. Researchers should
p.000079: regard communications as intrinsic to the ethical basis for the study.
p.000079: With the ethical basis for bidirectional communication assumed as a given, and the need
p.000079: for open and honest bidirectional communications having been well established in the previous
p.000079: sections that discussed relationships between the researchers and the participant (Section 5) and the
p.000079: researchers and the community (Section 6), this section discusses strategies and tools that researchers may
p.000079: find useful in developing
p.000079: effective communications. The focus in this section is primarily from the perspective of “getting the word out,”
p.000079: because that is the aspect of communication most under the control of the researchers. Nonetheless, effective
p.000079: communications will be bidirectional and involve effective listening. Researchers should keep in mind that it
p.000079: is as important to listen to the participants, community, and other stakeholders as it is for the researchers
p.000079: to provide them with information using the approaches described in this section.
p.000079:
p.000079: 7.1 Communication Strategy and Implementation Plan
...
p.000115: Health
p.000115: NRC National Research Council
p.000115: OHRP Office for Human Research Protections OMB Office of Management and Budget OSMB
p.000115: observational study monitoring board PM particulate matter
p.000115: Q&As questions and answers
p.000115: QAPP quality assurance project plan
p.000115: RfD reference dose
p.000115: SEAOES Scientific and Ethical Approaches for Observational Exposure Studies TEAL Tribal
p.000115: Efforts Against Lead
p.000115: TEAM Total Exposure Assessment Methodology TLV threshold limit value
p.000115: VOC volatile organic compound
p.000115: WHO World Health Organization
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
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p.000116: 116
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116: Appendix F
p.000116: Glossary
p.000116:
p.000116:
p.000116:
p.000116: Agent. A chemical, mineralogical, biological, or physical entity that may cause deleterious effects in an organism
p.000116: after the organism is exposed to it [EPA/600/Z-92/001, May 1992].
p.000116: Assent. A child’s affirmative agreement to participate in research. Mere failure to object should not, absent
p.000116: affirmative agreement, be construed as assent [45 CFR 46.402(d)].
p.000116: Autonomy. The capability and capacity to govern oneself.
p.000116: Beneficence. The ethical obligation to maximize benefits and to minimize harms. This principle gives rise to norms
p.000116: requiring that the risks of research be reasonable in light of the expected benefits, that the research design be
p.000116: sound, and that the investigators be competent both to conduct the research and to safeguard the welfare of the
p.000116: research subjects. Beneficence further proscribes the deliberate infliction of harm on persons; this aspect of
p.000116: beneficence is sometimes expressed as a separate principle, nonmaleficence (do no harm).
p.000116: Child. A person who has not attained the age of 18 years [40 CFR 26.202(a)]
p.000116: Collateral observations. Potentially unsafe hazards, conditions, or situations unrelated to the research study that
p.000116: are observed by the research staff
p.000116: Common Rule. The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects.” It was
p.000116: adopted by more than a dozen Federal departments or agencies in 1991, with EPA adapting it in Title 40 CFR Part 26
p.000116: Subpart A.
p.000116: Community-based participatory research (CBPR). Collaborative research with a community in which the community is
p.000116: involved in all phases of the research.
...
p.000117: Observational human exposure study. Studies that involve collection of human exposure data (including environmental,
p.000117: biological, survey, activity, and various other forms of data) under real-world field conditions during normal
p.000117: participant day-to-day activities, with no additional exposures to the chemical being studied because of participation
p.000117: in the study. The studies involve interaction with study participants but do not involve intervention or manipulation
p.000117: of the factors being studied, and there is no attempt by the researcher to affect the outcome.
p.000117: Observational research. Any human research that does not meet the definition of research involving intentional
p.000117: exposure of a human subject [40 CFR 26.302]
p.000117: Privacy. Control over the extent, timing, and circumstances of sharing oneself (physically, behaviorally, or
p.000117: intellectually) with others
p.000117: Research. A systematic investigation, including research development, testing, and evaluation, designed to develop or
p.000117: contribute to generalizable knowledge
p.000117: Research involving intentional exposure of a human subject. A study of a substance in which the exposure to the
p.000117: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
...
General/Other / Incapacitated
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p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
...
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p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
...
p.000117: participation in the study [40 CFR 26.202(b)]
p.000117: Respect for persons. A fundamental ethical value that is the basis of much of modern bioethical thought and
p.000117: regulation. The concept incorporates at least two fundamental ethical considerations, namely (1) respect for autonomy,
p.000117: which requires that those who are capable of deliberation about their personal choices should be treated with respect
p.000117: for their capacity for self- determination; and (2) protection of persons with impaired or diminished autonomy, which
p.000117: requires that those who are dependent or vulnerable be afforded security against harm or abuse.
p.000117: Source. The origin of an agent for the purposes of an exposure assessment
p.000117: Stakeholder. A person or group who has a valid interest in an activity, who can affect or is affected by the activity,
p.000117: and who stands to gain or lose depending on the decisions implemented
p.000117: Stressor. Any entity, stimulus, or condition that can modulate normal functions of the organism or induce an adverse
p.000117: response (e.g., agent, lack of food, drought)
p.000117: Vulnerability. A substantial incapacity to protect one’s own interests owing to such impediments as lack of capability
p.000117: to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being
p.000117: a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection
p.000117: of the rights and welfare of vulnerable persons.
p.000117: Vulnerable groups. Populations extended additional human subjects protections, such as children, individuals with
p.000117: questionable capacity to consent, prisoners, fetuses and pregnant women, the terminally ill, students and employees,
p.000117: and comatose patients, etc.
p.000117:
p.000117:
p.000117:
p.000118: 118
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p.000118:
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General/Other / Manipulable
Searching for indicator manipulated:
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p.000097: research domains, including human research that does not involve the study of exposures at all. This regulatory
p.000097: definition of observational is sufficiently broad, moreover, that it encompasses study types that
p.000097: this document is not intended to address. For example, it may be possible to design an intervention study that
p.000097: does not bring about or script in any way the participants’ exposure to a substance, but rather reduces or
p.000097: mitigates it. (Consider a study to test whether professional cleaning of the carpets, floors, walls, and
p.000097: other surfaces in a home might lead to a lower exposure to a residential contaminant or a study to determine if wearing
p.000097: a particle mask would reduce an individual’s exposure to smoke from forest fires.) Such a study
p.000097: might meet the regulatory definition of observational research (Note: The final decision in regard to whether
p.000097: any EPA study meets the definition of observational research resides with the Agency’s HSRRO), but it
p.000097: would not meet the authors’ intentions regarding “observational human exposure studies” as they are defined
p.000097: in this document. An intervention study, such as described in these two examples, does not involve
p.000097: observing people’s exposures in their everyday environments, as they go about their normal activities. In
p.000097: an intervention study, either the participant’s environment (cleaning of the household surfaces) or their
p.000097: behavior (wearing a particle mask) has been manipulated by the researcher. Secondly, the objective of these
p.000097: studies is not to understand exposures in everyday environments but would use changes in exposure
p.000097: to test the effectiveness of an intervention strategy. Such a study is not addressed in this document.
p.000097: Observational human exposure studies, as used by the authors of this document, generally meet the
p.000097: regulatory definition of observational research. But, not all studies meeting the CFR definition of
p.000097: observational research would be considered by the authors to be observational human exposure studies.
p.000097:
p.000097: Examples of NERL Observational Human Exposure Studies
p.000097: NERL and its predecessor organizations have
p.000097: conducted observational human exposure studies since 1980. Table A-1 lists many of those that NERL has
p.000097: conducted, supported, or participated in since 1980. The table gives the name of the study, dates, sample
p.000097: size, then type of study, a brief explanation of the research, and NERL’s role therein. The table represents a
p.000097: variety of first-party or second-party research efforts. In many cases, NERL staff would design,
p.000097: oversee, and, if possible, participate directly in the study (first-party), but often contractor
p.000097: support would be needed to accomplish the field sampling or some of the sample analysis. In other
p.000097: cases, NERL researchers would solicit proposals for exposure research to be conducted to address specific
...
General/Other / Natural Hazards
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p.000029: Being in the Study
p.000030: 30
p.000030: 2.8. Criteria and Standards for Monitoring Scientific and Ethical Issues 30
p.000030: 3. Ensuring Protection of Vulnerable Groups
p.000035: 35
p.000035: 3.1. Identification of Vulnerable Groups
p.000035: 35
p.000035: vii
p.000035:
p.000035: 3.2. Justification for Involving Vulnerable Persons in Observational Research 36
p.000035: 3.3. Minimal Risk and Vulnerable Groups
p.000037: 37
p.000037: 3.4. Research Involving Children
p.000037: 37
p.000037: 3.5. Women as Research Subjects
p.000038: 38
p.000038: 3.6. Other Potentially Vulnerable Groups
p.000039: 39
p.000039: 4. Privacy, Confidentiality, and Other Concerns Related to Observational
p.000039: Human Exposure Studies
p.000041: 41
p.000041: 4.1. Privacy Issues
p.000041: 41
p.000041: 4.2. Confidentiality
p.000042: 42
p.000042: 4.2.1. Confidentiality of Information
p.000043: 43
p.000043: 4.2.2. Confidentiality of Participation
p.000044: 44
p.000044: 4.3. Collateral Observations
p.000044: 44
p.000044: 4.3.1. Potential Nonstudy Hazards in the Residence 44
p.000044: 4.3.2. Collateral Observations with Mandated Reporting Requirements 45
p.000044: 4.3.3. Hazard Communication
p.000045: 45
p.000045: 4.3.4. Planning and Staff Training
p.000046: 46
p.000046: 4.4. Third-Party Issues
p.000046: 46
p.000046: 4.4.1. Determining Whether a Third Party Is a Human Subject 47
p.000046: 4.4.2. Informing Third Parties of Research Activities 47
p.000046: 4.4.3. Research Results and Third Parties
p.000047: 47
p.000047: 4.5. Data and Safety Monitoring and Oversight
p.000048: 48
p.000048: 5. Creating an Appropriate Relationship Between the Participant and Researcher 51
p.000048: 5.1. Informed Consent
p.000052: 52
p.000052: 5.1.1. Information
p.000052: 52
p.000052: 5.1.2. Comprehension
p.000054: 54
p.000054: 5.1.3. Voluntary Participation
p.000055: 55
p.000055: 5.2. Payments to Research Participants
p.000056: 56
p.000056: 5.2.1. Types and Amounts of Payments Offered in Research Studies 56
p.000056: 5.2.2. Regulations and Guidance Regarding Payment to Research Participants 58
p.000056: 5.2.3. Payments When Children or Other Vulnerable Populations Are Involved 59
p.000056: 5.2.4. Payments in Observational Human Exposure Studies 61
p.000056: 5.3. Research Rights and Grievance Procedures
p.000061: 61
p.000061: 5.3.1. Ombudsman
p.000061: 61
p.000061: 5.3.2. Community Advisory Board
p.000062: 62
p.000062: 5.4. Creating a Supportive Environment for Research and Interaction 62
...
p.000023: – Information and data needs, including data storage, security, access, and release;
p.000023: – nature of the measurement data (e.g., variability, quality assurance);
p.000023: – how the collected data will be used, and how the proposed analyses will address objectives of the study; and
p.000023: – hypotheses to be tested and statistical power and sample size required to test the hypotheses
p.000023: • Resources required or available
p.000023: • Project organization and management, including team members and roles and responsibilities
p.000023: • Schedule
p.000023:
p.000023: fairness in human subjects research is that scientific goals, considered in dynamic interaction with
p.000023: the potential for and distribution of risks and benefits, should guide the selection of subjects.”
p.000023: (Emmanuel et al, 2000). On the other hand, as discussed in Section 3, many study problems specifically
p.000023: address exposures of vulnerable groups to chemicals and other stressors. Researchers should not avoid
p.000023: research studies that will,
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024: of necessity, include vulnerable groups to address the study hypotheses or objectives simply to avoid the more
p.000024: stringent requirements for working with these groups.
p.000024:
p.000024: 2.4 Ensuring a Favorable Risk-Benefit Ratio
p.000024: 2.4.1 Designing in Benefits for the Participants
p.000024: Study designs vary depending on the objectives of the study, existing knowledge on the research question, and
p.000024: the hazard being studied (NRC & IOM, 2005). Recent ethical discussions about study designs in human subjects
p.000024: research (cf., Recommendation 7.1, p. 143, NRC & IOM [2005] and Emanuel et al. [2000]) support the development
p.000024: of innovative study designs to maximize the benefit9 to the study participants, as well as to
p.000024: the community and the greater society beyond. Observational human exposure studies generally collect data that
p.000024: contribute to generalizable knowledge that will benefit the community and society as a whole, but they often do not
p.000024: provide obvious direct benefit to study participants. Therefore, it is important to include elements
p.000024: in the study design that can offer benefits to the participants wherever possible. This is not always
p.000024: straightforward, but one way that participants, as well as communities, can benefit from these studies is
p.000024: by incorporating strong educational components into the conduct of the research. For example, brochures, videos,
p.000024: and other materials that educate study participants on safety around the home or on how to reduce their
p.000024: exposure to chemicals can be distributed during the study. EPA’s program offices, including the Office of
p.000024: Children’s Health Protection, the Office of Pollution Prevention and Toxics, the Office of Pesticide Programs,
p.000024: the Office of Drinking Water, and others have Web sites with substantial amounts of informational
...
p.000040: “expectations and constraints may be strikingly different than when research is carried out in a medical
p.000040: setting” (p. 64, NRC & IOM, 2005). The legal precept of freedom from unreasonable search and
p.000040: seizure and the historic and deeply rooted principle that “a man’s home is his castle” contribute to a belief in the
p.000040: “sanctity of the home” (see the discussion on pp. 62-66, NRC & IOM, 2005).
p.000040: The joint NRC and IOM report Ethical Considerations for Research on Housing-Related Health
p.000040: Hazards Involving Children discusses the ethical issues associated with entering a participant’s home to conduct
p.000040: research and explores the researchers’ responsibilities that derive from conducting research in people’s homes
p.000040: (NRC & IOM, 2005). These housing-related discussions are particularly relevant to observational human
p.000040: exposure studies, which often include environmental and
p.000040: biological measurements in people’s homes or personal locations. Many of the topics identified in that report are
p.000040: discussed in this section (Text Box 4-1).
p.000040:
p.000040:
p.000040: Text Box 4-1. Topics in Section 4
p.000040: Privacy Issues Confidentiality
p.000040: Confidentiality of Information Confidentiality of Participation
p.000040: Collateral Observations
p.000040: Potential Nonstudy Hazards in the Residence Collateral Observations with Mandated Reporting
p.000040: Requirements
p.000040: Hazard Communication Planning and Staff Training
p.000040: Third-Party Issues
p.000040: Determining Whether a Third Party is a Human Subject Informing Third Parties of Research Activities Research Results
p.000040: and Third Parties
p.000040: Data and Safety Monitoring and Oversight
p.000040:
p.000040:
p.000040:
p.000040: 4.1 Privacy Issues
p.000040: Privacy refers to an expectation that a person is free from intrusion into personal matters and is free from the
p.000040: presence or view of others. The Institutional Review Board Guidebook defines privacy as “control over the
p.000040: extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with
p.000040: others” (U.S. HHS, 1993). Beauchamp and Childress find that the right to privacy is based on the principle of
p.000040: respect for autonomy. “We often respect persons by respecting their autonomous wishes not to be observed, touched, or
p.000040: intruded upon…. A loss of privacy occurs if others use any of several forms of access, including intervening in zones
p.000040: of secrecy, anonymity, seclusion, or solitude” (pp. 295-296, Beauchamp and Childress, 2001).
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041: Although research participants may agree to allow researchers to enter their home or other zone of personal space
p.000041: to conduct their research measurements, they have not abrogated their right to privacy. “When individuals
...
p.000043: create potential for harm or distress in an observational human exposure study. Such risks might
p.000043: be limited to possible discomfort in attracting unwanted
p.000043: attention; this may be particularly true for adolescents. However, in some cases, the potential risks
p.000043: could be greater, for example, in cases where participation could provoke an adverse reaction from a
p.000043: landlord or employer. Oftentimes study protocols can be structured to minimize these potential risks. Through the
p.000043: informed consent process, prospective participants should be made aware of the limits of the researcher’s ability to
p.000043: protect knowledge of their participation in the study and of the possible risks of disclosure.
p.000043:
p.000043: 4.3 Collateral Observations
p.000043: In the course of conducting an observational human exposure study, research staff may observe potentially unsafe
p.000043: conditions or situations that are unrelated to the research study. Such “collateral observations” may
p.000043: involve physical hazards in the study participant’s residential environment or evidence of situations,
p.000043: such as child abuse, that have to be reported to proper authorities. In preparing for the
p.000043: research study, it is recommended that researchers carefully plan for possible collateral observations,
p.000043: including their identification, staff training, and hazard communication and reporting. This may be a major
p.000043: element in the data and safety monitoring and oversight for the study. The informed consent process
p.000043: should reflect procedures used to manage collateral observations. Potential participants should be
p.000043: informed of situations in which confidentiality might be breached, such as statutory requirements for reporting
p.000043: abuse or imminent harm to self or others.
p.000043:
p.000043: 4.3.1 Potential Nonstudy Hazards in the Residence
p.000043: Research staff conducting observational human exposure studies often will spend time in and around
p.000043: study participant residences. In the course of visiting a residence or conducting study-related
p.000043: observations, research staff may observe potential hazards unrelated to the research being performed (see Text Box
p.000043: 4-4). Some hazards may be associated with the potential for physical injury, whereas others may be related to
p.000043: exposure to chemical or biological agents. Some situations may be potential hazards only for young children,
p.000043: whereas other conditions may present potential hazards for all residents or occupants.
p.000043: The NRC & IOM recommend that researchers should consider such foreseeable observations and
p.000043: potential hazards in advance, develop responses to the risks, and submit the proposed plans to the IRB
p.000043: for review to ensure that they are appropriate “in the context of the research and the affected community.” The NRC
p.000043:
...
p.000044: • observed child or elder abuse or evidence of such abuse or neglect,
p.000044: • statements or actions of intent to harm self or others, and
p.000044: • certain communicable diseases.
p.000044: Because different reporting statutes pertain in different states, it is necessary for researchers to
p.000044: learn and understand the applicable reporting requirements for the study location. In the case of abuse, it is
p.000044: also
p.000044: important to understand what actions or situations are considered abusive in a particular state. Although direct
p.000044: physical harm or violence might be obvious to a research staff member, there are other conditions of neglect that
p.000044: might be more difficult to recognize or to know when to report.
p.000044: Study participants should be made aware of statutory requirements for reporting collateral observations as part of the
p.000044: informed consent process. Researchers should include the reporting requirements in the informed
p.000044: consent form (discussed in Section 5) and should ensure that the study participant fully comprehends this
p.000044: information and the impact on their privacy and confidentiality.
p.000044:
p.000044: 4.3.3 Hazard Communication
p.000044: It is difficult for researchers to determine when and how to communicate with study participants or third
p.000044: parties about collateral observations related to potential hazards. A hazard might present such an imminent
p.000044: threat to health or safety that staff would need to communicate immediately with the participant or take
p.000044: action to mitigate the threat. In some cases, such as instances of abuse with attendant statutory reporting
p.000044: requirements, it may be necessary to breach confidentiality. More often, however, a potential hazard identified as
p.000044: a result of collateral observation may not be an imminent threat or pose a potential risk that is situation
p.000044: dependent or is related to third parties. A number of considerations in hazard communication come
p.000044: into play regarding confidentiality, privacy, the ability of the researcher to provide accurate and
p.000044: effective information regarding the hazard and hazard mitigation, and the ability of the study participant or others
p.000044: to effectively mitigate the hazard without unintended adverse consequences. The National Academy of Sciences
p.000044: Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children, Youth, and
p.000044: Families discussed many of these issues in depth (NRC & IOM, 2005).
p.000044: Different communities, cultures, or demographic groups can have different risk perceptions, which may
p.000044: affect how collateral observations are assessed and reported from one study location to the next. The AAP
p.000044: Committee on Environmental Health has prepared information regarding perception, identification, and
p.000044: communication of environmental health risks (AAP, 2003). Researchers likely will benefit from including
p.000044: community members on the research team in developing the study design and research protocol or from
p.000044: consultation with community boards regarding identification of hazards and hazard communication.
p.000044:
p.000044:
p.000045: 45
p.000045:
p.000045: It is important that any advice that the researcher might provide to study participants regarding hazard
p.000045: mitigation should be carefully considered. Considerations in recommending an action may include
p.000045: whether the mitigation approach has been shown to be effective, whether the study participant can
p.000045: understand and effectively implement the action, and whether unintended adverse consequences might
p.000045: result from taking an action. In some cases, it may be reasonable to refer the participant to another
p.000045: organization that can provide expert advice or assistance.
p.000045:
p.000045: 4.3.4 Planning and Staff Training
p.000045: As part of the study planning process and protocol development, it is important that researchers
p.000045: be cognizant of the kinds of collateral observations that might occur in the implementation of the study
p.000045: protocol and to develop plans as to how such observations would be handled. Researchers may choose to
p.000045: include a systematic approach in hazard identification, such as using a home-hazard checklist that becomes an
p.000045: ancillary part of the study protocol. Alternatively, collateral observations could be handled on a
p.000045: case-by-case basis.
p.000045: Staff experience and training is a critical consideration for managing collateral observations. Staff
p.000045: members that visit study participant residences may not have expertise or experience in identifying many of the
p.000045: potential hazards without adequate training. All staff involved in a study, particularly those responsible
p.000045: for field data collection, should be trained on identification and reporting of collateral observations. This
p.000045: training should be study specific and likely will include, but not be limited to
p.000045: (1) identification of actions (e.g., child abuse) that have (state-specific) statutory reporting requirements,
p.000045: (2) conditions of neglect that may adversely impact study participants or third parties,
p.000045: (3) environmental hazards and situations that may be associated with imminent harm (e.g., combustible
p.000045: materials near an open flame, unsecured firearms accessible to very young children),
p.000045: (4) policies and procedures for reporting or intervention by members of the research team, and
p.000045: (5) local and state reporting requirements.
p.000045: It is advisable that this training be developed in consultation with community representatives who can
p.000045: provide input on potential hazards and situations that may be encountered in the study community,
p.000045: local norms and attitudes about potential interventions and reporting, and local agencies available to assist on
p.000045: these types of issues. It is also especially important to consider
p.000045: staff experience and training in hazard communication. Consistency in communication is very important, and
p.000045: researchers may decide to use materials prepared by other organizations that have expertise regarding
p.000045: a particular hazard.
p.000045: Another important element of planning for field data collection and training of research staff is on hazards and
p.000045: situations that the field staff may encounter during their field work. Although the previous discussion highlights the
p.000045: need to be prepared to report potentially negligent or illegal behaviors, these same behaviors may place the
p.000045: research staff in imminent danger during the conduct of their work in residences and communities. The research team
p.000045: should develop a plan for identifying potential situations, hazards, and dangers that may place the
p.000045: research team at risk of imminent harm. This should generally involve working with
p.000045: community representatives to identify the hazards and situations that may be of concern. For example, a
p.000045: researcher’s observation of illegal drugs in a study residence may place the researcher in potential
p.000045: danger. Similarly, if studies are conducted in areas with high crime rates, researchers need to be aware of
p.000045: the potential dangers and have a plan for addressing them. In some cases, situations may arise
p.000045: because of to inadvertent actions. For example, if an area has a high rate of daytime break- ins, the presence
p.000045: of researchers in the area may trigger calls to local authorities when the researchers, who are
...
p.000053:
p.000053:
p.000054: 54
p.000054:
p.000054: is how information is conveyed to the participant outside of the written form itself.
p.000054: Participant comprehension is contingent on all elements of a comprehensive consent process that involves ongoing
p.000054: information exchange between researchers and participants, as well as a written informed consent
p.000054: document (NRC & IOM, 2005).
p.000054: • The most effective way to improve comprehension is by talking one-on-one with study participants.
p.000054: “Having a study team member or a neutral educator spend more time talking one-on-one to study
p.000054: participants appears to be the most effective way of improving research participants’ understanding”
p.000054: (Flory and Emanuel, 2004).
p.000054: • The information being exchanged (e.g., explanation of the purpose of the research, description of the study
p.000054: procedures) should be written at a level that the participant can understand (NRC & IOM, 2005).
p.000054: • The researcher should describe the benefits of participation in the study [40 CFR 26.116(a)(3)], but
p.000054: should not promise any outputs or outcomes that he or she cannot deliver. Participants often misunderstand the
p.000054: purpose of the research. The researchers also should attempt to reduce the likelihood of “therapeutic
p.000054: misconception”19 or related misunderstandings in which the participant anticipates a benefit that does
p.000054: not really exist, such as reduction of the hazard in an observational study (NRC & IOM, 2005).
p.000054: • The consent procedure should include some test of the participants to demonstrate that they truly understand the
p.000054: information that is being conveyed (IOM, 2002).
p.000054: • Tools to assess comprehension have been developed, but, as described in NRC & IOM (2005), there are no standard
p.000054: mechanisms for assessing comprehension. Tests for appropriate grade-level language can be performed, but
p.000054: additional comprehension testing should be considered as well (Flory and Emanuel, 2004).
p.000054: • Researchers need to develop innovative approaches to improve comprehension. Multimedia, such as video or graphics,
p.000054: may be used but have had limited success in the past (NRC & IOM, 2005; Flory and Emanuel, 2004). NCS
p.000054: currently is developing a highly sophisticated video consent tool that may be able to
p.000054:
p.000054:
p.000054: 19 Therapeutic misconception is a term that refers to an inaccurate understanding on the part of a research participant
p.000054: that a direct therapeutic benefit will be provided by virtue of participation in a clinical trial.
p.000054: Researchers performing observational human exposure studies should be aware of the potential for misunderstandings to
p.000054: arise that are analogous to the misunderstanding represented by the therapeutic misconception. Ensuring comprehension
p.000054: of the study and its expected results is important to this issue.
p.000054: serve as a model going forward. The video presentation will include embedded questions
...
p.000058: for those who bear in their care. burdens of research on
p.000058: • Persons in different behalf of society. circumstances may view the
p.000058: same amount of payment quite differently.
p.000058: • Payments may alter the composition of the study sample and potentially could compromise study integrity.
p.000058: activities is thus justified on the grounds of fairness” (p. 112, NRC & IOM, 2005).
p.000058: Similarly, the IOM Committee on Clinical Research Involving Children found that “certain types of
p.000058: payments to parents or adolescents are usually if not always acceptable, for example, reimbursement
p.000058: for reasonable expenses that are necessary for research participation. The specifics may vary, but
p.000058: examples of reasonable expenses are costs of transportation to the research site, parking, lodging, meals,
p.000058: and babysitting. Other payments are never appropriate in pediatric research, for example, paying parents
p.000058: for the use of their child in research” (pp. 225-6, IOM, 2004).21
p.000058: The IOM committee recommends establishing policies on acceptable and unacceptable types of
p.000058: payments. They also recommend that the policies disclose any recompense in a full and open
p.000058: process,22 while not overemphasizing any recompense.
p.000058: Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
...
p.000059: study. He suggested that, for a study of pesticides, potential study participants provide documentation (such as
p.000059: receipts) that they routinely have been using a commercial pesticide service. This may be difficult
p.000059: for potential participants to do if they do not save receipts, and it would exclude all potential
p.000059: participants who purchase products and apply pesticides themselves. This likely would affect the study
p.000059: objectives and generalizability of the data collected. A survey of investigators (Iltis et al., 2006) found that
p.000059: payments were made in 52% of the pediatric research studies surveyed, and that payment practices varied,
p.000059: as did the reasons for decisions regarding payments. They found a range of payment values separated
p.000059: across cash, gifts, items, vouchers, and other categories. A survey of IRBs (Weise et al., 2002) found that payment
p.000059: for participation in research was allowed by 66% of responding institutions, but that many IRBs did not have
p.000059: specific policies, and that there was considerable variability regarding the basis for decisions on
p.000059: payments in studies with children. The types of payments included money, certificates, and bonds with large
p.000059: ranges in the amounts of payments for approved pediatric research. This research shows a lack of consistency and
p.000059: the need for guidance and institutional policies that describe acceptable and unacceptable
p.000059: payments and the basis for the amount of any payments.
p.000059: The NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children
p.000059: described many of the ethical considerations, practices, and policies regarding payments (NRC & IOM, 2005)
p.000059: for research conducted in the participants’ homes, rather than in a clinical facility. The research
p.000059: setting is similar to the setting of most observational
p.000059: human exposure studies, and the committee’s commentary and recommendations are also relevant. The
p.000059: committee notes that it would be unfair to expect families to make considerable sacrifices to
p.000059: participate in a time-consuming activity designed to advance generalizable scientific knowledge,
p.000059: rather than benefit themselves directly, and that payment for reimbursement of expenses and modest payment for
p.000059: time spent in research activities is justified on the grounds of fairness. But the committee then warns that if
p.000059: payments are too high, they may distort parents’ decisions about enrolling their children. The committee also
p.000059: found that “how the payment is made may also result in undue influence. For example, if payment for a long-term
p.000059: follow-up study is made in a lump sum and only if the subjects complete the entire study, then it
p.000059: could constitute an undue influence to stay in the study. If, on the other hand, the money is paid weekly, the
p.000059: effect would not constitute an undue influence.”
...
p.000059: researchers and IRBs determine what is appropriate with regard to payments within their community.
p.000059:
p.000059:
p.000059:
p.000059:
p.000060: 60
p.000060:
p.000060: 5.2.4 Payments in Observational Human Exposure Studies
p.000060: Observational human exposure studies most often involve minimal risks to study participants and few direct
p.000060: benefits, but may require considerable time and burden for participation. Study requirements can include multiple
p.000060: in-home visits; the burden of wearing personal air monitors for one or more 24-hour period; preparing and providing
p.000060: duplicate diet samples; collection of environmental samples inside and outside the home; completing
p.000060: questionnaires, food diaries, and time- activity diaries; and providing urine, blood, saliva, or hair
p.000060: samples. Monetary payments often have been included in these studies, with the level of payment
p.000060: related to the number of study days or visits or the specific kinds of environmental and biological
p.000060: samples and information that are collected or provided. Payment for direct participant costs has been included
p.000060: in some studies, such as a reasonable payment for providing researchers with duplicate diet samples.
p.000060: NERL scientists should review the commentary and recommendations in the literature before devising a
p.000060: payment program as part of a research protocol, especially the two recent National Academies of Science
p.000060: documents, Ethical Issues in Housing-Related Health Hazard Research Involving Children (NRC and IOM, 2005)
p.000060: and Ethical Conduct of Clinical Research Involving Children (IOM, 2004). They should seek
p.000060: guidance from EPA’s HSRRO to determine EPA’s latest policies and guidance in this regard. Input also should be sought
p.000060: from community representatives to ensure that any payment is adequate to compensate for expenses and reward
p.000060: participation, but that the payment is not so high as to constitute undue influence or coercion in the
p.000060: community. If the study includes several followup visits over a long term, NERL researchers should ensure that payment
p.000060: is made incrementally as the NRC & IOM committee suggested. NERL scientists also should adopt the IOM
p.000060: Recommendations 6.1 and 6.2, including ensuring that any payment should be for appropriate purposes
p.000060: and age-appropriate, and that the process should be open and fully disclosed, while not overly
p.000060: emphasizing payments during the recruiting or informed consent phases. The final decisions about the ethics of
p.000060: payments rest with the IRB, which will review, modify as needed, and approve the research protocol, and with the EPA
p.000060: HSRRO, who has final authority to approve, modify, or disapprove all of NERL’s human subjects research
p.000060: efforts.
...
p.000089: availability of results published in manuscripts and reports has been greatly enhanced by posting them on
p.000089: Internet Web sites. For example, all EPA reports are now available electronically via EPA’s National Service
p.000089: Center for Environmental Publications Web site (http://www.epa.gov/ncepihom/).
p.000089:
p.000089: 7.8 Reporting Unanticipated Results or Observations
p.000089: The previous subsection discussed reporting of routine results from observational human exposure
p.000089: studies. The communication plan should include processes and procedures for the dissemination of
p.000089: the study results. Additionally, the communication plan needs to integrate with the data and safety
p.000089: monitoring and oversight plans for the study and include a plan for reporting unanticipated results or
p.000089: observations. Unanticipated results may include measurements of a chemical at a concentration that
p.000089: exceeds what is considered to be an “acceptable” level in environmental media or biological fluids.
p.000089: Unanticipated observations might include observation of the use of a chemical not approved for indoor
p.000089: use, storage of chemicals in inappropriate containers, storage of chemicals in places accessible by
p.000089: children, etc. Unanticipated results or observations may be directly related to the research question
p.000089: being addressed in the study (e.g., measurements of pesticide residues in a home) or
p.000089: nonstudy hazards (e.g., frayed electrical cords that may pose a hazard to young children and residences).
p.000089: Section 4 discusses issues that may affect privacy and confidentiality. Section 4.3 covers
p.000089: collateral observations of nonstudy-related hazards, including those that States may mandate must
p.000089: be reported. Section 4.5 discusses the need for data and safety monitoring and oversight, including the
p.000089: development of plans to report and react to anticipated or unanticipated adverse events or conditions.
p.000089: As part of the study implementation plan and the communication plan, researchers should develop a
p.000089: protocol for how to identify contaminant measurements and exposures of “concern” that should be reported to the
p.000089: study participant as quickly as possible because of the potential risk associated with the exposure
p.000089: (see Section 4.5, Data and Safety Monitoring and Oversight, and also Section 2.7.1, Establishing Criteria
p.000089: and Standards for Monitoring Scientific and Ethical Issues During a Study.) The plan needs to include the
p.000089: protocol for making the determination and the criteria that will be used as the threshold or “trigger” for
p.000089: reporting. The plans should describe how the results will be reported to the participants and what additional
p.000089: action will be undertaken to assist the participant in reducing their exposures. The first step in
p.000089: developing the protocol is to identify what measurement will be used to identify exposures of concern. In
...
General/Other / Public Emergency
Searching for indicator emergency:
(return to top)
p.000076: 31(9):3-12.
p.000076:
p.000076: U.S. EPA (U.S. Environmental Protection Agency) (2003). Public Involvement Policy of the U.S. Environmental Protection
p.000076: Agency. EPA 233-B-03-022. Available: http://www.epa.gov/publicinvolvement/pdf/policy2003.pdf [Accessed 26 Sep 2007].
p.000076:
p.000076: Vega WA (1992). Theoretical and pragmatic implications of cultural diversity for community research. Am J Commun
p.000076: Psychol 20(3):375-91
p.000076:
p.000076: Williams R, Suggs J, Rea A, Leovic K, Vette A, Croghan C, Sheldon L, Rodes C, Thornburg J, Eijire A, Herbst M, Sanders
p.000076: W (2003). The Research Triangle Park particulate matter panel study: PM mass concentration relationships. Atmos Environ
p.000076: 37:5349-5363.
p.000076:
p.000076:
p.000076:
p.000076:
p.000077: 77
p.000077:
p.000077: Additional Information Resources
p.000077: Blumenthal DS (2006). A community coalition board creates a set of values for community-based research. Prev Chronic
p.000077: Dis 3(1):1-7. Available: http://www.cdc.gov/pcd/issues/2006/jan/pdf/05_0068.pdf [accessed 12 June 2007].
p.000077:
p.000077: Coleman CH, Menikoff JA, Goldner JA, Dubler NN (2005). The Ethics and Regulation of Research with Human Subjects.
p.000077: Newark: LexisNexis.
p.000077:
p.000077: Davies EF (2001). Early and meaningful community involvement. U.S. Environmental Protection Agency, Office of Solid
p.000077: Waste and Emergency Response. Washington, DC. OSWER Directive No. 9230.0-99, October 12. Available:
p.000077: http://www.epa.gov/superfund/policy/pdfs/early.pdf [accessed 12 June 2007].
p.000077:
p.000077: NACCHO (National Association of County and City Health Officials). Turning Point: Collaborating for a New Century in
p.000077: Public Health, see http://www.naccho.org/topics/infrastructure/TurningPoint.cf m [Specifically, Fourteen Policy
p.000077: Principles for Advancing Collaborative Activity Among and Between Tribal Communities and Surrounding Jurisdictions.
p.000077: http://archive.naccho.org/documents/TP-policy principles.pdf ].
p.000077:
p.000077: U.S. CDC (Centers for Disease Control and Prevention). Preventing Chronic Disease [online serial] Available:
p.000077: http://www.cdc.gov/pcd/ .
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2005). Superfund Community Involvement Handbook. [Specifically,
p.000077: chapters 1 through 3.] EPA 540-K-05-003, Available: http://www.epa.gov/superfund/community/cag/pdfs/ci_hand book.pdf
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (1999). Risk Assessment Guidance for Superfund: Volume I – Human Health
p.000077: Evaluation Manual. Supplement to Part A. Community Involvement in Superfund Risk Assessments. EPA/540/R-98/042, OSWER
p.000077: 9285.7-01E-P, PB99-963303.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2000). El Superfund Hoy Día: La Estimación de Riesgos: Como Lograr la
p.000077: Participación de La Communidad. U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response.
p.000077: Washington, DC. EPA 540-K 99-005, OWSER 9200.2-26K, PB99-963230. Available:
p.000077: http://www.epa.gov/superfund/community/today/pdfs/risk fs-0203.pdf
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2001). Improved Science-Based Environmental Stakeholder Processes: A
p.000077: Commentary by the EPA Science Advisory
p.000077: Board. EPA-SAB-EC-COM-01-006. EPA Science Advisory Board. Washington, DC. Available:
p.000077: http://yosemite.epa.gov/sab/sabproduct.nsf/CEE3F362F1A1 344E8525718E004EA078/$File/eecm01006_report_appna e.pdf
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2003). Framework for Cumulative Risk Assessment. Washington, DC:
p.000077: United States Environmental Protection Agency. EPA/600/P-02/001F. Available:
p.000077: http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=54944 .
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2003). Framework for Assessing Risks of Environmental Exposure to
p.000077: Children. Washington, DC. Available: http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=22521.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2005). Guidance on Selecting Age Groups for Monitoring and Assessing
p.000077: Childhood Exposures to Environmental Contaminants. Risk Assessment Forum, Washington, D.C. EPA/630/P-03/003F.
p.000077: Available: http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=146583.
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). Considerations for Developing Alternative Health Risk
p.000077: Assessment Approaches for Addressing Multiple Chemicals, Exposures, and Effects. External Review Draft. 71 FR 16306.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). Paper on Tribal Issues Related to Tribal Traditional Lifeways,
p.000077: Risk Assessment, and Health and Well Being: Documenting What We’ve Heard. The National EPA-Tribal Science Council.
p.000077: Available: http://epa.gov/osp/tribes/tribal/TribalIssues.pdf.
p.000077:
p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2006). EPA’s Public Involvement Policy. Available:
p.000077: http://www.epa.gov/publicinvolvement/policy2003/index.htm.
p.000077:
p.000077: U.S. Food and Drug Administration (FDA). Exception from informed consent requirements for emergency research. 21 CFR §
p.000077: 50.24
p.000077:
p.000077: University of Kansas Community Tool Box. Available: http://ctb.ku.edu/en/tablecontents/.
p.000077:
p.000077: University of Washington Community-Campus Partners for Health, Available: http://depts.washington.edu/ccph/index.html.
p.000077:
p.000077: Veazie MA, Teufel-Shone NI, Silverman G, Connolly A, Warne S, King B, et al. (2001). Building community capacity in
p.000077: public health: The role of action-oriented partnerships. J Public Health Manag Pract 7(2):21-32.
p.000077:
p.000077:
p.000078: 78
p.000078:
p.000078: U.S. EPA, Office of Environmental Justice Resources:
p.000078: Executive Office of the President. (1997). Environmental Justice: Guidance under the National Environmental Policy Act.
p.000078: Council on Environmental Quality, pp. 7-17).
p.000078: Available: http://epa.gov/compliance/resources/policies/ej/ej_guidance
p.000078: _nepa_ceq1297.pdf
p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2006). Future mechanisms to enhance stakeholder involvement
p.000078: and engagement to address environmental justice: A letter report. Available:
p.000078: http://epa.gov/compliance/resources/publications/ej/nejac/st akeholder-involv-9-27-06.pdf
p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2004). Environmental justices and federal facilities:
p.000078: Recommendations for improving stakeholder relations between federal facilities and environmental justice communities.
...
p.000111: that knowing agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian
p.000111: or other duly authorized representative.
p.000111: (26) An account of any economic or other compensation or incentives to prospective subjects to participate, such as
p.000111: offers of cash payments, gifts, or free services or facilities, and of any financial
p.000111: obligations assumed by the subjects, such as payment for medical services
p.000111: (27) The plans and procedures and the persons responsible for communicating to
p.000111: subjects information arising from the study (on harm or benefit, for example) or from other research on the same
p.000111: topic that could affect subjects’ willingness to continue in the study
p.000111: (28) The plans to inform subjects about the results of the study
p.000111: (29) The provisions for protecting the confidentiality of personal data and respecting the privacy of subjects,
p.000111: including the precautions that are in place to prevent disclosure of the results of a
p.000111: subject’s genetic tests to immediate family relatives without the consent of the subject
p.000111: (30) Information about how the code, if any, for the subjects’ identity is established; where it will be
p.000111: kept; and when, how, and by whom it can be broken in the event of an emergency
p.000111: (31) Any foreseen further uses of personal data or biological materials
p.000111: (32) A description of the plans for statistical analysis of the study, including plans for interim analyses, if
p.000111: any, and criteria for prematurely terminating the study if necessary
p.000111: (33) A list of the references cited in the protocol
p.000111: (34) The source and amount of funding of the research, including the organization that is sponsoring the research
p.000111: and a detailed account of the sponsor’s financial commitments to the research institution,
p.000111: the investigators, the research subjects, and, when relevant, the community
p.000111: (35) The arrangements for dealing with financial or other conflicts of interest that might affect
p.000111: the judgment of investigators or other research personnel, including informing the institutional
p.000111: conflict-of-interest committee of such conflicts of interest; the communication by that committee of the
p.000111: pertinent details of the information to the ethical review committee; and the transmission by that committee to
p.000111: the research subjects of the parts of the information that it decides should be passed on to them
p.000111: (36) The time schedule for completion of the study
p.000111: (37) Particularly in the case of an industrial sponsor, a contract stipulating who possesses the
p.000111: right to publish the results of the study and a mandatory obligation to prepare with and submit
p.000111: to the principal investigators the draft of the text reporting the results
p.000111: (38) The circumstances in which it might be considered inappropriate to publish findings, such as when the findings
...
General/Other / Relationship to Authority
Searching for indicator authority:
(return to top)
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
...
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
...
p.000028: Should this information be documented in files that the researchers can make available to the
p.000028: participants, community, stakeholders, and the public? At the present time, there is no clear approach as
p.000028: to how to address these issues. Because these issues are associated with the IRB, not the
p.000028: researcher, it is outside the scope of this document to recommend approaches for IRBs to address
p.000028: these concerns. IRB processes and procedures will continue to evolve as recommended by various committees and
p.000028: workgroups (e.g., as reported in NRC & IOM, 2005; NRC, 2003; U.S. HHS, 1993).
p.000028: All human subjects research conducted or sponsored by NERL is subject to both the 40 CFR 26 requirements and procedures
p.000028: set forth in EPA Order 1000.17 Change A1 (www.epa.gov/oamrtpnc/forms/1000_17a.pdf). The EPA order establishes as
p.000028: policy that all research will comply with the Common Rule and with the order. All human research studies must be
p.000028: reviewed and approved by the EPA HSRRO before the work can begin.
p.000028: In NERL, the director of the division conducting or funding the research is the manager with the primary
p.000028: responsibility for developing the human subjects research protocol and for having that protocol reviewed
p.000028: by an independent IRB acceptable to the EPA HSRRO. The protocol also will be reviewed by the NERL HSRRO
p.000028: and by the appropriate NERL associate director before it is submitted to the IRB. Under 40 CFR 26.109, the IRB can
p.000028: demand changes to the research protocol and is the final authority for approving or disapproving the research
p.000028: activity.
p.000028:
p.000028: 2.5.5 Internal EPA Review of Scientific and Ethical Issues
p.000028: After IRB approval is obtained, the division director will be the primary manager responsible for preparing a request
p.000028: for review and approval or exemption of the human subjects research by the EPA HSRRO. The division
p.000028: director will ensure that the request is consistent with EPA Order 1000.17 A1 and all other policies or
p.000028: procedures that the EPA HSRRO may have established. The EPA HSRRO shall be the final authority for
p.000028: approving or disapproving the research effort. The EPA HSRRO may request additional reviews or establish
p.000028: additional policies and procedures for seeking review and approval. No human subjects research
p.000028: will begin⎯not even recruiting of potential participants⎯until the EPA HSRRO has
p.000028: approved or exempted the research.
p.000028:
p.000028: 2.6 Informed Consent
p.000028: Informed consent is discussed extensively in Section 5 of this document. The major focus is that
p.000028: informed consent is a process, not a form, that “should be an on-going, interactive dialogue between research
p.000028: staff and research participants involving the disclosure and exchange of relevant information, discussion of that
p.000028: information, and assessment of the individual’s understanding of the discussion” (Recommendation 4.1,
p.000028: IOM, 2002). These comments emphasize how important true two-way communication is to comprehension, the second
p.000028: pillar in the informed consent process. Informed consent is built on three “pillars:” (1) information; (2)
p.000028:
p.000028:
p.000029: 29
p.000029:
p.000029: comprehension; and (3) voluntary participation, or “voluntariness” (U.S. DHEW, 1979). Informed consent
p.000029: requires “provision of information to subjects about the purpose of the research, its procedures, potential
...
p.000043: 4-4). Some hazards may be associated with the potential for physical injury, whereas others may be related to
p.000043: exposure to chemical or biological agents. Some situations may be potential hazards only for young children,
p.000043: whereas other conditions may present potential hazards for all residents or occupants.
p.000043: The NRC & IOM recommend that researchers should consider such foreseeable observations and
p.000043: potential hazards in advance, develop responses to the risks, and submit the proposed plans to the IRB
p.000043: for review to ensure that they are appropriate “in the context of the research and the affected community.” The NRC
p.000043:
p.000043:
p.000044: 44
p.000044:
p.000044: & IOM also advise that field staff should be trained in how to assess and respond to
p.000044: such risks (Recommendations 7.3 and 7.4, NRC & IOM, 2005). For other behaviors and risks that
p.000044: have not been specifically identified in advance, procedures should be included in the data and safety monitoring
p.000044: and oversight provisions of the study design and research protocol to address these issues. The fundamental
p.000044: ethical principle of beneficence would motivate researchers who observe serious harms to take steps to try to prevent
p.000044: those harms, even for observations that are not directly related to the study. The steps that they may take can
p.000044: range from immediate action to prevent an imminent and serious danger to statutory reporting of
p.000044: observations (see Section 4.3.2) to reporting the observation to the data and safety monitoring and oversight
p.000044: authority for advice on how to respond (see Section 4.5). (The reader is also referred to pages 59-61 and 134-144 of
p.000044: the NRC & IOM [2005] report for a more thorough discussion of researchers’ responsibilities in such
p.000044: cases.)
p.000044:
p.000044: Text Box 4-4. Potential Hazards that Might Be Encountered in a Residential Environment
p.000044: • Unsecured firearm
p.000044: • Uncovered electrical outlets
p.000044: • Unprotected stairways
p.000044: • Missing child-protective cabinet latches
p.000044: • Lack of window guards
p.000044: • Missing or inoperable smoke alarm
p.000044: • Housing code violations
p.000044: • Chipping or flaking paint—potential for lead exposure in older homes
p.000044: • Malfunctioning or unvented combustion appliances—potential for carbon monoxide exposure
p.000044: • Unsecured poisons or other dangerous products
p.000044: • Excessive mold growth
p.000044:
p.000044:
p.000044: 4.3.2 Collateral Observations with Mandated Reporting Requirements
p.000044: Some collateral observations may have statutory requirements for reporting to designated authorities.
p.000044: Examples of such observations include
p.000044: • observed child or elder abuse or evidence of such abuse or neglect,
p.000044: • statements or actions of intent to harm self or others, and
p.000044: • certain communicable diseases.
p.000044: Because different reporting statutes pertain in different states, it is necessary for researchers to
...
p.000047: committees (DMOCs) for observational research (NEI, 2001). The role of the DMOC is to “assist the NEI and the
p.000047: study investigators in protecting the interests of study participants and in preserving the integrity and
p.000047: credibility of the study.”
p.000047: When appropriate, formal procedures for routine monitoring of scientific and ethical issues will need to be
p.000047: incorporated into observational research and approved by the IRB to ensure participant safety and the integrity of
p.000047: the research. Even though most observational human exposure studies are considered low-risk, there is often a need to
p.000047: determine whether appropriate threshold values for biological or environmental levels of chemicals exist or can be
p.000047: determined that, if the threshold value is exceeded, it would trigger reporting or other actions. The safety of
p.000047: measurement procedures and equipment also has to be considered. Unanticipated adverse events also may be
p.000047: encountered in observational research. Participant consent and understanding of the research effort,
p.000047: participant recruitment, participant retention, and data accuracy and quality should all be monitored to ensure
p.000047: the scientific integrity of research results.
p.000047: The authors already have discussed (Section 2.8) the needs (1) to establish, in advance, criteria and standards for
p.000047: monitoring the research program in regard to both scientific and ethical issues; (2) to establish who
p.000047: will monitor and oversee the research progress (the monitoring and oversight authority, be it
p.000047: an individual, team, or review committee); and (3) to establish the roles, responsibilities, and authorities
p.000047: of the researchers and of the monitoring and oversight authority. The planning also should include steps
p.000047: to meet the IOM recommendations that researchers should “anticipate risks and behaviors that may be
p.000047: observed in the home… [and] develop anticipatory plans that specify how to assess and respond to risks when they
p.000047: are identified, and educate their staffs about the plan” (Recommendation 7.3, p. 144, NRC & IOM, 2005).
p.000047: Once the procedures and organization for monitoring and oversight of the observational study are approved by the IRB,
p.000047: it is the responsibility of the researchers and of the monitoring and oversight authority to ensure that the planned
p.000047: actions are implemented. Implementation of the monitoring and oversight function may include the following
p.000047: items.
p.000047: • Ensuring that procedures for identifying, reporting, and responding to anticipated or unanticipated adverse
p.000047: events and safety issues are in place and are being followed
p.000047:
p.000047:
p.000048: 48
p.000048:
p.000048: • Assessing and responding to risks when they are identified
p.000048: • Evaluating the performance and knowledge of the staff regarding identification of potential risks and the
p.000048: actions they should take
p.000048: • Implementing procedures for monitoring the informed consent process, participant behaviors, participant
p.000048: recruitment, participant retention, procedures to protect privacy and confidentiality, and other
p.000048: human requirements for adherence to the research protocol and compliance with ethical standards and with EPA’s
p.000048: human subjects rules
p.000048: • Ensuring that measurements and samples are collected as planned, and that data are reported on a timely basis
p.000048: • Evaluating whether the observed measurements exceed the pre-established threshold values and, if so,
p.000048: ensuring that reporting procedures and plans to respond to the potential risks are completed on a
p.000048: timely basis
p.000048: • Ensuring that quality assurance plans that define procedures for assessing and ensuring study
p.000048: protocol compliance are being met
p.000048: • Ensuring data quality targets are met through independent internal or external auditing
p.000048: requirements
...
p.000060: documents, Ethical Issues in Housing-Related Health Hazard Research Involving Children (NRC and IOM, 2005)
p.000060: and Ethical Conduct of Clinical Research Involving Children (IOM, 2004). They should seek
p.000060: guidance from EPA’s HSRRO to determine EPA’s latest policies and guidance in this regard. Input also should be sought
p.000060: from community representatives to ensure that any payment is adequate to compensate for expenses and reward
p.000060: participation, but that the payment is not so high as to constitute undue influence or coercion in the
p.000060: community. If the study includes several followup visits over a long term, NERL researchers should ensure that payment
p.000060: is made incrementally as the NRC & IOM committee suggested. NERL scientists also should adopt the IOM
p.000060: Recommendations 6.1 and 6.2, including ensuring that any payment should be for appropriate purposes
p.000060: and age-appropriate, and that the process should be open and fully disclosed, while not overly
p.000060: emphasizing payments during the recruiting or informed consent phases. The final decisions about the ethics of
p.000060: payments rest with the IRB, which will review, modify as needed, and approve the research protocol, and with the EPA
p.000060: HSRRO, who has final authority to approve, modify, or disapprove all of NERL’s human subjects research
p.000060: efforts.
p.000060: 5.3 Research Rights and Grievance Procedures
p.000060: Protecting the research rights of participants and providing independent access to information regarding
p.000060: those rights and to grievance procedures is an important element in developing and maintaining appropriate
p.000060: participant-investigator relationships. As part of the informed consent process, the Common Rule
p.000060: requires “An explanation of whom to contact for answers to pertinent questions about the research and
p.000060: human subjects’ rights, and whom to contact in the event of a research-related injury to the
p.000060: subject” [40 CFR 26.116(a)(7)].
p.000060: Information about the research often best can be answered by the researcher. However, it may benefit
p.000060: researchers and participants if information about the research can be obtained from or confirmed by a trusted
p.000060: independent person or organization. Participants also need to know how they can contact
p.000060: someone, independent from the researcher, who can answer questions concerning the rights of research
p.000060: participants and provide information on grievance procedures and research-related injuries. These questions
p.000060: could be addressed to the IRB, an ombudsman, an ethics committee, or other knowledgeable
...
p.000070: North Carolina Farmworkers, where the process of defining a community was complicated by language,
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
p.000070: sense of community was nurtured among the farmworkers collectively (O’Fallon and Dearry, 2002).
p.000070: Understanding and describing a community (CDC, 1997) involves exploring factors related to
p.000070: • people (including socioeconomics and demographics, health status, and cultural and ethnic characteristics),
p.000070: • location (geographic boundaries),
p.000070: • commonalities (including shared values, interests, and motivating forces), and
p.000070: • power relationships (including formal and informal lines of authority and influence, stakeholder relationships, and
p.000070: resource flows).
p.000070: It is important to distinguish between stakeholders and the community, but both should be engaged at some point
p.000070: in the course of a study. Stakeholders are groups or organizations that may affect, be affected by, or perceive
p.000070: themselves to be affected by a decision or activity. Stakeholders may have a direct or indirect interest in the
p.000070: “matter” of interest. They may include individuals; environmental, social, or community
p.000070: nongovernment organizations (NGOs); government entities; businesses; and industry. Stakeholders include
p.000070: business, industry, and various levels of government. A critical difference between the community and
p.000070: stakeholders is that the community has a right to speak for its own interests, but stakeholders cannot
p.000070: represent or speak for the community. Although relationships with stakeholders can, at times, be
p.000070: confrontational, stakeholders often provide useful information and expertise. When stakeholders
p.000070: and the community members overlap in particular individuals, it is important to distinguish the role in
p.000070: which the individual is acting (ERG, 2007).
p.000070:
p.000070: 6.2.2 Identifying Who Represents the Community
p.000070: To sufficiently represent the community, an individual has to have not only the right to speak for the
p.000070: community’s interests (a right afforded by legitimate membership in the group) but also should be able
p.000070: to describe those interests on behalf of the community. Identifying those who represent the community is
p.000070: not simply a matter of identifying the most vocal activists because those individuals do not necessarily
p.000070: represent the interests of the entire community. In fact, several individuals may be necessary to adequately
p.000070: represent the diversity of viewpoints within a community; in such cases, a CAB may be appropriate (ERG, 2007).
p.000070: One of the researcher’s first steps should be asking the potential participants from the community who they see
p.000070: as a
p.000070:
p.000070:
p.000071: 71
p.000071:
p.000071: legitimate representative (i.e., someone who can speak for them). Corburn cites an example of a locale
p.000071: in Brooklyn, NY, that contained individuals with widely different backgrounds. It was impossible to
p.000071: identify appropriate spokespeople, or even to define the nature of the community, without talking with
p.000071: community members (Corburn, 2007).
p.000071: The NRC & IOM (2005) Report also discusses the issue of who can represent the identified community. Some
p.000071: communities may have a formal governmental structure and a recognized political authority (e.g.,
p.000071: Native American tribes). Other communities may have clearly identifiable leaders (e.g., religious communities),
p.000071: whereas still other communities have no formal leadership structure at all. Whether there is a
p.000071: legitimate political authority or some other hierarchal leadership structure, the goal is to seek community input
p.000071: as to who best represents the interests of the community with regard to the proposed research project,
p.000071: rather than selecting those who are favorable to the research project. The NRC & IOM report cautions against
p.000071: the ethically questionable practice of seeking out population spokespeople and research participants
p.000071: whose positive response to a research plan can be predicted in advance and refers the reader to an article on this
p.000071: topic by Juengst (2000).
p.000071: With multiple sources of leadership and authority in many communities, careful consideration should be given
p.000071: to what aspect of the community a particular person will represent, and what efforts may be needed to ensure
p.000071: that the entire range of views in a community are obtained. Researchers should consider reaching out to multiple
p.000071: organizations such as churches, social service agencies, community-based organizations, and tenant and
p.000071: other community advocacy groups.
p.000071:
p.000071: 6.2.3 Building Relationships and Trust
p.000071: A key first step in developing trust is to establish a relationship with the community before the study. Trust must be
p.000071: built; it cannot be assumed. This relationship involves not only listening to community input but
p.000071: actually taking it into consideration (ERG, 2007). A long history of research with no direct benefits and
p.000071: no feedback of results to the community, however, has contributed to a general mistrust of
p.000071: researchers by community members (Israel et al., 1998). Moreover, the recurring abuse of trust in communities is a
p.000071: reality that researchers should be aware of when attempting to build a long-term relationship (Minkler and
p.000071: Wallerstein, 2003). Past ethical failures have created distrust among some communities and have produced great
p.000071: challenges
p.000071: for current community organizers. Although it may seem self-evident, researchers need to remember that ethical
p.000071: action, during all phases of the research, is necessary for developing and maintaining the trust of communities
p.000071: (Perkins and Wandersman, 1990; CDC, 1997).
...
General/Other / Undue Influence
Searching for indicator undue influence:
(return to top)
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undue influence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
p.000055: dialogue . . . involving the disclosure and exchange of relevant information” (IOM, 2002): it is not
p.000055: simply having a consent form signed. The process is most effective when the researcher spends time with
p.000055: potential participants to discuss the study and to answer questions.
p.000055:
p.000055: 5.2 Payments to Research Participants
p.000055: The decision whether to pay research participants, including the appropriate level of payment,20 is
p.000055: a complex ethical issue. Monetary or nonmonetary payments are not ethical if they constitute an
p.000055: undue inducement for participants to assume research risks that they would not otherwise accept. On the other
p.000055: hand, it may be ethically appropriate to offer reasonable payments in some research studies. Indeed,
...
p.000057: additional human subjects protections do not directly address payments to research participants, but the
p.000057: regulations do discuss providing additional safeguards for subjects vulnerable to coercion or undue
p.000057: influence [40 CFR 26.111(b)]. The NIH IRB guidebook advises IRBs to determine whether the rewards offered for
p.000057: participation in research constitute undue influence (U.S. HHS, 1993). According to the IRB guidebook undue
p.000057: inducement might blind prospective subjects to risks, impair their ability to exercise proper judgment, or may
p.000057: cause people to lie or to withhold information that would make them ineligible to enroll or continue
p.000057: participation.
p.000057: The U.S. Food and Drug Administration (FDA) has provided guidance for investigators and IRBs for clinical research
p.000057: studies (FDA, 1998). The guidance states that “payment to research subjects for participation in studies is not
p.000057: considered a benefit, it is a recruitment incentive.” FDA expects payments to accrue as the study progresses and not
p.000057: to be contingent on completing the study, although a “small proportion as an incentive for
p.000057: completion of the study is acceptable.” The guidance is concerned with the issue of coercion or undue influence, and
p.000057: it recognizes the IRB as the responsible party for deciding what is or is not acceptable.
p.000057: The U.S. Office of Management and Budget (OMB) develops standards and guidelines for statistical surveys performed by
p.000057: the Federal government. Under Guideline 2.3.2, OMB states that, while incentives are not typically used in Federal
p.000057: surveys, agencies may consider use of respondent incentives if they believe incentives would be necessary
p.000057: to use for a particular survey to achieve data of sufficient quality for their intended use (OMB,
p.000057: 2006a). OMB requires that agencies provide a justification for giving incentives to respondents.
p.000057: Some
p.000057: of the factors cited by OMB to be addressed include those particularly relevant to observational
p.000057: human exposure studies, including unusual reporting burdens (keeping data logs for extended periods,
p.000057: coordinating study team visits, participating in a medical examination, etc.), complex study designs (such as
p.000057: studies requiring ongoing participation of respondents), and past experience, especially when there is
p.000057: evidence of attrition or poor response rates (OMB, 2006b). Although OMB primarily considers incentives with
p.000057: regard to survey response rates and data quality, researchers need to consider payments to
p.000057: participants, including participation incentives, in the broader context discussed in this section.
p.000057: CIOMS also provides guidance and commentary on this issue in the International Ethical Guidelines for Biomedical
p.000057: Research Involving Human Subjects (2002). Guideline 7 and the associated commentary emphasize that payments to
p.000057: subjects for expenses incurred because of their participating in a research study are legitimate. The guideline
p.000057: also allows payment for inconvenience and time spent, so long as the payments or other direct benefits are not
p.000057: “so extensive as to induce prospective subjects to consent to participate in research against their better
p.000057: judgment.”
p.000057: The approaches of HHS, FDA, and CIOMS above are consistent in not considering payments to be a benefit
p.000057: to research participants when considering risks versus benefits. All of the guidelines recognize the
p.000057: legitimacy of some recompense, but they all are concerned with the issue of undue influence. “Payments or
p.000057: rewards that undermine a person’s capacity to exercise free choice invalidate consent” (CIOMS, 2002), and
p.000057: voluntariness is a pillar of legitimate informed consent.
p.000057: Text Box 5-4 lists some of the concerns about, and the reasons for, payment of participants.
p.000057: IRBs have considerable discretion with regard to payments and consider payments with regard to the
p.000057: specific circumstances of the research and of the population being studied. The issue of recompense
p.000057: can be a difficult but legitimate ethical issue involving weighing the different ethical principles
p.000057: of justice and fairness against the concerns about undue influence and the invalidation of consent. Ethical
p.000057: review committees, including IRBs, need to consider many factors when determining when it is appropriate to
p.000057: offer payments to research participants and the level and form of payments when they are appropriate. Review
p.000057: committees also should consider how and when information on payments is communicated to prospective study
p.000057: participants.
p.000057:
p.000057:
p.000058: 58
p.000058:
p.000058:
p.000058: Text Box 5-4. Weighing the Ethical Issues About Payments
p.000058: Concerns about Payments Reasons for Payments
p.000058: • Payments may compromise • Recognizing participant voluntary participation.
p.000058: contributions to the
p.000058: • Participants may accept risks research and knowledge they would not otherwise gained
p.000058: accept. • Providing reimbursement
p.000058: • Participants may continue in a for direct and indirect research study beyond a point
p.000058: participant costs
p.000058: they might ordinarily have • Providing reasonable withdrawn.
p.000058: payment for the time and
p.000058: • Payments may differentially effort associated with encourage research
p.000058: participation in research participation by economically • Providing incentives for disadvantaged people.
p.000058: participation in studies
p.000058: • The offer of payments may with low risk but no or few cause guardians or parents to
p.000058: direct benefits
...
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
p.000058: benefits, or they may be particularly vulnerable to undue influence resulting from the offer of a payment for
p.000058: research participation. In addition, payments made directly to parents or guardians could alter
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
p.000058: gestures of appreciation, investigators may also—if they minimize the potential for undue influence—act ethically to
p.000058: reduce certain barriers to research participation when they
p.000058: • reimburse reasonable expenses directly related to a child’s participation in research
p.000058: • provide reasonable, age-appropriate compensation for children based on the time involved in research that does not
p.000058: offer the prospect of direct benefit, and
p.000058: • offer evening or weekend hours, on-site child care, and other reasonable accommodations for parental work and
p.000058: family commitments.”
p.000058: 22 In recommending an open process, the IOM committee chose to reject the
p.000058: arguments from the American Academy of Pediatrics that “any token payment to children for participating in research
p.000058: should not be discussed with them until after research is completed for fear of unduly influencing their decisions
p.000058: (AAP, 2003)…. On balance, the committee agrees that it is best to mention token or other payments during the permission
p.000058: and assent processes” (p. 215, IOM, 2004).
p.000058: The IOM Recommendation 6.1 states, “Institutional review boards, research institutions, and sponsors of research that
p.000058: includes children and adolescents should adopt explicit written policies on acceptable and unacceptable types and
p.000058: amounts of payments related to research participation. These policies should specify that investigators
p.000058: • Disclose the amount, the recipient, the timing, and the purpose (e.g., an expense reimbursement or a token of
...
p.000059: ranges in the amounts of payments for approved pediatric research. This research shows a lack of consistency and
p.000059: the need for guidance and institutional policies that describe acceptable and unacceptable
p.000059: payments and the basis for the amount of any payments.
p.000059: The NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children
p.000059: described many of the ethical considerations, practices, and policies regarding payments (NRC & IOM, 2005)
p.000059: for research conducted in the participants’ homes, rather than in a clinical facility. The research
p.000059: setting is similar to the setting of most observational
p.000059: human exposure studies, and the committee’s commentary and recommendations are also relevant. The
p.000059: committee notes that it would be unfair to expect families to make considerable sacrifices to
p.000059: participate in a time-consuming activity designed to advance generalizable scientific knowledge,
p.000059: rather than benefit themselves directly, and that payment for reimbursement of expenses and modest payment for
p.000059: time spent in research activities is justified on the grounds of fairness. But the committee then warns that if
p.000059: payments are too high, they may distort parents’ decisions about enrolling their children. The committee also
p.000059: found that “how the payment is made may also result in undue influence. For example, if payment for a long-term
p.000059: follow-up study is made in a lump sum and only if the subjects complete the entire study, then it
p.000059: could constitute an undue influence to stay in the study. If, on the other hand, the money is paid weekly, the
p.000059: effect would not constitute an undue influence.”
p.000059: The NRC & IOM committee recognizes that the issue of payment for participation in research is
p.000059: controversial. They also discuss how “countervailing ethical guidelines” may complicate the issues even more.
p.000059: Citing Wendler et al. (2002), the NRC & IOM committee points out that payments that are trivial
p.000059: for some families may be substantial for low-income or disadvantaged families. “Yet to pay
p.000059: economically disadvantaged families less than more affluent families for participating in the research is
p.000059: unfair because it requires similar sacrifices of time and inconvenience from both” (p. 113, NRC & IOM, 2005).
p.000059: Similar ethical quandaries can arise in multisite studies with differing costs for living. If the same payment
p.000059: is used in high-cost cities as in low-cost areas, the payment may be inadequate to gain sufficient
p.000059: enrollment in the high-cost area, whereas the same dollar amount may be “coercive” in the low-cost area. The NRC & IOM
p.000059: committee notes that a similar situation can arise when a study enrolls participants from diverse
p.000059: socioeconomic backgrounds. There are social justice concerns that poorer people might incur a disproportionate
p.000059: share of research risk and burden if payments induce unequal participation rates in the population. Decisions
p.000059: regarding payment for research participation will require careful consideration by IRBs when economically
p.000059: disadvantaged people may be enrolled. Community advisory boards (CABs) can be very important in helping
...
p.000062: characteristics;
p.000062: • advertisement or word-of-mouth contacts through community groups, civic organizations, or other types of
p.000062: organizations; and
p.000062: • recruitment at physicians’ offices, hospitals, and clinics or at churches, schools, or other
p.000062: social institutions, either in person or through the use of advertisements or study brochures.
p.000062: CABs can be consulted regarding proposed approaches for recruitment in community-based
p.000062: research. All procedures and materials for participant recruitment are reviewed and approved by the IRB prior to
p.000062: implementation. Some of the materials prepared for recruitment might include the following.
p.000062: • Recruitment scripts⎯prepared scripts used for in- person or telephone study information and recruitment
p.000062: contacts
p.000062: • Printed materials⎯brochures, flyers, newspaper advertisements, letters, and information articles
p.000062: • Audio/visual materials⎯radio and television scripts, video segments, public service announcements
p.000062: • Internet postings⎯study announcements and information, links to study materials, links to
p.000062: related information.
p.000062: The IRB reviews all recruitment material to ensure that it does not adversely affect the informed
p.000062: consent process, is consistent with the study protocol, and is likely to result in equitable participant
p.000062: selection. IRBs will carefully consider how information regarding payment for participation is
p.000062: presented to potential participants so as not to create undue influence.
p.000062: Participant recruitment may be performed directly by the researcher or staff members of the researcher’s
p.000062: organization, or other individuals or organizations may be asked to recruit or make initial informational
p.000062: contacts with potential participants. All persons involved in recruiting must adhere to the procedures
p.000062: and materials approved by the IRB. It is recommended that sponsoring organizations should not pay recruiters
p.000062: on a per- individual basis to minimize the likelihood that individual recruiters will put undue
p.000062: pressure on potential participants to enroll.
p.000062:
p.000062: 5.6 Retention Strategies
p.000062: Some observational human exposure studies require only a single visit or a single set of visits with a
p.000062: participant over a relatively short time period (e.g., 24 hours or 1 week). Other studies may involve
p.000062: repeated interaction with participants over longer periods of time. Longitudinal study designs require retention
p.000062: strategies that ensure that adequate sample sizes are maintained for meeting study objectives. It is
p.000062: recommended that researchers and IRBs evaluate the level of burden in longitudinal studies and ensure
p.000062: that retention strategies are not likely to create conditions of coercion or undue influence.
p.000062: Some of the common strategies for maintaining high retention rates in longitudinal studies are listed in Text
p.000062: Box 5-6.
p.000062:
p.000062: Text Box 5-6. Common Strategies for Maintaining High Retention Rates in Longitudinal Studies
p.000062: • Developing and maintaining a strong study identity
p.000062: • Building participant trust
p.000062: • Communicating regularly with participants
p.000062: • Providing feedback that is of use to participants
p.000062: • Maintaining confidentiality
p.000062: • Incorporating active participant tracking mechanisms
p.000062: • Maintaining reasonable levels of burden
p.000062: • Providing periodic tokens of appreciation
p.000062: • Providing reasonable levels of payment at each time point, sometimes including escalating payments or a higher
p.000062: final payment for completion of all study activities
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000063: 63
p.000063:
p.000063: It is important that strategies that use payments to encourage retention should be carefully
p.000063: scrutinized against the possibility that they will result in undue influence or diminish voluntary
p.000063: participation. Payments that cover expenses and for time and burden at each visit have to be reasonable, and
p.000063: researchers and IRBs should consider whether the cumulative level of payments over time or the use of escalating
p.000063: payments or final bonus payments might present undue influence on decisionmaking regarding
p.000063: participation. Participants have to feel capable of withdrawing from participation at any time, and escalating
p.000063: payments or completion bonuses can impact decisions to withdraw. Withholding all payment until all study
p.000063: visits are completed or making payment contingent on completing all activities is not an acceptable practice in
p.000063: most longitudinal studies because it can diminish the capacity for voluntary participation. (See the
p.000063: discussion about payment issues in long-term studies in Section 5.2.3.)
p.000063: People are more likely to continue active participation in longitudinal studies when they
p.000063: believe that the research is important, and that they are making a valuable contribution, are receiving regular
p.000063: feedback, and are treated with courtesy and respect by researchers. Observational human exposure studies
p.000063: sometimes involve substantial burdens of time and effort. Over long periods, this level of burden can reduce retention.
p.000063: It may be necessary to develop novel methods that reduce participant time and effort or to focus the study
p.000063: design so that fewer study procedures are implemented at any time point. Because the time needed to analyze
...
General/Other / belmont
Searching for indicator belmont:
(return to top)
p.000117: obligations derive from the ethical principles of biomedical ethics. NERL scientists and managers are
p.000117: resolved to meet both the “letter” of the law as set forth in the regulations and also the “spirit” that
p.000117: derives from the most up-to-date thinking and consensus on these sensitive issues.
p.000117: This document provides information on regulatory requirements and ethical issues to consider when
p.000117: performing human subjects research. Knowledge about these requirements and issues will help NERL scientists meet
p.000117: their goal of conducting observational human exposure studies based on the most up-to-date and sound science
p.000117: and the highest ethical scientific standards.
p.000117: The ethical and moral issues associated with human subjects research has long been the subject of a great deal
p.000117: of thought and discussion, both in the United States and abroad. Issues in biomedical ethics continue to be
p.000117: discussed and debated in today’s headlines. Spurred by the atrocities of World War II concentration camps and by
p.000117: the disclosure of unethical treatment of undereducated African-American men and
p.000117: other vulnerable groups by medical staff in the United States, the U.S. and world communities were prompted
p.000117: to establish ethical principles for medical and scientific experiments that involve people as
p.000117: participants. In the United States, the Belmont Report (U.S. DHEW, 1979) is the foundational document in the
p.000117: development of the
p.000117:
p.000117:
p.000001: 1
p.000001:
p.000001: ethics of human subjects research. This report lays out the fundamental ethical principles behind research
p.000001: that involves humans as research subjects. These three basic principles, (1) respect for persons, (2) beneficence,
p.000001: and
p.000001: (3) justice, have become the cornerstones for regulations involving human subjects. Ethicists have expanded on
p.000001: those principles since 1979, translating them into ethical requirements that any human subjects research must be both
p.000001: ethically acceptable and scientifically sound.1 EPA’s Science Advisory Board has affirmed, “Bad
p.000001: science is always unethical” (U.S. EPA, 2000).
p.000001: In an effort to ensure that NERL’s observational human exposure studies are founded on the ethical
p.000001: principles of respect for persons, beneficence and nonmaleficence, and justice and adhering to the
p.000001: principle that bad science is always unethical, scientists and managers from NERL have assembled this
p.000001: document as a resource and reference for NERL exposure scientists. These same scientists and managers have sought
p.000001: expert advice, including input from an expert panel workshop; review and comment on the external review draft of the
p.000001: document by the Human Studies Review Board (HSRB), a Federal advisory committee; public comment on the external
p.000001: review draft of the document; and public input about the state of the science for scientific and ethical
...
p.000001: Review
p.000001: Develop Study Design
p.000001:
p.000001:
p.000001: Peer Review
p.000001: Scientific & Ethical Review
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: HSRRO
p.000001: Review
p.000001: Develop Human Subjects Protocol
p.000001:
p.000001:
p.000001: IRB Review
p.000001: Ethical & Scientific Review
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Disapprove No Study
p.000001:
p.000001: for both the structure and the content of this document (ERG, 2007). Following the advice of the Expert Panel,
p.000001:
p.000001: Implement Study
p.000001: Approve Conduct Study
p.000001:
p.000001: this document is organized in seven sections.
p.000001: & Monitor Progress
p.000001: Criteria OK
p.000001: Continue Study
p.000001: Implement
p.000001: & Monitor
p.000001: Criteria Exceeded
p.000001: Terminate Study
p.000001:
p.000001:
p.000001: 1 See, for example, the writings of Beauchamp and Childress in Principles of Biomedical Ethics (Beauchamp and
p.000001: Childress, 2001) and the discussion of “What Makes Clinical Research Ethical?” by Emanuel, Wendler, and Grady (Emanuel
p.000001: et al., 2000).
p.000001: Stages in the Development of a NERL Observational Human Exposure Study
p.000001:
p.000002: 2
p.000002:
p.000002:
p.000002: Table 1-4. Important References in Developing This Document:
p.000002: Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
p.000002:
p.000002:
p.000002: Year
p.000002: Event/Report
p.000002: Description
p.000002:
p.000002:
p.001979: 1979
p.001979:
p.001979: The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (U.S. DHEW,
p.001979: 1979)
p.001979:
p.001979: The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively created National
p.001979: Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. It is a statement of basic
p.001979: ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of
p.001979: research with human subjects. The three basic ethical principles are (1) respect for persons, (2) beneficence, and (3)
p.001979: justice.
p.001979:
p.001979:
p.001991: 1991
p.001991:
p.001991: The Common Rule
p.001991: 40 CFR 26, Subpart A
p.001991:
p.001991: The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects” and was adopted by more
p.001991: than a dozen Federal departments or agencies in 1991. Each agency incorporated the policy into its own Code of Federal
p.001991: Regulations (CFR), with EPA adapting it in Title 40 CFR Part 26, Subpart A.
p.001991:
p.001991:
p.001993: 1993
p.001993:
p.001993: The Institutional Review Board Guidebook (U.S. HHS, 1993)
p.001993:
p.001993: The document is intended as a resource and a reference document for IRB members, researchers, and institutional
p.001993: administrators. It is not designed to tell IRBs whether or not specific protocols should be approved; rather, the
p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
...
p.000003: April 2008].
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000003: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000003:
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000004: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000004:
p.000004: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
p.000004:
p.000004: ERG (Eastern Research Group) (2007). Report on the Workshop to Discuss State-of-the-Science Approaches for
p.000004: Observational Exposure Measurement Studies. Held in Durham, North Carolina on November 28-29, 2006. Final Report:
p.000004: January 25, 2007. (PB2007-108905).
p.000004:
p.000004: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000004: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000004: [accessed 12 June 2007].
p.000004:
p.000004: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000004: Housing-Related Health Hazards Involving Children.
p.000004: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000004: June 2007].
p.000004: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
p.000004: Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of Human Subjects
p.000004: of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 12 June
p.000004: 2007].
p.000004:
p.000004: U.S. EPA (U.S. Environmental Protection Agency) (2000) Comments on the Use of Data from the Testing of Human Subjects:
p.000004: A Report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. United States Environmental Protection
p.000004: Agency, Science Advisory Board, EPA-SAB-EC-00-017. Available: http://yosemite.epa.gov/sab/SABPRODUCT.NSF/E3AE0F3
p.000004: 0D7430436852571A7005325E8/$File/ec0017.pdf [accessed 12 June 2007].
p.000004:
p.000004: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000004: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000004: [accessed 12 June 2007].
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000005: 5
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
...
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
p.000008: from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in specified
p.000008: rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in this
p.000008: document.
p.000008: 5 The Glossary (Appendix F) lists definitions for a number of important terms; definitions that come from the
p.000008: regulatory language are identified with their specific CFR citation.
p.000008: about the most recent thinking and guidance on protection of human subjects.
p.000008: The Belmont Report (U.S. DHEW, 1979) is a foundational document in the development of the ethics of human
p.000008: subjects research in the United States. Because of the adverse publicity and political embarrassment arising
p.000008: from the unethical treatment of African- American men in the Tuskegee Syphilis Study, Congress passed
p.000008: the National Research Act of 1974, which called on the Department of Health, Education, and Welfare (DHEW) to
p.000008: codify its rules on human subjects research and established the National Commission for the Protection of
p.000008: Human Subjects of Biomedical and Behavioral Research. The commission was charged with identifying the
p.000008: basic ethical principles that should underlie human subjects research. The commission published the
p.000008: Belmont Report in 1979. This report established three basic principles: (1) respect for
p.000008: persons; (2) beneficence; and (3) justice, which have become the cornerstones for regulations involving
p.000008: human subjects (see Table 1-2).
p.000008: In 1981, the Department of Health and Human Services (HHS) issued regulations based on the Belmont Report. Ten
p.000008: years later, the core HHS regulations (Subpart A) were adopted by almost all of the Federal
p.000008: departments and agencies that conducted or sponsored human subjects research as the “Common Rule.”
p.000008: Since 1991, ethical thought and regulatory processes for the protection of human subjects have continued to
p.000008: evolve and grow. For example, many ethicists expand the elements contained in the principle of
p.000008: beneficence from the Belmont Report into two principles:
p.000008: (1) beneficence, meaning to prevent or remove harm and
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: to maximize the possible benefits; and
p.000009: (2) nonmaleficence, meaning not to inflict harm (Beauchamp and Childress, 2001).
p.000009:
p.000009: Table 1-2. The Belmont Report— Principles and Recommendations
p.000009:
p.000009: Ethical Principle Regulatory Manifestation
p.000009: addressed many important scientific and ethical issues on this topic, including the National Research
p.000009: Council (NRC) in its report, Protecting Participants and Facilitating Social and Behavioral Sciences
p.000009: Research (NRC, 2003), a joint NRC and Institute of Medicine (NRC & IOM, 2005) committee in the report on
p.000009: Ethical Considerations for Research on Housing-Related Health Hazards Involving Children; the Council
p.000009: for
p.000009:
p.000009: Respect for Persons
p.000009: • Individuals should be treated as autonomous agents.
p.000009: • Persons with diminished autonomy are entitled to protection.
p.000009:
p.000009: Beneficence
p.000009: • Human subjects should not be harmed.
p.000009: • Research should maximize possible benefits and minimize possible harms.
p.000009: Justice
p.000009: • The benefits and risks of research must be distributed fairly.
p.000009: Informed Consent
p.000009: • Subjects must be given the opportunity to choose what will or will not happen to them
p.000009: • The consent process must include
p.000009: (1) information,
p.000009: (2) comprehension, and
p.000009: (3) voluntariness
p.000009: Assessment of Risks and Benefits
p.000009: • The nature and scope of risks and benefits must be assessed in a systematic manner.
p.000009:
p.000009:
p.000009: Selection of Subjects
p.000009: • There must be fair procedures and outcomes in the selection of research subjects.
p.000009: International Organizations of Medical Sciences (CIOMS) under the World Health Organization in
p.000009: its International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002) and
p.000009: in the International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008); and
p.000009: the National Ethics Advisory Committee of New Zealand in the Ethical Guidelines for Observational Studies:
p.000009: Observational Research, Audits and Related Activities (NEAC, 2006).
p.000009:
p.000009:
p.000009: Table 1-3. Seven Ethical Requirements for Clinical Research
p.000009: From Emanuel, Wendler, and Grady (2000)
p.000009: Requirement Explanation
p.000009: Evaluation of a treatment, intervention, or theory
p.000009:
p.000009: In 2000, Emanuel, Wendler, and Grady considered the ethical principles involved in clinical research and
p.000009: proposed seven ethical requirements to be addressed in research with humans (Emanuel et al., 2000). Their
p.000009: published article specifically addressed clinical research, but the issues are similar for observational
p.000009: human exposure studies. Their ethical requirements are summarized and briefly explained in Table
p.000009: 1-3. The requirements are a logical extension of the ethical principles enunciated in the
p.000009: Belmont Report and manifest themselves in additional requirements for social or scientific value; for
p.000009: processes to ensure the scientific integrity of the research; and for independent review of the design,
p.000009: the subject population, and the risk-benefit ratio. The principle of respect for subjects also includes
p.000009: additional emphasis on the welfare of the subjects.
p.000009: More recently, there has been increased scrutiny and discussions of the ethics of research involving human
p.000009: participants,6 and a number of respected institutions have
p.000009:
p.000009:
p.000009: 6 The term “human participants” often is used in this document. It denotes the importance of the study participant
p.000009: being actively engaged in a partnership with the researchers to address the objectives and goals of the study. The term
p.000009: should be considered to be synonymous with the term “human subject” as used in the Common Rule and in documents used to
p.000009: describe regulatory requirements for studies involving human subjects.
p.000009: Social or scientific value
p.000009:
p.000009: Scientific validity
p.000009:
p.000009:
p.000009: Fair subject selection
p.000009:
p.000009:
p.000009: Favorable risk- benefit ratio
p.000009:
p.000009:
p.000009: Independent review
p.000009:
p.000009:
p.000009:
p.000009: Informed consent
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Respect for potential and enrolled subjects
p.000009: that will improve health and well-being or increase knowledge
p.000009: Use of accepted scientific principles and methods, including statistical techniques, to produce reliable and valid data
p.000009: Selection of subjects so that stigmatized and vulnerable individuals are not targeted for risky research, and the rich
p.000009: and socially powerful are not favored for potentially beneficial research
p.000009: Minimization of risks; enhancement of potential benefits and risks to the subject are proportionate to the benefits to
p.000009: the subject and to society
p.000009: Review of the design of the research trial, its proposed subject population, and risk-benefit ratio by individuals
p.000009: unaffiliated with the research
p.000009: Provision of information to subjects about the purpose of the research and its procedures, potential risks, benefits,
p.000009: and alternatives, so that the individual understands this information and can make a voluntary decision whether to
p.000009: enroll and continue to participate
p.000009: Respect for subjects by
p.000009: • permitting withdrawal from the research,
p.000009: • protecting privacy through confidentiality,
p.000009: • informing subjects of newly discovered risks or benefits,
p.000009: • informing subjects of results of the research, and
p.000009: • maintaining welfare of subjects.
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: Collectively, these documents have reaffirmed the basic ethical principles asserted in the Belmont Report
p.000010: and have attempted, in some cases, to expand scientific and ethical reasoning and understanding to define
p.000010: approaches for dealing with additional elements of human subjects research. These additional
p.000010: elements, which often have been identified because of specific incidents or case studies, include issues
p.000010: such as those described below.
p.000010: • Payment to participants⎯How much is adequate and fair, without being an undue inducement?
p.000010: • Non-study hazards⎯What is the researcher’s responsibility to identify hazards in the home that are
p.000010: not part of the study?
p.000010: • Third-party issues⎯Are there people other than the participant who may be impacted during the study and by the
p.000010: study results? If so, what needs to be done to protect their interests and to respect them as persons?
p.000010: • Community involvement⎯How should the community be involved in the design
p.000010: and implementation of studies?
p.000010: These documents, together with EPA’s regulatory requirements for the protection of human subjects, serve as
p.000010: important references for the subsequent sections of this document (see Table 1-4).
p.000010:
p.000010: 1.3 Purpose of This Document
p.000010: This document is meant to serve as a resource of current scientific and ethical information for
p.000010: NERL researchers as they develop and conduct observational human exposure studies. The increased
...
p.000010: scientific issues and approaches are discussed as they relate to and impact ethical issues. However, it
p.000010: is beyond the scope of this document to present a comprehensive discussion of the scientific approaches for
p.000010: observational human exposure studies. To include a comprehensive discussion of scientific approaches in
p.000010: this document would reduce the utility of the document by increasing the complexity of the presentation and the length
p.000010: of the document.
p.000010: This document does not provide solutions to all scientific and ethical issues that may arise as such
p.000010: studies are undertaken. That is, it is not possible to identify or address all potential issues in
p.000010: advance or develop a comprehensive checklist for all such studies. Rather, this document attempts to
p.000010: present and discuss the types of issues that will need to be considered and addressed as NERL
p.000010: researchers plan and implement observational human exposure studies. The researchers will need to work with
p.000010: others⎯the study team, IRB members, EPA HSRRO, the participants and their community, and other
p.000010: stakeholders⎯to identify and
p.000010:
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011: Table 1-4. Important References in Developing This Document:
p.000011: Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
p.000011:
p.000011:
p.000011: Year
p.000011: Event/Report
p.000011: Description
p.000011:
p.000011:
p.001979: 1979
p.001979:
p.001979: The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (U.S. DHEW,
p.001979: 1979)
p.001979:
p.001979: The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively created National
p.001979: Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. It is a statement of basic
p.001979: ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of
p.001979: research with human subjects. The three basic ethical principles are (1) respect for persons, (2) beneficence, and (3)
p.001979: justice.
p.001979:
p.001979:
p.001991: 1991
p.001991:
p.001991: The Common Rule
p.001991: 40 CFR 26, Subpart A
p.001991:
p.001991: The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects” and was adopted by more
p.001991: than a dozen Federal departments or agencies in 1991. Each agency incorporated the policy into its own Code of Federal
p.001991: Regulations (CFR), with EPA adapting it in Title 40 CFR Part 26, Subpart A.
p.001991:
p.001991:
p.001993: 1993
p.001993:
p.001993: The Institutional Review Board Guidebook (U.S. HHS, 1993)
p.001993:
p.001993: The document is intended as a resource and a reference document for IRB members, researchers, and institutional
p.001993: administrators. It is not designed to tell IRBs whether or not specific protocols should be approved; rather, the
p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
...
p.000013:
p.000013: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000013:
p.000013: NEAC (National Ethics Advisory Committee) (2006). Ethical Guidelines for Observational Studies: Observational research
p.000013: audits and related activities. Wellington, New Zealand: Ministry of Health. Available:
p.000013: http://www.neac.health.govt.nz/moh.nsf/indexcm/neac resources-publications-ethicalguidelines.
p.000013:
p.000013: NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing Research
p.000013: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000013: [accessed 16 August 2007].
p.000013:
p.000013: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000013: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000013: [accessed 12 June 2007].
p.000013:
p.000013: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000013: Housing-Related Health Hazards Involving Children.
p.000013: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000013: June 2007].
p.000013:
p.000013: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
p.000013: Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of Human Subjects
p.000013: of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 12 June
p.000013: 2007].
p.000013:
p.000013: U.S. EPA (U.S. Environmental Protection Agency) (1999). Air Quality Criteria for Particulate Matter. Environmental
p.000013: Protection Agency, National Center for Environmental
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014: Assessment, Office of Research and Development. EPA/600/P-99/002.
p.000014:
p.000014: U.S. EPA (U.S. Environmental Protection Agency) (1992). Guidelines for Exposure Assessment. Environmental Protection
p.000014: Agency, Risk Assessment Forum. EPA/600/Z 92/001. Available: http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_
p.000014: id=429103 [accessed 15 April 2008].
p.000014:
p.000014: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000014: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000014: [accessed 12 June 2007].
p.000014:
p.000014: U.S. OMB (U.S. Office of Management and Budget) (2007). Final Bulletin for Agency Good Guidance Practices, Section
p.000014: I(3). Federal Register 72:16 (25 January 2007) p. 3432. Available:
p.000014: http://www.whitehouse.gov/omb/fedreg/2007/012507_good
p.000014: _guidance.pdf [accessed 6 December 2007].
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
p.000014:
...
p.000018: small-scale and large-scale human exposure studies do involve human subjects. This means that the studies
p.000018: must meet both ethical standards and regulatory requirements. Regardless of the study’s scale,
p.000018: the scientific study design must be technically sound and appropriate to meet the objectives of the study. But
p.000018: the nature and objectives of the scientific inquiry will be different when the study is designed
p.000018: to test a methodology versus when the study is intended to measure a representative
p.000018: distribution of people’s exposures. Defining the study problem is a critical and fundamental first step
p.000018: in the scientific process, because it
p.000018: will establish the objectives that the research will be designed to achieve and the uses to which the research
p.000018: data will be put. The details of the scientific design of the study will naturally be strongly
p.000018: influenced by the objectives that the research is intended to meet.
p.000018:
p.000018: 2.1.2 Justifying the Study
p.000018: Justification of any human study includes both a scientific and an ethical justification. In the list of seven
p.000018: ethical requirements that must be met for human subjects research to be considered ethically acceptable, four of
p.000018: those requirements, (1) respect for subjects, (2) informed consent, (3) favorable risk-benefit ratio, and (4)
p.000018: fair subject selection, are founded on the traditional ethical principles enunciated in the Belmont
p.000018: Report and codified in the Common Rule (Emanuel et al., 2000). But three requirements, (1) social or
p.000018: scientific value,
p.000018: (2) scientific validity, and (3) independent review, apply directly to the scientific aspects of the study. Similarly,
p.000018: Guideline 1 from the CIOMS (2002) document reiterates the foundational principle that “scientifically invalid
p.000018: research is unethical.” Beyond the traditional ethical expectations of respect for, protection of, and fairness
p.000018: to the research subjects, CIOMS requires investigators and sponsors to ensure that the research be
p.000018: “scientifically sound,” that it “conform to generally accepted, scientific principles,” and that all researchers
p.000018: be “qualified” and “competent.”7 Text Box 2-1 identifies a number of elements that should be
p.000018: considered in justifying an observational human exposure study. As discussed below, a critical element to
p.000018: support justification of both the scientific and ethical elements of a study is the use of independent scientific and
p.000018: ethical peer review.
p.000018:
p.000018:
p.000018:
p.000018: 7 Guideline 1 states “research can be ethically justifiable only if it is carried out in ways that respect and
p.000018: protect, and are fair to, the subjects of that research and are morally acceptable within the communities in which the
p.000018: research is carried out. Moreover, because scientifically invalid research is unethical in that it exposes research
...
p.000027: a human subjects research protocol (Appendix 1, CIOMS, 2002). Many of the items that they identify are also
p.000027: useful for observational human exposure studies. (The CIOMS items can be found in Appendix C of this
p.000027: document.) The authors recommend that anyone developing a human subjects protocol for observational human
p.000027: exposure studies review and utilize the CIOMS list of topics, as appropriate. Text Box 2-5
p.000027: identifies a number of topics that should be considered in development of the human subjects research protocol.
p.000027: In addition, the authors’ experience leads them to suggest that three additional topics beyond those from
p.000027: the CIOMS (2002) document also may need to be considered in a human subjects protocol: (1) approaches to
p.000027: minimize changes in participant behavior because of participation in the study (see Section 2.3.4);
p.000027: (2) approaches to minimize therapeutic misconception (see Section 5.4.1); and (3) actions to involve
p.000027: the community in a community-based participatory research
p.000027:
p.000027: Text Box 2-5. Potential Topics in a Human Subjects Research Protocol
p.000027: 1. Title
p.000027: 2. Summary in lay language
p.000027: 3. Justification for the study
p.000027: 4. Ethical issues and proposed resolution
p.000027: 5. Summary of previous research
p.000027: 6. Affirmation of Belmont Principles and 40 CFR 26 compliance
p.000027: 7. Previous history or use of the protocol
p.000027: 8. Information on the location and demographics of research
p.000027: 9. Information on funding organization, researcher partners, and collaborators
p.000027: 10. Names, qualifications, and experience of investigators
p.000027: 11. Objectives, hypotheses, assumptions, and variables
p.000027: 12. Study design
p.000027: 13. Sample size and power and statistical analysis plan
p.000027: 14. Criteria and justification for subject selection
p.000027: 15. Justification for use of vulnerable groups, if any
p.000027: 16. Process of recruitment
p.000027: 17. Actions to involve the community in a community-based participatory research program
p.000027: 18. Description and explanation of any and all interventions
p.000027: 19. Measurements or data to be collected
p.000027: 20. Any clinical or other tests
p.000027: 21. Rules or criteria for removing subjects or terminating the study
p.000027: 22. Adverse events and unanticipated problems⎯reporting and responses
p.000027: 23. Potential benefits to subjects or others
p.000027: 24. Expected benefits of the research to the population
p.000027: 25. Informed consent process and responsibilities
p.000027: 26. Protections for the consent/assent of vulnerable participants
p.000027: 27. Efforts to minimize “therapeutic misconception”
p.000027: 28. Approaches to minimize changes in participant behavior
p.000027: 29. Payments
p.000027: 30. Plans for informing subjects about items that could affect subjects’ willingness to continue in the study
p.000027: 31. Plans to inform subjects about the results of the study
...
p.000031: review board. Environmental Health Perspectives 114(10): 1626-1629.
p.000031:
p.000031: Kraemer HC, Thiemann S (1987). How Many Subjects? Statistical Power Analysis in Research. Newbury Park, CA: Sage
p.000031: Publications.
p.000031:
p.000031: Lenth RV (2001). Some practical guidelines for effective sample size determination. American Statistician 55(3):
p.000031: 187-193. Available:
p.000031: http://www.stat.uiowa.edu/techrep/tr303.pdf [accessed 13
p.000031: June 2007].
p.000031:
p.000031: NRC (National Research Council) (2003). Protecting Participants and Facilitating Social and Behavioral Sciences
p.000031: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000031: [accessed 12 June 2007].
p.000031:
p.000031: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000031: Housing-Related Health Hazards Involving Children.
p.000031: Washington, DC: The National Academies Press. Available:
p.000031:
p.000031:
p.000032: 32
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p.000032: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12 June 2007].
p.000032:
p.000032: OHRP (Office for Human Research Protections) (2007). U.S. Department of Health and Human Services [Online].
p.000032: Available: http://www.hhs.gov/ohrp/ [accessed 13 June 2007].
p.000032:
p.000032: Resnik DB, Wing S (2007). Lessons learned from the Children's Environmental Exposure Research Study. Am J Public Health
p.000032: 97(3): 414-8.
p.000032:
p.000032: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979). The Belmont Report: Ethical Principles and
p.000032: Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: National Commission for the Protection
p.000032: of Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
p.000032: [accessed June 2007].
p.000032: U.S. EPA (U.S. Environmental Protection Agency) (2000). Comments on the use of data from the testing of human subjects:
p.000032: A report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. Environmental Protection Agency,
p.000032: Science Advisory Board. EPA-SAB-EC-00-017. Available: http://www.epa.gov/scipoly/sap/meetings/1999/november/e c0017.pdf
p.000032: [accessed 16 April 2008].
p.000032:
p.000032: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000032: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000032: [accessed 12 June 2007].
p.000032:
p.000032: Van Belle G, Fisher L (2004). Biostatistics: A Methodology for the Health Sciences (2nd Edition) Hoboken, NJ: John
p.000032: Wiley & Sons.
p.000032:
p.000032: Wackerly DD, Mendenhall W, Scheaffer RL (2001). Mathematical Statistics with Applications (6th Edition). Pacific Grove,
p.000032: CA: Duxbury Press.
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
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p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: SECTION 3
p.000033: Ensuring Protection of Vulnerable Groups
p.000033:
p.000033:
p.000033:
p.000033: Concern for the protection of vulnerable groups is fundamental to modern ethical thought and guidelines.
p.000033: The Belmont Report was “meant to provide broad principles that could be used to generate specific
p.000033: rules and regulations in response to [U.S.] research scandals such as Tuskegee and Willowbrook.11 It
p.000033: focuses on informed consent, favorable risk-benefit ratio, and the need to ensure that vulnerable
p.000033: populations are not targeted for risky research” [emphasis added] (Emanuel et al., 2000).
p.000033: The Common Rule requires IRBs to assure that “additional safeguards have been included in the study to protect
p.000033: the rights and welfare of these [vulnerable] subjects” [at 40 CFR 26.111(b) in CFR, 2006a]. If an
p.000033: observational human exposure study includes vulnerable research participants, it is essential that the investigators be
p.000033: cognizant of the special issues and requirements of research involving vulnerable populations. Researchers
p.000033: have to justify the involvement of vulnerable populations in the research study and
p.000033: include the appropriate safeguards for protection of their safety and welfare. The Common Rule protections are
...
p.000054: that a direct therapeutic benefit will be provided by virtue of participation in a clinical trial.
p.000054: Researchers performing observational human exposure studies should be aware of the potential for misunderstandings to
p.000054: arise that are analogous to the misunderstanding represented by the therapeutic misconception. Ensuring comprehension
p.000054: of the study and its expected results is important to this issue.
p.000054: serve as a model going forward. The video presentation will include embedded questions
p.000054: to assess the participant’s understanding of the key elements of NCS and what their participation
p.000054: will involve (NCS, 2007).
p.000054: • Development of written materials with appropriate languages and comprehension levels is only part of the
p.000054: communication challenge. In communities where languages other than English are spoken, it will be
p.000054: important that the research team be able to communicate orally with participants, often in ad hoc
p.000054: situations. Research protocols should address how translations will be accomplished. The use of
p.000054: untrained persons such as co-workers usually will not meet requirements for full understanding of human subject
p.000054: protections. Researchers should make plans for trained staff or trained community members, associated
p.000054: or affiliated with the research study, to be available for translations.
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
...
p.000064: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000064: [accessed 16 August 2007].
p.000064:
p.000064: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000064: Housing-Related Health Hazards Involving Children.
p.000064: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000064: June 2007].
p.000064:
p.000064: OMB (Office of Management and Budget). (2006a). Standards and Guidelines for Statistical Surveys. Section 2.3, Data
p.000064: Collection Methodology. http://www.whitehouse.gov/omb/inforeg/statpolicy/standard s_stat_surveys.pdf
p.000064:
p.000064: OMB (Office of Management and Budget). (2006b). Questions and Answers When Designing Surveys for Information
p.000064: Collection. Office of Information and Regulatory Affairs. January, 2006.
p.000064: http://www.whitehouse.gov/omb/inforeg/pmc_survey_guidanc e_2006.pdf
p.000064:
p.000064: Paasche-Orlow MK, Taylor HA, Brancati FL (2003). Readability standards for informed-consent forms as compared with
p.000064: actual readability. N Engl J Med 348(8):721 6.
p.000064:
p.000064: Russell ML, Moralejo DG, Burgess ED. (2000). Paying research subjects: participants' perspectives. J Med Ethics
p.000064: 26(2):126-30.
p.000064:
p.000064: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979). The Belmont Report: Ethical Principles and
p.000064: Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: National Commission for the Protection
p.000064: of Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
p.000064: [accessed June 2007].
p.000064:
p.000064: U.S. FDA (U.S. Food and Drug Administration) (1998). Information Sheets: Guidance for Institutional Review Boards and
p.000064: Clinical Investigators 1998 Update. U.S. Food and Drug Administration, Washington, DC. Available:
p.000064: http://www.fda.gov/oc/ohrt/irbs/toc4.html [accessed May 2007].
p.000064:
p.000064: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
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p.000065: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000065: [accessed 12 June 2007].
p.000065:
p.000065: VanderWalde A (2005). Undue inducement: the only objection to payment? Am J Bioethics 5(5):25-27.
p.000065: Weise KL, Smith ML, Maschke KJ, Copeland L (2002). National practices regarding payment to research subjects for
p.000065: participating in pediatric research. Pediatrics 110(3):577-582.
p.000065:
p.000065: Wendler D, Rackoff JE, Emanuel EJ, Grady C (2002). The ethics of paying for children’s participation in research. J
p.000065: Pediatr 141(2):166-171.
p.000065:
p.000065:
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...
p.000108: that should be considered for inclusion?
p.000108: 3. Is the information presented accurately and clearly in each section?
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000109: 109
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109: Appendix C
p.000109: Recommended Content of a Human Subjects Protocol
p.000109:
p.000109:
p.000109:
p.000109: The Council for International Organizations of Medical Sciences (CIOMS, 2002) has developed a comprehensive list of
p.000109: items that they recommend for inclusion in a human subjects research protocol. Many of the items that they identify
p.000109: are also useful for observational human exposure studies.
p.000109:
p.000109: Items Relevant to Observational Human Exposure Studies
p.000109:
p.000109: (1) The title of the study
p.000109: (2) A summary of the proposed research in lay or nontechnical language
p.000109: (3) A clear statement of the justification for the study
p.000109: (4) The investigators’ views of the ethical issues and considerations raised by the study and,
p.000109: if appropriate, how it is proposed to deal with them
p.000109: (5) A summary of previous studies on the research problem, including unpublished studies known to the
p.000109: investigators, and information on previously published research on the topic
p.000109: (6) A statement that the principles of the Belmont Report and requirements specified in 40 CFR 26 will
p.000109: be implemented
p.000109: (7) An account of previous submissions of the protocol for ethical review and their outcomes
p.000109: (8) A brief description of the sites where the research is to be conducted, including information about the
p.000109: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000109: epidemiological information about the population to be studied
p.000109: (9) The names and addresses of the funding organization, research partners, and collaborators
p.000109: (10) The names, addresses, institutional affiliations, qualifications, and experience of the
p.000109: principal investigator and other investigators
p.000109: (11) The objectives of the study, its hypotheses or research questions, its assumptions, and
p.000109: its variables
p.000109: (12) A detailed description of the design of the study
p.000109: (13) The number of research subjects needed to achieve the study objective, and how this was determined
p.000109: statistically
p.000109: (14) The criteria for inclusion or exclusion of potential subjects and justification for the exclusion of
p.000109: any groups on the basis of age, sex, social or economic factors, or other reasons
p.000109: (15) The justification for involving as research subjects any persons with limited capacity to consent or
p.000109: members of vulnerable social groups and a description of special measures to minimize risks and
p.000109: discomfort to such subjects
...
General/Other / cioms guidelines
Searching for indicator cioms:
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p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
p.002000: What Makes Clinical Research Ethical? (Emanuel et al., 2000)
p.002000:
p.002000: This journal article lays out seven areas of concern that need to be addressed if clinical research is deemed to be
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
...
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
...
p.000003: arise as observational human exposure studies are undertaken. No document could identify and address all
p.000003: potential issues in advance, nor is it possible to develop a comprehensive checklist for all such studies.
p.000003: Rather, this document attempts to present and discuss the types of ethical and scientific issues that will need
p.000003: to be considered and addressed as NERL researchers plan and implement observational human exposure studies. The
p.000003: researchers will need to work with others ― the study team, IRB members, EPA’s HSRRO, the participants
p.000003: and their community, and other stakeholders ― to identify and address all of the relevant issues
p.000003: for any particular study. The authors are confident that this document will be helpful to NERL scientists
p.000003: in their endeavors to assure that all of NERL’s observational human exposure studies will respect,
p.000003: safeguard, and protect the participants in that research.
p.000003:
p.000003: References
p.000003: Beauchamp TL, Childress, JF (2001). Principles of Biomedical Ethics: Fifth Edition. New York, NY: Oxford University
p.000003: Press.
p.000003:
p.000003: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000003: Subjects. U.S. Code of Federal Regulations.
p.000003: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2008). International Ethical Guidelines for
p.000003: Epidemiological Studies. World Health Organization. Geneva, Switzerland. Available:
p.000003: http://www.cioms.ch/080221feb_2008.pdf [accessed 25
p.000003: April 2008].
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000003: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000003:
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000004: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000004:
p.000004: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
p.000004:
p.000004: ERG (Eastern Research Group) (2007). Report on the Workshop to Discuss State-of-the-Science Approaches for
p.000004: Observational Exposure Measurement Studies. Held in Durham, North Carolina on November 28-29, 2006. Final Report:
p.000004: January 25, 2007. (PB2007-108905).
p.000004:
p.000004: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000004: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000004: [accessed 12 June 2007].
p.000004:
p.000004: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000004: Housing-Related Health Hazards Involving Children.
p.000004: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000004: June 2007].
p.000004: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
p.000004: Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of Human Subjects
p.000004: of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 12 June
p.000004: 2007].
p.000004:
...
p.000009: Council (NRC) in its report, Protecting Participants and Facilitating Social and Behavioral Sciences
p.000009: Research (NRC, 2003), a joint NRC and Institute of Medicine (NRC & IOM, 2005) committee in the report on
p.000009: Ethical Considerations for Research on Housing-Related Health Hazards Involving Children; the Council
p.000009: for
p.000009:
p.000009: Respect for Persons
p.000009: • Individuals should be treated as autonomous agents.
p.000009: • Persons with diminished autonomy are entitled to protection.
p.000009:
p.000009: Beneficence
p.000009: • Human subjects should not be harmed.
p.000009: • Research should maximize possible benefits and minimize possible harms.
p.000009: Justice
p.000009: • The benefits and risks of research must be distributed fairly.
p.000009: Informed Consent
p.000009: • Subjects must be given the opportunity to choose what will or will not happen to them
p.000009: • The consent process must include
p.000009: (1) information,
p.000009: (2) comprehension, and
p.000009: (3) voluntariness
p.000009: Assessment of Risks and Benefits
p.000009: • The nature and scope of risks and benefits must be assessed in a systematic manner.
p.000009:
p.000009:
p.000009: Selection of Subjects
p.000009: • There must be fair procedures and outcomes in the selection of research subjects.
p.000009: International Organizations of Medical Sciences (CIOMS) under the World Health Organization in
p.000009: its International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002) and
p.000009: in the International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008); and
p.000009: the National Ethics Advisory Committee of New Zealand in the Ethical Guidelines for Observational Studies:
p.000009: Observational Research, Audits and Related Activities (NEAC, 2006).
p.000009:
p.000009:
p.000009: Table 1-3. Seven Ethical Requirements for Clinical Research
p.000009: From Emanuel, Wendler, and Grady (2000)
p.000009: Requirement Explanation
p.000009: Evaluation of a treatment, intervention, or theory
p.000009:
p.000009: In 2000, Emanuel, Wendler, and Grady considered the ethical principles involved in clinical research and
p.000009: proposed seven ethical requirements to be addressed in research with humans (Emanuel et al., 2000). Their
p.000009: published article specifically addressed clinical research, but the issues are similar for observational
p.000009: human exposure studies. Their ethical requirements are summarized and briefly explained in Table
p.000009: 1-3. The requirements are a logical extension of the ethical principles enunciated in the
p.000009: Belmont Report and manifest themselves in additional requirements for social or scientific value; for
p.000009: processes to ensure the scientific integrity of the research; and for independent review of the design,
p.000009: the subject population, and the risk-benefit ratio. The principle of respect for subjects also includes
p.000009: additional emphasis on the welfare of the subjects.
...
p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
p.002000: What Makes Clinical Research Ethical? (Emanuel et al., 2000)
p.002000:
p.002000: This journal article lays out seven areas of concern that need to be addressed if clinical research is deemed to be
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
...
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000012: 12
p.000012:
p.000012: address all of the relevant issues for their particular study to ensure that the specific elements of
p.000012: the study will safeguard and protect the human research subjects.
p.000012: In addition to being an information resource for NERL researchers, this document provides useful
p.000012: information for contractors and grantees funded by NERL to consider during the design and implementation of
p.000012: their exposure science research. Although not its intended audience, this document also may prove to be useful
p.000012: to other researchers, within and outside of EPA, who are involved in observational human exposure
p.000012: studies.
p.000012:
p.000012: 1.4 Process for Developing the Document
p.000012: This document was written by exposure science researchers in EPA’s NERL, with substantial input from experts
p.000012: within and outside of the Agency. Information relevant to the process and the document has been routinely
p.000012: posted on the EPA Web site at http://www.epa.gov/nerl/sots.
p.000012: NERL staff began this work by hosting a series of stakeholder meetings in the summer of 2006 to seek
p.000012: input on the content and format of the document. In November 2006, NERL convened an expert panel to
p.000012: provide its advice and guidance about the scope and content of this document. The Expert Panel consisted of
...
p.000013: equity and of respect for persons to develop approaches to demonstrate respect for culture
p.000013: and to empower the participants’ community to endure, including the need to build trust in the community and
p.000013: with stakeholders through open and honest communications and legitimate power sharing.
p.000013: • Strategies for Effective Communication (Section 7) builds on the presumption of an ongoing, interactive
p.000013: dialogue and exchange of ideas between researchers and the participants, community, and stakeholders and focuses
p.000013: on steps that the researcher needs to take for effective communications. The section discusses communication
p.000013: strategies, implementation plans, communication tools, reporting of results, and approaches for
p.000013: effective communications, two-way communications between the researchers, participants, community, and other
p.000013: stakeholders.
p.000013:
p.000013: References
p.000013: Beauchamp TL, Childress, JF (2001). Principles of Biomedical Ethics: Fifth Edition. New York, NY: Oxford University
p.000013: Press.
p.000013:
p.000013: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000013: Subjects. U.S. Code of Federal Regulations.
p.000013: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06
p.000013: .html [accessed 12 June 2007].
p.000013:
p.000013: CIOMS (The Council for International Organizations of Medical Sciences) (2008). International Ethical Guidelines for
p.000013: Epidemiological Studies. Geneva, Switzerland: CIOMS. Available: http://www.cioms.ch/080221feb_2008.pdf [accessed 25
p.000013: April 2008].
p.000013:
p.000013: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000013: Biomedical Research Involving Human Subjects.
p.000013: Geneva, Switzerland: CIOMS. Available: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000013:
p.000013: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000013:
p.000013: NEAC (National Ethics Advisory Committee) (2006). Ethical Guidelines for Observational Studies: Observational research
p.000013: audits and related activities. Wellington, New Zealand: Ministry of Health. Available:
p.000013: http://www.neac.health.govt.nz/moh.nsf/indexcm/neac resources-publications-ethicalguidelines.
p.000013:
p.000013: NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing Research
p.000013: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000013: [accessed 16 August 2007].
p.000013:
p.000013: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000013: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000013: [accessed 12 June 2007].
p.000013:
p.000013: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000013: Housing-Related Health Hazards Involving Children.
p.000013: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000013: June 2007].
p.000013:
p.000013: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
...
p.000018: the nature and objectives of the scientific inquiry will be different when the study is designed
p.000018: to test a methodology versus when the study is intended to measure a representative
p.000018: distribution of people’s exposures. Defining the study problem is a critical and fundamental first step
p.000018: in the scientific process, because it
p.000018: will establish the objectives that the research will be designed to achieve and the uses to which the research
p.000018: data will be put. The details of the scientific design of the study will naturally be strongly
p.000018: influenced by the objectives that the research is intended to meet.
p.000018:
p.000018: 2.1.2 Justifying the Study
p.000018: Justification of any human study includes both a scientific and an ethical justification. In the list of seven
p.000018: ethical requirements that must be met for human subjects research to be considered ethically acceptable, four of
p.000018: those requirements, (1) respect for subjects, (2) informed consent, (3) favorable risk-benefit ratio, and (4)
p.000018: fair subject selection, are founded on the traditional ethical principles enunciated in the Belmont
p.000018: Report and codified in the Common Rule (Emanuel et al., 2000). But three requirements, (1) social or
p.000018: scientific value,
p.000018: (2) scientific validity, and (3) independent review, apply directly to the scientific aspects of the study. Similarly,
p.000018: Guideline 1 from the CIOMS (2002) document reiterates the foundational principle that “scientifically invalid
p.000018: research is unethical.” Beyond the traditional ethical expectations of respect for, protection of, and fairness
p.000018: to the research subjects, CIOMS requires investigators and sponsors to ensure that the research be
p.000018: “scientifically sound,” that it “conform to generally accepted, scientific principles,” and that all researchers
p.000018: be “qualified” and “competent.”7 Text Box 2-1 identifies a number of elements that should be
p.000018: considered in justifying an observational human exposure study. As discussed below, a critical element to
p.000018: support justification of both the scientific and ethical elements of a study is the use of independent scientific and
p.000018: ethical peer review.
p.000018:
p.000018:
p.000018:
p.000018: 7 Guideline 1 states “research can be ethically justifiable only if it is carried out in ways that respect and
p.000018: protect, and are fair to, the subjects of that research and are morally acceptable within the communities in which the
p.000018: research is carried out. Moreover, because scientifically invalid research is unethical in that it exposes research
p.000018: subjects to risks without possible benefit, investigators and sponsors must ensure that proposed studies involving
p.000018: human subjects conform to generally accepted scientific principles and are based on adequate knowledge of the pertinent
p.000018: scientific literature.” The commentary on the guideline goes on to say, “Among the essential features of ethically
p.000018: justified research involving human subjects, including research with identifiable human tissue or data, are that the
p.000018: research offers a means of developing information not otherwise obtainable, that the design of the research is
p.000018: scientifically sound, and that the investigators and other research personnel are competent. The methods to be used
...
p.000020: participants. If there is no solid analysis plan for a particular data item, such data should not be
p.000020: collected. If the researchers actually believe that some factor may represent a potentially overlooked
p.000020: variable, then they should collect the information to test that hypothesis correctly. But, just collecting
p.000020: the data “while we can,” with no plan for how to analyze and use the data, wastes resources, imposes unnecessary
p.000020: burden, and often proves tempting as a statistical correlation hunt. Finally, the study design must be described
p.000020: in sufficient detail to be properly evaluated. Preparation of the study design document is described
p.000020: in a later section, but the overriding goal is to provide enough information to allow proper review
p.000020: of the science behind the study design by the research team, the scientific peer community, and the
p.000020: IRB panel members.
p.000020:
p.000020: 2.2.2 Feasibility
p.000020: The authors consider the evaluation of the feasibility of accomplishing the study to be one of the most critical
p.000020: components of the development of the study design. Evaluating the feasibility of the research project involves
p.000020: considering not only whether there are sufficient resources to accomplish the study, but whether or not the
p.000020: study is feasible from a scientific and ethical perspective. If the research team concludes that the study is
p.000020: not feasible, there will be no further effort to develop the study. There may be practical limitations
p.000020: that preclude conduct of the study as initially conceived. Because “scientifically invalid research
p.000020: is unethical” (Guideline 1, CIOMS, 2002), it is essential that scientific and ethical considerations be
p.000020: considered together. Text
p.000020:
p.000020:
p.000021: 21
p.000021:
p.000021: Box 2-2 includes some examples of the types of questions that may be asked when evaluating
p.000021: the feasibility of a study.
p.000021:
p.000021: Text Box 2-2. Is the Study Feasible?
p.000021: • What are the sample size requirements? Can enough participants be enrolled into the study from the proposed
p.000021: community, considering the eligibility criteria and anticipated response rate? What is the predicted retention rate if
p.000021: this is a repeated measurements study? Is that acceptable?
p.000021: • Is the research question well defined, and can we measure the variables and the outcome metrics?
p.000021: • Are the measurement methods specific and accurate enough to accomplish the research?
p.000021: • Does the analysis plan provide results to test the research questions and to meet the study objectives?
p.000021: • Will the community be receptive to this study?
p.000021: • Are there cultural mores, societal values, or other factors associated with the community that would make it
p.000021: difficult to conduct the study in the community? Is the study morally acceptable to the community?
p.000021: • Is there a community structure that will allow the research team to engage the community in the study?
p.000021: • What is the burden on the community?
p.000021: • What is the burden on the participants? Is it acceptable?
p.000021: • What is the risk-benefit balance? Is it acceptable, considering the burden on the participants?
p.000021: • Are there sufficient resources available to conduct a study of this size?
...
p.000025: because the researchers and the community or participants may perceive the risks and benefits
p.000025: quite differently. (See the discussion in NRC & IOM [2005], for example.) To understand the
p.000025: community’s perspective better, the researcher may find it helpful to discuss the assessment of risks
p.000025: and benefits with members of the research team, community representatives, and relevant
p.000025: stakeholders. The research team should consider the use of a community advisory board (CAB) to provide
p.000025: input to the assessment of the risks and benefits of the study. The group could include individuals who are
p.000025: representative of the population to be studied, community representatives, exposure
p.000025: scientists, and bioethicists. The group should include experts familiar with the human subjects
p.000025: research regulations, preferably including someone who has served on IRBs. Obtaining input from the group can
p.000025: be accomplished by submitting the study concept and general study design to the group for
p.000025: review and feedback, even before a full study design has been developed. (See the discussions of CABs
p.000025: in Sections 5 and 6.) Ultimately, it will be the review by the members of the IRB that will determine whether
p.000025: the balance is appropriate and justifiable.
p.000025:
p.000025: 2.5 Independent Scientific and Ethical Review
p.000025: Because issues of science and ethics are intrinsically bound together in human subjects research (Emanuel et al.,
p.000025: 2000; CIOMS, 2002), it is important that scientific and ethical reviews be considered together,
p.000025: not separately. Scientific reviews are performed to ensure the scientific soundness of the study, whereas
p.000025: ethical reviews are performed to ensure proper action and the protection of the human subjects in a research
p.000025: study. A study that is not scientifically sound could expose study participants to unnecessary risk or
p.000025: inconvenience and burden, with no additional societal benefits (i.e., no increase in generalizable
p.000025: knowledge). EPA’s Science Advisory Board has stated that “bad science is always unethical” (U.S. EPA, 2000),
p.000025: and CIOMS declares that “scientifically invalid research is unethical” (CIOMS, 2002).10 It is clear, therefore,
p.000025: that the ethical review has to consider the scientific aspects of the study also.
p.000025: There may be multiple levels of review during development of the study design and human subjects
p.000025: research protocol for an observational human exposure study. The research team is responsible for the design of
p.000025: the study and for ensuring that adequate peer review is
p.000025:
p.000025:
p.000025: 10 CIOMS (2002) Guideline 2 asserts “Ethical review committees—All proposals to conduct research involving human
p.000025: subjects must be submitted for review of their scientific merit and ethical acceptability to one or more scientific
p.000025: review and ethical review committees. The review committees must be independent of the research team, and any direct
p.000025: financial or other material benefit they may derive from the research should not be contingent on the outcome of their
p.000025: review. The investigator must obtain their approval or clearance before undertaking the research. The ethical review
p.000025: committee should conduct further reviews as necessary in the course of the research, including monitoring of the
p.000025: progress of the study.” The CIOMS document continues, “According to the Declaration of Helsinki (Paragraph 11), medical
p.000025: research involving humans must conform to generally accepted scientific principles, and be based on a thorough
p.000025: knowledge of the scientific literature, other relevant sources of information, and adequate laboratory and, where
p.000025: indicated, animal experimentation. Scientific review must consider, inter alia, the study design, including the
p.000025: provisions for avoiding or minimizing risk and for monitoring safety. Committees competent to review and approve
p.000025: scientific aspects of research proposals must be multidisciplinary.”
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000026: performed to evaluate both the scientific and ethical approaches for the study. Following completion of a
p.000026: draft study design, researchers should engage a diverse group of experts to review the study design and human
p.000026: subjects aspects. The scope of the study should dictate the level of the review (i.e., internal
p.000026: or external independent peer review). A small pilot study to evaluate measurement methods or to
p.000026: collect screening level data in preparation for a large study may not require as extensive review as a larger
p.000026: study.
p.000026: When the scientific soundness of the study has been evaluated and found to be feasible, and the final study
p.000026: design is completed, the human subjects research protocol should be developed and submitted to the IRB for
p.000026: review and approval. For studies conducted or supported by EPA, additional review and certification of the
...
p.000026: independent and knowledgeable reviewers. Depending on the scope of the study, the appropriate NERL
p.000026: associate director or the NERL laboratory director will make the final determination about (1) the
p.000026: process for selecting scientific peer reviewers (including the range of disciplines to be
p.000026: included), (2) the nature and scope of the review process (e.g., charge to the reviewers and scope of the
p.000026: review; letter reviews, convening a peer panel, or both; the size and nature of the panel review; etc.),
p.000026: and (3) the adequacy of the responses to the scientific review.
p.000026:
p.000026: 2.5.2 Conflicts of Interest
p.000026: It is recommended that potential conflicts of interest among researchers or study participants be identified at all
p.000026: stages of study planning and implementation, but particularly early in the study during the planning stage. There
p.000026: can be many sources of potential conflicts of interest, including sources of project funding, pressures
p.000026: to publish, consulting arrangements of the investigators, employment of investigators’ family members with
p.000026: affected parties, participation in affected advocacy groups, collaborations or relationships with
p.000026: experts on the IRB or other independent review committees, institutional conflicts for any contractors
p.000026: who may be involved, or a wide range of other situations.
p.000026: Any situations that constitute actual conflicts of interest and all potential or apparent conflicts of interest
p.000026: must be reported to the IRB for their review and resolution. The CIOMS (2002) guidelines for
p.000026: research protocols involving human subjects specify that all sponsors of the research be identified,
p.000026: and that the protocol include actions to disclose and address potential conflicts of interest. Concerns about
p.000026: conflicts of interest also need to be identified and discussed with the researchers, community, and
p.000026: other stakeholders to make a determination of the existence of conflicts, and how they should be avoided or
p.000026: handled.
p.000026: Even if actual conflicts of interest do not exist, researchers should recognize that there can be perceived
p.000026: conflicts of interest that can be just as damaging as real conflicts of interest. Perceptions by
p.000026: participants, community members and representatives, stakeholder groups, and the public may be substantially
p.000026: different from the reality of the situation. This is especially likely to occur when external sources, such as
p.000026: industry, are
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027: involved in funding research. Even though researchers may develop agreements with funding organizations that
p.000027: ensure researcher autonomy, a perception may exist that the funding organization will bias the study (Resnik and Wing,
p.000027: 2007). Concerns about perceived conflicts of interest should be discussed with the IRB and other relevant
p.000027: review committees, in addition to the researchers, the community, and other stakeholders. The IRB must
p.000027: be made aware of any circumstances that may give rise to actual conflicts of interest or to the
p.000027: appearance or perception of a conflict of interest. The IRB’s recommendations about how to resolve any such
p.000027: conflicts must be strictly adhered to by NERL researchers.
p.000027:
p.000027: 2.5.3 Develop the Human Subjects Protocol for IRB Review
p.000027: IRBs may have specific format requirements for their human subject research protocols. Traditionally, the human
p.000027: subjects research protocols for research conducted or funded by NERL have included
p.000027: descriptions of the project, including title and description of the research; the duration of the project; the
p.000027: type of data to be collected; the objectives of the study; the number of samples; a description of the
p.000027: participants and participant recruitment procedures; the informed consent procedures and forms; estimates of
p.000027: participant risk and burden, an assessment of benefits and the risk-benefit ratio; and actions to protect the
p.000027: participants. CIOMS has developed a comprehensive list of items that they recommend for inclusion in
p.000027: a human subjects research protocol (Appendix 1, CIOMS, 2002). Many of the items that they identify are also
p.000027: useful for observational human exposure studies. (The CIOMS items can be found in Appendix C of this
p.000027: document.) The authors recommend that anyone developing a human subjects protocol for observational human
p.000027: exposure studies review and utilize the CIOMS list of topics, as appropriate. Text Box 2-5
p.000027: identifies a number of topics that should be considered in development of the human subjects research protocol.
p.000027: In addition, the authors’ experience leads them to suggest that three additional topics beyond those from
p.000027: the CIOMS (2002) document also may need to be considered in a human subjects protocol: (1) approaches to
p.000027: minimize changes in participant behavior because of participation in the study (see Section 2.3.4);
p.000027: (2) approaches to minimize therapeutic misconception (see Section 5.4.1); and (3) actions to involve
p.000027: the community in a community-based participatory research
p.000027:
p.000027: Text Box 2-5. Potential Topics in a Human Subjects Research Protocol
p.000027: 1. Title
p.000027: 2. Summary in lay language
p.000027: 3. Justification for the study
p.000027: 4. Ethical issues and proposed resolution
p.000027: 5. Summary of previous research
p.000027: 6. Affirmation of Belmont Principles and 40 CFR 26 compliance
p.000027: 7. Previous history or use of the protocol
p.000027: 8. Information on the location and demographics of research
p.000027: 9. Information on funding organization, researcher partners, and collaborators
p.000027: 10. Names, qualifications, and experience of investigators
p.000027: 11. Objectives, hypotheses, assumptions, and variables
p.000027: 12. Study design
p.000027: 13. Sample size and power and statistical analysis plan
p.000027: 14. Criteria and justification for subject selection
p.000027: 15. Justification for use of vulnerable groups, if any
p.000027: 16. Process of recruitment
p.000027: 17. Actions to involve the community in a community-based participatory research program
p.000027: 18. Description and explanation of any and all interventions
p.000027: 19. Measurements or data to be collected
p.000027: 20. Any clinical or other tests
p.000027: 21. Rules or criteria for removing subjects or terminating the study
...
p.000030: (1) permitting withdrawal from the research,
p.000030: (2) protecting privacy through confidentiality,
p.000030: (3) informing subjects of newly discovered risks or benefits,
p.000030: (4) informing subjects of results of other relevant research, and
p.000030: (5) maintaining welfare of subjects.
p.000030: The authors conclude that these requirements can be met by diligent exercise of data and safety monitoring and
p.000030: oversight of the research effort. (Data and safety monitoring and oversight also are discussed throughout
p.000030: Section 4, but especially in Section 4.5 entitled “Data and Safety Monitoring and Oversight” and
p.000030: in Section 7.8, “Reporting Unanticipated Results and Observations.” The reader also is referred
p.000030: to those sections.)
p.000030: Creation of data and safety monitoring and oversight organization and procedures, combined with careful
p.000030: consideration of actions to ensure the ethical protection of participants, is perhaps the most important aspect
p.000030: of planning and implementing an observational human subjects study. The monitoring must include both
p.000030: the technical aspects of the study—like planning for actions if unsafe environmental conditions are observed—and
p.000030: also the ethical aspects of the study, such as those items listed above. The team of people involved in data
p.000030: and safety monitoring and oversight have to establish and implement mechanisms to get feedback on a continuing
p.000030: basis from the participants, in addition to monitoring and reviewing the scientific data.
p.000030: CIOMS recommends that all human subjects research protocols contain “A description of the plans
p.000030: for statistical analysis of the study, including plans for interim analyses, if any, and criteria for
p.000030: prematurely terminating the study as a whole if necessary” (Appendix A, CIOMS, 2002). To be
p.000030: consistent with this recommendation, the research team will need to develop and implement an approach for monitoring
p.000030: the scientific and ethical issues during the study, so that changes can be made to the study, or the study can
p.000030: be stopped if necessary. Criteria and standards need to be established against which study activities and
p.000030: results can be evaluated, and these criteria and standards need to be incorporated into the study
p.000030: design, the human subjects research protocol, and the QAPP.
p.000030: In developing an approach to monitor scientific and ethical issues during the study, the research team may
p.000030: choose to
p.000030: • identify the individual, team, advisory committee, or
p.000030: data safety monitoring board (DSMB) responsible for monitoring the progress and results of the study;
p.000030: • develop roles and responsibilities;
p.000030: • develop a schedule and timeline for the activities to be conducted;
p.000030: • develop goals for interim data analysis and prepare an analysis plan;
p.000030: • identify what data will be analyzed, how it will be processed and validated, and who will perform
p.000030: the analyses;
p.000030: • develop a plan for reporting interim results to the research team;
p.000030: • develop standards for reporting scientific and ethical issues to the research team; or
p.000030: • develop criteria for evaluating scientific and ethical issues that arise during the study.
p.000030: In a well-designed observational study for which the research team has adequately prepared, it is unlikely that there
p.000030: will be scientific issues requiring that the study be stopped. Nonetheless, it is important for criteria to be
...
p.000031: activities
p.000031: • Burden⎯higher than predicted
p.000031: • Changes in participant behaviors⎯potential changes because of participation in the study
p.000031: • Grievances⎯participant issues
p.000031: • Retention⎯high dropout rates
p.000031: • Community issues⎯poor interactions, lack of support
p.000031: • Third-party issues⎯problems with landlords, spouses, or others
p.000031: • Collateral observations⎯identification of nonstudy hazards, difficulty reporting
p.000031: • Unanticipated results⎯high contaminant concentrations measured, unexpected results
p.000031: • New data indicating that participation in the study (or observations measured in the study) represent a risk to
p.000031: participants or others
p.000031:
p.000031:
p.000031:
p.000031: References
p.000031: Castelloe, JM (2000). Sample size computations and power analysis with the SAS system. Paper 265-25 in Proceedings of
p.000031: the 25th Annual SAS Users Group International Conference. Cary, NC: SAS Institute, Inc. Available:
p.000031: http://support.sas.com/rnd/app/papers/powersamplesize.pdf [accessed 16 April 2008].
p.000031:
p.000031: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of
p.000031: Human Subjects. U.S. Code of Federal Regulations. Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/
p.000031: 40cfr26_06.html [accessed 12 June 2007].
p.000031:
p.000031: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000031: Biomedical Research Involving Human Subjects.
p.000031: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000031:
p.000031: Coggon D, Rose G, Barker DJP (1997). Epidemiology for the Uninitiated, Fourth Edition. London: BMJ Publishing Group
p.000031: Ltd. Available at http://www.bmj.com/epidem/epid.html [accessed 29
p.000031: January 2008].
p.000031:
p.000031: Cohen Hubal EA, Sheldon LS, Zufall, MJ, Burke JM, Thomas KW (2000). The challenge of assessing children’s residential
p.000031: exposure to pesticides. Journal of Exposure Analysis and Environmental Epidemiology 10(6 part 2): 638-649.
p.000031:
p.000031: Dallal, GE (2001). Some aspects of study design. In The Little Handbook of Statistical Practice at
p.000031: www.StatisticalPractice.com, and at http://www.tufts.edu/~gdallal/STUDY.HTM [accessed 29
p.000031: January 2008]
p.000031: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000031:
p.000031: Gilbert, SG (2006). Supplementing the traditional institutional review board with an environmental health and community
p.000031: review board. Environmental Health Perspectives 114(10): 1626-1629.
p.000031:
p.000031: Kraemer HC, Thiemann S (1987). How Many Subjects? Statistical Power Analysis in Research. Newbury Park, CA: Sage
p.000031: Publications.
p.000031:
p.000031: Lenth RV (2001). Some practical guidelines for effective sample size determination. American Statistician 55(3):
p.000031: 187-193. Available:
p.000031: http://www.stat.uiowa.edu/techrep/tr303.pdf [accessed 13
p.000031: June 2007].
p.000031:
p.000031: NRC (National Research Council) (2003). Protecting Participants and Facilitating Social and Behavioral Sciences
p.000031: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000031: [accessed 12 June 2007].
p.000031:
...
p.000033: additional protections for children and for pregnant or nursing women (and their fetus or nursing child)
p.000033: in Subparts B, C, and D (CFR, 2006a).
p.000033: The section begins by identifying or defining vulnerable groups and then discusses ethical issues that
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
...
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
p.000035: broader definition of vulnerability as it relates to education, economics, social status, and other factors. As
p.000035: shown in Text Boxes 3-1 and 3-2 and described above, the concept of vulnerability is broader than that
p.000035: presented in the Common Rule. It is not adequate to simply check the list in Text Box 3-1 to identify if a potentially
p.000035: vulnerable group is included in an observational study. The researchers should assess the potential
p.000035: vulnerability of a study population within the study by evaluating the characteristics (e.g., socioeconomic
p.000035: status) of the study population within the context of the study by considering the various design elements of the
p.000035: study, as discussed in Section 2.
p.000035: 12 In the commentary on Guideline 13 in CIOMS (2002), the committee states that the central problem presented by plans
p.000035: to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
p.000035: the CIOMS document (Guidelines 14 and 15) and include children, and persons who, because of mental or behavioral
p.000035: disorders, are incapable of giving informed consent. Ethical justification of their involvement usually requires that
p.000035: • the research could not be carried out equally well with less vulnerable subjects;
p.000035: • the research is intended to obtain knowledge that will lead to improved diagnosis, prevention, or treatment of
p.000035: diseases or other health problems characteristic of, or unique to, the vulnerable class—either the actual subjects or
p.000035: other similarly situated members of the vulnerable class;
p.000035: • research subjects and other members of the vulnerable class from which subjects are recruited will ordinarily be
p.000035: assured reasonable access to any diagnostic, preventive, or therapeutic products that will become available as a
p.000035: consequence of the research;
p.000035: • the risks attached to interventions or procedures that do not hold out the prospect of direct health-related
p.000035: benefit will not exceed those associated
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036: CIOMS recommendations, although written to address biomedical research, also generally are
p.000036: applicable to observational human exposure studies. The authors of this document consider the CIOMS
p.000036: requirement that the research could not be carried out equally well with less vulnerable subjects
p.000036: to be particularly important. EPA and NERL researchers should include vulnerable groups in
p.000036: observational human exposure studies only if their participation is critical to the success and
p.000036: applicability of the research. Even then, EPA and NERL researchers will have to meet stringent standards for
p.000036: protecting the rights and safety of the vulnerable participants. For example, EPA regulations
p.000036: governing observational research with children are even more stringent than the CIOMS guideline.
p.000036: If such research does not hold out the prospect of direct benefit to the child, no increase whatsoever over
p.000036: minimal risk is permitted.
p.000036: However, many observational human exposure studies are developed specifically to study the exposures of
p.000036: selected vulnerable groups to chemicals and other environmental stressors in everyday environments. So,
p.000036: researchers should be prepared to address the issues associated with vulnerable groups in
p.000036: observational research. Furthermore, as discussed in Section 3.4, there has been increased concern in recent years that
p.000036: exclusion of vulnerable groups from research studies is not ethical. Failure to conduct research with vulnerable groups
p.000036: may deprive them of the benefits of research. NIH, for example, has a policy (NIH, 1998) with a
p.000036: goal of increasing participation of children in research.
p.000036:
p.000036: 3.3 Minimal Risk and Vulnerable Groups
p.000036: EPA has codified protections for children, pregnant or nursing women, and fetuses in Subparts B, C, and D of the EPA
...
p.000036: risk (CFR, 2006a).13 When considering vulnerable groups, The Institutional Review Board Guidebook (U.S. HHS,
p.000036: 1993) states that “IRBs should therefore determine whether the proposed subject population would be more sensitive or
p.000036: vulnerable to the risks posed by the research as a result of their general condition or disabilities. If so, the
p.000036: procedures would constitute more than minimal risk for those subjects.”
p.000036: When conducting observational human exposure studies, it is recommended that researchers consult these
p.000036: regulations and guidebooks. NERL researchers also will need to ensure that all of the requirements in Subparts B, C,
p.000036: and D of the EPA Human Subjects Rule are met.
p.000036:
p.000036: 3.4 Research Involving Children
p.000036: Children long have been recognized as a vulnerable group in research studies. EPA and HHS both extend special
p.000036: protections to children (CFR, 2006a,b). There are many books, reports, and research manuscripts that
p.000036: specifically address issues associated with research involving children (e.g., NRC & IOM, 2005; IOM,
p.000036: 2004; Kodish, 2005; NRC, 2003; AAP, 2003).
p.000036: CIOMS has drafted guidelines for including children in biomedical research (Guideline 14, CIOMS, 2002). The
p.000036: guidelines require an investigator to provide the assurances shown in Text Box 3-3 before undertaking
p.000036: research involving children.
p.000036:
p.000036: Text Box 3-3. Assurances Required by CIOMS Before Research Involving Children May Begin
p.000036: • the research might not equally well be carried out with adults;
p.000036: • the purpose of the research is to obtain knowledge relevant to the health needs of children;
p.000036: • a parent or legal representative of each child has given permission;
p.000036: • the agreement (assent) of each child has been obtained to the extent of the child’s capabilities; and
p.000036: • a child’s refusal to participate or continue in the research will be respected.
p.000036:
p.000036:
p.000036: The participation of children in some observational human exposure studies is critical to
p.000036: characterizing children’s exposures to chemicals in the environment. It is well recognized that children are not
p.000036: “little adults,”
p.000036: and that their
p.000036: exposures to chemicals differ (and, in
p.000036:
p.000036:
p.000036: with routine medical or psychological examination of such persons unless an ethical review committee authorizes a
p.000036: slight increase over this level of risk (Guideline 9); and,
p.000036: • when the prospective subjects are either incompetent or otherwise substantially unable to give informed consent,
...
p.000037: al., 2000), it is sometimes important that observational human exposure studies involve children.
p.000037: Because children are so vulnerable, there long has been concern about including them in research studies,
p.000037: and biomedical research often excluded children. However, in recent years, there has been concern
p.000037: that excluding children from research is not ethical. NIH’s Policy and Guidelines on the Inclusion of
p.000037: Children as Participants in Research Involving Human Subjects (NIH, 1998) has a goal of increasing
p.000037: participation of children in research. The policy of NIH is that children must be included in all human
p.000037: subjects research conducted or supported by NIH, unless there are scientific and ethical reasons
p.000037: not to include them. Proposals or applications to NIH for research have to present an acceptable
p.000037: justification if children will be excluded from a research study. Of course, as discussed above, if the research
p.000037: topic is irrelevant to children, the CIOMS guidelines would recommend that they be excluded from the
p.000037: research.
p.000037: Observational human exposure studies conducted by NERL are not expected to involve greater than minimal risk. It
p.000037: will be the responsibility of the NERL researchers to present adequate information for the IRB to
p.000037: demonstrate that the research does not involve greater than minimal risk. Researchers designing observational
p.000037: research studies should carefully evaluate the risks and benefits specific to their study and the
p.000037: participants involved. In developing the study design and human subjects protocols, researchers need to
p.000037: ensure that the protocols ensure the protection of the rights and welfare of the participant children, and that
p.000037: risks and harm are minimized. The perception of risks and benefits, both by
p.000037: the individual and by the family or community, may influence the risk-benefit determination. It may prove
p.000037: useful for the research team to consult with other experienced researchers who have conducted
p.000037: similar studies and with members of the IRB to ensure that the information included in the human subjects
p.000037: research protocol is adequate for the IRB’s review.
...
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
p.000037: biomedical research because of the potential for becoming pregnant during a study. The document continues, “A
p.000037: general policy of excluding from such clinical trials women biologically capable of becoming pregnant is
p.000037: unjust in that it deprives women as a class of persons of the benefits of new knowledge derived from the
p.000037: trials.” The second relevant CIOMS guideline, number 17, asserts that, if involved in a research study,
p.000037: pregnant women should be fully informed, and included only if the
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: research benefits pregnant women and is thoroughly supported by reliable evidence in animal studies.
p.000038: Although the CIOMS guideline specifically addresses biomedical research, the ethical concepts
p.000038: behind the guidelines generally may be applicable to observational human exposure studies. EPA’s human
p.000038: subjects rule is completely consistent with the HHS rule in adding additional protections for pregnant women and
p.000038: fetuses involved in observational research (40 CFR
p.000038: 26.304 and 45 CFR 46.204). These additional protections (specified in 45 CFR 46.204 subparagraphs a
p.000038: through j) reflect the CIOMS recommendations by requiring: availability of data from previously conducted
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
...
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
p.000038: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle A Department of Health and Human Services Part 46 Protection
p.000038: of Human Subjects. U.S. Code of Federal Regulations. Available:
p.000038: http://www.access.gpo.gov/nara/cfr/waisidx_06/45cfr46_06.ht ml [accessed 13 June 2007].
p.000038:
p.000038: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000038: Biomedical Research Involving Human Subjects.
p.000038: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000038:
p.000038: Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry MR, Rigas ML, Zartarian VG, Freeman NCG (2000).
p.000038: Children’s exposure assessment: a review of factors influencing children’s exposure, and the data available to
p.000038: characterize and assess that exposure. Environ Health Perspect 108(6): 475-486.
p.000038:
p.000038: Emanuel EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000038:
p.000038: IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Washington, DC: The
p.000038: National Academies Press. Available: http://www.nap.edu/catalog.php?record_id=10958 [accessed 16 April 2008].
p.000038:
p.000038: Kodish E (Ed.) (2005). Ethics and Research with Children: A Case-Based Approach. New York: Oxford University Press.
p.000038:
p.000038: NBAC (National Bioethics Advisory Commission) (2001). Ethical and Policy Issues in Research Involving Human
p.000038: Participants, Volume I: Report and Recommendations of the National Bioethics Advisory Commission. Bethesda, MD:
p.000038: National Bioethics Advisory Commission. Available: http://www.bioethics.gov/reports/past_commissions/nbac_h
p.000038: uman_part.pdf [accessed 3 September 2007].
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000039: 39
p.000039:
p.000039: NIH (National Institutes of Health) (2002) Human Participant Protections Education for Research Teams [online
p.000039: tutorial].
p.000039:
...
p.000042: confidentiality and to define limits on the researcher’s ability to provide or protect confidentiality.
p.000042: Explaining plans or procedures for protecting confidentiality and their limits14 to prospective research
p.000042: participants is an integral part of the informed consent process.
p.000042:
p.000042: 4.2.1 Confidentiality of Information
p.000042: Many types of information may be collected in observational human exposure studies. Information may be collected
p.000042: through questionnaires, staff observations of residential or other environments, diaries, personal sample
p.000042: collection, environmental or residential sample collection, and collection of biological specimens.
p.000042: Measurement data from the collected samples become part of the information for a participant. The
p.000042: specific information to be obtained to address the research questions should be determined in the
p.000042: development of the study design and research protocol.
p.000042: Disclosure of information that can be linked to an individual may cause harm or distress to that individual.
p.000042: Researchers are responsible for developing safeguards to protect the confidentiality of information and physical
p.000042: samples collected from research participants (see, for example, Guideline 18, CIOMS, 2002). 15
p.000042: Researchers also should be aware that certain combinations of information from a study
p.000042: may sometimes lead to the indirect identification of the individual. Certain combinations of
p.000042: demographic information, for example, may make it relatively simple
p.000042:
p.000042:
p.000042: 14 Beauchamp and Childress (2001) discuss when one may be ethically justified in infringing on an individual’s privacy
p.000042: and confidentiality⎯for example, because of risks to others evidenced by biomarkers of infectious disease. They also
p.000042: discuss similar ethical issues that may arise in regard to genetic data. CIOMS (2002) Guideline 18 provides suggestions
p.000042: for safeguarding or disclosing genetic information. If exposure scientists collaborate with medical researchers or
p.000042: epidemiologists and obtain such information, they need to be cognizant of the relevant ethical issues and of the CIOMS
p.000042: guidelines.
p.000042: 15 Guideline 18 states, “The investigator must establish secure safeguards of
p.000042: the confidentiality of subjects’ research data. Subjects should be told the limits, legal or other, to the
p.000042: investigators’ ability to safeguard confidentiality and the possible consequences of breaches of confidentiality.”
p.000042: Additional CIOMS commentary on the confidentiality guideline states, “Prospective subjects should be informed of limits
p.000042: to the ability of researchers to ensure strict confidentiality and of the foreseeable adverse social consequences of
p.000042: breaches of confidentiality. Some jurisdictions require the reporting to appropriate agencies of, for instance, certain
p.000042: communicable diseases or evidence of child abuse or neglect. These and similar limits to the ability
p.000042: to maintain confidentiality should be anticipated and disclosed to prospective subjects.”
p.000042: to identify an individual. Precise geographic location information may be sufficient to pinpoint a
p.000042: residence. Researchers may use several strategies to reduce the likelihood of indirect identification when
p.000042: study results are reported (see, also, Text Box 4-3).
p.000042: • Redact from publications, reports, or public data sets information that might be used to indirectly identify a
p.000042: research participant.
p.000042: • Generalize exact information; for example, replace birth date with age or year of birth or classify age as
p.000042: part of a range.
p.000042: • Aggregate information across individuals; for example, only report data in cells of sufficient size
p.000042: to make individual linkages unlikely.
p.000042: • Reduce the specificity of geographic coordinate information to a level that a specific residence or other
p.000042: location can not be identified.
p.000042:
p.000042: Text Box 4-3. Approaches for Protecting Personally Identifiable Information
...
p.000048: human subjects rules
p.000048: • Ensuring that measurements and samples are collected as planned, and that data are reported on a timely basis
p.000048: • Evaluating whether the observed measurements exceed the pre-established threshold values and, if so,
p.000048: ensuring that reporting procedures and plans to respond to the potential risks are completed on a
p.000048: timely basis
p.000048: • Ensuring that quality assurance plans that define procedures for assessing and ensuring study
p.000048: protocol compliance are being met
p.000048: • Ensuring data quality targets are met through independent internal or external auditing
p.000048: requirements
p.000048: • Taking all warranted oversight actions to ensure the safety of the participants and the integrity of the
p.000048: study, including terminating the research study if appropriate
p.000048:
p.000048: References
p.000048: AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric Environmental Health. (2nd
p.000048: Edition). Elk Grove Village, IL: American Academy of Pediatrics.
p.000048:
p.000048: Beauchamp TL, Childress JF (2001). Principles of Biomedical Ethics. (5th Edition). New York, NY: Oxford University
p.000048: Press.
p.000048:
p.000048: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I⎯Environmental Protection Agency Part 26 Protection of Human
p.000048: Subjects. U.S. Code of Federal Regulations.
p.000048: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed August 2007].
p.000048:
p.000048: CIOMS (Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000048: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000048: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed June 2007].
p.000048: Emanuel, EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000048:
p.000048: NCI (National Cancer Institute) (2001). Essential Elements of a Data and Safety Monitoring Plan for Clinical Trials
p.000048: Funded by the National Cancer Institute. Available: http://www3.cancer.gov/rrp/dsm_ess.html [accessed April 2007].
p.000048:
p.000048: NEI (National Eye Institute) (2001). National Eye Institute Guidelines for Data Monitoring and Oversight of
p.000048: Observational Studies. Available: http://www.nei.nih.gov/funding/datastudies.asp [accessed April 2007].
p.000048:
p.000048: NHLBI (National Heart Lung and Blood Institute) (2007). Monitoring Boards for Data and Safety (Interim Policy). Policy
p.000048: effective date: 14 May 2007. Available: http://public.nhlbi.nih.gov/ocr/home/GetPolicy.aspx?id=8 [accessed September
p.000048: 2007].
p.000048:
p.000048: NHRPAC (National Human Research Protections Advisory Committee) (2002). Clarification of the status of third parties
p.000048: when referenced by human subjects in research. Available: http://www.hhs.gov/ohrp/nhrpac/documents/third.pdf [accessed
p.000048: April 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (2002). Extramural Projects - Application Instructions (03/15/2002) - Detailed
p.000048: Application Instructions for Certificate of Confidentiality Involving Extramural Research Projects. Certificates of
p.000048: Confidentiality. Available: http://grants.nih.gov/grants/policy/coc/index.htm. [accessed April 2007]
p.000048:
p.000048: NIH (National Institutes of Health) (2001). Protection of third party information in research: Recommendations of the
...
p.000051: In observational human exposure studies, informed consent ensures that the participant
p.000051: accurately understands the range of risks and benefits (if any) associated with participation; emphasizes
p.000051: the voluntary nature of their participation; and provides essential protections to the participant. The
p.000051: three “pillars” of the informed consent process are (1) information;
p.000051: (2) comprehension; and (3) voluntary participation, or “voluntariness” (U.S. DHEW, 1979). Informed consent
p.000051: requires “provision of information to subjects about the purpose of the research, its procedures, potential
p.000051: risks, benefits, and alternatives, so that the individual understands this information and can
p.000051: make a voluntary decision whether to enroll and continue to participate” (Emanuel et al., 2000).
p.000051: The NRC & IOM document Ethical Considerations for Research on Housing-Related Health Hazards Involving
p.000051: Children (NRC & IOM, 2005) contains a comprehensive and very useful discussion of informed consent
p.000051: procedures and requirements in Chapter 6. The IOM report, Responsible Research: A Systems Approach to Protecting
p.000051: Research Participants, also includes a thoughtful discussion of participant-investigator
p.000051: interactions and the informed consent process (IOM, 2002). CIOMS also includes recommendations for both the
p.000051: process and content of informed consent (CIOMS, 2002). Some of the important points from those
p.000051: documents are summarized in Text Box 5-1, but the reader should refer to those documents for additional
p.000051: information about this topic.
p.000051: Federal regulations governing research that is either Federally conducted or Federally funded (i.e., all human subjects
p.000051: research at NERL) are codified in the Common Rule. The regulations set forth requirements for both the content of an
p.000051: informed consent and the process for obtaining and documenting an individual’s informed consent (see Text
p.000051: Box 5-2).16 General regulatory requirements for the elements of informed consent are codified in the
p.000051: Common Rule at 40 CFR 26.116(a)(1)
p.000051: (8) (CFR, 2006). The regulations also prescribe the use of a written consent form and describe how informed
p.000051: consent is to be documented (at 40 CFR 26.117). The regulatory requirements for informed consent highlight a
p.000051: number of issues that a NERL researcher needs to consider in developing and administering the informed
p.000051: consent process and the consent form document. The discussion of these issues, arising from
p.000051: regulatory
p.000051:
p.000051:
...
p.000051: informing and protecting participants, not the research institution.
p.000051: (2) Strengthen Process of Parental Permission and Children’s Assent if Children Are Involved in Research (NRC & IOM,
p.000051: 2005)
p.000051: The process begins with a community-based discussion and concludes with an assurance that individual parents understand
p.000051: the essential elements of the research.
p.000051: Educate parents on issues critical to informed decision making and assess their degree of understanding.
p.000051: Use informational materials in the form that is most appropriate to convey information to potential participants.
p.000051: Consult with community representatives to ensure that information is complete, clear, and understandable, and that any
p.000051: payment will not be exploitive.
p.000051: Expand the perspective about what information about risks and benefits is needed to make an informed choice.
p.000051: Ethically, it is critical to assure that participants and parents understand the crucial features of the research
p.000051: effort.
p.000051: (3) Informed Consent Is a Decision To Participate by an Informed, Competent Individual Without Undue Coercion,
p.000051: Influence, or Intimidation (CIOMS, 2002)
p.000051: Informed consent is a process that takes time and resources.
p.000051: It is not a ritual recitation of text from a form but informative communication in language that suits the individual’s
p.000051: level of understanding.
p.000051: Consent is ethically obtained, considering language and cultural issues, and is documented.
p.000051: Material changes in conditions or procedures require that informed consent be renewed.
p.000051: Consent should explain how samples will be used in current research, and, if applicable, how samples may be used in
p.000051: future research.
p.000051:
p.000051:
p.000051:
p.000051: 5.1.1 Information
p.000051: Some items that researchers should keep in mind as they provide information to the study participants are
p.000051: summarized below. These items may be based on regulatory requirements or currently may
p.000051: be recommendations as ethical “best practices.”
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: Text Box 5-2. Common Rule Requirements:
p.000052: Elements of Informed Consent
p.000052: (1) An explanation of the purposes of the research
p.000052: (2) The expected duration of the subject's participation
p.000052: (3) A description of the procedures to be followed and identification of any experimental procedures
...
p.000053: whenever this is developmentally possible and otherwise appropriate. Under both the EPA Rule and the HHS
p.000053: Rule, the IRB is responsible for determining that adequate provisions have been made for soliciting the assent of the
p.000053: children when, in the judgment of the IRB, the children are capable of providing assent. Assent, however, may
p.000053: be waived in those restricted circumstances in which consent may be waived under the Common Rule. Those
p.000053: circumstances and the required IRB documentation are described in the Common Rule at 40 CFR 26.116(d).
p.000053: • The consent form should clearly state that participation is voluntary and that study
p.000053: participants may “discontinue participation at any time without any penalty or loss of benefits to which the
p.000053: subject is otherwise entitled” [40 CFR 26.116(a)(8)]. If a subject chooses to withdraw from a study, the
p.000053: consequences of their decision and the process for orderly withdrawal should be clearly
p.000053: explained [40 CFR 26.116(b)(4)].
p.000053: • The consent form should address any foreseeable potential future use of samples and data (CIOMS, 2002).
p.000053: For example, effects of environmental exposures on gene expression are potentially very important.
p.000053: Therefore, biologic specimens for DNA analysis may be obtained from participants in future studies. But, it
p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45 CFR 46.408(b)
p.000053: for all research with children. Under the EPA Rule, greater than minimal risk observational research with children that
p.000053: does not hold out the prospect of direct benefit to the child is not permitted under any circumstances. Under the HHS
p.000053: Rule, greater than minimal risk research involving children without the prospect of direct benefit is permitted in very
p.000053: limited circumstances, but the consent of both parents is required in those cases (unless one parent is deceased,
p.000053: unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and
...
p.000057: it recognizes the IRB as the responsible party for deciding what is or is not acceptable.
p.000057: The U.S. Office of Management and Budget (OMB) develops standards and guidelines for statistical surveys performed by
p.000057: the Federal government. Under Guideline 2.3.2, OMB states that, while incentives are not typically used in Federal
p.000057: surveys, agencies may consider use of respondent incentives if they believe incentives would be necessary
p.000057: to use for a particular survey to achieve data of sufficient quality for their intended use (OMB,
p.000057: 2006a). OMB requires that agencies provide a justification for giving incentives to respondents.
p.000057: Some
p.000057: of the factors cited by OMB to be addressed include those particularly relevant to observational
p.000057: human exposure studies, including unusual reporting burdens (keeping data logs for extended periods,
p.000057: coordinating study team visits, participating in a medical examination, etc.), complex study designs (such as
p.000057: studies requiring ongoing participation of respondents), and past experience, especially when there is
p.000057: evidence of attrition or poor response rates (OMB, 2006b). Although OMB primarily considers incentives with
p.000057: regard to survey response rates and data quality, researchers need to consider payments to
p.000057: participants, including participation incentives, in the broader context discussed in this section.
p.000057: CIOMS also provides guidance and commentary on this issue in the International Ethical Guidelines for Biomedical
p.000057: Research Involving Human Subjects (2002). Guideline 7 and the associated commentary emphasize that payments to
p.000057: subjects for expenses incurred because of their participating in a research study are legitimate. The guideline
p.000057: also allows payment for inconvenience and time spent, so long as the payments or other direct benefits are not
p.000057: “so extensive as to induce prospective subjects to consent to participate in research against their better
p.000057: judgment.”
p.000057: The approaches of HHS, FDA, and CIOMS above are consistent in not considering payments to be a benefit
p.000057: to research participants when considering risks versus benefits. All of the guidelines recognize the
p.000057: legitimacy of some recompense, but they all are concerned with the issue of undue influence. “Payments or
p.000057: rewards that undermine a person’s capacity to exercise free choice invalidate consent” (CIOMS, 2002), and
p.000057: voluntariness is a pillar of legitimate informed consent.
p.000057: Text Box 5-4 lists some of the concerns about, and the reasons for, payment of participants.
p.000057: IRBs have considerable discretion with regard to payments and consider payments with regard to the
p.000057: specific circumstances of the research and of the population being studied. The issue of recompense
p.000057: can be a difficult but legitimate ethical issue involving weighing the different ethical principles
p.000057: of justice and fairness against the concerns about undue influence and the invalidation of consent. Ethical
p.000057: review committees, including IRBs, need to consider many factors when determining when it is appropriate to
p.000057: offer payments to research participants and the level and form of payments when they are appropriate. Review
p.000057: committees also should consider how and when information on payments is communicated to prospective study
p.000057: participants.
p.000057:
p.000057:
p.000058: 58
p.000058:
p.000058:
p.000058: Text Box 5-4. Weighing the Ethical Issues About Payments
p.000058: Concerns about Payments Reasons for Payments
p.000058: • Payments may compromise • Recognizing participant voluntary participation.
p.000058: contributions to the
p.000058: • Participants may accept risks research and knowledge they would not otherwise gained
p.000058: accept. • Providing reimbursement
...
p.000063: normal levels of exposure. Alternatively, the act of studying one set of conditions or activities in an observational
p.000063: human exposure study could lead participants to assume that those conditions or activities involve substantial
p.000063: risk. In response, they subsequently may change their activities in ways that could lead to possibly higher
p.000063: risks. The potential for such unintentional outcomes is difficult for researchers to gauge but requires
p.000063: researcher caution in how information and results are conveyed. However, if the informed consent process is
p.000063: truly “an on-going, interactive dialogue . . . involving the disclosure and exchange of relevant
p.000063: information,” then such misunderstandings should be minimized.
p.000063:
p.000063: References
p.000063: AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric and Environmental Health. (2nd
p.000063: Edition). Elk Grove Village, IL: American Academy of Pediatrics.
p.000063:
p.000063: Ackerman TF (1989). An ethical framework for the practice of paying research subjects. IRB 11(4):1-4.
p.000063:
p.000063: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000063: Subjects. U.S. Code of Federal Regulations.
p.000063: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/ 40cfr26_06.html [accessed 12 June 2007].
p.000063:
p.000063: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000063: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000063: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000063:
p.000063: Diekema DS (2005) “Payments for Participation of Children in Research.” Chapter in: Kodish, E, Editor. Ethics and
p.000063: Research with Children: A Case-Based Approach. New York, NY: Oxford University Press. 143-160.
p.000063:
p.000063: Dickert N, Emanuel E, Grady C (2002). Paying research subjects: an analysis of current policies. Ann Intern Med
p.000063: 136(5):368-373.
p.000063:
p.000063: Emanuel EJ (2004). Ending concerns about undue inducement. J Law Med Ethics 32(1):100-105.
p.000063:
p.000063: Emanuel, EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000063:
p.000063:
p.000063:
p.000064: 64
p.000064:
p.000064: Erlen JA, Sauder RJ, Mellors MP (1999). Incentives in research: ethical issues. Orthop Nurs 18(2):84-87.
p.000064:
p.000064: European Parliament (2001). On the approximation of the laws, regulations, and administrative provisions of the Member
p.000064: States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products
p.000064: for human use. Directive 2001/20/EC Article 4(d) of the European Parliament and of the Council of 4 April 2001.
p.000064:
p.000064: Flory J, Emanuel E (2004). Interventions to improve research participants’ understanding in informed consent for
p.000064: research: a systematic review. JAMA 292(13):1593-1601.
p.000064:
p.000064: Fry CL, Ritter A, Baldwin S, Bowen KJ, Gardiner P, Holt T, Jenkinson R, Johnston J (2005). Paying research
...
p.000108: 5. Creating an Appropriate Relationship Between Participant and Investigator
p.000108: 6. Building and Maintaining Appropriate Community and Stakeholder Relationships
p.000108: 7. Designing and Implementing Strategies for Effective Communication
p.000108:
p.000108: The Human Studies Review Board is asked to address the following questions for each section of the draft
p.000108: document:
p.000108: 1. One of the goals of the document is identify the major scientific and ethical areas and issues that researchers
p.000108: should address in the design and implementation of observational human exposure measurement studies, with the emphasis
p.000108: on the areas requiring ethical considerations. Does each section identify the major areas and issues where ethical
p.000108: considerations should be addressed?
p.000108: 2. The document is intended to serve as a reference and resource of information that researchers can use in the design
p.000108: and implementation of observational exposure studies. For each section, are there additional sources of information
p.000108: that should be considered for inclusion?
p.000108: 3. Is the information presented accurately and clearly in each section?
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000109: 109
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109: Appendix C
p.000109: Recommended Content of a Human Subjects Protocol
p.000109:
p.000109:
p.000109:
p.000109: The Council for International Organizations of Medical Sciences (CIOMS, 2002) has developed a comprehensive list of
p.000109: items that they recommend for inclusion in a human subjects research protocol. Many of the items that they identify
p.000109: are also useful for observational human exposure studies.
p.000109:
p.000109: Items Relevant to Observational Human Exposure Studies
p.000109:
p.000109: (1) The title of the study
p.000109: (2) A summary of the proposed research in lay or nontechnical language
p.000109: (3) A clear statement of the justification for the study
p.000109: (4) The investigators’ views of the ethical issues and considerations raised by the study and,
p.000109: if appropriate, how it is proposed to deal with them
p.000109: (5) A summary of previous studies on the research problem, including unpublished studies known to the
p.000109: investigators, and information on previously published research on the topic
p.000109: (6) A statement that the principles of the Belmont Report and requirements specified in 40 CFR 26 will
p.000109: be implemented
p.000109: (7) An account of previous submissions of the protocol for ethical review and their outcomes
p.000109: (8) A brief description of the sites where the research is to be conducted, including information about the
p.000109: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000109: epidemiological information about the population to be studied
p.000109: (9) The names and addresses of the funding organization, research partners, and collaborators
p.000109: (10) The names, addresses, institutional affiliations, qualifications, and experience of the
p.000109: principal investigator and other investigators
...
p.000111: and a detailed account of the sponsor’s financial commitments to the research institution,
p.000111: the investigators, the research subjects, and, when relevant, the community
p.000111: (35) The arrangements for dealing with financial or other conflicts of interest that might affect
p.000111: the judgment of investigators or other research personnel, including informing the institutional
p.000111: conflict-of-interest committee of such conflicts of interest; the communication by that committee of the
p.000111: pertinent details of the information to the ethical review committee; and the transmission by that committee to
p.000111: the research subjects of the parts of the information that it decides should be passed on to them
p.000111: (36) The time schedule for completion of the study
p.000111: (37) Particularly in the case of an industrial sponsor, a contract stipulating who possesses the
p.000111: right to publish the results of the study and a mandatory obligation to prepare with and submit
p.000111: to the principal investigators the draft of the text reporting the results
p.000111: (38) The circumstances in which it might be considered inappropriate to publish findings, such as when the findings
p.000111: of any study may present risks to or stigmatize the interests of a community or
p.000111: population or of a racially or ethnically defined group of people
p.000111: (39) A statement that any proven evidence of falsification of data will be dealt with in accordance
p.000111: with the policy of the sponsor to take appropriate action against such unacceptable procedures
p.000111:
p.000111: Source: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical
p.000111: Guidelines for Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland.
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000112: 112
p.000112:
p.000112:
p.000112:
p.000112:
p.000112:
p.000112:
p.000112:
p.000112: Appendix D
p.000112: Recommendations for Enhancing Public Trust
p.000112:
p.000112:
p.000112:
p.000112: Although the Report and Recommendations on Public Trust in Clinical Research for the NIH Director from the
p.000112: Director’s Council of Public Representatives (COPR) was developed in the context of NIH-supported clinical
p.000112: research, many of the recommendations are applicable to observational human exposure studies. A summary of
p.000112: recommendations from the report is provided below.
p.000112:
p.000112: Building Trust Through Community Partnerships
p.000112: Recommendation 1: Incorporate into the NIH mission and philosophy that it values the involvement of the
p.000112: community in research and create language that expresses this value.
p.000112: Recommendation 2: Encourage change in the culture of the scientific community to ensure that medical
p.000112: research is viewed in the context of a long- term commitment to the community, not a one-time research study.
p.000112: Recommendation 3: Investigate ways to provide mechanisms that allow for follow-up health care when a clinical
p.000112: trial or treatment ends.
p.000112:
...
p.000112: research.
p.000112: Recommendation 11: Review the role and impact of Institutional Review Boards and other patient protections
p.000112: in the clinical research process because the public views these protections as less effective than they
p.000112: should be.
p.000112: Recommendation 12: Document and publish “best practices” from efforts to reengineer the clinical research
p.000112: enterprise as soon as the NIH begins to see results, so that progress in improving public trust in medical research
p.000112: grows rapidly and steadily.
p.000112:
p.000112: Source: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for
p.000112: the NIH Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health,
p.000112: Director’s Council of Public Representatives, January 14, 2005. Available:
p.000112: http://copr.nih.gov/reports/public_trust.asp [accessed 12 June 2007].
p.000112:
p.000112:
p.000112:
p.000113: 113
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113:
p.000113: Appendix E
p.000113: List of Acronyms and Abbreviations
p.000113:
p.000113:
p.000113: AAP American Academy of Pediatrics
p.000113: ACGIH American Conference of Governmental Industrial Hygienists AHS Agricultural Health
p.000113: Study
p.000113: ATSDR Agency for Toxic Substances and Disease Registry BEI biological exposure index
p.000113: CAB community advisory board
p.000113: CBPR community-based participatory research CDC Centers for Disease Control and
p.000113: Prevention CFR Code of Federal Regulations
p.000113: CIOMS Council for International Organizations of Medical Sciences
p.000113: COPR National Institutes of Health Director’s Council of Public Representatives CPSC
p.000113: Consumer Product Safety Commission
p.000113: CTEPP Children’s Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants
p.000113: DEARS Detroit Exposure and Aerosol Research Study DHEW U.S. Department of Health, Education,
p.000113: and Welfare DMOC data monitoring and oversight committee
p.000113: DNA deoxyribonucleic acid
p.000113: DSMB data safety monitoring board DSMP data and safety monitoring plan
p.000113: EHCRB environmental health and community review board EPA U.S. Environmental Protection
p.000113: Agency
p.000113: ERG Eastern Research Group
p.000113: FCN Federal Communicators Network
p.000113: FDA Food and Drug Administration
p.000113: HHS U.S. Department of Health and Human Services HSRB Human Studies Review Board
p.000113: HSRRO Human Subjects Research Review Official
p.000113: HUD U.S. Department of Housing and Urban Development ICR information collection
p.000113: request
p.000113: IOM Institute of Medicine
p.000113: IRB institutional review board
p.000113: NAS National Academy of Sciences
p.000113: NBAC National Bioethics Advisory Commission NCI National Cancer Institute
...
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p.000033: in Subparts B, C, and D (CFR, 2006a).
p.000033: The section begins by identifying or defining vulnerable groups and then discusses ethical issues that
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
...
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
...
p.000037: general policy of excluding from such clinical trials women biologically capable of becoming pregnant is
p.000037: unjust in that it deprives women as a class of persons of the benefits of new knowledge derived from the
p.000037: trials.” The second relevant CIOMS guideline, number 17, asserts that, if involved in a research study,
p.000037: pregnant women should be fully informed, and included only if the
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: research benefits pregnant women and is thoroughly supported by reliable evidence in animal studies.
p.000038: Although the CIOMS guideline specifically addresses biomedical research, the ethical concepts
p.000038: behind the guidelines generally may be applicable to observational human exposure studies. EPA’s human
p.000038: subjects rule is completely consistent with the HHS rule in adding additional protections for pregnant women and
p.000038: fetuses involved in observational research (40 CFR
p.000038: 26.304 and 45 CFR 46.204). These additional protections (specified in 45 CFR 46.204 subparagraphs a
p.000038: through j) reflect the CIOMS recommendations by requiring: availability of data from previously conducted
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
...
p.000053: circumstances and the required IRB documentation are described in the Common Rule at 40 CFR 26.116(d).
p.000053: • The consent form should clearly state that participation is voluntary and that study
p.000053: participants may “discontinue participation at any time without any penalty or loss of benefits to which the
p.000053: subject is otherwise entitled” [40 CFR 26.116(a)(8)]. If a subject chooses to withdraw from a study, the
p.000053: consequences of their decision and the process for orderly withdrawal should be clearly
p.000053: explained [40 CFR 26.116(b)(4)].
p.000053: • The consent form should address any foreseeable potential future use of samples and data (CIOMS, 2002).
p.000053: For example, effects of environmental exposures on gene expression are potentially very important.
p.000053: Therefore, biologic specimens for DNA analysis may be obtained from participants in future studies. But, it
p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45 CFR 46.408(b)
p.000053: for all research with children. Under the EPA Rule, greater than minimal risk observational research with children that
p.000053: does not hold out the prospect of direct benefit to the child is not permitted under any circumstances. Under the HHS
p.000053: Rule, greater than minimal risk research involving children without the prospect of direct benefit is permitted in very
p.000053: limited circumstances, but the consent of both parents is required in those cases (unless one parent is deceased,
p.000053: unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and
p.000053: custody of the child).
p.000053: special concerns about the potential for discrimination, stigmatization, and impact on
p.000053: future employment or insurance. The informed consent process needs to explain what the plans may be
p.000053: for such specimens and recognize the rights of the subjects to decide about any such future use,
...
p.000115: Health
p.000115: NRC National Research Council
p.000115: OHRP Office for Human Research Protections OMB Office of Management and Budget OSMB
p.000115: observational study monitoring board PM particulate matter
p.000115: Q&As questions and answers
p.000115: QAPP quality assurance project plan
p.000115: RfD reference dose
p.000115: SEAOES Scientific and Ethical Approaches for Observational Exposure Studies TEAL Tribal
p.000115: Efforts Against Lead
p.000115: TEAM Total Exposure Assessment Methodology TLV threshold limit value
p.000115: VOC volatile organic compound
p.000115: WHO World Health Organization
p.000115:
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p.000116: 116
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116:
p.000116: Appendix F
p.000116: Glossary
p.000116:
p.000116:
p.000116:
p.000116: Agent. A chemical, mineralogical, biological, or physical entity that may cause deleterious effects in an organism
p.000116: after the organism is exposed to it [EPA/600/Z-92/001, May 1992].
p.000116: Assent. A child’s affirmative agreement to participate in research. Mere failure to object should not, absent
p.000116: affirmative agreement, be construed as assent [45 CFR 46.402(d)].
p.000116: Autonomy. The capability and capacity to govern oneself.
p.000116: Beneficence. The ethical obligation to maximize benefits and to minimize harms. This principle gives rise to norms
p.000116: requiring that the risks of research be reasonable in light of the expected benefits, that the research design be
p.000116: sound, and that the investigators be competent both to conduct the research and to safeguard the welfare of the
p.000116: research subjects. Beneficence further proscribes the deliberate infliction of harm on persons; this aspect of
p.000116: beneficence is sometimes expressed as a separate principle, nonmaleficence (do no harm).
p.000116: Child. A person who has not attained the age of 18 years [40 CFR 26.202(a)]
p.000116: Collateral observations. Potentially unsafe hazards, conditions, or situations unrelated to the research study that
p.000116: are observed by the research staff
p.000116: Common Rule. The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects.” It was
p.000116: adopted by more than a dozen Federal departments or agencies in 1991, with EPA adapting it in Title 40 CFR Part 26
p.000116: Subpart A.
...
Searching for indicator commonXrule:
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p.000001: Childress, 2001) and the discussion of “What Makes Clinical Research Ethical?” by Emanuel, Wendler, and Grady (Emanuel
p.000001: et al., 2000).
p.000001: Stages in the Development of a NERL Observational Human Exposure Study
p.000001:
p.000002: 2
p.000002:
p.000002:
p.000002: Table 1-4. Important References in Developing This Document:
p.000002: Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
p.000002:
p.000002:
p.000002: Year
p.000002: Event/Report
p.000002: Description
p.000002:
p.000002:
p.001979: 1979
p.001979:
p.001979: The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (U.S. DHEW,
p.001979: 1979)
p.001979:
p.001979: The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively created National
p.001979: Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. It is a statement of basic
p.001979: ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of
p.001979: research with human subjects. The three basic ethical principles are (1) respect for persons, (2) beneficence, and (3)
p.001979: justice.
p.001979:
p.001979:
p.001991: 1991
p.001991:
p.001991: The Common Rule
p.001991: 40 CFR 26, Subpart A
p.001991:
p.001991: The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects” and was adopted by more
p.001991: than a dozen Federal departments or agencies in 1991. Each agency incorporated the policy into its own Code of Federal
p.001991: Regulations (CFR), with EPA adapting it in Title 40 CFR Part 26, Subpart A.
p.001991:
p.001991:
p.001993: 1993
p.001993:
p.001993: The Institutional Review Board Guidebook (U.S. HHS, 1993)
p.001993:
p.001993: The document is intended as a resource and a reference document for IRB members, researchers, and institutional
p.001993: administrators. It is not designed to tell IRBs whether or not specific protocols should be approved; rather, the
p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
p.002000: What Makes Clinical Research Ethical? (Emanuel et al., 2000)
p.002000:
p.002000: This journal article lays out seven areas of concern that need to be addressed if clinical research is deemed to be
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
...
p.000008: subjects research in the United States. Because of the adverse publicity and political embarrassment arising
p.000008: from the unethical treatment of African- American men in the Tuskegee Syphilis Study, Congress passed
p.000008: the National Research Act of 1974, which called on the Department of Health, Education, and Welfare (DHEW) to
p.000008: codify its rules on human subjects research and established the National Commission for the Protection of
p.000008: Human Subjects of Biomedical and Behavioral Research. The commission was charged with identifying the
p.000008: basic ethical principles that should underlie human subjects research. The commission published the
p.000008: Belmont Report in 1979. This report established three basic principles: (1) respect for
p.000008: persons; (2) beneficence; and (3) justice, which have become the cornerstones for regulations involving
p.000008: human subjects (see Table 1-2).
p.000008: In 1981, the Department of Health and Human Services (HHS) issued regulations based on the Belmont Report. Ten
p.000008: years later, the core HHS regulations (Subpart A) were adopted by almost all of the Federal
p.000008: departments and agencies that conducted or sponsored human subjects research as the “Common Rule.”
p.000008: Since 1991, ethical thought and regulatory processes for the protection of human subjects have continued to
p.000008: evolve and grow. For example, many ethicists expand the elements contained in the principle of
p.000008: beneficence from the Belmont Report into two principles:
p.000008: (1) beneficence, meaning to prevent or remove harm and
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: to maximize the possible benefits; and
p.000009: (2) nonmaleficence, meaning not to inflict harm (Beauchamp and Childress, 2001).
p.000009:
p.000009: Table 1-2. The Belmont Report— Principles and Recommendations
p.000009:
p.000009: Ethical Principle Regulatory Manifestation
p.000009: addressed many important scientific and ethical issues on this topic, including the National Research
p.000009: Council (NRC) in its report, Protecting Participants and Facilitating Social and Behavioral Sciences
p.000009: Research (NRC, 2003), a joint NRC and Institute of Medicine (NRC & IOM, 2005) committee in the report on
p.000009: Ethical Considerations for Research on Housing-Related Health Hazards Involving Children; the Council
p.000009: for
p.000009:
p.000009: Respect for Persons
p.000009: • Individuals should be treated as autonomous agents.
...
p.000009:
p.000009: In 2000, Emanuel, Wendler, and Grady considered the ethical principles involved in clinical research and
p.000009: proposed seven ethical requirements to be addressed in research with humans (Emanuel et al., 2000). Their
p.000009: published article specifically addressed clinical research, but the issues are similar for observational
p.000009: human exposure studies. Their ethical requirements are summarized and briefly explained in Table
p.000009: 1-3. The requirements are a logical extension of the ethical principles enunciated in the
p.000009: Belmont Report and manifest themselves in additional requirements for social or scientific value; for
p.000009: processes to ensure the scientific integrity of the research; and for independent review of the design,
p.000009: the subject population, and the risk-benefit ratio. The principle of respect for subjects also includes
p.000009: additional emphasis on the welfare of the subjects.
p.000009: More recently, there has been increased scrutiny and discussions of the ethics of research involving human
p.000009: participants,6 and a number of respected institutions have
p.000009:
p.000009:
p.000009: 6 The term “human participants” often is used in this document. It denotes the importance of the study participant
p.000009: being actively engaged in a partnership with the researchers to address the objectives and goals of the study. The term
p.000009: should be considered to be synonymous with the term “human subject” as used in the Common Rule and in documents used to
p.000009: describe regulatory requirements for studies involving human subjects.
p.000009: Social or scientific value
p.000009:
p.000009: Scientific validity
p.000009:
p.000009:
p.000009: Fair subject selection
p.000009:
p.000009:
p.000009: Favorable risk- benefit ratio
p.000009:
p.000009:
p.000009: Independent review
p.000009:
p.000009:
p.000009:
p.000009: Informed consent
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Respect for potential and enrolled subjects
p.000009: that will improve health and well-being or increase knowledge
p.000009: Use of accepted scientific principles and methods, including statistical techniques, to produce reliable and valid data
p.000009: Selection of subjects so that stigmatized and vulnerable individuals are not targeted for risky research, and the rich
p.000009: and socially powerful are not favored for potentially beneficial research
p.000009: Minimization of risks; enhancement of potential benefits and risks to the subject are proportionate to the benefits to
p.000009: the subject and to society
p.000009: Review of the design of the research trial, its proposed subject population, and risk-benefit ratio by individuals
p.000009: unaffiliated with the research
p.000009: Provision of information to subjects about the purpose of the research and its procedures, potential risks, benefits,
p.000009: and alternatives, so that the individual understands this information and can make a voluntary decision whether to
p.000009: enroll and continue to participate
p.000009: Respect for subjects by
p.000009: • permitting withdrawal from the research,
...
p.000010: researchers plan and implement observational human exposure studies. The researchers will need to work with
p.000010: others⎯the study team, IRB members, EPA HSRRO, the participants and their community, and other
p.000010: stakeholders⎯to identify and
p.000010:
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011: Table 1-4. Important References in Developing This Document:
p.000011: Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
p.000011:
p.000011:
p.000011: Year
p.000011: Event/Report
p.000011: Description
p.000011:
p.000011:
p.001979: 1979
p.001979:
p.001979: The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (U.S. DHEW,
p.001979: 1979)
p.001979:
p.001979: The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively created National
p.001979: Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. It is a statement of basic
p.001979: ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of
p.001979: research with human subjects. The three basic ethical principles are (1) respect for persons, (2) beneficence, and (3)
p.001979: justice.
p.001979:
p.001979:
p.001991: 1991
p.001991:
p.001991: The Common Rule
p.001991: 40 CFR 26, Subpart A
p.001991:
p.001991: The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects” and was adopted by more
p.001991: than a dozen Federal departments or agencies in 1991. Each agency incorporated the policy into its own Code of Federal
p.001991: Regulations (CFR), with EPA adapting it in Title 40 CFR Part 26, Subpart A.
p.001991:
p.001991:
p.001993: 1993
p.001993:
p.001993: The Institutional Review Board Guidebook (U.S. HHS, 1993)
p.001993:
p.001993: The document is intended as a resource and a reference document for IRB members, researchers, and institutional
p.001993: administrators. It is not designed to tell IRBs whether or not specific protocols should be approved; rather, the
p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
p.002000: What Makes Clinical Research Ethical? (Emanuel et al., 2000)
p.002000:
p.002000: This journal article lays out seven areas of concern that need to be addressed if clinical research is deemed to be
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
...
p.000015: first hurdle: sound science is not necessarily ethical. NERL’s observational human exposure studies
p.000015: also must meet both the ethical requirements set forth in human subjects regulations and the ethical
p.000015: standards demanded of responsible researchers by their peers and society. Peer review will focus on the study
p.000015: design and the science but also necessarily will incorporate relevant ethical considerations. IRB review
p.000015: will focus on ethics and the protection of the human research participants but also necessarily will
p.000015: incorporate evaluation of the adequacy of the study design and other relevant aspects of the science. The
p.000015: principle that unsound science is unethical science demands that exposure of human subjects to any research risk
p.000015: whatsoever, even minimal risk, cannot be justified if the research will not answer the scientific
p.000015: questions that motivated the research in the first place.
p.000015: After independent reviews evaluate both the scientific and ethical aspects of the proposed
p.000015: research, EPA policy requires that the proposed study undergo internal EPA review, and that the
p.000015: human subjects research protocol undergo evaluation by the Agency’s Human Subjects Research Review Official
p.000015: (HSRRO). The HSRRO, located in the EPA Office of the Science Advisor, ensures that Agency studies comply with
p.000015: the Common Rule and all directives of 40 CFR 26 providing guidance and principles to govern Federal agency
p.000015: sponsored human subject research.. Only after HSRRO approval can any research actually begin. As the NERL study
p.000015: is implemented, project data and concerns of the participants will be monitored on a continuing basis and
p.000015: compared with previously established standards and
p.000015:
p.000015:
p.000017: 17
p.000017:
p.000017:
p.000017: Table 2.1. Seven Requirements for Determining Whether a Research Trial is Ethical
p.000017: From Emanuel, Wendler, and Grady (2000)
p.000017: Requirement Explanation
p.000017: Topics in this Section
p.000017:
p.000017:
p.000017: Social or scientific value
p.000017:
p.000017: Evaluation of a treatment, intervention, or theory that will improve health and well-being or increase knowledge
p.000017:
p.000017: Defining the study problem Justifying the study Identifying a research team
p.000017:
p.000017:
p.000017: Scientific validity
p.000017:
p.000017: Use of accepted scientific principles and methods, including statistical techniques, to produce reliable and valid data
p.000017:
p.000017: Study design Feasibility
p.000017: Sample size determination Representativeness of the sample Information collection rule
p.000017: Quality assurance Study design document
p.000017:
p.000017:
p.000017: Fair subject selection
p.000017:
p.000017: Selection of subjects so that stigmatized and vulnerable individuals are not targeted for risky research, and the rich
p.000017: and socially powerful are not favored for potentially beneficial research
p.000017:
p.000017: Ethical issues in fair subject selection
p.000017:
p.000017:
...
p.000027: 27. Efforts to minimize “therapeutic misconception”
p.000027: 28. Approaches to minimize changes in participant behavior
p.000027: 29. Payments
p.000027: 30. Plans for informing subjects about items that could affect subjects’ willingness to continue in the study
p.000027: 31. Plans to inform subjects about the results of the study
p.000027: 32. Privacy and confidentiality
p.000027: 33. Security of personal information and when, how, and by whom private information can be revealed
p.000027: 34. All foreseen uses of personal data or biological materials
p.000027: 35. Procedures for data and safety monitoring and oversight of the study and the criteria for identifying, reporting,
p.000027: and responding to adverse events, including ethical breaches, environmental measures in excess of reporting standards,
p.000027: and collateral observations, and criteria for prematurely terminating the study if necessary
p.000027: 36. A list of the references cited in the protocol
p.000027: 37. The source and amount of funding
p.000027: 38. Protocols for dealing with financial or other conflicts of interest
p.000027: 39. Schedule
p.000027: 40. Arrangements with sponsors regarding publication rights and procedures
p.000027: 41. Reasons for not publishing the study findings
p.000027: 42. Procedures for preventing falsification of data
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028: (CBPR) effort, as appropriate (see Section 6, especially Section 6.10).
p.000028:
p.000028: 2.5.4 Ethical Review
p.000028: In the United States, ethical reviews of studies involving human subjects are performed by IRBs.
p.000028: The Common Rule specifies requirements (40 CFR 26.107 –
p.000028: 115) for IRB membership, IRB functions and operations, IRB review of research, and other details related to IRB review
p.000028: and approval of research. Emanuel states that “the independent ethical review of [human subjects
p.000028: research] should involve individuals with training in science, statistics, ethics, and law, as well as
p.000028: reflective citizens who understand social values, priorities, and the vulnerability and concerns of
p.000028: potential subjects” (Emanuel et al., 2000). It is beyond the scope of this document to include
p.000028: detailed discussions on IRB membership, operations, processes, etc. The reader is referred to the Common
p.000028: Rule, as well as a number of other available references (e.g., OHRP, 2007; CFR, 2006; U.S. HHS,
p.000028: 1993; NRC, 2003).
p.000028: It is essential that research with human subjects be carried out or strictly supervised by suitably
p.000028: trained, qualified, and experienced investigators. For all research subject to the Common Rule, these qualified
p.000028: researchers are expected to prepare a human subjects research protocol (as in Section 2.5) and to submit
p.000028: the protocol to be ethically and scientifically appraised by one or more suitably constituted IRBs,
p.000028: independent of the investigators.
p.000028: There are a number of other issues associated with IRBs that may impact researchers
p.000028: conducting observational human exposure studies. As an example, there has been concern about the transparency of
p.000028: IRBs. Questions have been raised about what information the IRB should make available to the public
p.000028: regarding membership on the IRB for review of individual projects, the discussions held with the
p.000028: researchers, the IRB’s concerns about the research protocol, the researchers’ response, etc.
p.000028: Should this information be documented in files that the researchers can make available to the
p.000028: participants, community, stakeholders, and the public? At the present time, there is no clear approach as
p.000028: to how to address these issues. Because these issues are associated with the IRB, not the
p.000028: researcher, it is outside the scope of this document to recommend approaches for IRBs to address
p.000028: these concerns. IRB processes and procedures will continue to evolve as recommended by various committees and
p.000028: workgroups (e.g., as reported in NRC & IOM, 2005; NRC, 2003; U.S. HHS, 1993).
p.000028: All human subjects research conducted or sponsored by NERL is subject to both the 40 CFR 26 requirements and procedures
p.000028: set forth in EPA Order 1000.17 Change A1 (www.epa.gov/oamrtpnc/forms/1000_17a.pdf). The EPA order establishes as
p.000028: policy that all research will comply with the Common Rule and with the order. All human research studies must be
p.000028: reviewed and approved by the EPA HSRRO before the work can begin.
p.000028: In NERL, the director of the division conducting or funding the research is the manager with the primary
p.000028: responsibility for developing the human subjects research protocol and for having that protocol reviewed
p.000028: by an independent IRB acceptable to the EPA HSRRO. The protocol also will be reviewed by the NERL HSRRO
p.000028: and by the appropriate NERL associate director before it is submitted to the IRB. Under 40 CFR 26.109, the IRB can
p.000028: demand changes to the research protocol and is the final authority for approving or disapproving the research
p.000028: activity.
p.000028:
p.000028: 2.5.5 Internal EPA Review of Scientific and Ethical Issues
p.000028: After IRB approval is obtained, the division director will be the primary manager responsible for preparing a request
p.000028: for review and approval or exemption of the human subjects research by the EPA HSRRO. The division
p.000028: director will ensure that the request is consistent with EPA Order 1000.17 A1 and all other policies or
p.000028: procedures that the EPA HSRRO may have established. The EPA HSRRO shall be the final authority for
p.000028: approving or disapproving the research effort. The EPA HSRRO may request additional reviews or establish
p.000028: additional policies and procedures for seeking review and approval. No human subjects research
p.000028: will begin⎯not even recruiting of potential participants⎯until the EPA HSRRO has
...
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45 CFR 46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the Common Rule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
...
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: Common Rule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45 CFR 46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
...
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The Common Rule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
p.000035: broader definition of vulnerability as it relates to education, economics, social status, and other factors. As
p.000035: shown in Text Boxes 3-1 and 3-2 and described above, the concept of vulnerability is broader than that
p.000035: presented in the Common Rule. It is not adequate to simply check the list in Text Box 3-1 to identify if a potentially
p.000035: vulnerable group is included in an observational study. The researchers should assess the potential
p.000035: vulnerability of a study population within the study by evaluating the characteristics (e.g., socioeconomic
p.000035: status) of the study population within the context of the study by considering the various design elements of the
p.000035: study, as discussed in Section 2.
p.000035: 12 In the commentary on Guideline 13 in CIOMS (2002), the committee states that the central problem presented by plans
p.000035: to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
p.000035: the CIOMS document (Guidelines 14 and 15) and include children, and persons who, because of mental or behavioral
p.000035: disorders, are incapable of giving informed consent. Ethical justification of their involvement usually requires that
...
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the Common Rule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the Common Rule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
p.000038: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000038:
...
p.000051: requires “provision of information to subjects about the purpose of the research, its procedures, potential
p.000051: risks, benefits, and alternatives, so that the individual understands this information and can
p.000051: make a voluntary decision whether to enroll and continue to participate” (Emanuel et al., 2000).
p.000051: The NRC & IOM document Ethical Considerations for Research on Housing-Related Health Hazards Involving
p.000051: Children (NRC & IOM, 2005) contains a comprehensive and very useful discussion of informed consent
p.000051: procedures and requirements in Chapter 6. The IOM report, Responsible Research: A Systems Approach to Protecting
p.000051: Research Participants, also includes a thoughtful discussion of participant-investigator
p.000051: interactions and the informed consent process (IOM, 2002). CIOMS also includes recommendations for both the
p.000051: process and content of informed consent (CIOMS, 2002). Some of the important points from those
p.000051: documents are summarized in Text Box 5-1, but the reader should refer to those documents for additional
p.000051: information about this topic.
p.000051: Federal regulations governing research that is either Federally conducted or Federally funded (i.e., all human subjects
p.000051: research at NERL) are codified in the Common Rule. The regulations set forth requirements for both the content of an
p.000051: informed consent and the process for obtaining and documenting an individual’s informed consent (see Text
p.000051: Box 5-2).16 General regulatory requirements for the elements of informed consent are codified in the
p.000051: Common Rule at 40 CFR 26.116(a)(1)
p.000051: (8) (CFR, 2006). The regulations also prescribe the use of a written consent form and describe how informed
p.000051: consent is to be documented (at 40 CFR 26.117). The regulatory requirements for informed consent highlight a
p.000051: number of issues that a NERL researcher needs to consider in developing and administering the informed
p.000051: consent process and the consent form document. The discussion of these issues, arising from
p.000051: regulatory
p.000051:
p.000051:
p.000051: 16 An IRB may waive informed consent under some very limited conditions. See 40 CFR 26.116(c) and (d).
p.000051: requirements or identified in recent writings on ethical considerations in human subjects research, is
p.000051: grouped below, under the three pillars of informed consent:
p.000051: (1) information, (2) comprehension, and (3) voluntary participation.
p.000051:
...
p.000051: effort.
p.000051: (3) Informed Consent Is a Decision To Participate by an Informed, Competent Individual Without Undue Coercion,
p.000051: Influence, or Intimidation (CIOMS, 2002)
p.000051: Informed consent is a process that takes time and resources.
p.000051: It is not a ritual recitation of text from a form but informative communication in language that suits the individual’s
p.000051: level of understanding.
p.000051: Consent is ethically obtained, considering language and cultural issues, and is documented.
p.000051: Material changes in conditions or procedures require that informed consent be renewed.
p.000051: Consent should explain how samples will be used in current research, and, if applicable, how samples may be used in
p.000051: future research.
p.000051:
p.000051:
p.000051:
p.000051: 5.1.1 Information
p.000051: Some items that researchers should keep in mind as they provide information to the study participants are
p.000051: summarized below. These items may be based on regulatory requirements or currently may
p.000051: be recommendations as ethical “best practices.”
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: Text Box 5-2. Common Rule Requirements:
p.000052: Elements of Informed Consent
p.000052: (1) An explanation of the purposes of the research
p.000052: (2) The expected duration of the subject's participation
p.000052: (3) A description of the procedures to be followed and identification of any experimental procedures
p.000052: (4) A description of any reasonably foreseeable risks or discomforts to the subject
p.000052: (5) A description of any reasonably expected benefits to the subject or others
p.000052: (6) A disclosure of appropriate alternative procedures that might be advantageous to the subject
p.000052: (7) A description of the extent that confidentiality will be maintained
p.000052: (8) For research involving more than minimal risk, an explanation about whether compensation or medical treatments
p.000052: are available if injury occurs
p.000052: (9) An explanation of whom to contact with questions about the research or to report a research-related injury
p.000052: (10) A statement that participation is voluntary, refusal to participate will involve no penalty, and the subject may
p.000052: discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled
p.000052: (11*) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or
p.000052: fetus, if the subject is or may become pregnant) that are currently unforeseeable
p.000052: (12*) Anticipated circumstances under which the subject's participation may be terminated by the investigator without
...
p.000053: parents available), and that the consent of both parents be obtained, if possible. The IRB may decide
p.000053: that the permission of one parent is sufficient, but only when certain risk-benefit conditions are met.18
p.000053: • For studies involving children as participants, it is desirable for those children with sufficient capacity
p.000053: to be involved in the consent process. Moreover, it is generally accepted that the child’s assent be obtained
p.000053: whenever this is developmentally possible and otherwise appropriate. Under both the EPA Rule and the HHS
p.000053: Rule, the IRB is responsible for determining that adequate provisions have been made for soliciting the assent of the
p.000053: children when, in the judgment of the IRB, the children are capable of providing assent. Assent, however, may
p.000053: be waived in those restricted circumstances in which consent may be waived under the Common Rule. Those
p.000053: circumstances and the required IRB documentation are described in the Common Rule at 40 CFR 26.116(d).
p.000053: • The consent form should clearly state that participation is voluntary and that study
p.000053: participants may “discontinue participation at any time without any penalty or loss of benefits to which the
p.000053: subject is otherwise entitled” [40 CFR 26.116(a)(8)]. If a subject chooses to withdraw from a study, the
p.000053: consequences of their decision and the process for orderly withdrawal should be clearly
p.000053: explained [40 CFR 26.116(b)(4)].
p.000053: • The consent form should address any foreseeable potential future use of samples and data (CIOMS, 2002).
p.000053: For example, effects of environmental exposures on gene expression are potentially very important.
p.000053: Therefore, biologic specimens for DNA analysis may be obtained from participants in future studies. But, it
p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45 CFR 46.408(b)
p.000053: for all research with children. Under the EPA Rule, greater than minimal risk observational research with children that
...
p.000056: cause or reason) for participation. Many research organizations and IRBs do not have written policies or
p.000056: guidelines
p.000056:
p.000056: regarding the determination of reasonable payment. Decisions often are made based on the level
p.000056: of discomfort and burden, costs to participants, and population characteristics. However, large
p.000056: differences in payment levels have been found even in multisite studies in which the same protocol is
p.000056: administered across all sites.
p.000056: Grady et al. (2005) performed a survey of practices for paying research participants in the United States in
p.000056: Phase 1 to 4 clinical trials and physiologic, behavioral, and other types of research. Across 467
p.000056: studies of varying complexity that included payments, the median
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: payment was $155 (mean $266, range $5 to $2,000). The basis for dollar amounts was infrequently described, with
p.000057: 19% of the payments based on time, and 12% based on the procedures. In a model of payment factors,
p.000057: studies with some prospect of therapeutic benefit, studies having at least one invasive procedure, and studies with
p.000057: greater numbers of clinic visits were significantly associated with higher dollar amounts. About 9.5%
p.000057: of the studies offered completion bonuses, and a similar percentage offered escalating payments for
p.000057: followup study visits.
p.000057:
p.000057: 5.2.2 Regulations and Guidance Regarding Payment to Research Participants
p.000057: There is little specific guidance regarding payments in Federal human research regulations. The Common Rule and
p.000057: additional human subjects protections do not directly address payments to research participants, but the
p.000057: regulations do discuss providing additional safeguards for subjects vulnerable to coercion or undue
p.000057: influence [40 CFR 26.111(b)]. The NIH IRB guidebook advises IRBs to determine whether the rewards offered for
p.000057: participation in research constitute undue influence (U.S. HHS, 1993). According to the IRB guidebook undue
p.000057: inducement might blind prospective subjects to risks, impair their ability to exercise proper judgment, or may
p.000057: cause people to lie or to withhold information that would make them ineligible to enroll or continue
p.000057: participation.
p.000057: The U.S. Food and Drug Administration (FDA) has provided guidance for investigators and IRBs for clinical research
p.000057: studies (FDA, 1998). The guidance states that “payment to research subjects for participation in studies is not
p.000057: considered a benefit, it is a recruitment incentive.” FDA expects payments to accrue as the study progresses and not
p.000057: to be contingent on completing the study, although a “small proportion as an incentive for
p.000057: completion of the study is acceptable.” The guidance is concerned with the issue of coercion or undue influence, and
...
p.000069: asthmatic children in Detroit. The research partnership, Community Action Against Asthma (CAAA), consisted of
p.000069: representatives from local health organizations, community environmental advocacy groups, State and local
p.000069: governmental agencies, and academia. The CAAA partnership credits community involvement as active research
p.000069: partners in the research process with the success of the project to acquire “more relevant exposure data for
p.000069: the study of children in urban neighborhoods” and to provide “immediate knowledge and understanding of the outcomes
p.000069: and results of the combined environmental health analysis to the communities” (Keeler et al., 2002). There are,
p.000069: however, several drawbacks to utilizing CBPR methods that researchers should consider before developing a
p.000069: CBPR project. CBPR is time consuming (develop partnership, establish and agree on research aims and
p.000069: objectives, disseminate results to the community using appropriate methods, and review
p.000069: manuscripts and presentations) and not conducive to situations where rapid decisions are necessary given a
p.000069: tight timeline. Weighing the research need versus the community’s desire for an intervention is the
p.000069: greatest source of tension in conducting CBPR (Israel et al.,
p.000069: 2005b).
p.000069: One additional opportunity for community input may involve participation on an IRB. IRBs are required by the
p.000069: Common Rule to have members who are sensitive to “community attitudes” [40 CFR 26.107(a)]. How they meet this
p.000069: obligation is totally at their discretion, and NERL researchers have no influence. There have been a number of
p.000069: recent articles in the literature about IRBs that have envisioned a need for more regulatory reform
p.000069: (Ledford, 2007). Ideally, the IRB should take into account the views of the community. Quinn
p.000069: (2004) argues for extending protections now reserved for individuals to groups (populations and
p.000069: communities) through CABs. Her argument is that there are “ethical issues related to research with
p.000069: communities that are distinctly different from the ethical issues related to research with individuals.”
p.000069: CAB members have to be educated on human subjects’ protections, should represent their communities
p.000069: honestly, and need to be willing to interact with researchers on complex research issues.
p.000069: Gilbert (2006) goes even further. He suggests supplementing or even replacing traditional IRBs with
p.000069: environmental health and community review boards (EHCRBs). He argues that traditional IRBs
p.000069: are inadequate for the review of community-based research because they were developed to address issues related to
p.000069: individuals involved in research projects, not communities. He proposes EHCRBs that combine
p.000069: the fundamental and ethical concept of traditional IRBs with an expanded ethical construct of dignity,
...
p.000096: that some people understand the term to imply that the observations are both benign and often covert,
p.000096: that is, without interaction with the persons being studied. That is not the case in NERL’s observational human
p.000096: exposure studies. The research often takes place in and around the homes of the participants. Often, the research
p.000096: involves asking the participant to answer a questionnaire and to provide personal samples (e.g., urine,
p.000096: blood). Collection of survey information and personal urine and blood samples cannot be done covertly, and
p.000096: collecting a blood sample is not considered to be benign.
p.000096: Observational Research in NERL: NERL’s observational human exposure studies entail the
p.000096: collection of environmental or biological samples, data, and information from study participants and their
p.000096: surroundings in their everyday environments, as they go about their normal activities, for the purpose of
p.000096: quantifying the contact between the participant and the agent being studied. As such, the studies are designed
p.000096: to meet the regulatory definition of observational research in the CFR. NERL’s studies also meet the scientific
p.000096: definition of an observational study, because the variable being studied, exposure to some agent, is not controlled by
p.000096: the NERL scientists. The observations are not covert, and they may or may not be noninvasive (e.g.,
p.000096: sometimes blood samples may be collected).
p.000096: Because NERL’s observational human exposure studies meet the definition of human subjects research as set forth
p.000096: in the Common Rule, there is also a regulatory requirement to meet the ethical and scientific standards set forth in
p.000096: EPA’s human subjects regulations and in Agency rules. The research protocol must be evaluated and approved
p.000096: by an IRB and by EPA’s Human Studies Research Review Official (HSRRO) before any human subjects research effort
p.000096: can take place. But, even more compelling to NERL managers and scientists is the fact that NERL cannot
p.000096: conduct observational human exposure studies without the participation of willing individuals. Indeed,
p.000096: without the research participants, NERL’s human exposure research would be nothing. This intimate
p.000096: involvement of research subjects in NERL’s research imposes moral and ethical obligations to deal with
p.000096: participants respectfully and to ensure their safety, protection, and well-being.
p.000096: Regulatory Distinction Between Intentional Exposure and Observational Research
p.000096: Intentional Exposure: The CFR states, “Research involving intentional exposure of a human subject
p.000096: means a study of a substance in which the exposure to the substance experienced by a human
p.000096: subject participating in the study would not have occurred but for the human subject’s participation in
p.000096: the study” [40 CFR 26.202(a)]. This definition sets forth two requirements regarding an
p.000096: intentional exposure: (1) the exposure has to be to a substance that is being studied, and (2) at least one
...
p.000116: after the organism is exposed to it [EPA/600/Z-92/001, May 1992].
p.000116: Assent. A child’s affirmative agreement to participate in research. Mere failure to object should not, absent
p.000116: affirmative agreement, be construed as assent [45 CFR 46.402(d)].
p.000116: Autonomy. The capability and capacity to govern oneself.
p.000116: Beneficence. The ethical obligation to maximize benefits and to minimize harms. This principle gives rise to norms
p.000116: requiring that the risks of research be reasonable in light of the expected benefits, that the research design be
p.000116: sound, and that the investigators be competent both to conduct the research and to safeguard the welfare of the
p.000116: research subjects. Beneficence further proscribes the deliberate infliction of harm on persons; this aspect of
p.000116: beneficence is sometimes expressed as a separate principle, nonmaleficence (do no harm).
p.000116: Child. A person who has not attained the age of 18 years [40 CFR 26.202(a)]
p.000116: Collateral observations. Potentially unsafe hazards, conditions, or situations unrelated to the research study that
p.000116: are observed by the research staff
p.000116: Common Rule. The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects.” It was
p.000116: adopted by more than a dozen Federal departments or agencies in 1991, with EPA adapting it in Title 40 CFR Part 26
p.000116: Subpart A.
p.000116: Community-based participatory research (CBPR). Collaborative research with a community in which the community is
p.000116: involved in all phases of the research.
p.000116: A fundamental concept is that the research aims to combine knowledge with action and to achieve social
p.000116: change to improve health outcomes and eliminate health disparities.
p.000116: Confidentiality. The keeping safe or not redisclosing by one of the parties in a confidential relationship information
p.000116: that originally was disclosed in the confidential relationship
p.000116: Environmental justice. The fair treatment and meaningful involvement of all people regardless of race, color, national
p.000116: origin, or income with respect to the development, implementation, and enforcement of environmental laws, regulations,
p.000116: and policies
p.000116: Exposure. Contact of a chemical, physical, or biological agent with the outer boundary of an organism (e.g., a
p.000116: person). Exposure is quantified as the concentration of the agent in the medium in contact integrated over the time
p.000116: duration of that contact. (The definition is taken from Guidelines for Exposure Assessment [EPA/600/Z-92/001, May
p.000116: 1992]).
p.000116: Exposure concentration. The exposure mass divided by the contact volume or the exposure mass divided by the mass of
p.000116: contact volume depending on the medium
p.000116: Exposure duration. The length of time over which continuous or intermittent contacts occur between an agent and a
...
General/Other / cultural difference
Searching for indicator culturally:
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p.000072: Even when all partners and community members are speaking the same language, some terms are not
p.000072: necessarily understood by all. Communications with participants should be reviewed by all partners to ensure
p.000072: that the language used will be appropriate for all participants. At times, one method to
p.000072: communicate research findings will not fit all community members and partners. Even among the partners,
p.000072: understanding each other’s meanings is essential, so that all partners can move forward with a common
p.000072: understanding (Israel et al., 2005b).
p.000072: Furthermore, Minkler and Wallerstein (2003) note that “research must be produced, interpreted, and
p.000072: disseminated to community members in clear, useful, and respectful language.” Researchers, and especially
p.000072: researchers in a government agency, may have their own distinct lexicon. Researchers should be careful to avoid
p.000072: acronyms, jargon, or technical terms that may obscure the meaning or intimidate participants who are
p.000072: not familiar with the terms. Communicating in “plain language” to “explain the research in an
p.000072: honest, straightforward way” will help build a strong relationship with the community and the
p.000072: participants and
p.000072: also help enhance public trust (Recommendation 11, NIH, 2005).
p.000072: Culturally sensitive communication is necessary to developing effective research partnerships with
p.000072: communities. To develop effective communications, researchers must understand key aspects of the cultures
p.000072: influencing the intended audience and build that understanding into the communication strategy (Tillman,
p.000072: 2002). The symbols, metaphors, visuals (including clothing, jewelry, and hairstyles), types of
p.000072: actors, language, and music used in communication materials all convey culture. Discussions with
p.000072: community members can assist researchers in identifying messages and images that resonate across groups or
p.000072: suggesting situations in which different messages or images are likely to work best.
p.000072: As discussed above and in Sections 5 and 7, communication materials must be tailored for each
p.000072: individual community and must be written in a language and at a reading level that will ensure comprehension.
p.000072: Many IRBs require materials to be prepared at a 5th grade reading level. Researchers should evaluate the
p.000072: reading level of all data collection instruments and study communication materials and should objectively
p.000072: measure comprehension in pretests prior to use in the study. Similarly, if translations of materials are
p.000072: required, certified translating services should be used to ensure accuracy and comprehension.
p.000072:
p.000072: 6.2.5 Recognizing and Addressing Cultural Differences
...
p.000073: results of their work are expected to promote a strengthening of the community; however, it should be recognized
p.000073: that, given the heterogeneity and the diverse views within a community, the study findings potentially may
p.000073: conflict with the desires of the community or may promote feelings of anger or distrust among members
p.000073: of the community with each other. Enlisting the services of a third-party evaluator/mediator may be
p.000073: useful for sustaining positive relations between all research participants and the community at
p.000073: large.
p.000073: The Research Triangle Park Particulate Matter Panel Study (Williams et al., 2003), a NERL investigation of PM
p.000073: and related pollutants involving African-Americans in North Carolina, demonstrated an effective strategy for using
p.000073: communication to address cultural differences between the community and research personnel. Before beginning
p.000073: the research, the study design included time and a budget for building collaborations with
p.000073: organizations having close ties with the African- American community to establish trust between
p.000073: the community and research team. Using input from the community partner organizations, the
p.000073: researchers developed a systematic communication plan to establish rapport with the community and to guide
p.000073: interaction between study participants and the key study personnel. A well-designed and culturally sensitive
p.000073: communication plan was integral to the success of the study. Eighty percent of the original participants
p.000073: completed the four- season study (Williams et al., 2003).
p.000073:
p.000073: 6.2.6 Honesty, Power Relationships, and Partnerships
p.000073: The NRC & IOM report (NRC & IOM, 2005) describes a relational paradigm that acknowledges that research
p.000073: is part of a broader societal context, with the conduct of research often mirroring a system in which
p.000073: power is unequally and perhaps unfairly distributed. The trust and mutual commitment required from
p.000073: the researchers and the community are subject to the overall power relations in society.24 The Expert Panel convened to
p.000073: discuss the content of this document recognized that
p.000073:
p.000073:
p.000073: 24 A discussion of the evolution of theories on power relations, including the contribution of feminism,
p.000073: poststructuralism, and postcolonialism, can be found in Minker and Wallerstein (2003, Chapter 2).
p.000073: the researchers have a variety of forms of power that needed to be understood and acted on ethically
p.000073: (ERG, 2007). One form of power is resources, both funds and access to resources and decisionmakers. Other forms of
p.000073: power may be more subtle, including expertise, which can intimidate or limit a participant’s choices.
p.000073: Peer pressure, fear of intimidation, expectations of benefits from the research, and power to
p.000073: stigmatize the community all, whether real or perceived, can influence the relationship between the
...
p.000076: principle of who and what really counts. Acad Manage Rev 22(4):853-886.
p.000076:
p.000076: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for the NIH
p.000076: Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health, Director’s
p.000076: Council of Public Representatives, January 14, 2005. Available: http://copr.nih.gov/reports/public_trust.asp
p.000076: [accessed June 2007].
p.000076:
p.000076: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000076: Housing-Related Health Hazards Involving Children.
p.000076: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000076: June 2007].
p.000076:
p.000076: O’Fallon LR, Dearry A (2002). Community-based partici patory research as a tool to advance environmental health
p.000076: sciences. Environ Health Perspect 110 Suppl 2:155-9.
p.000076:
p.000076: Perkins DD, Wandersman A (1990). You’ll have to work to overcome our suspicions: the benefits and pitfalls of research
p.000076: with community organizations. Soc Policy 21(1):32-41.
p.000076:
p.000076: Quandt S, Arcury T, Pell A (2001). Something for everyone? A community and academic partnership to address farmworker
p.000076: pesticide exposure in North Carolina. Environ Health Perspect 109 Suppl 3:435-441.
p.000076:
p.000076: Quinn SC (2004). Ethics in public health research: protecting human subjects: the role of community advisory boards. Am
p.000076: J Public Health 94(6):918-22.
p.000076:
p.000076: Tillman, L. (2002). Culturally sensitive research approaches: an African-American perspective. Educ Researcher
p.000076: 31(9):3-12.
p.000076:
p.000076: U.S. EPA (U.S. Environmental Protection Agency) (2003). Public Involvement Policy of the U.S. Environmental Protection
p.000076: Agency. EPA 233-B-03-022. Available: http://www.epa.gov/publicinvolvement/pdf/policy2003.pdf [Accessed 26 Sep 2007].
p.000076:
p.000076: Vega WA (1992). Theoretical and pragmatic implications of cultural diversity for community research. Am J Commun
p.000076: Psychol 20(3):375-91
p.000076:
p.000076: Williams R, Suggs J, Rea A, Leovic K, Vette A, Croghan C, Sheldon L, Rodes C, Thornburg J, Eijire A, Herbst M, Sanders
p.000076: W (2003). The Research Triangle Park particulate matter panel study: PM mass concentration relationships. Atmos Environ
p.000076: 37:5349-5363.
p.000076:
p.000076:
p.000076:
p.000076:
p.000077: 77
p.000077:
p.000077: Additional Information Resources
p.000077: Blumenthal DS (2006). A community coalition board creates a set of values for community-based research. Prev Chronic
p.000077: Dis 3(1):1-7. Available: http://www.cdc.gov/pcd/issues/2006/jan/pdf/05_0068.pdf [accessed 12 June 2007].
p.000077:
p.000077: Coleman CH, Menikoff JA, Goldner JA, Dubler NN (2005). The Ethics and Regulation of Research with Human Subjects.
p.000077: Newark: LexisNexis.
p.000077:
p.000077: Davies EF (2001). Early and meaningful community involvement. U.S. Environmental Protection Agency, Office of Solid
...
General/Other / declaration of helsinki
Searching for indicator helsinki:
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p.000025: inconvenience and burden, with no additional societal benefits (i.e., no increase in generalizable
p.000025: knowledge). EPA’s Science Advisory Board has stated that “bad science is always unethical” (U.S. EPA, 2000),
p.000025: and CIOMS declares that “scientifically invalid research is unethical” (CIOMS, 2002).10 It is clear, therefore,
p.000025: that the ethical review has to consider the scientific aspects of the study also.
p.000025: There may be multiple levels of review during development of the study design and human subjects
p.000025: research protocol for an observational human exposure study. The research team is responsible for the design of
p.000025: the study and for ensuring that adequate peer review is
p.000025:
p.000025:
p.000025: 10 CIOMS (2002) Guideline 2 asserts “Ethical review committees—All proposals to conduct research involving human
p.000025: subjects must be submitted for review of their scientific merit and ethical acceptability to one or more scientific
p.000025: review and ethical review committees. The review committees must be independent of the research team, and any direct
p.000025: financial or other material benefit they may derive from the research should not be contingent on the outcome of their
p.000025: review. The investigator must obtain their approval or clearance before undertaking the research. The ethical review
p.000025: committee should conduct further reviews as necessary in the course of the research, including monitoring of the
p.000025: progress of the study.” The CIOMS document continues, “According to the Declaration of Helsinki (Paragraph 11), medical
p.000025: research involving humans must conform to generally accepted scientific principles, and be based on a thorough
p.000025: knowledge of the scientific literature, other relevant sources of information, and adequate laboratory and, where
p.000025: indicated, animal experimentation. Scientific review must consider, inter alia, the study design, including the
p.000025: provisions for avoiding or minimizing risk and for monitoring safety. Committees competent to review and approve
p.000025: scientific aspects of research proposals must be multidisciplinary.”
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000026: performed to evaluate both the scientific and ethical approaches for the study. Following completion of a
p.000026: draft study design, researchers should engage a diverse group of experts to review the study design and human
p.000026: subjects aspects. The scope of the study should dictate the level of the review (i.e., internal
p.000026: or external independent peer review). A small pilot study to evaluate measurement methods or to
p.000026: collect screening level data in preparation for a large study may not require as extensive review as a larger
p.000026: study.
p.000026: When the scientific soundness of the study has been evaluated and found to be feasible, and the final study
p.000026: design is completed, the human subjects research protocol should be developed and submitted to the IRB for
p.000026: review and approval. For studies conducted or supported by EPA, additional review and certification of the
p.000026: human subjects research protocol is required by EPA Order 1000.17 A1. (available online
...
General/Other / participants in a control group
Searching for indicator control group:
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p.000019: trials, where the variables are isolated and controlled (See discussion on experimental studies in
p.000019: Appendix A.) and (2) observational studies where the variables are not controlled intentionally, but are simply
p.000019:
p.000019:
p.000019: 8 A conceptual framework or model is often an effective approach to describe the relationship between the predicted
p.000019: exposures of the population and the population stressors, laying out the predicted pathways and routes of exposure
p.000019: (e.g., see Cohen Hubal et al., 2000). A conceptual model often is illustrated by a block diagram that represents the
p.000019: major scientific processes and interactions. The model is often very useful in developing an analysis plan that
p.000019: describes the hypotheses or objectives of the study, identifies the data needed to address the objectives, and
p.000019: specifies the analyses that will be done to test the hypotheses or address the objectives.
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: observed along with the outcome or response measures. Clearly, the NERL human exposure observational studies
p.000020: (see Table A-1) fall into the latter category. Such studies may be cross-sectional studies (where a subset of the
p.000020: population is observed at the same time); cohort studies (which measure the same variables and response measures
p.000020: in a group of people repeatedly over time); case control studies (where the observed population is
p.000020: separated into two groups based on the outcome or response measure [the case group and the control group], and
p.000020: exposure variables between the two groups are analyzed for differences); or studies that combine
p.000020: approaches. The research may collect data from the participants once (e.g., in a large-scale,
p.000020: randomized design to collect a representative sample of the population, like many of the National Human
p.000020: Exposure Assessment Survey [NHEXAS] studies); over a few days (e.g., NERL’s Particulate Matter [PM]
p.000020: panel studies); from a cohort in different seasons or years (e.g., NERL’s Detroit Exposure Aerosol Research
p.000020: Study [DEARS]; the NHEXAS study in Maryland); or a series of cross-sectional studies repeated one after another with a
p.000020: different group of participants each time. (This latter case often is necessitated to minimize time and expenses
p.000020: associated with being in the field and because of limitations of sampling equipment or field
p.000020: technicians to assist in the collection of the data.)
p.000020: Although much of the literature on study design involves experimental studies (like drug trials), there is much
p.000020: that can be learned about the design of observational studies in epidemiology,
p.000020: including understanding their strengths and weaknesses. Web sites, like “Epidemiology for the Uninitiated” (Coggin
p.000020: et al., 1997, available at www.bmj.com/epidem/epid.html), provide useful basic information on important topics
p.000020: for observational studies and their design.
p.000020: The specific details of the study design and the sampling approach to be used will depend very much on the
p.000020: objectives to be achieved in the study. Based on the objectives, a good study design must first clearly state
...
Searching for indicator placebo:
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p.000093: of watching people in context—in their natural environment, doing routine activities—and collecting
p.000093: the
p.000093:
p.000093:
p.000095: 95
p.000095:
p.000095: samples and relevant information from them and from their surroundings to measure and calculate
p.000095: the exposures that occurred in the same context.
p.000095: Scientific Study Design: From a scientific study design perspective, an observational study of the sort
p.000095: being considered in this document is one where the researcher does not control the variables but,
p.000095: rather, observes both the variable and the outcome and tries to infer the relationship between the variable
p.000095: and the outcome. This contrasts with a controlled study where the researcher isolates and controls
p.000095: one or more variables in a systematic way to assess the impact of changes in the variables on an
p.000095: outcome measure. Consider the intervention study examples cited in the section on regulatory
p.000095: distinctions below (cleaning a house to reduce exposure in the residence and wearing a particle mask to reduce
p.000095: exposure to smoke from forest fires). In those cases, participants would be assigned either to receive the
p.000095: intervention (treatment) or not (the control group). The outcomes (exposures) would be measured and compared
p.000095: between the two groups to assess the effectiveness of the intervention. Similarly, drug trials would randomly
p.000095: assign participants to receive either a test medication or a placebo. The medical outcome (e.g., pain
p.000095: relief, blood pressure, cholesterol levels in blood) would then be measured for all participants,
p.000095: and the outcomes compared between the treated group (getting the test medication) and the control
p.000095: group (receiving the placebo).
p.000095: Controlled studies are often desirable in science because, when properly designed, they provide
p.000095: unambiguous estimates of the impact of unique variables on the outcome (even if the impact of one variable could
p.000095: normally be overwhelmed by other factors) and eliminate the need for alternate explanations of
p.000095: the experimental results (because other factors are held constant). However, controlled studies are
p.000095: not always possible. They may be unethical (e.g., to “treat” a group of women with abortions to test if there
p.000095: is a linkage between having had an abortion and breast cancer), impractical (e.g., to follow a cohort large
p.000095: enough to yield statistically significant results in a test of rare side effects to a medication), or just
p.000095: impossible to accomplish (e.g., to measure nutritional levels of a population in the middle of a war zone).
p.000095: As a consequence, much medical research is observational in the scientific sense being considered
p.000095: here. Public health data represent observations of health outcomes, but the factors that may have led
p.000095: to or influenced those outcomes are not under the control of any researcher. Observational techniques long
p.000095: have been
p.000095: used in medical studies to infer information about the impacts of certain factors on health
p.000095: outcomes. Commonly used techniques include cohort studies, case- control studies, cross-sectional studies, case
p.000095: reports, case series, and descriptive studies (NEAC, 2006; Vandenbroucke et al., 2007).
p.000095: Observational human exposure studies as used in this document are considered to be observational from a
...
Orphaned Trigger Words
p.000001: As EPA employees, NERL scientists face both regulatory and moral obligations to ensure the protection of the
p.000001: human subjects participating in observational research. The regulatory requirements are set forth in
p.000001: EPA’s human subjects regulations (40 CFR 26). NERL scientists are resolved to meet both the “letter” of the law as set
p.000001: forth in the regulations and also the “spirit” that derives from the most up-to-date thinking and consensus on
p.000001: these sensitive issues. This document provides information on regulatory requirements and the state of
p.000001: the science for a number of issues associated with observational human exposure studies to help NERL scientists meet
p.000001: their goal of conducting these studies based on the most up-to-date and sound science and the highest ethical
p.000001: standards.
p.000001: To gather information for the scientific and ethical approaches for observational human exposure studies,
p.000001: NERL convened an expert panel workshop on November 28 and 29, 2006, to discuss the state of the science. The 11-member
p.000001: panel discussed their ideas for the content of this document and the state of the science for various elements
p.000001: of observational human exposure studies. The panel agreed that the document planned by EPA should
p.000001: include the following six major topic areas:
p.000001: (1) identifying elements to be considered in study conceptualization,
p.000001: (2) ensuring protection of vulnerable groups,
p.000001: (3) addressing privacy and other concerns related to observational human exposure studies,
p.000001: (4) creating an appropriate relationship between the participant and investigator,
p.000001:
p.000001:
p.000001: iv
p.000001:
p.000001: (5) building and maintaining appropriate community and stakeholder relationships, and
p.000001: (6) designing and implementing strategies for effective communication.
p.000001: The structure and content of the current document follow the recommendations of the Expert Panel. These
p.000001: recommendations include pragmatic steps that NERL scientists can undertake during the development and
p.000001: implementation of observational human exposure studies.
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: v
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Acknowledgments
p.000001:
p.000001:
p.000001: This document was developed through the joint efforts of many U.S. Environmental Protection Agency (EPA)
p.000001: staff. Roy Fortmann, Larry Cupitt, Kent W. Thomas, and Peter Egeghy, researchers in the National Exposure
p.000001: Research Laboratory, were primary authors of the document. Linda Sheldon provided input to the
...
p.000029: 2.6. Informed Consent
p.000029: 29
p.000029: 2.7. Ensuring That Participant Behaviors Are Not Changed Adversely Because of
p.000029: Being in the Study
p.000030: 30
p.000030: 2.8. Criteria and Standards for Monitoring Scientific and Ethical Issues 30
p.000030: 3. Ensuring Protection of Vulnerable Groups
p.000035: 35
p.000035: 3.1. Identification of Vulnerable Groups
p.000035: 35
p.000035: vii
p.000035:
p.000035: 3.2. Justification for Involving Vulnerable Persons in Observational Research 36
p.000035: 3.3. Minimal Risk and Vulnerable Groups
p.000037: 37
p.000037: 3.4. Research Involving Children
p.000037: 37
p.000037: 3.5. Women as Research Subjects
p.000038: 38
p.000038: 3.6. Other Potentially Vulnerable Groups
p.000039: 39
p.000039: 4. Privacy, Confidentiality, and Other Concerns Related to Observational
p.000039: Human Exposure Studies
p.000041: 41
p.000041: 4.1. Privacy Issues
p.000041: 41
p.000041: 4.2. Confidentiality
p.000042: 42
p.000042: 4.2.1. Confidentiality of Information
p.000043: 43
p.000043: 4.2.2. Confidentiality of Participation
p.000044: 44
p.000044: 4.3. Collateral Observations
p.000044: 44
p.000044: 4.3.1. Potential Nonstudy Hazards in the Residence 44
p.000044: 4.3.2. Collateral Observations with Mandated Reporting Requirements 45
p.000044: 4.3.3. Hazard Communication
p.000045: 45
p.000045: 4.3.4. Planning and Staff Training
p.000046: 46
p.000046: 4.4. Third-Party Issues
p.000046: 46
p.000046: 4.4.1. Determining Whether a Third Party Is a Human Subject 47
p.000046: 4.4.2. Informing Third Parties of Research Activities 47
p.000046: 4.4.3. Research Results and Third Parties
p.000047: 47
p.000047: 4.5. Data and Safety Monitoring and Oversight
p.000048: 48
p.000048: 5. Creating an Appropriate Relationship Between the Participant and Researcher 51
p.000048: 5.1. Informed Consent
p.000052: 52
p.000052: 5.1.1. Information
p.000052: 52
p.000052: 5.1.2. Comprehension
p.000054: 54
p.000054: 5.1.3. Voluntary Participation
p.000055: 55
p.000055: 5.2. Payments to Research Participants
p.000056: 56
p.000056: 5.2.1. Types and Amounts of Payments Offered in Research Studies 56
p.000056: 5.2.2. Regulations and Guidance Regarding Payment to Research Participants 58
p.000056: 5.2.3. Payments When Children or Other Vulnerable Populations Are Involved 59
p.000056: 5.2.4. Payments in Observational Human Exposure Studies 61
p.000056: 5.3. Research Rights and Grievance Procedures
p.000061: 61
p.000061: 5.3.1. Ombudsman
p.000061: 61
p.000061: 5.3.2. Community Advisory Board
p.000062: 62
p.000062: 5.4. Creating a Supportive Environment for Research and Interaction 62
p.000062: 5.5. Recruitment Strategies
p.000062: 62
p.000062: 5.6. Retention Strategies
p.000063: 63
p.000063: 5.7. Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk 64
p.000063: 6. Building and Maintaining Appropriate Community and Stakeholder Relationships 67
p.000063: 6.1. Approaches to Community Involvement
p.000068: 68
p.000068: 6.2. Issues in Community Involvement
p.000071: 71
p.000071: 6.2.1. Defining “Community”
p.000071: 71
p.000071: 6.2.2. Identifying Who Represents the Community 71
p.000071: 6.2.3. Building Relationships and Trust
p.000072: 72
p.000072: 6.2.4. Importance of Language and Communications with the Community 73
p.000072: 6.2.5. Recognizing and Addressing Cultural Differences 73
p.000072: 6.2.6. Honesty, Power Relationships, and Partnerships 74
p.000072: 6.2.7. Building a Lasting Infrastructure
p.000074: 74
p.000074: 6.3. Community Involvement in Observational Human Exposure Studies 75
p.000074: 6.4. Identifying and Interacting with Other Stakeholders 75
p.000074: viii
p.000074:
p.000074: 7. Designing and Implementing Strategies for Effective Communication 81
p.000074: 7.1 Communication Strategy and Implementation Plan 81
p.000074: 7.2 Individuals and Groups Involved in the Communications 82
p.000074: 7.3 Communications Timetables⎯When To Communicate 83
p.000074: 7.4 Communicating at Different Levels
p.000085: 85
p.000085: 7.5 Communications Materials
p.000085: 85
p.000085: 7.6 Informing the Study Participants and Communities 87
p.000085: 7.7 Reporting Study Results to the Participant and Community 87
p.000085: 7.8 Reporting Unanticipated Results or Observations 90
p.000085: 7.9 Anticipating and Responding to Criticism
p.000091: 91
p.000091: 7.10 Responding to the Media, Public Inquiries, and Other Stakeholders 92
...
p.000117: As EPA employees, NERL scientists face both regulatory and moral and ethical obligations to ensure
p.000117: the protection of the human subjects participating in their observational research. The
p.000117: regulatory requirements are set forth in EPA’s human subjects regulations (40 CFR 26). The moral
p.000117: obligations derive from the ethical principles of biomedical ethics. NERL scientists and managers are
p.000117: resolved to meet both the “letter” of the law as set forth in the regulations and also the “spirit” that
p.000117: derives from the most up-to-date thinking and consensus on these sensitive issues.
p.000117: This document provides information on regulatory requirements and ethical issues to consider when
p.000117: performing human subjects research. Knowledge about these requirements and issues will help NERL scientists meet
p.000117: their goal of conducting observational human exposure studies based on the most up-to-date and sound science
p.000117: and the highest ethical scientific standards.
p.000117: The ethical and moral issues associated with human subjects research has long been the subject of a great deal
p.000117: of thought and discussion, both in the United States and abroad. Issues in biomedical ethics continue to be
p.000117: discussed and debated in today’s headlines. Spurred by the atrocities of World War II concentration camps and by
p.000117: the disclosure of unethical treatment of undereducated African-American men and
p.000117: other vulnerable groups by medical staff in the United States, the U.S. and world communities were prompted
p.000117: to establish ethical principles for medical and scientific experiments that involve people as
p.000117: participants. In the United States, the Belmont Report (U.S. DHEW, 1979) is the foundational document in the
p.000117: development of the
p.000117:
p.000117:
p.000001: 1
p.000001:
p.000001: ethics of human subjects research. This report lays out the fundamental ethical principles behind research
p.000001: that involves humans as research subjects. These three basic principles, (1) respect for persons, (2) beneficence,
p.000001: and
p.000001: (3) justice, have become the cornerstones for regulations involving human subjects. Ethicists have expanded on
p.000001: those principles since 1979, translating them into ethical requirements that any human subjects research must be both
p.000001: ethically acceptable and scientifically sound.1 EPA’s Science Advisory Board has affirmed, “Bad
p.000001: science is always unethical” (U.S. EPA, 2000).
p.000001: In an effort to ensure that NERL’s observational human exposure studies are founded on the ethical
p.000001: principles of respect for persons, beneficence and nonmaleficence, and justice and adhering to the
p.000001: principle that bad science is always unethical, scientists and managers from NERL have assembled this
p.000001: document as a resource and reference for NERL exposure scientists. These same scientists and managers have sought
p.000001: expert advice, including input from an expert panel workshop; review and comment on the external review draft of the
p.000001: document by the Human Studies Review Board (HSRB), a Federal advisory committee; public comment on the external
p.000001: review draft of the document; and public input about the state of the science for scientific and ethical
p.000001: approaches for design and implementation of observational human exposure studies.
p.000001: A number of references, both from the bioethics literature and from U.S. regulations, have proven useful
p.000001: Section 1. Introduction: The background for observational human exposure studies, the scope
p.000001: of this document, and the important scientific and ethical issues that are critical to human subjects and
p.000001: observational research.
p.000001: Section 2. Elements to be considered in study conceptualization: Incorporating ethical concerns into
p.000001: the scientific effort from the onset and integrating them throughout all phases of study planning and
p.000001: implementation. As shown in the text box below, the planning process involves the initial identification of the
p.000001: research question and justification of the research effort during the problem conceptualization phase. If human
p.000001: subjects research is justified for the study, the scientific and ethical approaches are described in the study
p.000001: design and the human subjects research protocol. The basic elements that should be included in the
p.000001: study design and in the human subjects research protocol are described, and researchers are advised to consider
p.000001: alternative and innovative study designs that maximize the benefits to the study participants and their
p.000001: community. Information is provided on both scientific peer review and ethical review, and the integration
p.000001: of the two. Mandated procedures for review by external peers, by Institutional Review Boards (IRBs),
p.000001: and by the EPA Human Subjects Research Review Official (HSRRO) are detailed.
p.000001:
p.000001: to the authors as they have developed this document. Those references are listed in Table 1-4,
p.000001: which is replicated below.
p.000001: The authors also have relied extensively on the
p.000001: Problem Conceptualization
p.000001:
p.000001: Planning
p.000001: Define & Justify the Study
p.000001:
p.000001: advice of an expert panel that convened in November 2006 to provide advice and guidance about the structure and
p.000001: content of this document. The Expert Panel consisted of 11 nationally recognized authorities from
p.000001: diverse fields ― exposure science, environmental health, bioethics, epidemiology, community-based research, law,
p.000001: research in minority communities, public health, toxicology, pediatrics, and children’s environmental
p.000001: health.
p.000001: The Expert Panel Workshop resulted in suggestions
p.000001: & Scoping
p.000001:
p.000001:
p.000001: Independent Review
p.000001:
p.000001:
p.000001: Agency HSRRO
p.000001: Review
p.000001: Develop Study Design
p.000001:
p.000001:
p.000001: Peer Review
p.000001: Scientific & Ethical Review
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: HSRRO
p.000001: Review
p.000001: Develop Human Subjects Protocol
p.000001:
p.000001:
p.000001: IRB Review
p.000001: Ethical & Scientific Review
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Disapprove No Study
p.000001:
p.000001: for both the structure and the content of this document (ERG, 2007). Following the advice of the Expert Panel,
p.000001:
p.000001: Implement Study
p.000001: Approve Conduct Study
p.000001:
p.000001: this document is organized in seven sections.
p.000001: & Monitor Progress
p.000001: Criteria OK
p.000001: Continue Study
p.000001: Implement
p.000001: & Monitor
p.000001: Criteria Exceeded
p.000001: Terminate Study
p.000001:
p.000001:
p.000001: 1 See, for example, the writings of Beauchamp and Childress in Principles of Biomedical Ethics (Beauchamp and
p.000001: Childress, 2001) and the discussion of “What Makes Clinical Research Ethical?” by Emanuel, Wendler, and Grady (Emanuel
p.000001: et al., 2000).
p.000001: Stages in the Development of a NERL Observational Human Exposure Study
p.000001:
p.000002: 2
p.000002:
p.000002:
p.000002: Table 1-4. Important References in Developing This Document:
p.000002: Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
p.000002:
p.000002:
p.000002: Year
p.000002: Event/Report
p.000002: Description
p.000002:
p.000002:
p.001979: 1979
p.001979:
p.001979: The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (U.S. DHEW,
p.001979: 1979)
p.001979:
p.001979: The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively created National
p.001979: Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. It is a statement of basic
p.001979: ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of
p.001979: research with human subjects. The three basic ethical principles are (1) respect for persons, (2) beneficence, and (3)
p.001979: justice.
p.001979:
p.001979:
p.001991: 1991
p.001991:
p.001991: The CommonXRule
p.001991: 40 CFR 26, Subpart A
p.001991:
p.001991: The CommonXRule is a short name for “The Federal Policy for the Protection of Human Subjects” and was adopted by more
p.001991: than a dozen Federal departments or agencies in 1991. Each agency incorporated the policy into its own Code of Federal
p.001991: Regulations (CFR), with EPA adapting it in Title 40 CFR Part 26, Subpart A.
p.001991:
p.001991:
p.001993: 1993
p.001993:
p.001993: The Institutional Review Board Guidebook (U.S. HHS, 1993)
p.001993:
p.001993: The document is intended as a resource and a reference document for IRB members, researchers, and institutional
p.001993: administrators. It is not designed to tell IRBs whether or not specific protocols should be approved; rather, the
p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
p.002000: What Makes Clinical Research Ethical? (Emanuel et al., 2000)
p.002000:
p.002000: This journal article lays out seven areas of concern that need to be addressed if clinical research is deemed to be
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000003: 3
p.000003:
p.000003: Section 3. Ensuring protection of vulnerable groups: Protections afforded by EPA’s human subjects rules
p.000003: and the ethical concerns of involving such groups in observational research. Special requirements for the
p.000003: protection of potentially vulnerable groups, including children, prisoners, pregnant women, handicapped
p.000003: persons, mentally disabled persons, and economically or educationally disadvantaged persons, throughout the
p.000003: planning and implementation process are described.
p.000003: Section 4. Addressing privacy and other concerns related to observational human exposure studies:
p.000003: Ethical issues and regulatory requirements concerning privacy, including third-party involvement and
p.000003: observations of nonstudy hazards. Unlike clinical research that is conducted in an institutional
p.000003: setting, observational human exposure studies take place in the participants’ “personal” environments as
p.000003: they go about their everyday lives, presenting an even greater challenge in meeting the ethical obligation to respect
p.000003: the privacy of the participants.
p.000003: Section 5. Creating an appropriate relationship between participant and investigator: Issues surrounding
p.000003: recruitment, informed consent, payment, and the researcher’s need to support the welfare of the
p.000003: participants. An appropriate relationship built on openness and trust requires strong and
p.000003: effective bidirectional communication. Informed consent ensures that the participant understands the
p.000003: range of risks associated with participation and the voluntary nature of participation, and provides
p.000003: essential protections to the participant. Recent observations by various national and international review
p.000003: committees on the appropriate level of payment to research participants are presented. This is a
p.000003: complex ethical issue, balancing the issue of fairness against the possibility of undue influence
p.000003: and the loss of free consent. Other topics include participant recruitment, retention strategies, research
p.000003: rights, and grievance procedures.
p.000003: Section 6. Building and maintaining appropriate community and stakeholder relationships: Involving
p.000003: the community in the research effort to improve the research both scientifically and ethically.
p.000003: Various approaches are discussed related to issues such as defining the community, identifying who
p.000003: represents the community, recognizing and addressing cultural differences, and the importance of language,
p.000003: power relationships, and partnerships.
p.000003: Section 7. Designing and implementing strategies for effective communication: Ongoing, interactive
p.000003: dialogue among researchers, participants, the community, stakeholders, and the public to
p.000003: establish effective communications and to foster a relationship of trust. To facilitate information dissemination
p.000003: to participants, communities, and stakeholders, this section of the document describes communication
p.000003: strategies, implementation plans, communication groups, timetables, communication materials, and other
p.000003: tools available to researchers.
p.000003: This document does not and, indeed, could not provide solutions to all scientific and ethical issues that may
p.000003: arise as observational human exposure studies are undertaken. No document could identify and address all
p.000003: potential issues in advance, nor is it possible to develop a comprehensive checklist for all such studies.
p.000003: Rather, this document attempts to present and discuss the types of ethical and scientific issues that will need
p.000003: to be considered and addressed as NERL researchers plan and implement observational human exposure studies. The
p.000003: researchers will need to work with others ― the study team, IRB members, EPA’s HSRRO, the participants
p.000003: and their community, and other stakeholders ― to identify and address all of the relevant issues
p.000003: for any particular study. The authors are confident that this document will be helpful to NERL scientists
p.000003: in their endeavors to assure that all of NERL’s observational human exposure studies will respect,
p.000003: safeguard, and protect the participants in that research.
p.000003:
p.000003: References
p.000003: Beauchamp TL, Childress, JF (2001). Principles of Biomedical Ethics: Fifth Edition. New York, NY: Oxford University
p.000003: Press.
p.000003:
p.000003: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000003: Subjects. U.S. Code of Federal Regulations.
p.000003: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2008). International Ethical Guidelines for
p.000003: Epidemiological Studies. World Health Organization. Geneva, Switzerland. Available:
p.000003: http://www.cioms.ch/080221feb_2008.pdf [accessed 25
p.000003: April 2008].
p.000003:
p.000003: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000003: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000003:
p.000003:
p.000003:
p.000004: 4
p.000004:
p.000004: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000004:
p.000004: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 20:2701-2711.
p.000004:
p.000004: ERG (Eastern Research Group) (2007). Report on the Workshop to Discuss State-of-the-Science Approaches for
p.000004: Observational Exposure Measurement Studies. Held in Durham, North Carolina on November 28-29, 2006. Final Report:
p.000004: January 25, 2007. (PB2007-108905).
p.000004:
p.000004: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000004: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000004: [accessed 12 June 2007].
p.000004:
p.000004: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000004: Housing-Related Health Hazards Involving Children.
p.000004: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000004: June 2007].
p.000004: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
p.000004: Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of Human Subjects
p.000004: of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 12 June
p.000004: 2007].
p.000004:
p.000004: U.S. EPA (U.S. Environmental Protection Agency) (2000) Comments on the Use of Data from the Testing of Human Subjects:
p.000004: A Report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. United States Environmental Protection
p.000004: Agency, Science Advisory Board, EPA-SAB-EC-00-017. Available: http://yosemite.epa.gov/sab/SABPRODUCT.NSF/E3AE0F3
p.000004: 0D7430436852571A7005325E8/$File/ec0017.pdf [accessed 12 June 2007].
p.000004:
p.000004: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000004: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000004: [accessed 12 June 2007].
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p.000006: 6
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p.000006: SECTION 1
p.000006: Introduction, Purpose, and Scope
p.000006:
p.000006:
p.000006:
p.000006: Observational human exposure studies are an important research tool for understanding people’s
p.000006: contact with pollutants and other stressors in the environment, that is, their exposure.2 Such studies
p.000006: allow researchers to collect information about people’s exposures to chemicals and other stressors
p.000006: under real- world conditions during their normal day-to-day activities. Exposures occur through the
p.000006: air we breathe, the food we eat, the water and beverages we drink, and the surfaces that we touch as we go
p.000006: about our daily routines. To understand and characterize people’s exposures to chemicals, two things
p.000006: have to be known:
p.000006: (1) the concentrations of the chemicals in the environment that people inhale, ingest, or touch;
p.000006: and (2) the human activities that bring people into contact with the media containing the chemicals.3 This
p.000006: document addresses issues associated with observational human exposure studies that are conducted by the
p.000006: National Exposure Research Laboratory (NERL) of the U.S. Environmental Protection Agency (EPA) in an effort
p.000006: to understand and characterize the exposures that people encounter as they go about their daily lives.
p.000006: Because observational human exposure studies involve human participants, they are complex in their
p.000006: design and implementation. As in all research involving human participants, observational human exposure
p.000006: studies carry both regulatory obligations for the protection of human subjects (40 CFR 26) and
p.000006: ethical obligations to the study participants: namely, to respect
p.000006:
p.000006:
p.000006: 2 Exposure, as it is used throughout this document, is a technical term that is defined as the “contact of a chemical,
p.000006: physical, or biological agent with the outer boundary of an organism [e.g., a person]. Exposure is quantified as the
p.000006: concentration of the agent in the medium in contact integrated over the time duration of that contact.” (The definition
p.000006: is taken from Guidelines for Exposure Assessment [EPA/600/Z-92/001, May 1992]). See the Glossary for more information
p.000006: and the definition of additional terms.
p.000006: 3 The term “chemical” is used in this document as a surrogate term for all stressors, including chemical, physical, or
p.000006: biological agents.
p.000006: their autonomy, to not inflict harm (nonmaleficence), to avoid harm and to maximize their benefits (beneficence), and
p.000006: to treat all participants fairly (justice) (See, for example, Principles of Biomedical Ethics, Beauchamp
p.000006: and Childress, 2001). Ethical obligations have to be carefully considered as they relate to the
p.000006: scientific elements of these studies. Therefore, it is important that researchers recognize and understand these
p.000006: obligations and use the most up-to-date scientific and ethical approaches in the design and
p.000006: implementation of observational human exposure studies.
p.000006:
p.000006: 1.1 Observational Human Exposure Studies As we are using the term in this document, “observational
p.000006: human exposure studies” are studies that involve the collection of environmental samples, data, and
p.000006: information from study participants in their everyday environments as they go about their normal
p.000006: activities. These are studies where the NERL researchers do not intentionally try to control the study variables or
p.000006: outcomes, but instead merely observe both the variables and the outcomes. They involve neither the deliberate
p.000006: exposure of participants nor the control of environmental conditions in a way that impacts the
p.000006: participants’ naturally occurring exposures. This scientifically based definition needs to be distinguished
p.000006: at the outset from the broader regulatory term “observational” so that the scope and limits of this
p.000006: document are clear. EPA Regulation 40 CFR 26 (Protection of Human Subjects) at Subpart B, first, defines
p.000006: research involving intentional exposure of a human subject as “a study of a substance in which the exposure to the
p.000006: substance experienced by a human subject participating in the study would not have occurred but for the human subject’s
p.000006: participation in the study” [40 CFR 26.202(a)]. It then goes on at Subpart C to define observational research as “any
p.000006: human research that does not meet the definition of research involving intentional exposure of a human
p.000006: subject” (40 CFR
p.000006:
p.000006:
p.000007: 7
p.000007:
p.000007: 26.302). By defining “observational” so broadly, a regulatory category is created that encompasses a range
p.000007: of study types whose only common feature is that they do not entail “intentional exposure” as defined in the
p.000007: regulations. Moreover, some of these “observational” study types do not involve the study of exposures at all but
p.000007: rather “observe” other sorts of phenomena. The observational human exposure studies with which we are concerned
p.000007: here, on the other hand, are exposure studies, but they represent a narrower group of studies as defined scientifically
p.000007: at the beginning of this paragraph. Although they would generally be expected to fall within the
p.000007: regulatory category of “observational research”, they are not synonymous with it. (For a more thorough
p.000007: discussion of the scientific and regulatory meanings of observational and exposure, with examples, please
p.000007: see Appendix A.)
p.000007: Observational human exposure studies are performed for many different purposes. They have been used
p.000007: extensively in the fields of social behavioral, economic, biological, medical, epidemiological, and
p.000007: exposure research to collect information that relates one or more variables (e.g., exposure to a chemical) to
p.000007: its result (e.g., the concentration of an exposure biomarker in blood). There are many examples of observational
p.000007: human exposure studies that have been conducted over the past decade, and the reader is referred to the Journal
p.000007: of Exposure Science and Environmental Epidemiology and to Environmental Health Perspectives for examples of the
p.000007: objectives, designs, and results of these studies.
p.000007: NERL researchers have conducted and relied on observational human exposure studies for more than three
p.000007: decades. Examples of studies conducted or funded by NERL are listed in Appendix A, Table A-1. Common goals in those
p.000007: studies included those that follow.
p.000007: • Identify which chemicals or other stressors that people are exposed to during their normal activities in the
p.000007: environments that they occupy.
p.000007: • Measure the concentrations of the chemicals to which people are exposed.
p.000007: • Identify the most important routes and pathways of exposure.
p.000007: • Identify the factors that impact people’s exposures (i.e., determine the when, why, how, and how much
p.000007: that people are exposed to chemicals in the environment).
p.000007: These studies involve many different types of data collection efforts and typically include
p.000007: observations,
p.000007: measurements, and information on the following items.
p.000007: • Chemical concentrations in environmental media (air, water, soil, floor dust, and dust on surfaces)
p.000007: • Chemical concentrations in the diet (food and beverages).
p.000007: • Biomonitoring (measurements of biomarkers of exposure in urine, blood, and saliva)
p.000007: • Time, location, and activity information
p.000007: • Information on personal activities, product use, diet, occupation, and other factors that may
p.000007: impact exposure
p.000007: • Information on the characteristics of the environments that study participants occupy (homes, schools,
p.000007: offices, public access buildings, etc.)
p.000007: The information obtained in observational human exposure studies is used to better understand people’s
p.000007: contact with chemicals in the environment and to improve exposure assessments and risk assessments.
p.000007: This information is also essential for developing risk mitigation strategies and for developing
p.000007: educational materials and programs for reducing exposures and risks to chemicals or other stressors in the
p.000007: environment (see Table 1-1).
p.000007:
p.000007: 1.2 Ethical Issues in Observational Human Exposure Studies
p.000007: By definition, observational human exposure studies involve human subjects. Whenever their research
p.000007: involves human subjects, EPA researchers are required to ensure the protection of the study participants
p.000007: by complying with the Agency’s human subjects rules as set forth in 40 CFR 26.
p.000007: The Common Rule (Subpart A of the rules) represents basic regulatory actions (common to more than
p.000007: a dozen Federal departments or agencies) that are intended to ensure the protection of all human subjects. The
p.000007: central requirements of the Common Rule are twofold:
p.000007: (1) that people who participate as subjects in covered research are selected equitably and give
p.000007: their fully informed, fully voluntary written consent; and
p.000007: (2) that proposed research be reviewed by an independent oversight group referred to
p.000007: as an institutional review board (IRB) and approved only if risks to subjects have been minimized, and
p.000007: risks are reasonable in relation to anticipated benefits, if any, to the subjects and to the importance of the
p.000007: knowledge that may realistically be expected to result.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000008: 8
p.000008:
p.000008: Table 1-1. Examples of the Impact of Observational Human Exposure Studies on Pollution Levels and Regulatory Actions
p.000008: Pollutant Observational Study Result
p.000008: Impact/Action/Result
p.000008:
p.000008: Particulate Matter (PM)
p.000008: Observational panel studies demonstrated the appropriateness of ambient measurement of fine particles as a surrogate
p.000008: for a population’s longitudinal exposure to fine PM.
p.000008: Resolved questions in NAS review of PM science and provided a “generally consistent finding that ambient particle
p.000008: concentrations are a key determinant of the longitudinal variation in personal exposure.” (NRC, 2004). These results
p.000008: have been instrumental in support of the National Ambient Air Quality Standard for PM (U.S. EPA, 1999).
p.000008:
p.000008:
p.000008: Volatile Organic Compounds (VOCs)
p.000008:
p.000008: EPA's Total Exposure Assessment Methodology (TEAM) studies found levels of about a dozen common organic pollutants to
p.000008: be 2- to 5-times higher inside homes than outside. Use of products containing organic chemicals may result in very high
p.000008: and persistent pollutant levels.
p.000008:
p.000008: EPA, States, and the Consumer Product Safety Commission worked together to influence manufacturers to voluntarily
p.000008: reduce emissions of toxic chemicals from consumer products, building materials, and furnishings, and to develop
p.000008: mitigation strategies and educational materials to teach people how to reduce their contact with chemicals indoors. As
p.000008: a result, contact with toxic chemicals indoors has been reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html).
p.000008:
p.000008:
p.000008: Formaldehyde
p.000008:
p.000008: Studies found elevated formaldehyde levels indoors and helped identify indoor sources.
p.000008:
p.000008: EPA worked with HUD, CPSC, and other agencies to limit formaldehyde in building or consumer products and to educate the
p.000008: public on how to reduce exposures (see www. epa.gov/iaq/formalde.html).
p.000008:
p.000008:
p.000008: EPA has adopted additional protections for children and pregnant or nursing mothers in Subparts B through
p.000008: D. These sections apply to all research either conducted or funded by EPA and are, therefore, directly applicable to
p.000008: NERL’s observational human exposure studies.4 Subpart B prohibits EPA from conducting or supporting research
p.000008: that involves intentional exposure of “a pregnant woman (and, thereby, her fetus), a nursing woman,
p.000008: or a child.” NERL researchers conducting (or funding) observational human exposure studies must comply
p.000008: with all of these regulatory requirements, including seeking review and approval by an IRB and by the
p.000008: Agency’s Human Subjects Research Review Official (HSRRO) before beginning any human subjects research.
p.000008: EPA’s human subjects rules also define a variety of fundamental terms⎯from “human subject” to “research” to
p.000008: “intentional exposure” to “observational research.” Understanding these regulatory definitions is vital for
p.000008: NERL researchers to comply with the regulatory requirements.5
p.000008: To more effectively ensure the protection of human subjects, NERL scientists and managers need to
p.000008: understand the ethical principles and issues that prompted the development of the
p.000008: regulatory requirements in the first place and to be knowledgeable
p.000008:
p.000008:
p.000008: 4 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements that have to be met if human subjects data
p.000008: from a person or group external to EPA and not funded by EPA (a third party) are to be used by EPA in specified
p.000008: rulemaking actions. These subparts do not apply to NERL researchers and will not be discussed further in this
p.000008: document.
p.000008: 5 The Glossary (Appendix F) lists definitions for a number of important terms; definitions that come from the
p.000008: regulatory language are identified with their specific CFR citation.
p.000008: about the most recent thinking and guidance on protection of human subjects.
p.000008: The Belmont Report (U.S. DHEW, 1979) is a foundational document in the development of the ethics of human
p.000008: subjects research in the United States. Because of the adverse publicity and political embarrassment arising
p.000008: from the unethical treatment of African- American men in the Tuskegee Syphilis Study, Congress passed
p.000008: the National Research Act of 1974, which called on the Department of Health, Education, and Welfare (DHEW) to
p.000008: codify its rules on human subjects research and established the National Commission for the Protection of
p.000008: Human Subjects of Biomedical and Behavioral Research. The commission was charged with identifying the
p.000008: basic ethical principles that should underlie human subjects research. The commission published the
p.000008: Belmont Report in 1979. This report established three basic principles: (1) respect for
p.000008: persons; (2) beneficence; and (3) justice, which have become the cornerstones for regulations involving
p.000008: human subjects (see Table 1-2).
p.000008: In 1981, the Department of Health and Human Services (HHS) issued regulations based on the Belmont Report. Ten
p.000008: years later, the core HHS regulations (Subpart A) were adopted by almost all of the Federal
p.000008: departments and agencies that conducted or sponsored human subjects research as the “CommonXRule.”
p.000008: Since 1991, ethical thought and regulatory processes for the protection of human subjects have continued to
p.000008: evolve and grow. For example, many ethicists expand the elements contained in the principle of
p.000008: beneficence from the Belmont Report into two principles:
p.000008: (1) beneficence, meaning to prevent or remove harm and
p.000008:
p.000008:
p.000009: 9
p.000009:
p.000009: to maximize the possible benefits; and
p.000009: (2) nonmaleficence, meaning not to inflict harm (Beauchamp and Childress, 2001).
p.000009:
p.000009: Table 1-2. The Belmont Report— Principles and Recommendations
p.000009:
p.000009: Ethical Principle Regulatory Manifestation
p.000009: addressed many important scientific and ethical issues on this topic, including the National Research
p.000009: Council (NRC) in its report, Protecting Participants and Facilitating Social and Behavioral Sciences
p.000009: Research (NRC, 2003), a joint NRC and Institute of Medicine (NRC & IOM, 2005) committee in the report on
p.000009: Ethical Considerations for Research on Housing-Related Health Hazards Involving Children; the Council
p.000009: for
p.000009:
p.000009: Respect for Persons
p.000009: • Individuals should be treated as autonomous agents.
p.000009: • Persons with diminished autonomy are entitled to protection.
p.000009:
p.000009: Beneficence
p.000009: • Human subjects should not be harmed.
p.000009: • Research should maximize possible benefits and minimize possible harms.
p.000009: Justice
p.000009: • The benefits and risks of research must be distributed fairly.
p.000009: Informed Consent
p.000009: • Subjects must be given the opportunity to choose what will or will not happen to them
p.000009: • The consent process must include
p.000009: (1) information,
p.000009: (2) comprehension, and
p.000009: (3) voluntariness
p.000009: Assessment of Risks and Benefits
p.000009: • The nature and scope of risks and benefits must be assessed in a systematic manner.
p.000009:
p.000009:
p.000009: Selection of Subjects
p.000009: • There must be fair procedures and outcomes in the selection of research subjects.
p.000009: International Organizations of Medical Sciences (CIOMS) under the World Health Organization in
p.000009: its International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002) and
p.000009: in the International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008); and
p.000009: the National Ethics Advisory Committee of New Zealand in the Ethical Guidelines for Observational Studies:
p.000009: Observational Research, Audits and Related Activities (NEAC, 2006).
p.000009:
p.000009:
p.000009: Table 1-3. Seven Ethical Requirements for Clinical Research
p.000009: From Emanuel, Wendler, and Grady (2000)
p.000009: Requirement Explanation
p.000009: Evaluation of a treatment, intervention, or theory
p.000009:
p.000009: In 2000, Emanuel, Wendler, and Grady considered the ethical principles involved in clinical research and
p.000009: proposed seven ethical requirements to be addressed in research with humans (Emanuel et al., 2000). Their
p.000009: published article specifically addressed clinical research, but the issues are similar for observational
p.000009: human exposure studies. Their ethical requirements are summarized and briefly explained in Table
p.000009: 1-3. The requirements are a logical extension of the ethical principles enunciated in the
p.000009: Belmont Report and manifest themselves in additional requirements for social or scientific value; for
p.000009: processes to ensure the scientific integrity of the research; and for independent review of the design,
p.000009: the subject population, and the risk-benefit ratio. The principle of respect for subjects also includes
p.000009: additional emphasis on the welfare of the subjects.
p.000009: More recently, there has been increased scrutiny and discussions of the ethics of research involving human
p.000009: participants,6 and a number of respected institutions have
p.000009:
p.000009:
p.000009: 6 The term “human participants” often is used in this document. It denotes the importance of the study participant
p.000009: being actively engaged in a partnership with the researchers to address the objectives and goals of the study. The term
p.000009: should be considered to be synonymous with the term “human subject” as used in the CommonXRule and in documents used to
p.000009: describe regulatory requirements for studies involving human subjects.
p.000009: Social or scientific value
p.000009:
p.000009: Scientific validity
p.000009:
p.000009:
p.000009: Fair subject selection
p.000009:
p.000009:
p.000009: Favorable risk- benefit ratio
p.000009:
p.000009:
p.000009: Independent review
p.000009:
p.000009:
p.000009:
p.000009: Informed consent
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Respect for potential and enrolled subjects
p.000009: that will improve health and well-being or increase knowledge
p.000009: Use of accepted scientific principles and methods, including statistical techniques, to produce reliable and valid data
p.000009: Selection of subjects so that stigmatized and vulnerable individuals are not targeted for risky research, and the rich
p.000009: and socially powerful are not favored for potentially beneficial research
p.000009: Minimization of risks; enhancement of potential benefits and risks to the subject are proportionate to the benefits to
p.000009: the subject and to society
p.000009: Review of the design of the research trial, its proposed subject population, and risk-benefit ratio by individuals
p.000009: unaffiliated with the research
p.000009: Provision of information to subjects about the purpose of the research and its procedures, potential risks, benefits,
p.000009: and alternatives, so that the individual understands this information and can make a voluntary decision whether to
p.000009: enroll and continue to participate
p.000009: Respect for subjects by
p.000009: • permitting withdrawal from the research,
p.000009: • protecting privacy through confidentiality,
p.000009: • informing subjects of newly discovered risks or benefits,
p.000009: • informing subjects of results of the research, and
p.000009: • maintaining welfare of subjects.
p.000009:
p.000009:
p.000010: 10
p.000010:
p.000010: Collectively, these documents have reaffirmed the basic ethical principles asserted in the Belmont Report
p.000010: and have attempted, in some cases, to expand scientific and ethical reasoning and understanding to define
p.000010: approaches for dealing with additional elements of human subjects research. These additional
p.000010: elements, which often have been identified because of specific incidents or case studies, include issues
p.000010: such as those described below.
p.000010: • Payment to participants⎯How much is adequate and fair, without being an undue inducement?
p.000010: • Non-study hazards⎯What is the researcher’s responsibility to identify hazards in the home that are
p.000010: not part of the study?
p.000010: • Third-party issues⎯Are there people other than the participant who may be impacted during the study and by the
p.000010: study results? If so, what needs to be done to protect their interests and to respect them as persons?
p.000010: • Community involvement⎯How should the community be involved in the design
p.000010: and implementation of studies?
...
p.000010: is beyond the scope of this document to present a comprehensive discussion of the scientific approaches for
p.000010: observational human exposure studies. To include a comprehensive discussion of scientific approaches in
p.000010: this document would reduce the utility of the document by increasing the complexity of the presentation and the length
p.000010: of the document.
p.000010: This document does not provide solutions to all scientific and ethical issues that may arise as such
p.000010: studies are undertaken. That is, it is not possible to identify or address all potential issues in
p.000010: advance or develop a comprehensive checklist for all such studies. Rather, this document attempts to
p.000010: present and discuss the types of issues that will need to be considered and addressed as NERL
p.000010: researchers plan and implement observational human exposure studies. The researchers will need to work with
p.000010: others⎯the study team, IRB members, EPA HSRRO, the participants and their community, and other
p.000010: stakeholders⎯to identify and
p.000010:
p.000010:
p.000011: 11
p.000011:
p.000011:
p.000011: Table 1-4. Important References in Developing This Document:
p.000011: Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants
p.000011:
p.000011:
p.000011: Year
p.000011: Event/Report
p.000011: Description
p.000011:
p.000011:
p.001979: 1979
p.001979:
p.001979: The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research (U.S. DHEW,
p.001979: 1979)
p.001979:
p.001979: The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively created National
p.001979: Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. It is a statement of basic
p.001979: ethical principles and guidelines that should assist in resolving the ethical problems that surround the conduct of
p.001979: research with human subjects. The three basic ethical principles are (1) respect for persons, (2) beneficence, and (3)
p.001979: justice.
p.001979:
p.001979:
p.001991: 1991
p.001991:
p.001991: The CommonXRule
p.001991: 40 CFR 26, Subpart A
p.001991:
p.001991: The CommonXRule is a short name for “The Federal Policy for the Protection of Human Subjects” and was adopted by more
p.001991: than a dozen Federal departments or agencies in 1991. Each agency incorporated the policy into its own Code of Federal
p.001991: Regulations (CFR), with EPA adapting it in Title 40 CFR Part 26, Subpart A.
p.001991:
p.001991:
p.001993: 1993
p.001993:
p.001993: The Institutional Review Board Guidebook (U.S. HHS, 1993)
p.001993:
p.001993: The document is intended as a resource and a reference document for IRB members, researchers, and institutional
p.001993: administrators. It is not designed to tell IRBs whether or not specific protocols should be approved; rather, the
p.001993: Guidebook points out issues to which IRBs should pay attention and presents, wherever possible, areas where ethicists
p.001993: have arrived at a consensus on the ethical acceptability of a particular activity or method.
p.001993:
p.001993:
p.002000: 2000
p.002000:
p.002000: What Makes Clinical Research Ethical? (Emanuel et al., 2000)
p.002000:
p.002000: This journal article lays out seven areas of concern that need to be addressed if clinical research is deemed to be
p.002000: ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject selection, (4)
p.002000: favorable risk-benefit ratio, (5) independent review, (6) informed consent, and
p.002000: (7) respect for potential and enrolled subjects.
p.002000:
p.002000:
p.002001: 2001
p.002001:
p.002001: Principles of Biomedical Ethics:(Fifth Edition (Beauchamp and Childress, 2001)
p.002001:
p.002001: A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, beneficence, and
p.002001: justice. The chapter on professional-patient relationships discusses issues important to privacy, confidentiality, and
p.002001: protection of subjects. The fifth edition is an update that reflects developments in philosophical analysis, as well as
p.002001: developments in science and medicine.
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002: International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS, 2002)
p.002002:
p.002002: Developed by the Council for International Organizations of Medical Sciences particularly for use in developing
p.002002: countries, the guidelines relate mainly to ethical justification and scientific validity of research; ethical review;
p.002002: informed consent; vulnerability of individuals, groups, communities, and populations; women as research subjects;
p.002002: equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury;
p.002002: strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health care
p.002002: services.
p.002002:
p.002002:
p.002003: 2003
p.002003:
p.002003: Protecting Participants and Facilitating Social and Behavioral Sciences Research (NRC, 2003)
p.002003:
p.002003: This NRC publication targets policymakers, research administrators, research sponsors, IRB members, and investigators.
p.002003: It examines three key ethical issues: (1) obtaining informed, voluntary consent from prospective participants; (2)
p.002003: guaranteeing the confidentiality of information collected from participants, which is a particularly challenging
p.002003: problem in social sciences research; and
p.002003: (3) using appropriate review procedures for minimal-risk research.
p.002003:
p.002003:
p.002005: 2005
p.002005:
p.002005: Ethical Considerations for Research on Housing- Related Health Hazards Involving Children, (NRC & IOM, 2005)
p.002005:
p.002005: This National Research Council and Institute of Medicine report reviews the challenges and ethical issues in conducting
p.002005: housing-related health hazards research in the wake of the Maryland Court of Appeals ruling in the case of Grimes v.
p.002005: Kennedy Krieger Institute that has led to substantial controversy and confusion. The ruling highlighted a range of
p.002005: potential ethical concerns, such as issues involving adequacy of informed consent, parents' perception of risk, duties
p.002005: of researchers to child subjects and their parents, the role of IRBs, and the authority of parents to provide
p.002005: permission for their children to participate in research. This report offers much needed recommendations and practical
p.002005: guidance for the ethical conduct of this type of research.
p.002005:
p.002005:
p.002006: 2006
p.002006:
p.002006: EPA adds Additional Human Subjects Protections at
p.002006: 40 CFR 26
p.002006:
p.002006: EPA added additional human subjects protections in the Code of Federal Regulations to govern its actions. Subparts B
p.002006: through D apply to research conducted or supported by EPA and are directly applicable to NERL and this document.
p.002006: Subpart B prohibits research involving intentional exposure of children, pregnant women (and their fetuses), or nursing
p.002006: women. Subparts C and D provide additional protections for observational research involving pregnant women and their
p.002006: fetuses (Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use of
p.002006: third-party human research data.
p.002006:
p.002006:
p.002008: 2008
p.002008:
p.002008: International Ethical Guidelines for Epidemiological Studies (CIOMS, 2008)
p.002008:
p.002008: This document builds on the CIOMS (2002) document (see above) and extends the discussion to address the special
p.002008: features of epidemiological studies.
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.002008:
p.000012: 12
p.000012:
p.000012: address all of the relevant issues for their particular study to ensure that the specific elements of
p.000012: the study will safeguard and protect the human research subjects.
p.000012: In addition to being an information resource for NERL researchers, this document provides useful
p.000012: information for contractors and grantees funded by NERL to consider during the design and implementation of
p.000012: their exposure science research. Although not its intended audience, this document also may prove to be useful
p.000012: to other researchers, within and outside of EPA, who are involved in observational human exposure
p.000012: studies.
p.000012:
p.000012: 1.4 Process for Developing the Document
p.000012: This document was written by exposure science researchers in EPA’s NERL, with substantial input from experts
p.000012: within and outside of the Agency. Information relevant to the process and the document has been routinely
p.000012: posted on the EPA Web site at http://www.epa.gov/nerl/sots.
p.000012: NERL staff began this work by hosting a series of stakeholder meetings in the summer of 2006 to seek
p.000012: input on the content and format of the document. In November 2006, NERL convened an expert panel to
p.000012: provide its advice and guidance about the scope and content of this document. The Expert Panel consisted of
p.000012: 11 nationally recognized authorities in diverse fields: exposure science, environmental health,
p.000012: bioethics, epidemiology law, community-based research, research in minority communities, public health,
p.000012: toxicology, pediatrics, children’s environmental health, etc. Details about the Expert Panel and the workshop can
p.000012: be found in Appendix B. The summary report from the Expert Panel may be accessed
p.000012: online at http://www.epa.gov/nerl/sots/workshop-report.pdf.
p.000012: The structure and content of the current report follow the recommendations of the Expert
p.000012: Panel. Specifically, the Expert Panel recommended that this document should include the following six major
p.000012: topic areas:
p.000012: (1) elements to be considered in study conceptualization,
p.000012: (2) ensuring protection of vulnerable groups,
p.000012: (3) addressing privacy and other concerns related to observational human exposure studies,
p.000012: (4) creating an appropriate relationship between the participant and investigator,
p.000012: (5) building and maintaining appropriate community and stakeholder relationships, and
p.000012: (6) designing and implementing strategies for effective communication.
p.000012: These recommendations include pragmatic steps that NERL scientists can undertake during the development and
p.000012: implementation of observational human exposure studies. Note that each step may require consideration and
p.000012: application of multiple ethical and scientific principles, and the same ethical principle may
p.000012: be fundamental to several of the topic areas. As a result, the same ethical principle may be discussed in
p.000012: several sections throughout this document.
p.000012: Using the advice of the Expert Panel, an internal review draft of the document was written. Based on the
p.000012: comments from internal EPA reviewers, the internal review draft was revised, and an external review draft
p.000012: was prepared. The external review draft was submitted for peer review by EPA’s Human Subjects Review
p.000012: Board (HSRB), a Federal advisory committee consisting of a panel of experts chartered to review and advise the Agency
p.000012: on the scientific and ethical underpinnings of human subjects research efforts. The external review draft
p.000012: also was announced in the Federal Register and made available for public review and comment. The document
p.000012: subsequently was revised in response to comments from the HSRB and from the public in
p.000012: preparation for publication and release as an EPA report. EPA’s response to comments was posted to the draft
p.000012: report’s docket (EPA-HQ-ORD-2007-0972) at www.regulations.gov.
p.000012:
p.000012: 1.5 Organization of the Document
p.000012: The document is organized along the lines that the Expert Panel recommended. It has seven sections, an
p.000012: introduction followed by a section addressing each of the major topic areas. The content of each section also
p.000012: is based on recommendations from the Expert Panel Workshop. Because the authors concluded that
p.000012: the discussion for each topic area needed to be complete in and of itself (i.e., capable of standing
p.000012: independently without having to reference other sections), there may be some issues or topics that are
p.000012: discussed in several sections. Appendixes include additional descriptions of NERL observational human
p.000012: exposure studies, details about the process for developing this document, a list of acronyms and abbreviations,
p.000012: a glossary, and other supplemental information. The main body of the document includes the following
p.000012: sections.
p.000012: • Introduction, Purpose, and Scope (Section 1) lays out the background for observational human exposure studies,
p.000012: the scope of the document, and some of the important scientific and ethical issues that are critical to human
p.000012: subjects and observational research.
p.000012:
p.000012:
p.000012:
p.000013: 13
p.000013:
p.000013: • Study Conceptualization and Planning (Section 2) establishes that ethical concerns are to be incorporated in
p.000013: the scientific effort from the very beginning and includes ethical issues such as justifying the study
p.000013: because of its social and scientific merit and ensuring scientific validity and independent review.
p.000013: • Protection of Vulnerable Groups (Section 3) discusses some of the special protections afforded to vulnerable groups
p.000013: by EPA’s human subjects rules and the ethical issues of involving such groups in observational research.
p.000013: • Ensuring Privacy and Confidentiality (Section 4) lays out the ethical issues and the regulatory requirements,
p.000013: including observations of nonstudy hazards and the recently discussed issues of third-party involvement or
p.000013: concerns.
p.000013: • The Relationship Between the Participant and the Researcher (Section 5) builds on the ethical principles of
p.000013: respect for persons and beneficence to discuss the issues around recruitment, informed consent,
p.000013: payment, and the researcher’s need to support the welfare of the participants.
p.000013: • Community and Stakeholder Relationships (Section 6) begins with the principles of fairness, justice, and
p.000013: equity and of respect for persons to develop approaches to demonstrate respect for culture
p.000013: and to empower the participants’ community to endure, including the need to build trust in the community and
p.000013: with stakeholders through open and honest communications and legitimate power sharing.
p.000013: • Strategies for Effective Communication (Section 7) builds on the presumption of an ongoing, interactive
p.000013: dialogue and exchange of ideas between researchers and the participants, community, and stakeholders and focuses
p.000013: on steps that the researcher needs to take for effective communications. The section discusses communication
p.000013: strategies, implementation plans, communication tools, reporting of results, and approaches for
p.000013: effective communications, two-way communications between the researchers, participants, community, and other
p.000013: stakeholders.
p.000013:
p.000013: References
p.000013: Beauchamp TL, Childress, JF (2001). Principles of Biomedical Ethics: Fifth Edition. New York, NY: Oxford University
p.000013: Press.
p.000013:
p.000013: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000013: Subjects. U.S. Code of Federal Regulations.
p.000013: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06
p.000013: .html [accessed 12 June 2007].
p.000013:
p.000013: CIOMS (The Council for International Organizations of Medical Sciences) (2008). International Ethical Guidelines for
p.000013: Epidemiological Studies. Geneva, Switzerland: CIOMS. Available: http://www.cioms.ch/080221feb_2008.pdf [accessed 25
p.000013: April 2008].
p.000013:
p.000013: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000013: Biomedical Research Involving Human Subjects.
p.000013: Geneva, Switzerland: CIOMS. Available: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000013:
p.000013: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000013:
p.000013: NEAC (National Ethics Advisory Committee) (2006). Ethical Guidelines for Observational Studies: Observational research
p.000013: audits and related activities. Wellington, New Zealand: Ministry of Health. Available:
p.000013: http://www.neac.health.govt.nz/moh.nsf/indexcm/neac resources-publications-ethicalguidelines.
p.000013:
p.000013: NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing Research
p.000013: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000013: [accessed 16 August 2007].
p.000013:
p.000013: NRC (National Research Council) (2003) Protecting Participants and Facilitating Social and Behavioral Sciences
p.000013: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000013: [accessed 12 June 2007].
p.000013:
p.000013: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000013: Housing-Related Health Hazards Involving Children.
p.000013: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000013: June 2007].
p.000013:
p.000013: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979) The Belmont Report: Ethical Principles and
p.000013: Guidelines for the Protection of Human Subjects of Research. National Commission for the Protection of Human Subjects
p.000013: of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 12 June
p.000013: 2007].
p.000013:
p.000013: U.S. EPA (U.S. Environmental Protection Agency) (1999). Air Quality Criteria for Particulate Matter. Environmental
p.000013: Protection Agency, National Center for Environmental
p.000013:
p.000013:
p.000014: 14
p.000014:
p.000014: Assessment, Office of Research and Development. EPA/600/P-99/002.
p.000014:
p.000014: U.S. EPA (U.S. Environmental Protection Agency) (1992). Guidelines for Exposure Assessment. Environmental Protection
p.000014: Agency, Risk Assessment Forum. EPA/600/Z 92/001. Available: http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_
p.000014: id=429103 [accessed 15 April 2008].
p.000014:
p.000014: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000014: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000014: [accessed 12 June 2007].
p.000014:
p.000014: U.S. OMB (U.S. Office of Management and Budget) (2007). Final Bulletin for Agency Good Guidance Practices, Section
p.000014: I(3). Federal Register 72:16 (25 January 2007) p. 3432. Available:
p.000014: http://www.whitehouse.gov/omb/fedreg/2007/012507_good
p.000014: _guidance.pdf [accessed 6 December 2007].
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p.000015: 15
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p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: SECTION 2
p.000015: Elements to Be Considered in Study Conceptualization and Planning
p.000015:
p.000015:
p.000015:
p.000015: Consideration of the scientific and ethical approaches for observational human exposure
p.000015: studies begins at the very beginning of the study and continues throughout it. Because such studies involve
p.000015: human participants, researchers will have to consider the ethical issues associated with the regulatory
p.000015: requirements for human subjects review and approval. Beyond that, however, ethical principles and
p.000015: issues should be an integral part of all elements of the study and should be included as soon as a study is
p.000015: proposed.
p.000015: In laying out seven requirements for determining whether a research trial is ethical, Emanuel, Wendler,
p.000015: and Grady (Emanuel et al., 2000) listed the requirements in rough chronological order, from conception of the
p.000015: research to formulation of the plan and protocol to implementation of the research study. This
p.000015: section follows their outline as this document highlights areas that NERL exposure science researchers should
p.000015: consider as they develop plans for an observational human exposure study. Table 2-1 shows
p.000015: the ethical requirements and the topics in this section relevant to each requirement.
p.000015: The first stage in the research process is to understand the state of exposure science and EPA’s
p.000015: programmatic needs for exposure data. NERL scientists and managers must decide whether an observational human
p.000015: exposure study is necessary and justified to meet the Agency’s need. If so, then NERL staff will begin to plan for a
p.000015: study. A variety of important issues will need to be considered (identifying and enlisting stakeholders and
p.000015: community representatives, forming a research team, maximizing benefits for participants, precluding
p.000015: conflicts of interest, etc.).
p.000015: The planning phase will culminate in the development of a science-based study design in
p.000015: an ethically sound human subjects research protocol. Adhering to the principal that “Bad science is
p.000015: always
p.000015: unethical” (U.S. EPA, 2000), the research must first be judged to be scientifically sound to meet ethical
p.000015: standards. Peer review by independent and knowledgeable experts will be used by NERL to assess
p.000015: the scientific validity of its proposed research. But passing scientific peer review is just the
p.000015: first hurdle: sound science is not necessarily ethical. NERL’s observational human exposure studies
p.000015: also must meet both the ethical requirements set forth in human subjects regulations and the ethical
p.000015: standards demanded of responsible researchers by their peers and society. Peer review will focus on the study
p.000015: design and the science but also necessarily will incorporate relevant ethical considerations. IRB review
p.000015: will focus on ethics and the protection of the human research participants but also necessarily will
p.000015: incorporate evaluation of the adequacy of the study design and other relevant aspects of the science. The
p.000015: principle that unsound science is unethical science demands that exposure of human subjects to any research risk
p.000015: whatsoever, even minimal risk, cannot be justified if the research will not answer the scientific
p.000015: questions that motivated the research in the first place.
p.000015: After independent reviews evaluate both the scientific and ethical aspects of the proposed
p.000015: research, EPA policy requires that the proposed study undergo internal EPA review, and that the
p.000015: human subjects research protocol undergo evaluation by the Agency’s Human Subjects Research Review Official
p.000015: (HSRRO). The HSRRO, located in the EPA Office of the Science Advisor, ensures that Agency studies comply with
p.000015: the CommonXRule and all directives of 40 CFR 26 providing guidance and principles to govern Federal agency
p.000015: sponsored human subject research.. Only after HSRRO approval can any research actually begin. As the NERL study
p.000015: is implemented, project data and concerns of the participants will be monitored on a continuing basis and
p.000015: compared with previously established standards and
p.000015:
p.000015:
p.000017: 17
p.000017:
p.000017:
p.000017: Table 2.1. Seven Requirements for Determining Whether a Research Trial is Ethical
p.000017: From Emanuel, Wendler, and Grady (2000)
p.000017: Requirement Explanation
p.000017: Topics in this Section
p.000017:
p.000017:
p.000017: Social or scientific value
p.000017:
p.000017: Evaluation of a treatment, intervention, or theory that will improve health and well-being or increase knowledge
p.000017:
p.000017: Defining the study problem Justifying the study Identifying a research team
p.000017:
p.000017:
p.000017: Scientific validity
p.000017:
p.000017: Use of accepted scientific principles and methods, including statistical techniques, to produce reliable and valid data
p.000017:
p.000017: Study design Feasibility
p.000017: Sample size determination Representativeness of the sample Information collection rule
p.000017: Quality assurance Study design document
p.000017:
p.000017:
p.000017: Fair subject selection
p.000017:
p.000017: Selection of subjects so that stigmatized and vulnerable individuals are not targeted for risky research, and the rich
p.000017: and socially powerful are not favored for potentially beneficial research
p.000017:
...
p.000017: Act, the
p.000017:
p.000017:
p.000018: 18
p.000018:
p.000018: Clean Air Act, the Safe Drinking Water Act), program offices or research planning groups in the
p.000018: Agency, scientific peers and researchers, or collaborators. Communities also may identify
p.000018: concerns about exposures in their locales. NERL’s observational human exposure studies collect data to improve
p.000018: exposure and risk assessments, to develop risk management strategies, and to substantiate informational
p.000018: and educational materials for use by EPA program offices (e.g., Office of Pollution Prevention and Toxic
p.000018: Substances, Office of Air and Radiation, Office of Children’s Health Protection).
p.000018: Emanuel et al. (2000) contend that an ethical research study must provide a worthwhile social or
p.000018: scientific value. Ideally, observational human exposure studies can provide both a scientific value and a social
p.000018: value to the participants and their community when feasible. Whenever possible, researchers should work
p.000018: with communities to develop studies that can help address community problems and maximize the
p.000018: benefit to the participants and the community, both of which also assume a burden for participation in a
p.000018: research study.
p.000018: The study problems addressed in past observational human exposure studies conducted or supported by NERL
p.000018: have varied substantially, as described in Appendix A of this document. As shown in Table A-1, NERL’s studies
p.000018: have addressed exposures to particulate matter (PM), air toxics, persistent organic chemicals, and nonpersistent
p.000018: chemicals including pesticides. The studies have examined single routes of exposure (air) and multimedia
p.000018: exposures, including dietary exposure. The studies range from small-scale pilot studies to large
p.000018: probability-based samples. They have included cross- sectional, longitudinal, and convenience samples. Table A-1
p.000018: demonstrates that many of the studies are small in scale and were intended to test a methodology to see if it may
p.000018: prove useful for a subsequent large-scale probabilistic human exposure research effort. Both
p.000018: small-scale and large-scale human exposure studies do involve human subjects. This means that the studies
p.000018: must meet both ethical standards and regulatory requirements. Regardless of the study’s scale,
p.000018: the scientific study design must be technically sound and appropriate to meet the objectives of the study. But
p.000018: the nature and objectives of the scientific inquiry will be different when the study is designed
p.000018: to test a methodology versus when the study is intended to measure a representative
p.000018: distribution of people’s exposures. Defining the study problem is a critical and fundamental first step
p.000018: in the scientific process, because it
p.000018: will establish the objectives that the research will be designed to achieve and the uses to which the research
p.000018: data will be put. The details of the scientific design of the study will naturally be strongly
p.000018: influenced by the objectives that the research is intended to meet.
p.000018:
p.000018: 2.1.2 Justifying the Study
p.000018: Justification of any human study includes both a scientific and an ethical justification. In the list of seven
p.000018: ethical requirements that must be met for human subjects research to be considered ethically acceptable, four of
p.000018: those requirements, (1) respect for subjects, (2) informed consent, (3) favorable risk-benefit ratio, and (4)
p.000018: fair subject selection, are founded on the traditional ethical principles enunciated in the Belmont
p.000018: Report and codified in the Common Rule (Emanuel et al., 2000). But three requirements, (1) social or
p.000018: scientific value,
p.000018: (2) scientific validity, and (3) independent review, apply directly to the scientific aspects of the study. Similarly,
p.000018: Guideline 1 from the CIOMS (2002) document reiterates the foundational principle that “scientifically invalid
p.000018: research is unethical.” Beyond the traditional ethical expectations of respect for, protection of, and fairness
p.000018: to the research subjects, CIOMS requires investigators and sponsors to ensure that the research be
p.000018: “scientifically sound,” that it “conform to generally accepted, scientific principles,” and that all researchers
p.000018: be “qualified” and “competent.”7 Text Box 2-1 identifies a number of elements that should be
p.000018: considered in justifying an observational human exposure study. As discussed below, a critical element to
p.000018: support justification of both the scientific and ethical elements of a study is the use of independent scientific and
p.000018: ethical peer review.
p.000018:
p.000018:
p.000018:
p.000018: 7 Guideline 1 states “research can be ethically justifiable only if it is carried out in ways that respect and
p.000018: protect, and are fair to, the subjects of that research and are morally acceptable within the communities in which the
p.000018: research is carried out. Moreover, because scientifically invalid research is unethical in that it exposes research
p.000018: subjects to risks without possible benefit, investigators and sponsors must ensure that proposed studies involving
p.000018: human subjects conform to generally accepted scientific principles and are based on adequate knowledge of the pertinent
p.000018: scientific literature.” The commentary on the guideline goes on to say, “Among the essential features of ethically
p.000018: justified research involving human subjects, including research with identifiable human tissue or data, are that the
p.000018: research offers a means of developing information not otherwise obtainable, that the design of the research is
p.000018: scientifically sound, and that the investigators and other research personnel are competent. The methods to be used
p.000018: should be appropriate to the objectives of the research and the field of study. Investigators and sponsors must also
p.000018: ensure that all who participate in the conduct of the research are qualified by virtue of their education and
p.000018: experience to perform competently in their roles. These considerations should be adequately reflected in the research
p.000018: protocol submitted for review and clearance to scientific and ethical review committees.”
p.000018:
p.000018:
p.000019: 19
p.000019:
p.000019:
p.000019: Text Box 2-1. Elements to be Considered in Justifying a Study
p.000019: • The research problem and questions to be addressed in the study
p.000019: • The objectives of the study or the hypotheses to be tested
p.000019: • A discussion of why human participants are required for the study, including a discussion of alternative designs
p.000019: that were considered
p.000019: • Available information on the need for the study (i.e., it is not redundant and the research question has not been
p.000019: already answered)
p.000019: • Available information from the scientific literature demonstrating the relevance of the proposed study
p.000019: • A discussion of the general technical approach and scientific soundness of the approach
p.000019: • An assessment of the needed competencies and qualifications of all personnel involved in conducting the research
p.000019: • The likelihood of success in meeting the study goals and objectives (including an evaluation of the accuracy,
p.000019: precision, and quality assurance of the data needed to attain the study goals and objectives)
p.000019: • Justification for the investment of time and money
p.000019:
p.000019:
p.000019: 2.1.3 Identifying a Research Team To Plan and Implement the Study
p.000019: Once the study problem has been defined and justified, the next step in developing the research study is
p.000019: to form the research team. The team should be diverse, including the technical experts (e.g.,
p.000019: exposure researchers, statisticians, chemists), stakeholders, and representatives and members of the community in
p.000019: which the study likely will be performed. Information on identifying potential conflicts of
p.000019: interest among researchers early in the planning stage is discussed in Section 2.5.2. For scientific,
p.000019: ethical, and practical reasons, the community should be appropriately involved throughout the study,
p.000019: including throughout the planning phase. Information on identifying and engaging community members in the
p.000019: process is described in Section 6 of this document. The joint NRC-IOM committee reviewing
p.000019: ethical issues for research conducted in the homes and communities of the participants (like
p.000019: much of NERL’s human exposure research) concluded that “When researchers discuss a planned study with
p.000019: community representatives, understand their concerns and needs, and respond to them, protocols can be
p.000019: strengthened both scientifically and ethically” (p. xii, NRC & IOM, 2005).
p.000019:
p.000019: 2.2 Ensuring Scientific Validity of the Research Study
p.000019: To facilitate scientific and ethical review, the research team members should develop a comprehensive
p.000019: and detailed study design that describes the technical approach for the observational study. Although
p.000019: the format and scope may vary depending on the specific study, there are a number of basic elements
p.000019: generally included in the study design.
p.000019: Translating the information developed in defining the problem and justifying the study into a
p.000019: real, workable, feasible study design and human subjects protocol is an iterative process involving input from
p.000019: all of the members of the research team. Scientific and technical expertise is required to assure the
p.000019: scientific integrity of the research, including developing the conceptual model8 for the effort and
p.000019: devising a reliable sampling and analysis plan. Stakeholder input is critical to assuring that the generalizable
p.000019: research information from the study actually will be applicable for addressing the study problem. Community
p.000019: input is particularly important during the planning stage because the community representatives
p.000019: can provide valuable information about the community members (the future study cohort), the cultures of
p.000019: the community, community values, community concerns, feasibility of working in the community, information
p.000019: needed to develop the technical approach, and information on important factors like pollutant sources and
p.000019: other stressors in the community. (Additional considerations for communicating and
p.000019: working with both the participants and the community in which they live are the topics of Sections 5 through 7 of
p.000019: this document.)
p.000019: In developing the study design and the human subjects protocol, the research team often will have
p.000019: to deal with a variety of complex issues, including how to maximize benefits for participants, the community, and
p.000019: the stakeholders, and how to ensure the integrity, generalizability, and representativeness of the study.
p.000019:
p.000019: 2.2.1 Study Design
p.000019: In epidemiology, the concept of study design has been structured to include (1) experimental studies, like drug
p.000019: trials, where the variables are isolated and controlled (See discussion on experimental studies in
p.000019: Appendix A.) and (2) observational studies where the variables are not controlled intentionally, but are simply
p.000019:
p.000019:
p.000019: 8 A conceptual framework or model is often an effective approach to describe the relationship between the predicted
p.000019: exposures of the population and the population stressors, laying out the predicted pathways and routes of exposure
p.000019: (e.g., see Cohen Hubal et al., 2000). A conceptual model often is illustrated by a block diagram that represents the
p.000019: major scientific processes and interactions. The model is often very useful in developing an analysis plan that
p.000019: describes the hypotheses or objectives of the study, identifies the data needed to address the objectives, and
p.000019: specifies the analyses that will be done to test the hypotheses or address the objectives.
p.000019:
p.000019:
p.000020: 20
p.000020:
p.000020: observed along with the outcome or response measures. Clearly, the NERL human exposure observational studies
p.000020: (see Table A-1) fall into the latter category. Such studies may be cross-sectional studies (where a subset of the
p.000020: population is observed at the same time); cohort studies (which measure the same variables and response measures
p.000020: in a group of people repeatedly over time); case control studies (where the observed population is
p.000020: separated into two groups based on the outcome or response measure [the case group and the controlXgroup], and
p.000020: exposure variables between the two groups are analyzed for differences); or studies that combine
p.000020: approaches. The research may collect data from the participants once (e.g., in a large-scale,
p.000020: randomized design to collect a representative sample of the population, like many of the National Human
p.000020: Exposure Assessment Survey [NHEXAS] studies); over a few days (e.g., NERL’s Particulate Matter [PM]
p.000020: panel studies); from a cohort in different seasons or years (e.g., NERL’s Detroit Exposure Aerosol Research
p.000020: Study [DEARS]; the NHEXAS study in Maryland); or a series of cross-sectional studies repeated one after another with a
p.000020: different group of participants each time. (This latter case often is necessitated to minimize time and expenses
p.000020: associated with being in the field and because of limitations of sampling equipment or field
p.000020: technicians to assist in the collection of the data.)
p.000020: Although much of the literature on study design involves experimental studies (like drug trials), there is much
p.000020: that can be learned about the design of observational studies in epidemiology,
p.000020: including understanding their strengths and weaknesses. Web sites, like “Epidemiology for the Uninitiated” (Coggin
p.000020: et al., 1997, available at www.bmj.com/epidem/epid.html), provide useful basic information on important topics
p.000020: for observational studies and their design.
p.000020: The specific details of the study design and the sampling approach to be used will depend very much on the
p.000020: objectives to be achieved in the study. Based on the objectives, a good study design must first clearly state
p.000020: the research question (or hypothesis to be tested) and must also define in advance what outcome or
p.000020: response measure will be used to test the question or hypothesis. Study designs that are vague or which propose
p.000020: to test some outcome measures against a variety of potential factors do not represent sound science.
p.000020: Statistically, a correlation is likely to be found between an outcome and some factor if enough factors are
p.000020: tested—whether there is an actual biological or physical relationship or not. This highlights the importance of
p.000020: statistics as an integral part of the study design process. Including individuals
p.000020: with appropriate statistical knowledge and experience on the research team from its very beginning is critical to a
p.000020: scientifically sound study design. (See, for example, Dallal, 2001, “Some Aspects of Study Design” in The
p.000020: Little Handbook of Statistical Practice at www.StatisticalPractice.com, and at
p.000020: www.tufts.edu/~gda llal/LHSP.HTM).
p.000020: The study design must carefully consider each item of data or information that is to be collected during the study and
p.000020: how the data will be used in the analysis. All of the data needed to complete the analysis and test the hypothesis
p.000020: must be collected, otherwise the research objectives cannot be met, and the study should not go forward.
p.000020: Alternatively, data that are unrelated to the study analysis should not be collected. Collection of such
p.000020: data imposes a burden on both the participants and research staff with no known potential for benefit.
p.000020: Collecting, validating, and archiving such data wastes time and money and inappropriately burdens the
p.000020: participants. If there is no solid analysis plan for a particular data item, such data should not be
p.000020: collected. If the researchers actually believe that some factor may represent a potentially overlooked
p.000020: variable, then they should collect the information to test that hypothesis correctly. But, just collecting
p.000020: the data “while we can,” with no plan for how to analyze and use the data, wastes resources, imposes unnecessary
p.000020: burden, and often proves tempting as a statistical correlation hunt. Finally, the study design must be described
p.000020: in sufficient detail to be properly evaluated. Preparation of the study design document is described
p.000020: in a later section, but the overriding goal is to provide enough information to allow proper review
p.000020: of the science behind the study design by the research team, the scientific peer community, and the
p.000020: IRB panel members.
p.000020:
p.000020: 2.2.2 Feasibility
p.000020: The authors consider the evaluation of the feasibility of accomplishing the study to be one of the most critical
p.000020: components of the development of the study design. Evaluating the feasibility of the research project involves
p.000020: considering not only whether there are sufficient resources to accomplish the study, but whether or not the
p.000020: study is feasible from a scientific and ethical perspective. If the research team concludes that the study is
p.000020: not feasible, there will be no further effort to develop the study. There may be practical limitations
p.000020: that preclude conduct of the study as initially conceived. Because “scientifically invalid research
p.000020: is unethical” (Guideline 1, CIOMS, 2002), it is essential that scientific and ethical considerations be
p.000020: considered together. Text
p.000020:
p.000020:
p.000021: 21
p.000021:
p.000021: Box 2-2 includes some examples of the types of questions that may be asked when evaluating
p.000021: the feasibility of a study.
p.000021:
p.000021: Text Box 2-2. Is the Study Feasible?
p.000021: • What are the sample size requirements? Can enough participants be enrolled into the study from the proposed
p.000021: community, considering the eligibility criteria and anticipated response rate? What is the predicted retention rate if
p.000021: this is a repeated measurements study? Is that acceptable?
p.000021: • Is the research question well defined, and can we measure the variables and the outcome metrics?
p.000021: • Are the measurement methods specific and accurate enough to accomplish the research?
p.000021: • Does the analysis plan provide results to test the research questions and to meet the study objectives?
p.000021: • Will the community be receptive to this study?
p.000021: • Are there cultural mores, societal values, or other factors associated with the community that would make it
p.000021: difficult to conduct the study in the community? Is the study morally acceptable to the community?
p.000021: • Is there a community structure that will allow the research team to engage the community in the study?
p.000021: • What is the burden on the community?
p.000021: • What is the burden on the participants? Is it acceptable?
p.000021: • What is the risk-benefit balance? Is it acceptable, considering the burden on the participants?
p.000021: • Are there sufficient resources available to conduct a study of this size?
p.000021: • Are resources available for community outreach and sustained interactions with the community? Are resources
p.000021: available to support community members involved in the study?
p.000021:
p.000021:
p.000021:
p.000021: 2.2.3 Sample Size Determination
p.000021: One critical issue in assuring that an observational human exposure study is scientifically valid
p.000021: (and, thereby, not invalid and unethical) is the issue of sample size. EPA’s Science Advisory Board has stated,
p.000021: “Bad science is always unethical; research protocols that are fundamentally flawed, such as those with
p.000021: sample sizes inadequate to support reasonable inferences about the matter in question, are unjustifiable”
p.000021: (p. 2, U.S. EPA, 2000).
p.000021: A study has to have an adequate size to meet the study objectives. If the sample size is too small,
p.000021: the results may not be statistically significant, and the results may not be either valid or generalizable. Such
p.000021: a result would be a waste of resources or cause undue burden on study participants without generating the
p.000021: intended generalizable knowledge that will benefit society. On the other hand, if the study sample size is
p.000021: larger than necessary to meet a study objective, this also may result in a waste of resources or the imposition
p.000021: of needless burden on participants.
p.000021: Sample size determination is an important step in planning a study, but it can be a difficult task
p.000021: (Lenth, 2001). Sample size determination also may be confounded by other issues that will reduce the
p.000021: number of measurements that may be used in the analysis. For example, participants in a longitudinal study may
p.000021: “drop out” over time (some may move, others may tire of participation, etc.), so that the number of
p.000021: participants at the end of the study will be less than the number that started the study. The study design
p.000021: must account for the attrition of participants over time and plan ahead to recruit enough participants to
p.000021: ensure that a statistically useful number of participants complete the study. Often NERL scientists have used
p.000021: historical retention rates to estimate the sample size needed for a study. (See discussion of
p.000021: retention rates in NHEXAS publications.)
p.000021: In addition, some participants or their environments may not have concentrations above the detection limit.
p.000021: Depending on the nature of the research question, data below the analytical detection limit may, or may not, be
p.000021: useful in addressing the research question: sample size may need to be increased to account for missing values
p.000021: and values below detection. Pilot studies and environmental studies (with no participants as
p.000021: human subjects) may prove useful in understanding the range of concentrations to be expected and may provide
p.000021: insight into how to adjust the sample size appropriately. In surveys, like NERL’s National Human Activity
p.000021: Pattern Survey (NHAPS) for example, some randomly selected participants simply may refuse to participate, decreasing
p.000021: the number of samples and perhaps biasing the data.
p.000021: It is critical that sample size be determined at the time of study conceptualization and planning and
p.000021: not after the study already has been conducted. Researchers must include experts with the appropriate
p.000021: statistical expertise on the research team at its very inception. For additional information and insight, readers
p.000021: should refer to biostatistics books, Web sites, and other references (Lenth, 2001; Castelloe, 2000; Kraemer and
p.000021: Thiemann, 1987; Van Belle and Fisher, 2004; Wackerly et al., 2001; Dallal, 2001) about this very important topic.
p.000021:
p.000021: 2.2.4 Representativeness of the Sample
p.000021: In addition to concerns about the sample size being sufficient to provide statistically significant results,
p.000021: researchers also must be concerned about the individuals who participate in a study and of what group
p.000021: or population they may be representative. Research, as defined in the Common Rule, is “a
p.000021: systematic investigation … designed to develop or contribute to generalizable knowledge.” How
p.000021: “generalizable” the
p.000021:
p.000021:
p.000022: 22
p.000022:
p.000022: results of an observational study may be depends on the representativeness of the sample (the participants). A
p.000022: review of former NERL studies (Table A-1) shows a wide variety of approaches to selecting the participants,
p.000022: both probability sampling and nonprobability sampling. Some of the studies have involved randomized sampling (e.g.,
p.000022: NHAPS, NHEXAS), selecting a cohort of interest and then using a randomized sample (e.g., Children’s Total
p.000022: Exposure to Persistent Pesticides and Other Persistent Organic Pollutants [CTEPP], DEARS) or a
p.000022: convenience sample (e.g., some panel studies), purposeful selection (judgment sampling) by
p.000022: the research team (for methods testing studies), recruiting the whole population in a locale or of a particular
p.000022: cohort (e.g., as proposed for the National Children’s Study [NCS]), or simply a convenience sample (in small
p.000022: pilot studies).
p.000022: The approach used to select the participants has depended on the objectives of the study. Research to
p.000022: understand and describe the distribution of exposures in the general population (like NHEXAS) or of the
p.000022: population or cohort in a particular state or region (like CTEPP or Agricultural Health Study [AHS]), has
p.000022: required a large number of randomly-selected participants. Randomized selection is recognized
p.000022: as a valid statistical method to get a sample that is representative of the larger population
p.000022: from which the participants were selected. Pilot studies performed to evaluate a method or to estimate
p.000022: the likely range of exposure concentrations often have employed either purposeful sampling, where
p.000022: the researchers use information on the relevant characteristics of the population to select those
p.000022: participants who will exhibit a wide range of activity levels or potential exposure concentrations, or
p.000022: convenience sampling, where the researchers select the most accessible members of a population
p.000022: NERL’s observational human exposure studies also have routinely collected information about the
p.000022: participants’ activities by using questionnaires and surveys. Survey design is both a science and an
p.000022: art because the design of surveys is based on statistics and science, but designing a good and effective questionnaire
p.000022: is often an art that requires understanding the individuals being surveyed. Text Box 2-3 identifies some of the
p.000022: areas of art involved in designing an effective questionnaire.
p.000022: Understanding the process for selecting participants and the statistical-scientific requirements of
p.000022: questionnaire design are both components of survey sampling and design. A variety of references can provide
p.000022: the researcher with information about the issues in survey sampling and
p.000022: design. (See http://home.ubalt.edu/ntsbarsh/Business-stat/stat data/Surveys.htm and
p.000022: www.statpac.com/surveys/, for example.) But the research team must include or have access to the appropriate
p.000022: survey statistics expertise as it plans the research study.
p.000022:
p.000022: Text Box 2-3. Questionnaire Considerations
p.000022: • Questions should be simple and in a language the individual can understand.
p.000022: • Questions should be unambiguous.
p.000022: • Questions should be relevant to the study.
p.000022: • Questions should not be too personal.
p.000022: • The questionnaire should be as short as possible.
p.000022: • The questions should not be leading (e.g., internally suggestive of the answer).
p.000022: • Questions should follow a logical order.
p.000022:
p.000022:
p.000022:
p.000022: 2.2.5 Information Collection Rule
p.000022: As Federal employees, NERL researchers also must be aware of Information Collection Rule requirements. The
p.000022: Paperwork Reduction Act stipulates that every Federal agency must obtain approval from OMB before collecting
p.000022: the same or similar information from 10 or more members of the public. An Information Collection Request (ICR)
p.000022: is required if the same or similar information is being collected from 10 or more non- Federal
p.000022: respondents within a 12-month period, even if the information collection is voluntary. Generally, any
p.000022: survey, questionnaire, monitoring, reporting, or recordkeeping requirement imposed on
p.000022: non-Federal respondents by EPA will require an ICR. Information collections associated with all cooperative
p.000022: agreements funded by the EPA require an ICR. When an ICR is required, it must be approved by OMB
p.000022: before the collection begins, regardless of whether the collection of information is mandatory, voluntary,
p.000022: or required to receive a benefit. The principal investigator must prepare an ICR and submit it to the
p.000022: appropriate Office of Environmental Information Desk Officer.
p.000022: An ICR
p.000022: • describes the information to be collected,
p.000022: • provides justification for why the information is needed, and
p.000022: • estimates the time and cost for the public to answer the request.
p.000022: Information about ICRs and their requirements is available to NERL and other EPA staff members at
p.000022: http://intranet.epa.gov/icrintra/index.html.
p.000022:
p.000022:
p.000023: 23
p.000023:
p.000023: 2.2.6 Quality Assurance Project Plan
p.000023: Data of unknown or uncertain quality can undermine the scientific integrity of a study and render an otherwise sound
p.000023: study invalid. NERL scientists must be diligent in the implementation of the procedures and processes specified
p.000023: in a well-developed quality assurance project plan (QAPP). A discussion of quality assurance
p.000023: programs and QAPPs is outside of the scope of this document. There are many good references on the topic,
p.000023: including the EPA Web site, www.epa.gov/quality/.
p.000023:
p.000023: 2.2.7 The Study Design Document
p.000023: The study design document should contain sufficient detail to allow independent review and assessment of the scientific
p.000023: soundness of the study and the approaches that will be followed to ensure that the study meets the highest
p.000023: scientific and ethical standards. The research team can meet regularly to specifically evaluate the plan. It
p.000023: should be noted that a study design is not the same as an implementation plan. The latter includes an even
p.000023: greater level of detail describing how the study will be performed and includes protocols and
p.000023: operating procedures. Text Box 2-4 lists a number of elements that may be appropriate to include in a study design.
p.000023:
p.000023: 2.3 Ethical Issues in Ensuring Fair Subject Selection
p.000023: One of the ethical principles of human subjects research is that selection of participants should be fair. In
p.000023: Section 2.2.4, the discussion centers on understanding what population or cohort the participants in a research
p.000023: study represents, and how such a selection may be influenced by the research questions and
p.000023: study objectives. That consideration actually represents the first component of ensuring that subject selection is
p.000023: fair. That is, the scientific goals of the study should be the primary basis for determining what groups or
p.000023: individuals should be recruited and enrolled in a study. Participants should not be recruited either because of
p.000023: privilege or because of vulnerability or their inability to look out for their own interests properly.
p.000023: Similarly, groups or individuals should not be excluded peremptorily without consideration of the risks and
p.000023: benefits to them as individuals. Section 3 of this document discusses protection of
p.000023: vulnerable groups and concludes that NERL researchers should include vulnerable groups in observational
p.000023: human exposure studies only if their participation is critical to the success and applicability of the
p.000023: research. Even then, EPA and NERL researchers will have to meet stringent standards for protecting the rights and
p.000023: safety of the vulnerable participants. “The essence of
p.000023:
p.000023:
p.000023: Text Box 2-4. Elements That May Be Included in a Study Design
p.000023: • Introduction and background, including the purpose and scope of the study
p.000023: • The desired outputs and outcomes of the study, including the objectives and the hypotheses to be tested
p.000023: • A brief description or overview of the study
p.000023: • The technical approach and conceptual model that accounts for
p.000023: – sources of the chemicals being studied;
p.000023: – potential routes and pathways of exposure;
p.000023: – factors that may impact exposure and other relevant stressors;
p.000023: – selection and characteristics of the study participants; eligibility criteria; and recruitment, retention, and
p.000023: payment approaches;
p.000023: – justification for sample size, the methodology for selecting participants, and the sampling methods;
p.000023: – characteristics of the community in which the study will be performed;
p.000023: – environmental conditions, factors, or end points to be measured, including sampling and analysis approaches and
p.000023: methods (with description of expected performance);
p.000023: – survey design and questionnaires and other survey instruments, as applicable (with description of prior use and
p.000023: validation in similar studies);
p.000023: – pilot studies that may be undertaken;
p.000023: – quality assurance project plan and quality control;
p.000023: – timeframe for the study;
p.000023: – exposure scenarios to be considered;
p.000023: – burden of the study on the participants;
p.000023: – resources available; and
p.000023: – feasibility
p.000023: • Discussion of alternative study designs and approaches considered and reasons for rejecting other approaches and
p.000023: selecting the one proposed
p.000023: • An analysis plan that considers
p.000023: – Information and data needs, including data storage, security, access, and release;
p.000023: – nature of the measurement data (e.g., variability, quality assurance);
p.000023: – how the collected data will be used, and how the proposed analyses will address objectives of the study; and
p.000023: – hypotheses to be tested and statistical power and sample size required to test the hypotheses
p.000023: • Resources required or available
p.000023: • Project organization and management, including team members and roles and responsibilities
p.000023: • Schedule
p.000023:
p.000023: fairness in human subjects research is that scientific goals, considered in dynamic interaction with
p.000023: the potential for and distribution of risks and benefits, should guide the selection of subjects.”
p.000023: (Emmanuel et al, 2000). On the other hand, as discussed in Section 3, many study problems specifically
p.000023: address exposures of vulnerable groups to chemicals and other stressors. Researchers should not avoid
p.000023: research studies that will,
p.000023:
p.000023:
p.000024: 24
p.000024:
p.000024: of necessity, include vulnerable groups to address the study hypotheses or objectives simply to avoid the more
p.000024: stringent requirements for working with these groups.
p.000024:
p.000024: 2.4 Ensuring a Favorable Risk-Benefit Ratio
p.000024: 2.4.1 Designing in Benefits for the Participants
p.000024: Study designs vary depending on the objectives of the study, existing knowledge on the research question, and
p.000024: the hazard being studied (NRC & IOM, 2005). Recent ethical discussions about study designs in human subjects
p.000024: research (cf., Recommendation 7.1, p. 143, NRC & IOM [2005] and Emanuel et al. [2000]) support the development
p.000024: of innovative study designs to maximize the benefit9 to the study participants, as well as to
p.000024: the community and the greater society beyond. Observational human exposure studies generally collect data that
p.000024: contribute to generalizable knowledge that will benefit the community and society as a whole, but they often do not
p.000024: provide obvious direct benefit to study participants. Therefore, it is important to include elements
p.000024: in the study design that can offer benefits to the participants wherever possible. This is not always
p.000024: straightforward, but one way that participants, as well as communities, can benefit from these studies is
p.000024: by incorporating strong educational components into the conduct of the research. For example, brochures, videos,
p.000024: and other materials that educate study participants on safety around the home or on how to reduce their
p.000024: exposure to chemicals can be distributed during the study. EPA’s program offices, including the Office of
p.000024: Children’s Health Protection, the Office of Pollution Prevention and Toxics, the Office of Pesticide Programs,
p.000024: the Office of Drinking Water, and others have Web sites with substantial amounts of informational
p.000024: and educational materials available that could be distributed to study participants. Other organizations, such as
p.000024: the American Lung Association, the American Cancer Society, the American Academy of Pediatrics (AAP),
p.000024: and various environmental groups, have materials of which study participants may not be aware that could be used
p.000024: as educational materials when relevant.
p.000024: In addition, approaches that provide direct benefits to study participants will need to be tailored to
p.000024: the particular study population and community. Feedback from potential participants in focus groups and
p.000024: input from community representatives may be useful in identifying these approaches.
p.000024:
p.000024:
p.000024:
p.000024: 9 Payment to participants is never considered a benefit of a study.
p.000024: 2.4.2 Assessing Benefits and Risks of Study Participation
p.000024: For all research involving human participants, the Common Rule requires researchers to ensure that
p.000024: potential risks “are reasonable in relation to the anticipated benefits,” and that risks are
p.000024: minimized (40 CFR 26.111). It is most useful if the assessment of benefits and risks is begun early in
p.000024: the scoping and planning phase of a study.
p.000024: Unlike some biomedical research that involves the study of interventions or procedures that hold out the
p.000024: prospect of direct diagnostic, therapeutic, or preventative benefit for the study participants, observational
p.000024: human exposure studies often do not have a similar prospect of direct benefit to the participant. Therefore, the
p.000024: risk- benefit balance is based on the balance between the risks to the participants and the expected benefits to
p.000024: society (generalizable knowledge). The risks to participants must be reasonable [40 CFR 26.111(a)(2)] in
p.000024: relation to the importance of the knowledge gained. This assessment of the risk-benefit balance,
p.000024: therefore, needs to be performed in the initial planning of the study to be included in the justification for the
p.000024: study (Section 2.2).
p.000024: If there is no prospect of direct participant benefit, and the study participants are children, moreover, EPA
p.000024: is permitted to conduct or support only those observational human exposure studies that meet both the regulatory
p.000024: definition of “observational” and the regulatory definition of “minimal risk.” The latter is defined in
p.000024: the Common Rule at 40 CFR 26.102(i) and reiterated in Subpart D of the EPA Rule at 40 CFR 26.402(g):
p.000024: “Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not
p.000024: greater in and of themselves than those ordinarily encountered in daily life or during the
p.000024: performance of routine physical or psychological examinations or tests.” In applying this definition, EPA
p.000024: adheres to the consensus standard that the reference population for this definition is normal children living
p.000024: in safe, healthy environments. In its discussion of the perception of risks and benefits, the NRC & IOM (2005) report
p.000024: on housing health hazards in children notes that the children participating in these studies may be at
p.000024: risk for physical harms or adverse health outcomes because they live in housing (or otherwise occupy
p.000024: environments) with health hazards. However, such risks are not introduced by the research but, rather, would be present
p.000024: whether or not the children were involved in a research study. As a consequence, the study still
p.000024: would meet the regulatory criteria for minimal risk as long as the research itself introduced no risks over
p.000024: and above those minimal risks
p.000024:
p.000024:
p.000025: 25
p.000025:
p.000025: experienced by normal children living in safe healthy environments.
p.000025: However, the existence of greater than minimal background risks that are not introduced by the research,
p.000025: nonetheless, raises additional ethical considerations. The joint NRC & IOM Committee on Research on Housing- Related
p.000025: Health Hazards Involving Children discussed the ethical arguments that arise when scientists conduct research that
p.000025: observes children in poor-quality housing. They point out that a researcher’s first duty of beneficence
p.000025: under the Common Rule requires that the risks of the research actions be proportionate to
p.000025: [“reasonable in relation to”; 40 CFR 26.111(a)(2)] the benefits of the research, and that the risks be
p.000025: minimized. They acknowledge, however, that some have argued that the “best interests of the child” also obligates
p.000025: researchers to “rescue” children from harm and to provide better living conditions. They conclude that,
p.000025: properly applied, the ethical principle of beneficence does indeed direct researchers who observe serious harms
p.000025: to child subjects to take steps to try to prevent the harms. However, they also argue that the researcher’s duty does
p.000025: not extend to “personally and directly prevent harm by removing the child from the harmful environment” (p.
p.000025: 60, NRC & IOM, 2005). They conclude instead that “it is unrealistic and unfair to hold individual research
p.000025: investigators responsible for ameliorating the social circumstances that they study” and that “a nuanced
p.000025: balancing of the benefits and risks of research” is an ethically sound approach that is firmly established in
p.000025: Federal regulations (p. 60, NRC & IOM, 2005). Balancing the ethical obligation to mitigate risks or
p.000025: harms observed during research with the reasonable limits on an investigator’s moral responsibility for
p.000025: the social circumstances surrounding the research will be the subject of later sections of this
p.000025: document, particularly Section 4.3.1.
p.000025: Assessing the risks and benefits of the research study can be very difficult for the researchers, especially
p.000025: because the researchers and the community or participants may perceive the risks and benefits
p.000025: quite differently. (See the discussion in NRC & IOM [2005], for example.) To understand the
p.000025: community’s perspective better, the researcher may find it helpful to discuss the assessment of risks
p.000025: and benefits with members of the research team, community representatives, and relevant
p.000025: stakeholders. The research team should consider the use of a community advisory board (CAB) to provide
p.000025: input to the assessment of the risks and benefits of the study. The group could include individuals who are
p.000025: representative of the population to be studied, community representatives, exposure
p.000025: scientists, and bioethicists. The group should include experts familiar with the human subjects
p.000025: research regulations, preferably including someone who has served on IRBs. Obtaining input from the group can
p.000025: be accomplished by submitting the study concept and general study design to the group for
p.000025: review and feedback, even before a full study design has been developed. (See the discussions of CABs
p.000025: in Sections 5 and 6.) Ultimately, it will be the review by the members of the IRB that will determine whether
p.000025: the balance is appropriate and justifiable.
p.000025:
p.000025: 2.5 Independent Scientific and Ethical Review
p.000025: Because issues of science and ethics are intrinsically bound together in human subjects research (Emanuel et al.,
p.000025: 2000; CIOMS, 2002), it is important that scientific and ethical reviews be considered together,
p.000025: not separately. Scientific reviews are performed to ensure the scientific soundness of the study, whereas
p.000025: ethical reviews are performed to ensure proper action and the protection of the human subjects in a research
p.000025: study. A study that is not scientifically sound could expose study participants to unnecessary risk or
p.000025: inconvenience and burden, with no additional societal benefits (i.e., no increase in generalizable
p.000025: knowledge). EPA’s Science Advisory Board has stated that “bad science is always unethical” (U.S. EPA, 2000),
p.000025: and CIOMS declares that “scientifically invalid research is unethical” (CIOMS, 2002).10 It is clear, therefore,
p.000025: that the ethical review has to consider the scientific aspects of the study also.
p.000025: There may be multiple levels of review during development of the study design and human subjects
p.000025: research protocol for an observational human exposure study. The research team is responsible for the design of
p.000025: the study and for ensuring that adequate peer review is
p.000025:
p.000025:
p.000025: 10 CIOMS (2002) Guideline 2 asserts “Ethical review committees—All proposals to conduct research involving human
p.000025: subjects must be submitted for review of their scientific merit and ethical acceptability to one or more scientific
p.000025: review and ethical review committees. The review committees must be independent of the research team, and any direct
p.000025: financial or other material benefit they may derive from the research should not be contingent on the outcome of their
p.000025: review. The investigator must obtain their approval or clearance before undertaking the research. The ethical review
p.000025: committee should conduct further reviews as necessary in the course of the research, including monitoring of the
p.000025: progress of the study.” The CIOMS document continues, “According to the Declaration of Helsinki (Paragraph 11), medical
p.000025: research involving humans must conform to generally accepted scientific principles, and be based on a thorough
p.000025: knowledge of the scientific literature, other relevant sources of information, and adequate laboratory and, where
p.000025: indicated, animal experimentation. Scientific review must consider, inter alia, the study design, including the
p.000025: provisions for avoiding or minimizing risk and for monitoring safety. Committees competent to review and approve
p.000025: scientific aspects of research proposals must be multidisciplinary.”
p.000025:
p.000025:
p.000026: 26
p.000026:
p.000026: performed to evaluate both the scientific and ethical approaches for the study. Following completion of a
...
p.000026: affected parties, participation in affected advocacy groups, collaborations or relationships with
p.000026: experts on the IRB or other independent review committees, institutional conflicts for any contractors
p.000026: who may be involved, or a wide range of other situations.
p.000026: Any situations that constitute actual conflicts of interest and all potential or apparent conflicts of interest
p.000026: must be reported to the IRB for their review and resolution. The CIOMS (2002) guidelines for
p.000026: research protocols involving human subjects specify that all sponsors of the research be identified,
p.000026: and that the protocol include actions to disclose and address potential conflicts of interest. Concerns about
p.000026: conflicts of interest also need to be identified and discussed with the researchers, community, and
p.000026: other stakeholders to make a determination of the existence of conflicts, and how they should be avoided or
p.000026: handled.
p.000026: Even if actual conflicts of interest do not exist, researchers should recognize that there can be perceived
p.000026: conflicts of interest that can be just as damaging as real conflicts of interest. Perceptions by
p.000026: participants, community members and representatives, stakeholder groups, and the public may be substantially
p.000026: different from the reality of the situation. This is especially likely to occur when external sources, such as
p.000026: industry, are
p.000026:
p.000026:
p.000027: 27
p.000027:
p.000027: involved in funding research. Even though researchers may develop agreements with funding organizations that
p.000027: ensure researcher autonomy, a perception may exist that the funding organization will bias the study (Resnik and Wing,
p.000027: 2007). Concerns about perceived conflicts of interest should be discussed with the IRB and other relevant
p.000027: review committees, in addition to the researchers, the community, and other stakeholders. The IRB must
p.000027: be made aware of any circumstances that may give rise to actual conflicts of interest or to the
p.000027: appearance or perception of a conflict of interest. The IRB’s recommendations about how to resolve any such
p.000027: conflicts must be strictly adhered to by NERL researchers.
p.000027:
p.000027: 2.5.3 Develop the Human Subjects Protocol for IRB Review
p.000027: IRBs may have specific format requirements for their human subject research protocols. Traditionally, the human
p.000027: subjects research protocols for research conducted or funded by NERL have included
p.000027: descriptions of the project, including title and description of the research; the duration of the project; the
p.000027: type of data to be collected; the objectives of the study; the number of samples; a description of the
p.000027: participants and participant recruitment procedures; the informed consent procedures and forms; estimates of
p.000027: participant risk and burden, an assessment of benefits and the risk-benefit ratio; and actions to protect the
p.000027: participants. CIOMS has developed a comprehensive list of items that they recommend for inclusion in
p.000027: a human subjects research protocol (Appendix 1, CIOMS, 2002). Many of the items that they identify are also
p.000027: useful for observational human exposure studies. (The CIOMS items can be found in Appendix C of this
p.000027: document.) The authors recommend that anyone developing a human subjects protocol for observational human
p.000027: exposure studies review and utilize the CIOMS list of topics, as appropriate. Text Box 2-5
p.000027: identifies a number of topics that should be considered in development of the human subjects research protocol.
p.000027: In addition, the authors’ experience leads them to suggest that three additional topics beyond those from
p.000027: the CIOMS (2002) document also may need to be considered in a human subjects protocol: (1) approaches to
p.000027: minimize changes in participant behavior because of participation in the study (see Section 2.3.4);
p.000027: (2) approaches to minimize therapeutic misconception (see Section 5.4.1); and (3) actions to involve
p.000027: the community in a community-based participatory research
p.000027:
p.000027: Text Box 2-5. Potential Topics in a Human Subjects Research Protocol
p.000027: 1. Title
p.000027: 2. Summary in lay language
p.000027: 3. Justification for the study
p.000027: 4. Ethical issues and proposed resolution
p.000027: 5. Summary of previous research
p.000027: 6. Affirmation of Belmont Principles and 40 CFR 26 compliance
p.000027: 7. Previous history or use of the protocol
p.000027: 8. Information on the location and demographics of research
p.000027: 9. Information on funding organization, researcher partners, and collaborators
p.000027: 10. Names, qualifications, and experience of investigators
p.000027: 11. Objectives, hypotheses, assumptions, and variables
p.000027: 12. Study design
p.000027: 13. Sample size and power and statistical analysis plan
p.000027: 14. Criteria and justification for subject selection
p.000027: 15. Justification for use of vulnerable groups, if any
p.000027: 16. Process of recruitment
p.000027: 17. Actions to involve the community in a community-based participatory research program
p.000027: 18. Description and explanation of any and all interventions
p.000027: 19. Measurements or data to be collected
p.000027: 20. Any clinical or other tests
p.000027: 21. Rules or criteria for removing subjects or terminating the study
p.000027: 22. Adverse events and unanticipated problems⎯reporting and responses
p.000027: 23. Potential benefits to subjects or others
p.000027: 24. Expected benefits of the research to the population
p.000027: 25. Informed consent process and responsibilities
p.000027: 26. Protections for the consent/assent of vulnerable participants
p.000027: 27. Efforts to minimize “therapeutic misconception”
p.000027: 28. Approaches to minimize changes in participant behavior
p.000027: 29. Payments
p.000027: 30. Plans for informing subjects about items that could affect subjects’ willingness to continue in the study
p.000027: 31. Plans to inform subjects about the results of the study
p.000027: 32. Privacy and confidentiality
p.000027: 33. Security of personal information and when, how, and by whom private information can be revealed
p.000027: 34. All foreseen uses of personal data or biological materials
p.000027: 35. Procedures for data and safety monitoring and oversight of the study and the criteria for identifying, reporting,
p.000027: and responding to adverse events, including ethical breaches, environmental measures in excess of reporting standards,
p.000027: and collateral observations, and criteria for prematurely terminating the study if necessary
p.000027: 36. A list of the references cited in the protocol
p.000027: 37. The source and amount of funding
p.000027: 38. Protocols for dealing with financial or other conflicts of interest
p.000027: 39. Schedule
p.000027: 40. Arrangements with sponsors regarding publication rights and procedures
p.000027: 41. Reasons for not publishing the study findings
p.000027: 42. Procedures for preventing falsification of data
p.000027:
p.000027:
p.000027:
p.000027:
p.000028: 28
p.000028:
p.000028: (CBPR) effort, as appropriate (see Section 6, especially Section 6.10).
p.000028:
p.000028: 2.5.4 Ethical Review
p.000028: In the United States, ethical reviews of studies involving human subjects are performed by IRBs.
p.000028: The CommonXRule specifies requirements (40 CFR 26.107 –
p.000028: 115) for IRB membership, IRB functions and operations, IRB review of research, and other details related to IRB review
p.000028: and approval of research. Emanuel states that “the independent ethical review of [human subjects
p.000028: research] should involve individuals with training in science, statistics, ethics, and law, as well as
p.000028: reflective citizens who understand social values, priorities, and the vulnerability and concerns of
p.000028: potential subjects” (Emanuel et al., 2000). It is beyond the scope of this document to include
p.000028: detailed discussions on IRB membership, operations, processes, etc. The reader is referred to the Common
p.000028: Rule, as well as a number of other available references (e.g., OHRP, 2007; CFR, 2006; U.S. HHS,
p.000028: 1993; NRC, 2003).
p.000028: It is essential that research with human subjects be carried out or strictly supervised by suitably
p.000028: trained, qualified, and experienced investigators. For all research subject to the CommonXRule, these qualified
p.000028: researchers are expected to prepare a human subjects research protocol (as in Section 2.5) and to submit
p.000028: the protocol to be ethically and scientifically appraised by one or more suitably constituted IRBs,
p.000028: independent of the investigators.
p.000028: There are a number of other issues associated with IRBs that may impact researchers
p.000028: conducting observational human exposure studies. As an example, there has been concern about the transparency of
p.000028: IRBs. Questions have been raised about what information the IRB should make available to the public
p.000028: regarding membership on the IRB for review of individual projects, the discussions held with the
p.000028: researchers, the IRB’s concerns about the research protocol, the researchers’ response, etc.
p.000028: Should this information be documented in files that the researchers can make available to the
p.000028: participants, community, stakeholders, and the public? At the present time, there is no clear approach as
p.000028: to how to address these issues. Because these issues are associated with the IRB, not the
p.000028: researcher, it is outside the scope of this document to recommend approaches for IRBs to address
p.000028: these concerns. IRB processes and procedures will continue to evolve as recommended by various committees and
p.000028: workgroups (e.g., as reported in NRC & IOM, 2005; NRC, 2003; U.S. HHS, 1993).
p.000028: All human subjects research conducted or sponsored by NERL is subject to both the 40 CFR 26 requirements and procedures
p.000028: set forth in EPA Order 1000.17 Change A1 (www.epa.gov/oamrtpnc/forms/1000_17a.pdf). The EPA order establishes as
p.000028: policy that all research will comply with the CommonXRule and with the order. All human research studies must be
p.000028: reviewed and approved by the EPA HSRRO before the work can begin.
p.000028: In NERL, the director of the division conducting or funding the research is the manager with the primary
p.000028: responsibility for developing the human subjects research protocol and for having that protocol reviewed
p.000028: by an independent IRB acceptable to the EPA HSRRO. The protocol also will be reviewed by the NERL HSRRO
p.000028: and by the appropriate NERL associate director before it is submitted to the IRB. Under 40 CFR 26.109, the IRB can
p.000028: demand changes to the research protocol and is the final authority for approving or disapproving the research
p.000028: activity.
p.000028:
p.000028: 2.5.5 Internal EPA Review of Scientific and Ethical Issues
p.000028: After IRB approval is obtained, the division director will be the primary manager responsible for preparing a request
p.000028: for review and approval or exemption of the human subjects research by the EPA HSRRO. The division
p.000028: director will ensure that the request is consistent with EPA Order 1000.17 A1 and all other policies or
p.000028: procedures that the EPA HSRRO may have established. The EPA HSRRO shall be the final authority for
p.000028: approving or disapproving the research effort. The EPA HSRRO may request additional reviews or establish
p.000028: additional policies and procedures for seeking review and approval. No human subjects research
p.000028: will begin⎯not even recruiting of potential participants⎯until the EPA HSRRO has
p.000028: approved or exempted the research.
p.000028:
p.000028: 2.6 Informed Consent
p.000028: Informed consent is discussed extensively in Section 5 of this document. The major focus is that
p.000028: informed consent is a process, not a form, that “should be an on-going, interactive dialogue between research
p.000028: staff and research participants involving the disclosure and exchange of relevant information, discussion of that
p.000028: information, and assessment of the individual’s understanding of the discussion” (Recommendation 4.1,
p.000028: IOM, 2002). These comments emphasize how important true two-way communication is to comprehension, the second
p.000028: pillar in the informed consent process. Informed consent is built on three “pillars:” (1) information; (2)
p.000028:
p.000028:
p.000029: 29
p.000029:
p.000029: comprehension; and (3) voluntary participation, or “voluntariness” (U.S. DHEW, 1979). Informed consent
p.000029: requires “provision of information to subjects about the purpose of the research, its procedures, potential
p.000029: risks, benefits, and alternatives, so that the individual understands this information and can
p.000029: make a voluntary decision whether to enroll and continue to participate” (Emanuel et al., 2000).
p.000029:
p.000029: 2.7 Ensuring That Participant Behaviors Are Not Changed Adversely Because of Being in the Study
p.000029: The goal of observational human exposure studies is to collect information on people’s exposures to
p.000029: chemicals in their real-world environment as they carry on their normal daily activities. Researchers who
p.000029: conduct these studies, however, recognize that participation in a study may affect behavior. This cannot
p.000029: always be avoided, as simply agreeing to participate in a study may impact the participant’s activities and
p.000029: schedules. For example, this occurs when technicians visit homes to collect samples or when participants
p.000029: are asked to collect samples (e.g., food, urine), or to complete surveys, activity logs, or
p.000029: questionnaires. These types of changes in behavior may or may not affect the outcome of the study.
p.000029: Some changes in behavior can affect the study outcome. The Hawthorne Effect is a well-recognized
p.000029: phenomenon. It is an effect on an outcome variable caused by the fact that the participants of the study know
p.000029: they are participating in the study. The Hawthorne Effect originally referred to the increase in worker productivity
p.000029: observed when a worker is singled out and made to feel important; the increased productivity was not related to the
p.000029: environmental factors that were being studied. The effect was described based on a series of industrial
p.000029: productivity studies from 1927 to 1932. Similarly, some changes in participant behaviors may change the
p.000029: observations, measurements, and conclusions from observational human exposure studies. For
p.000029: example, participants may do more cleaning in their home because they do not want the researchers to think they are
p.000029: poor housekeepers; this could affect the measurement of environmental concentrations in the home. In a
p.000029: study of chemicals from consumer products, participants may think that because the researchers are
p.000029: studying the products, the products must be harmful. Therefore, study participants may elect not to use the products
p.000029: during the study in the same manner as they would normally. Alternatively, prospective participants may
p.000029: choose to use more of the household product to qualify for the
p.000029: study. As a result, the participant’s exposure to the chemicals could be either more or less than “normal.”
p.000029: Any change in a participant’s behavior that is related to the research question being addressed in the study
p.000029: may impact the study results. Researchers should try to anticipate how a study may impact participant behaviors and
p.000029: ensure that the study design and implementation protocols do not cause changes in behavior that may cause
p.000029: harm to a participant during a study. A number of study elements with the potential to influence
...
p.000030: and safety monitoring and oversight have to establish and implement mechanisms to get feedback on a continuing
p.000030: basis from the participants, in addition to monitoring and reviewing the scientific data.
p.000030: CIOMS recommends that all human subjects research protocols contain “A description of the plans
p.000030: for statistical analysis of the study, including plans for interim analyses, if any, and criteria for
p.000030: prematurely terminating the study as a whole if necessary” (Appendix A, CIOMS, 2002). To be
p.000030: consistent with this recommendation, the research team will need to develop and implement an approach for monitoring
p.000030: the scientific and ethical issues during the study, so that changes can be made to the study, or the study can
p.000030: be stopped if necessary. Criteria and standards need to be established against which study activities and
p.000030: results can be evaluated, and these criteria and standards need to be incorporated into the study
p.000030: design, the human subjects research protocol, and the QAPP.
p.000030: In developing an approach to monitor scientific and ethical issues during the study, the research team may
p.000030: choose to
p.000030: • identify the individual, team, advisory committee, or
p.000030: data safety monitoring board (DSMB) responsible for monitoring the progress and results of the study;
p.000030: • develop roles and responsibilities;
p.000030: • develop a schedule and timeline for the activities to be conducted;
p.000030: • develop goals for interim data analysis and prepare an analysis plan;
p.000030: • identify what data will be analyzed, how it will be processed and validated, and who will perform
p.000030: the analyses;
p.000030: • develop a plan for reporting interim results to the research team;
p.000030: • develop standards for reporting scientific and ethical issues to the research team; or
p.000030: • develop criteria for evaluating scientific and ethical issues that arise during the study.
p.000030: In a well-designed observational study for which the research team has adequately prepared, it is unlikely that there
p.000030: will be scientific issues requiring that the study be stopped. Nonetheless, it is important for criteria to be
p.000030: established for when the study needs to be changed or terminated. An example might be the
p.000030: participant retention rate. In a study with repeated measurements, a certain sample size is required to obtain
p.000030: statistically significant results. If the retention rate is poor, and too many participants drop out of
p.000030: the study, it may not be possible to meet the study objectives, and early termination of the
p.000030: study may be warranted (see Text Box 2-7 for issues that warrant early termination). However, it is
p.000030: anticipated that the study design would include contingency planning (for example, related to replacement).
p.000030: Developing criteria for study elements that may have associated ethical concerns as a study progresses will no doubt be
p.000030: more difficult than reviewing the measurement data. Nonetheless, assuring the ethical safety of the participants
p.000030: is critically important. There are no standard formulas for dealing with ethical concerns. For example, if the
p.000030: privacy of a number of study participants is compromised by a technician conducting the
p.000030: measurements in their homes, what criteria should be used to evaluate the severity of the issues? How
p.000030: many landlord-participant problems are too many before the study needs to be changed to exclude
p.000030: participants who rent their dwellings? Despite the challenges, the team of people involved in the data and
p.000030: safety monitoring and oversight effort should work diligently, with input from the community, to establish
p.000030: open and continuing channels of communication with participants, the community, and stakeholders –
p.000030: with the goal of ensuring that their involvement in the research effort is, and
p.000030:
p.000030:
p.000031: 31
p.000031:
p.000031: remains to be, based on the three pillars of informed consent: (1) that the parties are fully informed of all
p.000031: of the relevant and useful information, (2) that the information is understood by the parties, and (3)
p.000031: that all parties continue to participate voluntarily. With diligent effort to continue an open dialogue with the
p.000031: involved parties – combined with thoughtful review and oversight of the technical study results and procedures
p.000031: – the monitoring and oversight team can ensure that participants are free to withdraw from the
p.000031: research at any time; are fully informed about the technical study results; understand any new
p.000031: information about relevant risks and benefits; and that the privacy and confidentiality of
p.000031: the subjects is properly protected. Through these efforts, the monitoring and oversight team will ensure that
p.000031: the welfare of the research subjects remains a focus of the study effort.
p.000031:
p.000031: Text Box 2-7. Examples of Issues That May Cause a Study To Be Stopped Early
p.000031: • Participant recruiting and enrollment⎯low response rates, disproportionate enrollment of select groups, problems
p.000031: associated with advertising, inadequate selection criteria
p.000031: • Informed consent⎯difficulties with the process and materials, poor comprehension
p.000031: • Participation⎯poor response to questionnaires, poor compliance with researcher requests in data collection
p.000031: activities
p.000031: • Burden⎯higher than predicted
p.000031: • Changes in participant behaviors⎯potential changes because of participation in the study
p.000031: • Grievances⎯participant issues
p.000031: • Retention⎯high dropout rates
p.000031: • Community issues⎯poor interactions, lack of support
p.000031: • Third-party issues⎯problems with landlords, spouses, or others
p.000031: • Collateral observations⎯identification of nonstudy hazards, difficulty reporting
p.000031: • Unanticipated results⎯high contaminant concentrations measured, unexpected results
p.000031: • New data indicating that participation in the study (or observations measured in the study) represent a risk to
p.000031: participants or others
p.000031:
p.000031:
p.000031:
p.000031: References
p.000031: Castelloe, JM (2000). Sample size computations and power analysis with the SAS system. Paper 265-25 in Proceedings of
p.000031: the 25th Annual SAS Users Group International Conference. Cary, NC: SAS Institute, Inc. Available:
p.000031: http://support.sas.com/rnd/app/papers/powersamplesize.pdf [accessed 16 April 2008].
p.000031:
p.000031: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of
p.000031: Human Subjects. U.S. Code of Federal Regulations. Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/
p.000031: 40cfr26_06.html [accessed 12 June 2007].
p.000031:
p.000031: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000031: Biomedical Research Involving Human Subjects.
p.000031: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000031:
p.000031: Coggon D, Rose G, Barker DJP (1997). Epidemiology for the Uninitiated, Fourth Edition. London: BMJ Publishing Group
p.000031: Ltd. Available at http://www.bmj.com/epidem/epid.html [accessed 29
p.000031: January 2008].
p.000031:
p.000031: Cohen Hubal EA, Sheldon LS, Zufall, MJ, Burke JM, Thomas KW (2000). The challenge of assessing children’s residential
p.000031: exposure to pesticides. Journal of Exposure Analysis and Environmental Epidemiology 10(6 part 2): 638-649.
p.000031:
p.000031: Dallal, GE (2001). Some aspects of study design. In The Little Handbook of Statistical Practice at
p.000031: www.StatisticalPractice.com, and at http://www.tufts.edu/~gdallal/STUDY.HTM [accessed 29
p.000031: January 2008]
p.000031: Emanuel EJ, Wendler D, Grady C (2000). What Makes Clinical Research Ethical? JAMA 283(20): 2701-2711.
p.000031:
p.000031: Gilbert, SG (2006). Supplementing the traditional institutional review board with an environmental health and community
p.000031: review board. Environmental Health Perspectives 114(10): 1626-1629.
p.000031:
p.000031: Kraemer HC, Thiemann S (1987). How Many Subjects? Statistical Power Analysis in Research. Newbury Park, CA: Sage
p.000031: Publications.
p.000031:
p.000031: Lenth RV (2001). Some practical guidelines for effective sample size determination. American Statistician 55(3):
p.000031: 187-193. Available:
p.000031: http://www.stat.uiowa.edu/techrep/tr303.pdf [accessed 13
p.000031: June 2007].
p.000031:
p.000031: NRC (National Research Council) (2003). Protecting Participants and Facilitating Social and Behavioral Sciences
p.000031: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000031: [accessed 12 June 2007].
p.000031:
p.000031: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000031: Housing-Related Health Hazards Involving Children.
p.000031: Washington, DC: The National Academies Press. Available:
p.000031:
p.000031:
p.000032: 32
p.000032:
p.000032: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12 June 2007].
p.000032:
p.000032: OHRP (Office for Human Research Protections) (2007). U.S. Department of Health and Human Services [Online].
p.000032: Available: http://www.hhs.gov/ohrp/ [accessed 13 June 2007].
p.000032:
p.000032: Resnik DB, Wing S (2007). Lessons learned from the Children's Environmental Exposure Research Study. Am J Public Health
p.000032: 97(3): 414-8.
p.000032:
p.000032: U.S. DHEW (U.S. Department of Health, Education, and Welfare) (1979). The Belmont Report: Ethical Principles and
p.000032: Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: National Commission for the Protection
p.000032: of Human Subjects of Biomedical and Behavioral Research. Available: http://ohsr.od.nih.gov/guidelines/belmont.html
p.000032: [accessed June 2007].
p.000032: U.S. EPA (U.S. Environmental Protection Agency) (2000). Comments on the use of data from the testing of human subjects:
p.000032: A report by the Science Advisory Board and the FIFRA Scientific Advisory Panel. Environmental Protection Agency,
p.000032: Science Advisory Board. EPA-SAB-EC-00-017. Available: http://www.epa.gov/scipoly/sap/meetings/1999/november/e c0017.pdf
p.000032: [accessed 16 April 2008].
p.000032:
p.000032: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000032: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000032: [accessed 12 June 2007].
p.000032:
p.000032: Van Belle G, Fisher L (2004). Biostatistics: A Methodology for the Health Sciences (2nd Edition) Hoboken, NJ: John
p.000032: Wiley & Sons.
p.000032:
p.000032: Wackerly DD, Mendenhall W, Scheaffer RL (2001). Mathematical Statistics with Applications (6th Edition). Pacific Grove,
p.000032: CA: Duxbury Press.
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000032:
p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: SECTION 3
p.000033: Ensuring Protection of Vulnerable Groups
p.000033:
p.000033:
p.000033:
p.000033: Concern for the protection of vulnerable groups is fundamental to modern ethical thought and guidelines.
p.000033: The Belmont Report was “meant to provide broad principles that could be used to generate specific
p.000033: rules and regulations in response to [U.S.] research scandals such as Tuskegee and Willowbrook.11 It
p.000033: focuses on informed consent, favorable risk-benefit ratio, and the need to ensure that vulnerable
p.000033: populations are not targeted for risky research” [emphasis added] (Emanuel et al., 2000).
p.000033: The Common Rule requires IRBs to assure that “additional safeguards have been included in the study to protect
p.000033: the rights and welfare of these [vulnerable] subjects” [at 40 CFR 26.111(b) in CFR, 2006a]. If an
p.000033: observational human exposure study includes vulnerable research participants, it is essential that the investigators be
p.000033: cognizant of the special issues and requirements of research involving vulnerable populations. Researchers
p.000033: have to justify the involvement of vulnerable populations in the research study and
p.000033: include the appropriate safeguards for protection of their safety and welfare. The Common Rule protections are
p.000033: discussed further in the IRB guidebook (U.S. HHS, 1993). EPA regulations include not only the general
p.000033: protections for vulnerable populations found in the Common Rule (Subpart A) but also define
p.000033: additional protections for children and for pregnant or nursing women (and their fetus or nursing child)
p.000033: in Subparts B, C, and D (CFR, 2006a).
p.000033: The section begins by identifying or defining vulnerable groups and then discusses ethical issues that
p.000033:
p.000033:
p.000033: 11 For more information about these and other research scandals, see Ethical and Policy Issues in Research Involving
p.000033: Human Participants, Vol. I, Report and Recommendations of the National Bioethics Advisory Commission, Bethesda, MD,
p.000033: August, 2001. See p. 153 for information about the Willowbrook State School experiments. The report is available at
p.000033: www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf (Accessed September 3, 2007).
p.000033: may be important in conducting observational human exposure studies involving those groups, especially
p.000033: children and pregnant women. The discussions about the ethical issues are based largely on EPA’s human subjects
p.000033: regulations and on the recommendations from the Council for International Organizations of
p.000033: Medical Sciences document, International Ethical Guidelines for Biomedical Research Involving Human
p.000033: Subjects (CIOMS, 2002).
p.000033:
p.000033: 3.1 Identification of Vulnerable Groups
p.000033: In the United States, human subjects regulations (45XCFRX46 and 40 CFR 26) do not formally define
p.000033: vulnerable populations. Instead, the CommonXRule gives examples of potentially vulnerable groups (see Text Box 3-1).
p.000033: In addition, HHS extends added human subjects protections to pregnant women, human fetuses,
p.000033: neonates, prisoners, and children as vulnerable groups (45 CFR 46, Subparts B, C, and D, see CFR,
p.000033: 2006b). Analogous but somewhat more stringent protections for children, pregnant or nursing women, and fetuses
p.000033: are specified in Subparts B, C, and D of the EPA Rule (40 CFR 26). The regulations do not preclude other groups from
p.000033: being considered vulnerable, however, and the National Institutes of Health (NIH), in its Human
p.000033: Participant Protections Education for Research Teams online tutorial (NIH, 2002), lists students or employees and
p.000033: terminally ill or comatose patients as potentially vulnerable groups.
p.000033: CIOMS defines vulnerable persons as those who are relatively (or absolutely) incapable of protecting their own
p.000033: interests. Vulnerability here refers to a substantial incapacity to protect one’s own interests owing to such
p.000033: impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care
p.000033: or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Vulnerable persons
p.000033: may have insufficient power, intelligence, resources, strength, or needed attributes to protect their
p.000033:
p.000033:
p.000035: 35
p.000035:
p.000035: own interests (CIOMS, 2002) (see Text Box 3-2). Because of their incapacity to protect their own
p.000035: interests, ethically perceptive researchers will plan and implement special provisions for the protection of the
p.000035: rights and welfare of the vulnerable persons.
p.000035:
p.000035: Text Box 3-1. Potentially Vulnerable Groups Identified in U.S. Regulations
p.000035:
p.000035: Text Box 3-2. Potentially Vulnerable Groups Identified in International Guidance
p.000035: (Council for International Organizations of Medical Sciences, 2002)
p.000035:
p.000035: • Junior or subordinate members of a hierarchical group; examples include employees, students, members of the armed
p.000035: forces, police, and others who work for, or closely with re- searchers; they may have expectations of preferential
p.000035: treatment if they agree to participate or fear of disapproval or retaliation if they refuse to participate in a study.
p.000035:
p.000035: CommonXRule: Examples of vulnerable groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: EPA extends stringent protections to these groups
p.000035: (40 CFR 26)
p.000035:
p.000035:
p.000035: HHS extends additional protections to these groups
p.000035: (45XCFRX46)
p.000035:
p.000035: Additional vulnerable groups in NIH training materials
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates)
p.000035: • Prisoners
p.000035: • Handicapped persons
p.000035: • Mentally disabled persons
p.000035: • Economically disadvantaged persons
p.000035: • Educationally disadvantaged persons
p.000035:
p.000035: • Children
p.000035: • Pregnant women (and their fetuses)
p.000035: • Nursing women (and their neonates
p.000035:
p.000035: • Children
p.000035: • Pregnant women and fetuses
p.000035: • Nursing women and neonates
p.000035: • Prisoners
p.000035: • The terminally ill
p.000035: • Students and employees
p.000035: • Comatose patients
p.000035: • Elderly persons, who may acquire attributes that define them as vulnerable with advancing age.
p.000035: • Residents of nursing homes.
p.000035: • People receiving welfare benefits or social assistance.
p.000035: • People with low or no incomes (poor and unemployed).
p.000035: • Homeless persons.
p.000035: • Nomads.
p.000035: • Refugees or displaced persons.
p.000035: • Some ethnic and racial minority groups.
p.000035: • People with incurable diseases (in clinical studies).
p.000035: • The politically powerless.
p.000035: • Members of communities unfamiliar with modern medical concepts (applies to clinical studies)
p.000035:
p.000035:
p.000035: 3.2 Justification for Involving Vulnerable Persons in Observational Research
p.000035: The CommonXRule requires IRBs to ensure that the selection of subjects is equitable [40 CFR 26.111(a)(3)] and
p.000035: instructs the IRB to consider the “purposes of the research and the setting in which the research will
p.000035: be conducted.” CIOMS goes further and recommends that “Special justification is required for inviting
p.000035: vulnerable individuals to serve as research subjects” (CIOMS, 2002).12
p.000035: Although Federal regulations define vulnerability in terms
p.000035: of the person’s ability to protect their own
p.000035:
p.000035: interests or particular sensitivity to risks because of physical condition, the lay public may perceive a
p.000035: broader definition of vulnerability as it relates to education, economics, socialXstatus, and other factors. As
p.000035: shown in Text Boxes 3-1 and 3-2 and described above, the concept of vulnerability is broader than that
p.000035: presented in the CommonXRule. It is not adequate to simply check the list in Text Box 3-1 to identify if a potentially
p.000035: vulnerable group is included in an observational study. The researchers should assess the potential
p.000035: vulnerability of a study population within the study by evaluating the characteristics (e.g., socioeconomic
p.000035: status) of the study population within the context of the study by considering the various design elements of the
p.000035: study, as discussed in Section 2.
p.000035: 12 In the commentary on Guideline 13 in CIOMS (2002), the committee states that the central problem presented by plans
p.000035: to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the
p.000035: burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those
p.000035: with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in
p.000035: the CIOMS document (Guidelines 14 and 15) and include children, and persons who, because of mental or behavioral
p.000035: disorders, are incapable of giving informed consent. Ethical justification of their involvement usually requires that
p.000035: • the research could not be carried out equally well with less vulnerable subjects;
p.000035: • the research is intended to obtain knowledge that will lead to improved diagnosis, prevention, or treatment of
p.000035: diseases or other health problems characteristic of, or unique to, the vulnerable class—either the actual subjects or
p.000035: other similarly situated members of the vulnerable class;
p.000035: • research subjects and other members of the vulnerable class from which subjects are recruited will ordinarily be
p.000035: assured reasonable access to any diagnostic, preventive, or therapeutic products that will become available as a
p.000035: consequence of the research;
p.000035: • the risks attached to interventions or procedures that do not hold out the prospect of direct health-related
p.000035: benefit will not exceed those associated
p.000035:
p.000035:
p.000036: 36
p.000036:
p.000036: CIOMS recommendations, although written to address biomedical research, also generally are
p.000036: applicable to observational human exposure studies. The authors of this document consider the CIOMS
p.000036: requirement that the research could not be carried out equally well with less vulnerable subjects
p.000036: to be particularly important. EPA and NERL researchers should include vulnerable groups in
p.000036: observational human exposure studies only if their participation is critical to the success and
p.000036: applicability of the research. Even then, EPA and NERL researchers will have to meet stringent standards for
p.000036: protecting the rights and safety of the vulnerable participants. For example, EPA regulations
p.000036: governing observational research with children are even more stringent than the CIOMS guideline.
p.000036: If such research does not hold out the prospect of direct benefit to the child, no increase whatsoever over
p.000036: minimal risk is permitted.
p.000036: However, many observational human exposure studies are developed specifically to study the exposures of
p.000036: selected vulnerable groups to chemicals and other environmental stressors in everyday environments. So,
p.000036: researchers should be prepared to address the issues associated with vulnerable groups in
p.000036: observational research. Furthermore, as discussed in Section 3.4, there has been increased concern in recent years that
p.000036: exclusion of vulnerable groups from research studies is not ethical. Failure to conduct research with vulnerable groups
p.000036: may deprive them of the benefits of research. NIH, for example, has a policy (NIH, 1998) with a
p.000036: goal of increasing participation of children in research.
p.000036:
p.000036: 3.3 Minimal Risk and Vulnerable Groups
p.000036: EPA has codified protections for children, pregnant or nursing women, and fetuses in Subparts B, C, and D of the EPA
p.000036: human subjects rule (40 CFR 26). Subpart B strictly prohibits research involving intentional exposure of children
p.000036: or pregnant or nursing women (and, therefore, exposure of her fetus).
p.000036: EPA’s regulations do allow for observational research involving fetuses and pregnant women (40 CFR 26
p.000036: Subpart C) or children (40 CFR 26 Subpart D) but with additional protections in place and with
p.000036: strict limitations on research that presents more than minimal
p.000036: risk (CFR, 2006a).13 When considering vulnerable groups, The Institutional Review Board Guidebook (U.S. HHS,
p.000036: 1993) states that “IRBs should therefore determine whether the proposed subject population would be more sensitive or
p.000036: vulnerable to the risks posed by the research as a result of their general condition or disabilities. If so, the
p.000036: procedures would constitute more than minimal risk for those subjects.”
p.000036: When conducting observational human exposure studies, it is recommended that researchers consult these
p.000036: regulations and guidebooks. NERL researchers also will need to ensure that all of the requirements in Subparts B, C,
p.000036: and D of the EPA Human Subjects Rule are met.
p.000036:
p.000036: 3.4 Research Involving Children
p.000036: Children long have been recognized as a vulnerable group in research studies. EPA and HHS both extend special
p.000036: protections to children (CFR, 2006a,b). There are many books, reports, and research manuscripts that
p.000036: specifically address issues associated with research involving children (e.g., NRC & IOM, 2005; IOM,
p.000036: 2004; Kodish, 2005; NRC, 2003; AAP, 2003).
p.000036: CIOMS has drafted guidelines for including children in biomedical research (Guideline 14, CIOMS, 2002). The
p.000036: guidelines require an investigator to provide the assurances shown in Text Box 3-3 before undertaking
p.000036: research involving children.
p.000036:
p.000036: Text Box 3-3. Assurances Required by CIOMS Before Research Involving Children May Begin
p.000036: • the research might not equally well be carried out with adults;
p.000036: • the purpose of the research is to obtain knowledge relevant to the health needs of children;
p.000036: • a parent or legal representative of each child has given permission;
p.000036: • the agreement (assent) of each child has been obtained to the extent of the child’s capabilities; and
p.000036: • a child’s refusal to participate or continue in the research will be respected.
p.000036:
p.000036:
p.000036: The participation of children in some observational human exposure studies is critical to
p.000036: characterizing children’s exposures to chemicals in the environment. It is well recognized that children are not
p.000036: “little adults,”
p.000036: and that their
p.000036: exposures to chemicals differ (and, in
p.000036:
p.000036:
p.000036: with routine medical or psychological examination of such persons unless an ethical review committee authorizes a
p.000036: slight increase over this level of risk (Guideline 9); and,
p.000036: • when the prospective subjects are either incompetent or otherwise substantially unable to give informed consent,
p.000036: their agreement will be supplemented by the permission of their legal guardians or other appropriate representatives.
p.000036:
p.000036:
p.000036: 13 Minimal risk is defined at 40 CFR 26.102(i) and again at 40 CFR 26.402(g). It “means that the probability and
p.000036: magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily
p.000036: encountered in daily life or during the performance of routine physical or psychological examinations or tests.”
p.000036:
p.000036:
p.000037: 37
p.000037:
p.000037: some cases, are higher) from those of adults. Children are behaviorally and physiologically different
p.000037: from adults. Their interaction with their environment, through activities such as playing on floors, mouthing of
p.000037: hands and objects, and handling of food, may increase contact with contaminated surfaces. Children
p.000037: have proportionately higher breathing rates, relative surface area, and food intake requirements
p.000037: that also may increase exposure. Differences in absorption, metabolism, storage, and excretion
p.000037: may result in higher biologically effective doses to target tissues. Immature organ systems may be more
p.000037: susceptible to toxicological challenges. Windows of vulnerability, when specific toxicants may permanently
p.000037: alter the function of an organ system, are thought to exist at various stages of development. Because
p.000037: the factors influencing children’s exposures to chemicals are not characterized well (Cohen Hubal et
p.000037: al., 2000), it is sometimes important that observational human exposure studies involve children.
p.000037: Because children are so vulnerable, there long has been concern about including them in research studies,
p.000037: and biomedical research often excluded children. However, in recent years, there has been concern
p.000037: that excluding children from research is not ethical. NIH’s Policy and Guidelines on the Inclusion of
p.000037: Children as Participants in Research Involving Human Subjects (NIH, 1998) has a goal of increasing
p.000037: participation of children in research. The policy of NIH is that children must be included in all human
p.000037: subjects research conducted or supported by NIH, unless there are scientific and ethical reasons
p.000037: not to include them. Proposals or applications to NIH for research have to present an acceptable
p.000037: justification if children will be excluded from a research study. Of course, as discussed above, if the research
p.000037: topic is irrelevant to children, the CIOMS guidelines would recommend that they be excluded from the
p.000037: research.
p.000037: Observational human exposure studies conducted by NERL are not expected to involve greater than minimal risk. It
p.000037: will be the responsibility of the NERL researchers to present adequate information for the IRB to
p.000037: demonstrate that the research does not involve greater than minimal risk. Researchers designing observational
p.000037: research studies should carefully evaluate the risks and benefits specific to their study and the
p.000037: participants involved. In developing the study design and human subjects protocols, researchers need to
p.000037: ensure that the protocols ensure the protection of the rights and welfare of the participant children, and that
p.000037: risks and harm are minimized. The perception of risks and benefits, both by
p.000037: the individual and by the family or community, may influence the risk-benefit determination. It may prove
p.000037: useful for the research team to consult with other experienced researchers who have conducted
p.000037: similar studies and with members of the IRB to ensure that the information included in the human subjects
p.000037: research protocol is adequate for the IRB’s review.
p.000037: It is recommended that researchers consider all of the potential issues associated with involvement
p.000037: of children in their studies in developing the study design and research protocols, including the role of the
p.000037: family. EPA’s human subjects rule for observational research not involving greater than minimal risk to
p.000037: children (40 CFR 26.404) (i.e., the kinds of observational human exposure studies that NERL exposure research
p.000037: is likely to entail) focuses on obtaining assent of the children and permission of their parents or guardians. But the
p.000037: role of the family goes far beyond their involvement in the informed consent process. In observational
p.000037: human exposure studies, even when children are the participants, the parents or guardian play
p.000037: a key role in the collection of data and information during the study. For studies with very young children,
p.000037: family members supply all of the information relevant to the child. NERL researchers need to ensure that both
p.000037: the child and the parents or guardians and other caregivers are informed fully and are willing
p.000037: participants. Without their willing participation, the research cannot be successful.
p.000037:
p.000037: 3.5 Women as Research Subjects
p.000037: Women are routinely included as research participants in observational human exposure studies.
p.000037: However, pregnant women and their fetuses are vulnerable groups and require special protections.
p.000037: EPA’s human subjects rule prohibits intentional dosing studies and provides additional controls for
p.000037: observational research (40 CFR 26, Subparts B and C).
p.000037: CIOMS (2002) includes two guidelines for biomedical research involving women as research
p.000037: subjects. The first of these, number 16, states that women should not be excluded from
p.000037: biomedical research because of the potential for becoming pregnant during a study. The document continues, “A
p.000037: general policy of excluding from such clinical trials women biologically capable of becoming pregnant is
p.000037: unjust in that it deprives women as a class of persons of the benefits of new knowledge derived from the
p.000037: trials.” The second relevant CIOMS guideline, number 17, asserts that, if involved in a research study,
p.000037: pregnant women should be fully informed, and included only if the
p.000037:
p.000037:
p.000037:
p.000038: 38
p.000038:
p.000038: research benefits pregnant women and is thoroughly supported by reliable evidence in animal studies.
p.000038: Although the CIOMS guideline specifically addresses biomedical research, the ethical concepts
p.000038: behind the guidelines generally may be applicable to observational human exposure studies. EPA’s human
p.000038: subjects rule is completely consistent with the HHS rule in adding additional protections for pregnant women and
p.000038: fetuses involved in observational research (40 CFR
p.000038: 26.304 and 45 CFR 46.204). These additional protections (specified in 45XCFRX46.204 subparagraphs a
p.000038: through j) reflect the CIOMS recommendations by requiring: availability of data from previously conducted
p.000038: studies to assess the risk to pregnant women and fetuses; scientific necessity for inclusion of pregnant women and
p.000038: fetuses (i.e., providing benefit to the woman or fetus, or producing important, but otherwise unobtainable,
p.000038: biomedical knowledge); that risk is reduced to the least possible level for achieving the objectives of
p.000038: the research; and other protections.
p.000038:
p.000038: 3.6 Other Potentially Vulnerable Groups
p.000038: HHS specifies additional protections for prisoners as a potentially vulnerable group in Subpart C of 45 CFR
p.000038: 26. Additional requirements for other vulnerable groups in research studies are not specifically defined in either
p.000038: EPA’s or HHS’ human subjects rules. Nonetheless, other groups (as discussed in Section 3.1) may be considered to be
p.000038: vulnerable and, as such, may warrant additional consideration and protection as required in the CommonXRule. For
p.000038: these other potentially vulnerable groups, such as employees, students, handicapped persons, mentally disabled
p.000038: persons, and economically or educationally disadvantaged persons, nursing home residents or otherwise
p.000038: incapacitated elderly, etc., the CommonXRule requires researchers and IRBs to fully evaluate the
p.000038: protocols to ensure that the safety and welfare of the groups will be protected. As discussed in Section 3.1,
p.000038: It also should be noted that, although Federal regulations define vulnerability in terms of the ability
p.000038: to protect one’s own interests, the lay public may perceive a broader definition of vulnerability as
p.000038: it relates to education, economics, social status, and other factors. The researcher should evaluate
p.000038: vulnerability in this broader context to ensure that adequate safeguards are included for potentially
p.000038: vulnerable populations that do not meet the definition of the Federal regulations.
p.000038: References
p.000038: AAP (American Academy of Pediatrics) (2003). Pediatric Environmental Health. (2nd Edition). Elk Grove Village, IL:
p.000038: American Academy of Pediatrics.
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000038: Subjects. U.S. Code of Federal Regulations.
p.000038: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed 12 June 2007].
p.000038:
p.000038: CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle A Department of Health and Human Services Part 46 Protection
p.000038: of Human Subjects. U.S. Code of Federal Regulations. Available:
p.000038: http://www.access.gpo.gov/nara/cfr/waisidx_06/45cfr46_06.ht ml [accessed 13 June 2007].
p.000038:
p.000038: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000038: Biomedical Research Involving Human Subjects.
p.000038: Geneva, Switzerland: CIOMS. Available at http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000038:
p.000038: Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry MR, Rigas ML, Zartarian VG, Freeman NCG (2000).
p.000038: Children’s exposure assessment: a review of factors influencing children’s exposure, and the data available to
p.000038: characterize and assess that exposure. Environ Health Perspect 108(6): 475-486.
p.000038:
p.000038: Emanuel EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000038:
p.000038: IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Washington, DC: The
p.000038: National Academies Press. Available: http://www.nap.edu/catalog.php?record_id=10958 [accessed 16 April 2008].
p.000038:
p.000038: Kodish E (Ed.) (2005). Ethics and Research with Children: A Case-Based Approach. New York: Oxford University Press.
p.000038:
p.000038: NBAC (National Bioethics Advisory Commission) (2001). Ethical and Policy Issues in Research Involving Human
p.000038: Participants, Volume I: Report and Recommendations of the National Bioethics Advisory Commission. Bethesda, MD:
p.000038: National Bioethics Advisory Commission. Available: http://www.bioethics.gov/reports/past_commissions/nbac_h
p.000038: uman_part.pdf [accessed 3 September 2007].
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000039: 39
p.000039:
p.000039: NIH (National Institutes of Health) (2002) Human Participant Protections Education for Research Teams [online
p.000039: tutorial].
p.000039:
p.000039: NIH (National Institutes of Health) (1998). NIH Policy and Guidelines on The Inclusion of Children as Participants in
p.000039: Research Involving Human Subjects. Available: http://grants.nih.gov/grants/guide/notice-files/not98 024.html [accessed
p.000039: 13 June 2007].
p.000039:
p.000039: NRC (National Research Council) (2003). Protecting Participants and Facilitating Social and Behavioral Sciences
p.000039: Research. Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=10638
p.000039: [accessed 12 June 2007].
p.000039: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000039: Housing-Related Health Hazards Involving Children.
p.000039: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed 12
p.000039: June 2007].
p.000039:
p.000039: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000039: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000039: [accessed 12 June 2007].
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
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p.000039:
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p.000039:
p.000039:
p.000039:
p.000040: 40
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040:
p.000040: SECTION 4
p.000040: Privacy, Confidentiality, and Other Concerns Related to Observational Human Exposure Studies
p.000040:
p.000040:
p.000040:
p.000040: Observational human exposure studies are designed to describe people’s contact with pollutants as they go about
p.000040: their everyday lives. Of necessity then, these studies take place in the locations that participants often
p.000040: consider to be personal and private. Clinical research studies generally are conducted in a research
p.000040: facility, a clinic, a hospital, or some other institutional or medical setting. Survey research may be conducted by
p.000040: mail, over the phone, or in another “neutral” setting. But, observational human exposure studies are
p.000040: conducted in the participants’ “personal” environment⎯their home, daycare center, school, vehicle,
p.000040: workplace, or other environments that people occupy during their routine daily activities. This difference
p.000040: in the research setting means that researchers involved in observational human exposure studies have an
p.000040: even greater challenge in meeting the ethical obligation to respect the privacy of the participants.
p.000040: When exposure science researchers like those at NERL enter a home to carry out their studies, the
p.000040: “expectations and constraints may be strikingly different than when research is carried out in a medical
p.000040: setting” (p. 64, NRC & IOM, 2005). The legal precept of freedom from unreasonable search and
p.000040: seizure and the historic and deeply rooted principle that “a man’s home is his castle” contribute to a belief in the
p.000040: “sanctity of the home” (see the discussion on pp. 62-66, NRC & IOM, 2005).
p.000040: The joint NRC and IOM report Ethical Considerations for Research on Housing-Related Health
p.000040: Hazards Involving Children discusses the ethical issues associated with entering a participant’s home to conduct
p.000040: research and explores the researchers’ responsibilities that derive from conducting research in people’s homes
p.000040: (NRC & IOM, 2005). These housing-related discussions are particularly relevant to observational human
p.000040: exposure studies, which often include environmental and
p.000040: biological measurements in people’s homes or personal locations. Many of the topics identified in that report are
p.000040: discussed in this section (Text Box 4-1).
p.000040:
p.000040:
p.000040: Text Box 4-1. Topics in Section 4
p.000040: Privacy Issues Confidentiality
p.000040: Confidentiality of Information Confidentiality of Participation
p.000040: Collateral Observations
p.000040: Potential Nonstudy Hazards in the Residence Collateral Observations with Mandated Reporting
p.000040: Requirements
p.000040: Hazard Communication Planning and Staff Training
p.000040: Third-Party Issues
p.000040: Determining Whether a Third Party is a Human Subject Informing Third Parties of Research Activities Research Results
p.000040: and Third Parties
p.000040: Data and Safety Monitoring and Oversight
p.000040:
p.000040:
p.000040:
p.000040: 4.1 Privacy Issues
p.000040: Privacy refers to an expectation that a person is free from intrusion into personal matters and is free from the
p.000040: presence or view of others. The Institutional Review Board Guidebook defines privacy as “control over the
p.000040: extent, timing, and circumstances of sharing oneself (physically, behaviorally, or intellectually) with
p.000040: others” (U.S. HHS, 1993). Beauchamp and Childress find that the right to privacy is based on the principle of
p.000040: respect for autonomy. “We often respect persons by respecting their autonomous wishes not to be observed, touched, or
p.000040: intruded upon…. A loss of privacy occurs if others use any of several forms of access, including intervening in zones
p.000040: of secrecy, anonymity, seclusion, or solitude” (pp. 295-296, Beauchamp and Childress, 2001).
p.000040:
p.000040:
p.000041: 41
p.000041:
p.000041: Although research participants may agree to allow researchers to enter their home or other zone of personal space
p.000041: to conduct their research measurements, they have not abrogated their right to privacy. “When individuals
p.000041: voluntarily grant others some form of access to themselves, their act is an exercise of the
p.000041: right to privacy, not a waiver of that right” (p. 297, Beauchamp and Childress, 2001). Researchers should remember
p.000041: that they are guests in the homes for a specific purpose. “When people visit a home, there are social
p.000041: expectations about what is acceptable behavior. People who are invited into a home are expected to be
p.000041: sensitive to and respectful of the host’s customs and values” (p. 65, NRC & IOM, 2005).
p.000041: By their very nature, observational human exposure studies encroach on the privacy of a research participant. Entry in
p.000041: a participant’s home (or other personal zones) does represent a loss of privacy, but researchers should be
p.000041: careful to ensure that their presence does not become a violation of the individual’s right to privacy. The
p.000041: relationship between the researcher and the participant may be complicated, and there may be conflicts between
p.000041: the researcher’s role and their ethical obligations (NRC & IOM, 2005). In entering a participant’s
p.000041: personal space, it may be difficult, or impossible, to avoid making observations unrelated to the research question,
p.000041: thereby further intruding on the participant’s personal privacy. Indeed, there may be ethical and legal
p.000041: obligations for the researchers to respond to those observations. Beauchamp and Childress suggest that “policies
p.000041: carefully specify the conditions of access that will and will not count as a loss of privacy or a violation of
p.000041: the right to privacy. The policy should accurately define the zones that are considered private and
p.000041: not to be invaded, and should also identify interests that legitimately may be balanced against privacy
p.000041: interests” (Beauchamp and Childress, 2001).
p.000041: Observational human exposure studies also may infringe on the privacy of other individuals, for example,
p.000041: other members of the participant’s family or household. Researchers should strive to minimize the intrusion and loss
p.000041: of privacy and to show respect for the privacy of study participants and third parties at all times (see Text
p.000041: Box 4-2 for a list of relevant privacy issues). It is incumbent on the researcher to recognize privacy issues
p.000041: in the design and implementation of the research study. The NRC & IOM report suggests that researchers
p.000041: anticipate the ethical issues that arise from conducting research in a person’s home, and that they take steps
p.000041: to correct them (1) by thinking through the issues as part of the study design; (2) by discussing the issues during the
p.000041: informed consent process; and (3) by ensuring that the frontline staff that enter a
p.000041: participant’s home “understand their role as members of the research team, how that role differs from the role of
p.000041: neighbor or friend, and how they should respond when they make observations that are not part
p.000041: of the protocol” (p. 66, NRC & IOM, 2005).
p.000041:
p.000041: Text Box 4-2. Privacy Issues
p.000041: • Researchers should develop an anticipatory plan for how to deal with privacy issues during the study. The plan
p.000041: should include a list of potential observations that could be of concern and a plan for how they will be handled.
p.000041: • The plan needs to address both the legal and ethical obligations of the researcher in response to situations where
p.000041: privacy is compromised.
p.000041: • Privacy issues will vary depending on the culture of the population being studied. What one individual or group
p.000041: may find as an invasion of privacy, another group may not have a concern about.
p.000041: • Privacy issues involve individual participants and may extend to third parties, including the community.
p.000041: • Researchers may find a meeting with community representatives to learn about the community residents and potential
p.000041: privacy issues to be helpful. Community representatives can help the researcher identify potential privacy issues and
p.000041: offer advice on how to address them.
p.000041: • Researchers may wish to respect the privacy of occupants sharing the study participant’s household or other study
p.000041: locations by providing advance notification of study visits and by giving them the opportunity not to be present during
p.000041: those visits.
p.000041: • Field staff should be trained on how to minimize breaches of privacy and how to handle privacy issues.
p.000041: • The informed consent process and form should address how the researcher will handle privacy issues such as
p.000041: collateral observations of household hazards
p.000041:
p.000041:
p.000041:
p.000041: 4.2 Confidentiality
p.000041: Confidentiality and privacy are not the same thing. Confidentiality refers to limits on the dissemination
p.000041: of information disclosed by a person in a special professional relationship, such as the
p.000041: doctor-patient relationship or the participant-researcher relationship (Beauchamp and Childress, 2001).
p.000041: The Institutional Review Board Guidebook defines confidentiality as “pertains to the treatment of
p.000041: information that an individual has disclosed in a relationship of trust and with the expectation that it
p.000041: will not be divulged to others without permission in ways that are inconsistent with the understanding of the
p.000041: original disclosure” (U.S. HHS, 1993). Emanuel et al. (2000) state that one way to respect the privacy
p.000041: of the participants is “by managing the information in accordance with confidentiality
p.000041:
p.000041:
p.000042: 42
p.000042:
p.000042: rules.” Confidentiality in research also may extend to limiting dissemination of the knowledge
p.000042: that an individual is participating in a research study.
p.000042: As part of the research planning process, researchers are responsible for developing procedures to protect
p.000042: confidentiality and to define limits on the researcher’s ability to provide or protect confidentiality.
p.000042: Explaining plans or procedures for protecting confidentiality and their limits14 to prospective research
p.000042: participants is an integral part of the informed consent process.
p.000042:
p.000042: 4.2.1 Confidentiality of Information
p.000042: Many types of information may be collected in observational human exposure studies. Information may be collected
p.000042: through questionnaires, staff observations of residential or other environments, diaries, personal sample
p.000042: collection, environmental or residential sample collection, and collection of biological specimens.
p.000042: Measurement data from the collected samples become part of the information for a participant. The
p.000042: specific information to be obtained to address the research questions should be determined in the
p.000042: development of the study design and research protocol.
p.000042: Disclosure of information that can be linked to an individual may cause harm or distress to that individual.
p.000042: Researchers are responsible for developing safeguards to protect the confidentiality of information and physical
p.000042: samples collected from research participants (see, for example, Guideline 18, CIOMS, 2002). 15
p.000042: Researchers also should be aware that certain combinations of information from a study
p.000042: may sometimes lead to the indirect identification of the individual. Certain combinations of
p.000042: demographic information, for example, may make it relatively simple
p.000042:
p.000042:
p.000042: 14 Beauchamp and Childress (2001) discuss when one may be ethically justified in infringing on an individual’s privacy
p.000042: and confidentiality⎯for example, because of risks to others evidenced by biomarkers of infectious disease. They also
p.000042: discuss similar ethical issues that may arise in regard to genetic data. CIOMS (2002) Guideline 18 provides suggestions
p.000042: for safeguarding or disclosing genetic information. If exposure scientists collaborate with medical researchers or
p.000042: epidemiologists and obtain such information, they need to be cognizant of the relevant ethical issues and of the CIOMS
p.000042: guidelines.
p.000042: 15 Guideline 18 states, “The investigator must establish secure safeguards of
p.000042: the confidentiality of subjects’ research data. Subjects should be told the limits, legal or other, to the
p.000042: investigators’ ability to safeguard confidentiality and the possible consequences of breaches of confidentiality.”
p.000042: Additional CIOMS commentary on the confidentiality guideline states, “Prospective subjects should be informed of limits
p.000042: to the ability of researchers to ensure strict confidentiality and of the foreseeable adverse social consequences of
p.000042: breaches of confidentiality. Some jurisdictions require the reporting to appropriate agencies of, for instance, certain
p.000042: communicable diseases or evidence of child abuse or neglect. These and similar limits to the ability
p.000042: to maintain confidentiality should be anticipated and disclosed to prospective subjects.”
p.000042: to identify an individual. Precise geographic location information may be sufficient to pinpoint a
p.000042: residence. Researchers may use several strategies to reduce the likelihood of indirect identification when
p.000042: study results are reported (see, also, Text Box 4-3).
p.000042: • Redact from publications, reports, or public data sets information that might be used to indirectly identify a
p.000042: research participant.
p.000042: • Generalize exact information; for example, replace birth date with age or year of birth or classify age as
p.000042: part of a range.
p.000042: • Aggregate information across individuals; for example, only report data in cells of sufficient size
p.000042: to make individual linkages unlikely.
p.000042: • Reduce the specificity of geographic coordinate information to a level that a specific residence or other
p.000042: location can not be identified.
p.000042:
p.000042: Text Box 4-3. Approaches for Protecting Personally Identifiable Information
p.000042: • Developing procedures for safeguarding information prior to collecting the information
p.000042: • Ensuring that data or samples are anonymous by not collecting or by destroying identifying information or linkages
p.000042: • Restricting access to identifying information to only those requiring access
p.000042: • Assigning codes to participants, data, and samples rather than using identifiers
p.000042: • Physically separating identifying information and linkage files from other study information
p.000042: • Securing identifying information in locked files with limited access
p.000042: • Restricting identifying information from computers that are networked with other computers or electronic systems
p.000042: • Restricting identifying information from computers that are not kept in secure locations with limited access
p.000042: • Training researchXstaff members on human subject protection and on information security procedures
p.000042:
p.000042:
p.000042: Another step that can help protect confidentiality is to obtain a Certificate of Confidentiality. Certificates of
p.000042: Confidentiality are issued by NIH (2002) to protect identifiable research information from forced disclosure.
p.000042: They allow the investigator and others who have access to research records to refuse to disclose identifying
p.000042: information on research participants in any civil, criminal, administrative, legislative, or other
p.000042: proceeding, whether at the Federal, State, or local level. Certificates of Confidentiality may be granted for studies
p.000042: collecting information that, if disclosed, could have adverse consequences for subjects or damage
p.000042: their financial standing, employability, insurability, or reputation. By protecting researchers and
p.000042: institutions from being
p.000042:
p.000042:
p.000043: 43
p.000043:
p.000043: compelled to disclose information that would identify research subjects, Certificates of Confidentiality
p.000043: help achieve the research objectives and promote participation in studies by assuring
p.000043: confidentiality and privacy to participants. Any research project that collects sensitive, personally identifiable
p.000043: information and that has been approved by an IRB is eligible for a certificate. Identifying information is broadly
p.000043: defined as any item or combination of items in the research data that could lead directly or indirectly to the
p.000043: identification of a research subject.
p.000043: Federal funding is not a prerequisite for a certificate. A Certificate of Confidentiality does not
p.000043: diminish, however, the investigator’s need to protect the personally identifiable information as
p.000043: described above.
p.000043:
p.000043: 4.2.2 Confidentiality of Participation
p.000043: In some types of research, the knowledge that a person is participating in a particular research study
p.000043: could, potentially, put the participant at risk for harm or distress. This topic is discussed in The
p.000043: Institutional Review Board Guidebook, with special emphasis on behavioral and social research that deals
p.000043: with sensitive topics (U.S. HHS, 1993). The guidebook describes the need for additional safeguards to
p.000043: protect and prevent disclosure of the identity of participants, including the use of Certificates of
p.000043: Confidentiality for sensitive matters.
p.000043: Observational human exposure studies often pose particular challenges with regard to limiting
p.000043: dissemination of the knowledge of an individual’s participation in the study. Visiting the
p.000043: research participant’s residence to collect samples or to make observations will necessitate informing
p.000043: other family members or occupants about the visit and study procedures. Research participants may be
p.000043: asked to wear personal monitors over time periods ranging from a day to a week or more. Wearing these devices
p.000043: in public places, schools, or workplaces may identify them as a study participant or generate questions
p.000043: regarding the activity. Field staff visits to the participant’s home or setting up outdoor sample collection
p.000043: devices around the home also might disclose their participation. And, in some cases, third parties outside of
p.000043: the home have to be asked for permission or be informed that monitoring activities are taking place.
p.000043: Researchers and IRBs should consider whether knowledge of an individual’s participation by others might
p.000043: create potential for harm or distress in an observational human exposure study. Such risks might
p.000043: be limited to possible discomfort in attracting unwanted
p.000043: attention; this may be particularly true for adolescents. However, in some cases, the potential risks
p.000043: could be greater, for example, in cases where participation could provoke an adverse reaction from a
p.000043: landlord or employer. Oftentimes study protocols can be structured to minimize these potential risks. Through the
p.000043: informed consent process, prospective participants should be made aware of the limits of the researcher’s ability to
p.000043: protect knowledge of their participation in the study and of the possible risks of disclosure.
p.000043:
p.000043: 4.3 Collateral Observations
p.000043: In the course of conducting an observational human exposure study, research staff may observe potentially unsafe
p.000043: conditions or situations that are unrelated to the research study. Such “collateral observations” may
p.000043: involve physical hazards in the study participant’s residential environment or evidence of situations,
p.000043: such as child abuse, that have to be reported to proper authorities. In preparing for the
p.000043: research study, it is recommended that researchers carefully plan for possible collateral observations,
p.000043: including their identification, staff training, and hazard communication and reporting. This may be a major
p.000043: element in the data and safety monitoring and oversight for the study. The informed consent process
p.000043: should reflect procedures used to manage collateral observations. Potential participants should be
p.000043: informed of situations in which confidentiality might be breached, such as statutory requirements for reporting
p.000043: abuse or imminent harm to self or others.
p.000043:
p.000043: 4.3.1 Potential Nonstudy Hazards in the Residence
p.000043: Research staff conducting observational human exposure studies often will spend time in and around
p.000043: study participant residences. In the course of visiting a residence or conducting study-related
p.000043: observations, researchXstaff may observe potential hazards unrelated to the research being performed (see Text Box
p.000043: 4-4). Some hazards may be associated with the potential for physical injury, whereas others may be related to
p.000043: exposure to chemical or biological agents. Some situations may be potential hazards only for young children,
p.000043: whereas other conditions may present potential hazards for all residents or occupants.
p.000043: The NRC & IOM recommend that researchers should consider such foreseeable observations and
p.000043: potential hazards in advance, develop responses to the risks, and submit the proposed plans to the IRB
p.000043: for review to ensure that they are appropriate “in the context of the research and the affected community.” The NRC
p.000043:
p.000043:
p.000044: 44
p.000044:
p.000044: & IOM also advise that field staff should be trained in how to assess and respond to
p.000044: such risks (Recommendations 7.3 and 7.4, NRC & IOM, 2005). For other behaviors and risks that
p.000044: have not been specifically identified in advance, procedures should be included in the data and safety monitoring
p.000044: and oversight provisions of the study design and research protocol to address these issues. The fundamental
p.000044: ethical principle of beneficence would motivate researchers who observe serious harms to take steps to try to prevent
p.000044: those harms, even for observations that are not directly related to the study. The steps that they may take can
p.000044: range from immediate action to prevent an imminent and serious danger to statutory reporting of
p.000044: observations (see Section 4.3.2) to reporting the observation to the data and safety monitoring and oversight
p.000044: authority for advice on how to respond (see Section 4.5). (The reader is also referred to pages 59-61 and 134-144 of
p.000044: the NRC & IOM [2005] report for a more thorough discussion of researchers’ responsibilities in such
p.000044: cases.)
p.000044:
p.000044: Text Box 4-4. Potential Hazards that Might Be Encountered in a Residential Environment
p.000044: • Unsecured firearm
p.000044: • Uncovered electrical outlets
p.000044: • Unprotected stairways
p.000044: • Missing child-protective cabinet latches
p.000044: • Lack of window guards
p.000044: • Missing or inoperable smoke alarm
p.000044: • Housing code violations
p.000044: • Chipping or flaking paint—potential for lead exposure in older homes
p.000044: • Malfunctioning or unvented combustion appliances—potential for carbon monoxide exposure
p.000044: • Unsecured poisons or other dangerous products
p.000044: • Excessive mold growth
p.000044:
p.000044:
p.000044: 4.3.2 Collateral Observations with Mandated Reporting Requirements
p.000044: Some collateral observations may have statutory requirements for reporting to designated authorities.
p.000044: Examples of such observations include
p.000044: • observed child or elder abuse or evidence of such abuse or neglect,
p.000044: • statements or actions of intent to harm self or others, and
p.000044: • certain communicable diseases.
p.000044: Because different reporting statutes pertain in different states, it is necessary for researchers to
p.000044: learn and understand the applicable reporting requirements for the study location. In the case of abuse, it is
p.000044: also
p.000044: important to understand what actions or situations are considered abusive in a particular state. Although direct
p.000044: physical harm or violence might be obvious to a researchXstaff member, there are other conditions of neglect that
p.000044: might be more difficult to recognize or to know when to report.
p.000044: Study participants should be made aware of statutory requirements for reporting collateral observations as part of the
p.000044: informed consent process. Researchers should include the reporting requirements in the informed
p.000044: consent form (discussed in Section 5) and should ensure that the study participant fully comprehends this
p.000044: information and the impact on their privacy and confidentiality.
p.000044:
p.000044: 4.3.3 Hazard Communication
p.000044: It is difficult for researchers to determine when and how to communicate with study participants or third
p.000044: parties about collateral observations related to potential hazards. A hazard might present such an imminent
p.000044: threat to health or safety that staff would need to communicate immediately with the participant or take
p.000044: action to mitigate the threat. In some cases, such as instances of abuse with attendant statutory reporting
p.000044: requirements, it may be necessary to breach confidentiality. More often, however, a potential hazard identified as
p.000044: a result of collateral observation may not be an imminent threat or pose a potential risk that is situation
p.000044: dependent or is related to third parties. A number of considerations in hazard communication come
p.000044: into play regarding confidentiality, privacy, the ability of the researcher to provide accurate and
p.000044: effective information regarding the hazard and hazard mitigation, and the ability of the study participant or others
p.000044: to effectively mitigate the hazard without unintended adverse consequences. The National Academy of Sciences
p.000044: Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children, Youth, and
p.000044: Families discussed many of these issues in depth (NRC & IOM, 2005).
p.000044: Different communities, cultures, or demographic groups can have different risk perceptions, which may
p.000044: affect how collateral observations are assessed and reported from one study location to the next. The AAP
p.000044: Committee on Environmental Health has prepared information regarding perception, identification, and
p.000044: communication of environmental health risks (AAP, 2003). Researchers likely will benefit from including
p.000044: community members on the research team in developing the study design and research protocol or from
p.000044: consultation with community boards regarding identification of hazards and hazard communication.
p.000044:
p.000044:
p.000045: 45
p.000045:
p.000045: It is important that any advice that the researcher might provide to study participants regarding hazard
p.000045: mitigation should be carefully considered. Considerations in recommending an action may include
p.000045: whether the mitigation approach has been shown to be effective, whether the study participant can
p.000045: understand and effectively implement the action, and whether unintended adverse consequences might
p.000045: result from taking an action. In some cases, it may be reasonable to refer the participant to another
p.000045: organization that can provide expert advice or assistance.
p.000045:
p.000045: 4.3.4 Planning and Staff Training
p.000045: As part of the study planning process and protocol development, it is important that researchers
p.000045: be cognizant of the kinds of collateral observations that might occur in the implementation of the study
p.000045: protocol and to develop plans as to how such observations would be handled. Researchers may choose to
p.000045: include a systematic approach in hazard identification, such as using a home-hazard checklist that becomes an
p.000045: ancillary part of the study protocol. Alternatively, collateral observations could be handled on a
p.000045: case-by-case basis.
p.000045: Staff experience and training is a critical consideration for managing collateral observations. Staff
p.000045: members that visit study participant residences may not have expertise or experience in identifying many of the
p.000045: potential hazards without adequate training. All staff involved in a study, particularly those responsible
p.000045: for field data collection, should be trained on identification and reporting of collateral observations. This
p.000045: training should be study specific and likely will include, but not be limited to
p.000045: (1) identification of actions (e.g., child abuse) that have (state-specific) statutory reporting requirements,
p.000045: (2) conditions of neglect that may adversely impact study participants or third parties,
p.000045: (3) environmental hazards and situations that may be associated with imminent harm (e.g., combustible
p.000045: materials near an open flame, unsecured firearms accessible to very young children),
p.000045: (4) policies and procedures for reporting or intervention by members of the research team, and
p.000045: (5) local and state reporting requirements.
p.000045: It is advisable that this training be developed in consultation with community representatives who can
p.000045: provide input on potential hazards and situations that may be encountered in the study community,
p.000045: local norms and attitudes about potential interventions and reporting, and local agencies available to assist on
p.000045: these types of issues. It is also especially important to consider
p.000045: staff experience and training in hazard communication. Consistency in communication is very important, and
p.000045: researchers may decide to use materials prepared by other organizations that have expertise regarding
p.000045: a particular hazard.
p.000045: Another important element of planning for field data collection and training of researchXstaff is on hazards and
p.000045: situations that the field staff may encounter during their field work. Although the previous discussion highlights the
p.000045: need to be prepared to report potentially negligent or illegal behaviors, these same behaviors may place the
p.000045: researchXstaff in imminent danger during the conduct of their work in residences and communities. The research team
p.000045: should develop a plan for identifying potential situations, hazards, and dangers that may place the
p.000045: research team at risk of imminent harm. This should generally involve working with
p.000045: community representatives to identify the hazards and situations that may be of concern. For example, a
p.000045: researcher’s observation of illegal drugs in a study residence may place the researcher in potential
p.000045: danger. Similarly, if studies are conducted in areas with high crime rates, researchers need to be aware of
p.000045: the potential dangers and have a plan for addressing them. In some cases, situations may arise
p.000045: because of to inadvertent actions. For example, if an area has a high rate of daytime break- ins, the presence
p.000045: of researchers in the area may trigger calls to local authorities when the researchers, who are
p.000045: strangers, are observed in the neighborhood. Feedback from the community representatives should be solicited when
p.000045: developing a plan for responding to situations such as these. Comprehensive training should be developed for
p.000045: research field staff to assist them in identifying potentially dangerous situations and in responding to
p.000045: such situations.
p.000045:
p.000045: 4.4 Third-Party Issues
p.000045: Third-party issues can arise in observational human exposure studies in two ways. First, the study may collect
p.000045: limited information about or related to individuals other than the study participants. Second,
p.000045: study activities may affect or involve people or organizations other than the study participants.
p.000045: Examples of activities that may involve or affect third parties in observational human exposure studies
p.000045: could include, but are not limited to the following types.
p.000045: • Asking the participant about demographic, occupational, smoking, or product use information for
p.000045: other household members
p.000045: • Collecting residential environmental samples in multiperson households
p.000045:
p.000045:
p.000046: 46
p.000046:
p.000046: • Collecting environmental samples in common areas of multifamily housing units
p.000046: • Collecting personal or environmental samples in a day care, school, health care, or occupational setting
p.000046: • Measuring chemical occurrences or concentrations that may be of interest or import to other
p.000046: household members or to the community
p.000046: • Collecting activity or dietary information about a community
p.000046: It is important for researchers and research staff to understand whether and to what extent the research
p.000046: involves or affects third parties, and how third-party involvement might affect the study participants. Several
p.000046: examples of possible third-parties are listed in Text Box 4-5. Study planning; IRB review; and communication
p.000046: before, during, and after the study should take third- party issues into account.
p.000046:
p.000046: Text Box 4-5. Possible Third-Parties in Exposure Studies
p.000046: • Household members not enrolled in the study
p.000046: • Relatives
p.000046: • Care givers for children or elders
p.000046: • School staff
p.000046: • Employers
p.000046: • Other members of the community
p.000046: • Building managers or facility operators
p.000046: • Landlords
p.000046:
p.000046:
p.000046:
p.000046: 4.4.1 Determining Whether a Third Party Is a Human Subject
p.000046: It is up to the IRB to determine whether a third party is a human subject afforded human
p.000046: subject protections under the Common Rule. A third party would meet the Common Rule definition of
p.000046: a human subject [40 CFR 26.102(f)] if individually identifiable private information about them is collected
p.000046: (CFR, 2006). When this occurs, the informed consent of the third party must be obtained, or, if certain criteria are
p.000046: met, the IRB may determine that informed consent may be waived. It can be difficult to determine whether information
p.000046: about a third party is both individually identifiable and private. Discussions of this issue and
p.000046: recommendations for determining whether third-party information is identifiable and private have been
p.000046: submitted to the HHS Office of Human Research Protections by NIH (2001) and by the National Human
p.000046: Research Protections Advisory Committee (NHRPAC, 2002).
p.000046: Whether or not a third party is determined to be a human subject, the researcher should treat
p.000046: research
p.000046: information about a third party as confidential.
p.000046:
p.000046: 4.4.2 Informing Third Parties of Research Activities
p.000046: Obtaining permission from or informing third parties of certain types of activities may be needed in some
p.000046: observational human exposure studies. For example, household members living with a study participant need to
p.000046: be informed about home study visits and residential sample collection activities. Study activities that
p.000046: occur outside of the participant’s home or yard may require informing or gaining permission from third
p.000046: parties. A study may include collection of environmental samples (i.e., ambient air, dust, soil) from outdoor
p.000046: common areas of multifamily housing where the study participant lives. Issues regarding privacy, permission, and
p.000046: payments for third parties in housing-related studies have been discussed in the NRC & IOM (2005) report.
p.000046: Observational human exposure studies also may include cases when study participants are asked
p.000046: to collect personal samples (i.e., wearing a personal air monitor) over a time period that includes time
p.000046: they spend in a school, day care, or workplace. Such monitoring might require informing or
p.000046: gaining permission from an organization’s staff or an employer. In each case, the researcher and IRB have to
p.000046: consider whether obtaining permission from or informing a third party is appropriate and, if so, to define the
p.000046: procedures for doing so. The researcher and IRB have to also consider the potential impact of third-party
p.000046: knowledge of research activities on confidentiality and risk for the study participant and have to ensure that it is
p.000046: clearly and fully explained in the informed consent process.
p.000046:
p.000046: 4.4.3 Research Results and Third Parties
p.000046: Prior to initiating a research study, researchers should consider whether research results may
p.000046: be provided to third parties. In some studies, there may be reasons to inform household members living with a
p.000046: study participant about specific residential measurement results. In community research studies, aggregated or
p.000046: summary research results may provide a benefit to the community. In this case, it would be beneficial to seek
p.000046: out the advice of community representatives regarding results reporting prior to the study. Researchers
p.000046: also should determine whether there are State or local reporting requirements for some types of
p.000046: measurement results above specified action levels (i.e., blood-lead levels, heavy metal concentration in soil).
p.000046: It is important that the researcher and IRB ensure that confidentiality and privacy of study
p.000046: participants are carefully
p.000046:
p.000046:
p.000047: 47
p.000047:
p.000047: considered in any case where reporting study results to third parties is contemplated or may be required. Ideally,
p.000047: the informed consent process would make clear whether, under what conditions, and how research results might be
p.000047: provided to third parties.
p.000047:
p.000047: 4.5 Data and Safety Monitoring and Oversight
p.000047: The Common Rule requires for IRB approval that, “When appropriate, the research plan makes adequate
p.000047: provision for monitoring the data collected to ensure the safety of subjects.” [40 CFR 26.111(a)(6)].
p.000047: Data and safety monitoring plans (DSMPs) are developed and applied in all clinical trial
p.000047: research studies. Clinical trials are prospective studies designed to answer specific questions about the effects or
p.000047: impact of particular biomedical or behavioral interventions. The DSMPs are used to insure the safety of
p.000047: participants, the validity of data, and appropriate termination of studies for which significant risks
p.000047: or benefits have been uncovered or when it appears that the trial cannot be concluded successfully
p.000047: (NIH, 1998; NCI, 2001; U.S. FDA, 2001). Depending on the study scope and potential risks and benefits, a
p.000047: data safety monitoring board (DSMB) may be created to assess procedures for data and safety monitoring
p.000047: and to independently assess safety and outcomes on an ongoing basis during the study.
p.000047: Formal independent monitoring boards or committees, like DSMBs, have not seen widespread use in
p.000047: observational human exposure studies, although much of the information included in DSMPs often has been
p.000047: captured in the research protocols. Researchers and IRBs may, however, consider using monitoring and oversight boards
p.000047: to help assure participant safety and research integrity in observational human exposure studies,
p.000047: particularly in complex longitudinal studies and in studies that include vulnerable subjects.
p.000047: At least two NIH institutes have developed guidelines for monitoring and oversight in
p.000047: the observational research that they sponsor.
p.000047: (1) The National Heart, Lung, and Blood Institute (NHLBI) has developed an interim policy on the
p.000047: creation and role of observational study monitoring boards (OSMBs) for observational research
p.000047: sponsored by that institute (NHLBI, 2007). OSMBs may be established for large or complex studies on a case-by-case
p.000047: basis. The role of the OSMB is “to help assure the integrity of the study by closely monitoring data
p.000047: acquisition for comprehensiveness, accuracy, and timeliness; and monitoring other concerns such as
p.000047: participant confidentiality.”
p.000047: (2) The National Eye Institute (NEI) has developed guidelines for data monitoring and oversight
p.000047: committees (DMOCs) for observational research (NEI, 2001). The role of the DMOC is to “assist the NEI and the
p.000047: study investigators in protecting the interests of study participants and in preserving the integrity and
p.000047: credibility of the study.”
p.000047: When appropriate, formal procedures for routine monitoring of scientific and ethical issues will need to be
p.000047: incorporated into observational research and approved by the IRB to ensure participant safety and the integrity of
p.000047: the research. Even though most observational human exposure studies are considered low-risk, there is often a need to
p.000047: determine whether appropriate threshold values for biological or environmental levels of chemicals exist or can be
p.000047: determined that, if the threshold value is exceeded, it would trigger reporting or other actions. The safety of
p.000047: measurement procedures and equipment also has to be considered. Unanticipated adverse events also may be
p.000047: encountered in observational research. Participant consent and understanding of the research effort,
p.000047: participant recruitment, participant retention, and data accuracy and quality should all be monitored to ensure
p.000047: the scientific integrity of research results.
p.000047: The authors already have discussed (Section 2.8) the needs (1) to establish, in advance, criteria and standards for
p.000047: monitoring the research program in regard to both scientific and ethical issues; (2) to establish who
p.000047: will monitor and oversee the research progress (the monitoring and oversight authority, be it
p.000047: an individual, team, or review committee); and (3) to establish the roles, responsibilities, and authorities
p.000047: of the researchers and of the monitoring and oversight authority. The planning also should include steps
p.000047: to meet the IOM recommendations that researchers should “anticipate risks and behaviors that may be
p.000047: observed in the home… [and] develop anticipatory plans that specify how to assess and respond to risks when they
p.000047: are identified, and educate their staffs about the plan” (Recommendation 7.3, p. 144, NRC & IOM, 2005).
p.000047: Once the procedures and organization for monitoring and oversight of the observational study are approved by the IRB,
p.000047: it is the responsibility of the researchers and of the monitoring and oversight authority to ensure that the planned
p.000047: actions are implemented. Implementation of the monitoring and oversight function may include the following
p.000047: items.
p.000047: • Ensuring that procedures for identifying, reporting, and responding to anticipated or unanticipated adverse
p.000047: events and safety issues are in place and are being followed
p.000047:
p.000047:
p.000048: 48
p.000048:
p.000048: • Assessing and responding to risks when they are identified
p.000048: • Evaluating the performance and knowledge of the staff regarding identification of potential risks and the
p.000048: actions they should take
p.000048: • Implementing procedures for monitoring the informed consent process, participant behaviors, participant
p.000048: recruitment, participant retention, procedures to protect privacy and confidentiality, and other
p.000048: human requirements for adherence to the research protocol and compliance with ethical standards and with EPA’s
p.000048: human subjects rules
p.000048: • Ensuring that measurements and samples are collected as planned, and that data are reported on a timely basis
p.000048: • Evaluating whether the observed measurements exceed the pre-established threshold values and, if so,
p.000048: ensuring that reporting procedures and plans to respond to the potential risks are completed on a
p.000048: timely basis
p.000048: • Ensuring that quality assurance plans that define procedures for assessing and ensuring study
p.000048: protocol compliance are being met
p.000048: • Ensuring data quality targets are met through independent internal or external auditing
p.000048: requirements
p.000048: • Taking all warranted oversight actions to ensure the safety of the participants and the integrity of the
p.000048: study, including terminating the research study if appropriate
p.000048:
p.000048: References
p.000048: AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric Environmental Health. (2nd
p.000048: Edition). Elk Grove Village, IL: American Academy of Pediatrics.
p.000048:
p.000048: Beauchamp TL, Childress JF (2001). Principles of Biomedical Ethics. (5th Edition). New York, NY: Oxford University
p.000048: Press.
p.000048:
p.000048: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I⎯Environmental Protection Agency Part 26 Protection of Human
p.000048: Subjects. U.S. Code of Federal Regulations.
p.000048: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06. html [accessed August 2007].
p.000048:
p.000048: CIOMS (Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000048: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000048: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed June 2007].
p.000048: Emanuel, EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
p.000048:
p.000048: NCI (National Cancer Institute) (2001). Essential Elements of a Data and Safety Monitoring Plan for Clinical Trials
p.000048: Funded by the National Cancer Institute. Available: http://www3.cancer.gov/rrp/dsm_ess.html [accessed April 2007].
p.000048:
p.000048: NEI (National Eye Institute) (2001). National Eye Institute Guidelines for Data Monitoring and Oversight of
p.000048: Observational Studies. Available: http://www.nei.nih.gov/funding/datastudies.asp [accessed April 2007].
p.000048:
p.000048: NHLBI (National Heart Lung and Blood Institute) (2007). Monitoring Boards for Data and Safety (Interim Policy). Policy
p.000048: effective date: 14 May 2007. Available: http://public.nhlbi.nih.gov/ocr/home/GetPolicy.aspx?id=8 [accessed September
p.000048: 2007].
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p.000048: NHRPAC (National Human Research Protections Advisory Committee) (2002). Clarification of the status of third parties
p.000048: when referenced by human subjects in research. Available: http://www.hhs.gov/ohrp/nhrpac/documents/third.pdf [accessed
p.000048: April 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (2002). Extramural Projects - Application Instructions (03/15/2002) - Detailed
p.000048: Application Instructions for Certificate of Confidentiality Involving Extramural Research Projects. Certificates of
p.000048: Confidentiality. Available: http://grants.nih.gov/grants/policy/coc/index.htm. [accessed April 2007]
p.000048:
p.000048: NIH (National Institutes of Health) (2001). Protection of third party information in research: Recommendations of the
p.000048: National Institutes of Health to the Office for Human Research Protections. Available:
p.000048: http://bioethics.od.nih.gov/nih_third_party_rec.html [accessed March 2007].
p.000048:
p.000048: NIH (National Institutes of Health) (1998). NIH Guide: NIH Policy for Data and Safety Monitoring. Available:
p.000048: http://grants.nih.gov/grants/guide/notice-files/not98 084.html [accessed April 2007].
p.000048:
p.000048: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000048: Housing-Related Health Hazards Involving Children.
p.000048: Washington, DC: The National Academies Press. Available: http://books.nap.edu/catalog.php?record_id=11450 [accessed
p.000048: June 2007].
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p.000049: U.S. FDA (U.S. Food and Drug Administration) (2001). Draft Guidance for Clinical Trial Sponsors on the Establishment of
p.000049: Clinical Trial Data Monitoring Committees. U.S. Department of Health and Human Services, Food and Drug Administration,
p.000049: Rockville, MD. Available: http://www.fda.gov/cber/gdlns/clindatmon.pdf. [accessed April 2007].
p.000049: U.S. HHS (U.S. Department of Health and Human Services) (1993). Protecting Human Research Subjects: Institutional
p.000049: Review Board Guidebook. Office for Human Research Protections. Available: http://www.hhs.gov/ohrp/irb/irb_guidebook.htm
p.000049: [accessed June 2007].
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p.000050: 50
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p.000050:
p.000050: SECTION 5
p.000050: Creating an Appropriate Relationship Between the Participant and Researcher
p.000050:
p.000050:
p.000050:
p.000050: In observational human exposure studies, the researcher and the participant routinely interact
p.000050: with each other, often in the participant’s home or other private setting and often repeatedly over a
p.000050: number of days. The nature and setting of the interactions mean that exposure researchers should give special
p.000050: consideration to the many scientific and ethical issues that shape the relationship between participants and
p.000050: the researchers. In these studies, it is recommended that a strong relationship, built on
p.000050: openness and trust, should be developed between the researcher and participant. The nature of that
p.000050: relationship and the ethical principles underpinning an appropriate relationship are the focuses of this section of
p.000050: the document.
p.000050: This relationship should be established on the ethical values of respect for the participant’s autonomy and
p.000050: respect for their welfare. Emanuel and his co-authors find that these two ethical values translate into
p.000050: specific responsibilities for an ethical researcher in regard to informed consent and respect for potential and
p.000050: enrolled subjects (Emanuel et al., 2000). They describe the ethical principles for these responsible actions thusly,
p.000050: “Respect for potential and enrolled subjects is justified by multiple principles including beneficence,
p.000050: nonmaleficence, and respect for persons. Permitting subjects to withdraw and providing them additional information
p.000050: learned from the research are key aspects of respecting subject autonomy. Protecting confidentiality and monitoring
p.000050: well-being are motivated by respect for persons, beneficence, and nonmaleficence.” Section 4 already has
p.000050: described some of the particular concerns regarding privacy, confidentiality, and other issues
p.000050: related to observational human exposure studies. This section further describes elements of the relationship
p.000050: between researchers and participants that are important to consider and address during design and
p.000050: implementation of a study.
p.000050: Of course, the relationship between the researchers
p.000050: and the individual participants does not exist in isolation. The researcher-participant relationship may influence
p.000050: and be influenced by the relationship with the community in which the participant lives.
p.000050: Good, two- way communications are critical for the development and nourishment of an appropriate
p.000050: researcher-participant relationship. Although those two topics are the subject of the next sections of this document,
p.000050: elements from those topics unavoidably will color the discussions in this section as well.
p.000050: Researcher training is a key component for conducting research that incorporates human
p.000050: subject protections and fosters appropriate researcher-participant relationships. Most organizations require basic
p.000050: human subjects training on the essential elements for processes and procedures for research with human subjects. More
p.000050: in-depth training will improve researcher understanding in areas of the informed consent process, observational
p.000050: techniques, community-based research, and other topic areas. Such training will benefit principal
p.000050: investigators throughout the research study from the design stage through communication of research results.
p.000050: Training is also important for staff that will work directly or indirectly with research participants
p.000050: or their samples and data. This document can be used as both a training tool for researchers as well as a
p.000050: resource for designing training courses. There are a number of sources of training on human
p.000050: subjects protection. The Collaborative Institutional Training Initiative (CITI,
p.000050: http://www.citiprogram.org/) is a subscription service providing research ethics education to many institutions.
p.000050: Other training, such as that provided by the National Cancer Institute
p.000050: (http://cme.cancer.gov/clinicaltrials/lear ning/humanparticipant-protections.asp) and the U.S. Department
p.000050: of Health and Human Services (http://www.hrsa.gov/humansubjects/default.htm), are available
p.000050: on-line.
p.000050:
p.000050:
p.000051: 51
p.000051:
p.000051: 5.1 Informed Consent
p.000051: In observational human exposure studies, informed consent ensures that the participant
p.000051: accurately understands the range of risks and benefits (if any) associated with participation; emphasizes
p.000051: the voluntary nature of their participation; and provides essential protections to the participant. The
p.000051: three “pillars” of the informed consent process are (1) information;
p.000051: (2) comprehension; and (3) voluntary participation, or “voluntariness” (U.S. DHEW, 1979). Informed consent
p.000051: requires “provision of information to subjects about the purpose of the research, its procedures, potential
p.000051: risks, benefits, and alternatives, so that the individual understands this information and can
p.000051: make a voluntary decision whether to enroll and continue to participate” (Emanuel et al., 2000).
p.000051: The NRC & IOM document Ethical Considerations for Research on Housing-Related Health Hazards Involving
p.000051: Children (NRC & IOM, 2005) contains a comprehensive and very useful discussion of informed consent
p.000051: procedures and requirements in Chapter 6. The IOM report, Responsible Research: A Systems Approach to Protecting
p.000051: Research Participants, also includes a thoughtful discussion of participant-investigator
p.000051: interactions and the informed consent process (IOM, 2002). CIOMS also includes recommendations for both the
p.000051: process and content of informed consent (CIOMS, 2002). Some of the important points from those
p.000051: documents are summarized in Text Box 5-1, but the reader should refer to those documents for additional
p.000051: information about this topic.
p.000051: Federal regulations governing research that is either Federally conducted or Federally funded (i.e., all human subjects
p.000051: research at NERL) are codified in the CommonXRule. The regulations set forth requirements for both the content of an
p.000051: informed consent and the process for obtaining and documenting an individual’s informed consent (see Text
p.000051: Box 5-2).16 General regulatory requirements for the elements of informed consent are codified in the
p.000051: Common Rule at 40 CFR 26.116(a)(1)
p.000051: (8) (CFR, 2006). The regulations also prescribe the use of a written consent form and describe how informed
p.000051: consent is to be documented (at 40 CFR 26.117). The regulatory requirements for informed consent highlight a
p.000051: number of issues that a NERL researcher needs to consider in developing and administering the informed
p.000051: consent process and the consent form document. The discussion of these issues, arising from
p.000051: regulatory
p.000051:
p.000051:
p.000051: 16 An IRB may waive informed consent under some very limited conditions. See 40 CFR 26.116(c) and (d).
p.000051: requirements or identified in recent writings on ethical considerations in human subjects research, is
p.000051: grouped below, under the three pillars of informed consent:
p.000051: (1) information, (2) comprehension, and (3) voluntary participation.
p.000051:
p.000051: Text Box 5-1. Recommendations for Informed Consent In the United States and Internationally
p.000051: (1) Revitalize Informed Consent (IOM, 2002)
p.000051: Informed consent is a process, not a form. It is an on-going, interactive dialogue between researchXstaff and research
p.000051: participants with disclosure and exchange of relevant information, including assessment of understanding.
p.000051: Ethics Review Boards should ensure that the focus of both the informed consent process and the consent forms is on
p.000051: informing and protecting participants, not the research institution.
p.000051: (2) Strengthen Process of Parental Permission and Children’s Assent if Children Are Involved in Research (NRC & IOM,
p.000051: 2005)
p.000051: The process begins with a community-based discussion and concludes with an assurance that individual parents understand
p.000051: the essential elements of the research.
p.000051: Educate parents on issues critical to informed decision making and assess their degree of understanding.
p.000051: Use informational materials in the form that is most appropriate to convey information to potential participants.
p.000051: Consult with community representatives to ensure that information is complete, clear, and understandable, and that any
p.000051: payment will not be exploitive.
p.000051: Expand the perspective about what information about risks and benefits is needed to make an informed choice.
p.000051: Ethically, it is critical to assure that participants and parents understand the crucial features of the research
p.000051: effort.
p.000051: (3) Informed Consent Is a Decision To Participate by an Informed, Competent Individual Without Undue Coercion,
p.000051: Influence, or Intimidation (CIOMS, 2002)
p.000051: Informed consent is a process that takes time and resources.
p.000051: It is not a ritual recitation of text from a form but informative communication in language that suits the individual’s
p.000051: level of understanding.
p.000051: Consent is ethically obtained, considering language and cultural issues, and is documented.
p.000051: Material changes in conditions or procedures require that informed consent be renewed.
p.000051: Consent should explain how samples will be used in current research, and, if applicable, how samples may be used in
p.000051: future research.
p.000051:
p.000051:
p.000051:
p.000051: 5.1.1 Information
p.000051: Some items that researchers should keep in mind as they provide information to the study participants are
p.000051: summarized below. These items may be based on regulatory requirements or currently may
p.000051: be recommendations as ethical “best practices.”
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000052: 52
p.000052:
p.000052:
p.000052: Text Box 5-2. CommonXRule Requirements:
p.000052: Elements of Informed Consent
p.000052: (1) An explanation of the purposes of the research
p.000052: (2) The expected duration of the subject's participation
p.000052: (3) A description of the procedures to be followed and identification of any experimental procedures
p.000052: (4) A description of any reasonably foreseeable risks or discomforts to the subject
p.000052: (5) A description of any reasonably expected benefits to the subject or others
p.000052: (6) A disclosure of appropriate alternative procedures that might be advantageous to the subject
p.000052: (7) A description of the extent that confidentiality will be maintained
p.000052: (8) For research involving more than minimal risk, an explanation about whether compensation or medical treatments
p.000052: are available if injury occurs
p.000052: (9) An explanation of whom to contact with questions about the research or to report a research-related injury
p.000052: (10) A statement that participation is voluntary, refusal to participate will involve no penalty, and the subject may
p.000052: discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled
p.000052: (11*) A statement that the particular treatment or procedure may involve risks to the subject (or to the embryo or
p.000052: fetus, if the subject is or may become pregnant) that are currently unforeseeable
p.000052: (12*) Anticipated circumstances under which the subject's participation may be terminated by the investigator without
p.000052: regard to the subject's consent
p.000052: (13*) Any additional costs to the subject that may result from participation in the research
p.000052: (14*) The consequences of a subject's decision to withdraw from the research and procedures for orderly termination of
p.000052: participation by the subject
p.000052: (15*) A statement that significant new findings developed during the course of the research that may relate to the
p.000052: subject's willingness to continue participation will be provided to the subject.
p.000052: (16*) The approximate number of subjects in the study
p.000052: * Included if appropriate [40 CFR 26.116(b)]
p.000052:
p.000052:
p.000052:
p.000052: • The information “shall be in language understandable to the subject” (40 CFR 26.116). This may require forms
p.000052: to be written and administered in different languages during a study. For example, the National
p.000052: Children’s Study (NCS) plans to produce all consent materials in English and Spanish, with other
p.000052: translations made available as needed (NCS, 2007).
p.000052: Participants often find discussions with researchXstaff more useful than written consent forms (p. 103, NRC & IOM,
p.000052: 2005). NCS plans to pilot test an interactive, computer-based audio/video consent tool and to compare it
p.000052: with traditional written informed consent approaches (NCS, 2007).
p.000052: • The information being discussed, including the explanation of the purpose of the research and the
p.000052: description of the study procedures, should be written or discussed at a level that the participant can
p.000052: understand.17 The National Institutes of Health recommends writing consent forms as “plain language
p.000052: documents that explain the research in an honest, straightforward way” and suggest that doing so will
p.000052: help enhance public trust (Recommendation 11, NIH, 2005).
p.000052: • The consent form should contain sufficient information to describe the study procedures, but not
p.000052: so much information that it causes confusion and results in the participant not understanding the study. There
p.000052: is not agreement on what the appropriate level of information is. IRBs do not agree on the level of
p.000052: information; some require lengthy descriptions of the study, whereas others prefer concise information.
p.000052: Ultimately, the IRB dictates the language of the informed consent document, and the researcher will
p.000052: need to comply. It will benefit the researcher to discuss the consent process with their IRB when they develop
p.000052: the consent form document and process (p. 108, NRC & IOM, 2005).
p.000052: • In observational human exposure studies, information about the risks of the hazards being studied needs to be
p.000052: conveyed to the participants during the consent process. Information should be provided to the study participant
p.000052: on what hazards pertinent to the topic of the study may be present in the participant’s
p.000052: environment, particularly those microenvironments being studied, what hazards will continue to exist in
p.000052: those microenvironments after the research is completed, and how those hazards may adversely
p.000052: affect the participant’s health (NRC & IOM, 2005).
p.000052: • The informed consent process should describe whether any study results will be provided
p.000052: to
p.000052: Ethically, “language understandable to the subject”
p.000052: goes beyond simply using the appropriate language;
p.000052:
p.000052: the researcher is compelled also to consider readability and vocabulary (e.g., avoiding jargon
p.000052: or terminology that may be clear to the researcher but which may confuse or intimidate the potential subject)
p.000052: if the information is to be understandable.
p.000052: • Information may be presented orally in addition to an appropriately written document (40 CFR 26.117).
p.000052: 17 A survey of IRBs found that their readability standards ranged from 5th- to 10th-grade level (Paasche-Orlow et al.,
p.000052: 2003). Interestingly, the same report found that, 92% of the time, the sample consent forms provided by the IRBs did
p.000052: not meet their own readability standards. The NRC & IOM report (p. 107, NRC & IOM, 2005) discusses an NCI effort to
p.000052: simplify informed consent forms by using text targeted at 8th-grade reading level. More information about the NCI
p.000052: template may be found at www.nci.nih.gov/clinicaltrials/understanding/simplification-of-informed consent-docs/page2
p.000052: (accessed September 12, 2007).
p.000052:
p.000052:
p.000053: 53
p.000053:
p.000053: participants and, if so, how and when (p. 101, NRC & IOM, 2005).
p.000053: • For studies involving children as participants, it generally is regarded as desirable that the
p.000053: informed consent process should involve both parents (assuming that there are two competent
p.000053: parents available), and that the consent of both parents be obtained, if possible. The IRB may decide
p.000053: that the permission of one parent is sufficient, but only when certain risk-benefit conditions are met.18
p.000053: • For studies involving children as participants, it is desirable for those children with sufficient capacity
p.000053: to be involved in the consent process. Moreover, it is generally accepted that the child’s assent be obtained
p.000053: whenever this is developmentally possible and otherwise appropriate. Under both the EPA Rule and the HHS
p.000053: Rule, the IRB is responsible for determining that adequate provisions have been made for soliciting the assent of the
p.000053: children when, in the judgment of the IRB, the children are capable of providing assent. Assent, however, may
p.000053: be waived in those restricted circumstances in which consent may be waived under the Common Rule. Those
p.000053: circumstances and the required IRB documentation are described in the CommonXRule at 40 CFR 26.116(d).
p.000053: • The consent form should clearly state that participation is voluntary and that study
p.000053: participants may “discontinue participation at any time without any penalty or loss of benefits to which the
p.000053: subject is otherwise entitled” [40 CFR 26.116(a)(8)]. If a subject chooses to withdraw from a study, the
p.000053: consequences of their decision and the process for orderly withdrawal should be clearly
p.000053: explained [40 CFR 26.116(b)(4)].
p.000053: • The consent form should address any foreseeable potential future use of samples and data (CIOMS, 2002).
p.000053: For example, effects of environmental exposures on gene expression are potentially very important.
p.000053: Therefore, biologic specimens for DNA analysis may be obtained from participants in future studies. But, it
p.000053: is recognized that human genomic data are private, intimate, and sensitive, and they create
p.000053:
p.000053:
p.000053: 18 See the EPA Rule at 40 CFR 26.406(b) for observational research with children and the HHS Rule at 45XCFRX46.408(b)
p.000053: for all research with children. Under the EPA Rule, greater than minimal risk observational research with children that
p.000053: does not hold out the prospect of direct benefit to the child is not permitted under any circumstances. Under the HHS
p.000053: Rule, greater than minimal risk research involving children without the prospect of direct benefit is permitted in very
p.000053: limited circumstances, but the consent of both parents is required in those cases (unless one parent is deceased,
p.000053: unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and
p.000053: custody of the child).
p.000053: special concerns about the potential for discrimination, stigmatization, and impact on
p.000053: future employment or insurance. The informed consent process needs to explain what the plans may be
p.000053: for such specimens and recognize the rights of the subjects to decide about any such future use,
p.000053: including having the material destroyed. The informed consent process needs to explicitly discuss
p.000053: obtaining permission from participants on behalf of themselves and their child to obtain specimens for
p.000053: genetic analysis.
p.000053:
p.000053: 5.1.2 Comprehension
p.000053: Research participants frequently fail to understand the research protocols in which they agree to participate (NRC
p.000053: & IOM, 2005). In considering the ethical issues raised by the Grimes v. Kennedy Krieger case, the NRC & IOM
p.000053: committee “realized that the crucial issue regarding consent was not what information was
p.000053: contained in the consent forms, but rather what the parents understood about the study and the hazards
p.000053: present in the home before and after the study” (p. 19, NRC & IOM, 2005). The committee laments that “IRBs
p.000053: place their attention on consent forms rather than on the process of providing and discussing information” (p.
p.000053: 103, NRC & IOM, 2005). The IOM recommends that “the informed consent process should be an on-going,
p.000053: interactive dialogue between researchXstaff and research participants involving the disclosure and exchange of
p.000053: relevant information, discussion of that information, and assessment of the individual’s understanding of
p.000053: the discussion” (Recommendation 4.1, IOM, 2002). These comments emphasize how important true two-way
p.000053: communication is to comprehension, the second pillar in the informed consent process.
p.000053: The following items are a variety of issues concerning comprehension that NERL scientists should
p.000053: keep in mind as they develop an informed consent process in collaboration with the research team, the IRB and
p.000053: other peer reviewers, and EPA’s HSRRO. These items may be based on regulatory requirements or may simply be
p.000053: recommendations as ethical “best practices.”
p.000053: • Researchers need to assume responsibility for developing an interactive dialogue with
p.000053: participants for the exchange and discussion of relevant information as a part of the informed
p.000053: consent process, not just for conveying information. The dialogue should be ongoing, continuing throughout
p.000053: the research project (IOM, 2002).
p.000053: • The consent form and its content are only one part of the overall consent process. An equally important part
p.000053:
p.000053:
p.000054: 54
p.000054:
p.000054: is how information is conveyed to the participant outside of the written form itself.
p.000054: Participant comprehension is contingent on all elements of a comprehensive consent process that involves ongoing
p.000054: information exchange between researchers and participants, as well as a written informed consent
p.000054: document (NRC & IOM, 2005).
p.000054: • The most effective way to improve comprehension is by talking one-on-one with study participants.
p.000054: “Having a study team member or a neutral educator spend more time talking one-on-one to study
p.000054: participants appears to be the most effective way of improving research participants’ understanding”
p.000054: (Flory and Emanuel, 2004).
p.000054: • The information being exchanged (e.g., explanation of the purpose of the research, description of the study
p.000054: procedures) should be written at a level that the participant can understand (NRC & IOM, 2005).
p.000054: • The researcher should describe the benefits of participation in the study [40 CFR 26.116(a)(3)], but
p.000054: should not promise any outputs or outcomes that he or she cannot deliver. Participants often misunderstand the
p.000054: purpose of the research. The researchers also should attempt to reduce the likelihood of “therapeutic
p.000054: misconception”19 or related misunderstandings in which the participant anticipates a benefit that does
p.000054: not really exist, such as reduction of the hazard in an observational study (NRC & IOM, 2005).
p.000054: • The consent procedure should include some test of the participants to demonstrate that they truly understand the
p.000054: information that is being conveyed (IOM, 2002).
p.000054: • Tools to assess comprehension have been developed, but, as described in NRC & IOM (2005), there are no standard
p.000054: mechanisms for assessing comprehension. Tests for appropriate grade-level language can be performed, but
p.000054: additional comprehension testing should be considered as well (Flory and Emanuel, 2004).
p.000054: • Researchers need to develop innovative approaches to improve comprehension. Multimedia, such as video or graphics,
p.000054: may be used but have had limited success in the past (NRC & IOM, 2005; Flory and Emanuel, 2004). NCS
p.000054: currently is developing a highly sophisticated video consent tool that may be able to
p.000054:
p.000054:
p.000054: 19 Therapeutic misconception is a term that refers to an inaccurate understanding on the part of a research participant
p.000054: that a direct therapeutic benefit will be provided by virtue of participation in a clinical trial.
p.000054: Researchers performing observational human exposure studies should be aware of the potential for misunderstandings to
p.000054: arise that are analogous to the misunderstanding represented by the therapeutic misconception. Ensuring comprehension
p.000054: of the study and its expected results is important to this issue.
p.000054: serve as a model going forward. The video presentation will include embedded questions
p.000054: to assess the participant’s understanding of the key elements of NCS and what their participation
p.000054: will involve (NCS, 2007).
p.000054: • Development of written materials with appropriate languages and comprehension levels is only part of the
p.000054: communication challenge. In communities where languages other than English are spoken, it will be
p.000054: important that the research team be able to communicate orally with participants, often in ad hoc
p.000054: situations. Research protocols should address how translations will be accomplished. The use of
p.000054: untrained persons such as co-workers usually will not meet requirements for full understanding of human subject
p.000054: protections. Researchers should make plans for trained staff or trained community members, associated
p.000054: or affiliated with the research study, to be available for translations.
p.000054:
p.000054: 5.1.3 Voluntary Participation
p.000054: The third pillar of informed consent is voluntary participation. The Belmont Report emphasizes that
p.000054: participants “should understand clearly the range of risk and the voluntary nature of participation” [emphasis
p.000054: added]. The ethical principles of respect for persons and their autonomous decisions morally obligate
p.000054: the researcher to ensure that an individual’s decision to participate in a human research study is truly
p.000054: voluntary and uncoerced (Emanuel et al., 2000). A number of study characteristics may affect whether the
p.000054: participant’s actions are truly voluntary.
p.000054: • Access to study-dependent benefits or care that would otherwise not normally be received may impair
p.000054: voluntariness.
p.000054: • Voluntary participation also may be compromised when there is an existing relationship between the
p.000054: researcher and participants, such as employer and employee or teacher and student.
p.000054: • Restricted voluntariness may be an intrinsic part of belonging to certain vulnerable groups,
p.000054: including children, prisoners, handicapped persons, mentally disabled persons, and economically or
p.000054: educationally disadvantaged persons, or members of the military, for example. When research participants come from such
p.000054: groups, additional protections to insure voluntariness in the context of the research may be required
p.000054: (see also 40 CFR 26, Subparts B, C, and D).
p.000054: • Payments as incentives may have undueXinfluence and are discussed below.
p.000054:
p.000054:
p.000054:
p.000055: 55
p.000055:
p.000055: • Whether payments will lead to a coerced decision to participate often is difficult to determine without
p.000055: input from people from similar socioeconomic backgrounds as the participants (p. 111, NRC & IOM, 2005).
p.000055: Researchers should work with community representatives to develop a consent process that will be
p.000055: maximally effective in providing information, ensuring and documenting comprehension, and ensuring
p.000055: that participation is voluntary (also see Section 6).
p.000055: Researchers should remember that obtaining informed consent should be “an on-going, interactive
p.000055: dialogue . . . involving the disclosure and exchange of relevant information” (IOM, 2002): it is not
p.000055: simply having a consent form signed. The process is most effective when the researcher spends time with
p.000055: potential participants to discuss the study and to answer questions.
p.000055:
p.000055: 5.2 Payments to Research Participants
p.000055: The decision whether to pay research participants, including the appropriate level of payment,20 is
p.000055: a complex ethical issue. Monetary or nonmonetary payments are not ethical if they constitute an
p.000055: undue inducement for participants to assume research risks that they would not otherwise accept. On the other
p.000055: hand, it may be ethically appropriate to offer reasonable payments in some research studies. Indeed,
p.000055: payment of human subjects for their participation in scientific research is a common practice in the United
p.000055: States, with a history of well over 100 years (Grady, 2005). The difficulty for researchers and IRBs is that
p.000055: there is often little clear and uniform guidance for determining what constitutes “undue inducement”
p.000055: or “reasonable” payment for any particular research study, population, and level of risk. Additional
p.000055: considerations regarding payment to participants arise when working with vulnerable populations, including
p.000055: children.
p.000055:
p.000055:
p.000055:
p.000055:
p.000055: 20 There are many terms that may be found in the literature to describe both monetary and nonmonetary payments, like
p.000055: payment, remuneration, compensation, recompense, incentive, inducement, reimbursement, and reward. Each of these words
p.000055: has its own definition, and each word also may carry specific connotations. In general, these terms refer to money or
p.000055: other items that “are often given to acknowledge the time and inconvenience of participating in research or to
p.000055: reimburse participants for any costs they incur. The term compensation is often used in the context of compensation for
p.000055: research-related injuries” (p. 112, NRC & IOM, 2005). The authors have chosen to use “payment” as the general term for
p.000055: monetary and nonmonetary items provided to research subjects for their participation in the research. They may
p.000055: occasionally refer to compensation for research-related injuries, but the text should make it clear when they do.
p.000055: 5.2.1 Types and Amounts of Payments Offered in Research Studies
p.000055: Payments have been offered in a wide variety of research studies, ranging from clinical trials
p.000055: to behavioral and social research to observational human exposure studies. Payments can take various
p.000055: forms, including monetary payments (e.g., cash, gift certificates, reimbursement for expenses),
p.000055: nonmonetary payments (e.g., gifts, valuable information), or nothing at all (e.g., for a sense of
p.000055: altruism). Grady (2005) has described payment for the participation of research subjects as serving
p.000055: from one to four purposes: (1) an incentive, (2) compensation, (3) reimbursement, or
p.000055: (4) reward. Text Box 5-3 describes the roles that payments may serve, together with potential advantages
p.000055: and disadvantages or ethical concerns. The text comes mostly from Grady (2005) but builds also on the NRC & IOM
p.000055: document and other writings. (A number of authors have addressed issues associated with payments,
p.000055: including Ackerman, 1989; Dickert et al., 2002; Emanuel 2004; Erlen et al., 1999; Fry et al.,
p.000055: 2005; Grady, 2005; Grady et al., 2005; Iltis et al., 2006; IOM, 2004; NRC & IOM, 2005; Russell et al.,
p.000055: 2000; VanderWalde, 2005; Weise et al., 2002; Wendler et al., 2002). A number of specific issues or
p.000055: concerns regarding participant payments have been identified. Many researchers and ethicists argue that it
p.000055: is often appropriate to provide reasonable payment and have done so for many years. In the view of an NRC expert
p.000055: panel, the principles of “justice, fairness, and gratitude support payment to those who bear the burdens
p.000055: of research on behalf of society” (NRC, 2004).
p.000055: Direct reimbursement may be made to participants for out-of-pocket expenses for costs directly associated
p.000055: with participation in a study. These might include transportation costs, parking fees, or child
p.000055: care costs. When payment for time and burden is provided, it is often in the form of monetary
p.000055: payments. Different approaches may be considered for determining reasonable amounts for payment,
p.000055: including a set payment for each visit, a small daily payment, payment at the prevailing minimum hourly
p.000055: wage, or payment at some other hourly rate appropriate for the community⎯perhaps a
p.000055: prevailing rate for unskilled labor (Emanuel, 2004). Incentives to encourage enrollment are
p.000055: sometimes used when participants will receive little or no direct benefit from the research and can take
p.000055: the form of monetary or non-monetary payments. Incentives are kept modest so as not to impart undue
p.000055: influence. Researchers need to consider the possible effects of incentive payments on the potential
p.000055:
p.000055:
p.000056: 56
p.000056:
p.000056:
p.000056: Text Box 5-3. Payments for Participation of Research Subjects
p.000056: (based on Grady, 2005)
p.000056: Payment Serves As Amount Determined By Potential Advantages
p.000056: Potential Disadvantages
p.000056:
p.000056: Incentive Supply and demand; market rates
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: Compensation Standardized “wage” for time and effort, suggested to be commensurate with wages for
p.000056: unskilled, but essential jobs; additional payment for extra burdens such as endurance of uncomfortable procedures
p.000056: (a) More rapid recruitment
p.000056: (b) Completion bonuses encourage subject retention and high completion rate
p.000056: (c) Possibility of profit for participants
p.000056: (d) Little or no financial sacrifice by subject
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: (a) Recognizes contributions of participants
p.000056: (b) Uniform payment across studies
p.000056: (c) Equal pay for equal work
p.000056: (d) Less risk of undue inducement
p.000056: (a) Undue inducement possibly resulting in incomplete assessment of risks and benefits by subject; subject concealing
p.000056: information to ensure enrollment and retention
p.000056: (b) Competition between studies; better funded studies more likely to meet recruitment goals
p.000056: (c) Different levels of payment at different locations for multicenter research because of supply and demand
p.000056: (a) May have little impact on recruitment
p.000056: (b) Might undercompensate some subjects in relation to regular wage and preferentially attract others
p.000056:
p.000056:
p.000056: Provide “wage” for time and effort; base level of payment on some small fraction of participant’s or the community’s
p.000056: income, or on an appropriate hourly rate for the location, or on community-input about the appropriate level of payment
p.000056: (a) Recognizes contributions of participants
p.000056: (b) Decreases potential that payment would be undue inducement in some communities or locations and insufficient in
p.000056: others
p.000056: (c) Provides equivalent payment for participation across communities and locations (markets)
p.000056: (d) Less risk of undue inducement across study
p.000056: (a) Different levels of payment at different locations in multicenter research or in different communities
p.000056: (b) Unequal pay for equal work may violate one’s sense of justice
p.000056:
p.000056:
p.000056: Reimbursement Actual out-of-pocket cost to
p.000056: participant related to participation, such as parking, transportation, child care, cost of food samples, etc.
p.000056: (a) Lowers barriers to participation
p.000056: (b) Reduces burden and impact of research on participants
p.000056: (a) Few disadvantages
p.000056: (b) Possible differences in costs experienced by different participants
p.000056:
p.000056:
p.000056: Reward Token of appreciation at end of study
p.000056: (a) Expresses gratitude for contribution made
p.000056: (b) Not market dependent
p.000056: (c) Avoids undue inducement
p.000056: (a) Probably no impact on recruitment
p.000056: (b) No basis for consistency
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: for differential recruitment that could result in bias in the study sample.
p.000056: Determining appropriate level of payments or incentives for participants in a research study is
p.000056: complex. “No bright line distinguishes proper and reasonable payments to parents and children
p.000056: from payments that are inappropriate” (p. 214, IOM, 2004). The ethical issue is at what level might a
p.000056: payment change from being an incentive (an encouragement) to participate and become an inducement (the
p.000056: cause or reason) for participation. Many research organizations and IRBs do not have written policies or
p.000056: guidelines
p.000056:
p.000056: regarding the determination of reasonable payment. Decisions often are made based on the level
p.000056: of discomfort and burden, costs to participants, and population characteristics. However, large
p.000056: differences in payment levels have been found even in multisite studies in which the same protocol is
p.000056: administered across all sites.
p.000056: Grady et al. (2005) performed a survey of practices for paying research participants in the United States in
p.000056: Phase 1 to 4 clinical trials and physiologic, behavioral, and other types of research. Across 467
p.000056: studies of varying complexity that included payments, the median
p.000056:
p.000056:
p.000057: 57
p.000057:
p.000057: payment was $155 (mean $266, range $5 to $2,000). The basis for dollar amounts was infrequently described, with
p.000057: 19% of the payments based on time, and 12% based on the procedures. In a model of payment factors,
p.000057: studies with some prospect of therapeutic benefit, studies having at least one invasive procedure, and studies with
p.000057: greater numbers of clinic visits were significantly associated with higher dollar amounts. About 9.5%
p.000057: of the studies offered completion bonuses, and a similar percentage offered escalating payments for
p.000057: followup study visits.
p.000057:
p.000057: 5.2.2 Regulations and Guidance Regarding Payment to Research Participants
p.000057: There is little specific guidance regarding payments in Federal human research regulations. The CommonXRule and
p.000057: additional human subjects protections do not directly address payments to research participants, but the
p.000057: regulations do discuss providing additional safeguards for subjects vulnerable to coercion or undue
p.000057: influence [40 CFR 26.111(b)]. The NIH IRB guidebook advises IRBs to determine whether the rewards offered for
p.000057: participation in research constitute undue influence (U.S. HHS, 1993). According to the IRB guidebook undue
p.000057: inducement might blind prospective subjects to risks, impair their ability to exercise proper judgment, or may
p.000057: cause people to lie or to withhold information that would make them ineligible to enroll or continue
p.000057: participation.
p.000057: The U.S. Food and Drug Administration (FDA) has provided guidance for investigators and IRBs for clinical research
p.000057: studies (FDA, 1998). The guidance states that “payment to research subjects for participation in studies is not
p.000057: considered a benefit, it is a recruitment incentive.” FDA expects payments to accrue as the study progresses and not
p.000057: to be contingent on completing the study, although a “small proportion as an incentive for
p.000057: completion of the study is acceptable.” The guidance is concerned with the issue of coercion or undueXinfluence, and
p.000057: it recognizes the IRB as the responsible party for deciding what is or is not acceptable.
p.000057: The U.S. Office of Management and Budget (OMB) develops standards and guidelines for statistical surveys performed by
p.000057: the Federal government. Under Guideline 2.3.2, OMB states that, while incentives are not typically used in Federal
p.000057: surveys, agencies may consider use of respondent incentives if they believe incentives would be necessary
p.000057: to use for a particular survey to achieve data of sufficient quality for their intended use (OMB,
p.000057: 2006a). OMB requires that agencies provide a justification for giving incentives to respondents.
p.000057: Some
p.000057: of the factors cited by OMB to be addressed include those particularly relevant to observational
p.000057: human exposure studies, including unusual reporting burdens (keeping data logs for extended periods,
p.000057: coordinating study team visits, participating in a medical examination, etc.), complex study designs (such as
p.000057: studies requiring ongoing participation of respondents), and past experience, especially when there is
p.000057: evidence of attrition or poor response rates (OMB, 2006b). Although OMB primarily considers incentives with
p.000057: regard to survey response rates and data quality, researchers need to consider payments to
p.000057: participants, including participation incentives, in the broader context discussed in this section.
p.000057: CIOMS also provides guidance and commentary on this issue in the International Ethical Guidelines for Biomedical
p.000057: Research Involving Human Subjects (2002). Guideline 7 and the associated commentary emphasize that payments to
p.000057: subjects for expenses incurred because of their participating in a research study are legitimate. The guideline
p.000057: also allows payment for inconvenience and time spent, so long as the payments or other direct benefits are not
p.000057: “so extensive as to induce prospective subjects to consent to participate in research against their better
p.000057: judgment.”
p.000057: The approaches of HHS, FDA, and CIOMS above are consistent in not considering payments to be a benefit
p.000057: to research participants when considering risks versus benefits. All of the guidelines recognize the
p.000057: legitimacy of some recompense, but they all are concerned with the issue of undueXinfluence. “Payments or
p.000057: rewards that undermine a person’s capacity to exercise free choice invalidate consent” (CIOMS, 2002), and
p.000057: voluntariness is a pillar of legitimate informed consent.
p.000057: Text Box 5-4 lists some of the concerns about, and the reasons for, payment of participants.
p.000057: IRBs have considerable discretion with regard to payments and consider payments with regard to the
p.000057: specific circumstances of the research and of the population being studied. The issue of recompense
p.000057: can be a difficult but legitimate ethical issue involving weighing the different ethical principles
p.000057: of justice and fairness against the concerns about undueXinfluence and the invalidation of consent. Ethical
p.000057: review committees, including IRBs, need to consider many factors when determining when it is appropriate to
p.000057: offer payments to research participants and the level and form of payments when they are appropriate. Review
p.000057: committees also should consider how and when information on payments is communicated to prospective study
p.000057: participants.
p.000057:
p.000057:
p.000058: 58
p.000058:
p.000058:
p.000058: Text Box 5-4. Weighing the Ethical Issues About Payments
p.000058: Concerns about Payments Reasons for Payments
p.000058: • Payments may compromise • Recognizing participant voluntary participation.
p.000058: contributions to the
p.000058: • Participants may accept risks research and knowledge they would not otherwise gained
p.000058: accept. • Providing reimbursement
p.000058: • Participants may continue in a for direct and indirect research study beyond a point
p.000058: participant costs
p.000058: they might ordinarily have • Providing reasonable withdrawn.
p.000058: payment for the time and
p.000058: • Payments may differentially effort associated with encourage research
p.000058: participation in research participation by economically • Providing incentives for disadvantaged people.
p.000058: participation in studies
p.000058: • The offer of payments may with low risk but no or few cause guardians or parents to
p.000058: direct benefits
p.000058: not act in the best interests of • It is the just and fair thing incompetent persons or children to do
p.000058: for those who bear in their care. burdens of research on
p.000058: • Persons in different behalf of society. circumstances may view the
p.000058: same amount of payment quite differently.
p.000058: • Payments may alter the composition of the study sample and potentially could compromise study integrity.
p.000058: activities is thus justified on the grounds of fairness” (p. 112, NRC & IOM, 2005).
p.000058: Similarly, the IOM Committee on Clinical Research Involving Children found that “certain types of
p.000058: payments to parents or adolescents are usually if not always acceptable, for example, reimbursement
p.000058: for reasonable expenses that are necessary for research participation. The specifics may vary, but
p.000058: examples of reasonable expenses are costs of transportation to the research site, parking, lodging, meals,
p.000058: and babysitting. Other payments are never appropriate in pediatric research, for example, paying parents
p.000058: for the use of their child in research” (pp. 225-6, IOM, 2004).21
p.000058: The IOM committee recommends establishing policies on acceptable and unacceptable types of
p.000058: payments. They also recommend that the policies disclose any recompense in a full and open
p.000058: process,22 while not overemphasizing any recompense.
p.000058: Although the NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving
p.000058: Children and the IOM Committee on Clinical Research Involving Children both concluded that it is appropriate to
p.000058: reimburse expenses or compensate for time or inconvenience, neither committee endorsed incentive
p.000058: payments to parents. In Europe, too, incentive payments to induce parents to allow their children to
p.000058: 5.2.3 Payments When Children or Other
p.000058: Vulnerable Populations Are Involved
p.000058:
p.000058: It is essential that special care be taken with regard to payments when members of vulnerable populations are
p.000058: included in research studies. Vulnerable populations may include children and adolescents, those with
p.000058: cognitive impairments because of medical conditions or age, economically disadvantaged persons, and prisoners. These
p.000058: populations often are not capable of making autonomous, fully informed decisions regarding risks and
p.000058: benefits, or they may be particularly vulnerable to undueXinfluence resulting from the offer of a payment for
p.000058: research participation. In addition, payments made directly to parents or guardians could alter
p.000058: judgment regarding the best interests of minor or incompetent persons in their care.
p.000058: The ethical concern is that too high a payment may “undermine free and informed consent by leading parents
p.000058: to expose their children to unacceptable risks” (NRC & IOM, 2005). The NRC & IOM committee recognized
p.000058: that some commentators argued that children should never be paid, and that parents ought not to be paid to
p.000058: enroll their children in research. Yet, on balance, the committee felt that “reimbursement for expenses and some
p.000058: modest payment for time spent in research
p.000058: 21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or payments to parents and children as
p.000058: gestures of appreciation, investigators may also—if they minimize the potential for undueXinfluence—act ethically to
p.000058: reduce certain barriers to research participation when they
p.000058: • reimburse reasonable expenses directly related to a child’s participation in research
p.000058: • provide reasonable, age-appropriate compensation for children based on the time involved in research that does not
p.000058: offer the prospect of direct benefit, and
p.000058: • offer evening or weekend hours, on-site child care, and other reasonable accommodations for parental work and
p.000058: family commitments.”
p.000058: 22 In recommending an open process, the IOM committee chose to reject the
p.000058: arguments from the American Academy of Pediatrics that “any token payment to children for participating in research
p.000058: should not be discussed with them until after research is completed for fear of unduly influencing their decisions
p.000058: (AAP, 2003)…. On balance, the committee agrees that it is best to mention token or other payments during the permission
p.000058: and assent processes” (p. 215, IOM, 2004).
p.000058: The IOM Recommendation 6.1 states, “Institutional review boards, research institutions, and sponsors of research that
p.000058: includes children and adolescents should adopt explicit written policies on acceptable and unacceptable types and
p.000058: amounts of payments related to research participation. These policies should specify that investigators
p.000058: • Disclose the amount, the recipient, the timing, and the purpose (e.g., an expense reimbursement or a token of
p.000058: appreciation to a child) of any payments as part of the process of seeking parents’ permission, and, as appropriate,
p.000058: children’s assent to research participation;
p.000058: • Avoid emphasis on payments or descriptions of payments as benefits of participating in research during the
p.000058: permission or assent procedures; and
p.000058: • Obtain institutional review board approval for the disclosure of information about payments in advertisements and
p.000058: in permission and assent forms and procedures.”
p.000058:
p.000058:
p.000059: 59
p.000059:
p.000059: participate in research are unacceptable. The European Union requires that clinical trials on minors
p.000059: be undertaken only if “no incentives or financial inducements are given except compensation”
p.000059: (European Parliament, 2001).
p.000059: Payment for participation of children in research also is discussed in the literature. Diekema
p.000059: (2005) emphasizes the need to ensure that payments do not distort parental decisionmaking and do not tempt
p.000059: parents to consider other issues than the welfare of their child. Similarly, Menikoff (2005) suggested that
p.000059: there need to be relatively robust protections in place to ensure that families do not change their behaviors
p.000059: to participate in a study. He suggested that these may include determining payment as a percentage of a family’s
p.000059: income and developing criteria for documenting that behaviors have not changed to be eligible for participation in a
p.000059: study. He suggested that, for a study of pesticides, potential study participants provide documentation (such as
p.000059: receipts) that they routinely have been using a commercial pesticide service. This may be difficult
p.000059: for potential participants to do if they do not save receipts, and it would exclude all potential
p.000059: participants who purchase products and apply pesticides themselves. This likely would affect the study
p.000059: objectives and generalizability of the data collected. A survey of investigators (Iltis et al., 2006) found that
p.000059: payments were made in 52% of the pediatric research studies surveyed, and that payment practices varied,
p.000059: as did the reasons for decisions regarding payments. They found a range of payment values separated
p.000059: across cash, gifts, items, vouchers, and other categories. A survey of IRBs (Weise et al., 2002) found that payment
p.000059: for participation in research was allowed by 66% of responding institutions, but that many IRBs did not have
p.000059: specific policies, and that there was considerable variability regarding the basis for decisions on
p.000059: payments in studies with children. The types of payments included money, certificates, and bonds with large
p.000059: ranges in the amounts of payments for approved pediatric research. This research shows a lack of consistency and
p.000059: the need for guidance and institutional policies that describe acceptable and unacceptable
p.000059: payments and the basis for the amount of any payments.
p.000059: The NRC & IOM Committee on Ethical Issues in Housing-Related Health Hazard Research Involving Children
p.000059: described many of the ethical considerations, practices, and policies regarding payments (NRC & IOM, 2005)
p.000059: for research conducted in the participants’ homes, rather than in a clinical facility. The research
p.000059: setting is similar to the setting of most observational
p.000059: human exposure studies, and the committee’s commentary and recommendations are also relevant. The
p.000059: committee notes that it would be unfair to expect families to make considerable sacrifices to
p.000059: participate in a time-consuming activity designed to advance generalizable scientific knowledge,
p.000059: rather than benefit themselves directly, and that payment for reimbursement of expenses and modest payment for
p.000059: time spent in research activities is justified on the grounds of fairness. But the committee then warns that if
p.000059: payments are too high, they may distort parents’ decisions about enrolling their children. The committee also
p.000059: found that “how the payment is made may also result in undueXinfluence. For example, if payment for a long-term
p.000059: follow-up study is made in a lump sum and only if the subjects complete the entire study, then it
p.000059: could constitute an undueXinfluence to stay in the study. If, on the other hand, the money is paid weekly, the
p.000059: effect would not constitute an undueXinfluence.”
p.000059: The NRC & IOM committee recognizes that the issue of payment for participation in research is
p.000059: controversial. They also discuss how “countervailing ethical guidelines” may complicate the issues even more.
p.000059: Citing Wendler et al. (2002), the NRC & IOM committee points out that payments that are trivial
p.000059: for some families may be substantial for low-income or disadvantaged families. “Yet to pay
p.000059: economically disadvantaged families less than more affluent families for participating in the research is
p.000059: unfair because it requires similar sacrifices of time and inconvenience from both” (p. 113, NRC & IOM, 2005).
p.000059: Similar ethical quandaries can arise in multisite studies with differing costs for living. If the same payment
p.000059: is used in high-cost cities as in low-cost areas, the payment may be inadequate to gain sufficient
p.000059: enrollment in the high-cost area, whereas the same dollar amount may be “coercive” in the low-cost area. The NRC & IOM
p.000059: committee notes that a similar situation can arise when a study enrolls participants from diverse
p.000059: socioeconomic backgrounds. There are social justice concerns that poorer people might incur a disproportionate
p.000059: share of research risk and burden if payments induce unequal participation rates in the population. Decisions
p.000059: regarding payment for research participation will require careful consideration by IRBs when economically
p.000059: disadvantaged people may be enrolled. Community advisory boards (CABs) can be very important in helping
p.000059: researchers and IRBs determine what is appropriate with regard to payments within their community.
p.000059:
p.000059:
p.000059:
p.000059:
p.000060: 60
p.000060:
p.000060: 5.2.4 Payments in Observational Human Exposure Studies
p.000060: Observational human exposure studies most often involve minimal risks to study participants and few direct
p.000060: benefits, but may require considerable time and burden for participation. Study requirements can include multiple
p.000060: in-home visits; the burden of wearing personal air monitors for one or more 24-hour period; preparing and providing
p.000060: duplicate diet samples; collection of environmental samples inside and outside the home; completing
p.000060: questionnaires, food diaries, and time- activity diaries; and providing urine, blood, saliva, or hair
p.000060: samples. Monetary payments often have been included in these studies, with the level of payment
p.000060: related to the number of study days or visits or the specific kinds of environmental and biological
p.000060: samples and information that are collected or provided. Payment for direct participant costs has been included
p.000060: in some studies, such as a reasonable payment for providing researchers with duplicate diet samples.
p.000060: NERL scientists should review the commentary and recommendations in the literature before devising a
p.000060: payment program as part of a research protocol, especially the two recent National Academies of Science
p.000060: documents, Ethical Issues in Housing-Related Health Hazard Research Involving Children (NRC and IOM, 2005)
p.000060: and Ethical Conduct of Clinical Research Involving Children (IOM, 2004). They should seek
p.000060: guidance from EPA’s HSRRO to determine EPA’s latest policies and guidance in this regard. Input also should be sought
p.000060: from community representatives to ensure that any payment is adequate to compensate for expenses and reward
p.000060: participation, but that the payment is not so high as to constitute undue influence or coercion in the
p.000060: community. If the study includes several followup visits over a long term, NERL researchers should ensure that payment
p.000060: is made incrementally as the NRC & IOM committee suggested. NERL scientists also should adopt the IOM
p.000060: Recommendations 6.1 and 6.2, including ensuring that any payment should be for appropriate purposes
p.000060: and age-appropriate, and that the process should be open and fully disclosed, while not overly
p.000060: emphasizing payments during the recruiting or informed consent phases. The final decisions about the ethics of
p.000060: payments rest with the IRB, which will review, modify as needed, and approve the research protocol, and with the EPA
p.000060: HSRRO, who has final authority to approve, modify, or disapprove all of NERL’s human subjects research
p.000060: efforts.
p.000060: 5.3 Research Rights and Grievance Procedures
p.000060: Protecting the research rights of participants and providing independent access to information regarding
p.000060: those rights and to grievance procedures is an important element in developing and maintaining appropriate
p.000060: participant-investigator relationships. As part of the informed consent process, the Common Rule
p.000060: requires “An explanation of whom to contact for answers to pertinent questions about the research and
p.000060: human subjects’ rights, and whom to contact in the event of a research-related injury to the
p.000060: subject” [40 CFR 26.116(a)(7)].
p.000060: Information about the research often best can be answered by the researcher. However, it may benefit
p.000060: researchers and participants if information about the research can be obtained from or confirmed by a trusted
p.000060: independent person or organization. Participants also need to know how they can contact
p.000060: someone, independent from the researcher, who can answer questions concerning the rights of research
p.000060: participants and provide information on grievance procedures and research-related injuries. These questions
p.000060: could be addressed to the IRB, an ombudsman, an ethics committee, or other knowledgeable
p.000060: administrative body. Consent documents are expected to have at least two names with appropriate
p.000060: telephone contact information⎯one that can provide information regarding the research and
p.000060: another that can provide information regarding their rights as research participants. Grievance
p.000060: procedures should be structured so that grievances reach the approving IRBs and sponsoring
p.000060: organizations.
p.000060:
p.000060: 5.3.1 Ombudsman
p.000060: An ombudsman is a neutral independent advocate for research participants (and their families or guardians, where
p.000060: applicable). Institutions and IRBs may recommend or require the use of an ombudsman in
p.000060: certain types of research studies, particularly those seeking to study vulnerable populations.
p.000060: Ombudsmen can fill several roles as participant advocates. They may be an independent source of information
p.000060: regarding the study. They may be present during the informed consent process to ensure that risks, benefits,
p.000060: and study requirements are communicated correctly and understood by potential participants
p.000060: or their guardians. An ombudsman may be used in studies involving prisoners or military personnel to
p.000060: ensure that there is no coercion to participate. And the ombudsman may
p.000060:
p.000060:
p.000060:
p.000061: 61
p.000061:
p.000061: communicate problems or grievances raised by research participants to the IRB and sponsoring organization.
p.000061:
p.000061: 5.3.2 Community Advisory Board
p.000061: CABs can help ensure that participant rights are considered and addressed during the study design and can
p.000061: play an important role in monitoring the research process. Community members may choose to seek
p.000061: information about the study from the advisory panel, as an independent entity, before deciding whether to enroll.
p.000061: Representatives from such advisory boards can be included in the research team that designs the study (see
p.000061: Section 2.3). The role of CABs is more fully discussed in Section 6.
p.000061:
p.000061: 5.4 Creating a Supportive Environment for Research and Interaction
p.000061: It is recommended that researchers and institutions strive to create a supportive environment for research
p.000061: and interaction with research participants and communities. At the personal level,
p.000061: this means researchers building trust with individuals and treating them with respect. Following the IOM
p.000061: recommendations about the informed consent process⎯that it “should be an on-going, interactive dialogue between
p.000061: researchXstaff and research participants involving the disclosure and exchange of relevant information,
p.000061: discussion of that information, and assessment of the individual’s understanding of the discussion”
p.000061: (Recommendation 4.1, IOM, 2002)⎯should go a long way in establishing a supportive environment with the
p.000061: individual participants. At the community level, engagement of the community throughout the design, conduct of the
p.000061: study, and follow- up will support trust-building and positive interactions. Developing and providing this
p.000061: kind of support can be challenging in large-scale studies, and particularly those that cross communities or are
p.000061: conducted across large geographic areas. Institutions need to recognize the need for, and value of
p.000061: creating supportive research environments by providing adequate funding because effective interaction takes
p.000061: considerable time and effort.
p.000061: Many of the factors that create a supportive environment for research participants are described in
p.000061: the Report and Recommendations on Public Trust in Clinical Research for the NIH Director from the
p.000061: Director’s Council of Public Representatives (COPR) (NIH, 2005). Although the advice from this workshop was
p.000061: developed in the context of NIH-supported clinical research, many of the recommendations are applicable to
p.000061: observational human exposure studies and human subject research in general. A summary
p.000061: of
p.000061: recommendations from the report for enhancing public trust is provided in Appendix D. The recommendations are
p.000061: focused on the following areas.
p.000061: • Building trust through community partnerships
p.000061: • Building relationships with patients (participants) (True partnerships with patients may not be possible,
p.000061: but bidirectional relationships must be enhanced.)
p.000061: • Building partnerships with community providers
p.000061: • Building trust in scientists
p.000061: • Building trust in the (EPA) and scientific research.
p.000061:
p.000061: 5.5 Recruitment Strategies
p.000061: Many strategies are used to select and recruit people into research studies requiring human participation. The IRB is
p.000061: responsible for reviewing the selection process to ensure that it is, above all, equitable. The requirement for
p.000061: IRB review is stated in 40 CFR 26.111(a)3.
p.000061: Selection of subjects is equitable. In making this assessment, the IRB should take into account the
p.000061: purposes of the research and the setting in which the research will be conducted and should be particularly cognizant
p.000061: of the special problems of research involving vulnerable populations, such as children, prisoners,
p.000061: pregnant women, mentally disabled persons, or economically or educationally disadvantaged
p.000061: persons.
p.000061: The IRB guidebook is an excellent resource for consideration of concerns and elements for equitable
p.000061: participant selection (U.S. HHS, 1993). It states that “Defining the appropriate group of subjects
p.000061: for a research project involves a variety of factors⎯ requirements of scientific design,
p.000061: susceptibility to risk, likelihood of benefit, practicability, and considerations of fairness.” The IRB
p.000061: guidebook raises a number of points to consider in the process for selection of human participants (see Text Box
p.000061: 5-5).
p.000061: Various participant recruitment strategies may be used depending on the type of research being performed and the
p.000061: population of interest. This section addresses the strategies and approaches for identifying and contacting people and
p.000061: subsequent recruitment into a research study. Sampling design approaches and issues, such as statistical
p.000061: issues regarding representative and nonrandom sampling designs, oversampling of subpopulations, and environmental
p.000061: justice considerations are part of the study design process described in Section 2 and are critical
p.000061: for deciding which recruitment approaches will be used.
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000062: 62
p.000062:
p.000062:
p.000062: Text Box 5-5. IRB Guidebook Issues on Identifying Subjects
p.000062: 1. Who will bear the burden? Who will reap the benefits?
p.000062: 2. Is there a disproportionate burden on any single group?
p.000062: 3. Is the proposed subject population required or justified?
p.000062: 4. Are there susceptible groups of people who should be excluded from the research?
p.000062: 5. Are anticipated benefits distributed fairly? Do others have a greater need to receive any of the anticipated
p.000062: benefits?
p.000062: 6. Are the research burdens distributed fairly?
p.000062: 7. Will any special physiological, psychological, or social characteristics of the subject group pose special risks
p.000062: for them?
p.000062: 8. Would it be possible to conduct the study with other, less vulnerable subjects?
p.000062: 9. Has the selection process overprotected potential subjects who are considered vulnerable (e.g., children,
p.000062: cognitively impaired, economically or educationally disadvantaged persons, patients of researchers, seriously ill
p.000062: persons), so that they are denied opportunities to participate in research?
p.000062: 10. If the subjects are susceptible to pressures, are there mechanisms to reduce the pressures or minimize their
p.000062: impact?
p.000062:
p.000062:
p.000062: Some of the common approaches for identifying and making initial contact with potential participants include, but are
p.000062: not limited to
p.000062: • direct telephone or in-person contact with a person selected through a statistical sampling process
p.000062: to obtain a representative sample of the population being studied;
p.000062: • use of print or other media advertisements, often used to recruit people in a community with specific
p.000062: characteristics;
p.000062: • advertisement or word-of-mouth contacts through community groups, civic organizations, or other types of
p.000062: organizations; and
p.000062: • recruitment at physicians’ offices, hospitals, and clinics or at churches, schools, or other
p.000062: social institutions, either in person or through the use of advertisements or study brochures.
p.000062: CABs can be consulted regarding proposed approaches for recruitment in community-based
p.000062: research. All procedures and materials for participant recruitment are reviewed and approved by the IRB prior to
p.000062: implementation. Some of the materials prepared for recruitment might include the following.
p.000062: • Recruitment scripts⎯prepared scripts used for in- person or telephone study information and recruitment
p.000062: contacts
p.000062: • Printed materials⎯brochures, flyers, newspaper advertisements, letters, and information articles
p.000062: • Audio/visual materials⎯radio and television scripts, video segments, public service announcements
p.000062: • Internet postings⎯study announcements and information, links to study materials, links to
p.000062: related information.
p.000062: The IRB reviews all recruitment material to ensure that it does not adversely affect the informed
p.000062: consent process, is consistent with the study protocol, and is likely to result in equitable participant
p.000062: selection. IRBs will carefully consider how information regarding payment for participation is
p.000062: presented to potential participants so as not to create undueXinfluence.
p.000062: Participant recruitment may be performed directly by the researcher or staff members of the researcher’s
p.000062: organization, or other individuals or organizations may be asked to recruit or make initial informational
p.000062: contacts with potential participants. All persons involved in recruiting must adhere to the procedures
p.000062: and materials approved by the IRB. It is recommended that sponsoring organizations should not pay recruiters
p.000062: on a per- individual basis to minimize the likelihood that individual recruiters will put undue
p.000062: pressure on potential participants to enroll.
p.000062:
p.000062: 5.6 Retention Strategies
p.000062: Some observational human exposure studies require only a single visit or a single set of visits with a
p.000062: participant over a relatively short time period (e.g., 24 hours or 1 week). Other studies may involve
p.000062: repeated interaction with participants over longer periods of time. Longitudinal study designs require retention
p.000062: strategies that ensure that adequate sample sizes are maintained for meeting study objectives. It is
p.000062: recommended that researchers and IRBs evaluate the level of burden in longitudinal studies and ensure
p.000062: that retention strategies are not likely to create conditions of coercion or undueXinfluence.
p.000062: Some of the common strategies for maintaining high retention rates in longitudinal studies are listed in Text
p.000062: Box 5-6.
p.000062:
p.000062: Text Box 5-6. Common Strategies for Maintaining High Retention Rates in Longitudinal Studies
p.000062: • Developing and maintaining a strong study identity
p.000062: • Building participant trust
p.000062: • Communicating regularly with participants
p.000062: • Providing feedback that is of use to participants
p.000062: • Maintaining confidentiality
p.000062: • Incorporating active participant tracking mechanisms
p.000062: • Maintaining reasonable levels of burden
p.000062: • Providing periodic tokens of appreciation
p.000062: • Providing reasonable levels of payment at each time point, sometimes including escalating payments or a higher
p.000062: final payment for completion of all study activities
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000063: 63
p.000063:
p.000063: It is important that strategies that use payments to encourage retention should be carefully
p.000063: scrutinized against the possibility that they will result in undueXinfluence or diminish voluntary
p.000063: participation. Payments that cover expenses and for time and burden at each visit have to be reasonable, and
p.000063: researchers and IRBs should consider whether the cumulative level of payments over time or the use of escalating
p.000063: payments or final bonus payments might present undue influence on decisionmaking regarding
p.000063: participation. Participants have to feel capable of withdrawing from participation at any time, and escalating
p.000063: payments or completion bonuses can impact decisions to withdraw. Withholding all payment until all study
p.000063: visits are completed or making payment contingent on completing all activities is not an acceptable practice in
p.000063: most longitudinal studies because it can diminish the capacity for voluntary participation. (See the
p.000063: discussion about payment issues in long-term studies in Section 5.2.3.)
p.000063: People are more likely to continue active participation in longitudinal studies when they
p.000063: believe that the research is important, and that they are making a valuable contribution, are receiving regular
p.000063: feedback, and are treated with courtesy and respect by researchers. Observational human exposure studies
p.000063: sometimes involve substantial burdens of time and effort. Over long periods, this level of burden can reduce retention.
p.000063: It may be necessary to develop novel methods that reduce participant time and effort or to focus the study
p.000063: design so that fewer study procedures are implemented at any time point. Because the time needed to analyze
p.000063: samples, verify results, and perform data analyses can be long, it may be difficult to provide timely
p.000063: feedback to participants in observational human exposure studies. Researchers might consider including
p.000063: simple measures that can provide immediate and useful information of value to participants to
p.000063: encourage continued participation. Effective use of these strategies will reduce the need for
p.000063: higher payments to encourage retention.
p.000063:
p.000063: 5.7 Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk
p.000063: Researchers and IRBs need to ensure that the procedures and materials used to recruit and retain study
p.000063: participants in observational human exposure studies do not “undermine free and informed consent by leading
p.000063: parents to expose their children to unacceptable risks. (NRC and IOM, 2005)” Payments in these
p.000063: studies should not be so high that they would cause an undue
p.000063: inducement for a participant to use a product they would not normally use or to perform an activity that they
p.000063: would not normally perform. Not only would this bias the study results but may lead to higher than
p.000063: normal levels of exposure. Alternatively, the act of studying one set of conditions or activities in an observational
p.000063: human exposure study could lead participants to assume that those conditions or activities involve substantial
p.000063: risk. In response, they subsequently may change their activities in ways that could lead to possibly higher
p.000063: risks. The potential for such unintentional outcomes is difficult for researchers to gauge but requires
p.000063: researcher caution in how information and results are conveyed. However, if the informed consent process is
p.000063: truly “an on-going, interactive dialogue . . . involving the disclosure and exchange of relevant
p.000063: information,” then such misunderstandings should be minimized.
p.000063:
p.000063: References
p.000063: AAP (American Academy of Pediatrics Committee on Environmental Health) (2003). Pediatric and Environmental Health. (2nd
p.000063: Edition). Elk Grove Village, IL: American Academy of Pediatrics.
p.000063:
p.000063: Ackerman TF (1989). An ethical framework for the practice of paying research subjects. IRB 11(4):1-4.
p.000063:
p.000063: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000063: Subjects. U.S. Code of Federal Regulations.
p.000063: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/ 40cfr26_06.html [accessed 12 June 2007].
p.000063:
p.000063: CIOMS (The Council for International Organizations of Medical Sciences) (2002). International Ethical Guidelines for
p.000063: Biomedical Research Involving Human Subjects. World Health Organization. Geneva, Switzerland. Available:
p.000063: http://www.cioms.ch/frame_guidelines_nov_2002.htm [accessed 12 June 2007].
p.000063:
p.000063: Diekema DS (2005) “Payments for Participation of Children in Research.” Chapter in: Kodish, E, Editor. Ethics and
p.000063: Research with Children: A Case-Based Approach. New York, NY: Oxford University Press. 143-160.
p.000063:
p.000063: Dickert N, Emanuel E, Grady C (2002). Paying research subjects: an analysis of current policies. Ann Intern Med
p.000063: 136(5):368-373.
p.000063:
p.000063: Emanuel EJ (2004). Ending concerns about undue inducement. J Law Med Ethics 32(1):100-105.
p.000063:
p.000063: Emanuel, EJ, Wendler D, Grady C (2000). What makes clinical research ethical? JAMA 283(20): 2701-2711.
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p.000064: European Parliament (2001). On the approximation of the laws, regulations, and administrative provisions of the Member
p.000064: States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products
p.000064: for human use. Directive 2001/20/EC Article 4(d) of the European Parliament and of the Council of 4 April 2001.
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p.000064: Flory J, Emanuel E (2004). Interventions to improve research participants’ understanding in informed consent for
p.000064: research: a systematic review. JAMA 292(13):1593-1601.
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p.000064: Fry CL, Ritter A, Baldwin S, Bowen KJ, Gardiner P, Holt T, Jenkinson R, Johnston J (2005). Paying research
p.000064: participants: a study of current practices in Australia. J Med Ethics 31:542-547.
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p.000064: Grady, C (2005) Payment of clinical research subjects. J Clin Invest 115:1681-1687.
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p.000064: Grady C, Dickert N, Jawetz T, Gensler G, Emanuel E (2005). An analysis of U.S. practices of paying research
p.000064: participants. Contemp Clin Trials 26:365-375.
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p.000064: Iltis AS, DeVader S, Matsuo H (2006). Payments to children and adolescents enrolled in research: a pilot study.
p.000064: Pediatrics 118(4):1546-1552.
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p.000064: IOM (Institute of Medicine) (2004). Ethical Conduct of Clinical Research Involving Children. Marilyn J. Field and
p.000064: Richard E. Behrman (eds). Washington, DC: The National Academies Press.
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p.000064: IOM (Institute of Medicine) (2002). Responsible Research: A Systems Approach to Protecting Research Participants.
p.000064: Daniel D. Federman, Kathi E. Hanna, and Laura Lyman Rodriguez (eds). Washington, DC: The National Academies Press.
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p.000064: Res Law Policy Rep 4(14):586-512.
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p.000064: NCS (National Children’s Study) (2007) Research Plan, Volume 1, Version 1.1, June 20, 2007. Available:
p.000064: www.nationalchildrensstudy.gov/research/research_plan/upl oad/Research_Plan_Volume_1.pdf [accessed 12 September 2007.].
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p.000064: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for the NIH
p.000064: Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health, Director’s
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p.000064: 2005. Available: http://copr.nih.gov/reports/public_trust.asp
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p.000064: NRC (National Research Council) (2004) Research Priorities for Airborne Particulate Matter: IV. Continuing Research
p.000064: Progress. Washington, DC: The National Academies Press. Available: http://books.nap.edu/openbook.php?record_id=10957
p.000064: [accessed 16 August 2007].
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p.000064: NRC & IOM (National Research Council and Institute of Medicine) (2005). Ethical Considerations for Research on
p.000064: Housing-Related Health Hazards Involving Children.
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p.000064: June 2007].
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p.000064: Collection Methodology. http://www.whitehouse.gov/omb/inforeg/statpolicy/standard s_stat_surveys.pdf
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p.000064: Collection. Office of Information and Regulatory Affairs. January, 2006.
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p.000064: Paasche-Orlow MK, Taylor HA, Brancati FL (2003). Readability standards for informed-consent forms as compared with
p.000064: actual readability. N Engl J Med 348(8):721 6.
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p.000064: Russell ML, Moralejo DG, Burgess ED. (2000). Paying research subjects: participants' perspectives. J Med Ethics
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p.000064: Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: National Commission for the Protection
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p.000065: VanderWalde A (2005). Undue inducement: the only objection to payment? Am J Bioethics 5(5):25-27.
p.000065: Weise KL, Smith ML, Maschke KJ, Copeland L (2002). National practices regarding payment to research subjects for
p.000065: participating in pediatric research. Pediatrics 110(3):577-582.
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p.000065: Wendler D, Rackoff JE, Emanuel EJ, Grady C (2002). The ethics of paying for children’s participation in research. J
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p.000066: 66
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: SECTION 6
p.000066: Building and Maintaining Appropriate Community and Stakeholder Relationships
p.000066:
p.000066:
p.000066:
p.000066: Community engagement promotes active community involvement in the processes that shape
p.000066: research strategies and the conduct of research studies. In developing this document, NERL held an expert panel
p.000066: workshop to identify the content and organization of this document (ERG, 2007). That panel of experts concluded that
p.000066: the need to engage the community in observational research was based on the ethical principles of (1) respect
p.000066: for persons, which manifests itself in both a respect for the individual and, through respect for the
p.000066: community, their culture; (2) fairness, resulting in efforts to assure equity in resources, burden, and benefits; and
p.000066: (3) beneficence, including “empowering the community to endure.”
p.000066: Involving the community in the research effort can improve the research both scientifically and ethically. In
p.000066: the document, Ethical Considerations for Research on Housing-Related Health Hazards Involving Children, the
p.000066: joint NRC-IOM committee found that community involvement was a “guiding theme” of their findings (NRC &
p.000066: IOM, 2005). Because the researchers were working in the homes and communities of the
p.000066: participants, they faced issues that were different from a clinical setting. They were challenged to think about the
p.000066: fundamental ethical principles in the context of the research setting and about how those ethical
p.000066: principles should be interpreted in that setting. “When researchers discuss a planned study with community
p.000066: representatives, understand their concerns and needs, and respond to them, protocols can be strengthened
p.000066: both scientifically and ethically” (p. xii, NRC & IOM, 2005). Just as was described in Section 5, where the
p.000066: informed consent process was described as needing to be “an on-going, interactive dialogue between research
p.000066: staff and research participants involving the disclosure and exchange of relevant information, discussion of that
p.000066: information, and assessment of the individual’s understanding of the
p.000066: discussion” (Recommendation 4.1, IOM, 2004), so, too, the process of community involvement should be a process
p.000066: of effective two-way communication. These NRC & IOM comments emphasize how critical
p.000066: effective, bidirectional communication is to the scientific and ethical foundation of a research study in such
p.000066: a setting.
p.000066: EPA has established a public involvement policy to “improve the content of the Agency’s decisions and enhance
p.000066: the deliberative process” (U.S. EPA, 2003) (see Text Box 6-1). The policy is focused largely on Agency decisionmaking
p.000066: processes (e.g., rulemaking, permit issuance, Superfund remediation, etc.), whereas observa tional human
p.000066: exposure studies are intended to provide data to inform those decisionmaking efforts.
p.000066: Nonetheless, the Agency policy may be helpful in planning for community involvement in observational
p.000066: human exposure studies. The policy is intended to promote mutual trust and openness between EPA and the
p.000066: public, to improve the quality of the Agency’s actions, and to promote the public’s involvement in the Agency’s
p.000066: mission of promoting human health and the environment. The policy identifies seven basic steps
p.000066: for effective public involvement and offers guidance for implementing public involvement at EPA.
p.000066:
p.000066: Text Box 6-1. Seven Basic Steps for Public Involvement at EPA
p.000066: 1. Plan and budget for public involvement activities.
p.000066: 2. Identify the interested and affected public.
p.000066: 3. Consider providing technical or financial assistance to facilitate involvement.
p.000066: 4. Provide information and outreach to the public.
p.000066: 5. Conduct public consultation and involvement activities.
p.000066: 6. Review and use input, and provide feedback to the public.
p.000066: 7. Evaluate public involvement activities .
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000067: 67
p.000067:
p.000067: 6.1 Approaches to Community Involvement
p.000067: Community involvement can take many forms. The forms of community involvement are not mutually exclusive,
p.000067: and researchers may use several approaches for seeking community involvement. The nature and extent of
p.000067: community involvement reasonably would depend on the nature of the research itself and the affected
p.000067: community. In Section 2, the authors discussed some reasons for involving the community early in the research
p.000067: planning and scoping process and the benefits that community involvement may bring to the research effort.
p.000067: “Community residents can be involved in the research process as research staff, through community
p.000067: consultation and review, membership on community advisory boards, and involvement in a community-based
p.000067: participatory research process” if that is used (p. 83, NRC & IOM, 2005). In addition, IRBs may
p.000067: seek additional community representation on the IRB panel.
p.000067: The Centers for Disease Control and Prevention (CDC) recommends nine governing principles for
p.000067: “outsiders.” To help alleviate these potential issues, researchers should ensure an equitable
p.000067: distribution of paid research work among different communities within the larger community as to not promote a
p.000067: perceived bias among community members. Additionally, when possible, researchers should make efforts
p.000067: to provide payments to community members employed as researchXstaff through community partner
p.000067: organizations to prevent conflict of interest issues. Refer to Section 5 for further discussion on
p.000067: remuneration of community members as research participants.
p.000067:
p.000067:
p.000067: Text Box 6-2. Community Engagement Principles for Researchers
p.000067: (From CDC, 1997)
p.000067: Requirement Explanation
p.000067:
p.000067: Clarity Clear communication of the study objectives, research goals, and the populations or
p.000067: communities of interest.
p.000067:
p.000067: engaging communities in health-related research (see Text Box 6-2). Health research is a “privileged and
p.000067: empowered activity in that the researchers have special
p.000067: Knowledge of the Community
p.000067: Familiarity with the economic conditions, political structures, demographics, history, past research experiences, and
p.000067: research perceptions of the community.
p.000067:
p.000067: access to resources and sensitive information about people and, through the analysis and presentation
p.000067: of findings, are able to influence the way people think and have considerable influence on decisions regarding
p.000067: the allocation of resources” (CDC, 1997). Regardless of the approach utilized to involve the community in research,
p.000067: whether the process employs community-based participatory research (CBPR) or another community
p.000067: engagement method, researchers should guide their interactions with community members using these
p.000067: underlying principles to promote the aforementioned ethical principles of respect of persons, fairness, and
p.000067: beneficence.
p.000067: One form of community involvement is to include qualified members of the community on the researchXstaff.
p.000067: Section 2 advocates community representatives as part of the research team. Paid research staff members from
p.000067: the community could serve as valuable consultants for protocol development and research design, including how to
p.000067: collect the data, how to recruit and retain participants, and how to interpret and disseminate the
p.000067: results. However, including paid researchXstaff from the community may introduce a conflict of interest among
p.000067: community members: community representatives may feel a greater allegiance to the researchers providing the payment
p.000067: and be less inclined to uphold the interests of the community. In addition, the community may come to view
p.000067: the paid research staff from the community as
p.000067: Visibility Travel to the community, interact with formal
p.000067: and informal leadership, and establish relationships to build trust.
p.000067:
p.000067: Acceptance Acknowledge, without judging, the assets and deficits of the community.
p.000067:
p.000067: Partnership Balanced discussion and shared
p.000067: decisionmaking among participants concerning risks, responsibilities, expectations, benefits, and investment.
p.000067:
p.000067: Respect Value the diversity of culture, history, beliefs and opinions within the community for
p.000067: improved understanding.
p.000067:
p.000067: Asset Utilization Identify and mobilize community assets to
p.000067: improve scientific credibility of the interpretation and dissemination of results.
p.000067:
p.000067: Flexibility Anticipate changes within the community in
p.000067: regard to perceived benefits of research and stakeholder interest and additional time and resource needs.
p.000067:
p.000067: Commitment Prepare to engage the community beyond the constraints of the research projects, before and after,
p.000067: to promote longevity of the relationship for future research .
p.000067:
p.000067:
p.000067: Furthermore, institutional and community partners need to ensure that anyone involved as part of the
p.000067: research team has the requisite research and social skills. Researchers often place a greater emphasis on scientific
p.000067: over social skills and may, in turn, assume that they have
p.000067:
p.000067:
p.000068: 68
p.000068:
p.000068: the necessary expertise to conduct research in community settings. Likewise, research staff from
p.000068: the community should have knowledge of research fundamentals. Education and training targeted at
p.000068: both the institutional researcher and the community researcher may, respectively, improve the competence
p.000068: of researchers to work with communities and the scientific literacy of the public.
p.000068: A recent NERL study, the Detroit Exposure and Aerosol Research Study (DEARS), included community members as
p.000068: paid members of the research team. The community researchers were instrumental in recruiting study
p.000068: participants from the seven study neighborhoods in Detroit that required multiple door-to-door visits to
p.000068: the homes of potential participants to discuss the DEARS study. The success of DEARS was dependent
p.000068: on researchers developing strong relations with community leaders and State and local organizations.
p.000068: A second approach to community involvement is to seek community consultation and review. Researchers may
...
p.000068: the research would be responsive to the needs and concerns of the tribal residents. The CAB facilitated the researchers
p.000068: interactions with the target communities “by helping the investigators interpret data and distribute information to
p.000068: the communities” and “developing and conducting the training” of the community members on risk reduction
p.000068: strategies. The value of the research to the TEAL target communities would have been diminished had a CAB not been
p.000068: formed to assist the researchers with specific best practices to use when engaging the tribal members and
p.000068: the appropriate tribal leadership structures.
p.000068: Another potential approach to involve the community is to use a CBPR approach, wherein the
p.000068: community is actively involved in each step of the research process, including sharing of decisionmaking
p.000068: power and resources. This will impact decisions about study design, study methods, dissemination of findings,
p.000068: and resulting actions. “Under the principles of community-based participatory research, research
p.000068: must
p.000068:
p.000068:
p.000069: 69
p.000069:
p.000069: address the concerns, needs, and priorities of the communities where it is conducted and lead to
p.000069: actions and changes that benefit the community” (p. 86, NRC & IOM, 2005). Information about CBPR approaches can
p.000069: be found online at the HHS Web sites http://www.ahrq.gov/clinic/epcsums/cbprsum.htm
p.000069: and http://www.ahrq.gov/research/cbprrole.htm.
p.000069: Israel et al. (2005a) reviewed the results of CBPR efforts at six Children’s Centers co-funded by EPA and the
p.000069: National Institute of Environment Health Sciences. They found that considerable commitment of resources and
p.000069: time are needed for the approach to be successful, and the translation of research findings into interventions
p.000069: and policies is of the utmost importance. Community partners played little role in defining the research topics
p.000069: and data analysis, but were vital to disseminating the findings to the community. Keeler et al. (2002) describe
p.000069: using CBPR methods to evaluate personal and community-level exposures to particulate matter among
p.000069: asthmatic children in Detroit. The research partnership, Community Action Against Asthma (CAAA), consisted of
p.000069: representatives from local health organizations, community environmental advocacy groups, State and local
p.000069: governmental agencies, and academia. The CAAA partnership credits community involvement as active research
p.000069: partners in the research process with the success of the project to acquire “more relevant exposure data for
p.000069: the study of children in urban neighborhoods” and to provide “immediate knowledge and understanding of the outcomes
p.000069: and results of the combined environmental health analysis to the communities” (Keeler et al., 2002). There are,
p.000069: however, several drawbacks to utilizing CBPR methods that researchers should consider before developing a
p.000069: CBPR project. CBPR is time consuming (develop partnership, establish and agree on research aims and
p.000069: objectives, disseminate results to the community using appropriate methods, and review
p.000069: manuscripts and presentations) and not conducive to situations where rapid decisions are necessary given a
p.000069: tight timeline. Weighing the research need versus the community’s desire for an intervention is the
p.000069: greatest source of tension in conducting CBPR (Israel et al.,
p.000069: 2005b).
p.000069: One additional opportunity for community input may involve participation on an IRB. IRBs are required by the
p.000069: CommonXRule to have members who are sensitive to “community attitudes” [40 CFR 26.107(a)]. How they meet this
p.000069: obligation is totally at their discretion, and NERL researchers have no influence. There have been a number of
p.000069: recent articles in the literature about IRBs that have envisioned a need for more regulatory reform
p.000069: (Ledford, 2007). Ideally, the IRB should take into account the views of the community. Quinn
p.000069: (2004) argues for extending protections now reserved for individuals to groups (populations and
p.000069: communities) through CABs. Her argument is that there are “ethical issues related to research with
p.000069: communities that are distinctly different from the ethical issues related to research with individuals.”
p.000069: CAB members have to be educated on human subjects’ protections, should represent their communities
p.000069: honestly, and need to be willing to interact with researchers on complex research issues.
p.000069: Gilbert (2006) goes even further. He suggests supplementing or even replacing traditional IRBs with
p.000069: environmental health and community review boards (EHCRBs). He argues that traditional IRBs
p.000069: are inadequate for the review of community-based research because they were developed to address issues related to
p.000069: individuals involved in research projects, not communities. He proposes EHCRBs that combine
p.000069: the fundamental and ethical concept of traditional IRBs with an expanded ethical construct of dignity,
p.000069: veracity, sustainability, and justice, with added emphasis on community. He envisions that an
p.000069: EHCRB would function as an IRB with the requirements and responsibilities for review for the
p.000069: protection of human subjects, plus the additional role for review of community issues
p.000069: associated with the research project.
p.000069: Gilbert’s recommendation for EHCRBs is consistent with the recommendations of the authors of the NRC & IOM report who
p.000069: recommended that “Institutional review boards that review housing health hazards research involving
p.000069: children should ensure that those boards have the necessary expertise to conduct a complete and adequate
p.000069: review, including expertise on research involving children and community perspectives” (NRC & IOM,
p.000069: 2005).
p.000069: Involving community representatives in the IRB process is challenging for IRBs, however. One challenge could
p.000069: be the need to provide sufficient training to community members about the IRB process and the
p.000069: regulations governing IRBs. This can be significant if members sit on an IRB for a limited time to
p.000069: review specific community-based studies. In some cases, IRBs may invite community members to participate in the
p.000069: IRB process as nonvoting members to solicit the community perspective. This approach, which would be totally at the
p.000069: discretion of the IRB, might reduce the burden on the community representative by reducing
p.000069: training requirements.
p.000069:
p.000069:
p.000069:
p.000070: 70
p.000070:
p.000070: 6.2 Issues in Community Involvement
p.000070: There are a number of issues that need to be addressed in any efforts to ensure
p.000070: community involvement. The Expert Panel that was convened to advise NERL about scientific and ethical
p.000070: issues in observational human exposure studies discussed a number of challenges (ERG, 2007). The topics
p.000070: that the expert panel identified as issues are discussed below.
p.000070:
p.000070: 6.2.1 Defining “Community”
p.000070: “Community” refers to a group of people united by a shared attribute, and the attributes can be wide-ranging, such as
p.000070: geography, culture, social characteristics, values, interests, traditions, or experiences (ERG, 2007).
p.000070: Community can be defined broadly (as a system of interrelated groups operating to meet the needs of its
p.000070: members) or more narrowly (as the population from which study participants are selected). For observational
p.000070: field studies, the Expert Panel from the workshop suggested the narrow definition. A narrow
p.000070: definition allows social and cultural factors to be included but excludes government agencies, industry, and
p.000070: others who do not necessarily represent the interests of the participants (ERG, 2007).
p.000070: Central to the definition of a community is a sense of “who is included and who is excluded from
p.000070: membership” (NRC & IOM, 2005). A person may be a member of a community by choice, as with voluntary
p.000070: associations, or by virtue of their innate personal characteristics, such as age, gender, race, or
p.000070: ethnicity (NRC & IOM, 2005). As a result, individuals may belong to multiple communities at any one time. When
p.000070: initiating community engagement efforts, one should be aware of these complex associations in deciding which
p.000070: individuals to work with in the targeted community.
p.000070: Quandt et al. (2001) discuss a CBPR research project, Preventing Agricultural Chemical Exposure in
p.000070: North Carolina Farmworkers, where the process of defining a community was complicated by language,
p.000070: ethnic and racial stereotypes, and lack of organization. Many of the affected farmworkers originated outside the
p.000070: United States from several different Spanish-speaking countries and possessed contradicting viewpoints
p.000070: on research and the utility of community organization. Moreover, the community organization tailored
p.000070: for this farmworker demographic did not include enough members to adequately populate the
p.000070: study. The researchers utilized multiple approaches, including community forums, community advisory
p.000070: councils, and public presentations, to identify a diverse, yet viable, community within the broader
p.000070: farmworker population.
p.000070: Through this process of using multiple participatory strategies to define the community, a
p.000070: sense of community was nurtured among the farmworkers collectively (O’Fallon and Dearry, 2002).
p.000070: Understanding and describing a community (CDC, 1997) involves exploring factors related to
p.000070: • people (including socioeconomics and demographics, health status, and cultural and ethnic characteristics),
p.000070: • location (geographic boundaries),
p.000070: • commonalities (including shared values, interests, and motivating forces), and
p.000070: • power relationships (including formal and informal lines of authority and influence, stakeholder relationships, and
p.000070: resource flows).
p.000070: It is important to distinguish between stakeholders and the community, but both should be engaged at some point
p.000070: in the course of a study. Stakeholders are groups or organizations that may affect, be affected by, or perceive
p.000070: themselves to be affected by a decision or activity. Stakeholders may have a direct or indirect interest in the
p.000070: “matter” of interest. They may include individuals; environmental, social, or community
p.000070: nongovernment organizations (NGOs); government entities; businesses; and industry. Stakeholders include
p.000070: business, industry, and various levels of government. A critical difference between the community and
p.000070: stakeholders is that the community has a right to speak for its own interests, but stakeholders cannot
p.000070: represent or speak for the community. Although relationships with stakeholders can, at times, be
p.000070: confrontational, stakeholders often provide useful information and expertise. When stakeholders
p.000070: and the community members overlap in particular individuals, it is important to distinguish the role in
p.000070: which the individual is acting (ERG, 2007).
p.000070:
p.000070: 6.2.2 Identifying Who Represents the Community
p.000070: To sufficiently represent the community, an individual has to have not only the right to speak for the
p.000070: community’s interests (a right afforded by legitimate membership in the group) but also should be able
p.000070: to describe those interests on behalf of the community. Identifying those who represent the community is
p.000070: not simply a matter of identifying the most vocal activists because those individuals do not necessarily
p.000070: represent the interests of the entire community. In fact, several individuals may be necessary to adequately
p.000070: represent the diversity of viewpoints within a community; in such cases, a CAB may be appropriate (ERG, 2007).
p.000070: One of the researcher’s first steps should be asking the potential participants from the community who they see
p.000070: as a
p.000070:
p.000070:
p.000071: 71
p.000071:
p.000071: legitimate representative (i.e., someone who can speak for them). Corburn cites an example of a locale
p.000071: in Brooklyn, NY, that contained individuals with widely different backgrounds. It was impossible to
p.000071: identify appropriate spokespeople, or even to define the nature of the community, without talking with
p.000071: community members (Corburn, 2007).
p.000071: The NRC & IOM (2005) Report also discusses the issue of who can represent the identified community. Some
p.000071: communities may have a formal governmental structure and a recognized political authority (e.g.,
p.000071: Native American tribes). Other communities may have clearly identifiable leaders (e.g., religious communities),
p.000071: whereas still other communities have no formal leadership structure at all. Whether there is a
p.000071: legitimate political authority or some other hierarchal leadership structure, the goal is to seek community input
p.000071: as to who best represents the interests of the community with regard to the proposed research project,
p.000071: rather than selecting those who are favorable to the research project. The NRC & IOM report cautions against
p.000071: the ethically questionable practice of seeking out population spokespeople and research participants
p.000071: whose positive response to a research plan can be predicted in advance and refers the reader to an article on this
p.000071: topic by Juengst (2000).
p.000071: With multiple sources of leadership and authority in many communities, careful consideration should be given
p.000071: to what aspect of the community a particular person will represent, and what efforts may be needed to ensure
p.000071: that the entire range of views in a community are obtained. Researchers should consider reaching out to multiple
p.000071: organizations such as churches, social service agencies, community-based organizations, and tenant and
p.000071: other community advocacy groups.
p.000071:
p.000071: 6.2.3 Building Relationships and Trust
p.000071: A key first step in developing trust is to establish a relationship with the community before the study. Trust must be
p.000071: built; it cannot be assumed. This relationship involves not only listening to community input but
p.000071: actually taking it into consideration (ERG, 2007). A long history of research with no direct benefits and
p.000071: no feedback of results to the community, however, has contributed to a general mistrust of
p.000071: researchers by community members (Israel et al., 1998). Moreover, the recurring abuse of trust in communities is a
p.000071: reality that researchers should be aware of when attempting to build a long-term relationship (Minkler and
p.000071: Wallerstein, 2003). Past ethical failures have created distrust among some communities and have produced great
p.000071: challenges
p.000071: for current community organizers. Although it may seem self-evident, researchers need to remember that ethical
p.000071: action, during all phases of the research, is necessary for developing and maintaining the trust of communities
p.000071: (Perkins and Wandersman, 1990; CDC, 1997).
p.000071: Developing trust is a difficult and time-consuming process. Israel et al. (2005b) suggest a number of ways
p.000071: partners can gain each other’s trust. First, partners can show respect by seriously considering the ideas
p.000071: and opinions of others. Second, trustworthiness can be demonstrated by following through with those
p.000071: things that each partner commits to. Third, partners have to respect confidentiality. Fourth, they
p.000071: recommend attending to each other’s interests and needs by participating in activities beyond the
p.000071: specific work of the partnership.23 A history of prior positive working relationships is also beneficial
p.000071: (Israel et al., 1998).
p.000071: Trust cannot be separated from respect. Potential participants need to see researchers fostering respect for
p.000071: community members and leaders to gain trust. For example, meeting with key community leaders
p.000071: and groups in their surroundings helps to build trust for a true partnership. Such meetings provide
p.000071: organizers of engagement activities with more information about the community, its concerns, and factors
p.000071: that will facilitate and constrain participation. Once a successful rapport is established, the meetings
p.000071: and exchanges with community members can become an ongoing and substantive partnership (ERG, 2007).
p.000071: One mechanism for helping to build trust may be a contract with the community. A community contract outlines the
p.000071: roles and expectations of both the researcher and the community. Living up to these agreements builds
p.000071: trust with all partners, and the establishment of the agreement helps reduce misunderstandings.
p.000071: Contracts or memorandums of understanding that outline the roles and expectations of the researcher and the
p.000071: community are discussed in both Minkler and Wallerstein (2003) and Israel et al. (2005b). An example
p.000071: outlining expectations in a partnership with tribal communities is presented in Appendix E of Minkler and
p.000071: Wallerstein (2003), whereas an example discussing access to data and authorship issues is presented
p.000071: in Appendix I of Israel et al. (2005b). An example of a memorandum of understanding between the
p.000071: University of Michigan School of Public Health, Detroiter’s Working for Environmental Justice, the Detroit
p.000071: Hispanic
p.000071:
p.000071:
p.000071:
p.000071: 23 For a more detailed description of each of the suggestions for enhancing trust, please see Chapter 3 of Israel et
p.000071: al. (2005).
p.000071:
p.000072: 72
p.000072:
p.000072: Development Corporation, and the Warren Conner Development Coalition for a study investigating asthma is
p.000072: available at http://depts.washington.edu/ccph/pdf_files
p.000072: /MOU10.pdf.
p.000072: Work within communities involves a considerable investment of researchers’ and residents’ time. It should be an
p.000072: ongoing, interactive exchange of information and ideas between the researchers and the community members,
p.000072: where voices are both heard and honored. Trust is fostered when all interested parties feel that they have
p.000072: influence, and that their input contributes to the community effort. The collaborations should be
p.000072: inclusive of the entire community, including those members with incompatible interests and perceptions. If
p.000072: participation, influence, and benefits are limited only to some of the partners, then distrust is likely, and
p.000072: the potential benefits of community involvement may be lost. Being inclusive can create some
p.000072: organizing challenges, but the benefit of effective community involvement “has the potential to
p.000072: lead to greater understanding of community perspectives of the risk and benefits of research, improve informed
p.000072: consent, increase study enrollment, enhance data validity and quality, and build trust for research” (NRC & IOM, 2005).
p.000072:
p.000072: 6.2.4 Importance of Language and Communications with the Community
p.000072: Even when all partners and community members are speaking the same language, some terms are not
p.000072: necessarily understood by all. Communications with participants should be reviewed by all partners to ensure
p.000072: that the language used will be appropriate for all participants. At times, one method to
p.000072: communicate research findings will not fit all community members and partners. Even among the partners,
p.000072: understanding each other’s meanings is essential, so that all partners can move forward with a common
p.000072: understanding (Israel et al., 2005b).
p.000072: Furthermore, Minkler and Wallerstein (2003) note that “research must be produced, interpreted, and
p.000072: disseminated to community members in clear, useful, and respectful language.” Researchers, and especially
p.000072: researchers in a government agency, may have their own distinct lexicon. Researchers should be careful to avoid
p.000072: acronyms, jargon, or technical terms that may obscure the meaning or intimidate participants who are
p.000072: not familiar with the terms. Communicating in “plain language” to “explain the research in an
p.000072: honest, straightforward way” will help build a strong relationship with the community and the
p.000072: participants and
p.000072: also help enhance public trust (Recommendation 11, NIH, 2005).
p.000072: Culturally sensitive communication is necessary to developing effective research partnerships with
p.000072: communities. To develop effective communications, researchers must understand key aspects of the cultures
p.000072: influencing the intended audience and build that understanding into the communication strategy (Tillman,
p.000072: 2002). The symbols, metaphors, visuals (including clothing, jewelry, and hairstyles), types of
p.000072: actors, language, and music used in communication materials all convey culture. Discussions with
p.000072: community members can assist researchers in identifying messages and images that resonate across groups or
p.000072: suggesting situations in which different messages or images are likely to work best.
p.000072: As discussed above and in Sections 5 and 7, communication materials must be tailored for each
p.000072: individual community and must be written in a language and at a reading level that will ensure comprehension.
p.000072: Many IRBs require materials to be prepared at a 5th grade reading level. Researchers should evaluate the
p.000072: reading level of all data collection instruments and study communication materials and should objectively
p.000072: measure comprehension in pretests prior to use in the study. Similarly, if translations of materials are
p.000072: required, certified translating services should be used to ensure accuracy and comprehension.
p.000072:
p.000072: 6.2.5 Recognizing and Addressing Cultural Differences
p.000072: Building and maintaining appropriate community and stakeholder relationships requires acknowledgment of the
p.000072: diversity within communities with regard to many factors, including, but not limited to, race/ethnicity,
p.000072: religious beliefs, heritage, and lifestyles. Different groups in the study area may have different
p.000072: cultural norms and practices. The researchers should take these issues into consideration as they work in the
p.000072: community. Community partners can help researchers design the study to be attentive to the increasing
p.000072: heterogeneity of community groups (Minkler and Wallerstein, 2003, Chapter 4) and to the different
p.000072: boundaries of privacy (crucial when designing sampling strategies) of different groups (Israel et al., 2005b, Chapter
p.000072: 11).
p.000072: Vega (1992) provides a thorough discussion of the theoretical and pragmatic implications of
p.000072: cultural diversity for community research and explains that researchers should interact with
p.000072: communities using methods that promote understanding and demonstrate sensitivity and competence in
p.000072: working with diverse
p.000072:
p.000072:
p.000073: 73
p.000073:
p.000073: cultures (e.g., with respect to class, gender, ethnicity, race, age, and sexual orientation). To aid in this
p.000073: process, researchers should include sufficient time in their project timeline to interact and dialogue with the
p.000073: community before the study begins to understand the cultural issues that may affect the research. Researchers and the
p.000073: results of their work are expected to promote a strengthening of the community; however, it should be recognized
p.000073: that, given the heterogeneity and the diverse views within a community, the study findings potentially may
p.000073: conflict with the desires of the community or may promote feelings of anger or distrust among members
p.000073: of the community with each other. Enlisting the services of a third-party evaluator/mediator may be
p.000073: useful for sustaining positive relations between all research participants and the community at
p.000073: large.
p.000073: The Research Triangle Park Particulate Matter Panel Study (Williams et al., 2003), a NERL investigation of PM
p.000073: and related pollutants involving African-Americans in North Carolina, demonstrated an effective strategy for using
p.000073: communication to address cultural differences between the community and research personnel. Before beginning
p.000073: the research, the study design included time and a budget for building collaborations with
p.000073: organizations having close ties with the African- American community to establish trust between
p.000073: the community and research team. Using input from the community partner organizations, the
p.000073: researchers developed a systematic communication plan to establish rapport with the community and to guide
p.000073: interaction between study participants and the key study personnel. A well-designed and culturally sensitive
p.000073: communication plan was integral to the success of the study. Eighty percent of the original participants
p.000073: completed the four- season study (Williams et al., 2003).
p.000073:
p.000073: 6.2.6 Honesty, Power Relationships, and Partnerships
p.000073: The NRC & IOM report (NRC & IOM, 2005) describes a relational paradigm that acknowledges that research
p.000073: is part of a broader societal context, with the conduct of research often mirroring a system in which
p.000073: power is unequally and perhaps unfairly distributed. The trust and mutual commitment required from
p.000073: the researchers and the community are subject to the overall power relations in society.24 The Expert Panel convened to
p.000073: discuss the content of this document recognized that
p.000073:
p.000073:
p.000073: 24 A discussion of the evolution of theories on power relations, including the contribution of feminism,
p.000073: poststructuralism, and postcolonialism, can be found in Minker and Wallerstein (2003, Chapter 2).
p.000073: the researchers have a variety of forms of power that needed to be understood and acted on ethically
p.000073: (ERG, 2007). One form of power is resources, both funds and access to resources and decisionmakers. Other forms of
p.000073: power may be more subtle, including expertise, which can intimidate or limit a participant’s choices.
p.000073: Peer pressure, fear of intimidation, expectations of benefits from the research, and power to
p.000073: stigmatize the community all, whether real or perceived, can influence the relationship between the
p.000073: researcher and the community. Many forms of power may be tipped toward the researcher, but the community often
p.000073: has power in the form of knowledge about the community that can impact the quality of the research effort. An ethical
p.000073: balance of power can lead to benefits for all partners (ERG, 2007).
p.000073: In describing principles in Methods in Community- Based Participatory Research for Health, Israel et al.
p.000073: (2005b) describe CBPR as facilitating “a collaborative, equitable partnership in all phases of research,
p.000073: involving an empowering and power-sharing process that attends to social inequalities.” One way to address the
p.000073: inequities is to ensure that the roles and responsibilities are mutually acceptable to all parties.
p.000073: Researchers involved in CBPR should recognize and address the inequalities, thereby promoting trust, mutual
p.000073: respect, open communication, information sharing, collaborative decisionmaking, and resource sharing.
p.000073: It is important that researchers recognize that partnerships with the community are ongoing processes that
p.000073: need to be monitored and maintained. As a study progresses, the dynamics of the partnership may change as roles
p.000073: and responsibilities for the partners change. All partners need to be willing to make the investment of time
p.000073: and resources necessary to maintain an effective partnership.
p.000073:
p.000073: 6.2.7 Building a Lasting Infrastructure
...
p.000074: community involvement should be included in observational human exposure research efforts to the fullest
p.000074: extent possible. As the NRC & IOM committee observes (p. 98, NRC & IOM, 2005):
p.000074: Community involvement, though time and resource intensive, is a necessary and useful component of… research with
p.000074: the potential to enhance trust and increase the relevance of research to affected communities.
p.000074: Thus, attention to the issues raised by the community and consideration of the most appropriate
p.000074: method of community involvement for a given research project is warranted.
p.000074: NERL researchers also should consider the recommendations set forth in the NRC & IOM report
p.000074: (Recommendation 5.1, p. 98, NRC & IOM, 2005) as they develop their research plans and protocol.
p.000074: Researchers…should describe in their protocols and IRB submissions how they have involved and will continue
p.000074: to involve the affected community in the research project, justify the lack of such involvement, and report
p.000074: how they have responded to any community concerns.
p.000074: Researchers and the members of the communities in which they work should recognize, however that the primary
p.000074: role of the researcher is to be an advocate for the science, not an advocate for the community. Although being
p.000074: an advocate for the community is desirable, and in many projects achievable, it should be recognized that
p.000074: resource constraints and potential conflicts of interest may impact the researcher’s ability to advocate
p.000074: for the community, particularly if it involves regulatory activities of the Agency.
p.000074:
p.000074: 6.4 Identifying and Interacting with Other Stakeholders
p.000074: Like community involvement, stakeholder involvement in a research study can take many forms.
p.000074: Also like community involvement, researchers should engage stakeholders in their studies early in the planning
p.000074: stages. The relationship between the researchers and various stakeholders should be maintained during the
p.000074: study. How this relationship is maintained can be expected to vary with different stakeholders and
p.000074: may
p.000074:
p.000075: 75
p.000075:
p.000075: change as the study progresses. Stakeholders can provide useful information and perspective during the planning
p.000075: and implementation of observational human exposure studies.
p.000075: Stakeholders may include individuals, NGOs, businesses, industry, and various government entities or
p.000075: agencies with jurisdiction over or interest in the community. Stakeholders are a separate entity apart
p.000075: from the community, although they may conduct business or operate within the community or have a direct or indirect
p.000075: interest in the community’s activities. Even though they are not able to speak for the community, stakeholders
p.000075: may have knowledge of impacts and ideas about how to interpret and use the results of proposed research studies. Such
p.000075: knowledge may prove very helpful as part of the research planning and scoping (ERG, 2007). Including a variety
p.000075: of stakeholders in the planning process provides insight that comes from reconciling the disparate
p.000075: perspectives of different stakeholders.
p.000075: Observational human exposure studies conducted or supported by NERL may have many potential
p.000075: stakeholders, both internally in EPA and outside of the Agency. Internal stakeholders include the ORD Office of
p.000075: the Science Advisor, the Office of Science Policy, other laboratories and centers in ORD that may be interested in
p.000075: the study and its results, program offices, and the regional offices. Outside of the Agency, other
p.000075: Federal, State, and local agencies may be stakeholders. For example, CDC may be interested in
p.000075: biomonitoring studies. State agencies will be stakeholders when research is done in their state.
p.000075: Examples of NGOs that may be external stakeholders include the Natural Resources Defense Council,
p.000075: Environmental Defense, American Lung Association, American Academy of Pediatrics, American Chemistry
p.000075: Council, and literally hundreds of other organizations with interests in environmental or public
p.000075: health issues. Researchers should identify potential stakeholders and communicate with them early in the planning
p.000075: stages of a study if they are determined to be appropriate. Identifying the appropriate stakeholders who
p.000075: have a legitimate interest in the study will be done on a study-by-study basis and should be done in
p.000075: consultation with the research team, the community representatives, and senior management. In EPA, the Office
p.000075: of Public Affairs can assist in identifying contacts in stakeholder groups.
p.000075: The concept of “stakeholder” has been discussed in management literature since the 1980s. Mitchell et al. (1997)
p.000075: have developed an approach for identifying the relevant stakeholders through an assessment of their power,
p.000075: legitimacy, and urgency. Such an approach may
p.000075: be useful for identifying stakeholders to be involved in the research studies. In describing CBPR, Israel et
p.000075: al. (2005b) discuss the need to examine the advantages and disadvantages of extending membership beyond the
p.000075: “community of identity” at the outset. For example, they discuss the relative merits of including representatives of
p.000075: the agricultural industry in a study of farmworkers because of industry’s possible role in policy change
p.000075: and weigh their inclusion against the concerns that the true voice of the farmworkers may not be heard under
p.000075: such conditions. They also describe a possible solution of creating separate partnership groups.
p.000075: O’Fallon and Dearry (2002) explain the benefits of including diverse stakeholders for the dissemination of
p.000075: results.
p.000075: Successful interactions with stakeholders will require effective communication strategies
p.000075: and materials, as is discussed in the following section. After relevant stakeholders have been identified, they
p.000075: should be contacted to inform them of the proposed research study and to determine their interest in the study.
p.000075: If the stakeholders express an interest in participating, the research team should develop a plan for interacting
p.000075: with the stakeholders that includes roles and responsibilities, activities, and timelines that are mutually
p.000075: agreeable to the team, community representatives, and the stakeholders. There needs to be a clear
p.000075: agreement on the plan with all parties involved. Failure to have such an agreement may lead to
p.000075: misunderstandings of the roles of the stakeholders. As planning for the study proceeds, the plan for stakeholder
p.000075: involvement should be updated to reflect activities and timelines for longer term engagement.
p.000075: When developing relationships with stakeholders, researchers also should ensure that participation of the
p.000075: stakeholder in the study, regardless of level of participation, does not result in actual
p.000075: or perceived conflicts of interest. This should be addressed in the plan and agreement for stakeholder involvement.
p.000075:
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p.000077: Newark: LexisNexis.
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p.000077: Waste and Emergency Response. Washington, DC. OSWER Directive No. 9230.0-99, October 12. Available:
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p.000077: NACCHO (National Association of County and City Health Officials). Turning Point: Collaborating for a New Century in
p.000077: Public Health, see http://www.naccho.org/topics/infrastructure/TurningPoint.cf m [Specifically, Fourteen Policy
p.000077: Principles for Advancing Collaborative Activity Among and Between Tribal Communities and Surrounding Jurisdictions.
p.000077: http://archive.naccho.org/documents/TP-policy principles.pdf ].
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p.000077: U.S. EPA (U.S. Environmental Protection Agency) (2005). Superfund Community Involvement Handbook. [Specifically,
p.000077: chapters 1 through 3.] EPA 540-K-05-003, Available: http://www.epa.gov/superfund/community/cag/pdfs/ci_hand book.pdf
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p.000077: U.S. EPA (U.S. Environmental Protection Agency) (1999). Risk Assessment Guidance for Superfund: Volume I – Human Health
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p.000078: U.S. EPA, Office of Environmental Justice Resources:
p.000078: Executive Office of the President. (1997). Environmental Justice: Guidance under the National Environmental Policy Act.
p.000078: Council on Environmental Quality, pp. 7-17).
p.000078: Available: http://epa.gov/compliance/resources/policies/ej/ej_guidance
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p.000078:
p.000078: NEJAC (National Environmental Justice Advisory Council) (2006). Future mechanisms to enhance stakeholder involvement
p.000078: and engagement to address environmental justice: A letter report. Available:
p.000078: http://epa.gov/compliance/resources/publications/ej/nejac/st akeholder-involv-9-27-06.pdf
p.000078:
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p.000078: Recommendations for improving stakeholder relations between federal facilities and environmental justice communities.
p.000078: Waste and Facility Siting Subcommittee, Federal Facilities Working Group. Available:
p.000078: http://www.epa.gov/compliance/resources/publications/ej/n ejac/ffwg-final-rpt-102504.pdf
p.000078:
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p.000078: environmental regulatory programs. Indigenous Peoples Subcommittee. Available:
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p.000078:
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p.000078: tribal governments and the public participation of indigenous groups and tribal members in environmental decision
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p.000078:
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p.000078: Cooperative Agreement Program FACT SHEET. Office of Environmental Justice. Available:
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p.000078: U.S. EPA (U.S. Environmental Protection Agency). (1995). The EPA’s Environmental Justice Strategy. Available:
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p.000079:
p.000079:
p.000079:
p.000079:
p.000079: SECTION 7
p.000079: Designing and Implementing Strategies for Effective Communication
p.000079:
p.000079:
p.000079:
p.000079: Successful implementation of observational human exposure studies requires effective communications between
p.000079: the researchers, study participants, community representatives, community members, stakeholders, and the
p.000079: public. The previous two sections established the need for communications that are “on-going, interactive
p.000079: dialogue…involving the disclosure and exchange of relevant information, discussion of that information, and
p.000079: assessment of the individual’s understanding of the discussion” (Recommendation 4.1, IOM, 2002). NIH
p.000079: advocates “plain language” that explains the research “in an honest, straightforward way” (Recommendation 11, NIH,
p.000079: 2005). Indeed, strong relationships can be built with participants, the community, and stakeholders only if
p.000079: there are clear and effective communications between the researchers and the community. The previous section
p.000079: illustrates, also, that effective communication is bidirectional; it involves listening as well as
p.000079: “speaking.” The ethical value of respect for persons, including respect for one another’s
p.000079: autonomy and welfare, demands that researchers, participants, community members, and stakeholders
p.000079: strive to establish effective communications and to foster a relationship of trust and respect. The researchers
p.000079: should make a commitment to effective communications and make the appropriate investment of time and
p.000079: resources to ensure that the communications are at an appropriate level and are truly effective. Researchers should
p.000079: regard communications as intrinsic to the ethical basis for the study.
p.000079: With the ethical basis for bidirectional communication assumed as a given, and the need
p.000079: for open and honest bidirectional communications having been well established in the previous
p.000079: sections that discussed relationships between the researchers and the participant (Section 5) and the
p.000079: researchers and the community (Section 6), this section discusses strategies and tools that researchers may
p.000079: find useful in developing
p.000079: effective communications. The focus in this section is primarily from the perspective of “getting the word out,”
p.000079: because that is the aspect of communication most under the control of the researchers. Nonetheless, effective
p.000079: communications will be bidirectional and involve effective listening. Researchers should keep in mind that it
p.000079: is as important to listen to the participants, community, and other stakeholders as it is for the researchers
p.000079: to provide them with information using the approaches described in this section.
p.000079:
p.000079: 7.1 Communication Strategy and Implementation Plan
p.000079: Fundamental to achieving effective communications are a communications strategy and implementation plan. In general,
p.000079: the goal of the communication strategy and plan is to clearly define how effective bidirectional
p.000079: communications will be achieved in the study. Specific goals should be developed based on the specifics of the study
p.000079: design, the study population, the community, and the stakeholders. The plan will describe who will be involved
p.000079: in the communications, what communications are required, and how the communications will be
p.000079: performed. The communication strategy and implementation plan should be developed early in
p.000079: the planning stages of a study. The communication plan, however, needs to be dynamic, with revisions
p.000079: and updates occurring throughout the study and in collaboration with the community and
p.000079: stakeholders.
p.000079: Text Box 7-1 lists elements that should be included in a communication plan. The communication strategy should be
p.000079: developed based on the goals of the study and an understanding of the background, education, attitudes,
p.000079: and opinions of the stakeholders and the community that will be involved in the many different
p.000079: aspects of the study from the initial conceptualization to the final reporting of the study results.
p.000079:
p.000079:
p.000081: 81
p.000081:
p.000081:
p.000081: Text Box 7-1. Elements in a Communication Plan
p.000081: • Background information description (overview) of the study, relevant historical background information, statement
p.000081: of communication needs, and identification of communication opportunities and issues
p.000081: • Purpose and goals of the communication strategy
p.000081: • List of individuals and groups involved in the communications, plus relevant demographics and other information to
p.000081: profile the groups
p.000081: • Strategy and approach for achieving the goals, including a statement of the primary message to be conveyed and
p.000081: descriptions of the communication channels
p.000081: • Activities and materials to achieve the goals of specific elements of the plan to be performed
p.000081: • Timetable
p.000081: • Roles and responsibilities
p.000081: • Resources needed (budget)
p.000081: • Measures of effectiveness
p.000081:
p.000081: Careful planning is required to develop a communication plan that will be effective. The research
p.000081: team has to invest the time and resources necessary to develop and implement the plan. They also
p.000081: should recognize that the communication plan is essential for conducting the study and is just as important as
p.000081: the study design, human subjects research protocol, or QAPP. The observational study, if properly justified as
p.000081: described earlier, provides a social and scientific value and brings benefit to society (and perhaps the
p.000081: participants); it should be a program that the researchers want to discuss and explore with the public. The
p.000081: communication plan and strategy provide the researchers with an opportunity to create effective bidirectional
p.000081: communications with the participants, community, and stakeholders. They are not simply a way to “avoid problems” with
p.000081: the community, stakeholders or the media nor only a plan for reacting to “negative” feedback.
p.000081: Recognizing that the communication strategy must address the bidirectional nature of communications with the study
p.000081: participants and the community to be effective, it is important that the communication strategy and
p.000081: implementation plan be developed in collaboration with the community and other stakeholders. As discussed in
p.000081: previous sections, members of the community in which the study will be performed will provide valuable input into the
p.000081: development of the communication strategy by providing information about the community culture, norms,
p.000081: attitudes, perceptions, etc. They will provide, not only expertise about the community, but also
p.000081: experiences and lessons learned about previous communications activities in the community. It
p.000081: is important to engage community representatives and stakeholders early in the process of development of the
p.000081: communication strategy, the implementation plan, and the communication tools.
p.000081: Researchers also may find it helpful to seek guidance on how to communicate more effectively,
p.000081: especially because that is not a routine part of their training or experience. They may consult and learn from
p.000081: communications specialists in their organization. In addition, a wide variety of resources are
p.000081: available. For example, the Federal Communicators Network (FCN) (www.fcn.gov) has prepared a “communicators
p.000081: guide” that offers advice on how to communicate—in plain language, in easily digestible “chunks,” and in
p.000081: a form that will be used. They emphasize that “good communication is difficult because it
p.000081: requires a lot of effort, time, and patience” (FCN, 2001). Some tips from the guide to help federal communicators
p.000081: get their point across are listed in Text Box 7-2.
p.000081:
p.000081: Text Box 7-2. Tips for Getting Your Point Across
p.000081: • Be prepared.
p.000081: • Be confident.
p.000081: • Stay focused on your conversation and your listener.
p.000081: • Maintain eye contact with your listeners.
p.000081: • Make sure your listeners are following you by asking them for questions or feedback.
p.000081: • Do not lose your temper or get over-emotional.
p.000081: • Speak slowly and calmly; don’t raise your voice.
p.000081: • Speak clearly and concisely.
p.000081: • Get to the point; do not ramble.
p.000081: • Be kind, compassionate, and empathetic.
p.000081: • Be honest; do not play games.
p.000081: • Be assertive but tactful
p.000081:
p.000081:
p.000081: 7.2 Individuals and Groups Involved in the Communications
p.000081: An effective communication plan will identify and involve all of the individuals and relevant groups that
p.000081: should be included in the communications efforts. When conducting observational human exposure studies, this list
p.000081: may be quite long. Although researchers may desire to limit the number of individuals and groups involved to
p.000081: keep the effort as simple and focused as possible, they need to ensure that all potential stakeholders
p.000081: are identified. The communication plan should identify all groups, including community organizations
p.000081: and stakeholders, involved in a study, their roles and responsibilities in the study, how
p.000081: communications will be developed with each group, and the timing of the communications. It is likely
p.000081: that most studies will involve the individuals, community groups and stakeholders shown in Text
p.000081: Box 7-3.
p.000081:
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p.000082:
p.000082:
p.000082: Text Box 7-3. Individuals and Groups Involved in Communications
p.000082: • Principal investigator—the researcher with ultimate responsibility for the study
p.000082: • Research team
p.000082: • Study participants
p.000082: • Third parties associated with study participants (e.g., spouse, children, landlords)
p.000082: • Community representatives
p.000082: • Community members
p.000082: • Governments (local, State, and Federal)
p.000082: • Study institution management
p.000082: • Study sponsors or funding organization
p.000082: • Organizations with interest in the participants, the community, or the research question
p.000082: • Stakeholders that may be impacted by the results of the study
p.000082: • The scientific community
p.000082: • Media
p.000082: • The general public
p.000082:
p.000082: The study participants are a key group involved in communications during a study and are easily identified.
p.000082: Similarly, it is generally not difficult to identify the third parties associated with the study participants,
p.000082: because these groups must be identified when considering ethical issues in the study and when developing the
p.000082: human subjects research protocol. Research teams should ensure that the communication strategy includes the
p.000082: strategy and approach for third-party communications.
p.000082: As discussed in Section 6, it is critical that community representatives are identified early in
p.000082: the scoping and planning phase of the study. It is important that researchers are informed about the community
p.000082: in which they will conduct the study and understand the unique characteristics and culture of the community and
p.000082: the potential study participants to develop effective bidirectional communications. When
p.000082: possible, researchers should identify other research organizations who have worked in the community and attempt
p.000082: to gather information from them on the nature of the community, who represents the community, and what
p.000082: communication strategies have been used previously in the community. Understanding how the community
p.000082: defines itself or thinks of itself is critical to establishing effective communications.
p.000082: Identification of all relevant stakeholder groups may be more difficult. As defined in Section 6, the term
p.000082: stakeholder is used here to identify a person or group who has a valid interest in an activity or
p.000082: decision, but who does not speak directly for the community or the participants. There may be many
p.000082: organizations who consider themselves as stakeholders that represent the
p.000082: interests of the community, the participants, or the research problem. For example, there are many
p.000082: nonprofit organizations that advocate for the protection of children’s health. When conducting an
p.000082: observational study involving children, the research team should identify those groups that could have
p.000082: an interest in the study. They need to be identified in the communication plan, and an approach needs to
p.000082: be developed for communicating with them about the study. There are many sources of information on
p.000082: potentially interested stakeholder groups. This information can be obtained from the research team based on
p.000082: similar studies, the participants, the community representatives, sponsoring organizations, and “umbrella”
p.000082: organizations for various advocacy groups. The Internet has made identification of the various stakeholder groups
p.000082: easier and is a source of information on goals of the groups and contact information. Approaches for
p.000082: communications with these and other groups on the list are discussed further in the following subsections.
p.000082: Researchers should recognize that identifying and involving all pertinent community and stakeholder
p.000082: groups in their observational human exposure studies is important for effective communications and the potential
p.000082: success of the study, but that there is the potential for the group to become so large that it becomes
p.000082: difficult to manage. Large groups not only have the potential for impeding progress on a research effort
p.000082: simply because of the logistics of the interactions within the group, but, also, because of the potential
p.000082: for conflict between the groups. It is essential, therefore, that researchers attempt to maintain stakeholder
p.000082: groups of manageable size and be prepared to deal with potential conflict within the groups. There is
p.000082: extensive literature available on conflict management, but it is outside of the scope of this document to
p.000082: recommend specific approaches or literature references.
p.000082:
p.000082: 7.3 Communications Timetables⎯When To Communicate
p.000082: Communications begin with the initial conceptualization of the study and continue through the
p.000082: reporting of the study results and beyond. Even after a study has ended, followup communications
p.000082: may continue with the study participants, the community, the scientific community, and the public. It is beyond
p.000082: the scope of this document to lay out timetables for communications in observational human
p.000082: exposure studies because timing will differ with each study. The following discussion highlights a few
p.000082: of the issues associated with the timing of communications to ensure
p.000082:
p.000082:
p.000083: 83
p.000083:
p.000083: that they are effective. This section also does not discuss communications among the research team, research
p.000083: organization, or study sponsors.
p.000083: Researchers should begin the dialogue with the community as soon as possible during study
p.000083: conceptualization and planning. Once the community in which the study will be performed is identified,
p.000083: community representatives should be identified and contacted to discuss the potential study and to get input
p.000083: on how the study may be designed. As discussed in Section 6, the observational human exposure
p.000083: studies discussed in this document are generally not CBPR. Although the study objectives or hypotheses
p.000083: have been defined and the general approach has been developed, the community still can provide valuable
p.000083: input about their environmental or public health concerns. Again, as discussed earlier, the planning for the
p.000083: study should be flexible enough to incorporate community concerns where feasible. Recognizing that many
p.000083: observational human exposure studies will not be able to address all of the community’s concerns, it is
p.000083: important that the communications with the community accurately convey the value, merit, and benefits from the
p.000083: study that will be relevant to the community.
p.000083: Press releases can serve as useful tools for informing communities about upcoming studies and for identifying
p.000083: stakeholders. Assuming that community representatives have been identified early in the development of the
p.000083: study design and communications strategy, and that community buy-in for the study has been gained,
p.000083: researchers can work with community leaders and community members to develop press releases and other
p.000083: communication tools. Press releases can serve multiple purposes. They provide information to
p.000083: potential community representatives who may not have been identified by the researchers as potential
p.000083: collaborators in the study. They provide publicity that will inform community members about potential
p.000083: contacts by the research team (e.g., in a random sample design). They provide information to public
p.000083: interest and advocacy groups who may feel that they are stakeholders who should be involved in the
p.000083: study. Press releases also provide the transparency for the study and the research team that is essential for
p.000083: building trust.
p.000083: Studies also should be announced to stakeholders and the public (via the media, community interactions, or
p.000083: other means) well in advance of study implementation. Large grants expected to
p.000083: have significant impact in communities often are announced by EPA at the research institution receiving
p.000083: the grant and in press releases to the local media. These studies,
p.000083: therefore, are publicized at a very early stage. Cooperative agreements, which are another
p.000083: mechanism by which the government funds some research projects, are announced in the same way. Cooperative agreements
p.000083: and studies performed by EPA researchers receive additional public notice when they are reviewed by the
p.000083: Office of Management and Budget (OMB) under the Paperwork Reduction Act. All studies involving
p.000083: collection of survey information from more than nine people are reviewed by OMB. This involves submission of an
p.000083: Information Collection Request (ICR) to OMB, announcement of the ICR in the Federal Register, and an
p.000083: opportunity for public comment. A docket is established specifically to facilitate public comment.
p.000083: This process results in widespread publication of upcoming government research studies through scrutiny by
p.000083: concerned stakeholder groups who routinely review the announcements in the Federal Register.
p.000083: Prior to the start of data collection in a community, relatively large-scale communications may be required. These
p.000083: communications may involve notifications to public safety officials about the presence of the research team
p.000083: in the community, press releases to local media outlets about the study, and meetings with community
p.000083: groups to provide details about data collection activities.
p.000083: It is essential that the research team fosters continuing bidirectional communications with
p.000083: the participants, community, and stakeholder groups throughout the study to maintain transparency, trust,
p.000083: and interest in the study. This can be aided by providing project progress reports and interim
p.000083: results to the participants and the community through community meetings, mailings, or Web
p.000083: sites. In observational human exposure studies with repeated measurements over seasons or years,
p.000083: routinely meeting with participants can serve as a mechanism for providing study information to the
p.000083: participants and receiving feedback from the participants and the community about the study and their roles
p.000083: in it. Effective bidirectional communication with participants can be expected to improve their
p.000083: participation in the study (e.g., in completing surveys and collecting personal samples) and for improving
p.000083: retention in longitudinal studies. However, it is essential that the researcher recognize the implications
p.000083: of such meetings on privacy and confidentiality issues for the participants and develop
p.000083: communications to advise the participants of these issues.
p.000083: Community meetings also are effective for maintaining communications throughout a study. They
p.000083: provide the opportunity to disseminate information to
p.000083:
p.000083:
p.000084: 84
p.000084:
p.000084: community representatives and to obtain feedback. They also provide an opportune setting for news releases to
p.000084: the media to maintain or increase interest in the study.
p.000084:
p.000084: 7.4 Communicating at Different Levels
p.000084: The diversity of interested people and groups often means that communications materials should be
p.000084: developed at different levels of scientific literacy. In any case, the materials should all be written in
p.000084: “plain language” that is honest and straightforward. Stableford and Mettger (2007) state that “plain language
p.000084: embodies clear communication.” Many researchers mistakenly believe that the term means just using simple words,
p.000084: or worse, ‘‘dumbing things down.’’ It actually refers to communications that engage and are accessible to
p.000084: the intended audience.
p.000084: A 1998 Presidential memorandum required that “plain language” be used in all governmental
p.000084: communications with the public. That memorandum stated, “By using plain language, we send a
p.000084: clear message about what the Government is doing, what it requires and what services it offers. Plain language
p.000084: saves the Government and the private sector time, effort, and money.” Plain language is reader friendly and designed to
p.000084: increase the participant’s understanding of the communication material. It serves as a means by which lay
p.000084: audiences can access and understand scientific information. Researchers desiring to use plain language in
p.000084: their verbal and written communications with communities must decide on key messages to include and
p.000084: delete unnecessary descriptive, bureaucratic, or jargon-filled language. Researchers should use words that
p.000084: commonly are understood, rather than difficult abstract terms and concepts. A friendly,
p.000084: conversational tone is used to engage the lay audience, rather than a formal, scholarly tone that
p.000084: distances the community. Stableford and Mettger (2007) argue that proficiency in creating appropriate plain
p.000084: language materials is an acquired skill that requires knowledge and experience. “It is both an art and
p.000084: a science, requiring the ability to simultaneously think about the cognitive, emotional, and visual appeal of the
p.000084: piece as well as applying research- based strategies to ensure a truly easy-to-read and understand print
p.000084: material.”
p.000084: The Department of Health and Human Services (HHS) has developed a Web site that specifically
p.000084: address the issues related to “plain language” (see
p.000084: http://www.health.gov/communication/literacy/plainlang uage/PlainLanguage.htm). The site includes a list of
p.000084: references and other helpful resources.
p.000084: To maintain community engagement through the
p.000084: research process, it is critical that communications are at the appropriate level, and that materials are written at a
p.000084: reading level that is appropriate to the audience. For the nonscientist, many IRBs and other groups target
p.000084: materials to be used with participants and communities at a reading level no higher than the 8th grade to
p.000084: improve the likelihood of comprehension. In some communities, however, other factors, like primary languages other than
p.000084: English, educational disadvantages, etc., may require communications materials to be written in
p.000084: alternate languages and at different reading levels. The issue is comprehension, as was discussed in
p.000084: Section 5.1.2. Empirical testing of communication methods and content is essential to ensure
p.000084: comprehension (Health Canada, 2006).
p.000084: Researchers also should recognize that in this information age, dissemination of
p.000084: informational materials may be rapid and widespread. Therefore, even documents intended for scientific peers may
p.000084: benefit by including summary information in an executive summary or preface that a lay reader can
p.000084: understand.
p.000084:
p.000084: 7.5 Communications Materials
p.000084: Researchers need to communicate clearly with the many groups listed in Section 7.2 to develop their
p.000084: relationship with the participants in the study, to develop their partnership with the community, to gain
p.000084: support from stakeholders, and to inform the public. To achieve the multiple purposes of communications
p.000084: during a research study and to communicate with many diverse groups, a variety of communications materials may
p.000084: need to be developed. Different materials have different purposes and different types of
p.000084: information to be communicated. Because of diversity in interested individuals and groups with
p.000084: respect to education, cultures, information needs, etc., the format and content of communication materials
p.000084: likely will need to be diverse. Text Box 7-4 list activities and materials that may be helpful in
p.000084: facilitating communications.
p.000084: By definition, communication is an exchange of information. This has to be the primary goal of
p.000084: communication activities. The accuracy and completeness of the information transferred is
p.000084: important. There are many different ways to communicate, the effectiveness of which varies substantially.
p.000084: The way in which the information is conveyed is as important as the information itself. Effective communication
p.000084: should promote trust and credibility. Peters et al. (1997) found that three determinants, namely, (1)
p.000084: knowledge and expertise, (2) openness and honesty, and (3) concern and care, were important factors determining
p.000084: perceptions of
p.000084:
p.000084:
p.000085: 85
p.000085:
p.000085: trust and credibility. Therefore, the approach to communication in observational human exposure
p.000085: studies should consider these factors, and communication materials should be developed with these
p.000085: factors in mind.
p.000085:
p.000085: Text Box 7-4. Activities and Materials That May Be Useful in a Communication Plan
p.000085: • Flyers
p.000085: • Web sites
p.000085: • Brochures
p.000085: • Interviews
p.000085: • Newsletters
p.000085: • Focus groups
p.000085: • Presentations
p.000085: • Direct mailings
p.000085: • Press releases
p.000085: • Questions and answers
p.000085: • Desk statements (government)
p.000085: • Abstracts
p.000085: • Study reports
p.000085: • Talking points
p.000085: • Community meetings
p.000085: • Stakeholder meetings
p.000085: • Technical presentations
p.000085: • Study participant meetings
p.000085: • Scientific meeting presentations
p.000085: • Peer-reviewed scientific journal manuscripts
p.000085: • Final reports describing the total research effort
p.000085:
p.000085: When developing communication materials, the researcher should consider the needs of the reader,
p.000085: listener, or viewer with respect to content, scope, style, and the level at which the materials are written.
p.000085: There are many sources of information on design of informational materials, such as flyers or
p.000085: brochures. For example, Alderson (1995) provides an example of the recommended content and style for information
p.000085: leaflets (that also may be flyers or brochures) for pediatric medical research. She suggests that leaflets be
p.000085: provided to parents of children who will be study participants that can be read to the children. She recommends that
p.000085: these be provided at the time that the parent is being informed of the study, prior to requesting the informed
p.000085: consent. The content of the leaflet would include the following topics.
p.000085: • Nature and purpose of the research
p.000085: • Anticipated benefits of the research
p.000085: • Risks, harms, costs, and inconvenience to the participant
p.000085: • Assurance that the participant freely can refuse to participate in or withdraw from the study
p.000085: • Details about remuneration
p.000085: • Names of the project sponsors and the researchers
p.000085: • Contact information for the researchers
p.000085: • Respect for privacy and confidentiality
p.000085: Leaflets and brochures that contain this information provide a tool for communication with study
p.000085: participants. However, these materials need to be written carefully using everyday terms that the
p.000085: average nonresearcher can understand. The brochure should be written in a friendly style that conveys the intent
p.000085: of the researcher to engage the reader as a collaborator on the study, not as a study “subject,” who will be told to do
p.000085: a series of tasks while participating in the study.
p.000085: These same leaflets and brochures can be used to inform other groups that either may be involved or
p.000085: interested in the study, such as community representatives, stakeholder organizations,
p.000085: the media, and the general public. The researcher should ensure that any brochure developed for the study includes
p.000085: accurate and complete information that is less likely to be misinterpreted by anyone who might
p.000085: pick up the brochure. Brochures and flyers that are used to announce a study or are used as recruiting tools
p.000085: should be carefully written in plain language to ensure that there is not a perception of activities that are
p.000085: unethical. For example, if flyers announcing a study state that study participants will be compensated, the flyer
p.000085: needs to ensure that the compensation is not the focus of the flyer, and that the payment does not appear to
p.000085: be excessive and coercive (see Section 5.2). Flyers announcing a study generally do not include the dollar
p.000085: amounts of payment.
p.000085: Researchers need to have similar concerns about all of the communication materials that are developed,
p.000085: regardless of the type of material, whether it is a direct mailing, a Web site, a news release, or a set of questions
p.000085: and answers (Q&As) used to respond to media or stakeholder inquiries. In developing the communication
p.000085: materials, the research staff should seek the assistance, advice, and input of people in their
p.000085: organization and community groups with experience in developing such materials. With all of these
p.000085: materials, the researchers should be concerned with how the materials could be misinterpreted, and whether
p.000085: there could be a perception that the study would not meet the highest scientific and ethical standards. In this age
p.000085: of rapid communications and increased accessibility to information, it is essential that communication materials
p.000085: are well developed, accurate, and understandable to all audiences that may read them.
p.000085: Research study Web sites are especially useful for communicating information about observational human
p.000085: exposure studies. Web sites should be developed early in
p.000085:
p.000085:
p.000086: 86
p.000086:
p.000086: the study to disseminate information to stakeholders and the community. Additionally, the sites can be set up with
p.000086: participant-only pages to provide more detailed information to study participants, including information
p.000086: on study protocols that require participant assistance (e.g., protocols for collecting urine
p.000086: samples, time/activity log entries). However, researchers need to ensure that Internet access is available to their
p.000086: intended audience and be prepared to provide alternative communication tools for those without such
p.000086: access.
p.000086: The plan for disseminating information from the study should be developed in the early design phases of the
p.000086: study and should be included in the study design document. Sufficient resources, both time and funding,
p.000086: need to be budgeted for this activity.
p.000086:
p.000086: 7.6 Informing the Study Participants and Communities
p.000086: Effective communications require that all parties, researchers and participants alike, involved in the
p.000086: communication understand the content and context of the information being exchanged. “When researchers
p.000086: discuss a planned study with community representatives, understand their concerns and needs, and respond to
p.000086: them, protocols can be strengthened both scientifically and ethically” (p. xii, NRC & IOM,
p.000086: 2005). Comprehension is one of the key pillars of informed consent, and it means that participants
p.000086: understand the key elements of the research. The most effective way to improve comprehension is by talking
p.000086: one-on-one with study participants.
p.000086: To accomplish that, the researchers need to make a commitment to communicating with both the study
p.000086: participants and the community to inform them of the study and provide training as appropriate. This can
p.000086: require a substantial investment of time and resources, but it is critical to the success of the study.
p.000086: Working with study participants to inform them about the study and the scientific basis of the study will have
p.000086: many benefits. The more educated the participant is about the purpose of the study and the activities to be
p.000086: performed during the study, the more likely the participant will be to develop a beneficial
p.000086: researcher- participant relationship. By taking the time to inform the participant, the researcher demonstrates
p.000086: his or her commitment to the participant and conveys the importance or value of their
p.000086: participation in the study. If the researcher-participant relationship is well developed, the participant will have
p.000086: a higher level of trust in the researcher and will be likely to have more interest in the study and a positive
p.000086: outcome. If such a relationship is
p.000086: developed and the participant is informed about the study goals, the participant will take part more
p.000086: readily and effectively in the specific study activities. For example, a study participant who
p.000086: understands why time/activity information is critical to understanding exposure is likely to do a
p.000086: better job completing a time/activity log than a participant with no interest in the outcome of the study.
p.000086: In addition, an informed participant may have good suggestions for improving the study and the interactions
p.000086: with the participants and the community that the researchers should listen to and adopt. Developing the
p.000086: researcher-participant relationship and informing the participants also should improve retention in
p.000086: longitudinal, repeated measures studies because the participant feels that he or she is
p.000086: collaborating with the researcher and is not merely a study “subject.”
p.000086: Similarly, providing information on the research study to the community should provide significant
p.000086: benefits in terms of support to the research team and working with the team to facilitate the study in
p.000086: their community to address both the scientific issues and the community’s concerns. If community leaders understand
p.000086: the research problem, the study goals, and the study activities, they can more effectively articulate
p.000086: the community’s concerns to the researchers and integrate those issues into the study design. This will
p.000086: enhance their work with the research team during the design phase and will enable them to more
p.000086: effectively advise and assist during the implementation of the study.
p.000086:
p.000086: 7.7 Reporting Study Results to the Participant and Community
p.000086: Researchers need to develop the approach for reporting results to the participants,
p.000086: community, stakeholders, media, and others during the initial planning of the study. There are not
p.000086: well-developed guidelines for when and how to report study results (Parkin, 2004). In her systematic
p.000086: review of guidelines and frameworks for reporting study results, Parkin determined that locating
p.000086: guidance may be difficult and time consuming for researchers. She found agreement on the importance of
p.000086: disseminating study results to produce public health benefits, but there is not a consensus on when and how
p.000086: results should be reported to either communities or study participants. Although she did not identify
p.000086: well-developed guidance documents, she did identify some common themes. The first was that
p.000086: researchers are becoming aware of the importance of systematic planning of the research communications,
p.000086: planning that needs to be done early in the study.
p.000086:
p.000086:
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p.000087:
p.000087: Second, organizations are recognizing the importance of communicating with communities. And, third, research
p.000087: professions are recognizing the importance of research communication and their responsibilities.
p.000087: There is a large body of literature on processes for risk communication (e.g., see Covello et al., 1989, 2007;
p.000087: U.S. HHS, 2002; ASTDR, 2007). Processes for risk communication are highly relevant to reporting results
p.000087: from observational human exposure studies, even though they may not include measurements of health outcomes or risk
p.000087: assessments.
p.000087: HHS has prepared a useful document entitled Communication in a Crisis: Risk Communication
p.000087: Guidelines for Public Officials, 2002. It is available online and in hard copy and includes a chapter
p.000087: on communicating complex, scientific, and technical information (U.S. HHS, 2002). They recommend
p.000087: using clear, nontechnical language, avoiding jargon, and putting technical terms into frames of reference
...
p.000088: • Emotional distress among community members
p.000088: • Possible discrimination in obtaining employment or insurance for a participant identified by the research to be at
p.000088: high risk of developing complications
p.000088: • Financial costs to participants and to researchers
p.000088:
p.000088: There are a variety of methods for providing study results to participants and the community. Fact
p.000088: sheets can be used to describe the study and provide general study findings to the community and
p.000088: stakeholders.
p.000088:
p.000088:
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p.000089:
p.000089: Individualized fact sheets can be used to disseminate results to the individual participants. Meetings
p.000089: with study participants have been used to disseminate study information. Community meetings also can be
p.000089: used to provide updates on study progress and general results.
p.000089: Examples of the processes and the materials used for dissemination of information are included in case studies
p.000089: described by Israel et al. (2005) and others conducting CBPR studies.
p.000089: Overall study results generally are disseminated in peer-reviewed journal manuscripts and study reports. The
p.000089: availability of results published in manuscripts and reports has been greatly enhanced by posting them on
p.000089: Internet Web sites. For example, all EPA reports are now available electronically via EPA’s National Service
p.000089: Center for Environmental Publications Web site (http://www.epa.gov/ncepihom/).
p.000089:
p.000089: 7.8 Reporting Unanticipated Results or Observations
p.000089: The previous subsection discussed reporting of routine results from observational human exposure
p.000089: studies. The communication plan should include processes and procedures for the dissemination of
p.000089: the study results. Additionally, the communication plan needs to integrate with the data and safety
p.000089: monitoring and oversight plans for the study and include a plan for reporting unanticipated results or
p.000089: observations. Unanticipated results may include measurements of a chemical at a concentration that
p.000089: exceeds what is considered to be an “acceptable” level in environmental media or biological fluids.
p.000089: Unanticipated observations might include observation of the use of a chemical not approved for indoor
p.000089: use, storage of chemicals in inappropriate containers, storage of chemicals in places accessible by
p.000089: children, etc. Unanticipated results or observations may be directly related to the research question
p.000089: being addressed in the study (e.g., measurements of pesticide residues in a home) or
p.000089: nonstudy hazards (e.g., frayed electrical cords that may pose a hazard to young children and residences).
p.000089: Section 4 discusses issues that may affect privacy and confidentiality. Section 4.3 covers
p.000089: collateral observations of nonstudy-related hazards, including those that States may mandate must
p.000089: be reported. Section 4.5 discusses the need for data and safety monitoring and oversight, including the
p.000089: development of plans to report and react to anticipated or unanticipated adverse events or conditions.
p.000089: As part of the study implementation plan and the communication plan, researchers should develop a
p.000089: protocol for how to identify contaminant measurements and exposures of “concern” that should be reported to the
p.000089: study participant as quickly as possible because of the potential risk associated with the exposure
p.000089: (see Section 4.5, Data and Safety Monitoring and Oversight, and also Section 2.7.1, Establishing Criteria
p.000089: and Standards for Monitoring Scientific and Ethical Issues During a Study.) The plan needs to include the
p.000089: protocol for making the determination and the criteria that will be used as the threshold or “trigger” for
p.000089: reporting. The plans should describe how the results will be reported to the participants and what additional
p.000089: action will be undertaken to assist the participant in reducing their exposures. The first step in
p.000089: developing the protocol is to identify what measurement will be used to identify exposures of concern. In
p.000089: observational human exposure studies, this will generally be the chemical measurement in either environmental or
p.000089: biological samples. For example, measurement of lead concentration in blood would be an appropriate exposure
p.000089: metric if the research question being addressed involves lead exposure. The measurement is relatively simple and
p.000089: can be performed with a short turnaround time. Similarly, measurements of chemicals in blood may be
p.000089: appropriate for other persistent chemicals that have relatively long half-lives in blood. For nonpersistent
p.000089: chemicals, biomarkers of exposure measured in urine or saliva may be appropriate metrics to identify exposures of
p.000089: concern. For some chemicals (e.g., PM, volatile organic compounds [VOCs], ozone), biomarkers of
p.000089: exposure either are not available or difficult to measure or interpret. In these cases, measurements in
p.000089: environmental media may be the best exposure metric. Whatever metric is chosen, it is important that the
p.000089: chemical analyses can be performed relatively quickly to reduce such exposures as quickly as possible.
p.000089: The second, and more difficult, step in developing the reporting protocol is to determine the
p.000089: level of concern that triggers reporting of the concentration to the study participant. For some environmental
p.000089: media, such as drinking water, EPA (2007) has established maximum contaminant levels that can be used as
p.000089: triggers for reporting. For example, if the researcher measures a level of arsenic in drinking water above
p.000089: 0.010 mg/L, he or she would be expected to report the level to the study participant. For other environmental media,
p.000089: such as air, there are few applicable standards. The National Ambient Air Quality Standards might be
p.000089: used for the criteria pollutants. Guidelines for occupational exposures, such as threshold limit
p.000089: values (TLVs) and biological exposure indices (BEIs) published by the
p.000089:
p.000089:
p.000090: 90
p.000090:
p.000090: American Conference of Governmental Industrial Hygienists (ACGIH, 2008) also may be used. TLVs are not
p.000090: standards; ACGIH formulates a conclusion on the level of exposure that the typical worker can experience without
p.000090: adverse health effects. Many people would argue that the TLVs are not conservative enough for the average
p.000090: population, particularly not for vulnerable lifestages (e.g., children, the elderly) and TLVs are only for
p.000090: exposure by inhalation. WHO (2005) also publishes air quality guidelines. These types of guidelines can be used to
p.000090: advise study participants if their exposures are high relative to the guidelines. Reporting levels should
p.000090: be conservative, but not so low that reporting the level to the participant causes unwarranted concern and
p.000090: stress. For other environmental media measured in observational human exposure studies, such
p.000090: as house dust or surface wipes, the measurement results cannot be used easily to estimate exposures, and they
p.000090: are a poor metric if used alone.
p.000090: An alternative approach to comparison of measurement results against available guidelines and
p.000090: standards is the comparison of measurements in biological fluids to measurement data available from the
p.000090: National Health and Nutrition Examination Survey (NHANES). For example, results of measurements of
p.000090: chemicals or their metabolites in urine or blood can be compared to different percentiles (e.g., the
p.000090: 95th) reported in the NHANES national reports (CDC, 2005). This type of comparison shows that the participant’s
p.000090: measurements are at the high end of the distribution of the NHANES data, suggesting that action may need to be
p.000090: taken to mitigate exposures. However, researchers need to be judicious in the selection of the exposure
p.000090: metric. Biomarkers in blood and biomarkers in urine can be very different exposure metrics and may represent
p.000090: different aspects of the exposure event. A similar approach could be taken with
p.000090: measurements of chemicals in environmental media if there are sufficiently large databases
p.000090: available for comparison. For many chemicals and many media such databases are not available. In some NERL
p.000090: studies, one comparison approach that has been used is to compare an individual’s environmental
p.000090: media measurements to the 50th, 75th, or 95th percentile concentrations for the entire study population,
p.000090: so that the participant can evaluate his or her measurement results relative to those of the other study
p.000090: participants.
p.000090: A more complex approach than using simple data comparisons is to calculate a reporting level defined as a
p.000090: chemical or metabolite concentration indicative of an absorbed dose greater than that of a target level
p.000090: (for
p.000090: example one-tenth) of a lifetime reference dose (RfD) level. For a pesticide, the absorbed dose
p.000090: could be estimated from the urinary pesticide metabolite level using an approach similar to the methodology
p.000090: published by Fenske et al. (2000). This deterministic approach to dose estimation allows direct
p.000090: back-calculation of doses from urinary metabolite concentrations using few assumptions and is
p.000090: consistent with current pesticide regulatory procedures for risk assessment. When using this approach, the
p.000090: research team will need to determine how conservative the reporting level should be, as there are no guidelines
p.000090: available for using this approach. If the concentrations of a metabolite measured in a study participants’
p.000090: urine level are indicative of elevated exposures (i.e., above the reporting level), the
p.000090: researchers would be expected to report the information to the participants and provide information or local
p.000090: contacts that could assist in helping the participants identify sources of exposure and reduce their exposures.
p.000090: Although this would seem to be a reasonable approach for some classes of chemicals, the authors are not aware
p.000090: of reports of the use of this approach in the scientific literature.
p.000090:
p.000090: 7.9 Anticipating and Responding to Criticism
p.000090: As discussed in other parts of this document, in spite of researchers best intentions, there may be situations
p.000090: that arise in which people’s perceptions of the study design or implementation plan are not accurate, or their
p.000090: opinions and beliefs about the ethical issues associated with a study may not be in agreement with those of the
p.000090: research team and others involved in the study (e.g., the peer review panel, the IRB). Just as it is
p.000090: not unreasonable to expect differences in opinion on scientific approaches to an observational study, it is
p.000090: not unreasonable to expect differences of opinion on ethical approaches. The researchers, therefore, should
p.000090: be prepared to respond to criticism. The implementation plan and the communication plan should address
p.000090: how the research team should anticipate study elements that may be criticized. During study
p.000090: conceptualization, the research team should develop a list of potentially controversial study
p.000090: elements (many of which are discussed in this document). For each study element, the research team should
p.000090: describe how the ethical approaches to the study element were evaluated and selected. Both the
p.000090: process and the rationale for selection of a particular approach should be documented. At each step in the study
p.000090: planning and review process, the research team should document discussions related to
p.000090:
p.000090:
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p.000091:
p.000091: the specific element, considerations that were made, actions taken, and justification for the actions.
p.000091: Input from research team members, internal reviewers, external reviewers, community members, and
p.000091: others involved in the study should be documented for these controversial study elements. Similarly, for
p.000091: potentially controversial study elements, the review and actions by the IRB should be documented. All of this
p.000091: information should be compiled for potential use to prepare a set of Q&As that can be used by the
p.000091: research team and sponsoring organization to respond to criticism. When responding to criticism, establishing
p.000091: trust and credibility are essential, as discussed previously. The public’s perception of trust and
p.000091: credibility is determined by the public’s perceptions of the researchers’ knowledge and expertise, openness
p.000091: and honesty, and concern and care (Peters et al., 1997). These factors are important to consider in
p.000091: developing the information and approach that will be used to respond to criticism.
p.000091: There is a large volume of information available on “crisis communication” that the reader can use to
p.000091: develop a plan for anticipating and responding to criticism (e.g., FCN, 2001; ATSDR, 2007; U.S.
p.000091: HHS,
p.000091: 2002). The key is to be proactive and have a plan before any criticism is raised.
p.000091:
p.000091: 7.10 Responding to the Media, Public Inquiries, and Other Stakeholders
p.000091: Like crisis communications, the communication plan should include detailed plans for how to interact with the
p.000091: stakeholders, the media, and the public. Standard approaches have been developed for
p.000091: effective communications (e.g., the Federal Communicators Network's Communicators Guide [FCN, 2001]) with
p.000091: the media and will not be included in this document. A proactive plan, open and transparent
p.000091: communications, and easily to comprehend information will ensure effective communications with
p.000091: stakeholders and the public.
p.000091:
p.000091: References
p.000091: American Conference of Governmental Industrial Hygienists (ACGIH) (2008). TLV/BEI Resources. Available:
p.000091: http://www.acgih.org/tlv/.
p.000091:
p.000091: Alderson P (1995). Will you help us with our research? Arch Dis Child 72(6):541-42.
p.000091:
p.000091: Anderson B, Hall B (1995). Parents’ perceptions of decision making for children. J Law Med Ethics 23(1):15-9.
p.000091:
p.000091: ATSDR (Agency for Toxic Substances and Disease Registry) (2007). A Primer on Health Risk Communication Principles
p.000091: and Practices [online publication]. Available: http://www.atsdr.cdc.gov/risk/riskprimer/ [accessed 12 June 2007].
p.000091:
p.000091: CDC (Centers for Disease Control and Prevention) (2005). Third National Report on Human Exposure to Environmental
p.000091: Chemicals. National Center for Environmental Health, Atlanta, GA, NCEH Pub. No. 05 0570. Available:
p.000091: http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf [accessed 12 June 2007].
p.000091:
p.000091: Covello V, Allen F (1988). Seven Cardinal Rules of Risk Communication. OPA-87-020. U.S. Environmental Protection
p.000091: Agency, Office of Policy Analysis, Washington, DC. Distributed by the Pennsylvania Dept. of Environmental Resources.
p.000091: Available: http://www.epa.gov/stakeholders/pdf/risk.pdf [accessed 12
p.000091: June 2007].
p.000091:
p.000091: Covello VT, McCallum DB, Pavlova M (eds) (1989). Effective Risk Communication: the role and responsibility of
p.000091: Government and Non-Government Organizations. New York. NY: Plenum Press.
p.000091:
p.000091: Covello V, Minamyer S, Clayton K (2007). Effective risk and crisis communication during water security emergencies
p.000091: summary report of EPA sponsored message mapping.
p.000091: EPA/600/R-07/027. National Homeland Security Research Center, Office of Research and Development, U.S. Environmental
p.000091: Protection Agency, Washington, DC. Available: http://www.epa.gov/nhsrc/pubs/reportCrisisCom040207.pdf
p.000091:
p.000091: FCN (Federal Communicators Network) (2001). Communicators Guide For Federal, State, Regional, and Local Communicators
p.000091: by the Federal Communicators Network. Available: http://www.publicforuminstitute.org/activities/2002/fcn/co mmguid.pdf
p.000091: [accessed 12 June 2007].
p.000091:
p.000091: Fenske RA, Kissel JC, Lu C, Kalman DA, Simcox NJ, Allen EH, Keifer MC (2000) Biologically based pesticide dose
p.000091: estimates for children in an agricultural community.
p.000091: Environ Health Persp 108(6):515-20.
p.000091:
p.000091: Fernandez CV, Kodish E, Weijer C (2003). Informing study participants of research results: an ethical imperative. IRB
p.000091: 25(3):12-19.
p.000091:
p.000091: Health Canada (2006). The Strategic Risk Communications Framework. Available: http://www.riskcommunications.gc.ca
p.000091: [accessed 18
p.000091: September 2007].
p.000091:
p.000091: IOM (Institute of Medicine) (2002). Responsible Research: A Systems Approach to Protecting Research Participants.
p.000091: Daniel D. Federman, Kathi E. Hanna, and Laura Lyman
p.000091:
p.000091:
p.000092: 92
p.000092:
p.000092: Rodriguez (eds). Washington, DC: The National Academies Press.
p.000092:
p.000092: Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005). Methods in Community-Based Participatory Research for Health. San
p.000092: Francisco, CA: Jossey-Bass.
p.000092:
p.000092: NIH (National Institutes of Health) (2005). Report and Recommendations on Public Trust in Clinical Research for the NIH
p.000092: Director from the Director’s Council of Public Representatives (COPR). National Institutes of Health, Director’s
p.000092: Council of Public Representatives, January 14, 2005. Available: http://copr.nih.gov/reports/public_trust.asp
p.000092: [accessed June 2007].
p.000092:
p.000092: Parkin RT (2004). Communications with research participants and communities: foundations for best practices. J Expo
p.000092: Anal Environ Epidemiol 14(7):516-23.
p.000092:
p.000092: Peters RG, Covello VT, McCallum DB (1997). The determinants of trust and credibility in environmental risk
p.000092: communication: an empirical study. Risk Anal 17(1):43-54.
p.000092:
p.000092: Stableford S and Mettger W (2007). Plain language: a strategic response to the health literacy challenge. J Public
...
p.000093: word itself carries no connotation of intent, and it is not equivalent to intentional exposure, dose (dosing), or
p.000093: intentional dosing. A review of the dictionary definition of exposure shows that the word has many different
p.000093: meanings, and shades of meaning, in common, everyday English. However, when the authors use the word in this text it is
p.000093: being used in the technical sense that is defined above.
p.000093: The authors’ understanding of the word exposure is illustrated in Figure A-1. This graphic is a paradigm that ORD uses
p.000093: in formulating its human health research program. The graphic illustrates that exposure occurs at the
p.000093: intersection of both the chemical, physical, or biological agent and the person who is exposed. To
p.000093: understand exposure, one must understand the distribution of the “agent” throughout the
p.000093: environment over time and combine that understanding with knowledge about the location and
p.000093: activities of people that bring them into contact with the agent. Knowledge about the distribution of the agent
p.000093: in space and time generally involves measurements and data collection about environmental conditions
p.000093: external to the person. Knowledge about the person’s behaviors requires collection of personal
p.000093: information or observations of their location and activities. Understanding exposure, including the pathways,
p.000093: routes, duration, frequency, and magnitude of the exposure, requires combing both types of information.
p.000093: See the Glossary, Appendix F, for more information and the definition of additional and related terms.
p.000093:
p.000093: Observational
p.000093: Observational human exposure studies, as used in the context of this document, involve only the collection of
p.000093: environmental or biological samples and information for the purpose of quantifying the contact between the
p.000093: participant and the agent being studied. Observational human exposure studies are inherently the process
p.000093: of watching people in context—in their natural environment, doing routine activities—and collecting
p.000093: the
p.000093:
p.000093:
p.000095: 95
p.000095:
p.000095: samples and relevant information from them and from their surroundings to measure and calculate
p.000095: the exposures that occurred in the same context.
p.000095: Scientific Study Design: From a scientific study design perspective, an observational study of the sort
p.000095: being considered in this document is one where the researcher does not control the variables but,
p.000095: rather, observes both the variable and the outcome and tries to infer the relationship between the variable
p.000095: and the outcome. This contrasts with a controlled study where the researcher isolates and controls
p.000095: one or more variables in a systematic way to assess the impact of changes in the variables on an
p.000095: outcome measure. Consider the intervention study examples cited in the section on regulatory
p.000095: distinctions below (cleaning a house to reduce exposure in the residence and wearing a particle mask to reduce
p.000095: exposure to smoke from forest fires). In those cases, participants would be assigned either to receive the
p.000095: intervention (treatment) or not (the control group). The outcomes (exposures) would be measured and compared
p.000095: between the two groups to assess the effectiveness of the intervention. Similarly, drug trials would randomly
p.000095: assign participants to receive either a test medication or a placebo. The medical outcome (e.g., pain
p.000095: relief, blood pressure, cholesterol levels in blood) would then be measured for all participants,
p.000095: and the outcomes compared between the treated group (getting the test medication) and the control
p.000095: group (receiving the placebo).
p.000095: Controlled studies are often desirable in science because, when properly designed, they provide
p.000095: unambiguous estimates of the impact of unique variables on the outcome (even if the impact of one variable could
p.000095: normally be overwhelmed by other factors) and eliminate the need for alternate explanations of
p.000095: the experimental results (because other factors are held constant). However, controlled studies are
p.000095: not always possible. They may be unethical (e.g., to “treat” a group of women with abortions to test if there
p.000095: is a linkage between having had an abortion and breast cancer), impractical (e.g., to follow a cohort large
p.000095: enough to yield statistically significant results in a test of rare side effects to a medication), or just
p.000095: impossible to accomplish (e.g., to measure nutritional levels of a population in the middle of a war zone).
p.000095: As a consequence, much medical research is observational in the scientific sense being considered
p.000095: here. Public health data represent observations of health outcomes, but the factors that may have led
p.000095: to or influenced those outcomes are not under the control of any researcher. Observational techniques long
p.000095: have been
p.000095: used in medical studies to infer information about the impacts of certain factors on health
p.000095: outcomes. Commonly used techniques include cohort studies, case- control studies, cross-sectional studies, case
p.000095: reports, case series, and descriptive studies (NEAC, 2006; Vandenbroucke et al., 2007).
p.000095: Observational human exposure studies as used in this document are considered to be observational from a
p.000095: scientific study design perspective because the variables leading to exposure are not controlled by the researchers.
p.000095: Most of the observational human exposure studies conducted by NERL to date have been cross-sectional
p.000095: studies (sometimes repeated several times). While a particular variable may not be controlled by
p.000095: the researcher, the study design (e.g., selection of the population to be studied, location of the
p.000095: research, data selection to exclude confounding factors) can sometimes influence the range of values over which a
p.000095: variable may be observed. For example, NERL’s observational human exposure studies to understand exposure to PM
p.000095: (see www.epa.gov/heasd/sources/projects_completed/pm_pa nel_studies.htm and www.epa.gov/heasd/sources/project
p.000095: s/a3a_understanding_airshed_sources.htm) have traditionally excluded homes with smokers from the
p.000095: study population to avoid cigarette smoke as a confounding factor in the studies.
p.000095: Observational Studies in Market Research, Ethnography, and the Common Vernacular:
p.000095: Observational market research can involve covert observation, overt observation, or
p.000095: researcher participation. Covert observation is said to have a “key advantage” that “the respondent or consumer is
p.000095: unaware that they are being observed, allowing their behavior to be observed naturally”
p.000095: (see http://www.asiamarketresearch.com/glossary/observatio nal-research.htm). This means that the
p.000095: subject’s behavior will be natural and uncontaminated by the researcher’s presence. On the other hand, covert
p.000095: observation may be construed to be deceitful and ethically questionable. Overt observations involve
p.000095: sampling surveys, polls, interviews, focus groups, etc. Validity of the data obtained this way may
p.000095: be shaded by people’s natural tendency to behave or respond ideally when they know they are being watched.
p.000095: Motorists routinely slow down when they think they are being observed by the police. Finally, the researcher may
p.000095: participate in the activity being observed. Ethnography is a long-term investigation of a group
p.000095: (often a culture) that is based on observations made while immersed in and, useually, participating in that
p.000095: group. “Ethnography provides a detailed exploration of group activity and may include
p.000095:
p.000095:
p.000096: 96
p.000096:
p.000096: literature about and/ or by the group.” (See
p.000096: http://writing.colostate.edu/guides/research/observe/com 3a1.cfm). One obvious problem with immersion
p.000096: techniques is that the researcher may lose his or her objectivity.
p.000096: In the common language use of the term observational research, it appears to the authors
p.000096: that some people understand the term to imply that the observations are both benign and often covert,
p.000096: that is, without interaction with the persons being studied. That is not the case in NERL’s observational human
p.000096: exposure studies. The research often takes place in and around the homes of the participants. Often, the research
p.000096: involves asking the participant to answer a questionnaire and to provide personal samples (e.g., urine,
p.000096: blood). Collection of survey information and personal urine and blood samples cannot be done covertly, and
p.000096: collecting a blood sample is not considered to be benign.
p.000096: Observational Research in NERL: NERL’s observational human exposure studies entail the
p.000096: collection of environmental or biological samples, data, and information from study participants and their
p.000096: surroundings in their everyday environments, as they go about their normal activities, for the purpose of
p.000096: quantifying the contact between the participant and the agent being studied. As such, the studies are designed
p.000096: to meet the regulatory definition of observational research in the CFR. NERL’s studies also meet the scientific
p.000096: definition of an observational study, because the variable being studied, exposure to some agent, is not controlled by
p.000096: the NERL scientists. The observations are not covert, and they may or may not be noninvasive (e.g.,
p.000096: sometimes blood samples may be collected).
p.000096: Because NERL’s observational human exposure studies meet the definition of human subjects research as set forth
p.000096: in the CommonXRule, there is also a regulatory requirement to meet the ethical and scientific standards set forth in
p.000096: EPA’s human subjects regulations and in Agency rules. The research protocol must be evaluated and approved
p.000096: by an IRB and by EPA’s Human Studies Research Review Official (HSRRO) before any human subjects research effort
p.000096: can take place. But, even more compelling to NERL managers and scientists is the fact that NERL cannot
p.000096: conduct observational human exposure studies without the participation of willing individuals. Indeed,
p.000096: without the research participants, NERL’s human exposure research would be nothing. This intimate
p.000096: involvement of research subjects in NERL’s research imposes moral and ethical obligations to deal with
p.000096: participants respectfully and to ensure their safety, protection, and well-being.
p.000096: Regulatory Distinction Between Intentional Exposure and Observational Research
p.000096: Intentional Exposure: The CFR states, “Research involving intentional exposure of a human subject
p.000096: means a study of a substance in which the exposure to the substance experienced by a human
p.000096: subject participating in the study would not have occurred but for the human subject’s participation in
p.000096: the study” [40 CFR 26.202(a)]. This definition sets forth two requirements regarding an
p.000096: intentional exposure: (1) the exposure has to be to a substance that is being studied, and (2) at least one
p.000096: aspect of the exposure to the substance being studied has to be attributable to the subject’s
p.000096: participation in the study.
p.000096: The first requirement means the objective of the study must be to understand the impact or exposure of
p.000096: the substance being studied. In observational human exposure studies, like those that NERL conducts, the
p.000096: research protocol may require the use of isopropyl alcohol or some other chemical to collect a
p.000096: personal sample (e.g., to sterilize the puncture site immediately prior to collection of a personal sample of
p.000096: blood drawn by a trained phlebotomist). Indeed, it would be both unethical and bad medical practice not
p.000096: to sterilize the puncture site before drawing blood. But this requirement does not constitute intentional
p.000096: exposure because the research is not the study of isopropyl alcohol but of some other agent. Incidental
p.000096: exposures to chemicals like isopropyl alcohol still must be considered from a safety perspective, pass both scientific
p.000096: and ethical review, and be approved by the IRB, but such incidental exposures do not constitute intentional
p.000096: exposure.
p.000096: The second requirement is that the exposure as experienced by the subject “would not have occurred but for the
p.000096: human subject’s participation in the study.” The two primary ways in which intentional exposure studies commonly meet
p.000096: this definition are by the direct introduction of the study substance into the research environment
p.000096: under the control of the research protocol or by scripting the participants’ activities in such a way that their
p.000096: contact with the study substance is determined by the research. Although either would be sufficient to meet
p.000096: the regulatory definition, many, if not most, intentional exposure studies attempt to control both.
p.000096: Because “exposure is quantified as the concentration of the agent in the medium in contact integrated over the
p.000096: time duration of that contact,” intentional exposure studies are usually more scientifically robust if both
p.000096: the concentration of the agent and the duration of the exposure are controlled by the research.
p.000096:
p.000096:
p.000096:
p.000097: 97
p.000097:
p.000097: Observational Research: In the language of the Code of Federal Regulations, “observational research means
p.000097: any human research that does not meet the definition of research involving intentional exposure of a
p.000097: human subject” (40 CFR 26.302).
p.000097: By this definition, observational research encompasses all human research that does not meet the
p.000097: definition of intentional exposure. As a consequence, it is a broad regulatory category that includes a variety of
p.000097: research domains, including human research that does not involve the study of exposures at all. This regulatory
p.000097: definition of observational is sufficiently broad, moreover, that it encompasses study types that
p.000097: this document is not intended to address. For example, it may be possible to design an intervention study that
p.000097: does not bring about or script in any way the participants’ exposure to a substance, but rather reduces or
p.000097: mitigates it. (Consider a study to test whether professional cleaning of the carpets, floors, walls, and
p.000097: other surfaces in a home might lead to a lower exposure to a residential contaminant or a study to determine if wearing
p.000097: a particle mask would reduce an individual’s exposure to smoke from forest fires.) Such a study
p.000097: might meet the regulatory definition of observational research (Note: The final decision in regard to whether
p.000097: any EPA study meets the definition of observational research resides with the Agency’s HSRRO), but it
p.000097: would not meet the authors’ intentions regarding “observational human exposure studies” as they are defined
p.000097: in this document. An intervention study, such as described in these two examples, does not involve
p.000097: observing people’s exposures in their everyday environments, as they go about their normal activities. In
p.000097: an intervention study, either the participant’s environment (cleaning of the household surfaces) or their
p.000097: behavior (wearing a particle mask) has been manipulated by the researcher. Secondly, the objective of these
p.000097: studies is not to understand exposures in everyday environments but would use changes in exposure
p.000097: to test the effectiveness of an intervention strategy. Such a study is not addressed in this document.
p.000097: Observational human exposure studies, as used by the authors of this document, generally meet the
p.000097: regulatory definition of observational research. But, not all studies meeting the CFR definition of
p.000097: observational research would be considered by the authors to be observational human exposure studies.
p.000097:
p.000097: Examples of NERL Observational Human Exposure Studies
p.000097: NERL and its predecessor organizations have
p.000097: conducted observational human exposure studies since 1980. Table A-1 lists many of those that NERL has
p.000097: conducted, supported, or participated in since 1980. The table gives the name of the study, dates, sample
p.000097: size, then type of study, a brief explanation of the research, and NERL’s role therein. The table represents a
p.000097: variety of first-party or second-party research efforts. In many cases, NERL staff would design,
p.000097: oversee, and, if possible, participate directly in the study (first-party), but often contractor
p.000097: support would be needed to accomplish the field sampling or some of the sample analysis. In other
p.000097: cases, NERL researchers would solicit proposals for exposure research to be conducted to address specific
p.000097: exposure issues and then would fund researchers in academia or at nonprofit institutions to design and
p.000097: conduct the research (second-party research). In a few cases, grants might already be in place with research
p.000097: institutions, and NERL simply would augment the pre-existing funding to expand the exposure component
p.000097: (second-party). Some other cases involve research efforts initiated by other Federal agencies with which NERL
p.000097: would collaborate and participate in directly (first-party).
p.000097: An examination of the entries in the table shows that most of the agents being studied were chemicals, often
p.000097: air pollutants or pesticides. A few of the entries indicate that other agents, for example, molds and fungi or other
p.000097: microbes, were the subject of the study. The largest number of the studies involved small numbers
p.000097: of participants and often were designed to determine whether or not a method for collecting
p.000097: exposure-related data or samples was feasible or burdensome. Most of the smaller studies used convenience samples.
p.000097: Studies, like DEARS, CTEPP, NHEXAS, and TEAM, which
p.000097: involved large numbers of participants, employed randomized or probability-based approaches
p.000097: for selecting participants.
p.000097: Table A-2 shows the types of samples that often have been collected in NERL’s observational human
p.000097: exposure studies. Some of the samples, like air concentrations or surface wipes, allow NERL staff
p.000097: to determine the concentration of the studied chemicals in the environmental media with which the participants
p.000097: may come into contact. Other items, like time activity diaries or videotaping children to measure the amount of
p.000097: hand-to-mouth activity, allow NERL researchers to understand how people may come into contact with the agent
p.000097: and to estimate the duration or frequency of a potential exposure. Still other measures, like personal
p.000097: samplers or biological samples, represent an attempt to determine a time-integrated measure of exposure. NERL
p.000097:
p.000097:
p.000098: 98
p.000098:
p.000098: staff put all of this information together to estimate an individual participant’s exposure,
p.000098: either through relatively direct measures of exposure or through algorithms that combine the
p.000098: media concentrations measurements and the activity data.
p.000098:
p.000098: References
p.000098: CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I Environmental Protection Agency Part 26 Protection of Human
p.000098: Subjects. U.S. Code of Federal Regulations.
p.000098: Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/ 40cfr26_06.html [accessed 12 June 2007].
p.000098:
p.000098: NEAC (National Ethics Advisory Committee) (2006). Ethical Guidelines for Observational Studies: Observational research
p.000098: audits and related activities. Wellington, New
p.000098: Zealand: Ministry of Health. Available: http://www.neac.health.govt.nz/moh.nsf/indexcm/neac
p.000098: resources-publications-ethicalguidelines.
p.000098:
p.000098: U.S. EPA (U.S. Environmental Protection Agency) (1992), Guidelines for Exposure Assessment. Environmental Protection
p.000098: Agency, Risk Assessment Forum, EPA/600/Z 92/001. Available: http://www.epa.gov/nceawww1/raf/pdfs/exposure.pdf
p.000098: [accessed 1 May 2008].
p.000098:
p.000098: Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, et al. (2007). Strengthening the Report of Observation
p.000098: Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Medicine 4(10): e297.
p.000098: doi:10.1371/journal.pmed.0040297.
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000099: 99
p.000099:
p.000099: Table A-1. Examples of Observational Human Exposure Studies Conducted or Funded by NERL or Its Predecessor
p.000099: Organizations
p.000099: Study Date Size Type Brief Description
p.000099: NERL Role
p.000099: Total Exposure 1980-1984 400 Three-stage The TEAM study was designed to develop and
p.000099: demonstrate EPA designed and Assessment Households stratified
p.000099: methods to measure human exposure to toxic substances in run, contractor Methodology
p.000099: probability air and drinking water. The goals were to develop methods to conducted
p.000099:
p.000099: (TEAM) Studies
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: Additional TEAM Studies
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: Nonoccupationa l Pesticides Exposure Study (NOPES)
p.000099:
p.000099:
p.000099:
p.000099: Nine-Home Children’s Pilot Study
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: Particle Total Exposure Assessment Methodology (PTEAM) Study
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: National Human Activity Pattern Study (NHAPS)
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.001987: 1987
p.001987:
p.001987:
p.001987:
p.001987:
p.001987:
p.001987:
p.001987: 1986-1988
p.001987:
p.001987:
p.001987:
p.001987:
p.001987:
p.001990: 1990
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990: 1990
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990: 1992-1994
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990:
p.001990: 51 in LA area, 17 in NJ,
p.001990: and 75 in Baltimore
p.001990:
p.001990:
p.001990:
p.001990:
p.000259: 259
p.000259:
p.000259:
p.000259:
p.000259:
p.000259:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000178: 178
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: 9,386
p.000178: selection, cross- sectional
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Convenience sample
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Probability selection, mainly cross- sectional, partly longitudinal
p.000178:
p.000178: Convenience pilot study
p.000178: to test methodology
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Probability
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: Probability (national random dialing)
p.000178: measure individual total exposure (from air, food, and water) and the resulting body burden of toxic and carcinogenic
p.000178: chemicals and to apply these methods within a probability- based sampling framework to estimate exposures and body
p.000178: burdens of urban populations in several U.S. cities. Air sampling measured personal exposure to airborne toxic
p.000178: chemicals in indoor air and in exhaled breath. Related objectives were to determine the relationships between personal,
p.000178: indoor, and outdoor, and blood, urine, and exhaled breath concentrations; determine the variability of VOC
p.000178: concentrations within a home; and determine seasonal and multiyear variability. The study was conducted in New Jersey,
p.000178: North Carolina, and North Dakota in three phases.
p.000178: A separate VOC TEAM study was carried out in Baltimore, MD: Baltimore lacks the petroleum and chemical manufacturing
p.000178: plants present in most of the previous TEAM study sites and is more representative of many U.S. cities. Focused studies
p.000178: were also conducted in New Jersey and Los Angeles to further explore the sources and factors contributing to personal
p.000178: VOC exposures identified in the earlier TEAM studies.
p.000178: First attempt to develop a methodology for measuring the potential exposure of the general population to common
p.000178: household pesticides using probability-based sampling; questionnaire data collection; and personal monitoring of air,
p.000178: drinking water, food, and dermal contact. Conducted in Jacksonville, FL, and Springfield and Chicopee, MA, to capture
p.000178: high- and low-pesticide-use areas, respectively.
p.000178: A 9-home pilot study was conducted to evaluate monitoring methods in the field that may be used to assess the potential
p.000178: exposures of children aged 6 months to 5 years to pesticides found in the home environment. Newly developed methods
p.000178: were tested for measuring pesticide residues in indoor air, carpet dust, outdoor soil, and on children's hands.
p.000178: Information also was collected on household characteristics, pesticides used and stored at the residence, and
p.000178: children's activities.
p.000178: A study of nonsmokers age 10 years and older in Riverside, CA, in which indoor, outdoor, and personal monitoring of
p.000178: integrated particle mass over 12-hour day and night periods was conducted for PM10 and PM2.5. Polycyclic aromatic
p.000178: hydrocarbon and phthalate measurements were collected indoors and outdoors at a subset of 125 homes. A separate
p.000178: monitoring site provided ongoing 12-hour measurements of ambient particles throughout the study (48 days). Reference
p.000178: PM10 and dichotomous samplers were used at this site in addition to personal and stationary monitors identical to those
p.000178: used for participant monitoring. Nighttime and daytime recall time-activity questionnaires, as well as household
p.000178: questionnaires, were administered to each selected subject and household, respectively, and meteorological and air
p.000178: exchange rate data were recorded for each monitored home.
p.000178: This survey collected 24-hour activity diaries and other questionnaire data from participants from 48 states. It was
p.000178: conducted as a next-day telephone recall interview.
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178: EPA designed and run, contractor conducted
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000178:
p.000100: 100
p.000100:
p.000100: Table A-1. (Continued)
p.000100: Study Date Size Type Brief Description
p.000100: NERL Role
p.000100: Agricultural 1993- 84 applicators AHS survey A large-scale, long-term ongoing study of
p.000100: Iowa and North Collaboration with Health Study present; and a subset is a
p.000100: Carolina pesticide applicators and farm families. This other agencies; (AHS)
p.000100: PES 1999- of family longitudinal collaborative effort involving the National Cancer Institute
p.000100: NERL led a
p.000100: 2003 members in study of (NCI), the National Institute of Environmental Health Sciences
p.000100: contractor-
p.000100: PES pesticide (NIEHS), the National Institute for Occupational Safety and
p.000100: conducted applicators in Health (NIOSH), and the U.S. Environmental Protection substudy called two
p.000100: states. Agency (EPA) examines how lifestyle habits, genetic factors, the Pesticide PES, led by and
p.000100: agricultural exposures contribute to the risk of disease Exposure Study.
p.000100: NERL, was a using questionnaire survey data from 89,658 participants. This
p.000100: cross- is the largest, most comprehensive study of agricultural health sectional ever conducted
p.000100: in the United States. The interagency exposure study. assessment study (Pesticide Exposure Study (PES)),
p.000100: led by
p.000100: NERL, was performed to assess exposures and exposure
p.000100: classification procedures used in the epidemiological study.
p.000100: The National 1995-1998 See specifics A Federal interagency research effort
p.000100: coordinated by EPA and EPA oversaw Human in entries
p.000100: consisting of four demonstration studies using probability- general design for Exposure
p.000100: below. based sampling designs conducted in partnership
p.000100: with other the research, then Assessment
p.000100: Federal agencies (CDC, FDA, and NIST), universities, and solicited, evaluated
p.000100: Survey research
p.000100: institutions. Household environmental and personal and funded the
p.000100: (NHEXAS)— samples were collected and
p.000100: questionnaires were administered. individual studies
p.000100:
p.000100: Overview
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: NHEXAS-
p.000100: Arizona
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: NHEXAS-
p.000100: Maryland
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: NHEXAS-
p.000100: Region 5
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: Minnesota Children’s Pesticide Exposure Study (MNCPES)
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 1995-1998
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 1995-1996
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 1995-1997
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.001997: 1997
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.001997:
p.000179: 179
p.000179: Households
p.000179:
p.000179:
p.000179:
p.000179:
p.000080: 80
p.000080: Households
p.000080:
p.000080:
p.000080:
p.000080:
p.000080:
p.000250: 250
p.000250: Households
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: 102 Children
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: Probability, cross- sectional
p.000250:
p.000250:
p.000250:
p.000250: Probability, longitudinal
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: Probability, cross- sectional
p.000250:
p.000250:
p.000250:
p.000250:
p.000250: Probability, cross- sectional
p.000250: Biological media, including blood and urine, also were sampled and monitored for parent contaminants or their
p.000250: metabolites.
p.000250: The studies were undertaken to evaluate total human exposure to multiple chemicals on a community and regional scale
p.000250: with the following aims: provide a baseline of the normal range of exposure to chemicals in the general population;
p.000250: identify subgroups of the general population that are likely to be highly exposed; and evaluate and improve the
p.000250: accuracy of models developed to predict exposure to chemicals.
p.000250: The NHEXAS-Arizona study sampled residences determined by a population-based probability research design for the total
p.000250: population of Arizona and measured metals, pesticides, and volatile organic compounds (VOCs). The study was conducted
p.000250: by a consortium composed of the University of Arizona, Battelle Columbus, and the Illinois Institute of Technology.
p.000250: The study sampled residences of Baltimore and four adjacent counties and measured metals, pesticides, and polycyclic
p.000250: aromatic hydrocarbons (PAHs). Data collection occurred up to 6 times over 1 year for each of the participating
p.000250: households. The study was conducted by Harvard University, Emory University, Johns Hopkins University, and Westat. The
p.000250: study investigated temporal variability in multimedia, multipollutant exposures.
p.000250: The Region 5 study was conducted in EPA's Region 5 (Ohio, Michigan, Illinois, Indiana, Wisconsin, and Minnesota), and
p.000250: included personal exposure, residential concentration, and biomarker measurements of metals and VOCs. The study was
p.000250: conducted by the Research Triangle Institute (RTI) and the Environmental and Occupational Health Sciences Institute
p.000250: (EOHSI).
p.000250: Multimedia study of children 3-13 years conducted in Minnesota to evaluate children's pesticide exposure in urban and
p.000250: rural areas. The study provides exposure, environmental, and biologic data relating to multipathway exposures of
p.000250: children for four primary pesticides (chlorpyrifos, malathion, diazinon, and atrazine), 14 secondary pesticides, and 13
p.000250: polynuclear aromatic hydrocarbons (PAHs). This study complements and extends the populations and chemicals included in
p.000250: the NHEXAS-Region 5 study.
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000250:
p.000101: 101
p.000101: (see below).
p.000101:
p.000101: Details of research were established by recipients.
p.000101:
p.000101:
p.000101:
p.000101: Designed and conducted by award recipient (see above).
p.000101:
p.000101:
p.000101: Designed and conducted by award recipient (see above).
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: Designed and conducted by award recipient (see above).
p.000101:
p.000101:
p.000101:
p.000101: Designed and conducted by award recipient (see above).
p.000101:
p.000101: Table A-1. (Continued)
p.000101: Study Date Size Type Brief Description
p.000101: NERL Role
p.000101: Particulate 1998-2001 200 Longitudinal A series of longitudinal studies in a
p.000101: number of U.S. cities NERL conducted Matter (PM) Individuals
p.000101: conducted by EPA or by organizations sponsored through the one panel study
p.000101:
p.000101: Panel Studies
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: Dietary Intake of Young Children (DIYC)
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: Children’s Pesticide Post- Application Exposure Study (CPPAES)
p.000101:
p.000101:
p.000101:
p.000101: Develop Risk Assessment and Define Some Risk Management Options for Exposure of Children to Toxic Mold Using
p.000101: Stachybotrys chartarum as an Example
p.000101: Children’s Total Exposure to Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP)
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: Car-Related Occupational PM and Air Toxics Exposure to Patrolmen Study (COPP)
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: 1999-2000
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: 1999-2001
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.002000: 2000
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000: 2000-2001
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002000:
p.002001: 2001
p.002001: (5 to 63 per study)
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 3 Homes
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 10 Homes
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 8 cases and
p.002001: 8 controls
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.000257: 257
p.000257: Households
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000257:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience, multiday pilot study to test methodology
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Case control study
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Randomized, cross- sectional
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: Convenience, longitudinal
p.000009: National Exposure Research Laboratory (NERL). A primary goal was to determine the relationships between personal
p.000009: exposures to particles and associated gases relative to stationary outdoor monitor concentrations in high-risk
p.000009: subpopulations and to identify human activity patterns that might contribute to personal exposure. The investigators
p.000009: varied study locations, monitoring seasons, and study populations.
p.000009: Susceptible subpopulations of interest included chronic obstructive pulmonary disease (COPD) patients, individuals with
p.000009: cardiovascular disease, the elderly, asthmatics, and African Americans with hypertension. Panels of healthy individuals
p.000009: also were included. Because the elderly is the subpopulation most sensitive to health effects associated with PM
p.000009: exposures, the majority of subjects were over age 65.
p.000009: Performed in the Raleigh, NC, area in homes with children 1 to 3 years old. Homeowners reported either professional or
p.000009: self applications of diazinon. Goals of the study were to evaluate methods to measure excess dietary exposures
p.000009: resulting from food-handling activities by young children during eating and to assess whether the Children’s Dietary
p.000009: Intake Model (CDIM) accurately represents total dietary exposures of children. Study resulted in refinements of model
p.000009: parameters for transfer and activity.
p.000009: Observational measurement study of exposure to chlorpyrifos among children 2-5 years of age in urban New Jersey homes
p.000009: following crack and crevice treatment by a professional applicator. Study investigated decay of pesticide levels over
p.000009: time, transfer of pesticide from microenvironmental media to child, and factors that affect transfer. Dermal transfer
p.000009: evaluated with surface wipes, hand wipes, dermal wipes, cotton garments, and videotaping.
p.000009: Physicians at Case-Western Reserve treating children with idiopathic pulmonary hemorrhage evaluated the nature of the
p.000009: fungus found in homes of the afflicted and control children to determine if Stachybotrys was a potential factor in the
p.000009: illness. Three of the 8 cases, and none of the controls, had Stachybotrys strains that potentially were implicated.
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: The largest children’s exposure study undertaken to date. It examines aggregate exposures of children 18 months to 5
p.000009: years to pollutants commonly found in everyday environments. The major objectives were to quantify children’s aggregate
p.000009: exposures, apportion exposure pathways, and identify important exposure media. Participants were recruited from 12
p.000009: urban and rural counties in North Carolina and Ohio using a random digit dialing method. Monitoring was performed at
p.000009: both daycare centers and homes. Samples collected include food, beverages, indoor air, outdoor air, hand wipes, dust,
p.000009: soil, transferable residues, floor and surface wipes, and urine. The samples were analyzed for more than 40 pollutants,
p.000009: including insecticides, phthalate esters, phenols, polychlorinated biphenyls, and PAHs.
p.000009: Scientists monitored air pollutants inside and outside vehicles of healthy highway patrol officers in North Carolina
p.000009: while troopers were on patrol for 9-hour shifts and examined cardiovascular effects. The findings indicated that people
p.000009: driving in motor vehicles are exposed to PM2.5 and other pollutants generated from motor vehicles, and that these
p.000009: exposures appear to cause cardiovascular changes.
p.000009:
p.000009:
p.000102: 102
p.000102: with contractor support; funded and collaborated on others with Harvard School of Public Health, University. of
p.000102: Washington, and NYU.
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL designed, contractor conducted
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL funded the Environmental and Occupational Health Sciences Institute (EOHSI).
p.000102:
p.000102:
p.000102:
p.000102: NERL staff collaborated with Case-Western Reserve University by conducting lab analysis for Stachybotrys.
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: NERL designed, contractor conducted
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: EPA designed and conducted with contractor support
p.000102:
p.000102: Table A-1. (Continued)
p.000102: Study Date Size Type Brief Description
p.000102: NERL Role
p.000102: First National 2001 168 Child care Probability- A collaborative study with the Department
p.000102: of Housing and HUD and CPSC Environmental centers based
p.000102: Urban Development (HUD) and the Consumer Product Safety study. NERL Health Survey of
p.000102: selection on Commission (CPSC) of pesticide use and young children’s collaborated
p.000102: and
p.000102: Child Care national scale (less than 6 years old)
p.000102: potential exposure to pesticides and conducted analysis
p.000102:
p.000102: Centers (CCC)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: A Pilot Study Examining Translocation Pathways Following a Granular Application of Diazinon to Residential Lawns (PET)
p.000102: Biological and Environmental Monitoring for Organo- phosphate and Pyrethroid Pesticide Exposures in Children Living in
p.000102: Jacksonville, FL (JAX)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: Exposure Assessment for Community- Acquired Legionnaires Disease
p.000102: Center for the Health Assessment of Mothers and Children of Salinas Quantitative Exposure Assessment Study (CHAMACOS)
p.000102: Feasibility of Macroactivity Approach To Assess Dermal Exposure (Daycare)
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001:
p.002001: 2001
p.002001:
p.002001:
p.002001:
p.002001:
p.002002: 2002
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 2002
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 6 Households
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002: 9 Households in NERL exposure component
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.002002:
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 20 Children
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: 9 Daycare centers
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience, multiday pilot study to test methodology for exposure measure- ments
p.000021:
p.000021:
p.000021:
p.000021: Convenience, cross- sectional
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Case-control
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Convenience
p.000021: other pollutants in institutional childcare centers. This national study used multistage sampling with clustering.
p.000021: Indoor wipe and outdoor soil samples were analyzed for pesticides, lead, and allergens (mold/fungi). Pesticide use
p.000021: practices and application information were obtained from the commercial pest control applicators serving the centers.
p.000021: Observational pilot exposure measurement study of residential exposures after homeowner had routinely applied granular
p.000021: formulation diazinon-containing turf treatment to residential lawns. Study was performed near Raleigh, NC, and was
p.000021: preceded by a 1-home methodology feasibility study. Purpose was to evaluate methods for assessing pet-borne transfer,
p.000021: translocation and exposure pathways, and decay rates.
p.000021:
p.000021:
p.000021:
p.000021: The objectives of this investigation in Jacksonville, FL, were to
p.000021: (1) assess organophosphate (OP) and pyrethroid pesticide exposures in a group of 4- to 6-year-old children from
p.000021: Jacksonville by measuring the urine metabolite levels,
p.000021: (2) identify possible sources of these pesticides through screening measurements and pesticide inventories, and
p.000021: (3) examine the relationship between environmental and biological levels. The Duval County Health Department (DCHD)
p.000021: collected urine samples for CDC from 200 children visiting six public health clinics in Jacksonville, and collected
p.000021: environmental screening samples at approximately 25% of these children’s homes. A detailed aggregate exposure
p.000021: assessment at 9 homes was overseen by NERL and involved collection of surface wipes, transferable residues, air,
p.000021: duplicate diet, cotton garment samples, and urine samples. A time- activity diary of the children’s activities was
p.000021: included.
p.000021: Work with Veteran’s Administration hospital staff. Cases of Legionnaires Disease were evaluated for potential for
p.000021: exposure from residential drinking water taps. In about 24% of the tested cases, homes were found to have Legionella
p.000021: bacteria in water taps at home, compared to their absence in other cases and in controls
p.000021: Incidental pesticide exposure measurement study of farmworkers’ children ages 5 to 35 mo. Purpose is the evaluation of
p.000021: methods for aggregate exposure measurements and the evaluation of pathways of exposure and important factors that
p.000021: affect exposure. Measurements include pesticide distributions in microenvironments where children spend time, transfer
p.000021: of pesticides from microenvironmental media to child, and factors that affect transfer.
p.000021:
p.000021:
p.000021:
p.000021: Study identified daycare centers with previously established contracts for routine monthly pesticide applications and
p.000021: conducted screening sampling in each to evaluate the distributions of transferable pesticide residues on floor surfaces
p.000021: where children spend time. One daycare was selected for intensive measurements, and children from different age groups
p.000021: volunteered to wear full-body cotton suits for short time periods while their activities were videotaped.
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000103: 103
p.000103: of molds/fungi and helped with lead and pesticide measurements.
p.000103:
p.000103:
p.000103: EPA conducted with contractor support
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: Multiagency effort; NERL was a participant and led the 9-home exposure component.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL funded IAG with VA to conduct study.
p.000103:
p.000103:
p.000103:
p.000103: EPA grant to UC Berkeley; NERL augmented the existing research effort.
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: NERL designed, contractor conducted
p.000103:
p.000103: Table A-1. (Continued)
p.000103: Study Date Size Type Brief Description
p.000103: NERL Role
p.000103: Tampa 2002 9 Residences Convenience Pilot study on methods for measuring personal,
p.000103: indoor NERL designed, Asthmatic sample,
p.000103: pilot residential, outdoor residential, and ambient combustion- contractor
p.000103: Children's Study study to test related products, particulate
p.000103: matter, and air toxics. The study conducted
p.000103: (TACS) methods. identified microenvironmental
p.000103: factors affecting penetration of pollutants into homes and reduction of exposures to pollutants for asthmatic children
p.000103: (0-5 years of age).
p.000103:
p.000103: Pilot Study To Evaluate Data Collection Methods for Young Children’s and Household Activities
p.000103: Detroit Exposure and Aerosol Research Study (DEARS)
p.000103:
p.000103:
p.000103:
p.000103: Accelerometer Pilot Study
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: Pilot Study of Waterborne Infections
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004: 2004-2007
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004: 2004
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002004:
p.002005: 2005
p.002005: 3 Homes
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.002005:
p.000150: 150
p.000150:
p.000150:
p.000150:
p.000150:
p.000150:
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.001296: 1296
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Randomized household selection with qualification criteria; longitudinal
p.001296:
p.001296: Convenience, pilot study to test methodology
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Convenience, all volunteers from community using public water supply
p.001296: Pilot aggregate exposure study of three homes to assess burden of alternative exposure sample collection methods.
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: Recruitment from seven distinct neighborhoods in Detroit required strong community relations and partnership with State
p.001296: and local organizations. This study monitored for air pollutants at the personal level and evaluates how well centrally
p.001296: located (ambient) monitors represent exposure at the residential and personal level. Sampling is for 5 days duration in
p.001296: summer and again in winter.
p.001296: Nine children <24 months old and their primary caregivers participated in this study to (a) determine if very young
p.001296: children will wear an accelerometer for relatively long periods of time and comply with the protocol for its use, (b)
p.001296: evaluate how well a caregiver can estimate the activity level of his/her infant or toddler when completing an
p.001296: exposure-oriented time-activity diary, and (c) compare accelerometer count output with caregiver-provided estimates of
p.001296: children's activity level.
p.001296: Measure antibodies in people’s saliva for antibodies to Cryptosporidium, Noroviruses, Rotaviruses, Helicobacter pylori,
p.001296: and Toxoplasma gondii before and after installation of an ultraviolet treatment system for a public water supply. Also
p.001296: served as test of methodology for detecting people’s prior exposure to infectious agents.
p.001296: NERL designed, contractor conducted
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: NERL designed and run; with contractor support and collaborators such as the University of Michigan
p.001296: NERL designed and run, with contractor support
p.001296:
p.001296:
p.001296:
p.001296:
p.001296: EPA planned research (NERL is a collaborator), contractor conducted
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.001296:
p.000104: 104
p.000104:
p.000104: Table A-2. Types of Samples Collected in NERL Observational Human Exposure Studies
p.000104: Samples or Data Exposure Concern and Typical Type of Analysis
p.000104: Environmental Media
p.000104: Air pollutants Air pollutants being inhaled. Collect samples from central site, outside
p.000104: residence, and inside residence to assess
p.000104: pollutants in various locales. Measure gaseous and particle-bound pollutants.
p.000104: Soil Estimate track in and subsequent dermal or inhalation contact. Analyze for
p.000104: metals, pesticides, etc.
p.000104: House dust Dust from carpets and floors that may result in dermal contact or reentrainment
p.000104: and inhalation. Analyze for pesticides, metals, and tracers of outdoor sources.
p.000104: Surface wipes Dermal contact, children’s hand to mouth, and contact with food and subsequent
p.000104: ingestion. Analyze for metals and pesticides. Examine eating and food preparation areas too.
p.000104: Transferable residues Similar to surface wipes, using a surrogate for the transfer from the surface to the
p.000104: skin.
p.000104: Duplicate diet Use to assess ingestion exposures from food. Exact duplicate of amount and items
p.000104: eaten by participant and analyzed for pesticides, metals, etc. Includes drinking water samples as part of diet or other
p.000104: beverages consumed.
p.000104: Handled food Finger foods like cheese or luncheon meets that have been prepared and processed
p.000104: identically to foods children might eat to evaluate how much pollution may be removed from surfaces and ingested with
p.000104: the food.
p.000104: Human Activity Data
p.000104: Time-activity diaries Recall diaries to account for all times and activities in a day. Information
p.000104: includes location and activities.
p.000104: Activity loggers Device used to assess the nature of a person’s activities. Portable
p.000104: nephelometers have been used to keep up with people’s activities by showing when they were near PM sources.
p.000104: Accelerometers to measure level of activity of children at play. GIS and inertial devices to try to measure locations
p.000104: as a function of time of day.
p.000104: Questionnaires Query participants about things like daily activities for themselves or their
p.000104: children; housing characteristics; participant characteristics, including occupation, diet, smoking habits, hobbies,
p.000104: etc.; and recent use of pesticides or other consumer products.
p.000104: Videotaping Use videos to measure frequency and duration of mouthing activities in children.
p.000104: Household inventories Inventory consumer products in house. Use items to ask about usage frequency and
p.000104: history.
p.000104: Researcher observations Information about open doors and windows (air exchange), heating and cooking sources,
p.000104: pets, and other activities that may lead to potential exposures may be observed.
p.000104: Personal or Biological Samples
p.000104: Urine Urinary excretion of pollutants and their contaminants give important
p.000104: information about the nature of prior exposures and their magnitude.
p.000104: Personal air monitors Individual wears samplers on his/her person while going about normal activities to
p.000104: measure pollutants in breathing zone of individual.
p.000104: Hand wipes Hand wipes remove contaminants from skin surface. Analyze for pesticides, metals,
p.000104: organic chemicals, and use values to estimate dermal exposure and hand-to-mouth ingestion of pollutants.
p.000104: Dermal surrogates Participant may wear cotton garments or socks as a collector. Clothing is analyzed
p.000104: for pesticides, metals, organic chemicals, etc. Measured contaminant quantities are used to estimate potential for
p.000104: dermal exposure.
p.000104: Saliva samples Test for antibodies to infectious agents, suggesting prior exposure and infection
p.000104: by microbial agent. Blood Some epidemiological studies that NERL scientists have
p.000104: collaborated on have collected blood samples.
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000105: 105
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: Appendix B
p.000105: The Process for Development of This Document: Description of the Expert Panel Workshop (November 28 and 29, 2006),
p.000105: the External Peer Review by the HSRB (October 21-24, 2007), and Public Comment
p.000105:
p.000105:
p.000105:
p.000105: Expert Panel Workshop
p.000105: An Expert Panel Workshop was convened in Durham, NC, on November 28 and 29, 2006. An ad hoc panel of
p.000105: experts was assembled to discuss issues associated with the preparation of this document prior to beginning
p.000105: its first draft. The workshop was coordinated by ERG, Inc., who was also responsible for compiling information
p.000105: from the workshop in a final workshop report, available on the Scientific and Ethical
p.000105: Approaches for Observational Exposure Studies (SEAOES) Web site at www.epa.gov/nerl/sots.
p.000105:
p.000105: The charge to the Expert Panel Workshop members was as follows.
p.000105: The panel is asked to consider these issues prior to the workshop in preparation for discussion during
p.000105: this workshop meeting:
p.000105: 1. Provide recommendations on the content and organization of the document.
p.000105: a. Identify the major scientific and ethical areas/issues in the design and
p.000105: implementation of observational human exposure measurement studies that should be considered for inclusion
p.000105: in the document.
p.000105: b. Identify specific elements in each of these major areas that should be considered for inclusion in
p.000105: the document.
p.000105: c. Provide recommendations on the type and level of information that should be considered for
p.000105: inclusion in the document when describing state-of-the-science approaches, methods,
p.000105: techniques, or standards.
p.000105: d. Provide recommendations on the criteria that should be considered when evaluating and identifying
p.000105: the state-of-the-science for
p.000105: the approaches, methods, techniques, or standards.
p.000105: 2. Provide recommendations and listings of sources of information for developing the document including
p.000105: case studies where available.
p.000105: 3. Identify at least ten specific elements of the design and implementation of these studies that the
p.000105: panel considers to have the most uncertainty with regard to the “state-of-the-science,” discuss these elements, and
p.000105: provide recommendations on state-of-the-science approaches for them.
p.000105:
p.000105: The following individuals were members of the Expert Panel.
p.000105:
p.000105: Timothy Buckley (Chair)
p.000105: Division of Environmental Health Sciences School of Public Health
p.000105: Ohio State University Columbus, OH
p.000105:
p.000105: Sophie Balk
p.000105: Attending Pediatrician
p.000105: Children’s Hospital at Montefiore Professor of Clinical Pediatrics Albert Einstein College of Medicine Bronx, NY
p.000105:
p.000105: David Carpenter
p.000105: Director, Institute of Health and Environment University of Albany, SUNY
p.000105: Rensselaer, NY
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000107: 107
p.000107:
p.000107: Giselle Corbie-Smith Department of Social Medicine University of North Carolina Chapel Hill, NC
p.000107:
p.000107: Alan Fleischman
p.000107: Senior Advisor
p.000107: The New York Academy of Medicine New York, NY
p.000107:
p.000107: Natalie Freeman
p.000107: Center for Environmental and Human Toxicology Department of Physiological Sciences
p.000107: University of Florida Gainesville, FL
p.000107:
p.000107: Loretta Jones
p.000107: Healthy African American Families Los Angeles, CA
p.000107:
p.000107: Bruce Lanphear
p.000107: Professor of Pediatrics and of Environmental Health Division of General and Community Pediatrics Cincinnati Children’s
p.000107: Hospital Medical Center Cincinnati, OH
p.000107:
p.000107: Michael Lebowitz
p.000107: Arizona Health Sciences Center Colleges of Public Health and Medicine University of Arizona
p.000107: Tucson, AZ
p.000107:
p.000107: Jerry Menikoff
p.000107: Department of History and Philosophy of Medicine University of Kansas Medical Center
p.000107: Kansas City, KS
p.000107:
p.000107: Rebecca Parkin
p.000107: Associate Dean for Research and Public Health Practice Professor of Environmental and Occupational Health School of
p.000107: Public Health and Health Service
p.000107: George Washington University Medical Center Washington, DC
p.000107: Review by the EPA Human Studies Review Board and Public Comment
p.000107: The process for developing this document included the following steps after the Expert Panel Workshop.
p.000107: • A draft document was written by NERL researchers.
p.000107: • The draft document was distributed to internal EPA staff for review and comment (see Acknowledgements for the
p.000107: list of reviewers).
...
Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| 45XcfrX46 | common rule |
| abuse | Victim of Abuse |
| access | Access to Social Goods |
| age | Age |
| armed forces | Soldier |
| authority | Relationship to Authority |
| autonomy | Impaired Autonomy |
| belief | Religion |
| belmont | belmont |
| blind | visual impairment |
| child | Child |
| children | Child |
| cioms | cioms guidelines |
| coerced | Presence of Coercion |
| cognitive | Cognitive Impairment |
| comatose | Comatose |
| commonXrule | common rule |
| control group | participants in a control group |
| crime | Illegal Activity |
| criminal | criminal |
| culturally | cultural difference |
| dependent | Dependent |
| diminished | Diminished Autonomy |
| disabled | Mentally Disabled |
| displaced | displaced |
| drug | Drug Usage |
| education | education |
| educational | education |
| elderly | Elderly |
| embryo | embryo |
| emergencies | patients in emergency situations |
| emergency | Public Emergency |
| employees | employees |
| ethnic | Ethnicity |
| ethnicity | Ethnicity |
| family | Motherhood/Family |
| fetus | Fetus/Neonate |
| fetuses | Fetus/Neonate |
| gender | gender |
| hazard | Natural Hazards |
| helsinki | declaration of helsinki |
| home | Property Ownership |
| homeless | Homeless Persons |
| homeowner | Property Ownership |
| ill | ill |
| illegal | Illegal Activity |
| illness | Physically Disabled |
| impaired | Cognitive Impairment |
| incapable | Mentally Incapacitated |
| incapacitated | Incapacitated |
| incapacity | Incapacitated |
| indigenous | Indigenous |
| infant | Infant |
| influence | Drug Usage |
| job | Occupation |
| language | Linguistic Proficiency |
| literacy | Literacy |
| low-income | Economic/Poverty |
| manipulated | Manipulable |
| mentally | Mentally Disabled |
| military | Soldier |
| minor | Youth/Minors |
| minority | Racial Minority |
| mothers | Mothers |
| native | Indigenous |
| necessities | Access to Social Goods |
| neonates | Fetus/Neonate |
| nomads | nomad |
| occupation | Occupation |
| officer | Police Officer |
| opinion | philosophical differences/differences of opinion |
| parent | parents |
| parents | parents |
| party | political affiliation |
| philosophy | philosophical differences/differences of opinion |
| physically | Physically Disabled |
| placebo | participants in a control group |
| police | Police Officer |
| political | political affiliation |
| poor | Economic/Poverty |
| pregnant | Pregnant |
| prisoners | Criminal Convictions |
| race | Racial Minority |
| racial | Racial Minority |
| religious | Religion |
| research staff | Laboratory Staff |
| restricted | Incarcerated |
| single | Marital Status |
| social status | Economic/Poverty |
| stigmatization | Threat of Stigma |
| stigmatized | Threat of Stigma |
| student | Student |
| substance | Drug Usage |
| terminally | Terminally Ill |
| threat | Threat of Stigma |
| undue influence | Undue Influence |
| unemployed | Unemployment |
| union | Trade Union Membership |
| usage | Drug Usage |
| violence | Threat of Violence |
| volunteers | Healthy People |
| vulnerability | vulnerable |
| vulnerable | vulnerable |
| women | Women |
| youth | Youth/Minors |
Indicator Peers (Indicators in Same Vulnerability)
| Indicator | Peers |
|---|
| 45XcfrX46 | ['commonXrule'] |
| access | ['necessities'] |
| armed forces | ['military'] |
| belief | ['religious'] |
| child | ['children'] |
| children | ['child'] |
| cognitive | ['impaired'] |
| commonXrule | ['45XcfrX46'] |
| control group | ['placebo'] |
| crime | ['illegal'] |
| disabled | ['mentally'] |
| drug | ['influence', 'substance', 'usage'] |
| education | ['educational'] |
| educational | ['education'] |
| ethnic | ['ethnicity'] |
| ethnicity | ['ethnic'] |
| fetus | ['fetuses', 'neonates'] |
| fetuses | ['fetus', 'neonates'] |
| home | ['homeowner'] |
| homeowner | ['home'] |
| illegal | ['crime'] |
| illness | ['physically'] |
| impaired | ['cognitive'] |
| incapacitated | ['incapacity'] |
| incapacity | ['incapacitated'] |
| indigenous | ['native'] |
| influence | ['drug', 'substance', 'usage'] |
| job | ['occupation'] |
| low-income | ['poor', 'socialXstatus'] |
| mentally | ['disabled'] |
| military | ['armedXforces'] |
| minor | ['youth'] |
| minority | ['race', 'racial'] |
| native | ['indigenous'] |
| necessities | ['access'] |
| neonates | ['fetus', 'fetuses'] |
| occupation | ['job'] |
| officer | ['police'] |
| opinion | ['philosophy'] |
| parent | ['parents'] |
| parents | ['parent'] |
| party | ['political'] |
| philosophy | ['opinion'] |
| physically | ['illness'] |
| placebo | ['controlXgroup'] |
| police | ['officer'] |
| political | ['party'] |
| poor | ['low-income', 'socialXstatus'] |
| race | ['minority', 'racial'] |
| racial | ['minority', 'race'] |
| religious | ['belief'] |
| social status | ['poor', 'low-income'] |
| stigmatization | ['threat', 'stigmatized'] |
| stigmatized | ['threat', 'stigmatization'] |
| substance | ['drug', 'influence', 'usage'] |
| threat | ['stigmatization', 'stigmatized'] |
| usage | ['drug', 'influence', 'substance'] |
| vulnerability | ['vulnerable'] |
| vulnerable | ['vulnerability'] |
| youth | ['minor'] |
Trigger Words
capacity
coercion
consent
cultural
developing
ethics
harm
justice
protect
protection
risk
sensitive
welfare
Applicable Type / Vulnerability / Indicator Overlay for this Input