79C3C34C52B45572883A05D425EB0F82
CIOMS Guidelines
https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf
http://leaux.net/URLS/ConvertAPI Text Files/CF77FBF6CC6D44F030610BC073454849.en.txt
Examining the file media/Synopses/CF77FBF6CC6D44F030610BC073454849.html:
This file was generated: 2020-12-01 05:05:51
| 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.000007: groups are exposed to risks and burdens in order to generate the knowledge needed to protect and promote
p.000007: people’s health (see Guideline 1 – Scientific and social value and respect for rights). Equity in the distribution of
p.000007: burdens of research requires special care to ensure that individuals, communities or populations that are already
p.000007: disadvantaged or marginalized are not over-represented in research. A disproportionate selection of disadvantaged or
p.000007: convenient populations is morally problematic for several reasons. First, it is unjust to selectively invite poor or
p.000007: marginalized individuals or groups to participate in research because this concentrates the risks and burdens of
p.000007: research on people who already experience increased risks and burdens from social and economic disadvantage. Second,
p.000007: these individuals and groups are also the most likely to be excluded from, or to have difficulty accessing, the
p.000007: benefits of research. Third, the broad inclusion of different social groups helps to ensure that research is conducted
p.000007: in a socially and ethically acceptable manner. When research is concentrated in disadvantaged or marginalized groups,
p.000007: it may be easier to expose participants to unreasonable risks or undignified treatment. Furthermore, research results
p.000007: obtained from disadvantaged populations may not be appropriately extrapolated to the general population.
p.000007:
p.000007: In the past, certain groups have been over-used as research subjects. In some cases, this has been based on the easy
p.000007: availability of the populations. For example, in the United States prisoners were considered ideal persons for Phase I
p.000007: drug studies in the past. Other populations that may be over- represented in research because of their easy
p.000007: availability include students in researchers’ classes, residents of long-term care facilities and subordinate members
p.000007: of hierarchical organizations. In other cases, impoverished groups have been over-used because of their willingness to
p.000007: serve as subjects in exchange for relatively small stipends, their desire to access medical care, or because research
p.000007: hospitals are often located in places where members of the lowest socio-economic classes reside.
p.000007:
p.000007: Not only may certain groups within a society be inappropriately over-used as research participants, but also entire
p.000007: communities or societies may be over-used. Such over-use is especially problematic when the populations or communities
p.000007: concerned bear the burdens of participation in research but are unlikely to enjoy the benefits of new knowledge and
p.000007: products developed as a result of the research.
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p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000008:
p.000008: GUIDELINE 4:
p.000008: POTENTIAL INDIVIDUAL BENEFITS AND RISKS OF RESEARCH
p.000008:
p.000008: To justify imposing any research risks on participants in health research, the research must have social
p.000008: and scientific value. Before inviting potential participants to join a study, the researcher, sponsor and the
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p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
p.000034: factors can be internal to participants, such as mental illness, whereas other influences can be external, such as a
p.000034: dependent relationship between participants and clinician-researchers. Circumstances such as severe illness or poverty
p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
p.000034: consent in these situations. Research ethics committees must determine for each individual protocol if influences on
p.000034: voluntary consent cross the threshold of being undue, and if so, which safeguards are appropriate.
p.000034:
p.000034: Dependent relationship. There are different forms of dependent relationships, such as those between
p.000034: teachers and students, and guards and prisoners. In the context of clinical research, dependent
p.000034: relationships can result from pre-existing relationships between a treating physician and a patient, who
p.000034: becomes a potential participant when his or her treating physician assumes the role of researcher. The
p.000034: dependent relationship between patients and clinician-researchers may compromise the voluntariness of informed
p.000034: consent, since potential participants who are patients depend on the clinician-researcher for medical care and
p.000034: may be reluctant to refuse an invitation to enrol in research in which the treating clinician is involved. Therefore,
p.000034: in principle, in the case of a dependent relationship a neutral third party such as a research nurse or a
p.000034: qualified collaborator,
p.000034:
p.000034:
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p.000035:
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p.000035: should obtain informed consent. However, in some situations of dependency, it is preferable that the clinician provide
p.000035: the patient with information since he or she is most knowledgeable about the condition of the patient. However, to
p.000035: minimize the influence of the dependent relationship, several protective measures must be taken. Clinicians engaged in
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p.000087: affect the safety of participants, or other ethical matters that emerge during the course of the study.
p.000087: These further reviews include progress reports submitted by researchers and possible monitoring of researchers’
p.000087: compliance with approved protocols.
p.000087:
p.000087: Committee membership. The research ethics committee must be constituted according to a document that
p.000087: specifies the manner in which members and the chair will be appointed, reappointed, and replaced. Research ethics
p.000087: committees must have members capable of providing competent and thorough review of research proposals. Membership
p.000087: normally must include physicians, scientists and other professionals such as research coordinators, nurses,
p.000087: lawyers, and ethicists, as well as community members or representatives of patients’ groups who can represent
p.000087: the cultural and moral values of study participants. Ideally, one or more members should have experience as study
p.000087: participants since there is growing recognition that knowledge gained through personal experience as a participant can
p.000087: supplement the professional understanding of illness and medical care. Committees must include both men and women.
p.000087: When a proposed study involves vulnerable individuals or groups, as may be the case in research involving
p.000087: prisoners or illiterate persons, representatives of relevant advocacy groups should be invited to meetings where such
p.000087: protocols will be reviewed (see
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p.000088: Guideline 15 – Research involving vulnerable persons and groups). Regular rotation of members is desirable for
p.000088: balancing the advantage of experience with that of fresh perspectives.
p.000088:
p.000088: Members of research ethics committees must regularly update their knowledge about the ethical conduct of health-related
p.000088: research. If committees do not have the relevant expertise to adequately review a protocol, they must consult
p.000088: with external persons with the proper skills or certification. Committees must keep records of their
p.000088: deliberations and decisions.
p.000088:
p.000088: Conflicts of interests on the part of committee members. Research ethics committees must provide independent ethical
p.000088: opinions. Pressure can be brought to bear from many different directions, not just financial. Research ethics
p.000088: committees must therefore have mechanisms to ensure the independence of their operations. In particular, they
p.000088: must avoid any undue influence and minimize and manage conflicts of interests. Research ethics committees must
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Political / Illegal Activity
Searching for indicator illegal:
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p.000010: populations who stand to benefit most from the intervention under study. Measures to maximize potential individual
p.000010: benefits need to be carefully balanced with competing considerations. For example, sharing data or specimens for future
p.000010: research can pose risks to participants, especially when adequate safeguards to protect confidentiality are not in
p.000010: place.
p.000010:
p.000010: Risks to research participants. To evaluate the acceptability of risks in a given study, researchers, sponsors and
p.000010: research ethics committees must begin by ensuring that the study poses a socially valuable research question and
p.000010: employs sound scientific methods for addressing this question. They must then determine for each
p.000010: intervention and procedure in the study that the associated risks to participants are minimized and that
p.000010: mitigation procedures are in place. This can involve ensuring that plans and procedures exist to adequately
p.000010: manage and reduce risks, for example by:
p.000010: f monitoring the study and providing mechanisms for responding to adverse events;
p.000010: f establishing a Data Safety and Monitoring Committee (DSMC) to review and decide on data on harms and benefits as a
p.000010: study progresses;
p.000010: f instituting clear criteria for stopping a study;
p.000010: f installing safeguards to protect the confidentiality of sensitive personal data;
p.000010: f seeking exemptions, where possible, from requirements to report information about illegal activities of study
p.000010: participants (such as sex work in countries where prostitution is forbidden by law);
p.000010: f avoiding unnecessary procedures (for example, by performing laboratory tests on existing blood samples instead of
p.000010: drawing new blood, where scientifically appropriate); and
p.000010: f excluding participants who are at a significantly increased risk of being harmed from an intervention
p.000010: or procedure.
p.000010:
p.000010: Measures to minimize risks need to be carefully balanced with competing considerations regarding the scientific and
p.000010: value of research and fair subject selection. For example, decisions to stop a trial due to early,
p.000010: significant findings have to be balanced with the need to collect robust data on investigational interventions that are
p.000010: adequate to guide clinical practice.
p.000010:
p.000010: Researchers, sponsors and research ethics committees must then ensure that the risks of each intervention
p.000010: and procedure, once minimized, are appropriately balanced in relation to the intervention’s prospect of benefit for the
p.000010: individual participant and the social and scientific value of the research. For interventions that have a prospect of
p.000010: potential individual benefit, risks are acceptable if they are outweighed by the potential individual benefits for the
p.000010: individual participant and the intervention’s risk- benefit profile is at least as advantageous as any established
p.000010: effective alternative. Participants in the
p.000010:
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p.000033:
p.000033: Documentation of consent. Consent may be indicated in a number of ways. The participant may express consent orally, or
p.000033: sign a consent form. As a general rule, the participant should sign a consent form, or, where the individual lacks
p.000033: decisional capacity, a legal guardian or other duly authorized
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p.000033: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: representative must do so (see Guideline 16 – Research involving individuals incapable of giving informed
p.000034: consent, and Guideline 17 – Research involving children and adolescents). The research ethics committee may approve a
p.000034: waiver of the requirement of a signed consent document under certain conditions (see Guideline 10 – Modifications and
p.000034: waivers of informed consent). Such waivers may also be approved when existence of a signed consent form might pose a
p.000034: risk to the participant, for example in studies involving illegal behaviour. In some cases, especially when the
p.000034: information is complicated, participants should be given information sheets to retain; these may resemble
p.000034: conventional sheets in all respects except that participants are not required to sign them. Their wording
p.000034: must be approved by the research ethics committee. When consent has been obtained orally, researchers
p.000034: should provide to the research ethics committee documentation of consent, certified either by the person
p.000034: obtaining consent or by a witness at the time consent is obtained.
p.000034:
p.000034: Renewing consent. When substantive changes occur in any aspect of a study, the researcher must again seek
p.000034: informed consent from the participants. For example, new information may have come to light, either from the study
p.000034: itself or other sources, about the risks or benefits of products being tested or about alternatives to them.
p.000034: Participants must be given such information promptly. In most clinical trials, interim results are not disclosed to
p.000034: researchers or participants until the study has been concluded. In long-term studies, the willingness of each
p.000034: participant to continue in the study must be ensured.
p.000034:
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p.000057: committee when such proposals are under review (see commentary on Guideline 9 – Individuals capable of giving informed
p.000057: consent, section on Dependent relationship). Some individuals with this characteristic may also have diminished
p.000057: capacity to consent, and therefore require the additional protections noted earlier for participants who lack
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
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Political / Refugee Status
Searching for indicator asylum:
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p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
p.000057: committee when such proposals are under review (see commentary on Guideline 9 – Individuals capable of giving informed
p.000057: consent, section on Dependent relationship). Some individuals with this characteristic may also have diminished
p.000057: capacity to consent, and therefore require the additional protections noted earlier for participants who lack
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
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Political / displaced
Searching for indicator displaced:
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p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
p.000057: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000058: stereotypes. One proposed mechanism that can be used to avoid stereotyping is consultation with relevant stakeholders,
p.000058: where feasible, before, during and after the conduct of the research (see Guideline 7 – Community
p.000058: engagement).
p.000058:
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Political / nomad
Searching for indicator nomads:
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p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
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p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: stereotypes. One proposed mechanism that can be used to avoid stereotyping is consultation with relevant stakeholders,
p.000058: where feasible, before, during and after the conduct of the research (see Guideline 7 – Community
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Political / person under arrest
Searching for indicator arrest:
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p.000061: be sought. Surrogate decision-makers must evaluate to what extent study participation is consistent with the
p.000061: individual’s previously formed preferences and values (if any), and, in the case of research that offers participants a
p.000061: prospect of clinical benefit, to what extent study participation promotes the individual’s clinical interests.
p.000061: Previously stated preferences regarding the individual’s willingness to enrol in research or documented preferences in
p.000061: an advance directive should be respected. Researchers must recognize that surrogates may have their own
p.000061: interests that may call their permission into question. Furthermore, in situations where a legally
p.000061: authorized representative is not available to allow for timely enrolment, researchers may obtain the permission of a
p.000061: representative who is socially accepted but not formally recognized before the law.
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p.000062:
p.000062:
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p.000062: Emergency care situations in which the researcher anticipates that many participants will be unable to
p.000062: consent. Research protocols are sometimes designed to address conditions occurring suddenly and rendering the
p.000062: patients or participants incapable of giving informed consent. Examples are sepsis, head trauma, cardiopulmonary arrest
p.000062: and stroke. In such circumstances, it is often necessary to proceed with the research interventions very soon after the
p.000062: onset of the condition in order to evaluate an investigational treatment or develop the desired knowledge.
p.000062:
p.000062: If possible, an attempt must be made to identify a population that is likely to develop the condition to be studied.
p.000062: This can be done readily, for example, if the condition is one that recurs periodically in individuals, such as grand
p.000062: mal seizures and alcohol binges. In such cases, researchers should ideally contact potential participants while fully
p.000062: capable of informed consent, and obtain their agreement to be involved in the research during future periods of
p.000062: incapacitation, for example in an advance directive.
p.000062:
p.000062: If there is no opportunity to solicit informed consent of participants while fully capable of informed consent, plans
p.000062: to conduct emergency care research with incapacitated persons must be publicized within the community in which it will
p.000062: be carried out, where feasible. In the design and conduct of the research, the research ethics committee, the
p.000062: researchers and the sponsors must be responsive to the concerns of the community. The research must not be carried out
p.000062: if it does not have substantial support in the community concerned. (See commentary on Guideline 4 – Potential
p.000062: individual benefits and risks of research, section on Risks to groups of persons, and Guideline 7 – Community
p.000062: engagement).
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Political / political affiliation
Searching for indicator party:
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p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
p.000034: consent in these situations. Research ethics committees must determine for each individual protocol if influences on
p.000034: voluntary consent cross the threshold of being undue, and if so, which safeguards are appropriate.
p.000034:
p.000034: Dependent relationship. There are different forms of dependent relationships, such as those between
p.000034: teachers and students, and guards and prisoners. In the context of clinical research, dependent
p.000034: relationships can result from pre-existing relationships between a treating physician and a patient, who
p.000034: becomes a potential participant when his or her treating physician assumes the role of researcher. The
p.000034: dependent relationship between patients and clinician-researchers may compromise the voluntariness of informed
p.000034: consent, since potential participants who are patients depend on the clinician-researcher for medical care and
p.000034: may be reluctant to refuse an invitation to enrol in research in which the treating clinician is involved. Therefore,
p.000034: in principle, in the case of a dependent relationship a neutral third party such as a research nurse or a
p.000034: qualified collaborator,
p.000034:
p.000034:
p.000034: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: should obtain informed consent. However, in some situations of dependency, it is preferable that the clinician provide
p.000035: the patient with information since he or she is most knowledgeable about the condition of the patient. However, to
p.000035: minimize the influence of the dependent relationship, several protective measures must be taken. Clinicians engaged in
p.000035: research must acknowledge and inform patients that they have a dual role as the treating clinician and researcher. They
p.000035: must emphasize the voluntary nature of participation and the right to refuse or withdraw from the research. They must
p.000035: also assure patients that their decision whether to enrol or refuse participation will not affect the therapeutic
p.000035: relationship or other benefits to which they are entitled. In cases where it is necessary for the treating clinician to
p.000035: explain the details of the study protocol, the research ethics committee must consider whether the informed consent
p.000035: document must be signed in the presence of a neutral third party.
p.000035:
p.000035: Risks. Researchers must be completely objective in discussing the details of the experimental intervention,
p.000035: the pain or discomfort it may entail, and known risks and possible hazards. In some types of prevention research,
p.000035: potential participants must receive counselling about risks of acquiring a disease and steps they can take to reduce
p.000035: those risks. This is especially true of preventive research on communicable diseases, such as HIV/AIDS.
p.000035:
p.000035: Who obtains consent. Informed consent must be obtained by a member of the research team. Delegation of obtaining
p.000035: consent, for instance to a research nurse or another member of the research team, for instance in the case of a
p.000035: dependent relationship, is permissible as long as the person who obtains consent is duly qualified and has
p.000035: prior experience in obtaining consent. The principal investigator is responsible for ensuring that all personnel
p.000035: working on the project comply with this Guideline.
p.000035:
p.000035: Special considerations regarding informed consent for the use of data in health registries. The requirement to obtain
p.000035: informed consent for research on data in health-related registries may be waived, provided the conditions in Guideline
...
p.000107: (Ministry of Health-MoH). Main topics of interest include Infectious and Parasitic Illnesses, bioethics, public health
p.000107: and clinical immunology. He has participated in several working groups that gave rise to
p.000107: national/international guidelines related to ethics, prevention, care and treatment of HIV/AIDS and TB. He has
p.000107: frequently acted as temporary advisor to many national/international institutions, such as the Brazilian AIDS
p.000107: Programme, WHO, UNITAID, UNAIDS, CIOMS and WMA. From 2010 to 2013 he directed the Department of STD, AIDS and Viral
p.000107: Hepatitis (Secretary of Health Surveillance, MoH, Brazil).
p.000107:
p.000107: David Haerry
p.000107: David Haerry is a treatment writer and conference reporter since 1996. He is co-authoring a database on travel &
p.000107: residency restrictions for people living with HIV. David Haerry has been involved in health care professionals
p.000107: education projects since 2007. Since 2015, he is Secretary General of the Swiss Academic Foundation on Education in
p.000107: Infectious Diseases SAFE-ID. He is work package co-leader and member of the Executive Committee in the EUPATI-IMI
p.000107: project and involved in a number of European and global research networks and research collaborations, including the
p.000107: ENCePP Steering Group. He is co-chair of the Patient and Consumer Working Party at the European Medicines Agency and
p.000107: has served the European AIDS Treatment Group EATG in various positions since 2004. David has been involved in HIV and
p.000107: HCV drug development since 2005 and has specific interests in the areas of Personalised Medicine, Risk Communication,
p.000107: Pharmacovigilance, Observational Studies, Biomedical Prevention and HIV Eradication Research. He is living with HIV
p.000107: since 1986.
p.000107:
p.000107: Bocar Kouyaté
p.000107: Bocar A. Kouyaté is Senior Advisor to the Minister of Health, Burkina Faso and researcher at the Centre national de
p.000107: recherché et de formation sur le paludisme (CNRFP), Burkina Faso. Dr Kouyaté is a physician by training and holds
p.000107: a PhD degree in public health. He has worked throughout all levels of the health system in Burkina Faso from
p.000107: district medical officer to the intermediary level as
p.000107:
p.000107:
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p.000108: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108: Provincial Director of Health and to Secretary General of the Ministry of Health from 1983 to 1998. From 1989 to 2009,
p.000108: he was Director of two research centres in Burkina Faso (Centre de recherche en santé de Nouna and, later on, Centre
p.000108: national de recherche et de formation sur le paludisme). He served as member of the Comité national d’éthique
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Searching for indicator political:
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p.000119: in line with the Declaration of Helsinki.
p.000119:
p.000119: At the beginning of October 2016 the final draft was submitted to the CIOMS Executive Committee, which approved the
p.000119: text at its General Assembly meeting in Geneva in November 2016.
p.000119:
p.000119: The final draft replaces all previous versions of the CIOMS ethical guidelines, both in the domain of
p.000119: biomedical and epidemiological research. At the same time, research projects that have been ethically
p.000119: assessed on the basis of previous versions of the guidelines may be continued on the terms and conditions as set out in
p.000119: those previous versions.
p.000119:
p.000119: Reactions to the Guidelines are welcome and should be addressed to the Secretary-General, Council for International
p.000119: Organizations of Medical Sciences, P.O. Box 2100, CH-1211 Geneva 2, Switzerland; or by email to info@cioms.ch.
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119: x
p.000119:
p.000119: EVIDENCE RETRIEVAL AND SYNTHESIS
p.000119: In the revision process, literature reviews were used as sources for further ethical deliberation.
p.000119: Authoritative declarations, reports and guidance documents have had a prominent role in these discussions,
p.000119: such as the Nuremberg Code (1947), the Universal Declaration of Human Rights of the United Nations (1948), the
p.000119: International Covenant on Civil and Political Rights of the United Nations (1966), the Belmont Report (1979), the
p.000119: Guideline on Good Clinical Practice (GCP) of the International Conference on Harmonisation of Technical Requirements
p.000119: for Registration of Pharmaceuticals for Human Use (ICH) (1996), the Oviedo Convention of the Council of Europe (1997),
p.000119: the Universal Declaration on Bioethics and Human Rights of UNESCO (2005), the UNAIDS/WHO Ethical
p.000119: Considerations in Biomedical HIV Prevention Trials (2007/2012), Standards and operational guidance for
p.000119: ethics review of health-related research with human participants of the WHO (2011), and the Declaration of Helsinki of
p.000119: the World Medical Association (2013). Some of these guidelines have been extensively used, in particular the UNAIDS/WHO
p.000119: document (2012) for Guideline 7 on community engagement.
p.000119:
p.000119: Textbooks, existing ethical frameworks for human subjects research and reports on research involving human beings
p.000119: were also valuable sources of information. The Working Group reviewed papers in major ethics journals (in
p.000119: alphabetical order) such as the American Journal of Bioethics, Bioethics, BMC Medical Ethics, the Cambridge
p.000119: Quarterly of Healthcare Ethics, Developing World Bioethics, the Hastings Center Report, the Journal of Bioethical
...
p.000075:
p.000075: Research in disasters and disease outbreaks should ideally be planned ahead. Health officials and research
p.000075: ethics committees should develop procedures to ensure appropriate, expedient and flexible mechanisms and
p.000075: procedures for ethical review and oversight. For example, research ethics committees could pre-screen study
p.000075: protocols in order to facilitate and expedite ethical review in a situation of crisis. Similarly,
p.000075: researchers and sponsors could make pre-arrangements on data- and sample-sharing that research ethics committees
p.000075: review in advance.
p.000075:
p.000075: Sponsors and research ethics committees should evaluate and seek to minimize the risks to researchers and
p.000075: health professionals conducting research in a disaster context. Sponsors should include in the protocol a plan for
p.000075: mitigating adverse events. Furthermore, appropriate resources for mitigation measures should be included in the
p.000075: protocol budget.
p.000075:
p.000075:
p.000075: Commentary on Guideline 20
p.000075: Humanitarian response and research in the acute phase of disasters and diseases outbreaks. Disasters are sudden events
p.000075: that cause great suffering or loss of life. Disease and illness can either be the cause or a result of disasters. For
p.000075: example, epidemics can lead to disasters and destabilize political institutions or undermine economic activity.
p.000075: Conversely, natural and man-made disasters, such as earthquakes and war, can weaken or destroy health systems and have
p.000075: a devastating impact on individual and population health. The first and foremost obligation in acute
p.000075: disaster situations is to respond to the needs of those affected. At the same time, an obligation
p.000075: exists to conduct health-related research because disasters can be difficult to prevent, and the evidence
p.000075: base for effectively preventing or mitigating their public health impact is limited. These two obligations can come
p.000075: into conflict. This is because humanitarian response and health-related research often rely on the same infrastructure
p.000075: and the same personnel, so priorities between the two may need to be set. If nurses and physicians become
p.000075: researchers, this may also create dependent relationships (see Guideline 9 – Individuals capable of giving
p.000075: informed consent). Humanitarian workers, researchers and sponsors must be aware of these conflicts and ensure that
p.000075: their studies do not unduly compromise the disaster response. Researchers and sponsors should also aim to contribute to
p.000075: the infrastructure for the humanitarian response and integrate their research activities with this response.
p.000075: Importantly, all studies must be responsive to the health needs or priorities of the affected populations, and it must
p.000075: not be possible to conduct the research outside a disaster situation.
p.000075:
p.000075: General challenges in disaster research. In infectious disease outbreaks, there can be considerable pressure to conduct
p.000075: research. This is especially the case for diseases that have a high mortality rate and where the treatment options
p.000075: are limited (for example during the 2014 Ebola outbreak). Conversely, in natural or man-made disasters,
p.000075: research can be met with great scepticism or even hostility, and researchers can be at risk of physical harm.
p.000075: Researchers and sponsors must be equipped to negotiate these pressures in what are typically fragile political and
p.000075: social situations. They must also have sufficient operational and security support in order to work effectively in such
p.000075: challenging environments. Acute disasters pose numerous challenges for conducting ethically responsible
p.000075: research. For example, potential study participants often suffer from serious physical or psychological
p.000075:
p.000075:
p.000075: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000076: 76
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000076: trauma that can make it difficult for them to protect their rights and interests. Limited or damaged health
p.000076: infrastructures can challenge implementation of preferred study designs and data collection. Moreover, efforts to make
p.000076: available as soon as possible any interventions or products developed from the research to the affected communities are
p.000076: often more challenging in acute disaster situations (see Guideline 2 – Research conducted in low-resource
p.000076: settings). Despite these challenges, it is essential that researchers and sponsors uphold the ethical principles
p.000076: embodied in these Guidelines, even if the standard ways of respecting these principles may need to be modified. In
p.000076: fact, an acute disaster situation can require modifying standard procedures so that ethical principles can be upheld in
p.000076: the most expedient way possible. For example, while ethical oversight is essential in all research, accelerated ethical
p.000076: review during disasters may be necessary to ensure that valuable studies can begin as soon as possible without
p.000076: compromising ethical requirements (see below).
p.000076:
...
p.000076: research lacks social value and must not be conducted (see Guideline 1 – Scientific and social value and respect for
p.000076: rights). Research may even divert personnel or resources from the disaster response. In clinical trials, the
p.000076: randomised-controlled trial design is often considered the “gold standard” for collecting robust data. However,
p.000076: researchers, sponsors, research ethics committees and others must explore alternative trial designs that may increase
p.000076: trial efficiency and access to promising experimental interventions while still maintaining scientific validity. The
p.000076: methodological and ethical merits of alternative trial designs must be carefully assessed before these designs are
p.000076: used. For example, when testing experimental treatments or vaccines during an epidemic, the appropriate trial
p.000076: design will depend on the promise of the investigational agent,
p.000076:
p.000076:
p.000076: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077: a variation in critical background factors (for example mortality and infection rates), and measurement of outcomes,
p.000077: among others. Researchers and sponsors must carefully evaluate the relative merits of different designs (for example
p.000077: observational or placebo-controlled) based on these factors.
p.000077:
p.000077: Community engagement. Because disasters often lead to vulnerability and fragile political and social situations,
p.000077: engaging local communities about the research at an early stage is essential for maintaining public trust and ensuring
p.000077: that studies are conducted in a culturally sensitive manner (see Guideline 7 – Community engagement). Researchers and
p.000077: sponsors can use creative mechanisms to expedite and facilitate community engagement in a disaster situation (for
p.000077: example, by using social media). Fostering community leadership will often be important to address distrust and
p.000077: communicate effectively in order to gain support for the study design. In engaging with communities, researchers,
p.000077: sponsors and research ethics committees should be aware of potential conflicts of interest vis-à-vis the proposed
p.000077: research. For example, community leaders might seek to reassert their own authority by providing services to their
p.000077: communities through research.
p.000077:
p.000077: Ethical review and oversight. The standard mechanism for ethical review will often be too time-consuming
p.000077: to enable full research protocols to be prepared and reviewed at the outset of a disaster. Procedures
p.000077: should be developed to facilitate and accelerate ethical review in a situation of crisis. For example, research ethics
p.000077: committees or a specialist ethics committee (perhaps on a national or regional level) may conduct an initial
p.000077: accelerated review of study protocols and continue oversight if studies raise significant ethical concerns. Research in
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Political / vulnerable
Searching for indicator vulnerable:
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p.000007: GUIDELINE 3: EQUITABLE DISTRIBUTION OF BENEFITS AND BURDENS IN THE SELECTION OF INDIVIDUALS AND GROUPS OF PARTICIPANTS
p.000007: IN RESEARCH
p.000007: 7
p.000007: GUIDELINE 4: POTENTIAL INDIVIDUAL BENEFITS AND RISKS OF RESEARCH 9
p.000007: GUIDELINE 5: CHOICE OF CONTROL IN CLINICAL TRIALS 15
p.000007: GUIDELINE 6: CARING FOR PARTICIPANTS’ HEALTH NEEDS 21
p.000007: GUIDELINE 7: COMMUNITY ENGAGEMENT 25
p.000007: GUIDELINE 8: COLLABORATIVE PARTNERSHIP AND CAPACITY-BUILDING
p.000007: FOR RESEARCH AND RESEARCH REVIEW 29
p.000007: GUIDELINE 9: INDIVIDUALS CAPABLE OF GIVING INFORMED CONSENT 33
p.000007: GUIDELINE 10: MODIFICATIONS AND WAIVERS OF INFORMED CONSENT 37
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: v
p.000007:
p.000007: GUIDELINE 11: COLLECTION, STORAGE AND USE OF BIOLOGICAL
p.000007: MATERIALS AND RELATED DATA 41
p.000007: GUIDELINE 12: COLLECTION, STORAGE AND USE OF DATA IN HEALTH- RELATED RESEARCH
p.000047: 47
p.000047: GUIDELINE 13: REIMBURSEMENT AND COMPENSATION FOR
p.000047: RESEARCH PARTICIPANTS 53
p.000047: GUIDELINE 14: TREATMENT AND COMPENSATION FOR RESEARCH-
p.000047: RELATED HARMS
p.000055: 55
p.000055: GUIDELINE 15: RESEARCH INVOLVING VULNERABLE PERSONS
p.000055: AND GROUPS
p.000057: 57
p.000057: GUIDELINE 16: RESEARCH INVOLVING ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000061: 61
p.000061: GUIDELINE 17: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS 65
p.000061: GUIDELINE 18: WOMEN AS RESEARCH PARTICIPANTS 69
p.000061: GUIDELINE 19: PREGNANT AND BREASTFEEDING WOMEN AS
p.000061: RESEARCH PARTICIPANTS 71
p.000061: GUIDELINE 20: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS 75
p.000061: GUIDELINE 21: CLUSTER RANDOMIZED TRIALS 79
p.000061: GUIDELINE 22: USE OF DATA OBTAINED FROM THE ONLINE
p.000061: ENVIRONMENT AND DIGITAL TOOLS IN HEALTH-RELATED RESEARCH 83
p.000061: GUIDELINE 23: REQUIREMENTS FOR ESTABLISHING RESEARCH ETHICS COMMITTEES AND FOR THEIR REVIEW OF PROTOCOLS
p.000087: 87
p.000087: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000087: vi
p.000087:
p.000087: GUIDELINE 24: PUBLIC ACCOUNTABILITY FOR HEALTH-RELATED RESEARCH 91
p.000087: GUIDELINE 25: CONFLICTS OF INTEREST 95
p.000087: APPENDIX 1 ITEMS TO BE INCLUDED IN A PROTOCOL (OR ASSOCIATED DOCUMENTS) FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
...
p.000119: maintaining collaborative relations with the United Nations and its specialized agencies, especially UNESCO and WHO.
p.000119:
p.000119: The first version of the CIOMS Guidelines (1982)
p.000119: CIOMS, in association with WHO, undertook its work on ethics in biomedical research in the late 1970s.
p.000119: Accordingly, CIOMS set out, in cooperation with WHO, to prepare guidelines. The aim of the guidelines was (and still
p.000119: is) to provide internationally vetted ethical principles and detailed commentary on how universal ethical principles
p.000119: should be applied, with particular attention to conducting research in low-resource settings. The outcome of the
p.000119: CIOMS/WHO collaboration was entitled Proposed International Ethical Guidelines for Biomedical Research Involving
p.000119: Human Subjects.
p.000119:
p.000119: The second version of the CIOMS Guidelines (1993)
p.000119: The period that followed saw the outbreak of the HIV/AIDS pandemic and proposals for large-scale trials of prevention
p.000119: and treatment for the disease. These developments raised new ethical issues that had not been considered in the
p.000119: preparation of the Proposed Guidelines. There were other factors also – rapid advances in medicine and
p.000119: biotechnology, changing research practices such as multinational field trials, experimentation involving
p.000119: vulnerable population groups, and also a new perspective in both high- and low-resource settings, that research
p.000119: involving humans could be beneficial to participants rather than threatening. The World Medical Association’s
p.000119: Declaration of Helsinki was revised twice in the 1980s – in 1983 and 1989. It was timely to revise and update the 1982
p.000119: Guidelines, and CIOMS, with the collaboration of WHO and its Global Programme on AIDS, undertook the
p.000119: task. The outcome was the issue of two sets of guidelines: International Guidelines for Ethical Review of
p.000119: Epidemiological Studies in 1991, and International Ethical Guidelines for Biomedical Research Involving Human Subjects
p.000119: in 1993.
p.000119:
p.000119: The third version of the CIOMS Guidelines (2002)
p.000119: After 1993, ethical issues arose for which the 1993 CIOMS Guidelines had no specific provisions. They related mainly
p.000119: to externally sponsored clinical trials carried out in low-resource settings. In particular, the use of
p.000119: comparators other than an established effective intervention used in low- resource settings became a concern.
p.000119: Commentators took opposing sides on this issue. This debate necessitated the revision and updating of the 1993
p.000119: Guidelines. CIOMS organized a consultation meeting with eight commissioned papers. After this meeting, a WG was set
p.000119: up that laboured over a period of two years during which there was a public posting of a draft with a request for
p.000119: comments. The revision process was finished in 2002.
p.000119:
...
p.000119: epidemiological studies should be updated. Intending to ensure that ethical principles are consistently applied to all
p.000119: types of research, the core group decided to prepare a Supplement to the 2002 document that would address the special
p.000119: features of epidemiological studies. In February 2006, a draft of the supplement was posted on the CIOMS website and
p.000119: opened to comment from interested parties. The response from groups and individuals involved in biomedical research was
p.000119: largely positive, but many objected that epidemiologists were not necessarily conversant with the 2002 Guidelines and
p.000119: would therefore find it burdensome to have to switch back and forth between the epidemiology supplement and the
p.000119: biomedical research document. Eventually, therefore, the final version of the Guidelines (2009) combined both
p.000119: documents.
p.000119:
p.000119: The fourth version of the CIOMS Guidelines (2016)
p.000119: During its annual meeting in 2009 the Executive Committee of CIOMS considered the desirability of a revision of the
p.000119: CIOMS Ethical Guidelines for Biomedical Research. Since 2002 several developments had taken place including: a
p.000119: heightened emphasis on the importance of translational research, a felt need to clarify what counts as fair research in
p.000119: low-resource settings, more emphasis on community engagement in research, the awareness that exclusion of
p.000119: potentially vulnerable groups in many cases has resulted in a poor evidence base, and the increase of big data
p.000119: research. Moreover the Declaration of Helsinki of 2008 was revised again at that moment. The Executive Committee
p.000119: therefore decided to first explore the desirability of such a revision.
p.000119:
p.000119: The revision process of the 2002 version
p.000119: In 2011, the CIOMS Executive Committee decided to set up a Working Group to revise the CIOMS Guidelines
p.000119: and fund the work from internal means. This Group met three times each year from September 2012 until September
p.000119: 2015. Virtually all Guidelines underwent major revisions. Some Guidelines were merged (for example, 2002
p.000119: Guidelines 4 and 6 both dealt with informed consent), and others were newly created (for example,
p.000119: Guideline 20 on research in disaster and disease outbreaks). Furthermore, the Working Group decided to merge the
p.000119: CIOMS Guidelines for Biomedical Research with the CIOMS Guidelines for Epidemiological Research. At the same time, in
p.000119: order to ensure the epidemiological dimension, an epidemiologist, who was also a member of the Working Group, closely
p.000119: read the revisions from an epidemiological perspective.
p.000119:
p.000119: Scope of the 2016 version
p.000119: The Working Group decided to broaden the scope of the 2002 Guidelines from “biomedical research” to “health-related
...
p.000119: well as articles in leading medical or scientific journals, such as BMJ, The Lancet, the New England
p.000119: Journal of Medicine and Science.
p.000119:
p.000119: Literature reviews were used in three ways. First, we searched main ethical guidelines on research with humans and
p.000119: textbooks on research ethics to identify new topics or viewpoints in existing debates. For instance, many guidelines
p.000119: have included statements on biobanking which was one of the reasons to merge the CIOMS guidelines for epidemiological
p.000119: research with those for biomedical research.
p.000119:
p.000119: We performed searches in Embase and Medline on review papers and papers with strong positions on certain topics. For
p.000119: example, component analysis and the net risk test are two recent approaches to making risk-benefit assessments. There
p.000119: is no agreement among bioethicists on which of these approaches is preferable. The Working Group read relevant papers
p.000119: on these approaches and developed a middle ground. A similar process was adopted for vulnerability. A consensus emerged
p.000119: in recent publications that vulnerability can no longer be applied to entire groups. As a result, the
p.000119: Working Group eliminated the group approach. Instead, the Guidelines focus on characteristics that lead to considering
p.000119: certain groups as vulnerable and on the specific protections that are needed in those situations.
p.000119:
p.000119: Third, literature reviews were performed to address relatively new topics, such as opt-out procedures in biobanking or
p.000119: informing research participants of (un)solicited findings. The Working Group reviewed relevant papers on these topics
p.000119: and accordingly took a position.
p.000119:
p.000119: It is important to emphasize that the literature was used as a starting point for further discussion. Ultimately, the
p.000119: validity of the ethical positions in these Guidelines hinge on the strength of the arguments, not on the
p.000119: frequency of an ethical standpoint in the literature.
p.000119:
p.000119: All decisions by the Working Group were reasoned decisions. Members discussed all proposals for revision of
p.000119: particular texts during the meetings and electronically between meetings. Members deliberated until they had reached a
p.000119: well-argued consensus. If no consensus was reached, the previous text in the 2002 Guidelines remained in place.
p.000119:
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119: xi
p.000119:
p.000119: PREAMBLE
p.000119: The ethical principles set forth in these Guidelines should be upheld in the ethical review of research protocols. The
p.000119: ethical principles are regarded as universal. Moreover, the Guidelines should be read and interpreted as a whole. Some
p.000119: Guidelines have cross references to other Guidelines. The purpose of these cross references is to help the reader
p.000119: navigate through the Guidelines. However, absence of cross references to other Guidelines does not imply that other
p.000119: Guidelines may not be applicable.
p.000119:
...
p.000001:
p.000001:
p.000001: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000002: 2
p.000002:
p.000002:
p.000002:
p.000002:
p.000002:
p.000002: GUIDELINE 2:
p.000002: RESEARCH CONDUCTED IN LOW-RESOURCE SETTINGS
p.000002:
p.000002:
p.000002: Before instituting a plan to undertake research in a population or community in low-resource settings, the sponsor,
p.000002: researchers, and relevant public health authority must ensure that the research is responsive to the health needs or
p.000002: priorities of the communities or populations where the research will be conducted.
p.000002:
p.000002: As part of their obligation, sponsors, and researchers must also:
p.000002: f make every effort, in cooperation with government and other relevant stakeholders, to make available as soon
p.000002: as possible any intervention or product developed, and knowledge generated, for the population or community in
p.000002: which the research is carried out, and to assist in building local research capacity. In some cases, in order to
p.000002: ensure an overall fair distribution of the benefits and burdens of the research, additional benefits such
p.000002: as investments in the local health infrastructure should be provided to the population or community; and
p.000002: f consult with and engage communities in making plans for any intervention or product developed available, including
p.000002: the responsibilities of all relevant stakeholders.
p.000002:
p.000002:
p.000002: Commentary on Guideline 2
p.000002: General considerations. This Guideline pertains to settings in which resources are so limited that the
p.000002: population may be vulnerable to exploitation by sponsors and investigators from wealthier countries and communities.
p.000002: The ethical standards applied should be no less stringent than they would be for research carried out in
p.000002: high-resource settings. To ensure that people in low-resource settings receive equitable benefit from their
p.000002: participation in health-related research, this Guideline demands that local social value be created. Low-resource
p.000002: settings should not be interpreted narrowly as low-resource countries. These settings might also exist in middle- and
p.000002: high- income countries. Moreover, a setting can change over time and no longer be considered low-resource.
p.000002:
p.000002: Responsiveness of research to health needs or priorities. The responsiveness requirement can be met by demonstrating
p.000002: that research is needed to provide new knowledge about the best means of addressing a health condition present in that
p.000002: community or region. Where communities or policy- makers have determined that research on particular health needs
p.000002: constitutes a public health priority, studies that address such needs seek to provide social value to the community or
p.000002: population and are therefore responsive to their health needs. Concerns about responsiveness might hinge on the
p.000002: relevance to the community of the information a study is designed to produce. For example, a question about
p.000002: responsiveness might arise if a study of a new intervention is planned for a community in which
p.000002: established effective interventions for a health condition are not locally available and the new
p.000002:
p.000002:
p.000002: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000003: 3
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
...
p.000005: settings). Inclusion and exclusion criteria should not be based upon potentially discriminatory criteria, such as race,
p.000005: ethnicity, economic status, age or sex, unless there is a sound ethical or scientific reason to do so. For example, in
p.000005: cases where the under-representation of particular groups results in or perpetuates health disparities, equity may
p.000005: require special efforts to include members of those populations in research (see Guideline 17 – Research involving
p.000005: children and adolescents, Guideline 18
p.000005: – Women as research participants, and Guideline 19 – Pregnant women and breastfeeding women as research participants).
p.000005:
p.000005:
p.000005:
p.000005: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: Fair distribution of research benefits. Equity in the distribution of the benefits of research requires
p.000007: that research not disproportionately focus on the health needs of a limited class of people, but instead
p.000007: aims to address diverse health needs across different classes or groups. In the past, groups considered vulnerable
p.000007: were excluded from participation in research because it was considered the most expedient way of protecting
p.000007: those groups (for example, children, women of reproductive age, pregnant women). As a consequence of such exclusions,
p.000007: information about the diagnosis, prevention and treatment of diseases that afflict such groups is limited. This has
p.000007: resulted in a serious injustice. Since information about the management of diseases is considered a benefit to society,
p.000007: it is unjust to intentionally deprive specific groups of that benefit. The need to redress these injustices by
p.000007: encouraging the participation of previously excluded groups in basic and applied biomedical research is widely
p.000007: recognized.
p.000007:
p.000007: Fair distribution of research burdens. Research with human participants typically requires that some persons or
p.000007: groups are exposed to risks and burdens in order to generate the knowledge needed to protect and promote
p.000007: people’s health (see Guideline 1 – Scientific and social value and respect for rights). Equity in the distribution of
p.000007: burdens of research requires special care to ensure that individuals, communities or populations that are already
p.000007: disadvantaged or marginalized are not over-represented in research. A disproportionate selection of disadvantaged or
p.000007: convenient populations is morally problematic for several reasons. First, it is unjust to selectively invite poor or
...
p.000053: held beliefs (“undue inducement”).
p.000053:
p.000053: It can be difficult to determine whether undue inducement exists, in part because the compensation that makes some
p.000053: people volunteer against their better judgment depends on their personal situation. An unemployed person or a student
p.000053: may view compensation differently from an employed person. Research ethics committees must evaluate monetary and other
p.000053: forms of compensation in light of the traditions and socio-economic context of the particular culture and population in
p.000053: order to determine whether the average participant expected to enrol in the study is likely to participate in the
p.000053: research against his or her better judgment because of the compensation offered. The appropriateness of compensation
p.000053: is likely better judged by local research ethics committees than by international ones. Consultation with
p.000053: the local community may help to ascertain this even in the case of research conducted in the researcher’s own
p.000053: community.
p.000053:
p.000053: Compensation for persons who are incapable of giving informed consent. Persons who are incapable of giving informed
p.000053: consent may be vulnerable to exploitation for financial gain by their guardians. A legally authorized
p.000053: representative asked to give permission on behalf of a person who is incapable of giving informed consent must be
p.000053: offered no compensation other than reimbursement for travel and other direct or indirect expenses. Where it would be
p.000053: reasonable to provide compensation to the participants themselves, their lack of decisional capacity must not
p.000053: preclude researchers from doing so. When participants are incapable of giving informed consent, compensation must be
p.000053: provided in a way that participants themselves can benefit from it.
p.000053:
p.000053: Compensation after study withdrawal. When a researcher withdraws a participant from a study on
p.000053: health-related grounds, the person must be compensated for study participation up to the point of such
p.000053: withdrawal. When a person is withdrawn from a study due to a research-related harm, this harm must be treated and the
p.000053: participant is entitled to additional compensation as set out in Guideline 14 – Treatment and compensation for
p.000053: research-related harms. When researchers must withdraw a participant from the study for wilful noncompliance, they are
p.000053: entitled to withhold part or all of the payment. Participants who do not continue study participation for other reasons
p.000053: must be compensated in proportion to the amount of participation they completed. Researchers must not
...
p.000055: compensation for research-related harms, and provide oversight to ensure that researchers report such
p.000055: harms, how treatment is being paid for and compensation provided to participants, and what is being offered.
p.000055:
p.000055: Participants must not be asked to waive their rights to free treatment or compensation for research- related harms, nor
p.000055: must they be required to show negligence or lack of a reasonable degree of skill on the part of the researcher in order
p.000055: to claim free treatment or compensation. The informed consent process or form must not contain statements that would
p.000055: absolve a researcher from responsibility in the case of harm, or that would imply that participants waive their right
p.000055: to seek compensation (see Guideline 9 – Individuals capable of giving informed consent). They must also be
p.000055: told what medical service, organization or individual will provide the treatment and what organization will be
p.000055: responsible for providing compensation.
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p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: GUIDELINE 15:
p.000056: RESEARCH INVOLVING VULNERABLE PERSONS AND GROUPS
p.000056:
p.000056: When vulnerable individuals and groups are considered for recruitment in research, researchers and research
p.000056: ethics committees must ensure that specific protections are in place to safeguard the rights and welfare of these
p.000056: individuals and groups in the conduct of the research.
p.000056:
p.000056:
p.000056: Commentary on Guideline 15
p.000056: General considerations. According to the Declaration of Helsinki, vulnerable groups and individuals “may have an
p.000056: increased likelihood of being wronged or of incurring additional harm.” This implies that vulnerability involves
p.000056: judgments about both the probability and degree of physical, psychological, or social harm, as well as a greater
p.000056: susceptibility to deception or having confidentiality breached. It is important to recognize that vulnerability
p.000056: involves not only the ability to provide initial consent to participate in research, but also aspects of the ongoing
p.000056: participation in research studies. In some cases, persons are vulnerable because they are relatively (or
p.000056: absolutely) incapable of protecting their own interests. This may occur when persons have relative or absolute
p.000056: impairments in decisional capacity, education, resources, strength, or other attributes needed to protect their own
p.000056: interests. In other cases, persons can also be vulnerable because some feature of the circumstances (temporary or
p.000056: permanent) in which they live makes it less likely that others will be vigilant about, or sensitive to, their
p.000056: interests. This may happen when people are marginalized, stigmatized, or face social exclusion or prejudice
p.000056: that increases the likelihood that others place their interests at risk, whether intentionally or unintentionally.
p.000056: Although research ethics committees can require special protections only for potential participants collectively for a
p.000056: particular project, researchers and others involved in research must take into account factors that render individual
p.000056: participants vulnerable and take appropriate steps to mitigate those factors.
p.000056:
p.000056: A traditional approach to vulnerability in research has been to label entire classes of individuals as vulnerable. The
p.000056: account of vulnerability in this Guideline seeks to avoid considering members of entire classes of
p.000056: individuals as vulnerable. However, it is useful to look at the specific characteristics that may render individuals
p.000056: vulnerable, as this can aid in identifying the special protections needed for persons who may have an increased
p.000056: likelihood of being wronged or of incurring additional harm as participants in research. Different characteristics
p.000056: may also co-exist, making some individuals more vulnerable than others. This is highly dependent on the context.
p.000056: For example, persons who are illiterate, marginalized by virtue of their social status or behaviour, or living in an
p.000056: authoritarian environment, may have multiple factors that make them vulnerable.
p.000056:
p.000056: Some characteristics can make it reasonable to assume that certain individuals are vulnerable, for example:
p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
p.000056:
p.000056: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
p.000057: Examples are medical and nursing students, subordinate hospital and laboratory personnel, workers in settings
p.000057: where research studies are conducted, and members of the armed forces or police. Their agreement to volunteer may be
p.000057: unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate
p.000057: in the study or by fear of disapproval or retaliation if they refuse (see also commentary on Guideline 9 – Individuals
p.000057: capable of giving informed consent). The research protocol must include a description of provisions to protect such
p.000057: individuals from being conscripted into research.
p.000057:
p.000057: Institutionalized persons. Residents of nursing homes, mental institutions, and prisons are often considered vulnerable
p.000057: because in a confined setting they have few options and are denied certain freedoms that non-institutionalized persons
p.000057: enjoy. For example, prisons have been described as “an inherently coercive environment.” Also, they may be in a
p.000057: dependent relationship with caregivers or guardians (see commentary on Guideline 9 – Individuals capable of giving
p.000057: informed consent, section on Dependent relationship).
p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
p.000057: committee when such proposals are under review (see commentary on Guideline 9 – Individuals capable of giving informed
p.000057: consent, section on Dependent relationship). Some individuals with this characteristic may also have diminished
p.000057: capacity to consent, and therefore require the additional protections noted earlier for participants who lack
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
...
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p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: stereotypes. One proposed mechanism that can be used to avoid stereotyping is consultation with relevant stakeholders,
p.000058: where feasible, before, during and after the conduct of the research (see Guideline 7 – Community
p.000058: engagement).
p.000058:
p.000058: Special protections. Special protections for these groups can include allowing no more than minimal risks for
p.000058: procedures that offer no potential individual benefits for participants; supplementing the participant’s agreement by
p.000058: the permission of family members, legal guardians, or other appropriate representatives; or requiring that the research
p.000058: be carried out only when it is targeted at conditions that affect these groups. Safeguards can be designed to promote
p.000058: voluntary decision-making, limit the potential for confidentiality breaches, and otherwise work to protect the
p.000058: interests of those at increased risk of harm. Research ethics committees need to be sensitive to not overly excluding
p.000058: people, and allow them to participate by requiring that special protections be put in place.
p.000058:
p.000058: Group vulnerability. Despite the importance of avoiding classification of entire groups as inherently vulnerable,
p.000058: circumstances exist that require research ethics committees to pay special attention to research involving
p.000058: certain groups. In some resource-limited countries or communities, lack of access to medical care,
p.000058: membership in ethnic and racial minorities, or other disadvantaged or marginalized groups can be factors
p.000058: that constitute vulnerability. As is true of the vulnerability of individuals, the judgment that groups
p.000058: are vulnerable is context dependent and requires empirical evidence to document the need for special
p.000058: protections.
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p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059: GUIDELINE 16:
p.000059: RESEARCH INVOLVING
p.000059: ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000059:
p.000059: Adults who are not capable of giving informed consent must be included in health-related research unless a good
p.000059: scientific reason justifies their exclusion. As adults who are not capable of giving informed consent
p.000059: have distinctive physiologies and health needs, they merit special consideration by researchers and research
p.000059: ethics committees. At the same time, they may not be able to protect their own interests due to their lack of capacity
...
p.000068:
p.000068: Women of child-bearing potential must be informed in advance of the possibility of risks to the fetus
p.000068: should they become pregnant during their research participation. When participation in research might be
p.000068: hazardous to a fetus or a woman if she becomes pregnant, sponsors and researchers must guarantee access to pregnancy
p.000068: tests, effective contraceptive methods before and during the research and to safe, legal abortion.
p.000068:
p.000068:
p.000068: Commentary on Guideline 18
p.000068: General considerations. Women in many societies have been excluded from research. For example, most of the early
p.000068: cardiovascular disease studies have excluded women because these diseases were believed to be uncommon in women. In
p.000068: particular, women who are biologically capable of becoming pregnant have been traditionally excluded from clinical
p.000068: trials of drugs, vaccines and medical devices owing to concern about undetermined risks to the fetus (see
p.000068: Guideline 15 – Research involving vulnerable persons and groups). Although the presumption against including women
p.000068: has changed in recent years, they are still excluded in many cases without adequate justification. Much remains unknown
p.000068: about the safety and efficacy of most drugs, vaccines, or devices used by women in medical practice, and
p.000068: this lack of knowledge can be dangerous. For example, heart attacks in women are different from heart attacks in men,
p.000068: so research is necessary to determine the best means of diagnosis and treatment in women.
p.000068:
p.000068: Vulnerability of women. Despite the current general presumption that favours the inclusion of women in
p.000068: research, in many societies women remain socially vulnerable in the conduct of research. For example, they may
p.000068: suffer negligence or harm because of their submission to authority, their hesitancy or inability to ask
p.000068: questions, and a cultural tendency to deny or tolerate pain and suffering. When women in these situations are potential
p.000068: participants in research, researchers, sponsors and ethics committees must take special care in the research design,
p.000068: assessment of risks and benefits, as well as the process of informed consent, to ensure that women have
p.000068: the necessary time and appropriate environment to make decisions based on information provided to them.
p.000068:
p.000068: Some women become vulnerable in research because of heightened psychological, social, physical, or legal risks.
p.000068: Examples include surveys and interviews regarding intimate partner violence and rape; social and behavioural
p.000068: research involving sex workers or women who inject drugs; and studies that solicit information about sexual behaviour.
p.000068: When the research involves household surveys or interviews, researchers must take special care to ensure that the women
p.000068: are interviewed in a private
p.000068:
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p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: place without the possibility of intrusion by other family members. In such studies, women must be given
p.000069: the option of conducting the interview in a setting of their choosing outside the home. Breach of
p.000069: confidentiality in these types of research could result in serious harms to women, even if the only information
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
...
p.000076: Especially when disasters are caused by infectious diseases that are highly contagious or serious (for example
p.000076: influenza, Ebola), there is great pressure to develop effective treatments and vaccines. When facing a serious,
p.000076: life-threatening infection, many people are willing to assume high risks and use unproven agents within or
p.000076: outside of clinical trials. However, it is essential that researchers and sponsors realistically assess
p.000076: the potential individual benefits and risks of experimental interventions and communicate these clearly to
p.000076: potential participants and individuals at risk. Even in ordinary circumstances, many promising experimental agents
p.000076: may not be safe and effective, and experimental interventions must be systematically evaluated in clinical trials.
p.000076: Moreover, emergency use can compromise recruitment of research participants and therefore undermine the conclusion of
p.000076: trials. Widespread emergency use with inadequate data collection about patient outcomes must therefore be avoided.
p.000076:
p.000076: Equitable distribution of risks and benefits. Because experimental interventions are often limited in disaster
p.000076: situations, fair selection of participants is essential (Guideline 3 – Equitable distribution of benefits and burdens
p.000076: in the selection of individuals and groups of participants in research). Especially in dire emergencies, well-off and
p.000076: well-connected patients must not be further privileged (for example, community leaders). Moreover, the exclusion of
p.000076: especially vulnerable populations must be justified (Guideline 15 – Research involving vulnerable persons and groups).
p.000076: It may be acceptable to prioritize certain populations in study enrolment. For example, front line workers often put
p.000076: themselves at risk during a disaster such as an epidemic, and if experimental interventions are effective, these
p.000076: workers would be able to help more patients. The principles of reciprocity and helping the largest number of people
p.000076: could therefore justify their prioritization. Researchers, sponsors, and research ethics committees also need
p.000076: to ensure that burdens and benefits of participation are equitably distributed (see Guideline 3 – Equitable
p.000076: distribution of benefits and burdens in the selection of individuals and groups of participants in research).
p.000076:
p.000076: Scientific validity and alternative trial designs. Disasters unfold quickly and study designs need to be
p.000076: chosen so that studies will yield meaningful data in a rapidly evolving situation. Study designs must be feasible in a
p.000076: disaster situation but still appropriate to ensure the study’s scientific validity. Without scientific validity, the
p.000076: research lacks social value and must not be conducted (see Guideline 1 – Scientific and social value and respect for
p.000076: rights). Research may even divert personnel or resources from the disaster response. In clinical trials, the
p.000076: randomised-controlled trial design is often considered the “gold standard” for collecting robust data. However,
p.000076: researchers, sponsors, research ethics committees and others must explore alternative trial designs that may increase
...
p.000083: public, is used and sold by the commercial sector, and that therefore the normal protections and consent for
p.000083: research should not be required. However, users rarely adequately understand how their data are stored and
p.000083: used. And despite the insights that may result from this high volume of data, legal and ethical standards are unclear
p.000083: due to changing social norms and the blurring of boundaries of public and private information. Although the information
p.000083: may be collected from a public source, researchers should acknowledge that persons may be unwilling to
p.000083: have their data obtained for studies, and should account for the privacy norms in communities sharing information
p.000083: online. Users may not fully understand or appreciate the consequences of their actions, and may feel violated when
p.000083: their information is used in a context they did not anticipate.
p.000083:
p.000083: The existence of data and information already online does not relieve the researcher from the obligation
p.000083: to respect privacy and mitigate risks that could result from combining data from multiple sources and their subsequent
p.000083: use and publication. Instead, the risk of unauthorized or inadvertent disclosure, in combination with technological
p.000083: capabilities that increase the volume and nature of identifiable data, point to the need to heighten data
p.000083: security and privacy protection in this context. It is especially important to address potential risks to vulnerable
p.000083: groups and others who may face adverse consequences as a result of exposure through this type of research.
p.000083:
p.000083: Assessment of privacy risk. Assessment of privacy risk should encompass the range of threats to privacy, the aspects
p.000083: that exacerbate those threats, the likelihood of disclosure of information given those threats, and the
p.000083: extent, severity and likelihood of risks arising from those disclosures. Some privacy risks may be difficult to predict
p.000083: as data are accumulated, combined and used in a wide variety of contexts. For example, research on clinical or public
p.000083: health interventions using mobile devices is increasingly common. The convenience and reach of mobile
p.000083: devices, whether in the hands of persons or researchers, enables the convenient collection and rapid transmission of
p.000083: data in a variety of settings. Researchers using mobile phones and apps to collect data must be aware that these
p.000083: devices and applications each may have vastly different privacy-related characteristics and limitations.
p.000083:
p.000083: Privacy risks are not a simple function of the presence or absence of specific fields, attributes or keywords in a set
p.000083: of data. Much of the potential for privacy risks stems from what can be inferred about individuals from the data as a
p.000083: whole or when the data are linked with other available information. Approaches to privacy protection in common
p.000083: use often provide limited protection. Traditional de- identification techniques have notable limitations,
...
p.000087: particular if there are significant changes in the protocol that require re-consent by participants,
p.000087: affect the safety of participants, or other ethical matters that emerge during the course of the study.
p.000087: These further reviews include progress reports submitted by researchers and possible monitoring of researchers’
p.000087: compliance with approved protocols.
p.000087:
p.000087: Committee membership. The research ethics committee must be constituted according to a document that
p.000087: specifies the manner in which members and the chair will be appointed, reappointed, and replaced. Research ethics
p.000087: committees must have members capable of providing competent and thorough review of research proposals. Membership
p.000087: normally must include physicians, scientists and other professionals such as research coordinators, nurses,
p.000087: lawyers, and ethicists, as well as community members or representatives of patients’ groups who can represent
p.000087: the cultural and moral values of study participants. Ideally, one or more members should have experience as study
p.000087: participants since there is growing recognition that knowledge gained through personal experience as a participant can
p.000087: supplement the professional understanding of illness and medical care. Committees must include both men and women.
p.000087: When a proposed study involves vulnerable individuals or groups, as may be the case in research involving
p.000087: prisoners or illiterate persons, representatives of relevant advocacy groups should be invited to meetings where such
p.000087: protocols will be reviewed (see
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p.000088:
p.000088:
p.000088:
p.000088:
p.000088:
p.000088: Guideline 15 – Research involving vulnerable persons and groups). Regular rotation of members is desirable for
p.000088: balancing the advantage of experience with that of fresh perspectives.
p.000088:
p.000088: Members of research ethics committees must regularly update their knowledge about the ethical conduct of health-related
p.000088: research. If committees do not have the relevant expertise to adequately review a protocol, they must consult
p.000088: with external persons with the proper skills or certification. Committees must keep records of their
p.000088: deliberations and decisions.
p.000088:
p.000088: Conflicts of interests on the part of committee members. Research ethics committees must provide independent ethical
p.000088: opinions. Pressure can be brought to bear from many different directions, not just financial. Research ethics
p.000088: committees must therefore have mechanisms to ensure the independence of their operations. In particular, they
p.000088: must avoid any undue influence and minimize and manage conflicts of interests. Research ethics committees must
p.000088: require that their members disclose to the committee any interests they may have that could constitute a conflict of
p.000088: interest or otherwise bias their evaluation of a research proposal. Research ethics committees must evaluate each study
p.000088: in light of any disclosed interests and ensure that appropriate steps are taken to mitigate possible conflicts of
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p.000098: and other investigators (Guideline 1);
p.000098:
p.000098: 11. The objectives of the trial or study, its hypotheses or research questions, its assumptions, and its
p.000098: variables (Guideline 1);
p.000098:
p.000098: 12. A detailed description of the design of the trial or study. In the case of controlled clinical trials the
p.000098: description should include, but not be limited to, whether assignment to treatment groups
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p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: will be randomized (including the method of randomization), and whether the study will be blinded (single
p.000099: blind, double blind), or open (Guideline 5);
p.000099:
p.000099: 13. The number of research participants needed to achieve the study objective, and how this was statistically
p.000099: determined;
p.000099:
p.000099: 14. The criteria for inclusion or exclusion of potential participants, and justification for the exclusion of any
p.000099: groups on the basis of age, sex, social or economic factors, or for other reasons (Guideline 3);
p.000099:
p.000099: 15. The justification for involving as research participants children or adolescents, persons who are unable to give
p.000099: informed consent or vulnerable persons or groups, and a description of special measures to minimize risks to such
p.000099: persons (Guidelines 15, 16 and 17);
p.000099:
p.000099: 16. The process of recruitment, e.g. advertisements, and the steps to be taken to protect privacy and confidentiality
p.000099: during recruitment (Guideline 3);
p.000099:
p.000099: 17. Description and explanation of all interventions (the method of treatment administration, including
p.000099: route of administration, dose, dose interval and treatment period for investigational and comparator products used);
p.000099:
p.000099: 18. Plans and justification for withdrawing or withholding standard therapies in the course of the research, including
p.000099: any resulting risks to persons (Guidelines 4 and 5);
p.000099:
p.000099: 19. Any other treatment that may be given or permitted, or contraindicated, during the study (Guideline
p.000099: 6);
p.000099:
p.000099: 20. Clinical and laboratory tests and other tests that are to be carried out;
p.000099:
p.000099: 21. Samples of the standardized case-report forms to be used, the methods of recording therapeutic response
p.000099: (description and evaluation of methods and frequency of measurement), the follow-up procedures, and, if applicable, the
p.000099: measures proposed to determine the extent of compliance of persons with the treatment;
p.000099:
p.000099: 22. Rules or criteria according to which participants may be removed from the study or clinical trial, or (in a
p.000099: multi-centre study) a centre may be discontinued, or the study may be terminated;
p.000099:
p.000099: 23. Methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000099: complications (Guidelines 4 and 23);
p.000099:
...
p.000104: from unsafe abortion and subsequent complications; and, when pregnancy is not terminated, the guarantee for a medical
p.000104: follow-up for their own health and that of the infant and child and the information that it is often difficult to
p.000104: determine causality in cases of fetal or infant abnormalities (Guidelines 18 and 19);
p.000104:
p.000104:
p.000104:
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p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: 7. when concerning pregnant and breastfeeding women, the risks of participation in health-related research to
p.000105: themselves, their pregnancies, their fetuses, and their future offspring, what has been done to maximize potential
p.000105: individual benefits and minimize risks, that evidence concerning risks may be unknown or controversial, and that
p.000105: it is often difficult to determine causality in cases of fetal or infant abnormalities (Guidelines 4 and 19);
p.000105:
p.000105: 8. when concerning disaster victims who mostly are under duress, the difference between research and humanitarian
p.000105: aid (Guideline 20); and
p.000105:
p.000105: 9. when research is done in the online environment and using online or digital tools that may
p.000105: involve potentially vulnerable persons, information about the privacy and security controls that will be used to
p.000105: protect their data; and the limitations of the measures used and the risks that may remain despite the safeguards put
p.000105: in place (Guideline 22).
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
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p.000106:
p.000106:
p.000106:
p.000106:
p.000106: APPENDIX 3
p.000106: CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH INVOLVING
p.000106: HUMANS
p.000106:
p.000106: Chair
p.000106: Hans van Delden
p.000106: Johannes JM van Delden is professor of medical ethics at the medical school of Utrecht University, the Netherlands, and
p.000106: director of education at the Julius Center for health sciences. He has written more than two hundred articles in
p.000106: peer-reviewed scientific journals and (co)authored three books. He was secretary of the International Association of
p.000106: Bioethics. As a professor of medical ethics he has built a strong academic group within the University Medical Center
p.000106: Utrecht. The special fields of interest of this group are: research ethics, moral problems at the end of life and moral
p.000106: problems in the care for the elderly. He is currently the chair of the International Bioethics Committee at UNESCO and
p.000106: was president of CIOMS from 2011 to 2016.
p.000106:
p.000106: Secretary
p.000106: Rieke van der Graaf
p.000106: Rieke van der Graaf is an assistant professor of bioethics and employed at the University Medical Center Utrecht at the
p.000106: Julius Center, Department of Medical Humanities. Her current research interests are inclusion of “vulnerable
p.000106: populations” in clinical research, the integration of care and research, and the ethics of innovative research designs.
p.000106: She is teaching medical ethics at the UMC Utrecht and has been a member of the UMC Utrecht’s Hospital Ethics Committee
p.000106: for more than 10 years. She is a member of the Research Ethics Committee (REC) of the UMC Utrecht. She was the
p.000106: Secretary of the Working Group on the Revision of the CIOMS Guidelines.
p.000106:
p.000106: Members
p.000106: Anant Bhan
p.000106: Anant Bhan is trained as a medical doctor with a masters degree in bioethics from the University of Toronto. He is a
p.000106: researcher in the fields of Bioethics, Global Health and Health Policy based in India. He is also Adjunct
p.000106: Professor at Yenepoya University, Mangalore, India. In the past, he has worked for NGOs and a government
p.000106: public health training institution in India, as well as a consultant to a project on Ethical, Social and Cultural
p.000106: issues in health biotechnology based at the University of Toronto. Anant has published extensively in various national
p.000106: and international medical journals in the field of global/public health and bioethics, as well as contributed to
p.000106: popular mass media. Anant has been a resource person for trainings in global health, research methodology, research
...
p.000120: 76 - 80, 87 - 90, 95, 97, 100 - 103
p.000120: Protocol 2, 12, 18, 23, 25, 35, 36, 43, 49, 55, 56, 58, 76, 83, 87 - 90, 92, 96, 99, 101, 102, 105
p.000120: Public accountability 11, 13, 29, 31, 51, 91
p.000120: Publication ii, 29, 31, 84, 91, 92, 95, 102
p.000120: R
p.000120: Registries 36, 38, 39, 47, 49, 51, 72, 91
p.000120: Rehabilitation 55, 104
p.000120: Reimbursement 53, 54
p.000120: Research ethics committee 2, 9, 10, 12, 15, 17, 18, 23, 25, 27, 33, 34 - 39, 41, 43 - 45, 47,
p.000120: 49 - 51, 53, 54, 56, 58, 61 - 63, 65, 68, 71, 73, 79, 85, 87 - 91, 95, 96, 98, 102, 103, 105
p.000120: Residual tissue 41, 43, 44
p.000120: Responsiveness 3, 4, 17, 19, 63, 75, 76
p.000120: Return of results 44, 45, 51
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p.000121: Risks 2, 5, 7 - 13, 15 - 19, 23, 26, 34 - 39, 41, 44, 47, 49, 50, 53, 54, 58, 59, 61 - 63, 65 - 67,
p.000121: 69 - 73, 75 - 77, 80, 81, 83 - 85, 88, 91, 92, 96, 100, 102, 104 - 106
p.000121: S
p.000121: Scientific value 2, 9 - 13, 51, 91
p.000121: Secondary use 49
p.000121: Social value 1 - 4, 8 - 11, 19, 25, 26, 30, 37, 38, 41, 44, 47, 50, 62, 65, 71, 73, 75, 77, 88, 91
p.000121: Specific informed consent 41 - 44, 47, 48, 49
p.000121: Storage 36, 41, 43, 45, 47 - 50, 52, 105
p.000121: U
p.000121: (Un)solicited findings xi, 44, 45, 51
p.000121: Undue inducement 53, 54, 73
p.000121: Use of biological material 44, 105
p.000121: V
p.000121: Voluntary, voluntariness 10, 35, 36, 39, 58, 59, 78, 96, 103
p.000121: Vulnerable viii, ix, xi, 3, 8, 54, 57 - 59, 69, 77, 84, 88, 89, 100, 106
p.000121: W
p.000121: Waivers of informed consent 33, 35 - 37, 43, 49, 63, 68, 76, 78, 79
p.000121: Withdrawal 44, 49, 50, 54, 63
p.000121: Women 7, 8, 25, 58, 69, 70 - 73, 88, 101, 105, 106
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p.000122: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000122:
p.000122: CIOMS, in association with the World Health Organization, started its work on ethics in health-related
p.000122: research in the late 1970s. Accordingly, CIOMS set out, in cooperation with WHO, to prepare guidelines
p.000122: to indicate how the ethical principles set forth in the Declaration of Helsinki of the World Medical
p.000122: Association, could be effectively applied, particularly in low-resource settings, given their socio-economic
p.000122: circumstances, laws and regulations, and executive and administrative arrangements. Since then revised editions of
p.000122: the CIOMS ethical guidelines were published in 1993 and 2002. New developments in research have prompted
p.000122: CIOMS to again revise their ethical guidelines. The result is now available in this new publication.
p.000122:
p.000122: In the new 2016 version of the ethical guidelines, CIOMS provides answers to a number of pressing issues in research
p.000122: ethics. The Council does so by stressing the need for research having scientific and social value, by providing special
p.000122: guidelines for health-related research in low-resource settings, by detailing the provisions for involving
p.000122: vulnerable groups in research and for describing under what conditions biological samples and health-related data
p.000122: can be used for research.
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p.000122: International Ethical Guidelines for Health-related Research Involving Humans. Geneva: Council for International
p.000122: Organizations of Medical Sciences (CIOMS); 2016.
p.000122: CIOMS publications may be obtained directly from CIOMS by e-mail to info@cioms.ch.
p.000122: CIOMS, P.O. Box 2100, CH1211 Geneva 2, Switzerland, www.cioms.ch
p.000122: CIOMS publications are also distributed by the World Health Organization, 20 Avenue Appia, CH-1211 Geneva 27,
p.000122: Switzerland.
p.000122:
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p.000122: ISBN 978-929036088-9
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Searching for indicator vulnerability:
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p.000119: Inquiry, the Journal of Empirical Research on Human Research Ethics, the Journal of Law, Medicine and Ethics,
p.000119: the Journal of Medical Ethics, the Journal of Medicine and Philosophy, Medicine, Health Care and Philosophy, as
p.000119: well as articles in leading medical or scientific journals, such as BMJ, The Lancet, the New England
p.000119: Journal of Medicine and Science.
p.000119:
p.000119: Literature reviews were used in three ways. First, we searched main ethical guidelines on research with humans and
p.000119: textbooks on research ethics to identify new topics or viewpoints in existing debates. For instance, many guidelines
p.000119: have included statements on biobanking which was one of the reasons to merge the CIOMS guidelines for epidemiological
p.000119: research with those for biomedical research.
p.000119:
p.000119: We performed searches in Embase and Medline on review papers and papers with strong positions on certain topics. For
p.000119: example, component analysis and the net risk test are two recent approaches to making risk-benefit assessments. There
p.000119: is no agreement among bioethicists on which of these approaches is preferable. The Working Group read relevant papers
p.000119: on these approaches and developed a middle ground. A similar process was adopted for vulnerability. A consensus emerged
p.000119: in recent publications that vulnerability can no longer be applied to entire groups. As a result, the
p.000119: Working Group eliminated the group approach. Instead, the Guidelines focus on characteristics that lead to considering
p.000119: certain groups as vulnerable and on the specific protections that are needed in those situations.
p.000119:
p.000119: Third, literature reviews were performed to address relatively new topics, such as opt-out procedures in biobanking or
p.000119: informing research participants of (un)solicited findings. The Working Group reviewed relevant papers on these topics
p.000119: and accordingly took a position.
p.000119:
p.000119: It is important to emphasize that the literature was used as a starting point for further discussion. Ultimately, the
p.000119: validity of the ethical positions in these Guidelines hinge on the strength of the arguments, not on the
p.000119: frequency of an ethical standpoint in the literature.
p.000119:
p.000119: All decisions by the Working Group were reasoned decisions. Members discussed all proposals for revision of
p.000119: particular texts during the meetings and electronically between meetings. Members deliberated until they had reached a
p.000119: well-argued consensus. If no consensus was reached, the previous text in the 2002 Guidelines remained in place.
p.000119:
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119: xi
p.000119:
p.000119: PREAMBLE
p.000119: The ethical principles set forth in these Guidelines should be upheld in the ethical review of research protocols. The
p.000119: ethical principles are regarded as universal. Moreover, the Guidelines should be read and interpreted as a whole. Some
...
p.000042:
p.000042: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000043: 43
p.000043:
p.000043:
p.000043:
p.000043:
p.000043:
p.000043: interest to future researchers, it is good clinical practice to offer donors several options: to have their materials
p.000043: used only for their own treatment or benefit and then discarded; to allow stored materials to be used for
p.000043: a specifically described research project (specific informed consent); or to allow stored materials to be used for yet
p.000043: undefined research, with or without personal identifiers. However, following this practice in every situation in health
p.000043: care may be overly demanding and difficult to implement; therefore, an informed opt-out procedure may be acceptable.
p.000043: This implies that the material is stored and used for research unless the person from whom it originates explicitly
p.000043: objects.
p.000043:
p.000043: The informed opt-out procedure has to fulfil the following conditions: 1) patients need to be aware of its existence;
p.000043: 2) sufficient information needs to be provided; 3) patients need to be informed that they can withdraw their data; and
p.000043: 4) a genuine possibility to object has to be offered.
p.000043:
p.000043: An informed opt-out procedure for research on residual tissue may not be appropriate in certain
p.000043: circumstances, namely a) when the research involves more than minimal risks to the individual, or b) when controversial
p.000043: or high-impact techniques are used, for example the creation of immortal cell lines, or c) when research is conducted
p.000043: on certain tissue types, for example gametes, or d) when research is conducted in contexts of heightened
p.000043: vulnerability. A research ethics committee must determine whether explicit informed consent for the research is
p.000043: required.
p.000043:
p.000043: Withdrawal of consent. Donors or their legal representatives should be able to withdraw consent for maintenance and
p.000043: use of biological material stored in a biobank. The withdrawal of consent should be formalized by written
p.000043: documentation signed by the donor or their legal representative of the donor, and the samples should either be
p.000043: destroyed or returned to the donor. Future use of the biological materials and related data is not permitted after the
p.000043: withdrawal of consent.
p.000043:
p.000043: Authorization for research with archived materials. When biological materials and data collected and stored in the past
p.000043: without specific or broad informed consent contain important and otherwise unobtainable data, a research ethics
p.000043: committee needs to decide whether the use of such materials is justified. The most common justification for using
p.000043: records or materials collected in the past without consent is that it would be impracticable or prohibitively
p.000043: expensive to locate the persons whose materials or records are to be examined. For example, this may happen when
...
p.000048: data, whether limited to an already fully defined study or extending to a number of wholly or partially undefined
p.000048: studies; the intended goal of such use, whether only for basic or applied research, or also for commercial purposes;
p.000048: and the possibility of unsolicited findings and how they will be dealt with. The research ethics committee must ensure
p.000048: that the proposed collections, the storage protocol, and the consent procedure meet these specifications.
p.000048:
p.000048: Informed opt-out procedure for research with health-related data. In the absence of broad informed consent, an informed
p.000048: opt-out consent procedure can be used. This means that the data are stored and used for research unless a person from
p.000048: whom the data originate explicitly objects. The informed opt-out procedure has to fulfil the following conditions: 1)
p.000048: patients need to be aware of its existence; 2) sufficient information needs to be provided; 3) patients
p.000048: need to be informed that they can withdraw their data; and 4) a genuine possibility to object has to be offered.
p.000048: However, in certain circumstances the researcher must obtain explicit informed consent, whether specific or
p.000048: broad: 1) when the research involves more than minimal risks to the individual; or 2) when controversial
p.000048: or high-impact techniques are used; or 3) when research is conducted in contexts of heightened vulnerability. A
p.000048: research ethics committee must determine whether explicit informed consent is required.
p.000048:
p.000048: Secondary use of stored data. Sometimes data are collected in databanks, during research or during other activities
p.000048: (for example, clinical practice, health insurance), that can be used in future research. Typically the precise research
p.000048: questions will be unknown at the time of data collection. In those cases, it is acceptable to use the data for
p.000048: secondary analysis when the intended use falls within the scope of the original (broad) informed consent.
p.000048:
p.000048: Withdrawal of consent. Donors or their legal representatives at any time and without any charges or losses, should
p.000048: have the possibility to withdraw their consent for use of data in a databank. The withdrawal of consent
p.000048: should be formalized by written documentation signed by the donor or
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p.000048: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000049: the legal representative of the donor, and the data should be either destroyed or returned to the donor. Future use of
p.000049: the data is not permitted after the withdrawal of consent.
p.000049:
p.000049: Authorization for research with archived data. When existing data, collected and stored without a specific
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p.000056: GUIDELINE 15:
p.000056: RESEARCH INVOLVING VULNERABLE PERSONS AND GROUPS
p.000056:
p.000056: When vulnerable individuals and groups are considered for recruitment in research, researchers and research
p.000056: ethics committees must ensure that specific protections are in place to safeguard the rights and welfare of these
p.000056: individuals and groups in the conduct of the research.
p.000056:
p.000056:
p.000056: Commentary on Guideline 15
p.000056: General considerations. According to the Declaration of Helsinki, vulnerable groups and individuals “may have an
p.000056: increased likelihood of being wronged or of incurring additional harm.” This implies that vulnerability involves
p.000056: judgments about both the probability and degree of physical, psychological, or social harm, as well as a greater
p.000056: susceptibility to deception or having confidentiality breached. It is important to recognize that vulnerability
p.000056: involves not only the ability to provide initial consent to participate in research, but also aspects of the ongoing
p.000056: participation in research studies. In some cases, persons are vulnerable because they are relatively (or
p.000056: absolutely) incapable of protecting their own interests. This may occur when persons have relative or absolute
p.000056: impairments in decisional capacity, education, resources, strength, or other attributes needed to protect their own
p.000056: interests. In other cases, persons can also be vulnerable because some feature of the circumstances (temporary or
p.000056: permanent) in which they live makes it less likely that others will be vigilant about, or sensitive to, their
p.000056: interests. This may happen when people are marginalized, stigmatized, or face social exclusion or prejudice
p.000056: that increases the likelihood that others place their interests at risk, whether intentionally or unintentionally.
p.000056: Although research ethics committees can require special protections only for potential participants collectively for a
p.000056: particular project, researchers and others involved in research must take into account factors that render individual
p.000056: participants vulnerable and take appropriate steps to mitigate those factors.
p.000056:
p.000056: A traditional approach to vulnerability in research has been to label entire classes of individuals as vulnerable. The
p.000056: account of vulnerability in this Guideline seeks to avoid considering members of entire classes of
p.000056: individuals as vulnerable. However, it is useful to look at the specific characteristics that may render individuals
p.000056: vulnerable, as this can aid in identifying the special protections needed for persons who may have an increased
p.000056: likelihood of being wronged or of incurring additional harm as participants in research. Different characteristics
p.000056: may also co-exist, making some individuals more vulnerable than others. This is highly dependent on the context.
p.000056: For example, persons who are illiterate, marginalized by virtue of their social status or behaviour, or living in an
p.000056: authoritarian environment, may have multiple factors that make them vulnerable.
p.000056:
p.000056: Some characteristics can make it reasonable to assume that certain individuals are vulnerable, for example:
p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
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p.000057:
p.000057:
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p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
p.000057: Examples are medical and nursing students, subordinate hospital and laboratory personnel, workers in settings
p.000057: where research studies are conducted, and members of the armed forces or police. Their agreement to volunteer may be
p.000057: unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate
p.000057: in the study or by fear of disapproval or retaliation if they refuse (see also commentary on Guideline 9 – Individuals
p.000057: capable of giving informed consent). The research protocol must include a description of provisions to protect such
p.000057: individuals from being conscripted into research.
p.000057:
p.000057: Institutionalized persons. Residents of nursing homes, mental institutions, and prisons are often considered vulnerable
p.000057: because in a confined setting they have few options and are denied certain freedoms that non-institutionalized persons
p.000057: enjoy. For example, prisons have been described as “an inherently coercive environment.” Also, they may be in a
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p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
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p.000057: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: stereotypes. One proposed mechanism that can be used to avoid stereotyping is consultation with relevant stakeholders,
p.000058: where feasible, before, during and after the conduct of the research (see Guideline 7 – Community
p.000058: engagement).
p.000058:
p.000058: Special protections. Special protections for these groups can include allowing no more than minimal risks for
p.000058: procedures that offer no potential individual benefits for participants; supplementing the participant’s agreement by
p.000058: the permission of family members, legal guardians, or other appropriate representatives; or requiring that the research
p.000058: be carried out only when it is targeted at conditions that affect these groups. Safeguards can be designed to promote
p.000058: voluntary decision-making, limit the potential for confidentiality breaches, and otherwise work to protect the
p.000058: interests of those at increased risk of harm. Research ethics committees need to be sensitive to not overly excluding
p.000058: people, and allow them to participate by requiring that special protections be put in place.
p.000058:
p.000058: Group vulnerability. Despite the importance of avoiding classification of entire groups as inherently vulnerable,
p.000058: circumstances exist that require research ethics committees to pay special attention to research involving
p.000058: certain groups. In some resource-limited countries or communities, lack of access to medical care,
p.000058: membership in ethnic and racial minorities, or other disadvantaged or marginalized groups can be factors
p.000058: that constitute vulnerability. As is true of the vulnerability of individuals, the judgment that groups
p.000058: are vulnerable is context dependent and requires empirical evidence to document the need for special
p.000058: protections.
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p.000059:
p.000059: GUIDELINE 16:
p.000059: RESEARCH INVOLVING
p.000059: ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000059:
p.000059: Adults who are not capable of giving informed consent must be included in health-related research unless a good
p.000059: scientific reason justifies their exclusion. As adults who are not capable of giving informed consent
p.000059: have distinctive physiologies and health needs, they merit special consideration by researchers and research
p.000059: ethics committees. At the same time, they may not be able to protect their own interests due to their lack of capacity
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p.000068:
p.000068:
p.000068: Commentary on Guideline 18
p.000068: General considerations. Women in many societies have been excluded from research. For example, most of the early
p.000068: cardiovascular disease studies have excluded women because these diseases were believed to be uncommon in women. In
p.000068: particular, women who are biologically capable of becoming pregnant have been traditionally excluded from clinical
p.000068: trials of drugs, vaccines and medical devices owing to concern about undetermined risks to the fetus (see
p.000068: Guideline 15 – Research involving vulnerable persons and groups). Although the presumption against including women
p.000068: has changed in recent years, they are still excluded in many cases without adequate justification. Much remains unknown
p.000068: about the safety and efficacy of most drugs, vaccines, or devices used by women in medical practice, and
p.000068: this lack of knowledge can be dangerous. For example, heart attacks in women are different from heart attacks in men,
p.000068: so research is necessary to determine the best means of diagnosis and treatment in women.
p.000068:
p.000068: Vulnerability of women. Despite the current general presumption that favours the inclusion of women in
p.000068: research, in many societies women remain socially vulnerable in the conduct of research. For example, they may
p.000068: suffer negligence or harm because of their submission to authority, their hesitancy or inability to ask
p.000068: questions, and a cultural tendency to deny or tolerate pain and suffering. When women in these situations are potential
p.000068: participants in research, researchers, sponsors and ethics committees must take special care in the research design,
p.000068: assessment of risks and benefits, as well as the process of informed consent, to ensure that women have
p.000068: the necessary time and appropriate environment to make decisions based on information provided to them.
p.000068:
p.000068: Some women become vulnerable in research because of heightened psychological, social, physical, or legal risks.
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p.000076: disaster situation but still appropriate to ensure the study’s scientific validity. Without scientific validity, the
p.000076: research lacks social value and must not be conducted (see Guideline 1 – Scientific and social value and respect for
p.000076: rights). Research may even divert personnel or resources from the disaster response. In clinical trials, the
p.000076: randomised-controlled trial design is often considered the “gold standard” for collecting robust data. However,
p.000076: researchers, sponsors, research ethics committees and others must explore alternative trial designs that may increase
p.000076: trial efficiency and access to promising experimental interventions while still maintaining scientific validity. The
p.000076: methodological and ethical merits of alternative trial designs must be carefully assessed before these designs are
p.000076: used. For example, when testing experimental treatments or vaccines during an epidemic, the appropriate trial
p.000076: design will depend on the promise of the investigational agent,
p.000076:
p.000076:
p.000076: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000077: 77
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077: a variation in critical background factors (for example mortality and infection rates), and measurement of outcomes,
p.000077: among others. Researchers and sponsors must carefully evaluate the relative merits of different designs (for example
p.000077: observational or placebo-controlled) based on these factors.
p.000077:
p.000077: Community engagement. Because disasters often lead to vulnerability and fragile political and social situations,
p.000077: engaging local communities about the research at an early stage is essential for maintaining public trust and ensuring
p.000077: that studies are conducted in a culturally sensitive manner (see Guideline 7 – Community engagement). Researchers and
p.000077: sponsors can use creative mechanisms to expedite and facilitate community engagement in a disaster situation (for
p.000077: example, by using social media). Fostering community leadership will often be important to address distrust and
p.000077: communicate effectively in order to gain support for the study design. In engaging with communities, researchers,
p.000077: sponsors and research ethics committees should be aware of potential conflicts of interest vis-à-vis the proposed
p.000077: research. For example, community leaders might seek to reassert their own authority by providing services to their
p.000077: communities through research.
p.000077:
p.000077: Ethical review and oversight. The standard mechanism for ethical review will often be too time-consuming
p.000077: to enable full research protocols to be prepared and reviewed at the outset of a disaster. Procedures
p.000077: should be developed to facilitate and accelerate ethical review in a situation of crisis. For example, research ethics
p.000077: committees or a specialist ethics committee (perhaps on a national or regional level) may conduct an initial
...
Health / Cognitive Impairment
Searching for indicator cognitive:
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p.000061: expected, participants must be routinely screened. However, it is important to note that diagnosis of a mental or
p.000061: behavioural disorder does not necessarily imply that individuals are incapable of giving informed consent.
p.000061:
p.000061: Potential individual benefits and risks. The potential individual benefits and risks of research with adults incapable
p.000061: of giving informed consent should be evaluated based on Guideline 4 – Potential individual benefits and risks of
p.000061: research, and Guideline 5 – Choice of control in clinical trials.
p.000061:
p.000061: Assent and dissent. If participants cannot consent because they are incapacitated due to mental or behavioural
p.000061: disorders, they must be engaged in the research discussion at the level of their capacity to understand, and they must
p.000061: be given a fair opportunity to agree to or to decline participation in the study. This can also be called
p.000061: obtaining the participant’s assent or dissent. Assent must be considered as a process (see Guideline 9 –
p.000061: Individuals capable of giving informed consent) that responds to changes in the person’s cognitive status and is
p.000061: not merely the absence of dissent.
p.000061:
p.000061: Any explicit objection by persons who are incapable to give informed consent must be respected even if the legally
p.000061: authorized representative has given permission. An explicit objection may be overruled if the incapacitated person
p.000061: needs treatment that is not available outside the context of research, prior research has demonstrated a significant
p.000061: benefit (see Guideline 4 – Potential individual benefits and risks of research), and the treating physician and the
p.000061: legally authorized representative consider the research intervention to be the best available medical option for the
p.000061: person lacking capacity.
p.000061:
p.000061: Permission of a legally authorized representative. In accordance with relevant national regulations, the
p.000061: permission of an immediate family member or other person with a close personal relationship with the individual must
p.000061: be sought. Surrogate decision-makers must evaluate to what extent study participation is consistent with the
p.000061: individual’s previously formed preferences and values (if any), and, in the case of research that offers participants a
p.000061: prospect of clinical benefit, to what extent study participation promotes the individual’s clinical interests.
p.000061: Previously stated preferences regarding the individual’s willingness to enrol in research or documented preferences in
p.000061: an advance directive should be respected. Researchers must recognize that surrogates may have their own
...
p.000065: particularly susceptible, as well as for clinical trials of drugs that will be used for children and adolescents as
p.000065: well as adults. In the past, many new products were not tested in children or adolescents although they were
p.000065: directed at diseases also occurring in childhood. In some cases, this resulted in children or adolescents being
p.000065: exposed to interventions that were either not effective or were harmful. In general, this lack of information results
p.000065: in higher risks for children and adolescents from being exposed to interventions where little is known about their
p.000065: specific effects or safety in this population. Therefore, it is imperative to involve children and adolescents in
p.000065: research to study both investigational interventions for childhood conditions and established interventions in
p.000065: adults that are also relevant for children or adolescents, but that have not previously undergone rigorous testing in
p.000065: children and adolescents. Research ethics committees should recognize that research involving children or adolescents
p.000065: spans a wide range of individuals, from infants through to those just short of legal maturity, with very different
p.000065: physical, cognitive and emotional capacities. A nuanced approach to evaluating research with children and adolescents
p.000065: is therefore required.
p.000065:
p.000065: Order of involvement in research. There is controversy over whether research must be done first in
p.000065: adults or adolescents before it is done in younger children. Some believe that all studies must be done
p.000065: in adults first in order to minimize risks in children. Others argue that this requirement can preclude valuable and
p.000065: timely research in children, in particular when the research addresses an important health need or priority of
p.000065: children.
p.000065:
p.000065: These Guidelines acknowledge that the general rationale behind inclusion of adults before children is that children
p.000065: must be protected from unnecessary risks of harm. However, a strict adherence to this requirement may not always
p.000065: be tenable in pediatric research since children and adolescents face distinctive health problems. In the case
p.000065: of childhood-specific conditions, studies in adults would not be feasible or their results meaningful. Moreover, in
p.000065: rare cases (for example, when a disease affects large numbers of people, including children and adolescents, the
...
Searching for indicator impairment:
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p.000072: pregnancy with regard to both the health of the woman and the short-term and long-term health of the infant and child.
p.000072: Adverse events associated with research in pregnancy and during lactation may not occur immediately.
p.000072:
p.000072: Potential individual benefits and risks. The potential individual benefits and risks of research with pregnant and
p.000072: breastfeeding women should be evaluated based on Guideline 4 – Potential individual benefits and risks of research, and
p.000072: Guideline 5 – Choice of control in clinical trials.
p.000072:
p.000072: Serious harm and access to abortion. Research with pregnant women must be conducted only in settings where
p.000072: these women can be guaranteed access to a safe, legal abortion. This rule serves to prevent women from having to carry
p.000072: an unwanted fetus to term and deliver an affected baby against their wishes. Before pregnant women are enrolled,
p.000072: researchers must, at a minimum, determine whether fetal impairment and mental health conditions are recognised as legal
p.000072: grounds for abortion in that jurisdiction. If they are not, pregnant women must not be recruited for research in which
p.000072: there is a realistic basis for concern that significant fetal abnormality may occur as a consequence of
p.000072: participation in research. At the same time, this rule might restrict potentially valuable research in
p.000072: countries where women cannot be guaranteed access to abortion. In such cases, research projects can be
p.000072: conducted only if a local research ethics committee determines that the research has compelling social value for
p.000072: pregnant women and the women are informed about existing restrictions on abortion and possible options for obtaining an
p.000072: abortion in another country.
p.000072:
p.000072: Breastfeeding women. The father may need to be consulted in research involving breastfeeding women, in accordance with
...
Health / Drug Dependence
Searching for indicator dependency:
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p.000034:
p.000034: Dependent relationship. There are different forms of dependent relationships, such as those between
p.000034: teachers and students, and guards and prisoners. In the context of clinical research, dependent
p.000034: relationships can result from pre-existing relationships between a treating physician and a patient, who
p.000034: becomes a potential participant when his or her treating physician assumes the role of researcher. The
p.000034: dependent relationship between patients and clinician-researchers may compromise the voluntariness of informed
p.000034: consent, since potential participants who are patients depend on the clinician-researcher for medical care and
p.000034: may be reluctant to refuse an invitation to enrol in research in which the treating clinician is involved. Therefore,
p.000034: in principle, in the case of a dependent relationship a neutral third party such as a research nurse or a
p.000034: qualified collaborator,
p.000034:
p.000034:
p.000034: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000035: 35
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: should obtain informed consent. However, in some situations of dependency, it is preferable that the clinician provide
p.000035: the patient with information since he or she is most knowledgeable about the condition of the patient. However, to
p.000035: minimize the influence of the dependent relationship, several protective measures must be taken. Clinicians engaged in
p.000035: research must acknowledge and inform patients that they have a dual role as the treating clinician and researcher. They
p.000035: must emphasize the voluntary nature of participation and the right to refuse or withdraw from the research. They must
p.000035: also assure patients that their decision whether to enrol or refuse participation will not affect the therapeutic
p.000035: relationship or other benefits to which they are entitled. In cases where it is necessary for the treating clinician to
p.000035: explain the details of the study protocol, the research ethics committee must consider whether the informed consent
p.000035: document must be signed in the presence of a neutral third party.
p.000035:
p.000035: Risks. Researchers must be completely objective in discussing the details of the experimental intervention,
p.000035: the pain or discomfort it may entail, and known risks and possible hazards. In some types of prevention research,
p.000035: potential participants must receive counselling about risks of acquiring a disease and steps they can take to reduce
p.000035: those risks. This is especially true of preventive research on communicable diseases, such as HIV/AIDS.
p.000035:
...
Health / Drug Usage
Searching for indicator drug:
(return to top)
p.000003: which persons are drawn, patent-holders if they are other than the sponsor, and nongovernmental organizations such as
p.000003: health advocacy groups. The negotiation must address the health-care infrastructure required for safe and
p.000003: appropriate use of any intervention or product developed. When applicable, it must also consider the likelihood and
p.000003: conditions of authorization for distribution, and decisions regarding payments, royalties, subsidies, technology and
p.000003: intellectual property, as well as distribution costs, when such information is not proprietary. A plan to ensure the
p.000003: availability and distribution of successful products can require engaging with international organizations, donor
p.000003: governments and bilateral agencies, civil society organizations, and the private sector. The ability of the local
p.000003: health- care infrastructure to be able to provide the intervention must be facilitated at the outset so that delivery
p.000003: is possible following the completion of the research.
p.000003:
p.000003: Post-trial availability for communities and populations. Even if research addresses a question that has social value
p.000003: for the community or population where it is carried out, the community or population will not benefit from
p.000003: successful research unless the knowledge and interventions that it produces are made available to them and products are
p.000003: reasonably priced. Post-trial access plans are of particular concern for research conducted in low-resource settings
p.000003: where governments lack the means or infrastructure to make such products widely available.
p.000003:
p.000003: An investigational drug is unlikely to be generally available to the community or population until
p.000003: sometime after the conclusion of the study, as it may be in short supply, and in most cases could not be made generally
p.000003: available before a drug regulatory authority has approved it. However, other successful outcomes of research that
p.000003: do not require approval by a regulatory agency should be implemented as soon as feasible. An example is the
p.000003: introduction of male circumcision in countries with a high burden of HIV disease. Research demonstrated a significant
p.000003: preventive effect of male circumcision, following which, programmes to offer male circumcision were introduced in
p.000003: several countries.
p.000003:
p.000003: When the outcome is scientific knowledge rather than a commercial product, complex planning or negotiation among
p.000003: relevant stakeholders may not be needed. There must be assurance, however, that the scientific knowledge gained will be
p.000003: distributed and available for the benefit of the population. To that end, agreement must be reached with the local
p.000003: community about the form such dissemination
p.000003:
p.000003:
p.000003: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000004: 4
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: should take. One example might be a study that learns why a health condition such as neural tube defects is prevalent
p.000004: in a particular population. Another example could be a study that results in knowledge to educate the
p.000004: population about foods to eat or avoid in order to promote or maintain health.
p.000004:
p.000004: These requirements for post-trial availability to communities and populations must not be construed as precluding
p.000004: studies designed to evaluate novel therapeutic concepts. An example might be research designed to obtain
p.000004: preliminary evidence that a drug or a class of drugs is beneficial in treating a disease that occurs only
p.000004: in low-resource settings, when the research could not be carried out reasonably well in more developed
p.000004: communities. Such preliminary research may be justified ethically even if there will not be a specific product
p.000004: that could be made available to the population of the host country or community at the conclusion of the
p.000004: preliminary phase of its development. If the concept is found to be valid, subsequent phases of the research could
p.000004: result in a product that would be made reasonably available at its conclusion.
p.000004:
p.000004: Additional benefits to the population or community. Benefits other than those associated with study
p.000004: participation may accrue to the community or population, especially in resource-poor settings. Such benefits
p.000004: can include improving the health infrastructure, training laboratory personnel, and educating the public about the
p.000004: nature of research and the benefits resulting from a particular study. Whereas capacity-building should be a part of
p.000004: any research conducted in low-resource settings, other types of benefits will depend on the circumstances of the
p.000004: research and environment in which it is carried out. These additional benefits must be determined in consultation with
p.000004: the communities or the local population. Additional benefits may also include contributions that research or research
p.000004: partnerships make to the overall scientific environment of such countries and communities.
p.000004:
p.000004: Community engagement. From the inception of research planning, it is important to ensure full participation of
...
p.000007: people’s health (see Guideline 1 – Scientific and social value and respect for rights). Equity in the distribution of
p.000007: burdens of research requires special care to ensure that individuals, communities or populations that are already
p.000007: disadvantaged or marginalized are not over-represented in research. A disproportionate selection of disadvantaged or
p.000007: convenient populations is morally problematic for several reasons. First, it is unjust to selectively invite poor or
p.000007: marginalized individuals or groups to participate in research because this concentrates the risks and burdens of
p.000007: research on people who already experience increased risks and burdens from social and economic disadvantage. Second,
p.000007: these individuals and groups are also the most likely to be excluded from, or to have difficulty accessing, the
p.000007: benefits of research. Third, the broad inclusion of different social groups helps to ensure that research is conducted
p.000007: in a socially and ethically acceptable manner. When research is concentrated in disadvantaged or marginalized groups,
p.000007: it may be easier to expose participants to unreasonable risks or undignified treatment. Furthermore, research results
p.000007: obtained from disadvantaged populations may not be appropriately extrapolated to the general population.
p.000007:
p.000007: In the past, certain groups have been over-used as research subjects. In some cases, this has been based on the easy
p.000007: availability of the populations. For example, in the United States prisoners were considered ideal persons for Phase I
p.000007: drug studies in the past. Other populations that may be over- represented in research because of their easy
p.000007: availability include students in researchers’ classes, residents of long-term care facilities and subordinate members
p.000007: of hierarchical organizations. In other cases, impoverished groups have been over-used because of their willingness to
p.000007: serve as subjects in exchange for relatively small stipends, their desire to access medical care, or because research
p.000007: hospitals are often located in places where members of the lowest socio-economic classes reside.
p.000007:
p.000007: Not only may certain groups within a society be inappropriately over-used as research participants, but also entire
p.000007: communities or societies may be over-used. Such over-use is especially problematic when the populations or communities
p.000007: concerned bear the burdens of participation in research but are unlikely to enjoy the benefits of new knowledge and
p.000007: products developed as a result of the research.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000008: 8
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: GUIDELINE 4:
p.000008: POTENTIAL INDIVIDUAL BENEFITS AND RISKS OF RESEARCH
p.000008:
p.000008: To justify imposing any research risks on participants in health research, the research must have social
p.000008: and scientific value. Before inviting potential participants to join a study, the researcher, sponsor and the
...
p.000015: receive a treatment that is known to be inferior to an established treatment. Sponsors, researchers, and
p.000015: research ethics committees should evaluate the risks of providing no treatment (and no placebo) or an inferior
p.000015: treatment, compared to the risks and potential individual benefits of providing an established treatment, and apply the
p.000015: criteria for placebo use in this Guideline. In sum, when an established effective intervention exists, it may be
p.000015: withheld or substituted with an inferior intervention only if there are compelling scientific reasons for doing so; the
p.000015: risks of withholding the established intervention or substituting it with an inferior one will result in no
p.000015: more than a minor increase above minimal risk to participants; and the risks to participants are minimized.
p.000015:
p.000015: Placebo. An inert substance or sham procedure is provided to research participants with the aim of making it impossible
p.000015: for them, and usually the researchers themselves, to know who is receiving an active or inactive intervention. Placebo
p.000015: interventions are methodological tools used with the goal of isolating the clinical effects of the investigational drug
p.000015: or intervention. This enables researchers to treat participants in the study arm and the control arm in exactly the
p.000015: same way, except that the
p.000015:
p.000015:
p.000015:
p.000015: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000016: 16
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: study group receives an active substance and the control group does not. The risks of the placebo intervention itself
p.000016: are typically very low or non-existent (for example, ingestion of an inert substance).
p.000016:
p.000016: In some fields, such as surgery and anaesthesia, testing the effectiveness of interventions may require the use of sham
p.000016: interventions. For example, the participants in the active arm of a surgery trial may receive arthroscopic surgery
p.000016: on their knees, while participants in the control group may receive only a minor skin incision. In other
p.000016: cases, both groups may receive an invasive procedure, such as inserting a catheter into a person’s artery. The catheter
p.000016: is threaded into the heart of participants in the active arm, but stopped short of the heart in participants in the
p.000016: control arm. The risks of sham procedures can be considerable (for example, surgical incision under general
p.000016: anaesthesia) and must be carefully considered by a research ethics committee.
p.000016:
...
p.000017: established effective intervention, but may nonetheless be the only feasible or cost-effective and beneficial option
p.000017: in the circumstances. Considerable controversy exists in this situation regarding which trial design is
p.000017: both ethically acceptable and necessary to address the research question. Some argue that such studies should be
p.000017: conducted with a non-inferiority design that compares the study intervention with an established effective
p.000017: method. Others argue that a superiority design using a placebo can be acceptable.
p.000017:
p.000017: The use of placebo controls in these situations is ethically controversial for several reasons:
p.000017: 1. Researchers and sponsors knowingly withhold an established effective intervention from participants in the control
p.000017: arm. However, when researchers and sponsors are in a position to provide an intervention that would
p.000017: prevent or treat a serious disease, it is difficult to see why they are under no obligation to provide it. They could
p.000017: design the trial as an equivalency trial to determine whether the experimental intervention is as good or almost as
p.000017: good as the established effective intervention.
p.000017:
p.000017:
p.000017: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018: 2. Some argue that it is not necessary to conduct clinical trials in populations in low-resource settings in order to
p.000018: develop affordable interventions that are substandard compared to the available interventions in other
p.000018: countries. Instead, they argue that drug prices for established treatments should be negotiated and increased funding
p.000018: from international agencies should be sought.
p.000018:
p.000018: When controversial, placebo-controlled trials are planned, research ethics committees in the host country must:
p.000018: 1. seek expert opinion, if not available within the committee, as to whether use of placebo may lead to
p.000018: results that are responsive to the needs or priorities of the host country (see Guideline 2
p.000018: – Research conducted in low-resource settings); and
p.000018:
p.000018: 2. ascertain whether arrangements have been made for the transition to care after research for study
p.000018: participants (see Guideline 6 – Caring for participants’ health needs), including post-trial arrangements
p.000018: for implementing any positive trial results, taking into consideration the regulatory and health care policy framework
p.000018: in the country.
p.000018:
p.000018: Comparative effectiveness and standard of care trials. For many conditions and diseases, one or more
p.000018: established effective treatments exist. Physicians and hospitals may then use different treatments for the same
p.000018: condition. Yet often the relative merits of these treatments are unknown. Comparative effectiveness research, as well
p.000018: as systematic reviews, have received growing attention over the past few years. In comparative effectiveness research,
p.000018: two or more interventions regarded as standards of care are directly compared. Comparative effectiveness
...
p.000019: participants’ health needs during research and, if necessary, for the transition of participants to care when
p.000019: the research is concluded. The obligation to care for participants’ health needs is influenced, among other
p.000019: things, by the extent to which participants need assistance and established effective care is available locally.
p.000019:
p.000019: When participants’ health needs during and after research cannot be met by the local health
p.000019: infrastructure or the participant’s pre-existing health insurance, the researcher and sponsor must make
p.000019: prior arrangements for adequate care for participants with local health authorities, members of the
p.000019: communities from which persons are drawn, or nongovernmental organizations such as health advocacy groups.
p.000019:
p.000019: Addressing participants’ health needs requires at least that researchers and sponsors make plans for:
p.000019: f how care will be adequately provided for the condition under study;
p.000019: f how care will be provided during the research when researchers discover conditions other than those under study
p.000019: (“ancillary care”);
p.000019: f transitioning participants who continue to need care or preventive measures after the research to appropriate
p.000019: health services;
p.000019: f providing continued access to study interventions that have demonstrated significant benefit; and
p.000019: f consulting with other relevant stakeholders, if any, to determine everyone’s responsibilities and the conditions
p.000019: under which participants will receive continued access to a study intervention, such as an investigational drug, that
p.000019: has demonstrated significant benefit in the study.
p.000019:
p.000019: When access is provided after the research to investigational interventions that have demonstrated
p.000019: significant benefit, the provision may end as soon as the study intervention is made available through the local
p.000019: public health-care system or after a predetermined period of time that the sponsors, researchers and
p.000019: community members have agreed before the start of a trial.
p.000019:
p.000019: Information on care for participants’ health needs during and after the research must be included in the informed
p.000019: consent process.
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Commentary on Guideline 6
p.000021: General considerations. It is generally inappropriate to require researchers or sponsors to take on the role of a
p.000021: country’s health systems. Nevertheless, research with humans often involves interactions that enable researchers to
p.000021: detect or diagnose health problems during recruitment and the conduct of research. Similarly, clinical research
p.000021: often involves care and preventive measures in addition to the experimental interventions. In some cases,
p.000021: participants may continue to need the care or prevention provided during the research after their participation
p.000021: in the study has ended. This may include access to an investigational intervention that has demonstrated
...
p.000052: costs, and compensated reasonably for their inconvenience and time spent. Compensation can be monetary or non-monetary.
p.000052: The latter might include free health services unrelated to the research, medical insurance, educational materials, or
p.000052: other benefits.
p.000052:
p.000052: Compensation must not be so large as to induce potential participants to consent to participate in the
p.000052: research against their better judgment (“undue inducement”). A local research ethics committee must approve
p.000052: reimbursement and compensation for research participants.
p.000052:
p.000052:
p.000052: Commentary on Guideline 13
p.000052: General considerations. Both in observational studies and intervention research, participants should not have to pay
p.000052: for making a contribution to the social good of research, whether in the form of direct expenses (for
p.000052: example, transportation costs), and must therefore be reasonably reimbursed for such expenses. In addition,
p.000052: participants must be appropriately compensated for the time spent and other inconveniences resulting from study
p.000052: participation. The amount of compensation should be proportional to the time spent for research purposes and for travel
p.000052: to the research site. This amount should be calculated using the minimum hourly wage in the region or country as a
p.000052: reference value. The obligation to reasonably reimburse and compensate participants arises even when study
p.000052: enrolment offers participants potential individual benefits (for example, an investigational drug). This is
p.000052: because the vast majority of clinical research studies involve research procedures that have no potential individual
p.000052: benefits for participants but are performed for research purposes, such as additional blood draws, extra hospital
p.000052: visits and overnight stays. Moreover, it cannot be known before the research that investigational interventions
p.000052: will benefit participants. Indeed, some research interventions may cause more harm than good.
p.000052:
p.000052: Appropriate compensation. Participants must also be reasonably compensated for their inconvenience and time
p.000052: spent participating in research according to monetary value of the country in which the research is conducted.
p.000052: Compensation can be monetary or non-monetary and may include, for example, health services unrelated to the research,
p.000052: medical insurance, educational materials, counselling or food supplies. Especially when the research poses low risks,
p.000052: providing compensation for participation should not raise concerns about undue inducement.
p.000052:
p.000052: Unacceptable compensation. Compensation is not meant to compensate for risk that participants agree to undertake but
p.000052: rather, for inconvenience and time. Therefore, the level of compensation
p.000052:
p.000052: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: should not be related to the level of risk that participants agree to undertake. But especially as the
...
p.000069: women and breastfeeding women as research participants). Access to a pregnancy test, to effective
p.000069: contraceptive methods and to safe, legal abortion must be guaranteed before exposure to a potential teratogenic or
p.000069: mutagenic intervention. When effective contraception and safe abortion are not available and alternative study sites
p.000069: are not feasible, the informed consent discussion must include information about the risk of unintended pregnancy, the
p.000069: legal grounds for abortion, and information about reducing harms from unsafe abortion and subsequent complications.
p.000069: Also, if the pregnancy is not terminated, participants must be guaranteed a medical follow-up for their own health and
p.000069: that of the infant and child.
p.000069:
p.000069: Women who become pregnant during research. Many biomedical protocols call for terminating the participation of women
p.000069: who become pregnant during the research. In cases where a drug or biological product is known to be mutagenic or
p.000069: teratogenic, pregnant women must be removed from the study, and followed up and provided care through
p.000069: the duration of their pregnancy and delivery. Access to diagnostic tests must be provided to reveal any fetal
p.000069: anomalies. If anomalies are detected, women who wish may be referred for an abortion. When there is no evidence on the
p.000069: basis of which a potential harm to the fetus can be assumed, women who become pregnant should not automatically be
p.000069: removed from the study, but must be offered the option to continue or end their participation. For instance, in some
p.000069: cases it may be appropriate for a woman to stay in the study for safety monitoring but removed from the study drug. If
p.000069: the woman opts for continued participation, researchers and sponsors must offer adequate monitoring and support.
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000070: 70
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: GUIDELINE 19:
p.000070: PREGNANT AND BREASTFEEDING WOMEN AS RESEARCH PARTICIPANTS
p.000070:
p.000070: Pregnant and breastfeeding women have distinctive physiologies and health needs. Research designed to obtain
p.000070: knowledge relevant to the health needs of the pregnant and breastfeeding woman must be promoted. Research in pregnant
p.000070: women must be initiated only after careful consideration of the best available relevant data.
p.000070:
p.000070: In no case must the permission of another person replace the requirement of individual informed consent by the pregnant
p.000070: or breastfeeding woman.
p.000070:
...
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
p.000071: it is imperative to design research for pregnant and breastfeeding women to learn about the currently unknown
p.000071: risks and potential individual benefits to them, as well as to the fetus or nursing infant.
p.000071:
p.000071: A case in point is the thalidomide episode, in which about 10,000 babies around the world (many in Western Europe) were
p.000071: born with severely deformed limbs because their mothers had taken medication when pregnant. This tragedy is often cited
p.000071: as a reason for excluding pregnant women from health- related research, but the lesson to be learned is the opposite.
p.000071: Never having been tested in pregnant women, the drug came to market and was readily available for morning sickness, a
p.000071: relatively mild condition. Had the drug been tested in very few women in a clinical trial, the mutagenic effect would
p.000071: most likely have been discovered and the total number of babies born with deformities would have been much smaller.
p.000071:
p.000071: Research designed to obtain knowledge relevant to the health needs of pregnant and breastfeeding women should be
p.000071: promoted in the following areas:
p.000071: f interventions for conditions resulting from pregnancy;
p.000071: f interventions for conditions that affect the general population and are reasonably expected to be used without
p.000071: adequate evidence during pregnancy (for example off-label use of medications); and
p.000071: f interventions for conditions that affect the developing fetus.
p.000071:
p.000071: Informed consent and risks and potential individual benefits. The involvement of pregnant women in
p.000071: research is complicated by the fact that it may present risks and potential individual benefits to the
p.000071: fetus as well as to the woman. Participation of breastfeeding women in biomedical research may similarly pose risks
...
p.000093: establishing research ethics committees and for their review of protocols).
p.000093:
p.000093:
p.000093: Commentary on Guideline 25
p.000093: General considerations. A conflict of interest exists when there is a substantial risk that secondary interests of
p.000093: one or more stakeholders in research unduly influence their judgment and thereby compromise or undermine
p.000093: the primary goal of research. For example, a researcher may have a financial stake in the outcomes of the
p.000093: study that creates a financial conflict of interest. Given the competitive environment for academic researchers and the
p.000093: increasing commercialization of research, managing conflicts of interests is essential for safeguarding the scientific
p.000093: integrity of research and protecting the rights and interests of study participants. This commentary first explains
p.000093: conflicts of interests and then discusses their management.
p.000093:
p.000093: Conflicts of interest. Different stakeholders in research can have different types of conflicts of
p.000093: interest.
p.000093:
p.000093:
p.000093:
p.000093: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000095: 95
p.000095:
p.000095:
p.000095:
p.000095:
p.000095:
p.000095: 1. Researchers. Academic conflicts of interest can arise when researchers or senior members of a research team become
p.000095: overly invested in their own ideas. For example, a researcher who has worked for decades on an investigational HIV drug
p.000095: may find it difficult to stop a trial early when interim results clearly recommend this course of action. Furthermore,
p.000095: researchers’ careers depend on publishing interesting results, for example, when applying for research
p.000095: funding or promotion. This can create professional conflicts of interests.
p.000095: Some researchers also have personal financial conflicts of interest. For example, researchers sometimes receive part
p.000095: of their salary or a “finder’s fee” for recruiting research participants. When this income reflects a fair
p.000095: compensation for their time spent on recruitment, it does not present an inherent conflict of interest. However, a
p.000095: salary or “finder’s fee” may lead researchers
p.000095: – intentionally or unintentionally – to interpret the inclusion or exclusion criteria of a study too flexibly, thereby
p.000095: potentially exposing participants to excessive risks or compromising the scientific validity of the research.
p.000095: This situation is of particular concern when participants are dependent on a researcher who is also their clinician
p.000095: (see Guideline 9 – Individuals capable of giving informed consent, section on Dependent relationship), and when the
p.000095: salary of the clinician is considerably lower than what the researcher is paid. It may also lead researchers to
p.000095: pressure eligible participants to enrol, thus compromising or undermining participants’ voluntary consent. In addition,
p.000095: financial conflicts of interest can arise when researchers or senior members of the research team (or their close
...
p.000099:
p.000099: 16. The process of recruitment, e.g. advertisements, and the steps to be taken to protect privacy and confidentiality
p.000099: during recruitment (Guideline 3);
p.000099:
p.000099: 17. Description and explanation of all interventions (the method of treatment administration, including
p.000099: route of administration, dose, dose interval and treatment period for investigational and comparator products used);
p.000099:
p.000099: 18. Plans and justification for withdrawing or withholding standard therapies in the course of the research, including
p.000099: any resulting risks to persons (Guidelines 4 and 5);
p.000099:
p.000099: 19. Any other treatment that may be given or permitted, or contraindicated, during the study (Guideline
p.000099: 6);
p.000099:
p.000099: 20. Clinical and laboratory tests and other tests that are to be carried out;
p.000099:
p.000099: 21. Samples of the standardized case-report forms to be used, the methods of recording therapeutic response
p.000099: (description and evaluation of methods and frequency of measurement), the follow-up procedures, and, if applicable, the
p.000099: measures proposed to determine the extent of compliance of persons with the treatment;
p.000099:
p.000099: 22. Rules or criteria according to which participants may be removed from the study or clinical trial, or (in a
p.000099: multi-centre study) a centre may be discontinued, or the study may be terminated;
p.000099:
p.000099: 23. Methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000099: complications (Guidelines 4 and 23);
p.000099:
p.000099: 24. The known or foreseen risks of adverse reactions, including the risks attached to each proposed intervention and
p.000099: to any drug, vaccine or procedure to be tested (Guideline 4);
p.000099:
p.000099: 25. The potential individual benefits of the research to participants and to others (Guideline 4);
p.000099:
p.000099: 26. The expected benefits of the research to the population, including new knowledge that the study might
p.000099: generate (Guidelines 1 and 4);
p.000099:
p.000099: 27. For research carrying more than minimal risk of physical injury, details of plans, including
p.000099: insurance coverage, to provide treatment for such injury, including the funding of treatment, and to provide
p.000099: compensation for research-related disability or death (Guideline 14);
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000100: 100
p.000100: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 28. Provision for continued access to study interventions that have demonstrated significant benefit, indicating its
p.000100: modalities, the parties involved in continued care and the organization responsible for paying for it, and for how long
p.000100: it will continue (Guideline 6);
p.000100:
p.000100: 29. For research on pregnant women, a plan, if appropriate, for monitoring the outcome of the pregnancy
p.000100: with regard to both the health of the woman and the short-term and long-term health of the child (Guideline 19);
p.000100:
...
p.000101:
p.000101: 43. For research that is to be carried out in a low-resource setting, the contribution that the sponsor will make to
p.000101: capacity-building for scientific and ethical review and for health-related research in the host country, and an
p.000101: assurance that the capacity-building objectives are in keeping with the values and expectations of the participants and
p.000101: their communities (Guideline 8);
p.000101:
p.000101: 44. The research protocol or documents send to the research ethics committee should include a description of the plan
p.000101: for (continued) community engagement, and present resources allocated for the community engagement activities. This
p.000101: documentation must clarify what has been and will be done, when and by whom to ensure that the community is clearly
p.000101: mapped and defined and can be proactively engaged throughout the research to ensure that the research is relevant to
p.000101: the community and is accepted. The community should participate, when feasible, in the actual discussion
p.000101: and preparation of the research protocol and documents (Guideline 7);
p.000101:
p.000101: 45. Particularly in the case of an industrial sponsor, a contract stipulating who possesses the right to publish the
p.000101: results of the study, and a mandatory obligation to prepare with, and submit to, the principal investigators the draft
p.000101: of the text reporting the results (Guideline 24);
p.000101:
p.000101: 46. In the case of a negative outcome, an assurance that the results will be made available, as
p.000101: appropriate, through publication or by reporting to the drug registration authority (Guideline 24);
p.000101:
p.000101: 47. Plans for publication of research results in certain fields (for example, epidemiology, genetics, sociology) that
p.000101: may present risks to the interests of communities, societies, families, or racially or ethnically defined groups and
p.000101: for minimizing risks to these groups, notably by maintaining confidentiality during and after the study and publishing
p.000101: the resulting data in a manner that is respectful of the interests of all concerned (Guideline 4); and
p.000101:
p.000101: 48. A statement that any proven evidence of falsification of data will be dealt with in accordance with the policy of
p.000101: the sponsor to take appropriate action against such unacceptable procedures.
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:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000102: 102
p.000102: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: APPENDIX 2
p.000102: OBTAINING INFORMED CONSENT: ESSENTIAL INFORMATION
p.000102: FOR PROSPECTIVE RESEARCH PARTICIPANTS
p.000102:
p.000102: Before requesting an individual’s consent to participate in research, the researcher must provide the
p.000102: following information, in language or another form of communication that the individual can understand (see
p.000102: also Guideline 9):
...
p.000107: national/international guidelines related to ethics, prevention, care and treatment of HIV/AIDS and TB. He has
p.000107: frequently acted as temporary advisor to many national/international institutions, such as the Brazilian AIDS
p.000107: Programme, WHO, UNITAID, UNAIDS, CIOMS and WMA. From 2010 to 2013 he directed the Department of STD, AIDS and Viral
p.000107: Hepatitis (Secretary of Health Surveillance, MoH, Brazil).
p.000107:
p.000107: David Haerry
p.000107: David Haerry is a treatment writer and conference reporter since 1996. He is co-authoring a database on travel &
p.000107: residency restrictions for people living with HIV. David Haerry has been involved in health care professionals
p.000107: education projects since 2007. Since 2015, he is Secretary General of the Swiss Academic Foundation on Education in
p.000107: Infectious Diseases SAFE-ID. He is work package co-leader and member of the Executive Committee in the EUPATI-IMI
p.000107: project and involved in a number of European and global research networks and research collaborations, including the
p.000107: ENCePP Steering Group. He is co-chair of the Patient and Consumer Working Party at the European Medicines Agency and
p.000107: has served the European AIDS Treatment Group EATG in various positions since 2004. David has been involved in HIV and
p.000107: HCV drug development since 2005 and has specific interests in the areas of Personalised Medicine, Risk Communication,
p.000107: Pharmacovigilance, Observational Studies, Biomedical Prevention and HIV Eradication Research. He is living with HIV
p.000107: since 1986.
p.000107:
p.000107: Bocar Kouyaté
p.000107: Bocar A. Kouyaté is Senior Advisor to the Minister of Health, Burkina Faso and researcher at the Centre national de
p.000107: recherché et de formation sur le paludisme (CNRFP), Burkina Faso. Dr Kouyaté is a physician by training and holds
p.000107: a PhD degree in public health. He has worked throughout all levels of the health system in Burkina Faso from
p.000107: district medical officer to the intermediary level as
p.000107:
p.000107:
p.000107:
p.000107:
p.000108: 108
p.000108: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108: Provincial Director of Health and to Secretary General of the Ministry of Health from 1983 to 1998. From 1989 to 2009,
p.000108: he was Director of two research centres in Burkina Faso (Centre de recherche en santé de Nouna and, later on, Centre
p.000108: national de recherche et de formation sur le paludisme). He served as member of the Comité national d’éthique
p.000108: pour la recherche en santé (CERS) from 2003–2007 and was the Chair of the CERS from 2008–2013. He has
p.000108: considerable experience in research, research administration, capacity development and training, particularly in health
...
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p.000119: adequate prior knowledge base, and are likely to generate valuable information.
p.000119:
p.000119: Although scientific and social value are the fundamental justification for undertaking research, researchers,
p.000119: sponsors, research ethics committees and health authorities have a moral obligation to ensure that all research
p.000119: is carried out in ways that uphold human rights, and respect, protect, and are fair to study
p.000119: participants and the communities in which the research is conducted. Scientific and social value cannot legitimate
p.000119: subjecting study participants or host communities to mistreatment, or injustice.
p.000119:
p.000119:
p.000119: Commentary on Guideline 1
p.000119: General considerations. In order to be ethically permissible, health-related research with humans, including research
p.000119: with samples of human tissue or data, must have social value. The scientific and social value of research can be
p.000119: difficult to quantify, but it is generally grounded in three factors: the quality of the information to be
p.000119: produced, its relevance to significant health problems, and its contribution to the creation or evaluation of
p.000119: interventions, policies, or practices that promote individual or public health. It is essential to the social
p.000119: value of health-related research that its design is scientifically sound and that it offers a means of developing
p.000119: information not otherwise obtainable. For example, so-called “seeding trials” violate this requirement if their purpose
p.000119: is to influence clinicians who participate in the study to prescribe a new medication rather than to produce knowledge
p.000119: about the merits of these interventions.
p.000119:
p.000119: Social value. Social value refers to the importance of the information that a study is likely to produce. Information
p.000119: can be important because of its direct relevance for understanding or intervening on a significant health
p.000119: problem or because of its expected contribution to research likely to promote individual or public health. The
p.000119: importance of such information can vary depending on the significance of the health need, the novelty and expected
p.000119: merits of the approach, the merits of alternative means of addressing the problem, and other considerations. For
p.000119: example, a well-designed, late phase clinical trial could lack social value if its endpoints are
p.000119: unrelated to clinical decision-making so that clinicians and policy-makers are unlikely to alter their practices
p.000119: based on the study’s findings.
p.000119:
p.000119:
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000001: 1
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Similarly, although replication serves an important role in scientific research, well-designed studies that lack
p.000001: sufficient novelty may also lack social value.
p.000001:
p.000001: Researchers, sponsors, research ethics committees and relevant health authorities, such as regulators and
p.000001: policy-makers, must ensure that a study has sufficient social value to justify its associated risks, costs and burdens.
p.000001: In particular, there must be sufficient social value to justify risks to participants in studies that lack the prospect
...
p.000010: effective alternative. Participants in the
p.000010:
p.000010: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: control group of a clinical trial must be provided with an established effective intervention; exceptions to this
p.000011: general rule are set out and discussed in Guideline 5 – Choice of control in clinical trials.
p.000011:
p.000011: Judgments about the risk-benefit profile of study interventions, and how they compare with the risk- benefit profile of
p.000011: any established alternatives, must be based on the available evidence. Therefore, researchers and sponsors have an
p.000011: obligation to provide, in the research protocol and other documents submitted to the research ethics committee, a
p.000011: comprehensive and balanced overview of the available evidence that is relevant for evaluating the risks and potential
p.000011: individual benefits of the research. In research protocols for clinical trials, researchers and sponsors must clearly
p.000011: describe results from preclinical studies and, where applicable, early phase or exploratory trials of the study
p.000011: intervention involving humans. They must also note in the documents sent to the committee any limitations of the
p.000011: available data as well as any disagreement about the foreseeable risks and potential individual benefits, including
p.000011: potential conflicts of interests that might influence conflicting opinions. Researchers should provide a credible
p.000011: interpretation of the available evidence to support their judgment that an investigational agent has a favourable
p.000011: risk-benefit ratio, and that its risk-benefit profile is at least as advantageous as the risk-benefit profile
p.000011: of any established alternatives. It is important to note, however, that the risks and potential individual
p.000011: benefits of study interventions can be difficult to predict before larger clinical trials have been conducted.
p.000011: This means that sponsors, researchers and research ethics committees may need to judge the risk-benefit profile of such
p.000011: interventions under conditions of considerable uncertainty.
p.000011:
p.000011: Finally, researchers, sponsors and research ethics committees must ensure that the aggregate risks of all
p.000011: research interventions or procedures in a study are acceptable. For example, a study may involve numerous
p.000011: interventions or procedures that each pose limited risks, but these risks may add up to an overall
p.000011: significant level of risk that is unacceptable in relation to the social and scientific value of the study. To guard
p.000011: against this possibility, researchers, sponsors and research ethics committees must complete risk-benefit evaluations
...
p.000013:
p.000013: When there is an established effective intervention, placebo may be used as a comparator without providing the
p.000013: established effective intervention to participants only if:
p.000013: f there are compelling scientific reasons for using placebo; and
p.000013: f delaying or withholding the established effective intervention will result in no more than a minor
p.000013: increase above minimal risk to the participant and risks are minimized, including through the use of effective
p.000013: mitigation procedures.
p.000013:
p.000013: Risks and benefits of other study interventions and procedures should be evaluated according to the criteria set out in
p.000013: Guideline 4 – Potential individual benefits and risks of research.
p.000013:
p.000013:
p.000013: Commentary on Guideline 5
p.000013: General considerations for controlled clinical trials. The conduct of controlled clinical trials is
p.000013: methodologically essential in order to test the relative merits of investigational interventions. To obtain
p.000013: valid results in a controlled trial, researchers must compare the effects of an experimental intervention on
p.000013: participants assigned to the investigational arm (or arms) of a trial with the effects that a control intervention
p.000013: produces in persons drawn from the same population. Randomization is the preferred method for assigning
p.000013: participants to the arms of controlled trials. Assignment to treatment arms by randomization tends to produce study
p.000013: groups comparable with respect to factors that might influence study outcomes, removes researcher bias in the
p.000013: allocation of participants, and helps to ensure that the study results reflect the effects of administered
p.000013: interventions and not the influence of extraneous factors.
p.000013:
p.000013: The use of placebo controls in clinical trials creates the potential for conflict between the demands of sound
p.000013: science and the obligation to safeguard the health and welfare of study participants. In general, studies
p.000013: must be designed to generate accurate scientific information without delaying or withholding established effective
p.000013: interventions from participants. Researchers and sponsors may deviate from this rule when withholding such
p.000013: interventions is methodologically necessary and exposes participants to no more than a minor increase above minimal
p.000013: risk.
p.000013:
p.000013:
p.000013:
p.000013: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000015: 15
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: Although conventional randomized controlled clinical trials are often considered the gold standard, other study
p.000015: designs such as response-adaptive trial designs, observational studies, or historical comparisons can also
p.000015: yield valid research results. Researchers and sponsors must carefully consider whether the research question
p.000015: can be answered with an alternative design, and whether the risk-benefit profile of alternative designs is more
p.000015: favourable when compared to a conventional randomized controlled trial.
p.000015:
p.000015: Established effective intervention. An established effective intervention for the condition under study exists when it
...
p.000023: communities in a meaningful participatory process that involves them in an early and sustained manner in
p.000023: the design, development, implementation, design of the informed consent process and monitoring of research,
p.000023: and in the dissemination of its results.
p.000023:
p.000023:
p.000023: Commentary on Guideline 7
p.000023: General considerations. Proactive and sustained engagement with the communities from which participants will be invited
p.000023: to participate is a way of showing respect for them and the traditions and norms that they share. Community engagement
p.000023: is also valuable for the contribution it can make to the successful conduct of research. In particular, community
p.000023: engagement is a means of ensuring the relevance of proposed research to the affected community, as well as
p.000023: its acceptance by the community. In addition, active community involvement helps to ensure the ethical and social
p.000023: value and outcome of proposed research. Community engagement is especially important when the research
p.000023: involves minorities or marginalized groups, including persons with stigmatizing diseases such as HIV, in order to
p.000023: address any potential discrimination.
p.000023:
p.000023: A community consists not only of people living in the geographic area where research is to be carried out; it also
p.000023: comprises different sectors of society that have a stake in the proposed research, as well as sub-populations from
p.000023: which research participants will be recruited. Stakeholders are individuals, groups, organizations, government bodies,
p.000023: or any others who can influence or are affected by the conduct or outcome of the research project. The process must be
p.000023: fully collaborative and transparent, involving a wide variety of participants, including patients and consumer
p.000023: organizations, community leaders and representatives, relevant NGOs and advocacy groups, regulatory authorities,
p.000023: government agencies and community advisory boards. Also, it is important to ensure diversity of views within the
p.000023: consultation process. For instance, when community leaders are men only, researchers should actively include the views
p.000023: of women, as well. There may also be value in consulting individuals who have previously participated in comparable
p.000023: studies.
p.000023:
p.000023: The research protocol or other documents submitted to the research ethics committee should include a
p.000023: description of the plan for community engagement, and identify resources allocated for the proposed activities. This
p.000023: documentation must specify what has been and will be done, when and by whom, to ensure that the community is clearly
p.000023: defined and can be proactively engaged throughout the research to ensure that it is relevant to the community and is
p.000023: accepted. The community should participate, when feasible, in the actual discussion and preparation of the
p.000023: research protocol and documents.
p.000023:
p.000023: Researchers, sponsors, health authorities and relevant institutions should take care that community engagement does
p.000023: not lead to pressure or undue influence on individual community members to participate (see commentary on
p.000023: Guideline 9 – Individuals capable of giving informed consent, section
p.000023:
p.000023:
p.000023:
p.000023: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000025: 25
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: on Dependent relationship). In order to avoid such pressure, individual informed consent must always be sought by the
p.000025: researcher.
p.000025:
p.000025: Researchers and research ethics committees should be cognizant of the point at which the process of community
p.000025: engagement becomes a stage of formative research that itself requires ethics review. Examples of community engagement
p.000025: processes that may require ethics review include systematic data collection that can be generalized and disseminated in
p.000025: forums outside of the community in which they were implemented, as well as any data generation that could create social
p.000025: risks for participants.
p.000025:
p.000025: Engagement at the earliest opportunity. Before a study is initiated, the community from which participants will be
p.000025: recruited should, when feasible, be consulted about their research priorities, preferred trial designs,
p.000025: willingness to be involved in the preparation and conduct of the study. Engaging the community at the
...
p.000034: council of elders, or another designated authority. Such institutional procedures or cultural customs should be
p.000034: respected. In no case, however, may the permission of a community leader or other authority substitute for individual
p.000034: informed consent. In some populations, the use of local languages may facilitate the communication of information to
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
p.000034: factors can be internal to participants, such as mental illness, whereas other influences can be external, such as a
p.000034: dependent relationship between participants and clinician-researchers. Circumstances such as severe illness or poverty
p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
p.000034: consent in these situations. Research ethics committees must determine for each individual protocol if influences on
p.000034: voluntary consent cross the threshold of being undue, and if so, which safeguards are appropriate.
p.000034:
p.000034: Dependent relationship. There are different forms of dependent relationships, such as those between
p.000034: teachers and students, and guards and prisoners. In the context of clinical research, dependent
p.000034: relationships can result from pre-existing relationships between a treating physician and a patient, who
p.000034: becomes a potential participant when his or her treating physician assumes the role of researcher. The
p.000034: dependent relationship between patients and clinician-researchers may compromise the voluntariness of informed
p.000034: consent, since potential participants who are patients depend on the clinician-researcher for medical care and
p.000034: may be reluctant to refuse an invitation to enrol in research in which the treating clinician is involved. Therefore,
p.000034: in principle, in the case of a dependent relationship a neutral third party such as a research nurse or a
p.000034: qualified collaborator,
p.000034:
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p.000034: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: should obtain informed consent. However, in some situations of dependency, it is preferable that the clinician provide
p.000035: the patient with information since he or she is most knowledgeable about the condition of the patient. However, to
p.000035: minimize the influence of the dependent relationship, several protective measures must be taken. Clinicians engaged in
p.000035: research must acknowledge and inform patients that they have a dual role as the treating clinician and researcher. They
p.000035: must emphasize the voluntary nature of participation and the right to refuse or withdraw from the research. They must
p.000035: also assure patients that their decision whether to enrol or refuse participation will not affect the therapeutic
p.000035: relationship or other benefits to which they are entitled. In cases where it is necessary for the treating clinician to
p.000035: explain the details of the study protocol, the research ethics committee must consider whether the informed consent
p.000035: document must be signed in the presence of a neutral third party.
p.000035:
p.000035: Risks. Researchers must be completely objective in discussing the details of the experimental intervention,
p.000035: the pain or discomfort it may entail, and known risks and possible hazards. In some types of prevention research,
p.000035: potential participants must receive counselling about risks of acquiring a disease and steps they can take to reduce
p.000035: those risks. This is especially true of preventive research on communicable diseases, such as HIV/AIDS.
p.000035:
p.000035: Who obtains consent. Informed consent must be obtained by a member of the research team. Delegation of obtaining
...
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p.000092:
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p.000092:
p.000092: observe additional privacy protections beyond de-identification and data security, as appropriate, and appoint an
p.000092: independent panel that includes members of the public to review data requests. These safeguards must not
p.000092: unduly impede access to data.
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p.000093:
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p.000093:
p.000093:
p.000093: GUIDELINE 25:
p.000093: CONFLICTS OF INTEREST
p.000093:
p.000093: The primary goal of health-related research is to generate, in ethically appropriate ways, the knowledge necessary
p.000093: to promote people’s health. However, researchers, research institutions, sponsors, research ethics committees,
p.000093: and policy-makers have other interests (for example, scientific recognition or financial gain) that can
p.000093: conflict with the ethical conduct of research. Such conflicts between the primary goal of health-related research
p.000093: and secondary interests are defined as conflicts of interest.
p.000093:
p.000093: Conflicts of interest can influence the choice of research questions and methods, recruitment and retention of
p.000093: participants, interpretation and publication of data, and the ethical review of research. It is therefore necessary to
p.000093: develop and implement policies and procedures to identify, mitigate, eliminate, or otherwise manage such conflicts of
p.000093: interest.
p.000093:
p.000093: Research institutions, researchers and research ethics committees should take the following steps:
p.000093: f Research institutions should develop and implement policies and procedures to mitigate conflicts of interest and
p.000093: educate their staff about such conflicts;
p.000093: f Researchers should ensure that the materials submitted to a research ethics committee include a disclosure of
p.000093: interests that may affect the research;
p.000093: f Research ethics committees should evaluate each study in light of any disclosed interests and ensure
p.000093: that appropriate means of mitigation are taken in case of a conflict of interest; and
p.000093: f Research ethics committees should require their members to disclose their own interests to the committee and
p.000093: take appropriate means of mitigation in case of a conflict of interest (see Guideline 23 – Requirements for
p.000093: establishing research ethics committees and for their review of protocols).
p.000093:
p.000093:
p.000093: Commentary on Guideline 25
p.000093: General considerations. A conflict of interest exists when there is a substantial risk that secondary interests of
p.000093: one or more stakeholders in research unduly influence their judgment and thereby compromise or undermine
p.000093: the primary goal of research. For example, a researcher may have a financial stake in the outcomes of the
p.000093: study that creates a financial conflict of interest. Given the competitive environment for academic researchers and the
p.000093: increasing commercialization of research, managing conflicts of interests is essential for safeguarding the scientific
p.000093: integrity of research and protecting the rights and interests of study participants. This commentary first explains
p.000093: conflicts of interests and then discusses their management.
p.000093:
p.000093: Conflicts of interest. Different stakeholders in research can have different types of conflicts of
p.000093: interest.
p.000093:
p.000093:
p.000093:
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p.000095:
p.000095:
p.000095:
p.000095:
p.000095:
p.000095: 1. Researchers. Academic conflicts of interest can arise when researchers or senior members of a research team become
p.000095: overly invested in their own ideas. For example, a researcher who has worked for decades on an investigational HIV drug
p.000095: may find it difficult to stop a trial early when interim results clearly recommend this course of action. Furthermore,
p.000095: researchers’ careers depend on publishing interesting results, for example, when applying for research
p.000095: funding or promotion. This can create professional conflicts of interests.
p.000095: Some researchers also have personal financial conflicts of interest. For example, researchers sometimes receive part
...
p.000095:
p.000095: In order to evaluate the seriousness of a conflict of interest, and to determine appropriate measures for its
p.000095: management, research ethics committees need to judge the risk that the sponsor’s or investigator’s
p.000095: conflicts of interest unduly compromise or undermine the ethical or scientific conduct of a study. This involves
p.000095: judging both the likelihood that a secondary interest might compromise the rights or welfare of participants
p.000095: or the scientific validity of the research, as well as judging the magnitude of the secondary interest relative to the
p.000095: stakeholder’s personal situation. For example, an early-career researcher with a modest salary might have more
p.000095: significant academic and financial conflicts of interest than an established senior member of the research
p.000095: team. Research ethics committees have to exercise their judgment when evaluating the seriousness of conflicts of
p.000095: interest.
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p.000096:
p.000096:
p.000096:
p.000096:
p.000096: As a general rule, a potential serious conflict of interest exists when there is a significant possibility that the
p.000096: actions of an investigator resulting from professional, academic, or financial interests will result in biased study
p.000096: results or cause harm or wrong to participants.
p.000096:
p.000096: Conflicts of interests can influence researchers subconsciously. For example, researchers with a financial
p.000096: stake in a study may not intentionally manipulate the research findings. However, their financial interests may
p.000096: subconsciously influence their analysis and interpretation of the research data.
p.000096:
p.000096: Management of conflicts of interest. All stakeholders in research share responsibility for developing and implementing
p.000096: policies and procedures to identify, mitigate, eliminate, or otherwise manage conflicts of interest.
p.000096: Although this is a joint responsibility, research institutions play a critical role in creating an
p.000096: institutional culture that takes conflicts of interest seriously and adopts appropriate measures for their management.
p.000096: Measures for managing conflicts of interest must be proportional to their seriousness. For example, a minor
p.000096: conflict of interest may be appropriately managed by disclosure, while a potential serious conflict can, in some
p.000096: cases, justify excluding a researcher from the study team. Policies and measures for managing conflicts of interest
p.000096: must be transparent and actively communicated to those affected.
p.000096:
p.000096: 1. Education of researchers and research ethics committees. Raising awareness of conflicts of interest, as well as
p.000096: the importance of managing such conflicts, is essential for making procedures and policies effective.
p.000096:
p.000096: 2. Disclosure of interests to research ethics committees. Researchers must disclose conflicts of interest on their
p.000096: part to the ethical review committee or to other institutional committees designed to evaluate and manage
p.000096: such conflicts. Researchers will most likely come to recognize conflicts of interest if they are prompted to
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p.000015: intervention. When researchers propose to deviate from this option, they must provide a compelling methodological
p.000015: justification and evidence that the risks from withholding or delaying the established intervention are no greater than
p.000015: a minor increase above minimal risk.
p.000015:
p.000015: These principles on the use of placebo also apply to the use of control groups who receive no treatment or who
p.000015: receive a treatment that is known to be inferior to an established treatment. Sponsors, researchers, and
p.000015: research ethics committees should evaluate the risks of providing no treatment (and no placebo) or an inferior
p.000015: treatment, compared to the risks and potential individual benefits of providing an established treatment, and apply the
p.000015: criteria for placebo use in this Guideline. In sum, when an established effective intervention exists, it may be
p.000015: withheld or substituted with an inferior intervention only if there are compelling scientific reasons for doing so; the
p.000015: risks of withholding the established intervention or substituting it with an inferior one will result in no
p.000015: more than a minor increase above minimal risk to participants; and the risks to participants are minimized.
p.000015:
p.000015: Placebo. An inert substance or sham procedure is provided to research participants with the aim of making it impossible
p.000015: for them, and usually the researchers themselves, to know who is receiving an active or inactive intervention. Placebo
p.000015: interventions are methodological tools used with the goal of isolating the clinical effects of the investigational drug
p.000015: or intervention. This enables researchers to treat participants in the study arm and the control arm in exactly the
p.000015: same way, except that the
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p.000015: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000016: 16
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: study group receives an active substance and the control group does not. The risks of the placebo intervention itself
p.000016: are typically very low or non-existent (for example, ingestion of an inert substance).
p.000016:
p.000016: In some fields, such as surgery and anaesthesia, testing the effectiveness of interventions may require the use of sham
p.000016: interventions. For example, the participants in the active arm of a surgery trial may receive arthroscopic surgery
p.000016: on their knees, while participants in the control group may receive only a minor skin incision. In other
p.000016: cases, both groups may receive an invasive procedure, such as inserting a catheter into a person’s artery. The catheter
p.000016: is threaded into the heart of participants in the active arm, but stopped short of the heart in participants in the
p.000016: control arm. The risks of sham procedures can be considerable (for example, surgical incision under general
p.000016: anaesthesia) and must be carefully considered by a research ethics committee.
p.000016:
p.000016: Placebo controls. The use of placebo is usually uncontroversial in the absence of an established effective
p.000016: intervention. As a general rule, when an established effective intervention exists for the condition under
p.000016: investigation, study participants must receive that intervention within the trial. This does not preclude
p.000016: comparing the effects of potential new interventions against a placebo control in cases where all participants receive
p.000016: the established effective intervention and are then randomized to the investigational intervention or placebo. Such
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p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119: xi
p.000119:
p.000119: PREAMBLE
p.000119: The ethical principles set forth in these Guidelines should be upheld in the ethical review of research protocols. The
p.000119: ethical principles are regarded as universal. Moreover, the Guidelines should be read and interpreted as a whole. Some
p.000119: Guidelines have cross references to other Guidelines. The purpose of these cross references is to help the reader
p.000119: navigate through the Guidelines. However, absence of cross references to other Guidelines does not imply that other
p.000119: Guidelines may not be applicable.
p.000119:
p.000119: Although the Guidelines focus primarily on rules and principles to protect humans in research, both
p.000119: virtues and protections are essential to reliably safeguard the rights and welfare of humans.
p.000119:
p.000119: As a general rule, “must” has been used to attach greater moral weight to requirements when compared to
p.000119: “should”.
p.000119:
p.000119: The term “health-related research” in these Guidelines refers to activities designed to develop or
p.000119: contribute to generalizable health knowledge within the more classic realm of research with humans, such as
p.000119: observational research, clinical trials, biobanking and epidemiological studies. Generalizable health knowledge
p.000119: consists of theories, principles or relationships, or the accumulation of information on which they are based related
p.000119: to health, which can be corroborated by accepted scientific methods of observation and inference.
p.000119:
p.000119: These Guidelines address research involving humans. Usage in the bioethics literature varies. In this
p.000119: document, the terms “human beings”, “research participants”, and “human subjects” are used interchangeably.
p.000119:
p.000119: Progress towards a world where all can enjoy optimal health and health care is crucially dependent on all kinds of
p.000119: research including research involving humans.
p.000119:
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p.000119: xii
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119: GUIDELINE 1:
p.000119: SCIENTIFIC AND SOCIAL VALUE AND RESPECT FOR RIGHTS
p.000119:
p.000119: The ethical justification for undertaking health-related research involving humans is its scientific and
p.000119: social value: the prospect of generating the knowledge and the means necessary to protect and promote
p.000119: people’s health. Patients, health professionals, researchers, policy-makers, public health officials, pharmaceutical
p.000119: companies and others rely on the results of research for activities and decisions that impact individual and
p.000119: public health, welfare, and the use of limited resources. Therefore, researchers, sponsors, research ethics
p.000119: committees, and health authorities, must ensure that proposed studies are scientifically sound, build on an
...
Health / HIV/AIDS
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p.000119: The Council for International Organizations of Medical Sciences (CIOMS) is an international nongovernmental
p.000119: organization in official relationship with World Health Organization (WHO). It was founded under the auspices of WHO
p.000119: and the United Nations Educational, Scientific and Cultural and Organization (UNESCO) in 1949. Among its mandates is
p.000119: maintaining collaborative relations with the United Nations and its specialized agencies, especially UNESCO and WHO.
p.000119:
p.000119: The first version of the CIOMS Guidelines (1982)
p.000119: CIOMS, in association with WHO, undertook its work on ethics in biomedical research in the late 1970s.
p.000119: Accordingly, CIOMS set out, in cooperation with WHO, to prepare guidelines. The aim of the guidelines was (and still
p.000119: is) to provide internationally vetted ethical principles and detailed commentary on how universal ethical principles
p.000119: should be applied, with particular attention to conducting research in low-resource settings. The outcome of the
p.000119: CIOMS/WHO collaboration was entitled Proposed International Ethical Guidelines for Biomedical Research Involving
p.000119: Human Subjects.
p.000119:
p.000119: The second version of the CIOMS Guidelines (1993)
p.000119: The period that followed saw the outbreak of the HIV/AIDS pandemic and proposals for large-scale trials of prevention
p.000119: and treatment for the disease. These developments raised new ethical issues that had not been considered in the
p.000119: preparation of the Proposed Guidelines. There were other factors also – rapid advances in medicine and
p.000119: biotechnology, changing research practices such as multinational field trials, experimentation involving
p.000119: vulnerable population groups, and also a new perspective in both high- and low-resource settings, that research
p.000119: involving humans could be beneficial to participants rather than threatening. The World Medical Association’s
p.000119: Declaration of Helsinki was revised twice in the 1980s – in 1983 and 1989. It was timely to revise and update the 1982
p.000119: Guidelines, and CIOMS, with the collaboration of WHO and its Global Programme on AIDS, undertook the
p.000119: task. The outcome was the issue of two sets of guidelines: International Guidelines for Ethical Review of
p.000119: Epidemiological Studies in 1991, and International Ethical Guidelines for Biomedical Research Involving Human Subjects
p.000119: in 1993.
p.000119:
p.000119: The third version of the CIOMS Guidelines (2002)
p.000119: After 1993, ethical issues arose for which the 1993 CIOMS Guidelines had no specific provisions. They related mainly
p.000119: to externally sponsored clinical trials carried out in low-resource settings. In particular, the use of
p.000119: comparators other than an established effective intervention used in low- resource settings became a concern.
...
p.000119: biomedical and epidemiological research. At the same time, research projects that have been ethically
p.000119: assessed on the basis of previous versions of the guidelines may be continued on the terms and conditions as set out in
p.000119: those previous versions.
p.000119:
p.000119: Reactions to the Guidelines are welcome and should be addressed to the Secretary-General, Council for International
p.000119: Organizations of Medical Sciences, P.O. Box 2100, CH-1211 Geneva 2, Switzerland; or by email to info@cioms.ch.
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000119:
p.000119: EVIDENCE RETRIEVAL AND SYNTHESIS
p.000119: In the revision process, literature reviews were used as sources for further ethical deliberation.
p.000119: Authoritative declarations, reports and guidance documents have had a prominent role in these discussions,
p.000119: such as the Nuremberg Code (1947), the Universal Declaration of Human Rights of the United Nations (1948), the
p.000119: International Covenant on Civil and Political Rights of the United Nations (1966), the Belmont Report (1979), the
p.000119: Guideline on Good Clinical Practice (GCP) of the International Conference on Harmonisation of Technical Requirements
p.000119: for Registration of Pharmaceuticals for Human Use (ICH) (1996), the Oviedo Convention of the Council of Europe (1997),
p.000119: the Universal Declaration on Bioethics and Human Rights of UNESCO (2005), the UNAIDS/WHO Ethical
p.000119: Considerations in Biomedical HIV Prevention Trials (2007/2012), Standards and operational guidance for
p.000119: ethics review of health-related research with human participants of the WHO (2011), and the Declaration of Helsinki of
p.000119: the World Medical Association (2013). Some of these guidelines have been extensively used, in particular the UNAIDS/WHO
p.000119: document (2012) for Guideline 7 on community engagement.
p.000119:
p.000119: Textbooks, existing ethical frameworks for human subjects research and reports on research involving human beings
p.000119: were also valuable sources of information. The Working Group reviewed papers in major ethics journals (in
p.000119: alphabetical order) such as the American Journal of Bioethics, Bioethics, BMC Medical Ethics, the Cambridge
p.000119: Quarterly of Healthcare Ethics, Developing World Bioethics, the Hastings Center Report, the Journal of Bioethical
p.000119: Inquiry, the Journal of Empirical Research on Human Research Ethics, the Journal of Law, Medicine and Ethics,
p.000119: the Journal of Medical Ethics, the Journal of Medicine and Philosophy, Medicine, Health Care and Philosophy, as
p.000119: well as articles in leading medical or scientific journals, such as BMJ, The Lancet, the New England
...
p.000003: availability and distribution of successful products can require engaging with international organizations, donor
p.000003: governments and bilateral agencies, civil society organizations, and the private sector. The ability of the local
p.000003: health- care infrastructure to be able to provide the intervention must be facilitated at the outset so that delivery
p.000003: is possible following the completion of the research.
p.000003:
p.000003: Post-trial availability for communities and populations. Even if research addresses a question that has social value
p.000003: for the community or population where it is carried out, the community or population will not benefit from
p.000003: successful research unless the knowledge and interventions that it produces are made available to them and products are
p.000003: reasonably priced. Post-trial access plans are of particular concern for research conducted in low-resource settings
p.000003: where governments lack the means or infrastructure to make such products widely available.
p.000003:
p.000003: An investigational drug is unlikely to be generally available to the community or population until
p.000003: sometime after the conclusion of the study, as it may be in short supply, and in most cases could not be made generally
p.000003: available before a drug regulatory authority has approved it. However, other successful outcomes of research that
p.000003: do not require approval by a regulatory agency should be implemented as soon as feasible. An example is the
p.000003: introduction of male circumcision in countries with a high burden of HIV disease. Research demonstrated a significant
p.000003: preventive effect of male circumcision, following which, programmes to offer male circumcision were introduced in
p.000003: several countries.
p.000003:
p.000003: When the outcome is scientific knowledge rather than a commercial product, complex planning or negotiation among
p.000003: relevant stakeholders may not be needed. There must be assurance, however, that the scientific knowledge gained will be
p.000003: distributed and available for the benefit of the population. To that end, agreement must be reached with the local
p.000003: community about the form such dissemination
p.000003:
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p.000003: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000004: 4
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: should take. One example might be a study that learns why a health condition such as neural tube defects is prevalent
p.000004: in a particular population. Another example could be a study that results in knowledge to educate the
p.000004: population about foods to eat or avoid in order to promote or maintain health.
p.000004:
p.000004: These requirements for post-trial availability to communities and populations must not be construed as precluding
p.000004: studies designed to evaluate novel therapeutic concepts. An example might be research designed to obtain
p.000004: preliminary evidence that a drug or a class of drugs is beneficial in treating a disease that occurs only
p.000004: in low-resource settings, when the research could not be carried out reasonably well in more developed
p.000004: communities. Such preliminary research may be justified ethically even if there will not be a specific product
...
p.000022: communities are discussed in Guideline 2 – Research conducted in low-resource settings.
p.000022:
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p.000023:
p.000023:
p.000023:
p.000023:
p.000023: GUIDELINE 7:
p.000023: COMMUNITY ENGAGEMENT
p.000023:
p.000023: Researchers, sponsors, health authorities and relevant institutions should engage potential participants and
p.000023: communities in a meaningful participatory process that involves them in an early and sustained manner in
p.000023: the design, development, implementation, design of the informed consent process and monitoring of research,
p.000023: and in the dissemination of its results.
p.000023:
p.000023:
p.000023: Commentary on Guideline 7
p.000023: General considerations. Proactive and sustained engagement with the communities from which participants will be invited
p.000023: to participate is a way of showing respect for them and the traditions and norms that they share. Community engagement
p.000023: is also valuable for the contribution it can make to the successful conduct of research. In particular, community
p.000023: engagement is a means of ensuring the relevance of proposed research to the affected community, as well as
p.000023: its acceptance by the community. In addition, active community involvement helps to ensure the ethical and social
p.000023: value and outcome of proposed research. Community engagement is especially important when the research
p.000023: involves minorities or marginalized groups, including persons with stigmatizing diseases such as HIV, in order to
p.000023: address any potential discrimination.
p.000023:
p.000023: A community consists not only of people living in the geographic area where research is to be carried out; it also
p.000023: comprises different sectors of society that have a stake in the proposed research, as well as sub-populations from
p.000023: which research participants will be recruited. Stakeholders are individuals, groups, organizations, government bodies,
p.000023: or any others who can influence or are affected by the conduct or outcome of the research project. The process must be
p.000023: fully collaborative and transparent, involving a wide variety of participants, including patients and consumer
p.000023: organizations, community leaders and representatives, relevant NGOs and advocacy groups, regulatory authorities,
p.000023: government agencies and community advisory boards. Also, it is important to ensure diversity of views within the
p.000023: consultation process. For instance, when community leaders are men only, researchers should actively include the views
p.000023: of women, as well. There may also be value in consulting individuals who have previously participated in comparable
p.000023: studies.
p.000023:
p.000023: The research protocol or other documents submitted to the research ethics committee should include a
p.000023: description of the plan for community engagement, and identify resources allocated for the proposed activities. This
p.000023: documentation must specify what has been and will be done, when and by whom, to ensure that the community is clearly
p.000023: defined and can be proactively engaged throughout the research to ensure that it is relevant to the community and is
...
p.000035: the patient with information since he or she is most knowledgeable about the condition of the patient. However, to
p.000035: minimize the influence of the dependent relationship, several protective measures must be taken. Clinicians engaged in
p.000035: research must acknowledge and inform patients that they have a dual role as the treating clinician and researcher. They
p.000035: must emphasize the voluntary nature of participation and the right to refuse or withdraw from the research. They must
p.000035: also assure patients that their decision whether to enrol or refuse participation will not affect the therapeutic
p.000035: relationship or other benefits to which they are entitled. In cases where it is necessary for the treating clinician to
p.000035: explain the details of the study protocol, the research ethics committee must consider whether the informed consent
p.000035: document must be signed in the presence of a neutral third party.
p.000035:
p.000035: Risks. Researchers must be completely objective in discussing the details of the experimental intervention,
p.000035: the pain or discomfort it may entail, and known risks and possible hazards. In some types of prevention research,
p.000035: potential participants must receive counselling about risks of acquiring a disease and steps they can take to reduce
p.000035: those risks. This is especially true of preventive research on communicable diseases, such as HIV/AIDS.
p.000035:
p.000035: Who obtains consent. Informed consent must be obtained by a member of the research team. Delegation of obtaining
p.000035: consent, for instance to a research nurse or another member of the research team, for instance in the case of a
p.000035: dependent relationship, is permissible as long as the person who obtains consent is duly qualified and has
p.000035: prior experience in obtaining consent. The principal investigator is responsible for ensuring that all personnel
p.000035: working on the project comply with this Guideline.
p.000035:
p.000035: Special considerations regarding informed consent for the use of data in health registries. The requirement to obtain
p.000035: informed consent for research on data in health-related registries may be waived, provided the conditions in Guideline
p.000035: 10 – Modifications and waivers of informed consent - are met. When a researcher plans to contact persons based on their
p.000035: inclusion in a health-related registry, the researcher must bear in mind that these persons may be unaware that their
p.000035: data were submitted to the registry or unfamiliar with the process by which researchers obtain access to the data (see
p.000035: Guideline 12 – Collection, storage and use of data in health-related research). If researchers wish to contact persons
...
p.000093: take appropriate means of mitigation in case of a conflict of interest (see Guideline 23 – Requirements for
p.000093: establishing research ethics committees and for their review of protocols).
p.000093:
p.000093:
p.000093: Commentary on Guideline 25
p.000093: General considerations. A conflict of interest exists when there is a substantial risk that secondary interests of
p.000093: one or more stakeholders in research unduly influence their judgment and thereby compromise or undermine
p.000093: the primary goal of research. For example, a researcher may have a financial stake in the outcomes of the
p.000093: study that creates a financial conflict of interest. Given the competitive environment for academic researchers and the
p.000093: increasing commercialization of research, managing conflicts of interests is essential for safeguarding the scientific
p.000093: integrity of research and protecting the rights and interests of study participants. This commentary first explains
p.000093: conflicts of interests and then discusses their management.
p.000093:
p.000093: Conflicts of interest. Different stakeholders in research can have different types of conflicts of
p.000093: interest.
p.000093:
p.000093:
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p.000095:
p.000095:
p.000095:
p.000095:
p.000095:
p.000095: 1. Researchers. Academic conflicts of interest can arise when researchers or senior members of a research team become
p.000095: overly invested in their own ideas. For example, a researcher who has worked for decades on an investigational HIV drug
p.000095: may find it difficult to stop a trial early when interim results clearly recommend this course of action. Furthermore,
p.000095: researchers’ careers depend on publishing interesting results, for example, when applying for research
p.000095: funding or promotion. This can create professional conflicts of interests.
p.000095: Some researchers also have personal financial conflicts of interest. For example, researchers sometimes receive part
p.000095: of their salary or a “finder’s fee” for recruiting research participants. When this income reflects a fair
p.000095: compensation for their time spent on recruitment, it does not present an inherent conflict of interest. However, a
p.000095: salary or “finder’s fee” may lead researchers
p.000095: – intentionally or unintentionally – to interpret the inclusion or exclusion criteria of a study too flexibly, thereby
p.000095: potentially exposing participants to excessive risks or compromising the scientific validity of the research.
p.000095: This situation is of particular concern when participants are dependent on a researcher who is also their clinician
p.000095: (see Guideline 9 – Individuals capable of giving informed consent, section on Dependent relationship), and when the
p.000095: salary of the clinician is considerably lower than what the researcher is paid. It may also lead researchers to
p.000095: pressure eligible participants to enrol, thus compromising or undermining participants’ voluntary consent. In addition,
p.000095: financial conflicts of interest can arise when researchers or senior members of the research team (or their close
...
p.000106: researcher in the fields of Bioethics, Global Health and Health Policy based in India. He is also Adjunct
p.000106: Professor at Yenepoya University, Mangalore, India. In the past, he has worked for NGOs and a government
p.000106: public health training institution in India, as well as a consultant to a project on Ethical, Social and Cultural
p.000106: issues in health biotechnology based at the University of Toronto. Anant has published extensively in various national
p.000106: and international medical journals in the field of global/public health and bioethics, as well as contributed to
p.000106: popular mass media. Anant has been a resource person for trainings in global health, research methodology, research
p.000106: ethics and public health ethics, and also serves as guest faculty in various educational institutions in India and
p.000106: abroad. He is on the Editorial Board of ‘Public Health Ethics’ (www.phe.oxfordjournals.org),
p.000106:
p.000106:
p.000106: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000107: 107
p.000107:
p.000107:
p.000107:
p.000107:
p.000107:
p.000107: a quarterly journal of Oxford University Press and also serves on the International Advisory Board of the Asian
p.000107: Bioethics Review (http://www.asianbioethicsreview.com). He is also a member of the Ethics Working Group of the US
p.000107: NIH‐funded HIV Prevention Trials Network (http://www.hptn.org/hptnresearchethics.htm). He currently is a member of four
p.000107: ethics committees in India (in two of which he also serves as the chairperson), and has been as a reviewer for multiple
p.000107: journals, conference scientific committees and international grant competitions. Anant is also a member of
p.000107: the Steering Committee of the Global Forum on Bioethics in Research. He is also a member of the Board of
p.000107: the International Association of Bioethics.
p.000107:
p.000107: Eugenijus Gefenas
p.000107: Eugenijus Gefenas is a professor and director of the Department of Medical History and Ethics at the Medical Faculty of
p.000107: Vilnius University. He is also a director of the Lithuanian Bioethics Committee. Eugenijus Gefenas graduated from the
p.000107: Medical Faculty of Vilnius University in 1983 and obtained his PhD in medical ethics from the Institute of Philosophy,
p.000107: Sociology and Law in 1993. E. Gefenas teaches bioethics at the Medical Faculty of Vilnius University and
p.000107: together with colleagues from Clarkson University (USA) co-directs the Advanced Certificate Program in Research
p.000107: Ethics in Central and Eastern Europe. E. Gefenas is a member of the Council of Europe Committee on
p.000107: Bioethics; he was the chair of this Committee from 2011–2012. He was elected as the chairman of the
p.000107: Intergovernmental Bioethics Committee (IGBC) of UNESCO in 2015. The areas of his professional interest include
p.000107: ethical and policy-making issues related to human research and health care in transition societies.
p.000107:
p.000107: Dirceu Greco
p.000107: Dirceu Greco is full professor of Infectious Diseases and Bioethics at the School of Medicine, Federal University of
p.000107: Minas Gerais (UFMG), Belo Horizonte, Brazil. He received his MD degree and this PhD from UFMG. Chief, Infectious and
p.000107: Parasitic Diseases Service (2009-2011), Coordinator of UFMG University Hospital Centre for Clinical Research
p.000107: (2005-2010), member (2007-2010), Brazilian Research Ethics Commission (CONEP); member, Brazilian AIDS Commission
p.000107: (Ministry of Health-MoH). Main topics of interest include Infectious and Parasitic Illnesses, bioethics, public health
p.000107: and clinical immunology. He has participated in several working groups that gave rise to
p.000107: national/international guidelines related to ethics, prevention, care and treatment of HIV/AIDS and TB. He has
p.000107: frequently acted as temporary advisor to many national/international institutions, such as the Brazilian AIDS
p.000107: Programme, WHO, UNITAID, UNAIDS, CIOMS and WMA. From 2010 to 2013 he directed the Department of STD, AIDS and Viral
p.000107: Hepatitis (Secretary of Health Surveillance, MoH, Brazil).
p.000107:
p.000107: David Haerry
p.000107: David Haerry is a treatment writer and conference reporter since 1996. He is co-authoring a database on travel &
p.000107: residency restrictions for people living with HIV. David Haerry has been involved in health care professionals
p.000107: education projects since 2007. Since 2015, he is Secretary General of the Swiss Academic Foundation on Education in
p.000107: Infectious Diseases SAFE-ID. He is work package co-leader and member of the Executive Committee in the EUPATI-IMI
p.000107: project and involved in a number of European and global research networks and research collaborations, including the
p.000107: ENCePP Steering Group. He is co-chair of the Patient and Consumer Working Party at the European Medicines Agency and
p.000107: has served the European AIDS Treatment Group EATG in various positions since 2004. David has been involved in HIV and
p.000107: HCV drug development since 2005 and has specific interests in the areas of Personalised Medicine, Risk Communication,
p.000107: Pharmacovigilance, Observational Studies, Biomedical Prevention and HIV Eradication Research. He is living with HIV
p.000107: since 1986.
p.000107:
p.000107: Bocar Kouyaté
p.000107: Bocar A. Kouyaté is Senior Advisor to the Minister of Health, Burkina Faso and researcher at the Centre national de
p.000107: recherché et de formation sur le paludisme (CNRFP), Burkina Faso. Dr Kouyaté is a physician by training and holds
p.000107: a PhD degree in public health. He has worked throughout all levels of the health system in Burkina Faso from
p.000107: district medical officer to the intermediary level as
p.000107:
p.000107:
p.000107:
p.000107:
p.000108: 108
p.000108: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108: Provincial Director of Health and to Secretary General of the Ministry of Health from 1983 to 1998. From 1989 to 2009,
p.000108: he was Director of two research centres in Burkina Faso (Centre de recherche en santé de Nouna and, later on, Centre
p.000108: national de recherche et de formation sur le paludisme). He served as member of the Comité national d’éthique
p.000108: pour la recherche en santé (CERS) from 2003–2007 and was the Chair of the CERS from 2008–2013. He has
p.000108: considerable experience in research, research administration, capacity development and training, particularly in health
p.000108: systems, research ethics and malaria. His special interest is in the development of sustainable capacity and
p.000108: appropriate environment for research and getting research into policy and practice.
p.000108:
p.000108: Alex London
p.000108: Alex John London, PhD., is Professor of Philosophy and Director of The Center for Ethics and Policy at Carnegie Mellon
p.000108: University. An elected fellow of the Hastings Center, he has written extensively on problems in bioethics and
p.000108: ethical theory relating to uncertainty, risk, fairness, equality and justice. He is co-editor of Ethical Issues
p.000108: in Modern Medicine, one of the most widely used textbooks in medical ethics and recipient of the Elliott Dunlap
p.000108: Smith Award for Distinguished Teaching and Educational Service in the Dietrich College of Humanities and Social
p.000108: Sciences at Carnegie Mellon University. In 2016 Professor London was appointed to the U.S. National Academies of
p.000108: Sciences, Engineering and Medicine (formerly the Institute of Medicine) Committee on Clinical Trials During
p.000108: the 2014–2015 Ebola Outbreak. Since 2007 he has served as a member of the Ethics Working Group of the
p.000108: HIV Prevention Trials Network. He has served as an ethics expert in consultations with numerous national and
p.000108: international organizations including the U.S. National Institutes of Health, the World Health Organization,
p.000108: the World Medical Association and the World Bank.
p.000108:
p.000108: Ruth Macklin
p.000108: Ruth Macklin is Distinguished University Professor Emerita (Bioethics) in the Department of Epidemiology and Population
p.000108: Health at Albert Einstein College of Medicine in the Bronx, New York, USA. She has more than two hundred and
p.000108: seventy publications in professional journals and scholarly books in bioethics, law, medicine, philosophy, and
p.000108: the social sciences, in addition to articles in magazines and newspapers for general audiences. She is author or editor
p.000108: of thirteen books, including Mortal Choices (1988), Against Relativism (1999) and Double Standards in Medical Research
p.000108: in Developing Countries (2004). Dr Macklin is an elected member of the U.S. National Academy of Medicine and was
p.000108: president of the International Association of Bioethics from 1999–2001. She has served as consultant or
p.000108: adviser to the World Health Organization and UNAIDS, and chaired the external ethics committee of the Centers for
p.000108: Disease Control and Prevention from 2005 to 2008.
p.000108:
p.000108: Annette Rid
p.000108: Annette Rid is a Senior Lecturer in Bioethics and Society in the Department of Global Health & Social Medicine, King’s
...
p.000110: and lecturer for theory and history of medicine in 1993. Since 1998 Professor and Chair of Medical Ethics at the
p.000110: University of Tuebingen. Director of the Institute of History of Medicine at the University of Tuebingen. 2004-2013
p.000110: Chair of the Central Ethics-Committee of the Federal Board of Physicians.
p.000110:
p.000110: Hans-Joerg Ehni (Alternate), World Medical Association
p.000110: Hans-Joerg Ehni is the deputy director of the Institute for the Ethics and History of Medicine,
p.000110: University of Tuebingen, with a background in philosophy. His research is focused on the ethics of biomedical research
p.000110: involving human subjects and on the ethics of aging, particularly on the ethics of new biomedical interventions
p.000110: into the ageing process and increased longevity and on policies promoting healthy ageing. He is a member of
p.000110: the Research Ethics Committee of the Federal Board of Physicians, Baden-Württemberg.
p.000110:
p.000110: Carel IJsselmuiden, Council on Health Research for Development (COHRED)
p.000110: Carel is a physician, epidemiologist, public health practitioner, academic and social entrepreneur, with
p.000110: qualifications from universities in Belgium, Netherlands, South Africa and the United States. He spent 7
p.000110: years in rural medicine and public health, 4 years in peri-urban and urban health care, HIV/AIDS control and
p.000110: environmental services management as Deputy Medical Officer of Health for Johannesburg, South Africa. He
p.000110: was appointed as Professor and Head of Department of the department of community health at the University of
p.000110: Pretoria in 1995, where he became the founding Director of the School of Health Systems and Public Health in 1999. He
p.000110: held this position until his appointment as Executive Director at COHRED in 2004. As such, he is also member of the
p.000110: COHRED Board, President of COHRED USA and board member of COHRED Africa. He has published widely in applied research,
p.000110: nutrition, immunization, environmental health, research capacity building, global public health education and ethics of
p.000110: international collaborative health research. As part of community service, he was director of the Elim Care Group
p.000110: Project, a health and development NGO in the north of South Africa, served on the board of the Nokuthula
p.000110: Centre for Disabled Children in Alexandra township in South Africa and offers strategic research and innovation
p.000110: development support to low- and middle-income countries. Carel holds two nationalities – South African and Netherlands
p.000110: – and has worked and lived in Africa, Europe, the United States and the Caribbean.
p.000110:
p.000110: Observer
p.000110: Ingrid Callies
p.000110: Dr Ingrid Callies, PHD (University Paris Descartes), LLM (University of Virginia), a member of the New
...
Searching for indicator hiv/aids:
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Health / Healthy People
Searching for indicator volunteers:
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p.000089: continuing non-compliance with ethical standards in the conduct of previously approved research projects.
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000090: 90
p.000090:
p.000090:
p.000090:
p.000090:
p.000090:
p.000090: GUIDELINE 24:
p.000090: PUBLIC ACCOUNTABILITY FOR HEALTH-RELATED RESEARCH
p.000090:
p.000090: Public accountability is necessary for realizing the social and scientific value of health- related
p.000090: research. Therefore, researchers, sponsors, research ethics committees, funders, editors and publishers have an
p.000090: obligation to comply with recognized publication ethics for research and its results.
p.000090:
p.000090: Researchers should prospectively register their studies, publish the results and share the data on which these results
p.000090: are based in a timely manner. Negative and inconclusive as well as positive results of all studies should be published
p.000090: or otherwise be made publicly available. Any publication or report resulting from a research study should indicate
p.000090: which research ethics committee has authorized the study.
p.000090:
p.000090: Researchers and sponsors should also share information about and data from past research.
p.000090:
p.000090:
p.000090: Commentary on Guideline 24
p.000090: General considerations. In order to maximize benefits accruing from health research, reduce risks to future
p.000090: volunteers from undisclosed harms identified in previous clinical studies, reduce biases in evidence-based
p.000090: decision-making, improve efficiency of resource allocation for both research and development and financing of
p.000090: health interventions and promote societal trust in health-related research, researchers, sponsors, research ethics
p.000090: committees, funders, editors and publishers have an obligation to ensure public accountability. It is in the interest
p.000090: of all to improve the effectiveness of health care and public health to attain their fundamental goals: to prevent and
p.000090: cure disease, where possible, and alleviate pain and suffering (see Guideline 1 – Scientific and social value and
p.000090: respect for rights). Health-related research plays a vital role in this effort and therefore it is in the interest of
p.000090: society to promote such research for the benefit of all. At the same time, health-related research comes with risks
p.000090: and burdens for participants and with professional or financial benefits for the researchers and sponsors.
p.000090: Health-related research functions well only in the presence of professional and public trust. Trust can be enhanced by
p.000090: ensuring public accountability for research and its results. Therefore, researchers, sponsors, research ethics
p.000090: committees, editors and publishers all have ethical obligations to ensure the public accountability of research. This
p.000090: includes obligations to prospectively register studies (for example, in clinical trials registries), publish their
p.000090: results, and share the data on which these results are based. Moreover, given that many results from past
...
Health / Mentally Disabled
Searching for indicator disabled:
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p.000110:
p.000110: Carel IJsselmuiden, Council on Health Research for Development (COHRED)
p.000110: Carel is a physician, epidemiologist, public health practitioner, academic and social entrepreneur, with
p.000110: qualifications from universities in Belgium, Netherlands, South Africa and the United States. He spent 7
p.000110: years in rural medicine and public health, 4 years in peri-urban and urban health care, HIV/AIDS control and
p.000110: environmental services management as Deputy Medical Officer of Health for Johannesburg, South Africa. He
p.000110: was appointed as Professor and Head of Department of the department of community health at the University of
p.000110: Pretoria in 1995, where he became the founding Director of the School of Health Systems and Public Health in 1999. He
p.000110: held this position until his appointment as Executive Director at COHRED in 2004. As such, he is also member of the
p.000110: COHRED Board, President of COHRED USA and board member of COHRED Africa. He has published widely in applied research,
p.000110: nutrition, immunization, environmental health, research capacity building, global public health education and ethics of
p.000110: international collaborative health research. As part of community service, he was director of the Elim Care Group
p.000110: Project, a health and development NGO in the north of South Africa, served on the board of the Nokuthula
p.000110: Centre for Disabled Children in Alexandra township in South Africa and offers strategic research and innovation
p.000110: development support to low- and middle-income countries. Carel holds two nationalities – South African and Netherlands
p.000110: – and has worked and lived in Africa, Europe, the United States and the Caribbean.
p.000110:
p.000110: Observer
p.000110: Ingrid Callies
p.000110: Dr Ingrid Callies, PHD (University Paris Descartes), LLM (University of Virginia), a member of the New
p.000110: York Bar and a bioethicist, is Head of Ethics and Coordinator of the Code Authority and Ethics Committee (Codeem) for
p.000110: the pharmaceutical industry in France at Leem, the French federation of the pharmaceutical industry (www.leem.org).
p.000110: Previously, she was Ethics Advisor at the Institut Pasteur, worked for the French National Agency for Research on Aids
p.000110: and Viral Hepatitis, and practised law at Hogan & Hartson LLP, a law firm now called Hogan Lovells. Co-editor of the
p.000110: Ethics of Research Section in the Elsevier International Encyclopedia of the Social and Behavioural
p.000110: Sciences, Ingrid Callies has also participated in major research projects, including LeukoTreat (a
p.000110: collaborative European project on leukodystrophy) and Satori (Stakeholders Acting Together On the ethical impact
p.000110: assessment of Research and Innovation).
p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
p.000110: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000110:
...
Searching for indicator disability:
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p.000054: 54
p.000054:
p.000054:
p.000054:
p.000054:
p.000054:
p.000054: GUIDELINE 14:
p.000054: TREATMENT AND COMPENSATION FOR RESEARCH-RELATED HARMS
p.000054:
p.000054: Sponsors and researchers must ensure that research participants who suffer physical, psychological or social
p.000054: harm as a result of participating in health-related research receive free treatment and rehabilitation for such harms,
p.000054: as well as compensation for lost wages, as appropriate. Such treatment and compensation are owed to research
p.000054: participants who are harmed physically, psychologically or socially, as a consequence of interventions
p.000054: performed solely to accomplish the purposes of research, regardless of fault. In the case of death resulting from
p.000054: research participation, the participant’s dependents are entitled to compensation. Participants must not be asked to
p.000054: waive the right to free treatment and compensation for research-related harms.
p.000054:
p.000054: Research ethics committees must determine whether there is an adequate arrangement for treatment and compensation for
p.000054: research-related injuries.
p.000054:
p.000054:
p.000054: Commentary on Guideline 14
p.000054: General considerations. This Guideline focuses on the entitlement to free treatment and additional compensation when
p.000054: research participants are harmed by research interventions or procedures. In the commentary below, the thresholds for
p.000054: such entitlements are described. Dependents of participants are also entitled to material compensation for death
p.000054: or disability occurring as a direct result of study participation. Lack of a proper mechanism in place for
p.000054: compensation of research harms may serve as a disincentive for people to participate in research, and may negatively
p.000054: impact trust in the research enterprise. Therefore, it is not only just, but also pragmatic, to have appropriate
p.000054: provision for free treatment and compensation for research-related harms.
p.000054:
p.000054: Obligation of the sponsor with regard to free treatment and rehabilitation. Sponsors and researchers must
p.000054: ensure that research participants who suffer physical, psychological or social harm as a result of
p.000054: participating in health-related research receive free treatment and rehabilitation for such harms. This will usually
p.000054: mean that continuity of care for participants’ health needs related to research harms is guaranteed without any cost to
p.000054: the participant for as long as such care is needed (see Guideline 6 – Caring for participants’ health needs). The
p.000054: sponsor must provide this treatment or rehabilitation free of charge, since the harm resulted from the research.
p.000054:
p.000054: Obligation of the sponsor with regard to compensation. Before the research begins, the sponsor, whether a
p.000054: pharmaceutical company, other organization or institution, or a government (where government insurance is not
p.000054: precluded by law), must agree to provide compensation for any harm for which participants are entitled to
p.000054: compensation based on this Guideline. Alternatively, the sponsor may come to an agreement with the researcher
...
p.000099: 6);
p.000099:
p.000099: 20. Clinical and laboratory tests and other tests that are to be carried out;
p.000099:
p.000099: 21. Samples of the standardized case-report forms to be used, the methods of recording therapeutic response
p.000099: (description and evaluation of methods and frequency of measurement), the follow-up procedures, and, if applicable, the
p.000099: measures proposed to determine the extent of compliance of persons with the treatment;
p.000099:
p.000099: 22. Rules or criteria according to which participants may be removed from the study or clinical trial, or (in a
p.000099: multi-centre study) a centre may be discontinued, or the study may be terminated;
p.000099:
p.000099: 23. Methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000099: complications (Guidelines 4 and 23);
p.000099:
p.000099: 24. The known or foreseen risks of adverse reactions, including the risks attached to each proposed intervention and
p.000099: to any drug, vaccine or procedure to be tested (Guideline 4);
p.000099:
p.000099: 25. The potential individual benefits of the research to participants and to others (Guideline 4);
p.000099:
p.000099: 26. The expected benefits of the research to the population, including new knowledge that the study might
p.000099: generate (Guidelines 1 and 4);
p.000099:
p.000099: 27. For research carrying more than minimal risk of physical injury, details of plans, including
p.000099: insurance coverage, to provide treatment for such injury, including the funding of treatment, and to provide
p.000099: compensation for research-related disability or death (Guideline 14);
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
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p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 28. Provision for continued access to study interventions that have demonstrated significant benefit, indicating its
p.000100: modalities, the parties involved in continued care and the organization responsible for paying for it, and for how long
p.000100: it will continue (Guideline 6);
p.000100:
p.000100: 29. For research on pregnant women, a plan, if appropriate, for monitoring the outcome of the pregnancy
p.000100: with regard to both the health of the woman and the short-term and long-term health of the child (Guideline 19);
p.000100:
p.000100: 30. The means proposed to obtain individual informed consent and the procedure planned to communicate
p.000100: information to prospective participants, including the name and position of the person responsible for obtaining
p.000100: consent (Guideline 9);
p.000100:
p.000100: 31. When a prospective subject is not capable of informed consent, satisfactory assurance that permission will be
p.000100: obtained from a duly authorized person, or, in the case of a child who is sufficiently mature to
...
p.000103: (Guideline 9);
p.000103:
p.000103: 17. the provisions that will be made to ensure respect for the privacy of participants, and for the confidentiality of
p.000103: records in which participants are identified (Guidelines 11 and 22);
p.000103:
p.000103: 18. the limits, legal or other, to the researchers’ ability to safeguard confidentiality, and the possible
p.000103: consequences of breaches of confidentiality (Guidelines 12 and 22);
p.000103:
p.000103: 19. the sponsors of the research, the institutional affiliation of the researchers, and the nature and sources of
p.000103: funding for the research, and, when they exist, any conflicts of interest of researchers, research institutions and
p.000103: research ethics committees and how these conflicts will be managed (Guidelines 9 and 25);
p.000103:
p.000103: 20. whether the researcher is serving only as a researcher or as both researcher and the participant`s physician
p.000103: (Guideline 9);
p.000103:
p.000103: 21. the extent of the researcher’s responsibility to provide care for participants’ health needs during and after the
p.000103: research (Guideline 6);
p.000103:
p.000103: 22. that treatment and rehabilitation will be provided free of charge for specified types of research- related injury
p.000103: or for complications associated with the research, the nature and duration of such care, the name of
p.000103: the medical service or organization that will provide the treatment, and whether there is any uncertainty
p.000103: regarding funding of such treatment (Guideline 14);
p.000103:
p.000103: 23. in what way, and by what organization, the participant or the participant’s family or dependants will be
p.000103: compensated for disability or death resulting from such injury (or, when indicated, that there are no plans
p.000103: to provide such compensation) (Guideline 14);
p.000103:
p.000103: 24. whether or not, in the country in which the prospective participant is invited to participate in research, the
p.000103: right to compensation is legally guaranteed;
p.000103:
p.000103:
p.000103:
p.000104: 104
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: 25. that a research ethics committee has approved or cleared the research protocol (Guideline 23);
p.000104:
p.000104: 26. that they will be informed in case of protocol violations and how safety and welfare will be
p.000104: protected in such a case (Guideline 23).
p.000104:
p.000104: In specific cases, before requesting an individual’s consent to participate in research, the researcher must provide
p.000104: the following information, in language or another form of communication that the individual can understand:
p.000104: 1. for controlled trials, an explanation of features of the research design (e.g., randomization,
p.000104: double-blinding), that the participant will not be told of the assigned treatment until the study has been completed
p.000104: and the blind has been broken;
p.000104:
p.000104: 2. whether all essential information is disclosed and, if not, that they are asked to agree to receiving incomplete
...
Health / Mentally Incapacitated
Searching for indicator incapable:
(return to top)
p.000007: 7
p.000007: GUIDELINE 4: POTENTIAL INDIVIDUAL BENEFITS AND RISKS OF RESEARCH 9
p.000007: GUIDELINE 5: CHOICE OF CONTROL IN CLINICAL TRIALS 15
p.000007: GUIDELINE 6: CARING FOR PARTICIPANTS’ HEALTH NEEDS 21
p.000007: GUIDELINE 7: COMMUNITY ENGAGEMENT 25
p.000007: GUIDELINE 8: COLLABORATIVE PARTNERSHIP AND CAPACITY-BUILDING
p.000007: FOR RESEARCH AND RESEARCH REVIEW 29
p.000007: GUIDELINE 9: INDIVIDUALS CAPABLE OF GIVING INFORMED CONSENT 33
p.000007: GUIDELINE 10: MODIFICATIONS AND WAIVERS OF INFORMED CONSENT 37
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: v
p.000007:
p.000007: GUIDELINE 11: COLLECTION, STORAGE AND USE OF BIOLOGICAL
p.000007: MATERIALS AND RELATED DATA 41
p.000007: GUIDELINE 12: COLLECTION, STORAGE AND USE OF DATA IN HEALTH- RELATED RESEARCH
p.000047: 47
p.000047: GUIDELINE 13: REIMBURSEMENT AND COMPENSATION FOR
p.000047: RESEARCH PARTICIPANTS 53
p.000047: GUIDELINE 14: TREATMENT AND COMPENSATION FOR RESEARCH-
p.000047: RELATED HARMS
p.000055: 55
p.000055: GUIDELINE 15: RESEARCH INVOLVING VULNERABLE PERSONS
p.000055: AND GROUPS
p.000057: 57
p.000057: GUIDELINE 16: RESEARCH INVOLVING ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000061: 61
p.000061: GUIDELINE 17: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS 65
p.000061: GUIDELINE 18: WOMEN AS RESEARCH PARTICIPANTS 69
p.000061: GUIDELINE 19: PREGNANT AND BREASTFEEDING WOMEN AS
p.000061: RESEARCH PARTICIPANTS 71
p.000061: GUIDELINE 20: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS 75
p.000061: GUIDELINE 21: CLUSTER RANDOMIZED TRIALS 79
p.000061: GUIDELINE 22: USE OF DATA OBTAINED FROM THE ONLINE
p.000061: ENVIRONMENT AND DIGITAL TOOLS IN HEALTH-RELATED RESEARCH 83
p.000061: GUIDELINE 23: REQUIREMENTS FOR ESTABLISHING RESEARCH ETHICS COMMITTEES AND FOR THEIR REVIEW OF PROTOCOLS
p.000087: 87
p.000087: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000087: vi
p.000087:
p.000087: GUIDELINE 24: PUBLIC ACCOUNTABILITY FOR HEALTH-RELATED RESEARCH 91
p.000087: GUIDELINE 25: CONFLICTS OF INTEREST 95
p.000087: APPENDIX 1 ITEMS TO BE INCLUDED IN A PROTOCOL (OR ASSOCIATED DOCUMENTS) FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099: APPENDIX 2 OBTAINING INFORMED CONSENT: ESSENTIAL
p.000099: INFORMATION FOR PROSPECTIVE RESEARCH PARTICIPANTS 103
...
p.000008: they are minimized and outweighed by the prospect of potential individual benefit and the available evidence suggests
p.000008: that the intervention will be at least as advantageous, in the light of foreseeable risks and benefits, as any
p.000008: established effective alternative. Therefore, as a general rule, participants in the control group of a trial must
p.000008: receive an established effective intervention. The conditions under which a placebo may be used are spelled out in
p.000008: Guideline 5 – Choice of control in clinical trials.
p.000008: f For research interventions or procedures that offer no potential individual benefits to participants, the risks
p.000008: must be minimized and appropriate in relation to the social and scientific value of the knowledge to be gained
p.000008: (expected benefits to society from the generalizable knowledge).
p.000008: f In general, when it is not possible or feasible to obtain the informed consent of participants,
p.000008: research interventions or procedures that offer no potential individual benefits must pose no more than minimal
p.000008: risks. However, a research ethics committee may permit a minor increase above minimal risk when it is not possible to
p.000008: gather the necessary data in another population or in a less risky or burdensome manner, and the social and scientific
p.000008: value of the research is compelling (see Guideline 16 – Research involving adults incapable of giving informed
p.000008: consent, and Guideline 17 – Research involving children and adolescents).
p.000008:
p.000008: In a second step, the aggregate risks and potential individual benefits of the entire study must be assessed and must
p.000008: be considered appropriate.
p.000008: f The aggregate risks of all research interventions or procedures in a study must be considered
p.000008: appropriate in light of the potential individual benefits to participants and the scientific social value of the
p.000008: research.
p.000008: f The researcher, sponsor and research ethics committee must also consider risks to groups and
p.000008: populations, including strategies to minimize these risks.
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: f The potential individual benefits and risks of research studies must be evaluated in consultation with
p.000009: the communities to be involved in the research (see Guideline 7 – Community engagement).
p.000009:
p.000009:
p.000009: Commentary on Guideline 4
p.000009: General considerations. Participants in health research are often exposed to a variety of interventions or procedures,
p.000009: many of which pose some risk. In this Guideline, the term “intervention” refers to the objects of study, such as new or
p.000009: established therapies, diagnostic tests, preventive measures and various techniques (for example, financial
...
p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Informed consent is based on the principle that individuals capable of giving informed consent have a right to choose
p.000033: freely whether to participate in research. Informed consent protects the individual’s freedom of choice and respects
p.000033: the individual’s autonomy.
p.000033:
p.000033: The information must be provided in plain language understandable by the potential participant. The person
p.000033: obtaining informed consent must be knowledgeable about the research and capable of answering any questions from
p.000033: potential participants. Researchers in charge of the study must make themselves available to answer questions at the
p.000033: request of participants. Participants should be offered the opportunity to ask questions and receive answers before or
p.000033: during the research. Researchers should make every effort to address those questions in a timely and comprehensive
p.000033: manner.
p.000033:
p.000033: This Guideline applies to individuals capable of giving informed consent. Requirements for research with individuals
p.000033: who are not capable of giving informed consent or with children and adolescents are set out in Guideline 16 –
p.000033: Research involving adults incapable of giving informed consent, and Guideline 17 – Research involving children
p.000033: and adolescents.
p.000033:
p.000033: Process. Informed consent is a two-way communicative process that begins when initial contact is made with a potential
p.000033: participant and ends when consent is provided and documented, but can be revisited later during the conduct of the
p.000033: study. Each individual must be given as much time as needed to reach a decision, including time for consultation with
p.000033: family members or others. Adequate time and resources must be provided for informed-consent procedures.
p.000033:
p.000033: Language of the information leaflet and recruitment material. All potential participants should be provided with a
p.000033: written information leaflet that they may take with them. Informing the individual participant must not be simply a
p.000033: ritual recitation of the contents of a written document. The wording of the leaflet and any recruitment material
p.000033: must be in language understandable by the potential participant and be approved by the research ethics
p.000033: committee. The wording of the leaflet must be short and preferably not exceed two or three pages. An oral presentation
p.000033: of information or the use of appropriate audiovisual aids, including pictographs and summary tables, are important to
...
p.000033: Comprehension. The person obtaining consent must ensure that the potential participant has adequately
p.000033: understood the information provided. Researchers should use evidence-based methods for imparting information to ensure
p.000033: comprehension. The potential participant’s ability to understand the information depends, among other things, on the
p.000033: individual’s maturity, educational level and belief system. The participant’s understanding also depends on the
p.000033: researcher’s ability and willingness to communicate with patience and sensitivity, as well as the atmosphere, situation
p.000033: and location where the informed consent process takes place.
p.000033:
p.000033: Documentation of consent. Consent may be indicated in a number of ways. The participant may express consent orally, or
p.000033: sign a consent form. As a general rule, the participant should sign a consent form, or, where the individual lacks
p.000033: decisional capacity, a legal guardian or other duly authorized
p.000033:
p.000033:
p.000033: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000034: 34
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: representative must do so (see Guideline 16 – Research involving individuals incapable of giving informed
p.000034: consent, and Guideline 17 – Research involving children and adolescents). The research ethics committee may approve a
p.000034: waiver of the requirement of a signed consent document under certain conditions (see Guideline 10 – Modifications and
p.000034: waivers of informed consent). Such waivers may also be approved when existence of a signed consent form might pose a
p.000034: risk to the participant, for example in studies involving illegal behaviour. In some cases, especially when the
p.000034: information is complicated, participants should be given information sheets to retain; these may resemble
p.000034: conventional sheets in all respects except that participants are not required to sign them. Their wording
p.000034: must be approved by the research ethics committee. When consent has been obtained orally, researchers
p.000034: should provide to the research ethics committee documentation of consent, certified either by the person
p.000034: obtaining consent or by a witness at the time consent is obtained.
p.000034:
...
p.000037: Debriefing is an essential part of trying to rectify the wrong of deception. Participants who disapprove of having been
p.000037: deceived for research purposes must be offered an opportunity to refuse to allow the researcher to use their data
p.000037: obtained through deception. In exceptional cases, a research ethics committee may approve the retention of
p.000037: non-identifiable information. For example, an option to withdraw data may not be offered in cases where research is
p.000037: evaluating quality of services or competence of providers (for example, studies involving “mystery” clients or
p.000037: patients).
p.000037:
p.000037: Waiving informed consent. A research ethics committee may waive informed consent if it is convinced that
p.000037: the research would not be feasible or practicable to carry out without the waiver, the research has
p.000037: important social value, and the research poses no more than minimal risks to participants. These three
p.000037: conditions must also be met even when a study involves identifiable data or biological specimens, meaning that the data
p.000037: or specimens carry a person’s name or are linked to a person by a code. The conditions must also be met when studies
p.000037: analyse existing data from health-related registries, and when the participants are children, adolescents, and
p.000037: individuals not capable of giving informed consent (Guideline 16 – Research involving adults incapable of
p.000037: giving informed consent, and Guideline 17 – Research involving children and adolescents).
p.000037:
p.000037: In addition, the three conditions for waiving informed consent must be met when data or biological specimens are not
p.000037: personally identifiable and the research has important social value. In this situation, the participants are unknown to
p.000037: the researcher and hence cannot be contacted to obtain informed
p.000037:
p.000037: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000038: 38
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038: consent. Moreover, because the data or specimens are not personally identifiable, the risks to those individuals are no
p.000038: greater than minimal.
p.000038:
p.000038: Special considerations for waiving informed consent in studies using data in health- registries. The
p.000038: creation and maintenance of health-related registries (for example, cancer registries and databanks of genetic and
p.000038: other anomalies in newborn babies) provide a major resource for many public health and epidemiological research
p.000038: activities, ranging from disease prevention to resource allocation. Several considerations support the common practice
p.000038: of requiring that all practitioners submit relevant data to such registries: the importance of having
p.000038: comprehensive and accurate information about an entire population; the scientific need to include all
p.000038: cases in order to avoid undetectable selection bias; and the ethical principle that burdens and benefits must be
...
p.000042: biological samples should contradict or overrule conditions originally stated in (broad) informed consent documents and
p.000042: agreed to by research participants.
p.000042:
p.000042: Research ethics committees and biobanks. The protocol for every study using stored human biological materials and
p.000042: related data must be submitted to a research ethics committee, which must ensure that the proposed use of the materials
p.000042: falls within the scope specifically agreed to by the donor, if the donor has given broad informed consent for future
p.000042: research. If the proposed use falls outside the authorized scope of research, re-consent is necessary. Research ethics
p.000042: committees may waive the requirement of individual informed consent for research with historical materials provided the
p.000042: above three conditions mentioned in the bold text of this Guideline are met (see Guideline 10 – Modifications and
p.000042: waivers of informed consent).
p.000042:
p.000042: Specific informed consent. When the future use of the materials is known at the time of collection, specific informed
p.000042: consent must be obtained as described in Guideline 9, Individuals capable of giving informed consent. Persons who were
p.000042: incapable of giving informed consent at the time their bodily material was stored must be given the opportunity to give
p.000042: informed consent or refusal if researchers know, or reasonably should have known that the subject has become capable of
p.000042: giving informed consent (see also Guideline 16 – Research involving adults incapable of giving informed consent).
p.000042:
p.000042: Broad informed consent. Broad informed consent encompasses the range of future uses in research for which
p.000042: consent is given. Broad informed consent is not blanket consent that would allow future use of bodily
p.000042: material without any restriction. On the contrary, broad informed consent places certain limitations on the future
p.000042: use of bodily materials. Broad informed consent forms should specify: the purpose of the biobank; the
p.000042: conditions and duration of storage; the rules of access to the biobank; the ways in which the donor can contact
p.000042: the biobank custodian and remain informed about future use; the foreseeable uses of the materials, whether limited to
p.000042: an already fully defined study or extending to a number of wholly or partially undefined studies; the intended goal of
p.000042: such use, whether only for basic or applied research , or also for commercial purposes; and the possibility of
p.000042: unsolicited findings and how they will be dealt with. The research ethics committee must ensure that the
p.000042: proposed collections, the storage protocol, and the consent procedure meet these specifications.
p.000042:
...
p.000048: must be submitted to a research ethics committee, which must ensure that the proposed use of the data falls within the
p.000048: scope specifically agreed to by the donor, if the donor has given broad informed consent for future research. If the
p.000048: proposed use falls outside the authorized scope of research, re-consent is necessary. Research ethics committees may
p.000048: waive the requirement of individual informed consent for research with historical data provided the above three
p.000048: conditions mentioned in the bold text of this Guideline are met (see Guideline 10 – Modifications and waivers of
p.000048: informed consent). For population-based registries, internal institutional research activity of the registry may be
p.000048: exempted from review by a research ethics committee according to applicable law.
p.000048:
p.000048: Specific informed consent. When the future use in research of the collected data is known at the time
p.000048: of collection, specific informed consent must be obtained as described in Guideline 9 – Individuals
p.000048: capable of giving informed consent. Persons who were incapable of giving informed consent at the time their
p.000048: data were stored must be given the opportunity to give informed consent or refusal if researchers know, or
p.000048: reasonably should have known, that the subject has become capable of giving informed consent (see also
p.000048: Guideline 16 – Research involving adults incapable of giving informed consent).
p.000048:
p.000048: Broad informed consent. Broad informed consent encompasses the range of future uses in research for which
p.000048: consent is given (see Guideline 11 – Collection, storage and use of biological materials and related data). Broad
p.000048: informed consent should specify: the purpose of the databank; the conditions and duration of storage; the rules of
p.000048: access to the databank, the ways in which the donor can contact the databank custodian and remain informed about future
p.000048: use; the foreseeable uses of the data, whether limited to an already fully defined study or extending to a number of
p.000048: wholly or partially undefined studies; who will manage access to the data; the foreseeable uses of the
p.000048: data, whether limited to an already fully defined study or extending to a number of wholly or partially undefined
p.000048: studies; the intended goal of such use, whether only for basic or applied research, or also for commercial purposes;
p.000048: and the possibility of unsolicited findings and how they will be dealt with. The research ethics committee must ensure
p.000048: that the proposed collections, the storage protocol, and the consent procedure meet these specifications.
p.000048:
...
p.000053: risks of research procedures having no potential individual benefit for participants increase, so does the
p.000053: concern that compensation may constitute an undue inducement. Monetary or in-kind compensation for research
p.000053: participants must not be so large as to persuade them to volunteer against their better judgment or deeply
p.000053: held beliefs (“undue inducement”).
p.000053:
p.000053: It can be difficult to determine whether undue inducement exists, in part because the compensation that makes some
p.000053: people volunteer against their better judgment depends on their personal situation. An unemployed person or a student
p.000053: may view compensation differently from an employed person. Research ethics committees must evaluate monetary and other
p.000053: forms of compensation in light of the traditions and socio-economic context of the particular culture and population in
p.000053: order to determine whether the average participant expected to enrol in the study is likely to participate in the
p.000053: research against his or her better judgment because of the compensation offered. The appropriateness of compensation
p.000053: is likely better judged by local research ethics committees than by international ones. Consultation with
p.000053: the local community may help to ascertain this even in the case of research conducted in the researcher’s own
p.000053: community.
p.000053:
p.000053: Compensation for persons who are incapable of giving informed consent. Persons who are incapable of giving informed
p.000053: consent may be vulnerable to exploitation for financial gain by their guardians. A legally authorized
p.000053: representative asked to give permission on behalf of a person who is incapable of giving informed consent must be
p.000053: offered no compensation other than reimbursement for travel and other direct or indirect expenses. Where it would be
p.000053: reasonable to provide compensation to the participants themselves, their lack of decisional capacity must not
p.000053: preclude researchers from doing so. When participants are incapable of giving informed consent, compensation must be
p.000053: provided in a way that participants themselves can benefit from it.
p.000053:
p.000053: Compensation after study withdrawal. When a researcher withdraws a participant from a study on
p.000053: health-related grounds, the person must be compensated for study participation up to the point of such
p.000053: withdrawal. When a person is withdrawn from a study due to a research-related harm, this harm must be treated and the
p.000053: participant is entitled to additional compensation as set out in Guideline 14 – Treatment and compensation for
p.000053: research-related harms. When researchers must withdraw a participant from the study for wilful noncompliance, they are
p.000053: entitled to withhold part or all of the payment. Participants who do not continue study participation for other reasons
p.000053: must be compensated in proportion to the amount of participation they completed. Researchers must not
p.000053: withhold all or most of the money until the end of studies involving more than one session or intervention in order
p.000053: to induce unwilling participants to remain in the study. The conditions for compensation must be approved by
p.000053: the research ethics committee and disclosed in the informed consent process.
p.000053:
p.000053: Studies of financial incentives. In some studies, monetary or material incentives to participants are themselves a core
p.000053: object of study rather than a form of compensation. For example, incentives in the form of cash transfers or
...
p.000056: RESEARCH INVOLVING VULNERABLE PERSONS AND GROUPS
p.000056:
p.000056: When vulnerable individuals and groups are considered for recruitment in research, researchers and research
p.000056: ethics committees must ensure that specific protections are in place to safeguard the rights and welfare of these
p.000056: individuals and groups in the conduct of the research.
p.000056:
p.000056:
p.000056: Commentary on Guideline 15
p.000056: General considerations. According to the Declaration of Helsinki, vulnerable groups and individuals “may have an
p.000056: increased likelihood of being wronged or of incurring additional harm.” This implies that vulnerability involves
p.000056: judgments about both the probability and degree of physical, psychological, or social harm, as well as a greater
p.000056: susceptibility to deception or having confidentiality breached. It is important to recognize that vulnerability
p.000056: involves not only the ability to provide initial consent to participate in research, but also aspects of the ongoing
p.000056: participation in research studies. In some cases, persons are vulnerable because they are relatively (or
p.000056: absolutely) incapable of protecting their own interests. This may occur when persons have relative or absolute
p.000056: impairments in decisional capacity, education, resources, strength, or other attributes needed to protect their own
p.000056: interests. In other cases, persons can also be vulnerable because some feature of the circumstances (temporary or
p.000056: permanent) in which they live makes it less likely that others will be vigilant about, or sensitive to, their
p.000056: interests. This may happen when people are marginalized, stigmatized, or face social exclusion or prejudice
p.000056: that increases the likelihood that others place their interests at risk, whether intentionally or unintentionally.
p.000056: Although research ethics committees can require special protections only for potential participants collectively for a
p.000056: particular project, researchers and others involved in research must take into account factors that render individual
p.000056: participants vulnerable and take appropriate steps to mitigate those factors.
p.000056:
p.000056: A traditional approach to vulnerability in research has been to label entire classes of individuals as vulnerable. The
...
p.000056: likelihood of being wronged or of incurring additional harm as participants in research. Different characteristics
p.000056: may also co-exist, making some individuals more vulnerable than others. This is highly dependent on the context.
p.000056: For example, persons who are illiterate, marginalized by virtue of their social status or behaviour, or living in an
p.000056: authoritarian environment, may have multiple factors that make them vulnerable.
p.000056:
p.000056: Some characteristics can make it reasonable to assume that certain individuals are vulnerable, for example:
p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
p.000056:
p.000056: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
p.000057: Examples are medical and nursing students, subordinate hospital and laboratory personnel, workers in settings
p.000057: where research studies are conducted, and members of the armed forces or police. Their agreement to volunteer may be
p.000057: unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate
p.000057: in the study or by fear of disapproval or retaliation if they refuse (see also commentary on Guideline 9 – Individuals
p.000057: capable of giving informed consent). The research protocol must include a description of provisions to protect such
p.000057: individuals from being conscripted into research.
p.000057:
p.000057: Institutionalized persons. Residents of nursing homes, mental institutions, and prisons are often considered vulnerable
...
p.000058: circumstances exist that require research ethics committees to pay special attention to research involving
p.000058: certain groups. In some resource-limited countries or communities, lack of access to medical care,
p.000058: membership in ethnic and racial minorities, or other disadvantaged or marginalized groups can be factors
p.000058: that constitute vulnerability. As is true of the vulnerability of individuals, the judgment that groups
p.000058: are vulnerable is context dependent and requires empirical evidence to document the need for special
p.000058: protections.
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
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p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059: GUIDELINE 16:
p.000059: RESEARCH INVOLVING
p.000059: ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000059:
p.000059: Adults who are not capable of giving informed consent must be included in health-related research unless a good
p.000059: scientific reason justifies their exclusion. As adults who are not capable of giving informed consent
p.000059: have distinctive physiologies and health needs, they merit special consideration by researchers and research
p.000059: ethics committees. At the same time, they may not be able to protect their own interests due to their lack of capacity
p.000059: to provide informed consent. Specific protections to safeguard the rights and welfare of these persons in research are
p.000059: therefore necessary.
p.000059:
p.000059: Before undertaking research with adults who are not capable of giving informed consent, the researcher and the research
p.000059: ethics committee must ensure that:
p.000059: f a legally authorized representative of the person who is incapable of giving informed consent has given
p.000059: permission and this permission takes account of the participant’s previously formed preferences and values (if
p.000059: any); and
p.000059: f the assent of the subject has been obtained to the extent of that person’s capacity, after having
p.000059: been provided with adequate information about the research at the level of the subject’s capacity for understanding
p.000059: this information.
p.000059:
p.000059: If participants become capable of giving informed consent during the research, their consent to continued
p.000059: participation must be obtained.
p.000059:
p.000059: In general, a potential participant’s refusal to enrol in the research must be respected, unless, in
p.000059: exceptional circumstances, research participation is considered the best available medical option for an
p.000059: individual who is incapable of giving informed consent.
p.000059:
p.000059: If participants have made advance directives for participation in research while fully capable of giving
p.000059: informed consent, the directives should be respected.
p.000059:
p.000059: For research interventions or procedures that have the potential to benefit adults who are incapable of
p.000059: giving informed consent, the risks must be minimized and outweighed by the prospect of potential individual
p.000059: benefit. For research interventions or procedures that have no potential individual benefits for participants, two
p.000059: conditions apply:
p.000059: f the interventions and procedures should be studied first in persons who can give consent when these interventions
p.000059: and procedures target conditions that affect persons who are not capable of giving informed consent as well as those
p.000059: who are capable, unless the necessary data cannot be obtained without participation of persons who are incapable of
p.000059: giving informed consent; and
p.000059:
p.000059:
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p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061: f the risks must be minimized and no more than minimal.
p.000061:
p.000061: When the social value of the studies with such research interventions and procedures is compelling, and these
p.000061: studies cannot be conducted in persons who can give informed consent, a research ethics committee may permit a
p.000061: minor increase above minimal risk.
p.000061:
p.000061:
p.000061: Commentary on Guideline 16
p.000061: General considerations. In general, competence or decisional capacity is determined by the ability to
p.000061: understand material information, appreciate the situation and its consequences, consider the treatment options, and
p.000061: communicate a choice. Persons should be considered capable of giving informed consent unless it is proven otherwise. A
p.000061: person may be incapable to give informed consent for a variety of reasons (for example, dementia, some psychiatric
p.000061: conditions and accidents). Persons can become capable of giving informed consent after a certain period, or they can be
p.000061: incapable to decide whether they should be treated for a certain disease but capable to decide whether they want to
p.000061: enjoy a meal. This illustrates that a lack of decisional capacity is time-, task- and context-specific.
p.000061:
p.000061: When researchers have reason to believe that potential or current participants are incapacitated, the participant’s
p.000061: decisional capacity must be adequately assessed. In cases where incapacity to give informed consent might reasonably be
p.000061: expected, participants must be routinely screened. However, it is important to note that diagnosis of a mental or
p.000061: behavioural disorder does not necessarily imply that individuals are incapable of giving informed consent.
p.000061:
p.000061: Potential individual benefits and risks. The potential individual benefits and risks of research with adults incapable
p.000061: of giving informed consent should be evaluated based on Guideline 4 – Potential individual benefits and risks of
p.000061: research, and Guideline 5 – Choice of control in clinical trials.
p.000061:
p.000061: Assent and dissent. If participants cannot consent because they are incapacitated due to mental or behavioural
p.000061: disorders, they must be engaged in the research discussion at the level of their capacity to understand, and they must
p.000061: be given a fair opportunity to agree to or to decline participation in the study. This can also be called
p.000061: obtaining the participant’s assent or dissent. Assent must be considered as a process (see Guideline 9 –
p.000061: Individuals capable of giving informed consent) that responds to changes in the person’s cognitive status and is
p.000061: not merely the absence of dissent.
p.000061:
p.000061: Any explicit objection by persons who are incapable to give informed consent must be respected even if the legally
p.000061: authorized representative has given permission. An explicit objection may be overruled if the incapacitated person
p.000061: needs treatment that is not available outside the context of research, prior research has demonstrated a significant
p.000061: benefit (see Guideline 4 – Potential individual benefits and risks of research), and the treating physician and the
p.000061: legally authorized representative consider the research intervention to be the best available medical option for the
p.000061: person lacking capacity.
p.000061:
p.000061: Permission of a legally authorized representative. In accordance with relevant national regulations, the
p.000061: permission of an immediate family member or other person with a close personal relationship with the individual must
p.000061: be sought. Surrogate decision-makers must evaluate to what extent study participation is consistent with the
p.000061: individual’s previously formed preferences and values (if any), and, in the case of research that offers participants a
p.000061: prospect of clinical benefit, to what extent study participation promotes the individual’s clinical interests.
p.000061: Previously stated preferences regarding the individual’s willingness to enrol in research or documented preferences in
p.000061: an advance directive should be respected. Researchers must recognize that surrogates may have their own
p.000061: interests that may call their permission into question. Furthermore, in situations where a legally
p.000061: authorized representative is not available to allow for timely enrolment, researchers may obtain the permission of a
p.000061: representative who is socially accepted but not formally recognized before the law.
p.000061:
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p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062: Emergency care situations in which the researcher anticipates that many participants will be unable to
p.000062: consent. Research protocols are sometimes designed to address conditions occurring suddenly and rendering the
p.000062: patients or participants incapable of giving informed consent. Examples are sepsis, head trauma, cardiopulmonary arrest
p.000062: and stroke. In such circumstances, it is often necessary to proceed with the research interventions very soon after the
p.000062: onset of the condition in order to evaluate an investigational treatment or develop the desired knowledge.
p.000062:
p.000062: If possible, an attempt must be made to identify a population that is likely to develop the condition to be studied.
p.000062: This can be done readily, for example, if the condition is one that recurs periodically in individuals, such as grand
p.000062: mal seizures and alcohol binges. In such cases, researchers should ideally contact potential participants while fully
p.000062: capable of informed consent, and obtain their agreement to be involved in the research during future periods of
p.000062: incapacitation, for example in an advance directive.
p.000062:
p.000062: If there is no opportunity to solicit informed consent of participants while fully capable of informed consent, plans
p.000062: to conduct emergency care research with incapacitated persons must be publicized within the community in which it will
p.000062: be carried out, where feasible. In the design and conduct of the research, the research ethics committee, the
p.000062: researchers and the sponsors must be responsive to the concerns of the community. The research must not be carried out
...
p.000067:
p.000067: A research ethics committee may also allow a waiver of parental permission if the conditions set out in Guideline 10 –
p.000067: Modifications and waivers of informed consent - are satisfied.
p.000067:
p.000067: Observation of the study by a parent or guardian. A parent or legally appointed guardian who gives permission for a
p.000067: child or adolescent to participate in research must generally be given the opportunity, to a reasonable
p.000067: extent and without violating the privacy of other study participants, to observe the child’s participation as
p.000067: the study proceeds. This could enable the child to be withdrawn if the parent or guardian decides it is in the child’s
p.000067: best interests to do so.
p.000067:
p.000067: Emergency care situations in which the researcher anticipates that children and adolescents will participate. When
p.000067: children and adolescents participate in emergency care research, the principles of Guideline 16 – Research involving
p.000067: adults incapable of giving informed consent - apply.
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
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p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: GUIDELINE 18:
p.000068: WOMEN AS RESEARCH PARTICIPANTS
p.000068:
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
p.000068: physiologies and health needs, they merit special consideration by researchers and research ethics committees. Only the
p.000068: informed consent of the woman herself should be required for her research participation. Since some societies lack
p.000068: respect for women’s autonomy, in no case must the permission of another person replace the requirement of individual
p.000068: informed consent by the woman.
p.000068:
...
p.000077: disaster situations should ideally be planned in advance. This can involve, among other things, submitting partial
p.000077: study protocols for ethical “pre-screening” and drafting arrangements for data and sample sharing among collaborators.
p.000077: Health officials might also create an international network of specialists that could assist local review during a
p.000077: disaster. However, reviewing generic research protocols in advance cannot substitute for the ethical review of specific
p.000077: research protocols in a disaster. Local ethics review should be carried out whenever possible.
p.000077:
p.000077: Informed consent. Even though most disaster victims are under duress, it is important to obtain their informed consent
p.000077: for study participation and especially to emphasize the difference between research and humanitarian aid. To
p.000077: explain the difference is especially important in the context of clinical trials that test experimental
p.000077: interventions in the early phases of development. The fact that potential participants are under duress does not
p.000077: prevent them from making a voluntary decision (Guideline 9 – Individuals capable of giving informed consent). The
p.000077: informed consent process must be designed in a way that is comprehensible and sensitive to persons who are under
p.000077: duress.
p.000077:
p.000077: Special protections for individuals incapable of giving informed consent may apply, as described in
p.000077: Guideline 16 – Research involving adults incapable of giving informed consent, in the section on Emergency care
p.000077: situations in which the researcher anticipates that many participants will be unable to consent.
p.000077:
p.000077: Individual informed consent may be waived for the sharing and analysis of surveillance data provided that the
p.000077: conditions of Guideline 10 – Modifications and waivers of informed consent - are met and appropriate governance systems
p.000077: for these data are put in place.
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
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p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078: GUIDELINE 21:
p.000078: CLUSTER RANDOMIZED TRIALS
p.000078:
p.000078: In advance of initiating a cluster randomized trial, researchers, sponsors, relevant authorities, and
p.000078: research ethics committees should:
p.000078: f determine who are the research participants and what other individuals or groups are affected, even though they are
p.000078: not directly targeted;
p.000078: f determine whether it is required or feasible to obtain informed consent from patients, health care workers, or
p.000078: community members in certain studies;
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p.000033: obtaining informed consent must be knowledgeable about the research and capable of answering any questions from
p.000033: potential participants. Researchers in charge of the study must make themselves available to answer questions at the
p.000033: request of participants. Participants should be offered the opportunity to ask questions and receive answers before or
p.000033: during the research. Researchers should make every effort to address those questions in a timely and comprehensive
p.000033: manner.
p.000033:
p.000033: This Guideline applies to individuals capable of giving informed consent. Requirements for research with individuals
p.000033: who are not capable of giving informed consent or with children and adolescents are set out in Guideline 16 –
p.000033: Research involving adults incapable of giving informed consent, and Guideline 17 – Research involving children
p.000033: and adolescents.
p.000033:
p.000033: Process. Informed consent is a two-way communicative process that begins when initial contact is made with a potential
p.000033: participant and ends when consent is provided and documented, but can be revisited later during the conduct of the
p.000033: study. Each individual must be given as much time as needed to reach a decision, including time for consultation with
p.000033: family members or others. Adequate time and resources must be provided for informed-consent procedures.
p.000033:
p.000033: Language of the information leaflet and recruitment material. All potential participants should be provided with a
p.000033: written information leaflet that they may take with them. Informing the individual participant must not be simply a
p.000033: ritual recitation of the contents of a written document. The wording of the leaflet and any recruitment material
p.000033: must be in language understandable by the potential participant and be approved by the research ethics
p.000033: committee. The wording of the leaflet must be short and preferably not exceed two or three pages. An oral presentation
p.000033: of information or the use of appropriate audiovisual aids, including pictographs and summary tables, are important to
p.000033: supplement written information documents to aid understanding. Information should also be appropriate for the
p.000033: participant group and specific individual, for example, in braille. Informed consent shall not include any language
p.000033: through which the subject is made to waive or appear to waive any of the participant’s legal rights, or releases or
p.000033: appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.
p.000033:
p.000033: Contents of the information leaflet. Throughout these Guidelines, elements that need to be included in the
...
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
p.000057: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: stereotypes. One proposed mechanism that can be used to avoid stereotyping is consultation with relevant stakeholders,
p.000058: where feasible, before, during and after the conduct of the research (see Guideline 7 – Community
p.000058: engagement).
p.000058:
p.000058: Special protections. Special protections for these groups can include allowing no more than minimal risks for
p.000058: procedures that offer no potential individual benefits for participants; supplementing the participant’s agreement by
p.000058: the permission of family members, legal guardians, or other appropriate representatives; or requiring that the research
p.000058: be carried out only when it is targeted at conditions that affect these groups. Safeguards can be designed to promote
p.000058: voluntary decision-making, limit the potential for confidentiality breaches, and otherwise work to protect the
p.000058: interests of those at increased risk of harm. Research ethics committees need to be sensitive to not overly excluding
p.000058: people, and allow them to participate by requiring that special protections be put in place.
p.000058:
p.000058: Group vulnerability. Despite the importance of avoiding classification of entire groups as inherently vulnerable,
p.000058: circumstances exist that require research ethics committees to pay special attention to research involving
p.000058: certain groups. In some resource-limited countries or communities, lack of access to medical care,
p.000058: membership in ethnic and racial minorities, or other disadvantaged or marginalized groups can be factors
p.000058: that constitute vulnerability. As is true of the vulnerability of individuals, the judgment that groups
...
p.000061: disorders, they must be engaged in the research discussion at the level of their capacity to understand, and they must
p.000061: be given a fair opportunity to agree to or to decline participation in the study. This can also be called
p.000061: obtaining the participant’s assent or dissent. Assent must be considered as a process (see Guideline 9 –
p.000061: Individuals capable of giving informed consent) that responds to changes in the person’s cognitive status and is
p.000061: not merely the absence of dissent.
p.000061:
p.000061: Any explicit objection by persons who are incapable to give informed consent must be respected even if the legally
p.000061: authorized representative has given permission. An explicit objection may be overruled if the incapacitated person
p.000061: needs treatment that is not available outside the context of research, prior research has demonstrated a significant
p.000061: benefit (see Guideline 4 – Potential individual benefits and risks of research), and the treating physician and the
p.000061: legally authorized representative consider the research intervention to be the best available medical option for the
p.000061: person lacking capacity.
p.000061:
p.000061: Permission of a legally authorized representative. In accordance with relevant national regulations, the
p.000061: permission of an immediate family member or other person with a close personal relationship with the individual must
p.000061: be sought. Surrogate decision-makers must evaluate to what extent study participation is consistent with the
p.000061: individual’s previously formed preferences and values (if any), and, in the case of research that offers participants a
p.000061: prospect of clinical benefit, to what extent study participation promotes the individual’s clinical interests.
p.000061: Previously stated preferences regarding the individual’s willingness to enrol in research or documented preferences in
p.000061: an advance directive should be respected. Researchers must recognize that surrogates may have their own
p.000061: interests that may call their permission into question. Furthermore, in situations where a legally
p.000061: authorized representative is not available to allow for timely enrolment, researchers may obtain the permission of a
p.000061: representative who is socially accepted but not formally recognized before the law.
p.000061:
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p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062: Emergency care situations in which the researcher anticipates that many participants will be unable to
p.000062: consent. Research protocols are sometimes designed to address conditions occurring suddenly and rendering the
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p.000066: and Guideline 5 – Choice of control in clinical trials.
p.000066:
p.000066: Assent. Children and adolescents who are legally minors cannot give legally valid informed consent, but they may be
p.000066: able to give assent. To give assent means that the child or adolescent is meaningfully engaged in the research
p.000066: discussion in accordance with his or her capacities. Assent must be considered as a process (see Guideline 9
p.000066: – Individuals capable of giving informed consent) and is not merely the absence of dissent. Furthermore, the researcher
p.000066: must involve the child or adolescent in the actual decision-making process and use age-appropriate information. It is
p.000066: of major importance to inform the child or adolescent and obtain assent as described above, preferably in
p.000066: writing for children who are literate. The process of obtaining assent must take into account not only the age of
p.000066: children, but also their individual circumstances, life experiences, emotional and psychological maturity, intellectual
p.000066: capabilities and the child’s or adolescent’s family situation.
p.000066:
p.000066: As adolescents near the age of majority, their agreement to participate in research may be ethically
p.000066: (though not legally) equivalent to consent. In this situation, parental consent is ethically best
p.000066: considered as “co-consent” but legally, the adolescent’s agreement remains assent. If child or adolescent
p.000066: participants reach the legal age of majority according to applicable law and become capable of independent informed
p.000066: consent during the research, their written informed consent to continued participation must be sought and their
p.000066: decision respected.
p.000066:
p.000066: Deliberate objection. Some children and adolescents who are too immature to give assent may be able to register a
p.000066: “deliberate objection,” meaning an expression of disapproval or refusal of a proposed procedure. The deliberate
p.000066: objection of an older child or adolescent, for example, is to be distinguished from the behaviour of an
p.000066: infant likely to cry or withdraw in response to almost any adverse stimulus. A deliberate objection by
...
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
p.000067: psychological and medical support for the participating children and adolescents is another special
p.000067: protection, though this may be difficult to realize in some communities. In such communities, the study
p.000067: personnel must be sufficiently qualified to help children and adolescents who need medical and psychological support.
p.000067:
p.000067: A research ethics committee may also allow a waiver of parental permission if the conditions set out in Guideline 10 –
p.000067: Modifications and waivers of informed consent - are satisfied.
p.000067:
p.000067: Observation of the study by a parent or guardian. A parent or legally appointed guardian who gives permission for a
p.000067: child or adolescent to participate in research must generally be given the opportunity, to a reasonable
p.000067: extent and without violating the privacy of other study participants, to observe the child’s participation as
...
p.000068: participants in research, researchers, sponsors and ethics committees must take special care in the research design,
p.000068: assessment of risks and benefits, as well as the process of informed consent, to ensure that women have
p.000068: the necessary time and appropriate environment to make decisions based on information provided to them.
p.000068:
p.000068: Some women become vulnerable in research because of heightened psychological, social, physical, or legal risks.
p.000068: Examples include surveys and interviews regarding intimate partner violence and rape; social and behavioural
p.000068: research involving sex workers or women who inject drugs; and studies that solicit information about sexual behaviour.
p.000068: When the research involves household surveys or interviews, researchers must take special care to ensure that the women
p.000068: are interviewed in a private
p.000068:
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p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: place without the possibility of intrusion by other family members. In such studies, women must be given
p.000069: the option of conducting the interview in a setting of their choosing outside the home. Breach of
p.000069: confidentiality in these types of research could result in serious harms to women, even if the only information
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
...
p.000095: may find it difficult to stop a trial early when interim results clearly recommend this course of action. Furthermore,
p.000095: researchers’ careers depend on publishing interesting results, for example, when applying for research
p.000095: funding or promotion. This can create professional conflicts of interests.
p.000095: Some researchers also have personal financial conflicts of interest. For example, researchers sometimes receive part
p.000095: of their salary or a “finder’s fee” for recruiting research participants. When this income reflects a fair
p.000095: compensation for their time spent on recruitment, it does not present an inherent conflict of interest. However, a
p.000095: salary or “finder’s fee” may lead researchers
p.000095: – intentionally or unintentionally – to interpret the inclusion or exclusion criteria of a study too flexibly, thereby
p.000095: potentially exposing participants to excessive risks or compromising the scientific validity of the research.
p.000095: This situation is of particular concern when participants are dependent on a researcher who is also their clinician
p.000095: (see Guideline 9 – Individuals capable of giving informed consent, section on Dependent relationship), and when the
p.000095: salary of the clinician is considerably lower than what the researcher is paid. It may also lead researchers to
p.000095: pressure eligible participants to enrol, thus compromising or undermining participants’ voluntary consent. In addition,
p.000095: financial conflicts of interest can arise when researchers or senior members of the research team (or their close
p.000095: family members) have a financial stake in the company sponsoring the research, such as stock ownership.
p.000095:
p.000095: 2. Research institutions (universities, research centres, or pharmaceutical companies). Research institutions can
p.000095: have both reputational and financial conflicts of interests. For example, universities rely on the reputation of
p.000095: their research to attract faculty, students, or external funding. Some universities also patent the discoveries
p.000095: of their employees. Institutional conflicts of interest can also arise when a research centre derives substantial
p.000095: support (perhaps covering years of funding) from a single sponsor or a handful of sponsors. Pharmaceutical companies
p.000095: may feel pushed to accelerate a marketing authorization for getting a longer period of patent protection, or they may
p.000095: be tempted to downplay the side effects of new medicines to get broader prescription patterns.
p.000095:
p.000095: 3. Research ethics committees. Researchers often serve as members of research ethics committees and
p.000095: conflicts of interest can arise in this role. For example, a researcher may submit her own study protocol for review,
p.000095: or she may be reviewing the work of colleagues whom she knows personally, or whose work she considers critical for the
p.000095: success of her institution. Research ethics committees may also have financial interests when their members
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p.000100: obtained from a duly authorized person, or, in the case of a child who is sufficiently mature to
p.000100: understand the implications of informed consent but has not reached the legal age of consent, that knowing
p.000100: agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian or other duly
p.000100: authorized representative (Guidelines 16 and 17);
p.000100:
p.000100: 32. An account of any economic or other inducements or incentives to prospective participants to
p.000100: participate, such as offers of cash payments, gifts, or free services or facilities, and of any financial obligations
p.000100: assumed by the participants, such as payment for medical services;
p.000100:
p.000100: 33. Plans and procedures, and the persons responsible, for communicating to participants information arising from the
p.000100: study (on harm or benefit, for example), or from other research on the same topic, that could affect participants’
p.000100: willingness to continue in the study (Guideline 9);
p.000100:
p.000100: 34. Plans to inform participants about the results of the study;
p.000100:
p.000100: 35. The provisions for protecting the confidentiality of personal data, and respecting the privacy of persons,
p.000100: including the precautions that are in place to prevent disclosure of the results of a subject’s genetic
p.000100: tests to immediate family relatives without the consent of the subject (Guidelines 4, 11, 12 and 24);
p.000100:
p.000100: 36. Information about how the code, if any, for the persons’ identity is established, where it will be kept and when,
p.000100: how and by whom it can be broken in the event of an emergency (Guidelines 11 and 12);
p.000100:
p.000100: 37. Any foreseen further uses of personal data or biological materials (Guidelines 11 and 12);
p.000100:
p.000100: 38. A description of the plans for statistical analysis of the study, including plans for interim analyses, if any,
p.000100: and criteria for prematurely terminating the study as a whole if necessary (Guideline 4);
p.000100:
p.000100: 39. Plans for monitoring the continuing safety of drugs or other interventions administered for purposes
p.000100: of the study or trial and, if appropriate, the appointment for this purpose of an independent
p.000100: data-monitoring (data and safety monitoring) committee (Guideline 4);
p.000100:
p.000100: 40. A list of the references cited in the protocol;
p.000100:
p.000100: 41. The source and amount of funding of the research: the organization that is sponsoring the research
p.000100: and a detailed account of the sponsor’s financial commitments to the research institution, the
p.000100: investigators, the research participants, and, when relevant, the community (Guideline 25);
p.000100:
p.000100:
p.000100:
p.000100: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000100:
p.000101: 101
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: 42. The arrangements for dealing with financial or other conflicts of interest that might affect the judgement of
...
p.000103: 16. new information that may have come to light, either from the study itself or other sources
p.000103: (Guideline 9);
p.000103:
p.000103: 17. the provisions that will be made to ensure respect for the privacy of participants, and for the confidentiality of
p.000103: records in which participants are identified (Guidelines 11 and 22);
p.000103:
p.000103: 18. the limits, legal or other, to the researchers’ ability to safeguard confidentiality, and the possible
p.000103: consequences of breaches of confidentiality (Guidelines 12 and 22);
p.000103:
p.000103: 19. the sponsors of the research, the institutional affiliation of the researchers, and the nature and sources of
p.000103: funding for the research, and, when they exist, any conflicts of interest of researchers, research institutions and
p.000103: research ethics committees and how these conflicts will be managed (Guidelines 9 and 25);
p.000103:
p.000103: 20. whether the researcher is serving only as a researcher or as both researcher and the participant`s physician
p.000103: (Guideline 9);
p.000103:
p.000103: 21. the extent of the researcher’s responsibility to provide care for participants’ health needs during and after the
p.000103: research (Guideline 6);
p.000103:
p.000103: 22. that treatment and rehabilitation will be provided free of charge for specified types of research- related injury
p.000103: or for complications associated with the research, the nature and duration of such care, the name of
p.000103: the medical service or organization that will provide the treatment, and whether there is any uncertainty
p.000103: regarding funding of such treatment (Guideline 14);
p.000103:
p.000103: 23. in what way, and by what organization, the participant or the participant’s family or dependants will be
p.000103: compensated for disability or death resulting from such injury (or, when indicated, that there are no plans
p.000103: to provide such compensation) (Guideline 14);
p.000103:
p.000103: 24. whether or not, in the country in which the prospective participant is invited to participate in research, the
p.000103: right to compensation is legally guaranteed;
p.000103:
p.000103:
p.000103:
p.000104: 104
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: 25. that a research ethics committee has approved or cleared the research protocol (Guideline 23);
p.000104:
p.000104: 26. that they will be informed in case of protocol violations and how safety and welfare will be
p.000104: protected in such a case (Guideline 23).
p.000104:
p.000104: In specific cases, before requesting an individual’s consent to participate in research, the researcher must provide
p.000104: the following information, in language or another form of communication that the individual can understand:
p.000104: 1. for controlled trials, an explanation of features of the research design (e.g., randomization,
p.000104: double-blinding), that the participant will not be told of the assigned treatment until the study has been completed
p.000104: and the blind has been broken;
p.000104:
p.000104: 2. whether all essential information is disclosed and, if not, that they are asked to agree to receiving incomplete
p.000104: information and that full information will be provided before study results are analysed and participants are given
p.000104: the possibility to withdraw their data collected under the study (Guideline 10);
p.000104:
p.000104: 3. policy with regard to the use of results of genetic tests and familial genetic information, and the precautions
p.000104: in place to prevent disclosure of the results of a participant’s genetic tests to immediate family
p.000104: relatives or to others (e.g. insurance companies or employers) without the consent of the participant (Guideline 11);
p.000104:
p.000104: 4. the possible research uses, direct or secondary, of the participant`s medical records and of biological
p.000104: specimens taken in the course of clinical care;
p.000104:
p.000104: 5. for collection, storage and use of biological material and health-related data, that broad informed consent will
p.000104: be obtained, which should specify: the purpose of the biobank, the conditions and duration of storage; the rules of
p.000104: access to the biobank; the ways in which the donor can contact the biobank custodian and can remain informed about
p.000104: future use; the foreseeable uses of the materials, whether limited to an already fully defined study or extending to a
p.000104: number of wholly or partially undefined studies; the intended goal of such use, whether only for research, basic or
p.000104: applied, or also for commercial purposes, and whether the participant will receive monetary or other benefits from the
p.000104: development of commercial products developed from their biological specimens; the possibility of unsolicited findings
p.000104: and how they will be dealt with; the safeguards that will be taken to protect confidentiality as well as their
p.000104: limitations, whether it is planned that biological specimens collected in the research will be destroyed at its
p.000104: conclusion, and, if not, details about their storage (where, how, for how long, and final disposition) and possible
p.000104: future use, that participants have the right to decide about such future use, to refuse storage, and to have the
...
Health / Physically Disabled
Searching for indicator illness:
(return to top)
p.000012:
p.000012: Minor increase above minimal risk. While there is no precise definition of a “minor increase” above
p.000012: minimal risk, the increment in risk must only be a fraction above the minimal risk threshold and considered acceptable
p.000012: by a reasonable person. It is imperative that judgments about a minor increase above minimal risk pay careful attention
p.000012: to context. Thus, research ethics committees need to determine the meaning of a minor increase above minimal risk in
p.000012: light of the particular aspects of the study they are reviewing.
p.000012:
p.000012: Risks to groups. In order to achieve the social and scientific value of research, results must be made public (see
p.000012: Guideline 24 – Public accountability for health-related research). However, research results in certain fields (for
p.000012: example, epidemiology, genetics, and sociology) may present risks to the interests of communities, societies, families,
p.000012: or racially or ethnically defined groups. For example, results could indicate – rightly or wrongly – that a group has a
p.000012: higher than average prevalence of alcoholism, mental illness or sexually transmitted disease, or that it is
p.000012: particularly susceptible to certain genetic disorders. Research results could therefore stigmatize a group or expose
p.000012: its members to discrimination. Plans to conduct such research should be sensitive to these considerations and minimize
p.000012: risks to groups, notably by maintaining confidentiality during and after the study and publishing the
p.000012: resulting data in a manner that is respectful of the interests of all concerned.
p.000012:
p.000012: Similarly, conducting research may disrupt or interfere with providing health care to the local community
p.000012: and thereby pose risks to the community. Research ethics committees must ensure, as part of evaluating the
p.000012: risks and potential individual benefits of research studies, that the interests of all who may be affected are given
p.000012: due consideration. For example, researchers and sponsors could contribute to the local health infrastructure in
p.000012: a way that compensates for any disruption caused by the research.
p.000012:
p.000012: In assessing the risks and potential individual benefits that a study presents to a population, research ethics
p.000012: committees should consider the potential harm that could result from forgoing the research or from failing to publish
p.000012: the results.
p.000012:
p.000012: Risks to researchers. In addition to participants, investigators themselves can be exposed to risks that result from
p.000012: research activities. For example, research involving radiation can expose researchers to risks and studies on
...
p.000034: informed consent. In some populations, the use of local languages may facilitate the communication of information to
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
p.000034: factors can be internal to participants, such as mental illness, whereas other influences can be external, such as a
p.000034: dependent relationship between participants and clinician-researchers. Circumstances such as severe illness or poverty
p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
p.000034: consent in these situations. Research ethics committees must determine for each individual protocol if influences on
p.000034: voluntary consent cross the threshold of being undue, and if so, which safeguards are appropriate.
p.000034:
p.000034: Dependent relationship. There are different forms of dependent relationships, such as those between
p.000034: teachers and students, and guards and prisoners. In the context of clinical research, dependent
p.000034: relationships can result from pre-existing relationships between a treating physician and a patient, who
p.000034: becomes a potential participant when his or her treating physician assumes the role of researcher. The
p.000034: dependent relationship between patients and clinician-researchers may compromise the voluntariness of informed
p.000034: consent, since potential participants who are patients depend on the clinician-researcher for medical care and
p.000034: may be reluctant to refuse an invitation to enrol in research in which the treating clinician is involved. Therefore,
...
p.000075: low-resource settings, and Guideline 23
p.000075: – Requirements for establishing research ethics committees and for their review of protocols).
p.000075:
p.000075: Research in disasters and disease outbreaks should ideally be planned ahead. Health officials and research
p.000075: ethics committees should develop procedures to ensure appropriate, expedient and flexible mechanisms and
p.000075: procedures for ethical review and oversight. For example, research ethics committees could pre-screen study
p.000075: protocols in order to facilitate and expedite ethical review in a situation of crisis. Similarly,
p.000075: researchers and sponsors could make pre-arrangements on data- and sample-sharing that research ethics committees
p.000075: review in advance.
p.000075:
p.000075: Sponsors and research ethics committees should evaluate and seek to minimize the risks to researchers and
p.000075: health professionals conducting research in a disaster context. Sponsors should include in the protocol a plan for
p.000075: mitigating adverse events. Furthermore, appropriate resources for mitigation measures should be included in the
p.000075: protocol budget.
p.000075:
p.000075:
p.000075: Commentary on Guideline 20
p.000075: Humanitarian response and research in the acute phase of disasters and diseases outbreaks. Disasters are sudden events
p.000075: that cause great suffering or loss of life. Disease and illness can either be the cause or a result of disasters. For
p.000075: example, epidemics can lead to disasters and destabilize political institutions or undermine economic activity.
p.000075: Conversely, natural and man-made disasters, such as earthquakes and war, can weaken or destroy health systems and have
p.000075: a devastating impact on individual and population health. The first and foremost obligation in acute
p.000075: disaster situations is to respond to the needs of those affected. At the same time, an obligation
p.000075: exists to conduct health-related research because disasters can be difficult to prevent, and the evidence
p.000075: base for effectively preventing or mitigating their public health impact is limited. These two obligations can come
p.000075: into conflict. This is because humanitarian response and health-related research often rely on the same infrastructure
p.000075: and the same personnel, so priorities between the two may need to be set. If nurses and physicians become
p.000075: researchers, this may also create dependent relationships (see Guideline 9 – Individuals capable of giving
p.000075: informed consent). Humanitarian workers, researchers and sponsors must be aware of these conflicts and ensure that
p.000075: their studies do not unduly compromise the disaster response. Researchers and sponsors should also aim to contribute to
p.000075: the infrastructure for the humanitarian response and integrate their research activities with this response.
p.000075: Importantly, all studies must be responsive to the health needs or priorities of the affected populations, and it must
p.000075: not be possible to conduct the research outside a disaster situation.
p.000075:
...
p.000087: accelerated review process.
p.000087:
p.000087: Further review. The research ethics committee must conduct further reviews of approved studies as necessary, in
p.000087: particular if there are significant changes in the protocol that require re-consent by participants,
p.000087: affect the safety of participants, or other ethical matters that emerge during the course of the study.
p.000087: These further reviews include progress reports submitted by researchers and possible monitoring of researchers’
p.000087: compliance with approved protocols.
p.000087:
p.000087: Committee membership. The research ethics committee must be constituted according to a document that
p.000087: specifies the manner in which members and the chair will be appointed, reappointed, and replaced. Research ethics
p.000087: committees must have members capable of providing competent and thorough review of research proposals. Membership
p.000087: normally must include physicians, scientists and other professionals such as research coordinators, nurses,
p.000087: lawyers, and ethicists, as well as community members or representatives of patients’ groups who can represent
p.000087: the cultural and moral values of study participants. Ideally, one or more members should have experience as study
p.000087: participants since there is growing recognition that knowledge gained through personal experience as a participant can
p.000087: supplement the professional understanding of illness and medical care. Committees must include both men and women.
p.000087: When a proposed study involves vulnerable individuals or groups, as may be the case in research involving
p.000087: prisoners or illiterate persons, representatives of relevant advocacy groups should be invited to meetings where such
p.000087: protocols will be reviewed (see
p.000087:
p.000087:
p.000087: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000088: 88
p.000088:
p.000088:
p.000088:
p.000088:
p.000088:
p.000088: Guideline 15 – Research involving vulnerable persons and groups). Regular rotation of members is desirable for
p.000088: balancing the advantage of experience with that of fresh perspectives.
p.000088:
p.000088: Members of research ethics committees must regularly update their knowledge about the ethical conduct of health-related
p.000088: research. If committees do not have the relevant expertise to adequately review a protocol, they must consult
p.000088: with external persons with the proper skills or certification. Committees must keep records of their
p.000088: deliberations and decisions.
p.000088:
p.000088: Conflicts of interests on the part of committee members. Research ethics committees must provide independent ethical
p.000088: opinions. Pressure can be brought to bear from many different directions, not just financial. Research ethics
...
Searching for indicator physically:
(return to top)
p.000053:
p.000053: Studies of financial incentives. In some studies, monetary or material incentives to participants are themselves a core
p.000053: object of study rather than a form of compensation. For example, incentives in the form of cash transfers or
p.000053: vouchers might be tested as a means of overcoming economic obstacles to treatment (for example, to accessing
p.000053: health care and continuing treatment) or lack of effective motivation for treatment (for example, in long-term
p.000053: treatment for some chronic conditions). Concerns about undue inducement must not preclude the conduct of such research,
p.000053: but research ethics committees must be sensitive to risks that might emerge for research using incentives.
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000054: 54
p.000054:
p.000054:
p.000054:
p.000054:
p.000054:
p.000054: GUIDELINE 14:
p.000054: TREATMENT AND COMPENSATION FOR RESEARCH-RELATED HARMS
p.000054:
p.000054: Sponsors and researchers must ensure that research participants who suffer physical, psychological or social
p.000054: harm as a result of participating in health-related research receive free treatment and rehabilitation for such harms,
p.000054: as well as compensation for lost wages, as appropriate. Such treatment and compensation are owed to research
p.000054: participants who are harmed physically, psychologically or socially, as a consequence of interventions
p.000054: performed solely to accomplish the purposes of research, regardless of fault. In the case of death resulting from
p.000054: research participation, the participant’s dependents are entitled to compensation. Participants must not be asked to
p.000054: waive the right to free treatment and compensation for research-related harms.
p.000054:
p.000054: Research ethics committees must determine whether there is an adequate arrangement for treatment and compensation for
p.000054: research-related injuries.
p.000054:
p.000054:
p.000054: Commentary on Guideline 14
p.000054: General considerations. This Guideline focuses on the entitlement to free treatment and additional compensation when
p.000054: research participants are harmed by research interventions or procedures. In the commentary below, the thresholds for
p.000054: such entitlements are described. Dependents of participants are also entitled to material compensation for death
p.000054: or disability occurring as a direct result of study participation. Lack of a proper mechanism in place for
p.000054: compensation of research harms may serve as a disincentive for people to participate in research, and may negatively
p.000054: impact trust in the research enterprise. Therefore, it is not only just, but also pragmatic, to have appropriate
p.000054: provision for free treatment and compensation for research-related harms.
p.000054:
p.000054: Obligation of the sponsor with regard to free treatment and rehabilitation. Sponsors and researchers must
p.000054: ensure that research participants who suffer physical, psychological or social harm as a result of
...
p.000054: the participant for as long as such care is needed (see Guideline 6 – Caring for participants’ health needs). The
p.000054: sponsor must provide this treatment or rehabilitation free of charge, since the harm resulted from the research.
p.000054:
p.000054: Obligation of the sponsor with regard to compensation. Before the research begins, the sponsor, whether a
p.000054: pharmaceutical company, other organization or institution, or a government (where government insurance is not
p.000054: precluded by law), must agree to provide compensation for any harm for which participants are entitled to
p.000054: compensation based on this Guideline. Alternatively, the sponsor may come to an agreement with the researcher
p.000054: concerning the circumstances in which the researcher must rely on his or her own insurance coverage (for
p.000054: example, for negligence or failure of the researcher to follow the protocol, or where government insurance coverage
p.000054: is limited
p.000054:
p.000054:
p.000054: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000055: 55
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055: to negligence). In certain circumstances, it may be advisable to follow both courses. Sponsors must seek adequate
p.000055: insurance to cover compensation, independent of proof of fault. Arrangements for free treatment and compensation should
p.000055: be described in the protocol and the informed consent.
p.000055:
p.000055: Equitable compensation and free medical treatment. Compensation is owed to research participants who are
p.000055: harmed psychologically, physically or socially, as a consequence of interventions performed solely to accomplish the
p.000055: purposes of research. A harm is considered a consequence of the intervention when the harm would not have occurred but
p.000055: for the person’s participation in research, and is different in kind or magnitude from the sorts of harms that would
p.000055: have been reasonable to expect in the context of clinical care. Compensation must be equitable: researchers and
p.000055: sponsors do not have an obligation to pay for care for every harm that befalls a participant while in a study. The
p.000055: research ethics committee must be satisfied that there is an adequate arrangement for free treatment and
p.000055: compensation for research-related harms, and provide oversight to ensure that researchers report such
p.000055: harms, how treatment is being paid for and compensation provided to participants, and what is being offered.
p.000055:
p.000055: Participants must not be asked to waive their rights to free treatment or compensation for research- related harms, nor
p.000055: must they be required to show negligence or lack of a reasonable degree of skill on the part of the researcher in order
p.000055: to claim free treatment or compensation. The informed consent process or form must not contain statements that would
p.000055: absolve a researcher from responsibility in the case of harm, or that would imply that participants waive their right
...
Health / Pregnant
Searching for indicator pregnant:
(return to top)
p.000007: FOR RESEARCH AND RESEARCH REVIEW 29
p.000007: GUIDELINE 9: INDIVIDUALS CAPABLE OF GIVING INFORMED CONSENT 33
p.000007: GUIDELINE 10: MODIFICATIONS AND WAIVERS OF INFORMED CONSENT 37
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: v
p.000007:
p.000007: GUIDELINE 11: COLLECTION, STORAGE AND USE OF BIOLOGICAL
p.000007: MATERIALS AND RELATED DATA 41
p.000007: GUIDELINE 12: COLLECTION, STORAGE AND USE OF DATA IN HEALTH- RELATED RESEARCH
p.000047: 47
p.000047: GUIDELINE 13: REIMBURSEMENT AND COMPENSATION FOR
p.000047: RESEARCH PARTICIPANTS 53
p.000047: GUIDELINE 14: TREATMENT AND COMPENSATION FOR RESEARCH-
p.000047: RELATED HARMS
p.000055: 55
p.000055: GUIDELINE 15: RESEARCH INVOLVING VULNERABLE PERSONS
p.000055: AND GROUPS
p.000057: 57
p.000057: GUIDELINE 16: RESEARCH INVOLVING ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000061: 61
p.000061: GUIDELINE 17: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS 65
p.000061: GUIDELINE 18: WOMEN AS RESEARCH PARTICIPANTS 69
p.000061: GUIDELINE 19: PREGNANT AND BREASTFEEDING WOMEN AS
p.000061: RESEARCH PARTICIPANTS 71
p.000061: GUIDELINE 20: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS 75
p.000061: GUIDELINE 21: CLUSTER RANDOMIZED TRIALS 79
p.000061: GUIDELINE 22: USE OF DATA OBTAINED FROM THE ONLINE
p.000061: ENVIRONMENT AND DIGITAL TOOLS IN HEALTH-RELATED RESEARCH 83
p.000061: GUIDELINE 23: REQUIREMENTS FOR ESTABLISHING RESEARCH ETHICS COMMITTEES AND FOR THEIR REVIEW OF PROTOCOLS
p.000087: 87
p.000087: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000087: vi
p.000087:
p.000087: GUIDELINE 24: PUBLIC ACCOUNTABILITY FOR HEALTH-RELATED RESEARCH 91
p.000087: GUIDELINE 25: CONFLICTS OF INTEREST 95
p.000087: APPENDIX 1 ITEMS TO BE INCLUDED IN A PROTOCOL (OR ASSOCIATED DOCUMENTS) FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099: APPENDIX 2 OBTAINING INFORMED CONSENT: ESSENTIAL
p.000099: INFORMATION FOR PROSPECTIVE RESEARCH PARTICIPANTS 103
p.000099: APPENDIX 3 CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH
p.000099: INVOLVING HUMANS
p.000107: 107
p.000107: APPENDIX 4 COMMENTATORS 113
p.000107: INDEX
p.000119: 119
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
...
p.000005: populations requires that the benefits of research be distributed fairly and that no group or class of persons bears
p.000005: more than its fair share of the risks or burdens from research participation. When benefits or burdens of research are
p.000005: to be apportioned unequally among individuals or groups, the criteria for unequal distribution should be scientifically
p.000005: and ethically justified rather than arbitrarily or conveniently chosen. Situations where unequal distribution of
p.000005: benefits would be considered are those in which the research particularly affects the population under study.
p.000005: In general, equitable distribution requires that participants be drawn from the qualifying population in the
p.000005: geographic area of the study where the results can be applied (see Guideline 2 – Research conducted in low-resource
p.000005: settings). Inclusion and exclusion criteria should not be based upon potentially discriminatory criteria, such as race,
p.000005: ethnicity, economic status, age or sex, unless there is a sound ethical or scientific reason to do so. For example, in
p.000005: cases where the under-representation of particular groups results in or perpetuates health disparities, equity may
p.000005: require special efforts to include members of those populations in research (see Guideline 17 – Research involving
p.000005: children and adolescents, Guideline 18
p.000005: – Women as research participants, and Guideline 19 – Pregnant women and breastfeeding women as research participants).
p.000005:
p.000005:
p.000005:
p.000005: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: Fair distribution of research benefits. Equity in the distribution of the benefits of research requires
p.000007: that research not disproportionately focus on the health needs of a limited class of people, but instead
p.000007: aims to address diverse health needs across different classes or groups. In the past, groups considered vulnerable
p.000007: were excluded from participation in research because it was considered the most expedient way of protecting
p.000007: those groups (for example, children, women of reproductive age, pregnant women). As a consequence of such exclusions,
p.000007: information about the diagnosis, prevention and treatment of diseases that afflict such groups is limited. This has
p.000007: resulted in a serious injustice. Since information about the management of diseases is considered a benefit to society,
p.000007: it is unjust to intentionally deprive specific groups of that benefit. The need to redress these injustices by
p.000007: encouraging the participation of previously excluded groups in basic and applied biomedical research is widely
p.000007: recognized.
p.000007:
p.000007: Fair distribution of research burdens. Research with human participants typically requires that some persons or
p.000007: groups are exposed to risks and burdens in order to generate the knowledge needed to protect and promote
p.000007: people’s health (see Guideline 1 – Scientific and social value and respect for rights). Equity in the distribution of
p.000007: burdens of research requires special care to ensure that individuals, communities or populations that are already
p.000007: disadvantaged or marginalized are not over-represented in research. A disproportionate selection of disadvantaged or
p.000007: convenient populations is morally problematic for several reasons. First, it is unjust to selectively invite poor or
p.000007: marginalized individuals or groups to participate in research because this concentrates the risks and burdens of
p.000007: research on people who already experience increased risks and burdens from social and economic disadvantage. Second,
p.000007: these individuals and groups are also the most likely to be excluded from, or to have difficulty accessing, the
...
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
...
p.000066: research unless it is supplemented by the permission of a parent, legal guardian or other duly authorized
p.000066: representative. The decision to continue or discontinue participation by children or adolescents who become legally
p.000066: capable during the study trumps the decision of their parents or legal guardians.
p.000066:
p.000066: Waiver of parental permission. In certain circumstances, research ethics committees may waive parental permission. In
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
p.000066:
p.000066: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000067: 67
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
p.000067: psychological and medical support for the participating children and adolescents is another special
...
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000068: 68
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: GUIDELINE 18:
p.000068: WOMEN AS RESEARCH PARTICIPANTS
p.000068:
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
p.000068: physiologies and health needs, they merit special consideration by researchers and research ethics committees. Only the
p.000068: informed consent of the woman herself should be required for her research participation. Since some societies lack
p.000068: respect for women’s autonomy, in no case must the permission of another person replace the requirement of individual
p.000068: informed consent by the woman.
p.000068:
p.000068: Women of child-bearing potential must be informed in advance of the possibility of risks to the fetus
p.000068: should they become pregnant during their research participation. When participation in research might be
p.000068: hazardous to a fetus or a woman if she becomes pregnant, sponsors and researchers must guarantee access to pregnancy
p.000068: tests, effective contraceptive methods before and during the research and to safe, legal abortion.
p.000068:
p.000068:
p.000068: Commentary on Guideline 18
p.000068: General considerations. Women in many societies have been excluded from research. For example, most of the early
p.000068: cardiovascular disease studies have excluded women because these diseases were believed to be uncommon in women. In
p.000068: particular, women who are biologically capable of becoming pregnant have been traditionally excluded from clinical
p.000068: trials of drugs, vaccines and medical devices owing to concern about undetermined risks to the fetus (see
p.000068: Guideline 15 – Research involving vulnerable persons and groups). Although the presumption against including women
p.000068: has changed in recent years, they are still excluded in many cases without adequate justification. Much remains unknown
p.000068: about the safety and efficacy of most drugs, vaccines, or devices used by women in medical practice, and
p.000068: this lack of knowledge can be dangerous. For example, heart attacks in women are different from heart attacks in men,
p.000068: so research is necessary to determine the best means of diagnosis and treatment in women.
p.000068:
p.000068: Vulnerability of women. Despite the current general presumption that favours the inclusion of women in
p.000068: research, in many societies women remain socially vulnerable in the conduct of research. For example, they may
p.000068: suffer negligence or harm because of their submission to authority, their hesitancy or inability to ask
...
p.000069: the option of conducting the interview in a setting of their choosing outside the home. Breach of
p.000069: confidentiality in these types of research could result in serious harms to women, even if the only information
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
p.000069: could include risks to the fetus if they become pregnant during the research (see Guideline 19 – Pregnant
p.000069: women and breastfeeding women as research participants). Access to a pregnancy test, to effective
p.000069: contraceptive methods and to safe, legal abortion must be guaranteed before exposure to a potential teratogenic or
p.000069: mutagenic intervention. When effective contraception and safe abortion are not available and alternative study sites
p.000069: are not feasible, the informed consent discussion must include information about the risk of unintended pregnancy, the
p.000069: legal grounds for abortion, and information about reducing harms from unsafe abortion and subsequent complications.
p.000069: Also, if the pregnancy is not terminated, participants must be guaranteed a medical follow-up for their own health and
p.000069: that of the infant and child.
p.000069:
p.000069: Women who become pregnant during research. Many biomedical protocols call for terminating the participation of women
p.000069: who become pregnant during the research. In cases where a drug or biological product is known to be mutagenic or
p.000069: teratogenic, pregnant women must be removed from the study, and followed up and provided care through
p.000069: the duration of their pregnancy and delivery. Access to diagnostic tests must be provided to reveal any fetal
p.000069: anomalies. If anomalies are detected, women who wish may be referred for an abortion. When there is no evidence on the
p.000069: basis of which a potential harm to the fetus can be assumed, women who become pregnant should not automatically be
p.000069: removed from the study, but must be offered the option to continue or end their participation. For instance, in some
p.000069: cases it may be appropriate for a woman to stay in the study for safety monitoring but removed from the study drug. If
p.000069: the woman opts for continued participation, researchers and sponsors must offer adequate monitoring and support.
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000070: 70
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: GUIDELINE 19:
p.000070: PREGNANT AND BREASTFEEDING WOMEN AS RESEARCH PARTICIPANTS
p.000070:
p.000070: Pregnant and breastfeeding women have distinctive physiologies and health needs. Research designed to obtain
p.000070: knowledge relevant to the health needs of the pregnant and breastfeeding woman must be promoted. Research in pregnant
p.000070: women must be initiated only after careful consideration of the best available relevant data.
p.000070:
p.000070: In no case must the permission of another person replace the requirement of individual informed consent by the pregnant
p.000070: or breastfeeding woman.
p.000070:
p.000070: For research interventions or procedures that have the potential to benefit either pregnant or breastfeeding women or
p.000070: their fetus or infant, risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000070:
p.000070: For research interventions or procedures that have no potential individual benefits for pregnant and
p.000070: breastfeeding women:
p.000070: f the risks must be minimized and no more than minimal; and
p.000070: f the purpose of the research must be to obtain knowledge relevant to the particular health needs of
p.000070: pregnant or breastfeeding women or their fetuses or infants.
p.000070:
p.000070: When the social value of the research for pregnant or breastfeeding women or their fetus or infant is compelling,
p.000070: and the research cannot be conducted in non-pregnant or non- breastfeeding women, a research ethics committee
p.000070: may permit a minor increase above minimal risk.
p.000070:
p.000070: Short-term and long‐term follow-up of the fetus and the child may be required in research involving pregnant and
p.000070: breastfeeding women depending upon the study intervention and its potential risks.
p.000070:
p.000070: As a general rule, health-related research involving pregnant women that has the potential for harm to the fetus should
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
p.000070:
p.000070:
p.000070: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000071: 71
p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
p.000071: routine exclusion of pregnant women from clinical trials is their use of medications (both prescription and
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
p.000071: it is imperative to design research for pregnant and breastfeeding women to learn about the currently unknown
p.000071: risks and potential individual benefits to them, as well as to the fetus or nursing infant.
p.000071:
p.000071: A case in point is the thalidomide episode, in which about 10,000 babies around the world (many in Western Europe) were
p.000071: born with severely deformed limbs because their mothers had taken medication when pregnant. This tragedy is often cited
p.000071: as a reason for excluding pregnant women from health- related research, but the lesson to be learned is the opposite.
p.000071: Never having been tested in pregnant women, the drug came to market and was readily available for morning sickness, a
p.000071: relatively mild condition. Had the drug been tested in very few women in a clinical trial, the mutagenic effect would
p.000071: most likely have been discovered and the total number of babies born with deformities would have been much smaller.
p.000071:
p.000071: Research designed to obtain knowledge relevant to the health needs of pregnant and breastfeeding women should be
p.000071: promoted in the following areas:
p.000071: f interventions for conditions resulting from pregnancy;
p.000071: f interventions for conditions that affect the general population and are reasonably expected to be used without
p.000071: adequate evidence during pregnancy (for example off-label use of medications); and
p.000071: f interventions for conditions that affect the developing fetus.
p.000071:
p.000071: Informed consent and risks and potential individual benefits. The involvement of pregnant women in
p.000071: research is complicated by the fact that it may present risks and potential individual benefits to the
p.000071: fetus as well as to the woman. Participation of breastfeeding women in biomedical research may similarly pose risks
p.000071: to the nursing infant. Research in pregnant and breastfeeding women must be initiated only after careful
p.000071: consideration of the best available data from preclinical research in pregnant animal models, research in non‐pregnant
p.000071: women, retrospective observational studies, and pregnancy registries.
p.000071:
p.000071: Researchers and research ethics committees must ensure that potential research participants are adequately
p.000071: informed about the risks to breastfeeding women and their infants, and about the risks to pregnant women (including
p.000071: future fertility), their pregnancies, their fetuses, and their future offspring. Information must also include steps
p.000071: taken to maximize potential individual benefits and minimize risks (see Guideline 4 – Potential individual benefits and
p.000071: risks of research). When evidence concerning risks is unknown or conflicting, this must be disclosed to the pregnant or
p.000071: breastfeeding woman as part of the informed consent process. She is the one to make the final decision about the
p.000071: acceptability of these risks to her and her fetus or infant. Women must also be informed that it is often difficult to
p.000071: determine causality in cases of fetal or infant abnormalities. Pregnant women may be recruited for research in which
p.000071: there is no prospect of potential individual benefit to them or the fetus only if the risks of the
p.000071: intervention are minimal. Examples include minimally invasive studies of new diagnostic techniques. In
p.000071: special circumstances, a minor increase above minimal risk may be acceptable.
p.000071:
p.000071: Some research involving pregnant women may be directed at the health of the fetus. In such cases, the role of the woman
p.000071: remains the same: she is the decision-maker for any interventions that affect her. This does not exclude the
p.000071: possibility of the woman consulting with the father of the fetus, if she wishes.
p.000071:
p.000071: Especially in communities or societies in which cultural beliefs accord more importance to the fetus than to the
p.000071: woman’s life or health, women may feel constrained to participate, or not to participate,
p.000071:
p.000071: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000072: 72
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: in research. Special safeguards must be established to prevent undue inducement to pregnant women to
p.000072: participate in research in which interventions hold out the prospect of potential individual benefit to the fetus but
p.000072: not to the woman herself.
p.000072:
p.000072: Researchers must include in protocols on research involving pregnant women a plan for monitoring the outcome of the
p.000072: pregnancy with regard to both the health of the woman and the short-term and long-term health of the infant and child.
p.000072: Adverse events associated with research in pregnancy and during lactation may not occur immediately.
p.000072:
p.000072: Potential individual benefits and risks. The potential individual benefits and risks of research with pregnant and
p.000072: breastfeeding women should be evaluated based on Guideline 4 – Potential individual benefits and risks of research, and
p.000072: Guideline 5 – Choice of control in clinical trials.
p.000072:
p.000072: Serious harm and access to abortion. Research with pregnant women must be conducted only in settings where
p.000072: these women can be guaranteed access to a safe, legal abortion. This rule serves to prevent women from having to carry
p.000072: an unwanted fetus to term and deliver an affected baby against their wishes. Before pregnant women are enrolled,
p.000072: researchers must, at a minimum, determine whether fetal impairment and mental health conditions are recognised as legal
p.000072: grounds for abortion in that jurisdiction. If they are not, pregnant women must not be recruited for research in which
p.000072: there is a realistic basis for concern that significant fetal abnormality may occur as a consequence of
p.000072: participation in research. At the same time, this rule might restrict potentially valuable research in
p.000072: countries where women cannot be guaranteed access to abortion. In such cases, research projects can be
p.000072: conducted only if a local research ethics committee determines that the research has compelling social value for
p.000072: pregnant women and the women are informed about existing restrictions on abortion and possible options for obtaining an
p.000072: abortion in another country.
p.000072:
p.000072: Breastfeeding women. The father may need to be consulted in research involving breastfeeding women, in accordance with
p.000072: Guideline 17 – Research involving children and adolescents. If a breast- fed infant may be exposed to an
p.000072: investigational product through the ingestion of breast milk (or it is unknown whether an infant would be exposed),
p.000072: such research should be conducted in accordance with Guideline 17 – Research involving children and adolescents.
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000073: 73
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073: GUIDELINE 20:
p.000073: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS
p.000073:
...
p.000099:
p.000099: 23. Methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000099: complications (Guidelines 4 and 23);
p.000099:
p.000099: 24. The known or foreseen risks of adverse reactions, including the risks attached to each proposed intervention and
p.000099: to any drug, vaccine or procedure to be tested (Guideline 4);
p.000099:
p.000099: 25. The potential individual benefits of the research to participants and to others (Guideline 4);
p.000099:
p.000099: 26. The expected benefits of the research to the population, including new knowledge that the study might
p.000099: generate (Guidelines 1 and 4);
p.000099:
p.000099: 27. For research carrying more than minimal risk of physical injury, details of plans, including
p.000099: insurance coverage, to provide treatment for such injury, including the funding of treatment, and to provide
p.000099: compensation for research-related disability or death (Guideline 14);
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000100: 100
p.000100: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 28. Provision for continued access to study interventions that have demonstrated significant benefit, indicating its
p.000100: modalities, the parties involved in continued care and the organization responsible for paying for it, and for how long
p.000100: it will continue (Guideline 6);
p.000100:
p.000100: 29. For research on pregnant women, a plan, if appropriate, for monitoring the outcome of the pregnancy
p.000100: with regard to both the health of the woman and the short-term and long-term health of the child (Guideline 19);
p.000100:
p.000100: 30. The means proposed to obtain individual informed consent and the procedure planned to communicate
p.000100: information to prospective participants, including the name and position of the person responsible for obtaining
p.000100: consent (Guideline 9);
p.000100:
p.000100: 31. When a prospective subject is not capable of informed consent, satisfactory assurance that permission will be
p.000100: obtained from a duly authorized person, or, in the case of a child who is sufficiently mature to
p.000100: understand the implications of informed consent but has not reached the legal age of consent, that knowing
p.000100: agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian or other duly
p.000100: authorized representative (Guidelines 16 and 17);
p.000100:
p.000100: 32. An account of any economic or other inducements or incentives to prospective participants to
p.000100: participate, such as offers of cash payments, gifts, or free services or facilities, and of any financial obligations
...
p.000104:
p.000104: 5. for collection, storage and use of biological material and health-related data, that broad informed consent will
p.000104: be obtained, which should specify: the purpose of the biobank, the conditions and duration of storage; the rules of
p.000104: access to the biobank; the ways in which the donor can contact the biobank custodian and can remain informed about
p.000104: future use; the foreseeable uses of the materials, whether limited to an already fully defined study or extending to a
p.000104: number of wholly or partially undefined studies; the intended goal of such use, whether only for research, basic or
p.000104: applied, or also for commercial purposes, and whether the participant will receive monetary or other benefits from the
p.000104: development of commercial products developed from their biological specimens; the possibility of unsolicited findings
p.000104: and how they will be dealt with; the safeguards that will be taken to protect confidentiality as well as their
p.000104: limitations, whether it is planned that biological specimens collected in the research will be destroyed at its
p.000104: conclusion, and, if not, details about their storage (where, how, for how long, and final disposition) and possible
p.000104: future use, that participants have the right to decide about such future use, to refuse storage, and to have the
p.000104: material destroyed (Guidelines 11 and 12);
p.000104:
p.000104: 6. when women of childbearing potential are participating in health-related research, information about the
p.000104: possible risks, if they become pregnant during the research, to themselves (including future fertility), their
p.000104: pregnancies, their fetuses, and their future offspring; and the guaranteed access to a pregnancy test, to effective
p.000104: contraceptive methods and to safe, legal abortion before exposure to a potential teratogenic or mutagenic intervention.
p.000104: When effective contraception and/ or safe abortion are not available and alternative study sites are not feasible, the
p.000104: women must be given information about: the risk of unintended pregnancy; the legal grounds for abortion; reducing harms
p.000104: from unsafe abortion and subsequent complications; and, when pregnancy is not terminated, the guarantee for a medical
p.000104: follow-up for their own health and that of the infant and child and the information that it is often difficult to
p.000104: determine causality in cases of fetal or infant abnormalities (Guidelines 18 and 19);
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000105: 105
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: 7. when concerning pregnant and breastfeeding women, the risks of participation in health-related research to
p.000105: themselves, their pregnancies, their fetuses, and their future offspring, what has been done to maximize potential
p.000105: individual benefits and minimize risks, that evidence concerning risks may be unknown or controversial, and that
p.000105: it is often difficult to determine causality in cases of fetal or infant abnormalities (Guidelines 4 and 19);
p.000105:
p.000105: 8. when concerning disaster victims who mostly are under duress, the difference between research and humanitarian
p.000105: aid (Guideline 20); and
p.000105:
p.000105: 9. when research is done in the online environment and using online or digital tools that may
p.000105: involve potentially vulnerable persons, information about the privacy and security controls that will be used to
p.000105: protect their data; and the limitations of the measures used and the risks that may remain despite the safeguards put
p.000105: in place (Guideline 22).
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
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p.000106: 106
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p.000119:
p.000119:
p.000119:
p.000119:
p.000120: 120
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
p.000120: Low-resource settings viii, ix, 3 - 5, 7, 17, 19, 22, 23, 26, 45, 47, 52, 75 - 77, 80, 89, 92
p.000120: M
p.000120: Management (of risks) 8, 42, 45, 48, 51, 85, 95 - 97
p.000120: Material Transfer Agreement 41, 45
p.000120: Minimal risk 9, 13, 15, 16, 18, 38, 62, 65, 66, 71, 72, 80, 88, 100
p.000120: Minor increase above minimal risk 13, 18
p.000120: Mitigation 11, 15, 76, 85, 95, 97
p.000120: Modification of informed consent 33, 37
p.000120: Money 54, 103
p.000120: Multi-centre research 87, 89
p.000120: O
p.000120: Observational ix, xii, 16, 53, 72, 78
p.000120: Online 27, 83 - 85, 106
p.000120: Opt-out/opt-in. See Informed opt-out/opt-in
p.000120: P
p.000120: Parent 65, 67, 68, 101
p.000120: Payment 54, 88, 101
p.000120: Permission 35, 38, 54, 58, 59, 61 - 63, 65, 67 - 71, 79, 80, 81, 83, 101
p.000120: Placebo 9, 15 - 19, 35, 78, 80
p.000120: Post-trial access. See Continued access
p.000120: Pregnant women 7, 8, 58, 70 - 73, 101
p.000120: Privacy 68, 83 - 85, 92, 93, 100, 101, 104, 106
p.000120: Procedures xi, 9 - 12, 15, 17, 19, 23, 26, 33 - 35, 37, 38, 42, 53 - 55, 59, 61, 62, 65 - 67, 71,
p.000120: 76 - 80, 87 - 90, 95, 97, 100 - 103
p.000120: Protocol 2, 12, 18, 23, 25, 35, 36, 43, 49, 55, 56, 58, 76, 83, 87 - 90, 92, 96, 99, 101, 102, 105
p.000120: Public accountability 11, 13, 29, 31, 51, 91
p.000120: Publication ii, 29, 31, 84, 91, 92, 95, 102
p.000120: R
p.000120: Registries 36, 38, 39, 47, 49, 51, 72, 91
p.000120: Rehabilitation 55, 104
p.000120: Reimbursement 53, 54
p.000120: Research ethics committee 2, 9, 10, 12, 15, 17, 18, 23, 25, 27, 33, 34 - 39, 41, 43 - 45, 47,
p.000120: 49 - 51, 53, 54, 56, 58, 61 - 63, 65, 68, 71, 73, 79, 85, 87 - 91, 95, 96, 98, 102, 103, 105
p.000120: Residual tissue 41, 43, 44
p.000120: Responsiveness 3, 4, 17, 19, 63, 75, 76
p.000120: Return of results 44, 45, 51
p.000120:
p.000120:
p.000120:
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000121: 121
p.000121:
p.000121: Risks 2, 5, 7 - 13, 15 - 19, 23, 26, 34 - 39, 41, 44, 47, 49, 50, 53, 54, 58, 59, 61 - 63, 65 - 67,
p.000121: 69 - 73, 75 - 77, 80, 81, 83 - 85, 88, 91, 92, 96, 100, 102, 104 - 106
p.000121: S
p.000121: Scientific value 2, 9 - 13, 51, 91
p.000121: Secondary use 49
p.000121: Social value 1 - 4, 8 - 11, 19, 25, 26, 30, 37, 38, 41, 44, 47, 50, 62, 65, 71, 73, 75, 77, 88, 91
p.000121: Specific informed consent 41 - 44, 47, 48, 49
p.000121: Storage 36, 41, 43, 45, 47 - 50, 52, 105
p.000121: U
p.000121: (Un)solicited findings xi, 44, 45, 51
p.000121: Undue inducement 53, 54, 73
...
Health / alcoholism
Searching for indicator alcoholism:
(return to top)
p.000012:
p.000012: Minor increase above minimal risk. While there is no precise definition of a “minor increase” above
p.000012: minimal risk, the increment in risk must only be a fraction above the minimal risk threshold and considered acceptable
p.000012: by a reasonable person. It is imperative that judgments about a minor increase above minimal risk pay careful attention
p.000012: to context. Thus, research ethics committees need to determine the meaning of a minor increase above minimal risk in
p.000012: light of the particular aspects of the study they are reviewing.
p.000012:
p.000012: Risks to groups. In order to achieve the social and scientific value of research, results must be made public (see
p.000012: Guideline 24 – Public accountability for health-related research). However, research results in certain fields (for
p.000012: example, epidemiology, genetics, and sociology) may present risks to the interests of communities, societies, families,
p.000012: or racially or ethnically defined groups. For example, results could indicate – rightly or wrongly – that a group has a
p.000012: higher than average prevalence of alcoholism, mental illness or sexually transmitted disease, or that it is
p.000012: particularly susceptible to certain genetic disorders. Research results could therefore stigmatize a group or expose
p.000012: its members to discrimination. Plans to conduct such research should be sensitive to these considerations and minimize
p.000012: risks to groups, notably by maintaining confidentiality during and after the study and publishing the
p.000012: resulting data in a manner that is respectful of the interests of all concerned.
p.000012:
p.000012: Similarly, conducting research may disrupt or interfere with providing health care to the local community
p.000012: and thereby pose risks to the community. Research ethics committees must ensure, as part of evaluating the
p.000012: risks and potential individual benefits of research studies, that the interests of all who may be affected are given
p.000012: due consideration. For example, researchers and sponsors could contribute to the local health infrastructure in
p.000012: a way that compensates for any disruption caused by the research.
p.000012:
p.000012: In assessing the risks and potential individual benefits that a study presents to a population, research ethics
p.000012: committees should consider the potential harm that could result from forgoing the research or from failing to publish
p.000012: the results.
p.000012:
p.000012: Risks to researchers. In addition to participants, investigators themselves can be exposed to risks that result from
...
Health / breastfeeding
Searching for indicator breastfeeding:
(return to top)
p.000007: GUIDELINE 9: INDIVIDUALS CAPABLE OF GIVING INFORMED CONSENT 33
p.000007: GUIDELINE 10: MODIFICATIONS AND WAIVERS OF INFORMED CONSENT 37
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: v
p.000007:
p.000007: GUIDELINE 11: COLLECTION, STORAGE AND USE OF BIOLOGICAL
p.000007: MATERIALS AND RELATED DATA 41
p.000007: GUIDELINE 12: COLLECTION, STORAGE AND USE OF DATA IN HEALTH- RELATED RESEARCH
p.000047: 47
p.000047: GUIDELINE 13: REIMBURSEMENT AND COMPENSATION FOR
p.000047: RESEARCH PARTICIPANTS 53
p.000047: GUIDELINE 14: TREATMENT AND COMPENSATION FOR RESEARCH-
p.000047: RELATED HARMS
p.000055: 55
p.000055: GUIDELINE 15: RESEARCH INVOLVING VULNERABLE PERSONS
p.000055: AND GROUPS
p.000057: 57
p.000057: GUIDELINE 16: RESEARCH INVOLVING ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000061: 61
p.000061: GUIDELINE 17: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS 65
p.000061: GUIDELINE 18: WOMEN AS RESEARCH PARTICIPANTS 69
p.000061: GUIDELINE 19: PREGNANT AND BREASTFEEDING WOMEN AS
p.000061: RESEARCH PARTICIPANTS 71
p.000061: GUIDELINE 20: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS 75
p.000061: GUIDELINE 21: CLUSTER RANDOMIZED TRIALS 79
p.000061: GUIDELINE 22: USE OF DATA OBTAINED FROM THE ONLINE
p.000061: ENVIRONMENT AND DIGITAL TOOLS IN HEALTH-RELATED RESEARCH 83
p.000061: GUIDELINE 23: REQUIREMENTS FOR ESTABLISHING RESEARCH ETHICS COMMITTEES AND FOR THEIR REVIEW OF PROTOCOLS
p.000087: 87
p.000087: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000087: vi
p.000087:
p.000087: GUIDELINE 24: PUBLIC ACCOUNTABILITY FOR HEALTH-RELATED RESEARCH 91
p.000087: GUIDELINE 25: CONFLICTS OF INTEREST 95
p.000087: APPENDIX 1 ITEMS TO BE INCLUDED IN A PROTOCOL (OR ASSOCIATED DOCUMENTS) FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099: APPENDIX 2 OBTAINING INFORMED CONSENT: ESSENTIAL
p.000099: INFORMATION FOR PROSPECTIVE RESEARCH PARTICIPANTS 103
p.000099: APPENDIX 3 CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH
p.000099: INVOLVING HUMANS
p.000107: 107
p.000107: APPENDIX 4 COMMENTATORS 113
p.000107: INDEX
p.000119: 119
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
...
p.000005: more than its fair share of the risks or burdens from research participation. When benefits or burdens of research are
p.000005: to be apportioned unequally among individuals or groups, the criteria for unequal distribution should be scientifically
p.000005: and ethically justified rather than arbitrarily or conveniently chosen. Situations where unequal distribution of
p.000005: benefits would be considered are those in which the research particularly affects the population under study.
p.000005: In general, equitable distribution requires that participants be drawn from the qualifying population in the
p.000005: geographic area of the study where the results can be applied (see Guideline 2 – Research conducted in low-resource
p.000005: settings). Inclusion and exclusion criteria should not be based upon potentially discriminatory criteria, such as race,
p.000005: ethnicity, economic status, age or sex, unless there is a sound ethical or scientific reason to do so. For example, in
p.000005: cases where the under-representation of particular groups results in or perpetuates health disparities, equity may
p.000005: require special efforts to include members of those populations in research (see Guideline 17 – Research involving
p.000005: children and adolescents, Guideline 18
p.000005: – Women as research participants, and Guideline 19 – Pregnant women and breastfeeding women as research participants).
p.000005:
p.000005:
p.000005:
p.000005: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: Fair distribution of research benefits. Equity in the distribution of the benefits of research requires
p.000007: that research not disproportionately focus on the health needs of a limited class of people, but instead
p.000007: aims to address diverse health needs across different classes or groups. In the past, groups considered vulnerable
p.000007: were excluded from participation in research because it was considered the most expedient way of protecting
p.000007: those groups (for example, children, women of reproductive age, pregnant women). As a consequence of such exclusions,
p.000007: information about the diagnosis, prevention and treatment of diseases that afflict such groups is limited. This has
p.000007: resulted in a serious injustice. Since information about the management of diseases is considered a benefit to society,
p.000007: it is unjust to intentionally deprive specific groups of that benefit. The need to redress these injustices by
p.000007: encouraging the participation of previously excluded groups in basic and applied biomedical research is widely
p.000007: recognized.
p.000007:
p.000007: Fair distribution of research burdens. Research with human participants typically requires that some persons or
...
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
...
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
p.000069: could include risks to the fetus if they become pregnant during the research (see Guideline 19 – Pregnant
p.000069: women and breastfeeding women as research participants). Access to a pregnancy test, to effective
p.000069: contraceptive methods and to safe, legal abortion must be guaranteed before exposure to a potential teratogenic or
p.000069: mutagenic intervention. When effective contraception and safe abortion are not available and alternative study sites
p.000069: are not feasible, the informed consent discussion must include information about the risk of unintended pregnancy, the
p.000069: legal grounds for abortion, and information about reducing harms from unsafe abortion and subsequent complications.
p.000069: Also, if the pregnancy is not terminated, participants must be guaranteed a medical follow-up for their own health and
p.000069: that of the infant and child.
p.000069:
p.000069: Women who become pregnant during research. Many biomedical protocols call for terminating the participation of women
p.000069: who become pregnant during the research. In cases where a drug or biological product is known to be mutagenic or
p.000069: teratogenic, pregnant women must be removed from the study, and followed up and provided care through
p.000069: the duration of their pregnancy and delivery. Access to diagnostic tests must be provided to reveal any fetal
p.000069: anomalies. If anomalies are detected, women who wish may be referred for an abortion. When there is no evidence on the
p.000069: basis of which a potential harm to the fetus can be assumed, women who become pregnant should not automatically be
p.000069: removed from the study, but must be offered the option to continue or end their participation. For instance, in some
p.000069: cases it may be appropriate for a woman to stay in the study for safety monitoring but removed from the study drug. If
p.000069: the woman opts for continued participation, researchers and sponsors must offer adequate monitoring and support.
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000070: 70
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: GUIDELINE 19:
p.000070: PREGNANT AND BREASTFEEDING WOMEN AS RESEARCH PARTICIPANTS
p.000070:
p.000070: Pregnant and breastfeeding women have distinctive physiologies and health needs. Research designed to obtain
p.000070: knowledge relevant to the health needs of the pregnant and breastfeeding woman must be promoted. Research in pregnant
p.000070: women must be initiated only after careful consideration of the best available relevant data.
p.000070:
p.000070: In no case must the permission of another person replace the requirement of individual informed consent by the pregnant
p.000070: or breastfeeding woman.
p.000070:
p.000070: For research interventions or procedures that have the potential to benefit either pregnant or breastfeeding women or
p.000070: their fetus or infant, risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000070:
p.000070: For research interventions or procedures that have no potential individual benefits for pregnant and
p.000070: breastfeeding women:
p.000070: f the risks must be minimized and no more than minimal; and
p.000070: f the purpose of the research must be to obtain knowledge relevant to the particular health needs of
p.000070: pregnant or breastfeeding women or their fetuses or infants.
p.000070:
p.000070: When the social value of the research for pregnant or breastfeeding women or their fetus or infant is compelling,
p.000070: and the research cannot be conducted in non-pregnant or non- breastfeeding women, a research ethics committee
p.000070: may permit a minor increase above minimal risk.
p.000070:
p.000070: Short-term and long‐term follow-up of the fetus and the child may be required in research involving pregnant and
p.000070: breastfeeding women depending upon the study intervention and its potential risks.
p.000070:
p.000070: As a general rule, health-related research involving pregnant women that has the potential for harm to the fetus should
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
p.000070:
p.000070:
p.000070: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000071: 71
p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
p.000071: routine exclusion of pregnant women from clinical trials is their use of medications (both prescription and
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
p.000071: it is imperative to design research for pregnant and breastfeeding women to learn about the currently unknown
p.000071: risks and potential individual benefits to them, as well as to the fetus or nursing infant.
p.000071:
p.000071: A case in point is the thalidomide episode, in which about 10,000 babies around the world (many in Western Europe) were
p.000071: born with severely deformed limbs because their mothers had taken medication when pregnant. This tragedy is often cited
p.000071: as a reason for excluding pregnant women from health- related research, but the lesson to be learned is the opposite.
p.000071: Never having been tested in pregnant women, the drug came to market and was readily available for morning sickness, a
p.000071: relatively mild condition. Had the drug been tested in very few women in a clinical trial, the mutagenic effect would
p.000071: most likely have been discovered and the total number of babies born with deformities would have been much smaller.
p.000071:
p.000071: Research designed to obtain knowledge relevant to the health needs of pregnant and breastfeeding women should be
p.000071: promoted in the following areas:
p.000071: f interventions for conditions resulting from pregnancy;
p.000071: f interventions for conditions that affect the general population and are reasonably expected to be used without
p.000071: adequate evidence during pregnancy (for example off-label use of medications); and
p.000071: f interventions for conditions that affect the developing fetus.
p.000071:
p.000071: Informed consent and risks and potential individual benefits. The involvement of pregnant women in
p.000071: research is complicated by the fact that it may present risks and potential individual benefits to the
p.000071: fetus as well as to the woman. Participation of breastfeeding women in biomedical research may similarly pose risks
p.000071: to the nursing infant. Research in pregnant and breastfeeding women must be initiated only after careful
p.000071: consideration of the best available data from preclinical research in pregnant animal models, research in non‐pregnant
p.000071: women, retrospective observational studies, and pregnancy registries.
p.000071:
p.000071: Researchers and research ethics committees must ensure that potential research participants are adequately
p.000071: informed about the risks to breastfeeding women and their infants, and about the risks to pregnant women (including
p.000071: future fertility), their pregnancies, their fetuses, and their future offspring. Information must also include steps
p.000071: taken to maximize potential individual benefits and minimize risks (see Guideline 4 – Potential individual benefits and
p.000071: risks of research). When evidence concerning risks is unknown or conflicting, this must be disclosed to the pregnant or
p.000071: breastfeeding woman as part of the informed consent process. She is the one to make the final decision about the
p.000071: acceptability of these risks to her and her fetus or infant. Women must also be informed that it is often difficult to
p.000071: determine causality in cases of fetal or infant abnormalities. Pregnant women may be recruited for research in which
p.000071: there is no prospect of potential individual benefit to them or the fetus only if the risks of the
p.000071: intervention are minimal. Examples include minimally invasive studies of new diagnostic techniques. In
p.000071: special circumstances, a minor increase above minimal risk may be acceptable.
p.000071:
p.000071: Some research involving pregnant women may be directed at the health of the fetus. In such cases, the role of the woman
p.000071: remains the same: she is the decision-maker for any interventions that affect her. This does not exclude the
p.000071: possibility of the woman consulting with the father of the fetus, if she wishes.
p.000071:
p.000071: Especially in communities or societies in which cultural beliefs accord more importance to the fetus than to the
p.000071: woman’s life or health, women may feel constrained to participate, or not to participate,
p.000071:
p.000071: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000072: 72
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: in research. Special safeguards must be established to prevent undue inducement to pregnant women to
p.000072: participate in research in which interventions hold out the prospect of potential individual benefit to the fetus but
p.000072: not to the woman herself.
p.000072:
p.000072: Researchers must include in protocols on research involving pregnant women a plan for monitoring the outcome of the
p.000072: pregnancy with regard to both the health of the woman and the short-term and long-term health of the infant and child.
p.000072: Adverse events associated with research in pregnancy and during lactation may not occur immediately.
p.000072:
p.000072: Potential individual benefits and risks. The potential individual benefits and risks of research with pregnant and
p.000072: breastfeeding women should be evaluated based on Guideline 4 – Potential individual benefits and risks of research, and
p.000072: Guideline 5 – Choice of control in clinical trials.
p.000072:
p.000072: Serious harm and access to abortion. Research with pregnant women must be conducted only in settings where
p.000072: these women can be guaranteed access to a safe, legal abortion. This rule serves to prevent women from having to carry
p.000072: an unwanted fetus to term and deliver an affected baby against their wishes. Before pregnant women are enrolled,
p.000072: researchers must, at a minimum, determine whether fetal impairment and mental health conditions are recognised as legal
p.000072: grounds for abortion in that jurisdiction. If they are not, pregnant women must not be recruited for research in which
p.000072: there is a realistic basis for concern that significant fetal abnormality may occur as a consequence of
p.000072: participation in research. At the same time, this rule might restrict potentially valuable research in
p.000072: countries where women cannot be guaranteed access to abortion. In such cases, research projects can be
p.000072: conducted only if a local research ethics committee determines that the research has compelling social value for
p.000072: pregnant women and the women are informed about existing restrictions on abortion and possible options for obtaining an
p.000072: abortion in another country.
p.000072:
p.000072: Breastfeeding women. The father may need to be consulted in research involving breastfeeding women, in accordance with
p.000072: Guideline 17 – Research involving children and adolescents. If a breast- fed infant may be exposed to an
p.000072: investigational product through the ingestion of breast milk (or it is unknown whether an infant would be exposed),
p.000072: such research should be conducted in accordance with Guideline 17 – Research involving children and adolescents.
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000073: 73
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073: GUIDELINE 20:
p.000073: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS
p.000073:
p.000073: Disasters arising from events such as earthquakes, tsunamis or military conflicts, and disease outbreaks, can
p.000073: have a sudden and devastating impact on the health of large affected populations. In order to identify effective ways
p.000073: of mitigating the health impact of disasters and disease outbreaks, health-related research should form an integral
p.000073: part of disaster response. However, the conduct of research must not unduly impact the response to the victims of a
p.000073: disaster.
p.000073:
p.000073: In the conduct of research in disasters and disease outbreaks, it is essential to uphold the ethical principles
...
p.000104: possible risks, if they become pregnant during the research, to themselves (including future fertility), their
p.000104: pregnancies, their fetuses, and their future offspring; and the guaranteed access to a pregnancy test, to effective
p.000104: contraceptive methods and to safe, legal abortion before exposure to a potential teratogenic or mutagenic intervention.
p.000104: When effective contraception and/ or safe abortion are not available and alternative study sites are not feasible, the
p.000104: women must be given information about: the risk of unintended pregnancy; the legal grounds for abortion; reducing harms
p.000104: from unsafe abortion and subsequent complications; and, when pregnancy is not terminated, the guarantee for a medical
p.000104: follow-up for their own health and that of the infant and child and the information that it is often difficult to
p.000104: determine causality in cases of fetal or infant abnormalities (Guidelines 18 and 19);
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000104:
p.000105: 105
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: 7. when concerning pregnant and breastfeeding women, the risks of participation in health-related research to
p.000105: themselves, their pregnancies, their fetuses, and their future offspring, what has been done to maximize potential
p.000105: individual benefits and minimize risks, that evidence concerning risks may be unknown or controversial, and that
p.000105: it is often difficult to determine causality in cases of fetal or infant abnormalities (Guidelines 4 and 19);
p.000105:
p.000105: 8. when concerning disaster victims who mostly are under duress, the difference between research and humanitarian
p.000105: aid (Guideline 20); and
p.000105:
p.000105: 9. when research is done in the online environment and using online or digital tools that may
p.000105: involve potentially vulnerable persons, information about the privacy and security controls that will be used to
p.000105: protect their data; and the limitations of the measures used and the risks that may remain despite the safeguards put
p.000105: in place (Guideline 22).
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
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p.000106: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000116: Institution/Organization Country Surname First name
p.000116:
p.000116: 55 U.S. Department of Health and Human Services, Washington DC
p.000116: 56 Washington University in St Louis, St Louis
p.000116: 57 World Health Organization (partial), Geneva
p.000116: United States Carr Sarah
p.000116:
p.000116:
p.000116: United States Dresser Rebecca Switzerland Van Ommeren
p.000116: Mark
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p.000116: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000116:
p.000117: 117
p.000117:
p.000117: INDEX
p.000117: A
p.000117: Abortion 58, 68 - 71, 73, 105
p.000117: Accelerated review 78, 88
p.000117: Accountability. See Public accountability
p.000117: Adolescent(s) 7, 9, 34, 35, 38, 45, 52, 58, 65 - 68, 73, 100
p.000117: Adult(s) xi, 44, 45, 51 Alternative trial designs 77 Ancillary care 21 - 23, 26
p.000117: Anonymous 44, 50
p.000117: Assent 61, 62, 65 - 67, 101
p.000117: Authorization 4, 41, 42, 44, 47, 48, 50, 70, 96
p.000117: B
p.000117: Benefit xi, 2 - 5, 7 - 12, 16, 19, 21 - 23, 29, 44, 53, 54, 61, 62, 65 - 67, 71 - 73, 91, 101
p.000117: Biobank 42 - 45, 105
p.000117: Biological material 41, 42, 44, 45, 50, 103, 105
p.000117: Breastfeeding 7, 58, 70 - 73, 106
p.000117: Broad informed consent 41 - 44, 47, 48 - 50, 52, 105
p.000117: C
p.000117: Capable of giving informed consent 10, 25, 33, 34, 37, 38, 41, 43, 47, 49, 50, 51, 56, 58,
p.000117: 61 - 63, 67, 76, 78, 96
p.000117: Capacity-building 5, 27, 29, 30, 45, 52, 102
p.000117: Cluster randomized trials 79, 80
p.000117: Coding 41, 44, 47, 50, 51, 90
p.000117: Collaborative partnership 27, 29, 30, 42, 45, 47, 52, 89
p.000117: Collection, collecting 26, 36, 39, 41 - 43, 47 - 50, 77, 80, 83 - 85, 92, 103, 105
p.000117: Community engagement ix, xi, 5, 10, 23, 25, 26, 29, 30, 42, 45, 47, 52, 59, 63, 75, 78, 102
p.000117: Comparative effectiveness research 16, 19
p.000117: Compassionate use 22
p.000117: Compelling scientific reasons 15 - 18
p.000117: Compensation 13, 53 - 56, 96, 100, 104 Competent. See Capable of giving informed consent Comprehension 34
p.000117: Confidentiality 11, 13, 41, 42, 44, 47, 48, 50, 51, 57, 59, 70, 100, 101, 102, 104, 105
p.000117: Conflicts of interest 5, 30, 34, 78, 89, 92, 95 - 97, 102, 104
p.000117: Continued access 21 - 23, 101, 104
p.000117: Control 9, 12, 15 - 18, 22, 26, 45, 51, 62, 67, 73, 79, 80, 83, 85,
p.000117: Custodian 41, 43, 44, 47, 49, 50, 105
p.000117: D
p.000117: Databank 47 - 52
p.000117:
p.000117:
p.000117: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000117:
p.000119: 119
p.000119:
p.000119: Data mining 50
p.000119: Data sharing 29, 31, 51, 85, 92
p.000119: Deception, deceiving 33, 38, 57
p.000119: Deliberate objection 67
...
p.000119: Dissemination 2, 4, 25, 85, 92
p.000119: Dissent 62, 67
p.000119: E
p.000119: Education 2, 30, 57, 89, 97
p.000119: Emergency care 63, 68, 78
p.000119: Equitable distribution 4, 7, 42, 45, 47, 52, 75, 77
p.000119: Established effective intervention viii, 9, 12, 15 - 19
p.000119: Ethical review xii, 2, 29, 30, 39, 76 - 78, 87 - 90, 95, 97, 99, 102
p.000119: Externally sponsored research 87, 89
p.000119: F
p.000119: Fairness 2
p.000119: Fetus 58, 69, 70 - 73
p.000119: Free medical treatment 56
p.000119: G
p.000119: Gatekeeping 80
p.000119: Governance 41 - 43, 44, 47, 48, 50, 51, 78
p.000119: H
p.000119: Harms 10, 11, 12, 18, 54, 55, 56, 70, 72, 91, 105
p.000119: Health needs 2 - 4, 8, 17, 19, 21 - 23, 26, 55, 61, 65, 69, 71, 72, 75, 76, 104
p.000119: I
p.000119: Identifiable 38, 39, 51, 84
p.000119: Implementation research 80
p.000119: Incentives 10, 54, 92, 101
p.000119: Information leaflet 34
p.000119: Informed consent ix, 2, 9, 10, 21, 25, 26, 33 - 39, 41 - 45, 47 - 52, 54, 56, 58, 61 - 65, 67 - 72, 75,
p.000119: 76, 78 - 80, 89, 96, 97, 100, 101, 103, 105
p.000119: Informed opt-out /opt-in 41, 44, 47, 49, 83
p.000119: In-kind 54
p.000119: Interventions 1 - 4, 9 - 12, 15 - 19, 21 - 23, 26, 30, 53, 55, 56, 61 - 63, 65, 66, 71 - 73, 75 - 81, 84,
p.000119: 88, 91, 100, 101, 104
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000120: 120
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
p.000120: Low-resource settings viii, ix, 3 - 5, 7, 17, 19, 22, 23, 26, 45, 47, 52, 75 - 77, 80, 89, 92
p.000120: M
p.000120: Management (of risks) 8, 42, 45, 48, 51, 85, 95 - 97
p.000120: Material Transfer Agreement 41, 45
p.000120: Minimal risk 9, 13, 15, 16, 18, 38, 62, 65, 66, 71, 72, 80, 88, 100
p.000120: Minor increase above minimal risk 13, 18
p.000120: Mitigation 11, 15, 76, 85, 95, 97
p.000120: Modification of informed consent 33, 37
p.000120: Money 54, 103
p.000120: Multi-centre research 87, 89
p.000120: O
p.000120: Observational ix, xii, 16, 53, 72, 78
p.000120: Online 27, 83 - 85, 106
p.000120: Opt-out/opt-in. See Informed opt-out/opt-in
p.000120: P
p.000120: Parent 65, 67, 68, 101
p.000120: Payment 54, 88, 101
p.000120: Permission 35, 38, 54, 58, 59, 61 - 63, 65, 67 - 71, 79, 80, 81, 83, 101
p.000120: Placebo 9, 15 - 19, 35, 78, 80
p.000120: Post-trial access. See Continued access
p.000120: Pregnant women 7, 8, 58, 70 - 73, 101
p.000120: Privacy 68, 83 - 85, 92, 93, 100, 101, 104, 106
...
Health / patients in emergency situations
Searching for indicator emergencies:
(return to top)
p.000076:
p.000076: Potential individual benefits and risks of investigational interventions and emergency use outside clinical trials.
p.000076: Especially when disasters are caused by infectious diseases that are highly contagious or serious (for example
p.000076: influenza, Ebola), there is great pressure to develop effective treatments and vaccines. When facing a serious,
p.000076: life-threatening infection, many people are willing to assume high risks and use unproven agents within or
p.000076: outside of clinical trials. However, it is essential that researchers and sponsors realistically assess
p.000076: the potential individual benefits and risks of experimental interventions and communicate these clearly to
p.000076: potential participants and individuals at risk. Even in ordinary circumstances, many promising experimental agents
p.000076: may not be safe and effective, and experimental interventions must be systematically evaluated in clinical trials.
p.000076: Moreover, emergency use can compromise recruitment of research participants and therefore undermine the conclusion of
p.000076: trials. Widespread emergency use with inadequate data collection about patient outcomes must therefore be avoided.
p.000076:
p.000076: Equitable distribution of risks and benefits. Because experimental interventions are often limited in disaster
p.000076: situations, fair selection of participants is essential (Guideline 3 – Equitable distribution of benefits and burdens
p.000076: in the selection of individuals and groups of participants in research). Especially in dire emergencies, well-off and
p.000076: well-connected patients must not be further privileged (for example, community leaders). Moreover, the exclusion of
p.000076: especially vulnerable populations must be justified (Guideline 15 – Research involving vulnerable persons and groups).
p.000076: It may be acceptable to prioritize certain populations in study enrolment. For example, front line workers often put
p.000076: themselves at risk during a disaster such as an epidemic, and if experimental interventions are effective, these
p.000076: workers would be able to help more patients. The principles of reciprocity and helping the largest number of people
p.000076: could therefore justify their prioritization. Researchers, sponsors, and research ethics committees also need
p.000076: to ensure that burdens and benefits of participation are equitably distributed (see Guideline 3 – Equitable
p.000076: distribution of benefits and burdens in the selection of individuals and groups of participants in research).
p.000076:
p.000076: Scientific validity and alternative trial designs. Disasters unfold quickly and study designs need to be
p.000076: chosen so that studies will yield meaningful data in a rapidly evolving situation. Study designs must be feasible in a
p.000076: disaster situation but still appropriate to ensure the study’s scientific validity. Without scientific validity, the
p.000076: research lacks social value and must not be conducted (see Guideline 1 – Scientific and social value and respect for
p.000076: rights). Research may even divert personnel or resources from the disaster response. In clinical trials, the
...
Health / sexually transmitted disases
Searching for indicator sexually transmitted:
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p.000066:
p.000066: Waiver of parental permission. In certain circumstances, research ethics committees may waive parental permission. In
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
p.000066:
p.000066: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000067: 67
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
p.000067: psychological and medical support for the participating children and adolescents is another special
p.000067: protection, though this may be difficult to realize in some communities. In such communities, the study
p.000067: personnel must be sufficiently qualified to help children and adolescents who need medical and psychological support.
p.000067:
...
Searching for indicator std:
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p.000107: Ethics in Central and Eastern Europe. E. Gefenas is a member of the Council of Europe Committee on
p.000107: Bioethics; he was the chair of this Committee from 2011–2012. He was elected as the chairman of the
p.000107: Intergovernmental Bioethics Committee (IGBC) of UNESCO in 2015. The areas of his professional interest include
p.000107: ethical and policy-making issues related to human research and health care in transition societies.
p.000107:
p.000107: Dirceu Greco
p.000107: Dirceu Greco is full professor of Infectious Diseases and Bioethics at the School of Medicine, Federal University of
p.000107: Minas Gerais (UFMG), Belo Horizonte, Brazil. He received his MD degree and this PhD from UFMG. Chief, Infectious and
p.000107: Parasitic Diseases Service (2009-2011), Coordinator of UFMG University Hospital Centre for Clinical Research
p.000107: (2005-2010), member (2007-2010), Brazilian Research Ethics Commission (CONEP); member, Brazilian AIDS Commission
p.000107: (Ministry of Health-MoH). Main topics of interest include Infectious and Parasitic Illnesses, bioethics, public health
p.000107: and clinical immunology. He has participated in several working groups that gave rise to
p.000107: national/international guidelines related to ethics, prevention, care and treatment of HIV/AIDS and TB. He has
p.000107: frequently acted as temporary advisor to many national/international institutions, such as the Brazilian AIDS
p.000107: Programme, WHO, UNITAID, UNAIDS, CIOMS and WMA. From 2010 to 2013 he directed the Department of STD, AIDS and Viral
p.000107: Hepatitis (Secretary of Health Surveillance, MoH, Brazil).
p.000107:
p.000107: David Haerry
p.000107: David Haerry is a treatment writer and conference reporter since 1996. He is co-authoring a database on travel &
p.000107: residency restrictions for people living with HIV. David Haerry has been involved in health care professionals
p.000107: education projects since 2007. Since 2015, he is Secretary General of the Swiss Academic Foundation on Education in
p.000107: Infectious Diseases SAFE-ID. He is work package co-leader and member of the Executive Committee in the EUPATI-IMI
p.000107: project and involved in a number of European and global research networks and research collaborations, including the
p.000107: ENCePP Steering Group. He is co-chair of the Patient and Consumer Working Party at the European Medicines Agency and
p.000107: has served the European AIDS Treatment Group EATG in various positions since 2004. David has been involved in HIV and
p.000107: HCV drug development since 2005 and has specific interests in the areas of Personalised Medicine, Risk Communication,
p.000107: Pharmacovigilance, Observational Studies, Biomedical Prevention and HIV Eradication Research. He is living with HIV
p.000107: since 1986.
p.000107:
p.000107: Bocar Kouyaté
p.000107: Bocar A. Kouyaté is Senior Advisor to the Minister of Health, Burkina Faso and researcher at the Centre national de
...
Health / visual impairment
Searching for indicator blind:
(return to top)
p.000098: nature, extent and relevance of animal studies and other preclinical and clinical studies (Guideline 4);
p.000098:
p.000098: 6. A statement that the principles set out in these Guidelines will be implemented;
p.000098:
p.000098: 7. An account of previous submissions of the protocol for ethical review and their outcome;
p.000098:
p.000098: 8. A brief description of the site(s) where the research is to be conducted, including information about the
p.000098: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000098: epidemiological information about the country or region concerned;
p.000098:
p.000098: 9. Name and address of the sponsor;
p.000098:
p.000098: 10. Names, addresses, institutional affiliations, qualifications and experience of the principal investigator
p.000098: and other investigators (Guideline 1);
p.000098:
p.000098: 11. The objectives of the trial or study, its hypotheses or research questions, its assumptions, and its
p.000098: variables (Guideline 1);
p.000098:
p.000098: 12. A detailed description of the design of the trial or study. In the case of controlled clinical trials the
p.000098: description should include, but not be limited to, whether assignment to treatment groups
p.000098:
p.000098:
p.000098: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: will be randomized (including the method of randomization), and whether the study will be blinded (single
p.000099: blind, double blind), or open (Guideline 5);
p.000099:
p.000099: 13. The number of research participants needed to achieve the study objective, and how this was statistically
p.000099: determined;
p.000099:
p.000099: 14. The criteria for inclusion or exclusion of potential participants, and justification for the exclusion of any
p.000099: groups on the basis of age, sex, social or economic factors, or for other reasons (Guideline 3);
p.000099:
p.000099: 15. The justification for involving as research participants children or adolescents, persons who are unable to give
p.000099: informed consent or vulnerable persons or groups, and a description of special measures to minimize risks to such
p.000099: persons (Guidelines 15, 16 and 17);
p.000099:
p.000099: 16. The process of recruitment, e.g. advertisements, and the steps to be taken to protect privacy and confidentiality
p.000099: during recruitment (Guideline 3);
p.000099:
p.000099: 17. Description and explanation of all interventions (the method of treatment administration, including
p.000099: route of administration, dose, dose interval and treatment period for investigational and comparator products used);
p.000099:
p.000099: 18. Plans and justification for withdrawing or withholding standard therapies in the course of the research, including
p.000099: any resulting risks to persons (Guidelines 4 and 5);
p.000099:
p.000099: 19. Any other treatment that may be given or permitted, or contraindicated, during the study (Guideline
p.000099: 6);
p.000099:
p.000099: 20. Clinical and laboratory tests and other tests that are to be carried out;
...
p.000103:
p.000103: 23. in what way, and by what organization, the participant or the participant’s family or dependants will be
p.000103: compensated for disability or death resulting from such injury (or, when indicated, that there are no plans
p.000103: to provide such compensation) (Guideline 14);
p.000103:
p.000103: 24. whether or not, in the country in which the prospective participant is invited to participate in research, the
p.000103: right to compensation is legally guaranteed;
p.000103:
p.000103:
p.000103:
p.000104: 104
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: 25. that a research ethics committee has approved or cleared the research protocol (Guideline 23);
p.000104:
p.000104: 26. that they will be informed in case of protocol violations and how safety and welfare will be
p.000104: protected in such a case (Guideline 23).
p.000104:
p.000104: In specific cases, before requesting an individual’s consent to participate in research, the researcher must provide
p.000104: the following information, in language or another form of communication that the individual can understand:
p.000104: 1. for controlled trials, an explanation of features of the research design (e.g., randomization,
p.000104: double-blinding), that the participant will not be told of the assigned treatment until the study has been completed
p.000104: and the blind has been broken;
p.000104:
p.000104: 2. whether all essential information is disclosed and, if not, that they are asked to agree to receiving incomplete
p.000104: information and that full information will be provided before study results are analysed and participants are given
p.000104: the possibility to withdraw their data collected under the study (Guideline 10);
p.000104:
p.000104: 3. policy with regard to the use of results of genetic tests and familial genetic information, and the precautions
p.000104: in place to prevent disclosure of the results of a participant’s genetic tests to immediate family
p.000104: relatives or to others (e.g. insurance companies or employers) without the consent of the participant (Guideline 11);
p.000104:
p.000104: 4. the possible research uses, direct or secondary, of the participant`s medical records and of biological
p.000104: specimens taken in the course of clinical care;
p.000104:
p.000104: 5. for collection, storage and use of biological material and health-related data, that broad informed consent will
p.000104: be obtained, which should specify: the purpose of the biobank, the conditions and duration of storage; the rules of
p.000104: access to the biobank; the ways in which the donor can contact the biobank custodian and can remain informed about
p.000104: future use; the foreseeable uses of the materials, whether limited to an already fully defined study or extending to a
p.000104: number of wholly or partially undefined studies; the intended goal of such use, whether only for research, basic or
...
Searching for indicator blinded:
(return to top)
p.000021: ability to
p.000021:
p.000021:
p.000021: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000022: 22
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: communicate or function independently, or significantly reduce a quality of life they had attained during
p.000022: the study, then the obligation will be greater than if the intervention provides relief for a minor or
p.000022: transient condition. Similarly, the obligation will be greater when participants are not able to access the needed care
p.000022: or prevention within the local health system than in cases where this is readily available. The obligation may also be
p.000022: greater when there are no available alternatives with clinical effectiveness similar to the intervention that
p.000022: has demonstrated significant benefit than in cases where such alternatives exist. However, the obligation
p.000022: may not be able to be completely met if the total number of qualifying individuals is very large.
p.000022: Continued access to interventions that have demonstrated significant benefit but await regulatory approval should be
p.000022: consistent with the relevant regulatory requirements for pre-licensure access and should not delay the process of
p.000022: obtaining regulatory approval.
p.000022:
p.000022: Providing continued access to a beneficial study intervention can create several dilemmas:
p.000022: f In the case of blinded controlled trials, it may take time to unblind the results and find out who has received
p.000022: which intervention. Researchers and sponsors should make provisions for this transition period and inform
p.000022: participants if they will be temporarily receiving the current standard of care before the study intervention can be
p.000022: administered.
p.000022: f A research ethics committee may discuss whether researchers and sponsors are under an obligation to
p.000022: provide participants with continued access to the experimental intervention in a non-inferiority trial. When
p.000022: the tested intervention is not inferior to the standard of care, there is no obligation to provide participants with
p.000022: the tested intervention.
p.000022:
p.000022: As stated in this Guideline, sponsors and researchers may no longer have an obligation to provide continued access to
p.000022: a study intervention that has demonstrated significant benefit when the intervention becomes available in the
p.000022: public health system. Moreover, sponsors, researchers and community members may agree before a trial starts that any
p.000022: intervention that has demonstrated significant benefit will be provided only for a predetermined period of time.
p.000022:
p.000022: Consultation with relevant stakeholders. The obligation to care for participants’ health needs rests with the
p.000022: researcher and the sponsor. However, the delivery of care may involve other parties, for example, local health
p.000022: authorities, insurance companies, members of the communities from which participants are drawn, or
...
p.000098: 5. Summary of all previous studies on the topic, including unpublished studies known to the
p.000098: investigators and sponsors, and information on previously published research on the topic, including the
p.000098: nature, extent and relevance of animal studies and other preclinical and clinical studies (Guideline 4);
p.000098:
p.000098: 6. A statement that the principles set out in these Guidelines will be implemented;
p.000098:
p.000098: 7. An account of previous submissions of the protocol for ethical review and their outcome;
p.000098:
p.000098: 8. A brief description of the site(s) where the research is to be conducted, including information about the
p.000098: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000098: epidemiological information about the country or region concerned;
p.000098:
p.000098: 9. Name and address of the sponsor;
p.000098:
p.000098: 10. Names, addresses, institutional affiliations, qualifications and experience of the principal investigator
p.000098: and other investigators (Guideline 1);
p.000098:
p.000098: 11. The objectives of the trial or study, its hypotheses or research questions, its assumptions, and its
p.000098: variables (Guideline 1);
p.000098:
p.000098: 12. A detailed description of the design of the trial or study. In the case of controlled clinical trials the
p.000098: description should include, but not be limited to, whether assignment to treatment groups
p.000098:
p.000098:
p.000098: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: will be randomized (including the method of randomization), and whether the study will be blinded (single
p.000099: blind, double blind), or open (Guideline 5);
p.000099:
p.000099: 13. The number of research participants needed to achieve the study objective, and how this was statistically
p.000099: determined;
p.000099:
p.000099: 14. The criteria for inclusion or exclusion of potential participants, and justification for the exclusion of any
p.000099: groups on the basis of age, sex, social or economic factors, or for other reasons (Guideline 3);
p.000099:
p.000099: 15. The justification for involving as research participants children or adolescents, persons who are unable to give
p.000099: informed consent or vulnerable persons or groups, and a description of special measures to minimize risks to such
p.000099: persons (Guidelines 15, 16 and 17);
p.000099:
p.000099: 16. The process of recruitment, e.g. advertisements, and the steps to be taken to protect privacy and confidentiality
p.000099: during recruitment (Guideline 3);
p.000099:
p.000099: 17. Description and explanation of all interventions (the method of treatment administration, including
p.000099: route of administration, dose, dose interval and treatment period for investigational and comparator products used);
p.000099:
p.000099: 18. Plans and justification for withdrawing or withholding standard therapies in the course of the research, including
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Social / Access to Social Goods
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p.000001: research personnel are qualified by virtue of their education and experience to perform competently and
p.000001: with integrity. This includes receiving appropriate ethics education and training. Qualifications of
p.000001: research personnel must be adequately described in the materials submitted to the research ethics committee
p.000001: (Appendix I).
p.000001:
p.000001: Respect for rights and welfare. Although the social value of research is a necessary condition for its ethical
p.000001: acceptability, it is not sufficient. All research with humans must be carried out in ways that show respect and concern
p.000001: for the rights and welfare of individual participants and the communities in which research is carried out. This
p.000001: respect and concern is manifest in requirements for informed consent, ensuring that risks are minimized and are
p.000001: reasonable in light of the importance of the research, and other requirements discussed in this document. Research must
p.000001: also be sensitive to issues of justice and fairness. This concern is manifest in choosing whose health needs
p.000001: are investigated; how risks, burdens, and anticipated benefits of individual studies are distributed; and who will
p.000001: have access to any resulting knowledge and interventions. These and other ethical aspects of research are discussed in
p.000001: the following guidelines and commentaries. The research protocol submitted for ethical review must include, when
p.000001: relevant, the items specified in Appendix I, and must be carefully followed in conducting the research.
p.000001:
p.000001: Dissemination of results of research. Dissemination is essential to achieving social value. The importance
p.000001: of disseminating scientific information, including negative findings, is discussed in Guideline 23 – Requirements
p.000001: for establishing research ethics committees and for their review of protocols.
p.000001:
p.000001:
p.000001: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000002: 2
p.000002:
p.000002:
p.000002:
p.000002:
p.000002:
p.000002: GUIDELINE 2:
p.000002: RESEARCH CONDUCTED IN LOW-RESOURCE SETTINGS
p.000002:
p.000002:
p.000002: Before instituting a plan to undertake research in a population or community in low-resource settings, the sponsor,
p.000002: researchers, and relevant public health authority must ensure that the research is responsive to the health needs or
p.000002: priorities of the communities or populations where the research will be conducted.
p.000002:
p.000002: As part of their obligation, sponsors, and researchers must also:
p.000002: f make every effort, in cooperation with government and other relevant stakeholders, to make available as soon
p.000002: as possible any intervention or product developed, and knowledge generated, for the population or community in
...
p.000003: include representatives in the community or country, including, where appropriate, the national government, the health
p.000003: ministry, local health authorities, relevant scientific and ethics groups, as well as members of the communities from
p.000003: which persons are drawn, patent-holders if they are other than the sponsor, and nongovernmental organizations such as
p.000003: health advocacy groups. The negotiation must address the health-care infrastructure required for safe and
p.000003: appropriate use of any intervention or product developed. When applicable, it must also consider the likelihood and
p.000003: conditions of authorization for distribution, and decisions regarding payments, royalties, subsidies, technology and
p.000003: intellectual property, as well as distribution costs, when such information is not proprietary. A plan to ensure the
p.000003: availability and distribution of successful products can require engaging with international organizations, donor
p.000003: governments and bilateral agencies, civil society organizations, and the private sector. The ability of the local
p.000003: health- care infrastructure to be able to provide the intervention must be facilitated at the outset so that delivery
p.000003: is possible following the completion of the research.
p.000003:
p.000003: Post-trial availability for communities and populations. Even if research addresses a question that has social value
p.000003: for the community or population where it is carried out, the community or population will not benefit from
p.000003: successful research unless the knowledge and interventions that it produces are made available to them and products are
p.000003: reasonably priced. Post-trial access plans are of particular concern for research conducted in low-resource settings
p.000003: where governments lack the means or infrastructure to make such products widely available.
p.000003:
p.000003: An investigational drug is unlikely to be generally available to the community or population until
p.000003: sometime after the conclusion of the study, as it may be in short supply, and in most cases could not be made generally
p.000003: available before a drug regulatory authority has approved it. However, other successful outcomes of research that
p.000003: do not require approval by a regulatory agency should be implemented as soon as feasible. An example is the
p.000003: introduction of male circumcision in countries with a high burden of HIV disease. Research demonstrated a significant
p.000003: preventive effect of male circumcision, following which, programmes to offer male circumcision were introduced in
p.000003: several countries.
p.000003:
p.000003: When the outcome is scientific knowledge rather than a commercial product, complex planning or negotiation among
p.000003: relevant stakeholders may not be needed. There must be assurance, however, that the scientific knowledge gained will be
p.000003: distributed and available for the benefit of the population. To that end, agreement must be reached with the local
p.000003: community about the form such dissemination
p.000003:
p.000003:
p.000003: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000004: 4
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
...
p.000004: to raise questions or concerns, and helps to build trust between the community and researchers (see Guideline 7 –
p.000004: Community engagement).
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: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000005: 5
p.000005:
p.000005:
p.000005:
p.000005:
p.000005:
p.000005: GUIDELINE 3:
p.000005: EQUITABLE DISTRIBUTION OF BENEFITS AND BURDENS IN THE SELECTION OF INDIVIDUALS AND
p.000005: GROUPS OF PARTICIPANTS IN RESEARCH
p.000005:
p.000005: Sponsors, researchers, governmental authorities, research ethics committees and other stakeholders must ensure that the
p.000005: benefits and burdens of research are equitably distributed. Groups, communities and individuals invited to participate
p.000005: in research must be selected for scientific reasons and not because they are easy to recruit because of their
p.000005: compromised social or economic position or their ease of manipulation. Because categorical exclusion from research
p.000005: can result in or exacerbate health disparities, the exclusion of groups in need of special protection must
p.000005: be justified. Groups that are unlikely to benefit from any knowledge gained from the research should not bear a
p.000005: disproportionate share of the risks and burdens of research participation. Groups that are under-represented
p.000005: in medical research should be provided appropriate access to participate.
p.000005:
p.000005:
p.000005: Commentary on Guideline 3
p.000005: General considerations. The equitable distribution of benefits and burdens in the selection of study
p.000005: populations requires that the benefits of research be distributed fairly and that no group or class of persons bears
p.000005: more than its fair share of the risks or burdens from research participation. When benefits or burdens of research are
p.000005: to be apportioned unequally among individuals or groups, the criteria for unequal distribution should be scientifically
p.000005: and ethically justified rather than arbitrarily or conveniently chosen. Situations where unequal distribution of
p.000005: benefits would be considered are those in which the research particularly affects the population under study.
p.000005: In general, equitable distribution requires that participants be drawn from the qualifying population in the
p.000005: geographic area of the study where the results can be applied (see Guideline 2 – Research conducted in low-resource
p.000005: settings). Inclusion and exclusion criteria should not be based upon potentially discriminatory criteria, such as race,
p.000005: ethnicity, economic status, age or sex, unless there is a sound ethical or scientific reason to do so. For example, in
p.000005: cases where the under-representation of particular groups results in or perpetuates health disparities, equity may
p.000005: require special efforts to include members of those populations in research (see Guideline 17 – Research involving
p.000005: children and adolescents, Guideline 18
...
p.000007: marginalized individuals or groups to participate in research because this concentrates the risks and burdens of
p.000007: research on people who already experience increased risks and burdens from social and economic disadvantage. Second,
p.000007: these individuals and groups are also the most likely to be excluded from, or to have difficulty accessing, the
p.000007: benefits of research. Third, the broad inclusion of different social groups helps to ensure that research is conducted
p.000007: in a socially and ethically acceptable manner. When research is concentrated in disadvantaged or marginalized groups,
p.000007: it may be easier to expose participants to unreasonable risks or undignified treatment. Furthermore, research results
p.000007: obtained from disadvantaged populations may not be appropriately extrapolated to the general population.
p.000007:
p.000007: In the past, certain groups have been over-used as research subjects. In some cases, this has been based on the easy
p.000007: availability of the populations. For example, in the United States prisoners were considered ideal persons for Phase I
p.000007: drug studies in the past. Other populations that may be over- represented in research because of their easy
p.000007: availability include students in researchers’ classes, residents of long-term care facilities and subordinate members
p.000007: of hierarchical organizations. In other cases, impoverished groups have been over-used because of their willingness to
p.000007: serve as subjects in exchange for relatively small stipends, their desire to access medical care, or because research
p.000007: hospitals are often located in places where members of the lowest socio-economic classes reside.
p.000007:
p.000007: Not only may certain groups within a society be inappropriately over-used as research participants, but also entire
p.000007: communities or societies may be over-used. Such over-use is especially problematic when the populations or communities
p.000007: concerned bear the burdens of participation in research but are unlikely to enjoy the benefits of new knowledge and
p.000007: products developed as a result of the research.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000008: 8
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: GUIDELINE 4:
p.000008: POTENTIAL INDIVIDUAL BENEFITS AND RISKS OF RESEARCH
p.000008:
p.000008: To justify imposing any research risks on participants in health research, the research must have social
p.000008: and scientific value. Before inviting potential participants to join a study, the researcher, sponsor and the
p.000008: research ethics committee must ensure that risks to participants are minimized and appropriately balanced in
p.000008: relation to the prospect of potential individual benefit and the social and scientific value of the research.
p.000008:
p.000008: The potential individual benefits and risks of research must be evaluated in a two-step process. First,
p.000008: the potential individual benefits and risks of each individual research intervention or procedure in the study
p.000008: must be evaluated.
...
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000019: 19
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: GUIDELINE 6:
p.000019: CARING FOR PARTICIPANTS’ HEALTH NEEDS
p.000019:
p.000019: Especially in the context of clinical trials, researchers and sponsors must make adequate provisions for addressing
p.000019: participants’ health needs during research and, if necessary, for the transition of participants to care when
p.000019: the research is concluded. The obligation to care for participants’ health needs is influenced, among other
p.000019: things, by the extent to which participants need assistance and established effective care is available locally.
p.000019:
p.000019: When participants’ health needs during and after research cannot be met by the local health
p.000019: infrastructure or the participant’s pre-existing health insurance, the researcher and sponsor must make
p.000019: prior arrangements for adequate care for participants with local health authorities, members of the
p.000019: communities from which persons are drawn, or nongovernmental organizations such as health advocacy groups.
p.000019:
p.000019: Addressing participants’ health needs requires at least that researchers and sponsors make plans for:
p.000019: f how care will be adequately provided for the condition under study;
p.000019: f how care will be provided during the research when researchers discover conditions other than those under study
p.000019: (“ancillary care”);
p.000019: f transitioning participants who continue to need care or preventive measures after the research to appropriate
p.000019: health services;
p.000019: f providing continued access to study interventions that have demonstrated significant benefit; and
p.000019: f consulting with other relevant stakeholders, if any, to determine everyone’s responsibilities and the conditions
p.000019: under which participants will receive continued access to a study intervention, such as an investigational drug, that
p.000019: has demonstrated significant benefit in the study.
p.000019:
p.000019: When access is provided after the research to investigational interventions that have demonstrated
p.000019: significant benefit, the provision may end as soon as the study intervention is made available through the local
p.000019: public health-care system or after a predetermined period of time that the sponsors, researchers and
p.000019: community members have agreed before the start of a trial.
p.000019:
p.000019: Information on care for participants’ health needs during and after the research must be included in the informed
p.000019: consent process.
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019:
p.000019: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000021: 21
p.000021:
p.000021:
p.000021:
p.000021:
p.000021:
p.000021: Commentary on Guideline 6
p.000021: General considerations. It is generally inappropriate to require researchers or sponsors to take on the role of a
p.000021: country’s health systems. Nevertheless, research with humans often involves interactions that enable researchers to
p.000021: detect or diagnose health problems during recruitment and the conduct of research. Similarly, clinical research
p.000021: often involves care and preventive measures in addition to the experimental interventions. In some cases,
p.000021: participants may continue to need the care or prevention provided during the research after their participation
p.000021: in the study has ended. This may include access to an investigational intervention that has demonstrated
p.000021: significant benefit. In all these situations, researchers and sponsors must show care and concern for the health and
p.000021: welfare of study participants. This is justified by the principle of beneficence, which requires researchers and
p.000021: sponsors to safeguard the health of participants when it is in their power to do so. It is also supported by the
p.000021: principle of reciprocity; participants assist researchers in generating valuable data and, in return,
p.000021: researchers should ensure that participants receive needed care or preventive measures to safeguard their health.
p.000021: Importantly, the obligation to care for participants’ health needs is not limited to research in countries with limited
p.000021: resources (see Guideline 2 – Research conducted in low-resource settings) but is a universal ethical requirement in
p.000021: research. Furthermore, even though the provision of care during and after the trial may be an incentive for people in
p.000021: low-resource settings to enrol, it should not be considered an undue influence.
p.000021:
p.000021: Ancillary care. Sponsors are, in general, not obliged to finance interventions or to provide health-care services
p.000021: beyond that which is necessary for the safe and ethical conduct of research. Nevertheless, when prospective
p.000021: participants cannot be enrolled in a study because they do not meet the inclusion criteria, or enrolled participants
p.000021: are found to have diseases unrelated to the research, researchers should advise them to obtain or refer them for
p.000021: medical care. In some circumstances, it may be relatively easy for researchers to treat the condition or refer
...
p.000021: treat the condition effectively, and appropriate treatment may not be available locally as part of the public health
p.000021: system. How to provide ancillary care in this situation is a complex issue and decisions will need to be made on a
p.000021: case-by-case basis following discussion with research ethics committees, clinicians, researchers and
p.000021: representatives of government and health authorities in the host country. Accordingly, before research begins agreement
p.000021: must be reached on how to provide care to participants who already have, or who develop, diseases or conditions other
p.000021: than those being studied (for example, whether care will be provided for health conditions that are readily treated in
p.000021: the local health-care system).
p.000021:
p.000021: Transition to care or preventive measures after research. Because gaps in care and prevention can have significant
p.000021: impact on the welfare of participants, researchers and sponsors must make arrangements to transition participants to
p.000021: health care after the research has ended. At a minimum, researchers must link participants in need of continued medical
p.000021: attention to an appropriate health service at the end of their participation in the study and communicate
p.000021: relevant information to the health service. The researchers themselves might continue to provide follow-up
p.000021: for a certain period of time, possibly for research purposes, and then transfer care to an appropriate provider. The
p.000021: obligation to provide transition to care following the research applies to both participants in the control arm and the
p.000021: intervention arm.
p.000021:
p.000021: Continued access to beneficial interventions. As part of their obligation to transition to care after research,
p.000021: researchers and sponsors may have to provide continued access to interventions that have demonstrated significant
p.000021: benefit in the study or to established effective interventions that were provided as part of the
p.000021: standard of care or prevention to all participants during the research. Access should also be provided, when
p.000021: pertinent, in the interval between the end of the individual’s participation and the end of the study. In this
p.000021: situation, access could be arranged by an extension study or by compassionate use. This obligation depends on several
p.000021: factors. For example, if discontinuing an intervention will deprive participants of basic capabilities, such as the
p.000021: ability to
p.000021:
p.000021:
p.000021: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000022: 22
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: communicate or function independently, or significantly reduce a quality of life they had attained during
p.000022: the study, then the obligation will be greater than if the intervention provides relief for a minor or
p.000022: transient condition. Similarly, the obligation will be greater when participants are not able to access the needed care
p.000022: or prevention within the local health system than in cases where this is readily available. The obligation may also be
p.000022: greater when there are no available alternatives with clinical effectiveness similar to the intervention that
p.000022: has demonstrated significant benefit than in cases where such alternatives exist. However, the obligation
p.000022: may not be able to be completely met if the total number of qualifying individuals is very large.
p.000022: Continued access to interventions that have demonstrated significant benefit but await regulatory approval should be
p.000022: consistent with the relevant regulatory requirements for pre-licensure access and should not delay the process of
p.000022: obtaining regulatory approval.
p.000022:
p.000022: Providing continued access to a beneficial study intervention can create several dilemmas:
p.000022: f In the case of blinded controlled trials, it may take time to unblind the results and find out who has received
p.000022: which intervention. Researchers and sponsors should make provisions for this transition period and inform
p.000022: participants if they will be temporarily receiving the current standard of care before the study intervention can be
p.000022: administered.
p.000022: f A research ethics committee may discuss whether researchers and sponsors are under an obligation to
p.000022: provide participants with continued access to the experimental intervention in a non-inferiority trial. When
p.000022: the tested intervention is not inferior to the standard of care, there is no obligation to provide participants with
p.000022: the tested intervention.
p.000022:
p.000022: As stated in this Guideline, sponsors and researchers may no longer have an obligation to provide continued access to
p.000022: a study intervention that has demonstrated significant benefit when the intervention becomes available in the
p.000022: public health system. Moreover, sponsors, researchers and community members may agree before a trial starts that any
p.000022: intervention that has demonstrated significant benefit will be provided only for a predetermined period of time.
p.000022:
p.000022: Consultation with relevant stakeholders. The obligation to care for participants’ health needs rests with the
p.000022: researcher and the sponsor. However, the delivery of care may involve other parties, for example, local health
p.000022: authorities, insurance companies, members of the communities from which participants are drawn, or
p.000022: nongovernmental organizations such as health advocacy groups. Researchers and sponsors must describe their provisions
p.000022: for continued care in the study protocol and show that any other parties involved in continued care have agreed to the
p.000022: plan. Research ethics committees must determine whether the arrangements for continued care are adequate.
p.000022:
p.000022: Decisions on how to fulfil the obligation to provide transition to care are best made for each study through a
p.000022: transparent and participatory process that involves all relevant stakeholders before the study begins (see Guideline 7
p.000022: – Community engagement). This process must explore options and determine the core obligations in the particular
p.000022: situation with regard to the level, scope, and duration of any post-trial care and treatment package; equitable access
p.000022: to services; and the responsibility for provision of services. Agreements on who will finance, deliver, and monitor
p.000022: care and treatment must be documented.
p.000022:
p.000022: Information to participants. Participants must be informed before the trial how the transition to care
p.000022: after research is arranged and to what extent they will be able to receive beneficial study interventions post-trial.
p.000022: Participants who receive continued access before regulatory approval must be informed about the risks of receiving
p.000022: unregistered interventions. When participants are informed about the extent of ancillary care, if any, to be provided,
p.000022: this information should be clearly separated from information about the study interventions and research procedures.
p.000022:
p.000022: Access to study interventions for communities. Obligations to provide beneficial post-trial interventions to
p.000022: communities are discussed in Guideline 2 – Research conducted in low-resource settings.
p.000022:
p.000022: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000023: 23
p.000023:
p.000023:
p.000023:
p.000023:
p.000023:
p.000023: GUIDELINE 7:
p.000023: COMMUNITY ENGAGEMENT
p.000023:
p.000023: Researchers, sponsors, health authorities and relevant institutions should engage potential participants and
p.000023: communities in a meaningful participatory process that involves them in an early and sustained manner in
p.000023: the design, development, implementation, design of the informed consent process and monitoring of research,
p.000023: and in the dissemination of its results.
p.000023:
p.000023:
p.000023: Commentary on Guideline 7
p.000023: General considerations. Proactive and sustained engagement with the communities from which participants will be invited
p.000023: to participate is a way of showing respect for them and the traditions and norms that they share. Community engagement
p.000023: is also valuable for the contribution it can make to the successful conduct of research. In particular, community
p.000023: engagement is a means of ensuring the relevance of proposed research to the affected community, as well as
p.000023: its acceptance by the community. In addition, active community involvement helps to ensure the ethical and social
p.000023: value and outcome of proposed research. Community engagement is especially important when the research
p.000023: involves minorities or marginalized groups, including persons with stigmatizing diseases such as HIV, in order to
...
p.000029: collaboration and before even beginning a specific research project: i) determine the local research agenda; ii)
p.000029: determine capacity needs or priorities assessment amongst partners of international health research; and iii) create a
p.000029: Memorandum of Understanding (MoU).
p.000029:
p.000029: Collaborative partnership also helps to ensure the social value of research by engaging the communities, thereby
p.000029: focusing on research the community considers valuable (see Guideline 1 – Scientific and social value and respect for
p.000029: rights, and Guideline 7 – Community engagement).
p.000029:
p.000029: Strengthening research capacity. The specific capacity-building objectives should be determined and achieved through
p.000029: dialogue and negotiation among the sponsor, researchers and other relevant stakeholders, such as community boards and
p.000029: host-country authorities. These stakeholders should agree on joint efforts to strengthen research capacity as a
p.000029: component of the country’s health system, and optimize its sustainability for further generation of new knowledge.
p.000029: Local principal investigators should be involved in the research project.
p.000029:
p.000029: Capacity-building and conflicts of interest. Capacity-building may give rise to conflicts of interests. The
p.000029: following interests may conflict: the desire of the sponsor to conduct the research; the wishes of potential
p.000029: participants regarding their enrolment; the desire of investigators to access the latest medications for their patients
p.000029: and contribute to knowledge; and the commitment of local community leaders to compensate for inadequate research
p.000029: funding by bringing in sponsored research to build their infrastructure. Research ethics committees should evaluate
p.000029: whether capacity-building efforts may involve such conflicts of interests and seek ways to mitigate them (see Guideline
p.000029: 25 – Conflicts of interest).
p.000029:
p.000029: Strengthening ethical review. Researchers and sponsors who plan to perform research in settings where research ethics
p.000029: committees are absent or lack adequate training should help to establish such committees, to the extent
p.000029: reasonably possible, before the research is initiated and make provisions for their education in research
p.000029: ethics. To avoid conflicts of interest and safeguard the independence of review committees, financial
p.000029: assistance from researchers and sponsors must not be provided directly and must never be tied to the committee’s
p.000029: decision about specific protocols (see Guideline 25 – Conflicts of interest). Rather, funds must be made
p.000029: available specifically for research ethics capacity-building. It is in everyone’s interest to have truly independent
p.000029: scientific and ethical review.
p.000029:
p.000029: Education of research personnel. Sponsors are expected to employ and, if necessary, educate individuals to function
p.000029: as researchers, research assistants and coordinators and data managers, for example, and to provide, as
p.000029: necessary, reasonable amounts of financial, educational and other assistance for capacity-building.
p.000029:
p.000029: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030: Joint publication and data sharing. Collaborative research should lead to jointly (external and in-country)
p.000030: authored, open-access publications (see Guideline 24 – Public accountability for health- related research). Researchers
p.000030: and sponsors must provide fair opportunities to enable joint authorship consistent with recognized authorship
p.000030: requirements, such as those of the International Committee of Medical Journal Editors (ICMJE).
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
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p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: GUIDELINE 9:
p.000031: INDIVIDUALS CAPABLE OF GIVING INFORMED CONSENT
p.000031:
p.000031: Researchers have a duty to provide potential research participants with the information and the opportunity to give
p.000031: their free and informed consent to participate in research, or to decline to do so, unless a research ethics committee
p.000031: has approved a waiver or modification of informed consent (see Guideline 10 – Modifications and waivers of informed
...
p.000033: ritual recitation of the contents of a written document. The wording of the leaflet and any recruitment material
p.000033: must be in language understandable by the potential participant and be approved by the research ethics
p.000033: committee. The wording of the leaflet must be short and preferably not exceed two or three pages. An oral presentation
p.000033: of information or the use of appropriate audiovisual aids, including pictographs and summary tables, are important to
p.000033: supplement written information documents to aid understanding. Information should also be appropriate for the
p.000033: participant group and specific individual, for example, in braille. Informed consent shall not include any language
p.000033: through which the subject is made to waive or appear to waive any of the participant’s legal rights, or releases or
p.000033: appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.
p.000033:
p.000033: Contents of the information leaflet. Throughout these Guidelines, elements that need to be included in the
p.000033: information leaflet are specified. Appendix 2 contains the details of information that must be provided, as well
p.000033: as possible supplementary information. This list mentions, but is not limited to, information about the aims,
p.000033: methods, sources of funding, possible conflicts of interest, institutional affiliations of the researcher, the
p.000033: anticipated benefits and potential risks of the study and the discomfort it may entail, post-trial access and
p.000033: any other relevant aspects of the study.
p.000033:
p.000033: Comprehension. The person obtaining consent must ensure that the potential participant has adequately
p.000033: understood the information provided. Researchers should use evidence-based methods for imparting information to ensure
p.000033: comprehension. The potential participant’s ability to understand the information depends, among other things, on the
p.000033: individual’s maturity, educational level and belief system. The participant’s understanding also depends on the
p.000033: researcher’s ability and willingness to communicate with patience and sensitivity, as well as the atmosphere, situation
p.000033: and location where the informed consent process takes place.
p.000033:
p.000033: Documentation of consent. Consent may be indicated in a number of ways. The participant may express consent orally, or
p.000033: sign a consent form. As a general rule, the participant should sign a consent form, or, where the individual lacks
p.000033: decisional capacity, a legal guardian or other duly authorized
p.000033:
p.000033:
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p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
...
p.000034: information is complicated, participants should be given information sheets to retain; these may resemble
p.000034: conventional sheets in all respects except that participants are not required to sign them. Their wording
p.000034: must be approved by the research ethics committee. When consent has been obtained orally, researchers
p.000034: should provide to the research ethics committee documentation of consent, certified either by the person
p.000034: obtaining consent or by a witness at the time consent is obtained.
p.000034:
p.000034: Renewing consent. When substantive changes occur in any aspect of a study, the researcher must again seek
p.000034: informed consent from the participants. For example, new information may have come to light, either from the study
p.000034: itself or other sources, about the risks or benefits of products being tested or about alternatives to them.
p.000034: Participants must be given such information promptly. In most clinical trials, interim results are not disclosed to
p.000034: researchers or participants until the study has been concluded. In long-term studies, the willingness of each
p.000034: participant to continue in the study must be ensured.
p.000034:
p.000034: Individual informed consent and access to research populations. In some circumstances, a researcher may
p.000034: enter a community or institution to conduct research or approach potential participants for their individual
p.000034: consent only after obtaining permission from an institution such as a school or a prison, or from a community leader, a
p.000034: council of elders, or another designated authority. Such institutional procedures or cultural customs should be
p.000034: respected. In no case, however, may the permission of a community leader or other authority substitute for individual
p.000034: informed consent. In some populations, the use of local languages may facilitate the communication of information to
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
...
p.000035: those risks. This is especially true of preventive research on communicable diseases, such as HIV/AIDS.
p.000035:
p.000035: Who obtains consent. Informed consent must be obtained by a member of the research team. Delegation of obtaining
p.000035: consent, for instance to a research nurse or another member of the research team, for instance in the case of a
p.000035: dependent relationship, is permissible as long as the person who obtains consent is duly qualified and has
p.000035: prior experience in obtaining consent. The principal investigator is responsible for ensuring that all personnel
p.000035: working on the project comply with this Guideline.
p.000035:
p.000035: Special considerations regarding informed consent for the use of data in health registries. The requirement to obtain
p.000035: informed consent for research on data in health-related registries may be waived, provided the conditions in Guideline
p.000035: 10 – Modifications and waivers of informed consent - are met. When a researcher plans to contact persons based on their
p.000035: inclusion in a health-related registry, the researcher must bear in mind that these persons may be unaware that their
p.000035: data were submitted to the registry or unfamiliar with the process by which researchers obtain access to the data (see
p.000035: Guideline 12 – Collection, storage and use of data in health-related research). If researchers wish to contact persons
p.000035: included in a health registry to obtain additional information from them for new research, such studies require
p.000035: informed consent.
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
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p.000035: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036: GUIDELINE 10:
p.000036: MODIFICATIONS AND WAIVERS OF INFORMED CONSENT
p.000036:
p.000036: Researchers must not initiate research involving humans without obtaining each participant’s individual informed
p.000036: consent or that of a legally authorized representative, unless researchers have received explicit approval to do so
p.000036: from a research ethics committee. Before a waiver of informed consent is granted, researchers and research
p.000036: ethics committees should first seek to establish whether informed consent could be modified in a way
p.000036: that would preserve the participant’s ability to understand the general nature of the investigation and to
p.000036: decide whether to participate.
p.000036:
...
p.000038: other anomalies in newborn babies) provide a major resource for many public health and epidemiological research
p.000038: activities, ranging from disease prevention to resource allocation. Several considerations support the common practice
p.000038: of requiring that all practitioners submit relevant data to such registries: the importance of having
p.000038: comprehensive and accurate information about an entire population; the scientific need to include all
p.000038: cases in order to avoid undetectable selection bias; and the ethical principle that burdens and benefits must be
p.000038: distributed equitably across the population. Hence, registries established as mandatory by governmental
p.000038: authorities usually involve obligatory rather than voluntary collection of data.
p.000038:
p.000038: When a study is performed under a public health mandate or by public health authorities, such as disease surveillance,
p.000038: normally neither ethical review nor a waiver of consent is needed because the activity is mandated by law. At the same
p.000038: time, consent cannot be waived when public health authorities conduct studies in which data in the registries are
p.000038: combined with new activities that involve direct contact with persons, such as studies in which they obtain
p.000038: information from individuals by using questionnaires. Although the extent and limits of data collection are
p.000038: determined by law, researchers must still consider whether, in a given case, it is ethical to use their authority to
p.000038: access personal data for research purposes. When the use of such data does not constitute (or no longer clearly
p.000038: constitutes) a public health activity, the researcher must seek individual consent for the use of the data or
p.000038: demonstrate that the research meets the conditions for waiving informed consent, as set out in this Guideline. Research
p.000038: projects using data from one or more mandatory population-based registries should be submitted to a research ethics
p.000038: committee, except for data analyses involving internal institutional activity of a registry.
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
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p.000038: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: GUIDELINE 11:
p.000039: COLLECTION, STORAGE AND USE OF BIOLOGICAL MATERIALS AND RELATED DATA
p.000039:
p.000039: When biological materials and related data, such as health or employment records, are collected and stored,
p.000039: institutions must have a governance system to obtain authorization for future use of these materials in research.
p.000039: Researchers must not adversely affect the rights and welfare of individuals from whom the materials were collected.
p.000039:
...
p.000039: are stored for future research, a specific or broad informed consent may be used or may be substituted by an
p.000039: informed opt-out procedure. This means that the material is stored and used for research unless the
p.000039: person from whom it originates explicitly objects. The informed opt-out procedure must fulfil the
p.000039: following conditions:
p.000039: 1) patients need to be aware of its existence; 2) sufficient information needs to be provided;
p.000039: 3) patients need to be told that they can withdraw their data; and 4) a genuine possibility to object has to be
p.000039: offered.
p.000039:
p.000039: When researchers seek to use stored materials collected for past research, clinical or other purposes
p.000039: without having obtained informed consent for their future use for research, the research ethics committee may waive the
p.000039: requirement of individual informed consent if:
p.000039: 1) the research would not be feasible or practicable to carry out without the waiver; 2) the research has important
p.000039: social value; and 3) the research poses no more than minimal risks to participants or to the group to which
p.000039: the participant belongs.
p.000039:
p.000039: Custodians of biological materials must arrange to protect the confidentiality of the information linked
p.000039: to the material, by sharing only anonymized or coded data with researchers, and limiting access to the
p.000039: material of third parties. The key to the code must remain with the custodian of the biological material.
p.000039:
p.000039: The transfer of biological materials must be covered by a Material Transfer Agreement (MTA).
p.000039:
p.000039: Biological materials and related data should only be collected and stored in collaboration with local health
p.000039: authorities. The governance structure of such collection should have representation of the original
p.000039: setting. If the specimen and data are stored outside the
p.000039:
p.000039:
p.000039: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000041: 41
p.000041:
p.000041:
p.000041:
p.000041:
p.000041:
p.000041: original setting, there should be provisions to return all materials to that setting and share possible results and
p.000041: benefits (see Guideline 3 – Equitable distribution of benefits and burdens in the selection of individuals and
p.000041: groups of participants in research, Guideline 7
p.000041: – Community engagement, and Guideline 8 – Collaborative partnership and capacity building for research and
p.000041: review).
p.000041:
p.000041:
p.000041: Commentary on Guideline 11
p.000041: General considerations. Research involving human biological materials may include: tissues, organs, blood,
p.000041: plasma, skin, serum, DNA, RNA, proteins, cells, hair, nail clippings, urine, saliva, or other bodily fluids.
p.000041: These biological materials may come from a variety of places but the materials will mostly come from patients following
p.000041: diagnostic or therapeutic procedures, autopsy specimens, and donations of organs or tissue from living or dead
...
p.000041: use by one of the mechanisms described in this Guideline. Since the precise nature of the research is
p.000041: typically unknown, it is impossible to obtain specific informed consent at the time the material is collected.
p.000041: Therefore, broad informed consent for future use is an acceptable alternative to specific informed consent.
p.000041: Broad informed consent requires proper governance and management of the biobank.
p.000041:
p.000041: Governance. Institutions in which biological material and related data are archived after collection for research
p.000041: purposes or as “left-overs” from clinical diagnosis or treatment must have a governance structure in place in which at
p.000041: least the following items are regulated:
p.000041: f to which legal entity the material is entrusted; f how authorization from the donor is obtained; f how the
p.000041: donor can retract this authorization;
p.000041: f in which circumstances donors need to be recontacted;
p.000041: f a procedure for determining whether unsolicited findings should be disclosed, and if so, how they should be
p.000041: managed;
p.000041: f how the quality of the material is controlled;
p.000041: f how confidentiality of the link between biological specimens and personal identifiers of the donors is maintained;
p.000041:
p.000041:
p.000041: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000042: 42
p.000042:
p.000042:
p.000042:
p.000042:
p.000042:
p.000042: f who may have access to the materials for future research, and under what circumstances;
p.000042: f which body may review research proposals for future use of the material;
p.000042: f appropriate mechanisms for keeping donors informed of research outcomes;
p.000042: f how participatory engagement with patient groups or the wider community is organized;
p.000042: f to which other sources of personal information the results of analyses on biological materials may be linked;
p.000042: f in broad terms, which types of research will be pursued;
p.000042: f which types of research will be excluded or included only after recontacting the donor for consent;
p.000042: f to whom any benefits from the research are expected to accrue;
p.000042: f appropriate mechanisms for keeping participants informed of research outcomes; and
p.000042: f how the rights and welfare of individuals from whom the materials were collected are not adversely
p.000042: affected.
p.000042:
p.000042: All governance systems should follow the principle of accountability and should maintain good stewardship
p.000042: of stored biological materials and related data. None of the regulations concerning the storage, use and final fate of
p.000042: biological samples should contradict or overrule conditions originally stated in (broad) informed consent documents and
p.000042: agreed to by research participants.
p.000042:
p.000042: Research ethics committees and biobanks. The protocol for every study using stored human biological materials and
...
p.000042: incapable of giving informed consent at the time their bodily material was stored must be given the opportunity to give
p.000042: informed consent or refusal if researchers know, or reasonably should have known that the subject has become capable of
p.000042: giving informed consent (see also Guideline 16 – Research involving adults incapable of giving informed consent).
p.000042:
p.000042: Broad informed consent. Broad informed consent encompasses the range of future uses in research for which
p.000042: consent is given. Broad informed consent is not blanket consent that would allow future use of bodily
p.000042: material without any restriction. On the contrary, broad informed consent places certain limitations on the future
p.000042: use of bodily materials. Broad informed consent forms should specify: the purpose of the biobank; the
p.000042: conditions and duration of storage; the rules of access to the biobank; the ways in which the donor can contact
p.000042: the biobank custodian and remain informed about future use; the foreseeable uses of the materials, whether limited to
p.000042: an already fully defined study or extending to a number of wholly or partially undefined studies; the intended goal of
p.000042: such use, whether only for basic or applied research , or also for commercial purposes; and the possibility of
p.000042: unsolicited findings and how they will be dealt with. The research ethics committee must ensure that the
p.000042: proposed collections, the storage protocol, and the consent procedure meet these specifications.
p.000042:
p.000042: Informed opt-out procedure for research on residual tissue. Given that human biological materials left over
p.000042: after clinical diagnosis or treatment (so-called “residual tissue”) are frequently of
p.000042:
p.000042: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000043: 43
p.000043:
p.000043:
p.000043:
p.000043:
p.000043:
p.000043: interest to future researchers, it is good clinical practice to offer donors several options: to have their materials
p.000043: used only for their own treatment or benefit and then discarded; to allow stored materials to be used for
p.000043: a specifically described research project (specific informed consent); or to allow stored materials to be used for yet
p.000043: undefined research, with or without personal identifiers. However, following this practice in every situation in health
p.000043: care may be overly demanding and difficult to implement; therefore, an informed opt-out procedure may be acceptable.
...
p.000043: without specific or broad informed consent contain important and otherwise unobtainable data, a research ethics
p.000043: committee needs to decide whether the use of such materials is justified. The most common justification for using
p.000043: records or materials collected in the past without consent is that it would be impracticable or prohibitively
p.000043: expensive to locate the persons whose materials or records are to be examined. For example, this may happen when
p.000043: the study involves review of hospital records or performing new tests on blood collected at a time when consent to
p.000043: future research uses of such materials was not usually sought. In addition, the research must have important social
p.000043: value, and the research must pose no more than minimal risks to participants or to the group from which the participant
p.000043: originates.
p.000043:
p.000043: Confidentiality. An important aspect of storing human biological material is confidentiality guaranteed to the donor.
p.000043: The information resulting from analysis of the material could, if disclosed to third parties, cause harm,
p.000043: stigma or distress. Those responsible for biobanks must arrange to protect the confidentiality of such information
p.000043: by, for example, providing only anonymized or coded data to researchers and limiting access of the material of
p.000043: third parties. During the process of obtaining informed consent, those responsible for the biobank must inform
p.000043: the potential donors about the safeguards that will be taken to protect confidentiality as well as their
p.000043: limitations. Biological material stored in biobanks must be anonymized or coded. When researchers use coded materials
p.000043: obtained from biobanks in later studies, the key to the code must remain with the custodian of the biobank. Thus
p.000043: researchers can use only anonymized or coded material. It should be acknowledged that the possibility of complete
p.000043: anonymization is becoming increasingly illusory as the possibility of cross- matching large datasets improves. The
p.000043: more difficult it becomes to anonymize data, the more important it will be to retain the ability to remove
p.000043: personal data from a dataset. This is a crucial part of the governance system specified above.
p.000043:
p.000043: Return of results and disclosure of (un)solicited findings. Generally, biobanks store coded material in
p.000043: order to be able to link this material to health data. This means that research findings,
p.000043:
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p.000043: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044: whether unsolicited or not, can be returned to the donor. The informed consent process must clearly stipulate whether
p.000044: return of information derived from analysis of the materials is foreseen, if the donor wishes. The information given to
...
p.000045: giving informed consent.
p.000045:
p.000045: When data are used that were collected in the context of routine clinical care, an informed opt-out procedure must
p.000045: be used. This means that the data may be stored and used for research unless a person explicitly objects.
p.000045: However, a person’s objection is not applicable when it is mandatory to include data in population-based registries.
p.000045: The informed opt-out procedure must fulfil the following conditions: 1) patients need to be aware of its existence;
p.000045: 2) sufficient information needs to be provided; 3) patients need to be informed that they can withdraw their data; and
p.000045: 4) a genuine possibility to object has to be offered.
p.000045:
p.000045: When researchers seek to use stored data collected for past research, clinical or other purposes without having
p.000045: obtained informed consent for their future use for research, the research ethics committee may consider to
p.000045: waive the requirement of individual informed consent if: 1) the research would not be feasible or practicable to carry
p.000045: out without the waiver; and 2) the research has important social value; and 3) the research poses no more
p.000045: than minimal risks to participants or to the group to which the participant belongs.
p.000045:
p.000045: Custodians of the data must arrange to protect the confidentiality of the information linked to the data, by
p.000045: sharing only anonymised or coded data with researchers, and limiting access to the material of third parties.
p.000045: The key to the code must remain with the custodian of the data.
p.000045:
p.000045: Data from low-resource settings should only be collected and stored in collaboration with local health
p.000045: authorities. The governance structure of such a databank must have representation of the original setting. If
p.000045: the collection is stored outside the original setting there should be provisions to return all data to that setting and
p.000045: share possible results and benefits (see Guideline 3 – Equitable distribution of benefits and burdens in the selection
p.000045: of individuals and groups of participants in research, Guideline 7 – Community engagement, and Guideline 8 –
p.000045: Collaborative partnership and capacity building for research and review).
p.000045:
p.000045:
p.000045:
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p.000047:
p.000047:
p.000047:
p.000047:
p.000047:
p.000047: Commentary on Guideline 12
p.000047: General considerations. The value of data collections for longitudinal studies of specific diseases is widely
p.000047: recognized. Databanks may include all types of health-related data, including medical records, and patient
p.000047: health records. This Guideline is intended to cover health-related data beyond the individual care of patients.
p.000047:
p.000047: As with biobanks, the vast majority of people do not object to their data being stored in collections and used for
p.000047: research for the common good. The person whose data are stored (the donor) must, in principle, explicitly authorize
p.000047: future use by one of the mechanisms described in this Guideline. Since the precise nature of the
p.000047: research is typically unknown, it is impossible to obtain specific informed consent at the time the data are
p.000047: collected. Therefore, broad informed consent for future use is an acceptable alternative to specific informed
p.000047: consent. Broad informed consent requires proper governance and management of the databank.
p.000047:
p.000047: Governance. Institutions where data are collected and archived must have a governance structure in place in which at
p.000047: least the following items are regulated:
p.000047: f to which legal entity the material is entrusted; f how authorization from the donor is obtained; f how the
p.000047: donor can retract this authorization;
p.000047: f in which circumstances donors need to be recontacted;
p.000047: f a procedure for determining whether unsolicited findings should be disclosed, and if so, how they should be
p.000047: managed;
p.000047: f how the quality of the data collection is controlled;
p.000047: f how confidentiality of the link between collected data and personal identifiers of the donors is maintained;
p.000047: f who may have access to the data for future research, and under what circumstances;
p.000047: f which body may review research proposals for future use of the data;
p.000047: f appropriate mechanisms for keeping donors informed of research outcomes;
p.000047: f how participatory engagement with patient groups or the wider community is organized;
p.000047: f to which other sources of personal information the results of analyses with data may be linked;
p.000047: f in broad terms, which types of research will be pursued;
p.000047: f which types of research will be excluded or included only after recontacting the donor for consent;
p.000047: f to whom any benefits from the research are expected to accrue;
p.000047: f appropriate mechanisms for keeping participants informed of research outcomes; and
p.000047: f how the rights and welfare of individuals from whom the data were collected are not adversely affected.
p.000047:
p.000047: All governance systems should follow the principle of accountability and should maintain good stewardship
p.000047: of stored data. None of the regulations concerning the storage, use and final fate of health-related data should
p.000047: contradict or overrule conditions originally stated in (broad) informed consent documents and agreed to by
p.000047: research participants.
p.000047:
p.000047:
p.000047:
p.000047:
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p.000048:
p.000048:
p.000048:
p.000048:
p.000048:
p.000048: Research ethics committees and storing health-related data. The protocol for every study using collected data
...
p.000048:
p.000048: Specific informed consent. When the future use in research of the collected data is known at the time
p.000048: of collection, specific informed consent must be obtained as described in Guideline 9 – Individuals
p.000048: capable of giving informed consent. Persons who were incapable of giving informed consent at the time their
p.000048: data were stored must be given the opportunity to give informed consent or refusal if researchers know, or
p.000048: reasonably should have known, that the subject has become capable of giving informed consent (see also
p.000048: Guideline 16 – Research involving adults incapable of giving informed consent).
p.000048:
p.000048: Broad informed consent. Broad informed consent encompasses the range of future uses in research for which
p.000048: consent is given (see Guideline 11 – Collection, storage and use of biological materials and related data). Broad
p.000048: informed consent should specify: the purpose of the databank; the conditions and duration of storage; the rules of
p.000048: access to the databank, the ways in which the donor can contact the databank custodian and remain informed about future
p.000048: use; the foreseeable uses of the data, whether limited to an already fully defined study or extending to a number of
p.000048: wholly or partially undefined studies; who will manage access to the data; the foreseeable uses of the
p.000048: data, whether limited to an already fully defined study or extending to a number of wholly or partially undefined
p.000048: studies; the intended goal of such use, whether only for basic or applied research, or also for commercial purposes;
p.000048: and the possibility of unsolicited findings and how they will be dealt with. The research ethics committee must ensure
p.000048: that the proposed collections, the storage protocol, and the consent procedure meet these specifications.
p.000048:
p.000048: Informed opt-out procedure for research with health-related data. In the absence of broad informed consent, an informed
p.000048: opt-out consent procedure can be used. This means that the data are stored and used for research unless a person from
p.000048: whom the data originate explicitly objects. The informed opt-out procedure has to fulfil the following conditions: 1)
p.000048: patients need to be aware of its existence; 2) sufficient information needs to be provided; 3) patients
p.000048: need to be informed that they can withdraw their data; and 4) a genuine possibility to object has to be offered.
p.000048: However, in certain circumstances the researcher must obtain explicit informed consent, whether specific or
p.000048: broad: 1) when the research involves more than minimal risks to the individual; or 2) when controversial
p.000048: or high-impact techniques are used; or 3) when research is conducted in contexts of heightened vulnerability. A
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p.000049: the past without consent is that it would be impracticable or prohibitively expensive to locate the persons whose data
p.000049: are to be examined. This may happen when, for instance, the study involves reviewing hospital records from a time when
p.000049: consent to future research uses of such data was not usually sought. In addition, the research must have important
p.000049: social value, and the research must pose no more than minimal risks to participants or to the group from which the
p.000049: participant originates.
p.000049:
p.000049: Re-contacting participants. Long-term projects often include plans to search for and re-contact participants who have
p.000049: been lost to follow-up. Such outreach might also occur when researchers wish to obtain consent for a new use of stored
p.000049: biological material or data that still has personal identifiers. Participants or service users must be made aware of
p.000049: this possibility at the time of initial consent and given the choice to opt-out of being re-contacted. Researchers must
p.000049: also establish acceptable modalities for establishing contact with those participants or service users who
p.000049: are willing to be reached out to for the above-mentioned purposes.
p.000049:
p.000049: In cases where a researcher does plan to contact persons based on their inclusion in a health-related registry, the
p.000049: researcher must bear in mind that these persons may be unaware that their data were submitted to the registry or
p.000049: unfamiliar with the process by which researchers obtain access to the data. If researchers wish to
p.000049: contact persons included in a health registry to obtain additional information from them for new
p.000049: research, such studies require individual informed consent (see Guideline 9 – Individuals capable of giving
p.000049: informed consent).
p.000049:
p.000049: Data mining. Some entities collect data that may be “mined” for health-related research, even if they are not
p.000049: collecting health-related data deliberately (for example, queries in search engines, consumer choices on websites).
p.000049: Such entities must strive for governance structures and mechanisms to obtain authorization for future use of these data
p.000049: in research as discussed in this Guideline.
p.000049:
p.000049: Confidentiality. Health-related data may contain a very large range of information. Therefore, an important
p.000049: aspect of storing health-related data is confidentiality. The collection and storage of information could, if disclosed
p.000049: to third parties, cause harm, stigma or distress. Those responsible for databanks must arrange to protect the
p.000049: confidentiality of such information by, for example, providing only anonymized or coded data to
p.000049: researchers and limiting access of the data to third parties. During the process of obtaining informed consent,
p.000049: those responsible for the databank must inform the potential donors about the safeguards that will be taken to protect
p.000049: confidentiality as well as their limitations. Data stored in databanks must be anonymized or coded. When
p.000049: researchers use coded materials obtained from databanks in later studies, the key to the code must
p.000049: remain with the custodian of the databank. Thus researchers can only use anonymized or coded material. It should be
p.000049: acknowledged that the possibility of complete anonymization is becoming increasingly illusory as the possibility of
p.000049: cross-matching large datasets improves. The more difficult it becomes to anonymize data, the more important it will be
p.000049: to retain the ability to remove personal data from a dataset. This is a crucial part of the governance system specified
p.000049: above.
p.000049:
p.000049: When linked data are used, researchers customarily discard personal identifying information when consolidating data for
p.000049: purposes of statistical analysis; this also occurs when researchers have linked (or coded) different sets of data
p.000049: regarding individuals with the consent of individual participants. When project plans require personal
p.000049: identifiers to remain on records used for a study, researchers must explain to research ethics committees why
p.000049: this is necessary and how confidentiality will be
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p.000050: strict confidentiality and of the potential adverse consequences of breaches of confidentiality. Confidentiality is
p.000050: limited for three reasons. First, even with good governance structures, there is some background risk that data are
p.000050: leaked or stolen and thus are obtained by unauthorized third parties. Second, data from different sources (for example,
p.000050: health records, employment records, etc.) may be linked due to technological advances, which increasingly enable
p.000050: researchers or others to identify individuals even when working with anonymized or coded data. Identification is also
p.000050: possible when the context in which the research is conducted is narrow (for example, small hospital) or very specific
p.000050: (for example, patients with rare diseases). Pooling data from a number of comparable sources may reduce but not
p.000050: completely eliminate the possibility of identifying individuals. In addition, genetic information derived
p.000050: through comprehensive technologies (for example, whole-genome sequencing) increasingly allows identifying individuals.
p.000050: Third, releasing confidential data can be required by law. For example, some jurisdictions require the reporting to
p.000050: appropriate agencies of certain communicable diseases or evidence of child abuse or neglect. Similarly, (health)
p.000050: authorities and research ethics committee accrediting agencies may have the legal right to inspect study records, and a
p.000050: sponsor’s compliance audit staff may require and obtain access to confidential data. These and similar limits to the
p.000050: ability to maintain confidentiality must be anticipated and disclosed to potential participants (see Guideline 9 –
p.000050: Individuals capable of giving informed consent). The more difficult it becomes to truly anonymize data, the
p.000050: more important it becomes for the participant to retain the ability to remove personal data from a dataset. Therefore,
p.000050: this is a crucial part of the governance system specified above.
p.000050:
p.000050: Mandatory population-based registries. Research projects using data from mandatory population- based registries must
p.000050: be submitted for review to a research ethics committee except for data analyses inherent to the internal
p.000050: institutional research activity of the registry.
p.000050:
p.000050: Return of results and (un)solicited findings. Especially in the context of data collections in which large data bases
p.000050: are combined (big data research), the informed consent must clearly stipulate whether return of
p.000050: information derived from analysis of the data is foreseen, if the donor wishes. The information given to
p.000050: the donor should clearly state that providing individual diagnoses is not the purpose of the databank or future
p.000050: research project, in order to prevent that donors being falsely reassured by the absence of unsolicited findings.
p.000050:
p.000050: There is an emerging consensus that at least some findings in genetic research must be returned to individual donors if
...
p.000058: where feasible, before, during and after the conduct of the research (see Guideline 7 – Community
p.000058: engagement).
p.000058:
p.000058: Special protections. Special protections for these groups can include allowing no more than minimal risks for
p.000058: procedures that offer no potential individual benefits for participants; supplementing the participant’s agreement by
p.000058: the permission of family members, legal guardians, or other appropriate representatives; or requiring that the research
p.000058: be carried out only when it is targeted at conditions that affect these groups. Safeguards can be designed to promote
p.000058: voluntary decision-making, limit the potential for confidentiality breaches, and otherwise work to protect the
p.000058: interests of those at increased risk of harm. Research ethics committees need to be sensitive to not overly excluding
p.000058: people, and allow them to participate by requiring that special protections be put in place.
p.000058:
p.000058: Group vulnerability. Despite the importance of avoiding classification of entire groups as inherently vulnerable,
p.000058: circumstances exist that require research ethics committees to pay special attention to research involving
p.000058: certain groups. In some resource-limited countries or communities, lack of access to medical care,
p.000058: membership in ethnic and racial minorities, or other disadvantaged or marginalized groups can be factors
p.000058: that constitute vulnerability. As is true of the vulnerability of individuals, the judgment that groups
p.000058: are vulnerable is context dependent and requires empirical evidence to document the need for special
p.000058: protections.
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p.000059:
p.000059:
p.000059:
p.000059:
p.000059: GUIDELINE 16:
p.000059: RESEARCH INVOLVING
p.000059: ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000059:
p.000059: Adults who are not capable of giving informed consent must be included in health-related research unless a good
p.000059: scientific reason justifies their exclusion. As adults who are not capable of giving informed consent
...
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
p.000068: physiologies and health needs, they merit special consideration by researchers and research ethics committees. Only the
p.000068: informed consent of the woman herself should be required for her research participation. Since some societies lack
p.000068: respect for women’s autonomy, in no case must the permission of another person replace the requirement of individual
p.000068: informed consent by the woman.
p.000068:
p.000068: Women of child-bearing potential must be informed in advance of the possibility of risks to the fetus
p.000068: should they become pregnant during their research participation. When participation in research might be
p.000068: hazardous to a fetus or a woman if she becomes pregnant, sponsors and researchers must guarantee access to pregnancy
p.000068: tests, effective contraceptive methods before and during the research and to safe, legal abortion.
p.000068:
p.000068:
p.000068: Commentary on Guideline 18
p.000068: General considerations. Women in many societies have been excluded from research. For example, most of the early
p.000068: cardiovascular disease studies have excluded women because these diseases were believed to be uncommon in women. In
p.000068: particular, women who are biologically capable of becoming pregnant have been traditionally excluded from clinical
p.000068: trials of drugs, vaccines and medical devices owing to concern about undetermined risks to the fetus (see
p.000068: Guideline 15 – Research involving vulnerable persons and groups). Although the presumption against including women
p.000068: has changed in recent years, they are still excluded in many cases without adequate justification. Much remains unknown
p.000068: about the safety and efficacy of most drugs, vaccines, or devices used by women in medical practice, and
p.000068: this lack of knowledge can be dangerous. For example, heart attacks in women are different from heart attacks in men,
p.000068: so research is necessary to determine the best means of diagnosis and treatment in women.
p.000068:
...
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
p.000069: could include risks to the fetus if they become pregnant during the research (see Guideline 19 – Pregnant
p.000069: women and breastfeeding women as research participants). Access to a pregnancy test, to effective
p.000069: contraceptive methods and to safe, legal abortion must be guaranteed before exposure to a potential teratogenic or
p.000069: mutagenic intervention. When effective contraception and safe abortion are not available and alternative study sites
p.000069: are not feasible, the informed consent discussion must include information about the risk of unintended pregnancy, the
p.000069: legal grounds for abortion, and information about reducing harms from unsafe abortion and subsequent complications.
p.000069: Also, if the pregnancy is not terminated, participants must be guaranteed a medical follow-up for their own health and
p.000069: that of the infant and child.
p.000069:
p.000069: Women who become pregnant during research. Many biomedical protocols call for terminating the participation of women
p.000069: who become pregnant during the research. In cases where a drug or biological product is known to be mutagenic or
p.000069: teratogenic, pregnant women must be removed from the study, and followed up and provided care through
p.000069: the duration of their pregnancy and delivery. Access to diagnostic tests must be provided to reveal any fetal
p.000069: anomalies. If anomalies are detected, women who wish may be referred for an abortion. When there is no evidence on the
p.000069: basis of which a potential harm to the fetus can be assumed, women who become pregnant should not automatically be
p.000069: removed from the study, but must be offered the option to continue or end their participation. For instance, in some
p.000069: cases it may be appropriate for a woman to stay in the study for safety monitoring but removed from the study drug. If
p.000069: the woman opts for continued participation, researchers and sponsors must offer adequate monitoring and support.
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p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: GUIDELINE 19:
p.000070: PREGNANT AND BREASTFEEDING WOMEN AS RESEARCH PARTICIPANTS
p.000070:
...
p.000070: and the research cannot be conducted in non-pregnant or non- breastfeeding women, a research ethics committee
p.000070: may permit a minor increase above minimal risk.
p.000070:
p.000070: Short-term and long‐term follow-up of the fetus and the child may be required in research involving pregnant and
p.000070: breastfeeding women depending upon the study intervention and its potential risks.
p.000070:
p.000070: As a general rule, health-related research involving pregnant women that has the potential for harm to the fetus should
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
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p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
p.000071: routine exclusion of pregnant women from clinical trials is their use of medications (both prescription and
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
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p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: in research. Special safeguards must be established to prevent undue inducement to pregnant women to
p.000072: participate in research in which interventions hold out the prospect of potential individual benefit to the fetus but
p.000072: not to the woman herself.
p.000072:
p.000072: Researchers must include in protocols on research involving pregnant women a plan for monitoring the outcome of the
p.000072: pregnancy with regard to both the health of the woman and the short-term and long-term health of the infant and child.
p.000072: Adverse events associated with research in pregnancy and during lactation may not occur immediately.
p.000072:
p.000072: Potential individual benefits and risks. The potential individual benefits and risks of research with pregnant and
p.000072: breastfeeding women should be evaluated based on Guideline 4 – Potential individual benefits and risks of research, and
p.000072: Guideline 5 – Choice of control in clinical trials.
p.000072:
p.000072: Serious harm and access to abortion. Research with pregnant women must be conducted only in settings where
p.000072: these women can be guaranteed access to a safe, legal abortion. This rule serves to prevent women from having to carry
p.000072: an unwanted fetus to term and deliver an affected baby against their wishes. Before pregnant women are enrolled,
p.000072: researchers must, at a minimum, determine whether fetal impairment and mental health conditions are recognised as legal
p.000072: grounds for abortion in that jurisdiction. If they are not, pregnant women must not be recruited for research in which
p.000072: there is a realistic basis for concern that significant fetal abnormality may occur as a consequence of
p.000072: participation in research. At the same time, this rule might restrict potentially valuable research in
p.000072: countries where women cannot be guaranteed access to abortion. In such cases, research projects can be
p.000072: conducted only if a local research ethics committee determines that the research has compelling social value for
p.000072: pregnant women and the women are informed about existing restrictions on abortion and possible options for obtaining an
p.000072: abortion in another country.
p.000072:
p.000072: Breastfeeding women. The father may need to be consulted in research involving breastfeeding women, in accordance with
p.000072: Guideline 17 – Research involving children and adolescents. If a breast- fed infant may be exposed to an
p.000072: investigational product through the ingestion of breast milk (or it is unknown whether an infant would be exposed),
p.000072: such research should be conducted in accordance with Guideline 17 – Research involving children and adolescents.
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p.000076: It may be acceptable to prioritize certain populations in study enrolment. For example, front line workers often put
p.000076: themselves at risk during a disaster such as an epidemic, and if experimental interventions are effective, these
p.000076: workers would be able to help more patients. The principles of reciprocity and helping the largest number of people
p.000076: could therefore justify their prioritization. Researchers, sponsors, and research ethics committees also need
p.000076: to ensure that burdens and benefits of participation are equitably distributed (see Guideline 3 – Equitable
p.000076: distribution of benefits and burdens in the selection of individuals and groups of participants in research).
p.000076:
p.000076: Scientific validity and alternative trial designs. Disasters unfold quickly and study designs need to be
p.000076: chosen so that studies will yield meaningful data in a rapidly evolving situation. Study designs must be feasible in a
p.000076: disaster situation but still appropriate to ensure the study’s scientific validity. Without scientific validity, the
p.000076: research lacks social value and must not be conducted (see Guideline 1 – Scientific and social value and respect for
p.000076: rights). Research may even divert personnel or resources from the disaster response. In clinical trials, the
p.000076: randomised-controlled trial design is often considered the “gold standard” for collecting robust data. However,
p.000076: researchers, sponsors, research ethics committees and others must explore alternative trial designs that may increase
p.000076: trial efficiency and access to promising experimental interventions while still maintaining scientific validity. The
p.000076: methodological and ethical merits of alternative trial designs must be carefully assessed before these designs are
p.000076: used. For example, when testing experimental treatments or vaccines during an epidemic, the appropriate trial
p.000076: design will depend on the promise of the investigational agent,
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p.000077: a variation in critical background factors (for example mortality and infection rates), and measurement of outcomes,
p.000077: among others. Researchers and sponsors must carefully evaluate the relative merits of different designs (for example
p.000077: observational or placebo-controlled) based on these factors.
p.000077:
p.000077: Community engagement. Because disasters often lead to vulnerability and fragile political and social situations,
p.000077: engaging local communities about the research at an early stage is essential for maintaining public trust and ensuring
p.000077: that studies are conducted in a culturally sensitive manner (see Guideline 7 – Community engagement). Researchers and
p.000077: sponsors can use creative mechanisms to expedite and facilitate community engagement in a disaster situation (for
p.000077: example, by using social media). Fostering community leadership will often be important to address distrust and
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p.000091:
p.000091:
p.000091:
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p.000091:
p.000091: before they actually start, thus enabling others to see what is going on and make inquiries if reports fail to come out
p.000091: of the study.
p.000091:
p.000091: Prospective registration of health-related research enables comparison of data reported with hypotheses the
p.000091: protocol was initially designed to test and helps to determine the number of times a hypothesis has been tested so that
p.000091: trial results can be understood in a broader context.
p.000091:
p.000091: Publication and dissemination of the results of research. A next step in achieving accountability is publication and
p.000091: dissemination of the results of studies. Researchers have a duty to make the results of their health-related research
p.000091: involving human beings publicly available and are accountable for the completeness and accuracy of their reports.
p.000091: Negative and inconclusive as well as positive results must be published or otherwise made publicly available. In
p.000091: journal publications, all involved parties must adhere to accepted guidelines, such as those of the International
p.000091: Committee of Medical Journal Editors (ICMJE) for ethical reporting. Sources of funding, institutional
p.000091: affiliations and conflicts of interest must be disclosed in the publication. Reports of research that fail to comply
p.000091: with recognized guidelines must not be accepted for publication. Sponsors must not prevent researchers from publishing
p.000091: unwelcome findings that restrict their freedom of publication. As the persons directly responsible for their work,
p.000091: researchers must not enter into agreements that interfere unduly with their access to the data or their ability to
p.000091: analyse the data independently, prepare manuscripts, or publish them. Researchers must also communicate the results of
p.000091: their work to the lay public. Ideally, researchers should take steps to promote and enhance public discussion.
p.000091: Knowledge resulting from the research should be made accessible to the communities in which the research was conducted,
p.000091: either through publication in scientific journals or through other channels (see Guideline 2 – Research conducted in
p.000091: low-resource settings).
p.000091:
p.000091: Data sharing. There are compelling reasons to share the data of health-related research. Responsible sharing of
p.000091: clinical trial data serves the public interest by strengthening the science that is the foundation of safe
p.000091: and effective clinical care and public health practice. Sharing also fosters sound regulatory decisions, generates new
p.000091: research hypotheses, and increases the scientific knowledge gained from the contributions of clinical trial
p.000091: participants, the efforts of clinical trial researchers, and the resources of clinical trial funders.
p.000091:
p.000091: Data sharing requires careful balancing of competing considerations. Sharing of study data presents risks, burdens, and
p.000091: challenges as well potential individual benefits for various stakeholders. When sharing data, researchers must respect
p.000091: the privacy and consent of study participants. Researchers want a fair opportunity to publish their analyses and
p.000091: receive credit for carrying out studies and collecting data. Other researchers want to analyse data that would
p.000091: otherwise not be published in a timely manner and to replicate the findings of a published paper. Sponsors want
...
p.000091:
p.000091: It is crucial to create a culture of responsible data sharing and mutually reinforcing incentives for sharing. Funders
p.000091: and sponsors must require funded researchers to share study data and must provide appropriate support
p.000091: for sharing. Researchers and sponsors must share data and design and carry out future studies assuming that
p.000091: data will be shared. Research institutions and universities must encourage researchers to share data. In their review
p.000091: of protocols, research ethics committees should consider a researcher’s and sponsor’s record in reporting results.
p.000091: Medical journals should request that authors share the analytical data set supporting the publication of study results.
p.000091: Patient advocacy organizations should consider data sharing plans as a criterion for funding grants and
p.000091: promoting studies to their constituents. Regulatory agencies around the globe should harmonize requirements
p.000091: and practices for data sharing. The risks of data sharing may be mitigated by controlling with whom the data are
p.000091: shared and under what conditions, without compromising the scientific usefulness of the shared data.
p.000091: Organizations that share data should employ data use agreements,
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p.000092: observe additional privacy protections beyond de-identification and data security, as appropriate, and appoint an
p.000092: independent panel that includes members of the public to review data requests. These safeguards must not
p.000092: unduly impede access to data.
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p.000093:
p.000093: GUIDELINE 25:
p.000093: CONFLICTS OF INTEREST
p.000093:
p.000093: The primary goal of health-related research is to generate, in ethically appropriate ways, the knowledge necessary
p.000093: to promote people’s health. However, researchers, research institutions, sponsors, research ethics committees,
p.000093: and policy-makers have other interests (for example, scientific recognition or financial gain) that can
p.000093: conflict with the ethical conduct of research. Such conflicts between the primary goal of health-related research
p.000093: and secondary interests are defined as conflicts of interest.
p.000093:
p.000093: Conflicts of interest can influence the choice of research questions and methods, recruitment and retention of
p.000093: participants, interpretation and publication of data, and the ethical review of research. It is therefore necessary to
p.000093: develop and implement policies and procedures to identify, mitigate, eliminate, or otherwise manage such conflicts of
p.000093: interest.
p.000093:
...
p.000099: measures proposed to determine the extent of compliance of persons with the treatment;
p.000099:
p.000099: 22. Rules or criteria according to which participants may be removed from the study or clinical trial, or (in a
p.000099: multi-centre study) a centre may be discontinued, or the study may be terminated;
p.000099:
p.000099: 23. Methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000099: complications (Guidelines 4 and 23);
p.000099:
p.000099: 24. The known or foreseen risks of adverse reactions, including the risks attached to each proposed intervention and
p.000099: to any drug, vaccine or procedure to be tested (Guideline 4);
p.000099:
p.000099: 25. The potential individual benefits of the research to participants and to others (Guideline 4);
p.000099:
p.000099: 26. The expected benefits of the research to the population, including new knowledge that the study might
p.000099: generate (Guidelines 1 and 4);
p.000099:
p.000099: 27. For research carrying more than minimal risk of physical injury, details of plans, including
p.000099: insurance coverage, to provide treatment for such injury, including the funding of treatment, and to provide
p.000099: compensation for research-related disability or death (Guideline 14);
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000100: 100
p.000100: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 28. Provision for continued access to study interventions that have demonstrated significant benefit, indicating its
p.000100: modalities, the parties involved in continued care and the organization responsible for paying for it, and for how long
p.000100: it will continue (Guideline 6);
p.000100:
p.000100: 29. For research on pregnant women, a plan, if appropriate, for monitoring the outcome of the pregnancy
p.000100: with regard to both the health of the woman and the short-term and long-term health of the child (Guideline 19);
p.000100:
p.000100: 30. The means proposed to obtain individual informed consent and the procedure planned to communicate
p.000100: information to prospective participants, including the name and position of the person responsible for obtaining
p.000100: consent (Guideline 9);
p.000100:
p.000100: 31. When a prospective subject is not capable of informed consent, satisfactory assurance that permission will be
p.000100: obtained from a duly authorized person, or, in the case of a child who is sufficiently mature to
p.000100: understand the implications of informed consent but has not reached the legal age of consent, that knowing
p.000100: agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian or other duly
...
p.000102:
p.000102: 2. that the individual is invited to participate in research, the reasons for considering the individual suitable
p.000102: for the research, and that participation is voluntary (Guideline 9);
p.000102:
p.000102: 3. that the individual is free to refuse to participate and will be free to withdraw from the research at any time
p.000102: without penalty or loss of benefits to which he or she would otherwise be entitled (Guideline 9);
p.000102:
p.000102: 4. the expected duration of the individual’s participation (including number and duration of visits to the
p.000102: research centre and the total time involved) and the possibility of early termination of the trial or of
p.000102: the individual’s participation in it;
p.000102:
p.000102: 5. whether money or other forms of material goods will be provided in return for the individual’s participation,
p.000102: and, if so, the kind and amount, and that the time spent on the research and other inconveniences resulting from study
p.000102: participation will be appropriately compensated, monetary or non-monetary (Guideline 13);
p.000102:
p.000102: 6. that, after the completion of the study, participants will be informed of the outcomes of the
p.000102: research in general, if they so wish;
p.000102:
p.000102: 7. that individual participants during or after a study or collection of their biological material and
p.000102: health-related data will be informed of life-saving information and data of immediate clinical utility
p.000102: involving a significant health problem (see also Guideline 11);
p.000102:
p.000102: 8. that unsolicited findings will be disclosed if they occur (Guideline 11);
p.000102:
p.000102: 9. that participants have the right of access to their clinically relevant data obtained during a study on demand
p.000102: (unless the research ethics committee has approved temporary or permanent non-disclosure
p.000102:
p.000102:
p.000102:
p.000102: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000102:
p.000103: 103
p.000103:
p.000103:
p.000103:
p.000103:
p.000103:
p.000103: of data, in which case the participant should be informed of, and given, the reasons for such non-disclosure);
p.000103:
p.000103: 10. pain and discomfort of experimental interventions, known risks and possible hazards, to the individual (or others)
p.000103: associated with participation in the research, including risks to the health or well-being of a participant’s direct
p.000103: relatives (Guideline 4);
p.000103:
p.000103: 11. the potential clinical benefits, if any, expected to result to participants from participating in the research
p.000103: (Guidelines 4 and 9);
p.000103:
p.000103: 12. the expected benefits of the research to the community or to society at large, or contributions to scientific
p.000103: knowledge (Guideline 1);
p.000103:
p.000103: 13. how the transition to care after research is arranged and to what extent they will be able to
p.000103: receive beneficial study interventions post-trial and whether they will be expected to pay for them (Guidelines 6 and
p.000103: 9);
p.000103:
p.000103: 14. the risks of receiving unregistered interventions if they receive continued access to a study
p.000103: intervention before regulatory approval (Guideline 6);
p.000103:
p.000103: 15. any currently available alternative interventions or courses of treatment;
p.000103:
p.000103: 16. new information that may have come to light, either from the study itself or other sources
p.000103: (Guideline 9);
p.000103:
p.000103: 17. the provisions that will be made to ensure respect for the privacy of participants, and for the confidentiality of
p.000103: records in which participants are identified (Guidelines 11 and 22);
p.000103:
p.000103: 18. the limits, legal or other, to the researchers’ ability to safeguard confidentiality, and the possible
p.000103: consequences of breaches of confidentiality (Guidelines 12 and 22);
p.000103:
p.000103: 19. the sponsors of the research, the institutional affiliation of the researchers, and the nature and sources of
p.000103: funding for the research, and, when they exist, any conflicts of interest of researchers, research institutions and
p.000103: research ethics committees and how these conflicts will be managed (Guidelines 9 and 25);
p.000103:
p.000103: 20. whether the researcher is serving only as a researcher or as both researcher and the participant`s physician
p.000103: (Guideline 9);
p.000103:
p.000103: 21. the extent of the researcher’s responsibility to provide care for participants’ health needs during and after the
p.000103: research (Guideline 6);
p.000103:
p.000103: 22. that treatment and rehabilitation will be provided free of charge for specified types of research- related injury
p.000103: or for complications associated with the research, the nature and duration of such care, the name of
p.000103: the medical service or organization that will provide the treatment, and whether there is any uncertainty
...
p.000104: 1. for controlled trials, an explanation of features of the research design (e.g., randomization,
p.000104: double-blinding), that the participant will not be told of the assigned treatment until the study has been completed
p.000104: and the blind has been broken;
p.000104:
p.000104: 2. whether all essential information is disclosed and, if not, that they are asked to agree to receiving incomplete
p.000104: information and that full information will be provided before study results are analysed and participants are given
p.000104: the possibility to withdraw their data collected under the study (Guideline 10);
p.000104:
p.000104: 3. policy with regard to the use of results of genetic tests and familial genetic information, and the precautions
p.000104: in place to prevent disclosure of the results of a participant’s genetic tests to immediate family
p.000104: relatives or to others (e.g. insurance companies or employers) without the consent of the participant (Guideline 11);
p.000104:
p.000104: 4. the possible research uses, direct or secondary, of the participant`s medical records and of biological
p.000104: specimens taken in the course of clinical care;
p.000104:
p.000104: 5. for collection, storage and use of biological material and health-related data, that broad informed consent will
p.000104: be obtained, which should specify: the purpose of the biobank, the conditions and duration of storage; the rules of
p.000104: access to the biobank; the ways in which the donor can contact the biobank custodian and can remain informed about
p.000104: future use; the foreseeable uses of the materials, whether limited to an already fully defined study or extending to a
p.000104: number of wholly or partially undefined studies; the intended goal of such use, whether only for research, basic or
p.000104: applied, or also for commercial purposes, and whether the participant will receive monetary or other benefits from the
p.000104: development of commercial products developed from their biological specimens; the possibility of unsolicited findings
p.000104: and how they will be dealt with; the safeguards that will be taken to protect confidentiality as well as their
p.000104: limitations, whether it is planned that biological specimens collected in the research will be destroyed at its
p.000104: conclusion, and, if not, details about their storage (where, how, for how long, and final disposition) and possible
p.000104: future use, that participants have the right to decide about such future use, to refuse storage, and to have the
p.000104: material destroyed (Guidelines 11 and 12);
p.000104:
p.000104: 6. when women of childbearing potential are participating in health-related research, information about the
p.000104: possible risks, if they become pregnant during the research, to themselves (including future fertility), their
p.000104: pregnancies, their fetuses, and their future offspring; and the guaranteed access to a pregnancy test, to effective
p.000104: contraceptive methods and to safe, legal abortion before exposure to a potential teratogenic or mutagenic intervention.
p.000104: When effective contraception and/ or safe abortion are not available and alternative study sites are not feasible, the
p.000104: women must be given information about: the risk of unintended pregnancy; the legal grounds for abortion; reducing harms
p.000104: from unsafe abortion and subsequent complications; and, when pregnancy is not terminated, the guarantee for a medical
p.000104: follow-up for their own health and that of the infant and child and the information that it is often difficult to
p.000104: determine causality in cases of fetal or infant abnormalities (Guidelines 18 and 19);
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000104:
p.000105: 105
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: 7. when concerning pregnant and breastfeeding women, the risks of participation in health-related research to
p.000105: themselves, their pregnancies, their fetuses, and their future offspring, what has been done to maximize potential
p.000105: individual benefits and minimize risks, that evidence concerning risks may be unknown or controversial, and that
...
p.000117: Adult(s) xi, 44, 45, 51 Alternative trial designs 77 Ancillary care 21 - 23, 26
p.000117: Anonymous 44, 50
p.000117: Assent 61, 62, 65 - 67, 101
p.000117: Authorization 4, 41, 42, 44, 47, 48, 50, 70, 96
p.000117: B
p.000117: Benefit xi, 2 - 5, 7 - 12, 16, 19, 21 - 23, 29, 44, 53, 54, 61, 62, 65 - 67, 71 - 73, 91, 101
p.000117: Biobank 42 - 45, 105
p.000117: Biological material 41, 42, 44, 45, 50, 103, 105
p.000117: Breastfeeding 7, 58, 70 - 73, 106
p.000117: Broad informed consent 41 - 44, 47, 48 - 50, 52, 105
p.000117: C
p.000117: Capable of giving informed consent 10, 25, 33, 34, 37, 38, 41, 43, 47, 49, 50, 51, 56, 58,
p.000117: 61 - 63, 67, 76, 78, 96
p.000117: Capacity-building 5, 27, 29, 30, 45, 52, 102
p.000117: Cluster randomized trials 79, 80
p.000117: Coding 41, 44, 47, 50, 51, 90
p.000117: Collaborative partnership 27, 29, 30, 42, 45, 47, 52, 89
p.000117: Collection, collecting 26, 36, 39, 41 - 43, 47 - 50, 77, 80, 83 - 85, 92, 103, 105
p.000117: Community engagement ix, xi, 5, 10, 23, 25, 26, 29, 30, 42, 45, 47, 52, 59, 63, 75, 78, 102
p.000117: Comparative effectiveness research 16, 19
p.000117: Compassionate use 22
p.000117: Compelling scientific reasons 15 - 18
p.000117: Compensation 13, 53 - 56, 96, 100, 104 Competent. See Capable of giving informed consent Comprehension 34
p.000117: Confidentiality 11, 13, 41, 42, 44, 47, 48, 50, 51, 57, 59, 70, 100, 101, 102, 104, 105
p.000117: Conflicts of interest 5, 30, 34, 78, 89, 92, 95 - 97, 102, 104
p.000117: Continued access 21 - 23, 101, 104
p.000117: Control 9, 12, 15 - 18, 22, 26, 45, 51, 62, 67, 73, 79, 80, 83, 85,
p.000117: Custodian 41, 43, 44, 47, 49, 50, 105
p.000117: D
p.000117: Databank 47 - 52
p.000117:
p.000117:
p.000117: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000117:
p.000119: 119
p.000119:
p.000119: Data mining 50
p.000119: Data sharing 29, 31, 51, 85, 92
p.000119: Deception, deceiving 33, 38, 57
p.000119: Deliberate objection 67
p.000119: Dependent relationship 26, 35, 36, 58, 96
p.000119: Digital 83, 106
p.000119: Disaster ix, 75 - 78, 106
p.000119: Disclosure 44, 45, 51, 84, 85, 91, 95, 97, 101, 103 - 105
p.000119: Disease outbreak ii, x, 19, 34, 41, 44, 47, 49, 83, 96, 97, 99, 103, 105
p.000119: Dissemination 2, 4, 25, 85, 92
p.000119: Dissent 62, 67
p.000119: E
p.000119: Education 2, 30, 57, 89, 97
p.000119: Emergency care 63, 68, 78
p.000119: Equitable distribution 4, 7, 42, 45, 47, 52, 75, 77
p.000119: Established effective intervention viii, 9, 12, 15 - 19
p.000119: Ethical review xii, 2, 29, 30, 39, 76 - 78, 87 - 90, 95, 97, 99, 102
p.000119: Externally sponsored research 87, 89
p.000119: F
p.000119: Fairness 2
p.000119: Fetus 58, 69, 70 - 73
p.000119: Free medical treatment 56
p.000119: G
p.000119: Gatekeeping 80
p.000119: Governance 41 - 43, 44, 47, 48, 50, 51, 78
p.000119: H
p.000119: Harms 10, 11, 12, 18, 54, 55, 56, 70, 72, 91, 105
p.000119: Health needs 2 - 4, 8, 17, 19, 21 - 23, 26, 55, 61, 65, 69, 71, 72, 75, 76, 104
p.000119: I
p.000119: Identifiable 38, 39, 51, 84
p.000119: Implementation research 80
p.000119: Incentives 10, 54, 92, 101
...
p.000119: 88, 91, 100, 101, 104
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000120: 120
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
p.000120: Low-resource settings viii, ix, 3 - 5, 7, 17, 19, 22, 23, 26, 45, 47, 52, 75 - 77, 80, 89, 92
p.000120: M
p.000120: Management (of risks) 8, 42, 45, 48, 51, 85, 95 - 97
p.000120: Material Transfer Agreement 41, 45
p.000120: Minimal risk 9, 13, 15, 16, 18, 38, 62, 65, 66, 71, 72, 80, 88, 100
p.000120: Minor increase above minimal risk 13, 18
p.000120: Mitigation 11, 15, 76, 85, 95, 97
p.000120: Modification of informed consent 33, 37
p.000120: Money 54, 103
p.000120: Multi-centre research 87, 89
p.000120: O
p.000120: Observational ix, xii, 16, 53, 72, 78
p.000120: Online 27, 83 - 85, 106
p.000120: Opt-out/opt-in. See Informed opt-out/opt-in
p.000120: P
p.000120: Parent 65, 67, 68, 101
p.000120: Payment 54, 88, 101
p.000120: Permission 35, 38, 54, 58, 59, 61 - 63, 65, 67 - 71, 79, 80, 81, 83, 101
p.000120: Placebo 9, 15 - 19, 35, 78, 80
p.000120: Post-trial access. See Continued access
p.000120: Pregnant women 7, 8, 58, 70 - 73, 101
p.000120: Privacy 68, 83 - 85, 92, 93, 100, 101, 104, 106
p.000120: Procedures xi, 9 - 12, 15, 17, 19, 23, 26, 33 - 35, 37, 38, 42, 53 - 55, 59, 61, 62, 65 - 67, 71,
p.000120: 76 - 80, 87 - 90, 95, 97, 100 - 103
p.000120: Protocol 2, 12, 18, 23, 25, 35, 36, 43, 49, 55, 56, 58, 76, 83, 87 - 90, 92, 96, 99, 101, 102, 105
p.000120: Public accountability 11, 13, 29, 31, 51, 91
p.000120: Publication ii, 29, 31, 84, 91, 92, 95, 102
p.000120: R
p.000120: Registries 36, 38, 39, 47, 49, 51, 72, 91
p.000120: Rehabilitation 55, 104
p.000120: Reimbursement 53, 54
p.000120: Research ethics committee 2, 9, 10, 12, 15, 17, 18, 23, 25, 27, 33, 34 - 39, 41, 43 - 45, 47,
p.000120: 49 - 51, 53, 54, 56, 58, 61 - 63, 65, 68, 71, 73, 79, 85, 87 - 91, 95, 96, 98, 102, 103, 105
p.000120: Residual tissue 41, 43, 44
p.000120: Responsiveness 3, 4, 17, 19, 63, 75, 76
p.000120: Return of results 44, 45, 51
p.000120:
p.000120:
p.000120:
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000121: 121
p.000121:
p.000121: Risks 2, 5, 7 - 13, 15 - 19, 23, 26, 34 - 39, 41, 44, 47, 49, 50, 53, 54, 58, 59, 61 - 63, 65 - 67,
p.000121: 69 - 73, 75 - 77, 80, 81, 83 - 85, 88, 91, 92, 96, 100, 102, 104 - 106
p.000121: S
p.000121: Scientific value 2, 9 - 13, 51, 91
p.000121: Secondary use 49
p.000121: Social value 1 - 4, 8 - 11, 19, 25, 26, 30, 37, 38, 41, 44, 47, 50, 62, 65, 71, 73, 75, 77, 88, 91
p.000121: Specific informed consent 41 - 44, 47, 48, 49
p.000121: Storage 36, 41, 43, 45, 47 - 50, 52, 105
p.000121: U
...
Social / Age
Searching for indicator age:
(return to top)
p.000005: be justified. Groups that are unlikely to benefit from any knowledge gained from the research should not bear a
p.000005: disproportionate share of the risks and burdens of research participation. Groups that are under-represented
p.000005: in medical research should be provided appropriate access to participate.
p.000005:
p.000005:
p.000005: Commentary on Guideline 3
p.000005: General considerations. The equitable distribution of benefits and burdens in the selection of study
p.000005: populations requires that the benefits of research be distributed fairly and that no group or class of persons bears
p.000005: more than its fair share of the risks or burdens from research participation. When benefits or burdens of research are
p.000005: to be apportioned unequally among individuals or groups, the criteria for unequal distribution should be scientifically
p.000005: and ethically justified rather than arbitrarily or conveniently chosen. Situations where unequal distribution of
p.000005: benefits would be considered are those in which the research particularly affects the population under study.
p.000005: In general, equitable distribution requires that participants be drawn from the qualifying population in the
p.000005: geographic area of the study where the results can be applied (see Guideline 2 – Research conducted in low-resource
p.000005: settings). Inclusion and exclusion criteria should not be based upon potentially discriminatory criteria, such as race,
p.000005: ethnicity, economic status, age or sex, unless there is a sound ethical or scientific reason to do so. For example, in
p.000005: cases where the under-representation of particular groups results in or perpetuates health disparities, equity may
p.000005: require special efforts to include members of those populations in research (see Guideline 17 – Research involving
p.000005: children and adolescents, Guideline 18
p.000005: – Women as research participants, and Guideline 19 – Pregnant women and breastfeeding women as research participants).
p.000005:
p.000005:
p.000005:
p.000005: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: Fair distribution of research benefits. Equity in the distribution of the benefits of research requires
p.000007: that research not disproportionately focus on the health needs of a limited class of people, but instead
p.000007: aims to address diverse health needs across different classes or groups. In the past, groups considered vulnerable
p.000007: were excluded from participation in research because it was considered the most expedient way of protecting
p.000007: those groups (for example, children, women of reproductive age, pregnant women). As a consequence of such exclusions,
p.000007: information about the diagnosis, prevention and treatment of diseases that afflict such groups is limited. This has
p.000007: resulted in a serious injustice. Since information about the management of diseases is considered a benefit to society,
p.000007: it is unjust to intentionally deprive specific groups of that benefit. The need to redress these injustices by
p.000007: encouraging the participation of previously excluded groups in basic and applied biomedical research is widely
p.000007: recognized.
p.000007:
p.000007: Fair distribution of research burdens. Research with human participants typically requires that some persons or
p.000007: groups are exposed to risks and burdens in order to generate the knowledge needed to protect and promote
p.000007: people’s health (see Guideline 1 – Scientific and social value and respect for rights). Equity in the distribution of
p.000007: burdens of research requires special care to ensure that individuals, communities or populations that are already
p.000007: disadvantaged or marginalized are not over-represented in research. A disproportionate selection of disadvantaged or
p.000007: convenient populations is morally problematic for several reasons. First, it is unjust to selectively invite poor or
p.000007: marginalized individuals or groups to participate in research because this concentrates the risks and burdens of
p.000007: research on people who already experience increased risks and burdens from social and economic disadvantage. Second,
p.000007: these individuals and groups are also the most likely to be excluded from, or to have difficulty accessing, the
...
p.000044: the donor should clearly state that providing individual diagnoses is not the purpose of the biobank or future
p.000044: research project, in order to prevent that donors are falsely reassured by the absence of unsolicited findings.
p.000044:
p.000044: There is an emerging consensus that at least some findings in genetic research must be returned to individual donors if
p.000044: they wish. Tiered consent, meaning the possibility of obtaining packages or subsets of information, gives donors a
p.000044: range of choices and allows them to choose some options to give them greater control over the use of their biological
p.000044: materials. In general, the three guiding principles for return of results need to be followed: results must
p.000044: have analytical validity, clinical significance and actionability to qualify for being returned. This implies that
p.000044: life-saving information and data of immediate clinical utility involving a significant health problem must
p.000044: be offered for disclosure, whereas information of uncertain scientific validity or clinical significance
p.000044: would not qualify for communication to the participant. The research ethics committee should also evaluate whether
p.000044: individual counselling is necessary when returning particular genetic findings. Some cases may require making an
p.000044: ethically responsible management plan for returning (un)solicited findings.
p.000044:
p.000044: Children and adolescents. Children and adolescents who reach the age of maturity during the research
p.000044: project should be given the opportunity to give informed consent for the continued storage and use of their
p.000044: material and related data, and they should also be able to withdraw consent for future research. An
p.000044: informed, opt-out system in which such persons are alerted to their right to withdraw could also be
p.000044: acceptable.
p.000044:
p.000044: Material Transfer Agreement. The transfer of human biological materials must be covered by a material transfer
p.000044: agreement (MTA). This MTA must ensure that the biological materials are documented in such a way that they can be
p.000044: retrieved. The range and duration of use and what needs to happen at the end of the period of use must also be
p.000044: specified. All responsibilities concerning these elements of an MTA need to be clearly stated in the agreement. An MTA
p.000044: is also needed in multinational research projects in which one entity collects samples from persons in all
p.000044: participating countries and stores them in a single biobank.
p.000044:
p.000044: Closure of a biobank. In the event of closure of the biobank, plans for appropriate transfer or
p.000044: disposal of the biological material and data should be developed in collaboration with local health authorities.
p.000044:
p.000044: Storing and using material from low-resource settings in biobanks. Biobanks have become a global phenomenon.
p.000044: Nevertheless, some low-resource settings may be inexperienced in storing and using biological materials. In
...
p.000050: they wish. Tiered consent, meaning the possibility of obtaining packages or subsets of information, gives donors a
p.000050: range of choices and allows them to choose some options to give them greater control over the use of their
p.000050: data. In general, the three guiding principles for return of results need to be followed: results must have
p.000050: analytical validity, clinical significance and actionability to qualify for being returned. This implies that
p.000050: life-saving information and data of immediate clinical utility involving a significant health problem must be offered
p.000050: for disclosure, whereas information of uncertain scientific validity or clinical significance would not qualify for
p.000050: communication to the donor. The research ethics committee should also evaluate whether individual counselling is
p.000050: necessary when returning particular genetic findings. Some cases may require making an ethically responsible management
p.000050: plan for returning (un)solicited findings.
p.000050:
p.000050: Data-sharing. Researchers, sponsors and research ethics committees must share data for further research where possible.
p.000050: The conditions for data sharing are spelled out in Guideline 24 – Public accountability for health-related research.
p.000050:
p.000050:
p.000050:
p.000050: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000051: 51
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051: Children and adolescents. Children and adolescents who reach the age of maturity must be given the opportunity to give
p.000051: broad informed consent for the continued storage and use of their data and should also be able to withdraw consent for
p.000051: future research. An informed, opt-out system in which such persons are alerted to their right to withdraw, could also
p.000051: be acceptable.
p.000051:
p.000051: Closure of a databank. In the event of closure of the databank, plans for appropriate transfer or disposal of the
p.000051: health-related data should be developed in collaboration with local health authorities.
p.000051:
p.000051: Storing and using data from low-resource settings in databanks. Databanks have become a global phenomenon.
p.000051: Nevertheless, some low-resource settings may be inexperienced in storing and using biological materials. In addition to
p.000051: what is stated in this Guideline, requirements for community engagement, capacity-building and equitable
p.000051: distribution of burdens and benefits of research as described in other guidelines also apply to databank
p.000051: research in low-resource settings (see Guideline 3 – Equitable distribution of benefits and burdens in the
p.000051: selection of individuals and groups of participants in research, Guideline 7 – Community engagement, and Guideline 8 –
p.000051: Collaborative partnership and capacity building for research and review).
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
...
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
p.000057: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: stereotypes. One proposed mechanism that can be used to avoid stereotyping is consultation with relevant stakeholders,
p.000058: where feasible, before, during and after the conduct of the research (see Guideline 7 – Community
p.000058: engagement).
p.000058:
p.000058: Special protections. Special protections for these groups can include allowing no more than minimal risks for
p.000058: procedures that offer no potential individual benefits for participants; supplementing the participant’s agreement by
p.000058: the permission of family members, legal guardians, or other appropriate representatives; or requiring that the research
p.000058: be carried out only when it is targeted at conditions that affect these groups. Safeguards can be designed to promote
p.000058: voluntary decision-making, limit the potential for confidentiality breaches, and otherwise work to protect the
...
p.000063: research. Moreover, without appropriate support, they may not be able to protect their own interests due to
p.000063: their evolving capacity to give informed consent. Specific protections to safeguard children’s rights and welfare in
p.000063: the research are therefore necessary.
p.000063:
p.000063: Before undertaking research involving children and adolescents, the researcher and the research ethics committee must
p.000063: ensure that:
p.000063: f a parent or a legally authorized representative of the child or adolescent has given permission; and
p.000063: f the agreement (assent) of the child or adolescent has been obtained in keeping with the child’s or adolescent’s
p.000063: capacity, after having been provided with adequate information about the research tailored to the child’s or
p.000063: adolescent’s level of maturity.
p.000063:
p.000063: If children reach the legal age of maturity during the research, their consent to continued participation should be
p.000063: obtained.
p.000063:
p.000063: In general, the refusal of a child or adolescent to participate or continue in the research must be respected,
p.000063: unless, in exceptional circumstances, research participation is considered the best medical option for a child or
p.000063: adolescent.
p.000063:
p.000063: For research interventions or procedures that have the potential to benefit children or adolescents, the
p.000063: risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000063:
p.000063: For research interventions or procedures that have no potential individual benefits for participants, two
p.000063: conditions apply:
p.000063: f the interventions and procedures should be studied in adults first, when these interventions and
p.000063: procedures target conditions that affect adults as well as children and adolescents, unless the necessary data
p.000063: cannot be obtained without participation of children or adolescents; and
p.000063: f the risks must be minimized and no more than minimal.
p.000063:
p.000063: When the social value of the studies with such research interventions and procedures is compelling, and these studies
...
p.000065: new drugs. First exploring the possible toxicity of new drugs in adult populations represents a way of reducing risk
p.000065: for children and adolescents who might be involved in subsequent investigations of the same intervention.
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000066: 66
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: Potential individual benefits and risks. The potential individual benefits and risks of research with
p.000066: children or adolescents should be evaluated based on Guideline 4 – Potential individual benefits and risks of research,
p.000066: and Guideline 5 – Choice of control in clinical trials.
p.000066:
p.000066: Assent. Children and adolescents who are legally minors cannot give legally valid informed consent, but they may be
p.000066: able to give assent. To give assent means that the child or adolescent is meaningfully engaged in the research
p.000066: discussion in accordance with his or her capacities. Assent must be considered as a process (see Guideline 9
p.000066: – Individuals capable of giving informed consent) and is not merely the absence of dissent. Furthermore, the researcher
p.000066: must involve the child or adolescent in the actual decision-making process and use age-appropriate information. It is
p.000066: of major importance to inform the child or adolescent and obtain assent as described above, preferably in
p.000066: writing for children who are literate. The process of obtaining assent must take into account not only the age of
p.000066: children, but also their individual circumstances, life experiences, emotional and psychological maturity, intellectual
p.000066: capabilities and the child’s or adolescent’s family situation.
p.000066:
p.000066: As adolescents near the age of majority, their agreement to participate in research may be ethically
p.000066: (though not legally) equivalent to consent. In this situation, parental consent is ethically best
p.000066: considered as “co-consent” but legally, the adolescent’s agreement remains assent. If child or adolescent
p.000066: participants reach the legal age of majority according to applicable law and become capable of independent informed
p.000066: consent during the research, their written informed consent to continued participation must be sought and their
p.000066: decision respected.
p.000066:
p.000066: Deliberate objection. Some children and adolescents who are too immature to give assent may be able to register a
p.000066: “deliberate objection,” meaning an expression of disapproval or refusal of a proposed procedure. The deliberate
p.000066: objection of an older child or adolescent, for example, is to be distinguished from the behaviour of an
p.000066: infant likely to cry or withdraw in response to almost any adverse stimulus. A deliberate objection by
p.000066: a child or adolescent to taking part in research must be respected even if the parents have given permission,
p.000066: unless the child or adolescent needs treatment that is not available outside the context of research, the research
p.000066: intervention has a clear prospect of clinical benefit, and the treating physician and the legally authorized
p.000066: representative consider the research intervention to be the best available medical option for the given
p.000066: child or adolescent. In such cases, particularly if the child is very young or immature, a parent or guardian may
p.000066: override the child`s objections. However, in some situations parents may press a researcher to persist with an
p.000066: investigational intervention against the child`s wishes. Sometimes this pressure is meant to serve the parents’
p.000066: interests rather than the child’s. In this case, the parents’ decision must be overridden if the researcher believes it
p.000066: is not in the child’s best clinical interest to enrol or continue study participation.
p.000066:
p.000066: Permission of a parent or legally authorized representative. The researcher must obtain the permission of
p.000066: at least one parent or guardian in writing, consistent with applicable laws and regulations. The age at
p.000066: which a child becomes legally capable to give consent differs substantially from one jurisdiction to another.
p.000066: Often children who have not yet reached the legally established age of consent can understand the implications
p.000066: of research participation and go through standard informed consent procedures; however, legally they can only assent to
p.000066: serve as research participants. Independent of its quality, assent is never sufficient to permit participation in
p.000066: research unless it is supplemented by the permission of a parent, legal guardian or other duly authorized
p.000066: representative. The decision to continue or discontinue participation by children or adolescents who become legally
p.000066: capable during the study trumps the decision of their parents or legal guardians.
p.000066:
p.000066: Waiver of parental permission. In certain circumstances, research ethics committees may waive parental permission. In
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
p.000066:
p.000066: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
...
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
p.000069: could include risks to the fetus if they become pregnant during the research (see Guideline 19 – Pregnant
p.000069: women and breastfeeding women as research participants). Access to a pregnancy test, to effective
p.000069: contraceptive methods and to safe, legal abortion must be guaranteed before exposure to a potential teratogenic or
p.000069: mutagenic intervention. When effective contraception and safe abortion are not available and alternative study sites
p.000069: are not feasible, the informed consent discussion must include information about the risk of unintended pregnancy, the
p.000069: legal grounds for abortion, and information about reducing harms from unsafe abortion and subsequent complications.
p.000069: Also, if the pregnancy is not terminated, participants must be guaranteed a medical follow-up for their own health and
p.000069: that of the infant and child.
p.000069:
p.000069: Women who become pregnant during research. Many biomedical protocols call for terminating the participation of women
...
p.000098: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000098: epidemiological information about the country or region concerned;
p.000098:
p.000098: 9. Name and address of the sponsor;
p.000098:
p.000098: 10. Names, addresses, institutional affiliations, qualifications and experience of the principal investigator
p.000098: and other investigators (Guideline 1);
p.000098:
p.000098: 11. The objectives of the trial or study, its hypotheses or research questions, its assumptions, and its
p.000098: variables (Guideline 1);
p.000098:
p.000098: 12. A detailed description of the design of the trial or study. In the case of controlled clinical trials the
p.000098: description should include, but not be limited to, whether assignment to treatment groups
p.000098:
p.000098:
p.000098: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: will be randomized (including the method of randomization), and whether the study will be blinded (single
p.000099: blind, double blind), or open (Guideline 5);
p.000099:
p.000099: 13. The number of research participants needed to achieve the study objective, and how this was statistically
p.000099: determined;
p.000099:
p.000099: 14. The criteria for inclusion or exclusion of potential participants, and justification for the exclusion of any
p.000099: groups on the basis of age, sex, social or economic factors, or for other reasons (Guideline 3);
p.000099:
p.000099: 15. The justification for involving as research participants children or adolescents, persons who are unable to give
p.000099: informed consent or vulnerable persons or groups, and a description of special measures to minimize risks to such
p.000099: persons (Guidelines 15, 16 and 17);
p.000099:
p.000099: 16. The process of recruitment, e.g. advertisements, and the steps to be taken to protect privacy and confidentiality
p.000099: during recruitment (Guideline 3);
p.000099:
p.000099: 17. Description and explanation of all interventions (the method of treatment administration, including
p.000099: route of administration, dose, dose interval and treatment period for investigational and comparator products used);
p.000099:
p.000099: 18. Plans and justification for withdrawing or withholding standard therapies in the course of the research, including
p.000099: any resulting risks to persons (Guidelines 4 and 5);
p.000099:
p.000099: 19. Any other treatment that may be given or permitted, or contraindicated, during the study (Guideline
p.000099: 6);
p.000099:
p.000099: 20. Clinical and laboratory tests and other tests that are to be carried out;
p.000099:
p.000099: 21. Samples of the standardized case-report forms to be used, the methods of recording therapeutic response
p.000099: (description and evaluation of methods and frequency of measurement), the follow-up procedures, and, if applicable, the
p.000099: measures proposed to determine the extent of compliance of persons with the treatment;
p.000099:
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p.000100: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 28. Provision for continued access to study interventions that have demonstrated significant benefit, indicating its
p.000100: modalities, the parties involved in continued care and the organization responsible for paying for it, and for how long
p.000100: it will continue (Guideline 6);
p.000100:
p.000100: 29. For research on pregnant women, a plan, if appropriate, for monitoring the outcome of the pregnancy
p.000100: with regard to both the health of the woman and the short-term and long-term health of the child (Guideline 19);
p.000100:
p.000100: 30. The means proposed to obtain individual informed consent and the procedure planned to communicate
p.000100: information to prospective participants, including the name and position of the person responsible for obtaining
p.000100: consent (Guideline 9);
p.000100:
p.000100: 31. When a prospective subject is not capable of informed consent, satisfactory assurance that permission will be
p.000100: obtained from a duly authorized person, or, in the case of a child who is sufficiently mature to
p.000100: understand the implications of informed consent but has not reached the legal age of consent, that knowing
p.000100: agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian or other duly
p.000100: authorized representative (Guidelines 16 and 17);
p.000100:
p.000100: 32. An account of any economic or other inducements or incentives to prospective participants to
p.000100: participate, such as offers of cash payments, gifts, or free services or facilities, and of any financial obligations
p.000100: assumed by the participants, such as payment for medical services;
p.000100:
p.000100: 33. Plans and procedures, and the persons responsible, for communicating to participants information arising from the
p.000100: study (on harm or benefit, for example), or from other research on the same topic, that could affect participants’
p.000100: willingness to continue in the study (Guideline 9);
p.000100:
p.000100: 34. Plans to inform participants about the results of the study;
p.000100:
p.000100: 35. The provisions for protecting the confidentiality of personal data, and respecting the privacy of persons,
p.000100: including the precautions that are in place to prevent disclosure of the results of a subject’s genetic
p.000100: tests to immediate family relatives without the consent of the subject (Guidelines 4, 11, 12 and 24);
p.000100:
p.000100: 36. Information about how the code, if any, for the persons’ identity is established, where it will be kept and when,
p.000100: how and by whom it can be broken in the event of an emergency (Guidelines 11 and 12);
p.000100:
...
Social / Child
Searching for indicator child:
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p.000050:
p.000050: protected. It can be acceptable to store personally identifiable data to enhance their value for future research; by
p.000050: implication, efforts to de-identify data in order to safeguard confidentiality and the resulting trade-offs
p.000050: in the scientific value of the given data need to be carefully balanced.
p.000050:
p.000050: Limits of confidentiality. Donors must be informed of the limits to the ability of researchers to ensure
p.000050: strict confidentiality and of the potential adverse consequences of breaches of confidentiality. Confidentiality is
p.000050: limited for three reasons. First, even with good governance structures, there is some background risk that data are
p.000050: leaked or stolen and thus are obtained by unauthorized third parties. Second, data from different sources (for example,
p.000050: health records, employment records, etc.) may be linked due to technological advances, which increasingly enable
p.000050: researchers or others to identify individuals even when working with anonymized or coded data. Identification is also
p.000050: possible when the context in which the research is conducted is narrow (for example, small hospital) or very specific
p.000050: (for example, patients with rare diseases). Pooling data from a number of comparable sources may reduce but not
p.000050: completely eliminate the possibility of identifying individuals. In addition, genetic information derived
p.000050: through comprehensive technologies (for example, whole-genome sequencing) increasingly allows identifying individuals.
p.000050: Third, releasing confidential data can be required by law. For example, some jurisdictions require the reporting to
p.000050: appropriate agencies of certain communicable diseases or evidence of child abuse or neglect. Similarly, (health)
p.000050: authorities and research ethics committee accrediting agencies may have the legal right to inspect study records, and a
p.000050: sponsor’s compliance audit staff may require and obtain access to confidential data. These and similar limits to the
p.000050: ability to maintain confidentiality must be anticipated and disclosed to potential participants (see Guideline 9 –
p.000050: Individuals capable of giving informed consent). The more difficult it becomes to truly anonymize data, the
p.000050: more important it becomes for the participant to retain the ability to remove personal data from a dataset. Therefore,
p.000050: this is a crucial part of the governance system specified above.
p.000050:
p.000050: Mandatory population-based registries. Research projects using data from mandatory population- based registries must
p.000050: be submitted for review to a research ethics committee except for data analyses inherent to the internal
p.000050: institutional research activity of the registry.
p.000050:
p.000050: Return of results and (un)solicited findings. Especially in the context of data collections in which large data bases
p.000050: are combined (big data research), the informed consent must clearly stipulate whether return of
p.000050: information derived from analysis of the data is foreseen, if the donor wishes. The information given to
p.000050: the donor should clearly state that providing individual diagnoses is not the purpose of the databank or future
...
p.000063: exclusion. As children and adolescents have distinctive physiologies and health needs, they merit special
p.000063: consideration by researchers and research ethics committees. However, their distinctive physiologies and
p.000063: emotional development may also place children and adolescents at increased risk of being harmed in the conduct of
p.000063: research. Moreover, without appropriate support, they may not be able to protect their own interests due to
p.000063: their evolving capacity to give informed consent. Specific protections to safeguard children’s rights and welfare in
p.000063: the research are therefore necessary.
p.000063:
p.000063: Before undertaking research involving children and adolescents, the researcher and the research ethics committee must
p.000063: ensure that:
p.000063: f a parent or a legally authorized representative of the child or adolescent has given permission; and
p.000063: f the agreement (assent) of the child or adolescent has been obtained in keeping with the child’s or adolescent’s
p.000063: capacity, after having been provided with adequate information about the research tailored to the child’s or
p.000063: adolescent’s level of maturity.
p.000063:
p.000063: If children reach the legal age of maturity during the research, their consent to continued participation should be
p.000063: obtained.
p.000063:
p.000063: In general, the refusal of a child or adolescent to participate or continue in the research must be respected,
p.000063: unless, in exceptional circumstances, research participation is considered the best medical option for a child or
p.000063: adolescent.
p.000063:
p.000063: For research interventions or procedures that have the potential to benefit children or adolescents, the
p.000063: risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000063:
p.000063: For research interventions or procedures that have no potential individual benefits for participants, two
p.000063: conditions apply:
p.000063: f the interventions and procedures should be studied in adults first, when these interventions and
p.000063: procedures target conditions that affect adults as well as children and adolescents, unless the necessary data
p.000063: cannot be obtained without participation of children or adolescents; and
p.000063: f the risks must be minimized and no more than minimal.
p.000063:
p.000063: When the social value of the studies with such research interventions and procedures is compelling, and these studies
p.000063: cannot be conducted in adults, a research ethics committee may permit a minor increase above minimal risk.
p.000063:
p.000063:
p.000063: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: Commentary on Guideline 17
...
p.000065: scientific reasons for performing the research in younger children first.
p.000065:
p.000065: Research must always be conducted in adults before it is conducted in children when exploring the possible toxicity of
p.000065: new drugs. First exploring the possible toxicity of new drugs in adult populations represents a way of reducing risk
p.000065: for children and adolescents who might be involved in subsequent investigations of the same intervention.
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000066: 66
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: Potential individual benefits and risks. The potential individual benefits and risks of research with
p.000066: children or adolescents should be evaluated based on Guideline 4 – Potential individual benefits and risks of research,
p.000066: and Guideline 5 – Choice of control in clinical trials.
p.000066:
p.000066: Assent. Children and adolescents who are legally minors cannot give legally valid informed consent, but they may be
p.000066: able to give assent. To give assent means that the child or adolescent is meaningfully engaged in the research
p.000066: discussion in accordance with his or her capacities. Assent must be considered as a process (see Guideline 9
p.000066: – Individuals capable of giving informed consent) and is not merely the absence of dissent. Furthermore, the researcher
p.000066: must involve the child or adolescent in the actual decision-making process and use age-appropriate information. It is
p.000066: of major importance to inform the child or adolescent and obtain assent as described above, preferably in
p.000066: writing for children who are literate. The process of obtaining assent must take into account not only the age of
p.000066: children, but also their individual circumstances, life experiences, emotional and psychological maturity, intellectual
p.000066: capabilities and the child’s or adolescent’s family situation.
p.000066:
p.000066: As adolescents near the age of majority, their agreement to participate in research may be ethically
p.000066: (though not legally) equivalent to consent. In this situation, parental consent is ethically best
p.000066: considered as “co-consent” but legally, the adolescent’s agreement remains assent. If child or adolescent
p.000066: participants reach the legal age of majority according to applicable law and become capable of independent informed
p.000066: consent during the research, their written informed consent to continued participation must be sought and their
p.000066: decision respected.
p.000066:
p.000066: Deliberate objection. Some children and adolescents who are too immature to give assent may be able to register a
p.000066: “deliberate objection,” meaning an expression of disapproval or refusal of a proposed procedure. The deliberate
p.000066: objection of an older child or adolescent, for example, is to be distinguished from the behaviour of an
p.000066: infant likely to cry or withdraw in response to almost any adverse stimulus. A deliberate objection by
p.000066: a child or adolescent to taking part in research must be respected even if the parents have given permission,
p.000066: unless the child or adolescent needs treatment that is not available outside the context of research, the research
p.000066: intervention has a clear prospect of clinical benefit, and the treating physician and the legally authorized
p.000066: representative consider the research intervention to be the best available medical option for the given
p.000066: child or adolescent. In such cases, particularly if the child is very young or immature, a parent or guardian may
p.000066: override the child`s objections. However, in some situations parents may press a researcher to persist with an
p.000066: investigational intervention against the child`s wishes. Sometimes this pressure is meant to serve the parents’
p.000066: interests rather than the child’s. In this case, the parents’ decision must be overridden if the researcher believes it
p.000066: is not in the child’s best clinical interest to enrol or continue study participation.
p.000066:
p.000066: Permission of a parent or legally authorized representative. The researcher must obtain the permission of
p.000066: at least one parent or guardian in writing, consistent with applicable laws and regulations. The age at
p.000066: which a child becomes legally capable to give consent differs substantially from one jurisdiction to another.
p.000066: Often children who have not yet reached the legally established age of consent can understand the implications
p.000066: of research participation and go through standard informed consent procedures; however, legally they can only assent to
p.000066: serve as research participants. Independent of its quality, assent is never sufficient to permit participation in
p.000066: research unless it is supplemented by the permission of a parent, legal guardian or other duly authorized
p.000066: representative. The decision to continue or discontinue participation by children or adolescents who become legally
p.000066: capable during the study trumps the decision of their parents or legal guardians.
p.000066:
p.000066: Waiver of parental permission. In certain circumstances, research ethics committees may waive parental permission. In
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
p.000066:
p.000066: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000067: 67
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
p.000067: psychological and medical support for the participating children and adolescents is another special
p.000067: protection, though this may be difficult to realize in some communities. In such communities, the study
p.000067: personnel must be sufficiently qualified to help children and adolescents who need medical and psychological support.
p.000067:
p.000067: A research ethics committee may also allow a waiver of parental permission if the conditions set out in Guideline 10 –
p.000067: Modifications and waivers of informed consent - are satisfied.
p.000067:
p.000067: Observation of the study by a parent or guardian. A parent or legally appointed guardian who gives permission for a
p.000067: child or adolescent to participate in research must generally be given the opportunity, to a reasonable
p.000067: extent and without violating the privacy of other study participants, to observe the child’s participation as
p.000067: the study proceeds. This could enable the child to be withdrawn if the parent or guardian decides it is in the child’s
p.000067: best interests to do so.
p.000067:
p.000067: Emergency care situations in which the researcher anticipates that children and adolescents will participate. When
p.000067: children and adolescents participate in emergency care research, the principles of Guideline 16 – Research involving
p.000067: adults incapable of giving informed consent - apply.
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000068: 68
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: GUIDELINE 18:
p.000068: WOMEN AS RESEARCH PARTICIPANTS
p.000068:
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
p.000068: physiologies and health needs, they merit special consideration by researchers and research ethics committees. Only the
p.000068: informed consent of the woman herself should be required for her research participation. Since some societies lack
p.000068: respect for women’s autonomy, in no case must the permission of another person replace the requirement of individual
p.000068: informed consent by the woman.
p.000068:
p.000068: Women of child-bearing potential must be informed in advance of the possibility of risks to the fetus
p.000068: should they become pregnant during their research participation. When participation in research might be
p.000068: hazardous to a fetus or a woman if she becomes pregnant, sponsors and researchers must guarantee access to pregnancy
p.000068: tests, effective contraceptive methods before and during the research and to safe, legal abortion.
p.000068:
p.000068:
p.000068: Commentary on Guideline 18
p.000068: General considerations. Women in many societies have been excluded from research. For example, most of the early
p.000068: cardiovascular disease studies have excluded women because these diseases were believed to be uncommon in women. In
p.000068: particular, women who are biologically capable of becoming pregnant have been traditionally excluded from clinical
p.000068: trials of drugs, vaccines and medical devices owing to concern about undetermined risks to the fetus (see
p.000068: Guideline 15 – Research involving vulnerable persons and groups). Although the presumption against including women
...
p.000069: 69
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: place without the possibility of intrusion by other family members. In such studies, women must be given
p.000069: the option of conducting the interview in a setting of their choosing outside the home. Breach of
p.000069: confidentiality in these types of research could result in serious harms to women, even if the only information
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
p.000069: could include risks to the fetus if they become pregnant during the research (see Guideline 19 – Pregnant
p.000069: women and breastfeeding women as research participants). Access to a pregnancy test, to effective
p.000069: contraceptive methods and to safe, legal abortion must be guaranteed before exposure to a potential teratogenic or
p.000069: mutagenic intervention. When effective contraception and safe abortion are not available and alternative study sites
p.000069: are not feasible, the informed consent discussion must include information about the risk of unintended pregnancy, the
p.000069: legal grounds for abortion, and information about reducing harms from unsafe abortion and subsequent complications.
p.000069: Also, if the pregnancy is not terminated, participants must be guaranteed a medical follow-up for their own health and
p.000069: that of the infant and child.
p.000069:
p.000069: Women who become pregnant during research. Many biomedical protocols call for terminating the participation of women
p.000069: who become pregnant during the research. In cases where a drug or biological product is known to be mutagenic or
p.000069: teratogenic, pregnant women must be removed from the study, and followed up and provided care through
p.000069: the duration of their pregnancy and delivery. Access to diagnostic tests must be provided to reveal any fetal
p.000069: anomalies. If anomalies are detected, women who wish may be referred for an abortion. When there is no evidence on the
p.000069: basis of which a potential harm to the fetus can be assumed, women who become pregnant should not automatically be
p.000069: removed from the study, but must be offered the option to continue or end their participation. For instance, in some
p.000069: cases it may be appropriate for a woman to stay in the study for safety monitoring but removed from the study drug. If
p.000069: the woman opts for continued participation, researchers and sponsors must offer adequate monitoring and support.
...
p.000070: breastfeeding women:
p.000070: f the risks must be minimized and no more than minimal; and
p.000070: f the purpose of the research must be to obtain knowledge relevant to the particular health needs of
p.000070: pregnant or breastfeeding women or their fetuses or infants.
p.000070:
p.000070: When the social value of the research for pregnant or breastfeeding women or their fetus or infant is compelling,
p.000070: and the research cannot be conducted in non-pregnant or non- breastfeeding women, a research ethics committee
p.000070: may permit a minor increase above minimal risk.
p.000070:
p.000070: Short-term and long‐term follow-up of the fetus and the child may be required in research involving pregnant and
p.000070: breastfeeding women depending upon the study intervention and its potential risks.
p.000070:
p.000070: As a general rule, health-related research involving pregnant women that has the potential for harm to the fetus should
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
p.000070:
p.000070:
...
p.000071: remains the same: she is the decision-maker for any interventions that affect her. This does not exclude the
p.000071: possibility of the woman consulting with the father of the fetus, if she wishes.
p.000071:
p.000071: Especially in communities or societies in which cultural beliefs accord more importance to the fetus than to the
p.000071: woman’s life or health, women may feel constrained to participate, or not to participate,
p.000071:
p.000071: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000072: 72
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: in research. Special safeguards must be established to prevent undue inducement to pregnant women to
p.000072: participate in research in which interventions hold out the prospect of potential individual benefit to the fetus but
p.000072: not to the woman herself.
p.000072:
p.000072: Researchers must include in protocols on research involving pregnant women a plan for monitoring the outcome of the
p.000072: pregnancy with regard to both the health of the woman and the short-term and long-term health of the infant and child.
p.000072: Adverse events associated with research in pregnancy and during lactation may not occur immediately.
p.000072:
p.000072: Potential individual benefits and risks. The potential individual benefits and risks of research with pregnant and
p.000072: breastfeeding women should be evaluated based on Guideline 4 – Potential individual benefits and risks of research, and
p.000072: Guideline 5 – Choice of control in clinical trials.
p.000072:
p.000072: Serious harm and access to abortion. Research with pregnant women must be conducted only in settings where
p.000072: these women can be guaranteed access to a safe, legal abortion. This rule serves to prevent women from having to carry
p.000072: an unwanted fetus to term and deliver an affected baby against their wishes. Before pregnant women are enrolled,
p.000072: researchers must, at a minimum, determine whether fetal impairment and mental health conditions are recognised as legal
...
p.000079: research), but health care workers must nevertheless be notified that a study is taking place. If the
p.000079: interventions are directly carried out on patients, they would normally also be considered research subjects and their
p.000079: consent to receive the intervention would be required.
p.000079:
p.000079: Although in many CRTs participants cannot consent to being randomized, depending on the type of study design they may
p.000079: be able to give informed consent to receive the intervention. The intervention may be delivered at the individual level
p.000079: while the communities to which the individuals belong are randomized at the cluster level (for example, a vaccination
p.000079: campaign applied at the school level). These trials are called individual-cluster randomized trials. In some
p.000079: individual-cluster randomized trials, individuals may be able to consent to the intervention before it is administered
p.000079: in that cluster. For example, parents will not be able to consent to their children’s school being randomized to a
p.000079: vaccination programme or to being allocated to that cluster, but they could consent or refuse to consent to their
p.000079: child’s vaccination at school. In other CRTs, both the intervention and the community are randomized at the cluster
p.000079: level. These trials are called cluster-cluster randomized trials (for example, all the students in a school or
p.000079: all residents of a community). In cluster-cluster randomized trials, individual informed consent for receiving the
p.000079: intervention is typically difficult to obtain since it is almost impossible to avoid the intervention. At the same
p.000079: time, individual consent for data collection procedures is usually possible in both types of cluster randomized trials.
p.000079:
p.000079: Ethical acceptability of a no-intervention group. Some CRTs investigate interventions that have been proven
p.000079: to be effective elsewhere; this is termed implementation research. This type of research is often conducted in
p.000079: low-resource settings. An ethical question pertaining to this type of study is whether it is acceptable
p.000079: to withhold the proven intervention from a control group in a CRT. This situation is analogous to that of
p.000079: placebo controls in a randomized, controlled trial when an established, effective prevention or treatment exists. If
p.000079: withholding the proven intervention from the control cluster would expose participants to more than a minor
p.000079: increase above minimal risk, it would be unethical to use that study design. An example would be the introduction of
...
p.000099: to any drug, vaccine or procedure to be tested (Guideline 4);
p.000099:
p.000099: 25. The potential individual benefits of the research to participants and to others (Guideline 4);
p.000099:
p.000099: 26. The expected benefits of the research to the population, including new knowledge that the study might
p.000099: generate (Guidelines 1 and 4);
p.000099:
p.000099: 27. For research carrying more than minimal risk of physical injury, details of plans, including
p.000099: insurance coverage, to provide treatment for such injury, including the funding of treatment, and to provide
p.000099: compensation for research-related disability or death (Guideline 14);
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
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p.000100: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000100:
p.000100:
p.000100:
p.000100:
p.000100:
p.000100: 28. Provision for continued access to study interventions that have demonstrated significant benefit, indicating its
p.000100: modalities, the parties involved in continued care and the organization responsible for paying for it, and for how long
p.000100: it will continue (Guideline 6);
p.000100:
p.000100: 29. For research on pregnant women, a plan, if appropriate, for monitoring the outcome of the pregnancy
p.000100: with regard to both the health of the woman and the short-term and long-term health of the child (Guideline 19);
p.000100:
p.000100: 30. The means proposed to obtain individual informed consent and the procedure planned to communicate
p.000100: information to prospective participants, including the name and position of the person responsible for obtaining
p.000100: consent (Guideline 9);
p.000100:
p.000100: 31. When a prospective subject is not capable of informed consent, satisfactory assurance that permission will be
p.000100: obtained from a duly authorized person, or, in the case of a child who is sufficiently mature to
p.000100: understand the implications of informed consent but has not reached the legal age of consent, that knowing
p.000100: agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian or other duly
p.000100: authorized representative (Guidelines 16 and 17);
p.000100:
p.000100: 32. An account of any economic or other inducements or incentives to prospective participants to
p.000100: participate, such as offers of cash payments, gifts, or free services or facilities, and of any financial obligations
p.000100: assumed by the participants, such as payment for medical services;
p.000100:
p.000100: 33. Plans and procedures, and the persons responsible, for communicating to participants information arising from the
p.000100: study (on harm or benefit, for example), or from other research on the same topic, that could affect participants’
p.000100: willingness to continue in the study (Guideline 9);
p.000100:
p.000100: 34. Plans to inform participants about the results of the study;
p.000100:
p.000100: 35. The provisions for protecting the confidentiality of personal data, and respecting the privacy of persons,
p.000100: including the precautions that are in place to prevent disclosure of the results of a subject’s genetic
p.000100: tests to immediate family relatives without the consent of the subject (Guidelines 4, 11, 12 and 24);
p.000100:
...
p.000104: limitations, whether it is planned that biological specimens collected in the research will be destroyed at its
p.000104: conclusion, and, if not, details about their storage (where, how, for how long, and final disposition) and possible
p.000104: future use, that participants have the right to decide about such future use, to refuse storage, and to have the
p.000104: material destroyed (Guidelines 11 and 12);
p.000104:
p.000104: 6. when women of childbearing potential are participating in health-related research, information about the
p.000104: possible risks, if they become pregnant during the research, to themselves (including future fertility), their
p.000104: pregnancies, their fetuses, and their future offspring; and the guaranteed access to a pregnancy test, to effective
p.000104: contraceptive methods and to safe, legal abortion before exposure to a potential teratogenic or mutagenic intervention.
p.000104: When effective contraception and/ or safe abortion are not available and alternative study sites are not feasible, the
p.000104: women must be given information about: the risk of unintended pregnancy; the legal grounds for abortion; reducing harms
p.000104: from unsafe abortion and subsequent complications; and, when pregnancy is not terminated, the guarantee for a medical
p.000104: follow-up for their own health and that of the infant and child and the information that it is often difficult to
p.000104: determine causality in cases of fetal or infant abnormalities (Guidelines 18 and 19);
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000104:
p.000105: 105
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: 7. when concerning pregnant and breastfeeding women, the risks of participation in health-related research to
p.000105: themselves, their pregnancies, their fetuses, and their future offspring, what has been done to maximize potential
p.000105: individual benefits and minimize risks, that evidence concerning risks may be unknown or controversial, and that
p.000105: it is often difficult to determine causality in cases of fetal or infant abnormalities (Guidelines 4 and 19);
p.000105:
p.000105: 8. when concerning disaster victims who mostly are under duress, the difference between research and humanitarian
p.000105: aid (Guideline 20); and
p.000105:
p.000105: 9. when research is done in the online environment and using online or digital tools that may
p.000105: involve potentially vulnerable persons, information about the privacy and security controls that will be used to
p.000105: protect their data; and the limitations of the measures used and the risks that may remain despite the safeguards put
p.000105: in place (Guideline 22).
p.000105:
p.000105:
...
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p.000007: GUIDELINE 7: COMMUNITY ENGAGEMENT 25
p.000007: GUIDELINE 8: COLLABORATIVE PARTNERSHIP AND CAPACITY-BUILDING
p.000007: FOR RESEARCH AND RESEARCH REVIEW 29
p.000007: GUIDELINE 9: INDIVIDUALS CAPABLE OF GIVING INFORMED CONSENT 33
p.000007: GUIDELINE 10: MODIFICATIONS AND WAIVERS OF INFORMED CONSENT 37
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: v
p.000007:
p.000007: GUIDELINE 11: COLLECTION, STORAGE AND USE OF BIOLOGICAL
p.000007: MATERIALS AND RELATED DATA 41
p.000007: GUIDELINE 12: COLLECTION, STORAGE AND USE OF DATA IN HEALTH- RELATED RESEARCH
p.000047: 47
p.000047: GUIDELINE 13: REIMBURSEMENT AND COMPENSATION FOR
p.000047: RESEARCH PARTICIPANTS 53
p.000047: GUIDELINE 14: TREATMENT AND COMPENSATION FOR RESEARCH-
p.000047: RELATED HARMS
p.000055: 55
p.000055: GUIDELINE 15: RESEARCH INVOLVING VULNERABLE PERSONS
p.000055: AND GROUPS
p.000057: 57
p.000057: GUIDELINE 16: RESEARCH INVOLVING ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000061: 61
p.000061: GUIDELINE 17: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS 65
p.000061: GUIDELINE 18: WOMEN AS RESEARCH PARTICIPANTS 69
p.000061: GUIDELINE 19: PREGNANT AND BREASTFEEDING WOMEN AS
p.000061: RESEARCH PARTICIPANTS 71
p.000061: GUIDELINE 20: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS 75
p.000061: GUIDELINE 21: CLUSTER RANDOMIZED TRIALS 79
p.000061: GUIDELINE 22: USE OF DATA OBTAINED FROM THE ONLINE
p.000061: ENVIRONMENT AND DIGITAL TOOLS IN HEALTH-RELATED RESEARCH 83
p.000061: GUIDELINE 23: REQUIREMENTS FOR ESTABLISHING RESEARCH ETHICS COMMITTEES AND FOR THEIR REVIEW OF PROTOCOLS
p.000087: 87
p.000087: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000087: vi
p.000087:
p.000087: GUIDELINE 24: PUBLIC ACCOUNTABILITY FOR HEALTH-RELATED RESEARCH 91
p.000087: GUIDELINE 25: CONFLICTS OF INTEREST 95
p.000087: APPENDIX 1 ITEMS TO BE INCLUDED IN A PROTOCOL (OR ASSOCIATED DOCUMENTS) FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099: APPENDIX 2 OBTAINING INFORMED CONSENT: ESSENTIAL
p.000099: INFORMATION FOR PROSPECTIVE RESEARCH PARTICIPANTS 103
p.000099: APPENDIX 3 CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH
p.000099: INVOLVING HUMANS
p.000107: 107
...
p.000005:
p.000005:
p.000005: Commentary on Guideline 3
p.000005: General considerations. The equitable distribution of benefits and burdens in the selection of study
p.000005: populations requires that the benefits of research be distributed fairly and that no group or class of persons bears
p.000005: more than its fair share of the risks or burdens from research participation. When benefits or burdens of research are
p.000005: to be apportioned unequally among individuals or groups, the criteria for unequal distribution should be scientifically
p.000005: and ethically justified rather than arbitrarily or conveniently chosen. Situations where unequal distribution of
p.000005: benefits would be considered are those in which the research particularly affects the population under study.
p.000005: In general, equitable distribution requires that participants be drawn from the qualifying population in the
p.000005: geographic area of the study where the results can be applied (see Guideline 2 – Research conducted in low-resource
p.000005: settings). Inclusion and exclusion criteria should not be based upon potentially discriminatory criteria, such as race,
p.000005: ethnicity, economic status, age or sex, unless there is a sound ethical or scientific reason to do so. For example, in
p.000005: cases where the under-representation of particular groups results in or perpetuates health disparities, equity may
p.000005: require special efforts to include members of those populations in research (see Guideline 17 – Research involving
p.000005: children and adolescents, Guideline 18
p.000005: – Women as research participants, and Guideline 19 – Pregnant women and breastfeeding women as research participants).
p.000005:
p.000005:
p.000005:
p.000005: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: Fair distribution of research benefits. Equity in the distribution of the benefits of research requires
p.000007: that research not disproportionately focus on the health needs of a limited class of people, but instead
p.000007: aims to address diverse health needs across different classes or groups. In the past, groups considered vulnerable
p.000007: were excluded from participation in research because it was considered the most expedient way of protecting
p.000007: those groups (for example, children, women of reproductive age, pregnant women). As a consequence of such exclusions,
p.000007: information about the diagnosis, prevention and treatment of diseases that afflict such groups is limited. This has
p.000007: resulted in a serious injustice. Since information about the management of diseases is considered a benefit to society,
p.000007: it is unjust to intentionally deprive specific groups of that benefit. The need to redress these injustices by
p.000007: encouraging the participation of previously excluded groups in basic and applied biomedical research is widely
p.000007: recognized.
p.000007:
p.000007: Fair distribution of research burdens. Research with human participants typically requires that some persons or
p.000007: groups are exposed to risks and burdens in order to generate the knowledge needed to protect and promote
p.000007: people’s health (see Guideline 1 – Scientific and social value and respect for rights). Equity in the distribution of
p.000007: burdens of research requires special care to ensure that individuals, communities or populations that are already
p.000007: disadvantaged or marginalized are not over-represented in research. A disproportionate selection of disadvantaged or
p.000007: convenient populations is morally problematic for several reasons. First, it is unjust to selectively invite poor or
p.000007: marginalized individuals or groups to participate in research because this concentrates the risks and burdens of
...
p.000008: established effective alternative. Therefore, as a general rule, participants in the control group of a trial must
p.000008: receive an established effective intervention. The conditions under which a placebo may be used are spelled out in
p.000008: Guideline 5 – Choice of control in clinical trials.
p.000008: f For research interventions or procedures that offer no potential individual benefits to participants, the risks
p.000008: must be minimized and appropriate in relation to the social and scientific value of the knowledge to be gained
p.000008: (expected benefits to society from the generalizable knowledge).
p.000008: f In general, when it is not possible or feasible to obtain the informed consent of participants,
p.000008: research interventions or procedures that offer no potential individual benefits must pose no more than minimal
p.000008: risks. However, a research ethics committee may permit a minor increase above minimal risk when it is not possible to
p.000008: gather the necessary data in another population or in a less risky or burdensome manner, and the social and scientific
p.000008: value of the research is compelling (see Guideline 16 – Research involving adults incapable of giving informed
p.000008: consent, and Guideline 17 – Research involving children and adolescents).
p.000008:
p.000008: In a second step, the aggregate risks and potential individual benefits of the entire study must be assessed and must
p.000008: be considered appropriate.
p.000008: f The aggregate risks of all research interventions or procedures in a study must be considered
p.000008: appropriate in light of the potential individual benefits to participants and the scientific social value of the
p.000008: research.
p.000008: f The researcher, sponsor and research ethics committee must also consider risks to groups and
p.000008: populations, including strategies to minimize these risks.
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: f The potential individual benefits and risks of research studies must be evaluated in consultation with
p.000009: the communities to be involved in the research (see Guideline 7 – Community engagement).
p.000009:
p.000009:
p.000009: Commentary on Guideline 4
p.000009: General considerations. Participants in health research are often exposed to a variety of interventions or procedures,
p.000009: many of which pose some risk. In this Guideline, the term “intervention” refers to the objects of study, such as new or
p.000009: established therapies, diagnostic tests, preventive measures and various techniques (for example, financial
p.000009: incentives) that might be used to modify health-related behaviours. The term “procedure” refers to research
p.000009: activities that provide information about the object of study, for example the safety and efficacy of a new therapy.
...
p.000015: yield valid research results. Researchers and sponsors must carefully consider whether the research question
p.000015: can be answered with an alternative design, and whether the risk-benefit profile of alternative designs is more
p.000015: favourable when compared to a conventional randomized controlled trial.
p.000015:
p.000015: Established effective intervention. An established effective intervention for the condition under study exists when it
p.000015: is part of the medical professional standard. The professional standard includes, but is not limited to, the best
p.000015: proven intervention for treating, diagnosing or preventing the given condition. In addition, the professional
p.000015: standard includes interventions that may not be the very best when compared to available alternatives, but are
p.000015: nonetheless professionally recognized as a reasonable option (for example, as evidenced in treatment guidelines).
p.000015:
p.000015: Yet established effective interventions may need further testing, especially when their merits are subject
p.000015: to reasonable disagreement among medical professionals and other knowledgeable persons. Clinical trials may be
p.000015: warranted in this case, in particular if the efficacy of an intervention or procedure has not been determined in
p.000015: rigorous clinical trials. Trials may also be useful when the risk-benefit profile of a treatment is not clearly
p.000015: favourable, such that patients might reasonably forgo the usual intervention for the condition (for example, antibiotic
p.000015: treatment for otitis media in children, or arthroscopic knee surgery). When there are several treatment
p.000015: options but it remains unknown which treatment works best for whom, comparative effectiveness research may help to
p.000015: further determine the effectiveness of an intervention or procedure for specific groups. This may include testing an
p.000015: established effective intervention against a placebo, provided the conditions of this Guideline are met.
p.000015:
p.000015: Some people contend that it is never acceptable for researchers to withhold or withdraw established effective
p.000015: interventions. Others argue that it may be acceptable, provided that the risks of withholding an established
p.000015: intervention are acceptable, and withholding the established effective intervention is necessary to ensure that
p.000015: the results are interpretable and valid. In such cases, an intervention known to be inferior, a placebo (see below) or
p.000015: no intervention may be substituted for the established intervention. This Guideline takes a middle stance on
p.000015: this issue. The preferred option is to test potential new interventions against an established effective
p.000015: intervention. When researchers propose to deviate from this option, they must provide a compelling methodological
p.000015: justification and evidence that the risks from withholding or delaying the established intervention are no greater than
p.000015: a minor increase above minimal risk.
p.000015:
p.000015: These principles on the use of placebo also apply to the use of control groups who receive no treatment or who
...
p.000031: deception.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Informed consent is based on the principle that individuals capable of giving informed consent have a right to choose
p.000033: freely whether to participate in research. Informed consent protects the individual’s freedom of choice and respects
p.000033: the individual’s autonomy.
p.000033:
p.000033: The information must be provided in plain language understandable by the potential participant. The person
p.000033: obtaining informed consent must be knowledgeable about the research and capable of answering any questions from
p.000033: potential participants. Researchers in charge of the study must make themselves available to answer questions at the
p.000033: request of participants. Participants should be offered the opportunity to ask questions and receive answers before or
p.000033: during the research. Researchers should make every effort to address those questions in a timely and comprehensive
p.000033: manner.
p.000033:
p.000033: This Guideline applies to individuals capable of giving informed consent. Requirements for research with individuals
p.000033: who are not capable of giving informed consent or with children and adolescents are set out in Guideline 16 –
p.000033: Research involving adults incapable of giving informed consent, and Guideline 17 – Research involving children
p.000033: and adolescents.
p.000033:
p.000033: Process. Informed consent is a two-way communicative process that begins when initial contact is made with a potential
p.000033: participant and ends when consent is provided and documented, but can be revisited later during the conduct of the
p.000033: study. Each individual must be given as much time as needed to reach a decision, including time for consultation with
p.000033: family members or others. Adequate time and resources must be provided for informed-consent procedures.
p.000033:
p.000033: Language of the information leaflet and recruitment material. All potential participants should be provided with a
p.000033: written information leaflet that they may take with them. Informing the individual participant must not be simply a
p.000033: ritual recitation of the contents of a written document. The wording of the leaflet and any recruitment material
p.000033: must be in language understandable by the potential participant and be approved by the research ethics
p.000033: committee. The wording of the leaflet must be short and preferably not exceed two or three pages. An oral presentation
p.000033: of information or the use of appropriate audiovisual aids, including pictographs and summary tables, are important to
p.000033: supplement written information documents to aid understanding. Information should also be appropriate for the
...
p.000033: comprehension. The potential participant’s ability to understand the information depends, among other things, on the
p.000033: individual’s maturity, educational level and belief system. The participant’s understanding also depends on the
p.000033: researcher’s ability and willingness to communicate with patience and sensitivity, as well as the atmosphere, situation
p.000033: and location where the informed consent process takes place.
p.000033:
p.000033: Documentation of consent. Consent may be indicated in a number of ways. The participant may express consent orally, or
p.000033: sign a consent form. As a general rule, the participant should sign a consent form, or, where the individual lacks
p.000033: decisional capacity, a legal guardian or other duly authorized
p.000033:
p.000033:
p.000033: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000034: 34
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: representative must do so (see Guideline 16 – Research involving individuals incapable of giving informed
p.000034: consent, and Guideline 17 – Research involving children and adolescents). The research ethics committee may approve a
p.000034: waiver of the requirement of a signed consent document under certain conditions (see Guideline 10 – Modifications and
p.000034: waivers of informed consent). Such waivers may also be approved when existence of a signed consent form might pose a
p.000034: risk to the participant, for example in studies involving illegal behaviour. In some cases, especially when the
p.000034: information is complicated, participants should be given information sheets to retain; these may resemble
p.000034: conventional sheets in all respects except that participants are not required to sign them. Their wording
p.000034: must be approved by the research ethics committee. When consent has been obtained orally, researchers
p.000034: should provide to the research ethics committee documentation of consent, certified either by the person
p.000034: obtaining consent or by a witness at the time consent is obtained.
p.000034:
p.000034: Renewing consent. When substantive changes occur in any aspect of a study, the researcher must again seek
...
p.000037: research. Such informing, commonly called “debriefing”, ordinarily entails explaining the reasons for the deception.
p.000037: Debriefing is an essential part of trying to rectify the wrong of deception. Participants who disapprove of having been
p.000037: deceived for research purposes must be offered an opportunity to refuse to allow the researcher to use their data
p.000037: obtained through deception. In exceptional cases, a research ethics committee may approve the retention of
p.000037: non-identifiable information. For example, an option to withdraw data may not be offered in cases where research is
p.000037: evaluating quality of services or competence of providers (for example, studies involving “mystery” clients or
p.000037: patients).
p.000037:
p.000037: Waiving informed consent. A research ethics committee may waive informed consent if it is convinced that
p.000037: the research would not be feasible or practicable to carry out without the waiver, the research has
p.000037: important social value, and the research poses no more than minimal risks to participants. These three
p.000037: conditions must also be met even when a study involves identifiable data or biological specimens, meaning that the data
p.000037: or specimens carry a person’s name or are linked to a person by a code. The conditions must also be met when studies
p.000037: analyse existing data from health-related registries, and when the participants are children, adolescents, and
p.000037: individuals not capable of giving informed consent (Guideline 16 – Research involving adults incapable of
p.000037: giving informed consent, and Guideline 17 – Research involving children and adolescents).
p.000037:
p.000037: In addition, the three conditions for waiving informed consent must be met when data or biological specimens are not
p.000037: personally identifiable and the research has important social value. In this situation, the participants are unknown to
p.000037: the researcher and hence cannot be contacted to obtain informed
p.000037:
p.000037: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000038: 38
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038: consent. Moreover, because the data or specimens are not personally identifiable, the risks to those individuals are no
p.000038: greater than minimal.
p.000038:
p.000038: Special considerations for waiving informed consent in studies using data in health- registries. The
p.000038: creation and maintenance of health-related registries (for example, cancer registries and databanks of genetic and
p.000038: other anomalies in newborn babies) provide a major resource for many public health and epidemiological research
p.000038: activities, ranging from disease prevention to resource allocation. Several considerations support the common practice
p.000038: of requiring that all practitioners submit relevant data to such registries: the importance of having
p.000038: comprehensive and accurate information about an entire population; the scientific need to include all
p.000038: cases in order to avoid undetectable selection bias; and the ethical principle that burdens and benefits must be
p.000038: distributed equitably across the population. Hence, registries established as mandatory by governmental
...
p.000044: return of information derived from analysis of the materials is foreseen, if the donor wishes. The information given to
p.000044: the donor should clearly state that providing individual diagnoses is not the purpose of the biobank or future
p.000044: research project, in order to prevent that donors are falsely reassured by the absence of unsolicited findings.
p.000044:
p.000044: There is an emerging consensus that at least some findings in genetic research must be returned to individual donors if
p.000044: they wish. Tiered consent, meaning the possibility of obtaining packages or subsets of information, gives donors a
p.000044: range of choices and allows them to choose some options to give them greater control over the use of their biological
p.000044: materials. In general, the three guiding principles for return of results need to be followed: results must
p.000044: have analytical validity, clinical significance and actionability to qualify for being returned. This implies that
p.000044: life-saving information and data of immediate clinical utility involving a significant health problem must
p.000044: be offered for disclosure, whereas information of uncertain scientific validity or clinical significance
p.000044: would not qualify for communication to the participant. The research ethics committee should also evaluate whether
p.000044: individual counselling is necessary when returning particular genetic findings. Some cases may require making an
p.000044: ethically responsible management plan for returning (un)solicited findings.
p.000044:
p.000044: Children and adolescents. Children and adolescents who reach the age of maturity during the research
p.000044: project should be given the opportunity to give informed consent for the continued storage and use of their
p.000044: material and related data, and they should also be able to withdraw consent for future research. An
p.000044: informed, opt-out system in which such persons are alerted to their right to withdraw could also be
p.000044: acceptable.
p.000044:
p.000044: Material Transfer Agreement. The transfer of human biological materials must be covered by a material transfer
p.000044: agreement (MTA). This MTA must ensure that the biological materials are documented in such a way that they can be
p.000044: retrieved. The range and duration of use and what needs to happen at the end of the period of use must also be
p.000044: specified. All responsibilities concerning these elements of an MTA need to be clearly stated in the agreement. An MTA
p.000044: is also needed in multinational research projects in which one entity collects samples from persons in all
p.000044: participating countries and stores them in a single biobank.
p.000044:
p.000044: Closure of a biobank. In the event of closure of the biobank, plans for appropriate transfer or
p.000044: disposal of the biological material and data should be developed in collaboration with local health authorities.
p.000044:
p.000044: Storing and using material from low-resource settings in biobanks. Biobanks have become a global phenomenon.
p.000044: Nevertheless, some low-resource settings may be inexperienced in storing and using biological materials. In
...
p.000050:
p.000050: There is an emerging consensus that at least some findings in genetic research must be returned to individual donors if
p.000050: they wish. Tiered consent, meaning the possibility of obtaining packages or subsets of information, gives donors a
p.000050: range of choices and allows them to choose some options to give them greater control over the use of their
p.000050: data. In general, the three guiding principles for return of results need to be followed: results must have
p.000050: analytical validity, clinical significance and actionability to qualify for being returned. This implies that
p.000050: life-saving information and data of immediate clinical utility involving a significant health problem must be offered
p.000050: for disclosure, whereas information of uncertain scientific validity or clinical significance would not qualify for
p.000050: communication to the donor. The research ethics committee should also evaluate whether individual counselling is
p.000050: necessary when returning particular genetic findings. Some cases may require making an ethically responsible management
p.000050: plan for returning (un)solicited findings.
p.000050:
p.000050: Data-sharing. Researchers, sponsors and research ethics committees must share data for further research where possible.
p.000050: The conditions for data sharing are spelled out in Guideline 24 – Public accountability for health-related research.
p.000050:
p.000050:
p.000050:
p.000050: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000051: 51
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051: Children and adolescents. Children and adolescents who reach the age of maturity must be given the opportunity to give
p.000051: broad informed consent for the continued storage and use of their data and should also be able to withdraw consent for
p.000051: future research. An informed, opt-out system in which such persons are alerted to their right to withdraw, could also
p.000051: be acceptable.
p.000051:
p.000051: Closure of a databank. In the event of closure of the databank, plans for appropriate transfer or disposal of the
p.000051: health-related data should be developed in collaboration with local health authorities.
p.000051:
p.000051: Storing and using data from low-resource settings in databanks. Databanks have become a global phenomenon.
p.000051: Nevertheless, some low-resource settings may be inexperienced in storing and using biological materials. In addition to
p.000051: what is stated in this Guideline, requirements for community engagement, capacity-building and equitable
p.000051: distribution of burdens and benefits of research as described in other guidelines also apply to databank
p.000051: research in low-resource settings (see Guideline 3 – Equitable distribution of benefits and burdens in the
p.000051: selection of individuals and groups of participants in research, Guideline 7 – Community engagement, and Guideline 8 –
p.000051: Collaborative partnership and capacity building for research and review).
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
p.000051:
...
p.000056: may also co-exist, making some individuals more vulnerable than others. This is highly dependent on the context.
p.000056: For example, persons who are illiterate, marginalized by virtue of their social status or behaviour, or living in an
p.000056: authoritarian environment, may have multiple factors that make them vulnerable.
p.000056:
p.000056: Some characteristics can make it reasonable to assume that certain individuals are vulnerable, for example:
p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
p.000056:
p.000056: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
p.000057: Examples are medical and nursing students, subordinate hospital and laboratory personnel, workers in settings
p.000057: where research studies are conducted, and members of the armed forces or police. Their agreement to volunteer may be
p.000057: unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate
p.000057: in the study or by fear of disapproval or retaliation if they refuse (see also commentary on Guideline 9 – Individuals
p.000057: capable of giving informed consent). The research protocol must include a description of provisions to protect such
p.000057: individuals from being conscripted into research.
p.000057:
p.000057: Institutionalized persons. Residents of nursing homes, mental institutions, and prisons are often considered vulnerable
p.000057: because in a confined setting they have few options and are denied certain freedoms that non-institutionalized persons
...
p.000062: permission of a legally authorized representative must be sought. This permission must take account of the
p.000062: participant’s previously expressed preferences and values, if any.
p.000062:
p.000062: In all cases in which research has been approved to begin without prior consent of incapacitated persons because of
p.000062: suddenly occurring conditions, they must be given all relevant information as soon as they regain capacity, and their
p.000062: consent to remain in the study must be obtained as soon as reasonably possible. In addition, they must be given the
p.000062: opportunity to opt out of the study.
p.000062:
p.000062: Waivers of the permission by a legally authorized representative. Research ethics committees may waive the
p.000062: requirement to obtain permission from a legally authorized representative if the conditions for waiving
p.000062: informed consent in research with participants who are capable of giving informed consent are satisfied
p.000062: (Guideline 10 – Modifications and waivers of informed consent).
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000063: 63
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063: GUIDELINE 17:
p.000063: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS
p.000063:
p.000063: Children and adolescents must be included in health-related research unless a good scientific reason justifies their
p.000063: exclusion. As children and adolescents have distinctive physiologies and health needs, they merit special
p.000063: consideration by researchers and research ethics committees. However, their distinctive physiologies and
p.000063: emotional development may also place children and adolescents at increased risk of being harmed in the conduct of
p.000063: research. Moreover, without appropriate support, they may not be able to protect their own interests due to
p.000063: their evolving capacity to give informed consent. Specific protections to safeguard children’s rights and welfare in
p.000063: the research are therefore necessary.
p.000063:
p.000063: Before undertaking research involving children and adolescents, the researcher and the research ethics committee must
p.000063: ensure that:
p.000063: f a parent or a legally authorized representative of the child or adolescent has given permission; and
p.000063: f the agreement (assent) of the child or adolescent has been obtained in keeping with the child’s or adolescent’s
p.000063: capacity, after having been provided with adequate information about the research tailored to the child’s or
p.000063: adolescent’s level of maturity.
p.000063:
p.000063: If children reach the legal age of maturity during the research, their consent to continued participation should be
p.000063: obtained.
p.000063:
p.000063: In general, the refusal of a child or adolescent to participate or continue in the research must be respected,
p.000063: unless, in exceptional circumstances, research participation is considered the best medical option for a child or
p.000063: adolescent.
p.000063:
p.000063: For research interventions or procedures that have the potential to benefit children or adolescents, the
p.000063: risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000063:
p.000063: For research interventions or procedures that have no potential individual benefits for participants, two
p.000063: conditions apply:
p.000063: f the interventions and procedures should be studied in adults first, when these interventions and
p.000063: procedures target conditions that affect adults as well as children and adolescents, unless the necessary data
p.000063: cannot be obtained without participation of children or adolescents; and
p.000063: f the risks must be minimized and no more than minimal.
p.000063:
p.000063: When the social value of the studies with such research interventions and procedures is compelling, and these studies
p.000063: cannot be conducted in adults, a research ethics committee may permit a minor increase above minimal risk.
p.000063:
p.000063:
p.000063: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000065: 65
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: Commentary on Guideline 17
p.000065: Justification of the involvement of children and adolescents in health-related research. The participation of
p.000065: children and adolescents is indispensable for research into diseases of childhood and conditions to which they are
p.000065: particularly susceptible, as well as for clinical trials of drugs that will be used for children and adolescents as
p.000065: well as adults. In the past, many new products were not tested in children or adolescents although they were
p.000065: directed at diseases also occurring in childhood. In some cases, this resulted in children or adolescents being
p.000065: exposed to interventions that were either not effective or were harmful. In general, this lack of information results
p.000065: in higher risks for children and adolescents from being exposed to interventions where little is known about their
p.000065: specific effects or safety in this population. Therefore, it is imperative to involve children and adolescents in
p.000065: research to study both investigational interventions for childhood conditions and established interventions in
p.000065: adults that are also relevant for children or adolescents, but that have not previously undergone rigorous testing in
p.000065: children and adolescents. Research ethics committees should recognize that research involving children or adolescents
p.000065: spans a wide range of individuals, from infants through to those just short of legal maturity, with very different
p.000065: physical, cognitive and emotional capacities. A nuanced approach to evaluating research with children and adolescents
p.000065: is therefore required.
p.000065:
p.000065: Order of involvement in research. There is controversy over whether research must be done first in
p.000065: adults or adolescents before it is done in younger children. Some believe that all studies must be done
p.000065: in adults first in order to minimize risks in children. Others argue that this requirement can preclude valuable and
p.000065: timely research in children, in particular when the research addresses an important health need or priority of
p.000065: children.
p.000065:
p.000065: These Guidelines acknowledge that the general rationale behind inclusion of adults before children is that children
p.000065: must be protected from unnecessary risks of harm. However, a strict adherence to this requirement may not always
p.000065: be tenable in pediatric research since children and adolescents face distinctive health problems. In the case
p.000065: of childhood-specific conditions, studies in adults would not be feasible or their results meaningful. Moreover, in
p.000065: rare cases (for example, when a disease affects large numbers of people, including children and adolescents, the
p.000065: available treatment options are limited, and an investigational agent shows great promise), waiting for conclusive
p.000065: results from research in adults before initiating pediatric studies can significantly delay the acquisition of relevant
p.000065: data and the development of beneficial interventions for children.
p.000065:
p.000065: The current Guidelines do not require that research first be conducted in adults if the research
p.000065: includes interventions that have a prospect for potential individual benefit for children and adolescents. This
p.000065: prospect is sufficient to justify the risks associated with the interventions and procedures, provided that
p.000065: the cumulative risk of all study interventions and procedures that do not have a prospect of potential individual
p.000065: benefit are no more than minimal. If research meets these conditions but the cumulative risk of all study interventions
p.000065: and procedures that do not have a prospect of potential individual benefit is only a minor increment above
p.000065: minimal risk, then research ethics committees must be convinced that the research is of special relevance to
p.000065: children or adolescents and could not be carried out equally well in an adult population. In such cases, older children
p.000065: who are more capable of giving assent must be selected before younger children or infants, unless there are sound
p.000065: scientific reasons for performing the research in younger children first.
p.000065:
p.000065: Research must always be conducted in adults before it is conducted in children when exploring the possible toxicity of
p.000065: new drugs. First exploring the possible toxicity of new drugs in adult populations represents a way of reducing risk
p.000065: for children and adolescents who might be involved in subsequent investigations of the same intervention.
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000066: 66
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: Potential individual benefits and risks. The potential individual benefits and risks of research with
p.000066: children or adolescents should be evaluated based on Guideline 4 – Potential individual benefits and risks of research,
p.000066: and Guideline 5 – Choice of control in clinical trials.
p.000066:
p.000066: Assent. Children and adolescents who are legally minors cannot give legally valid informed consent, but they may be
p.000066: able to give assent. To give assent means that the child or adolescent is meaningfully engaged in the research
p.000066: discussion in accordance with his or her capacities. Assent must be considered as a process (see Guideline 9
p.000066: – Individuals capable of giving informed consent) and is not merely the absence of dissent. Furthermore, the researcher
p.000066: must involve the child or adolescent in the actual decision-making process and use age-appropriate information. It is
p.000066: of major importance to inform the child or adolescent and obtain assent as described above, preferably in
p.000066: writing for children who are literate. The process of obtaining assent must take into account not only the age of
p.000066: children, but also their individual circumstances, life experiences, emotional and psychological maturity, intellectual
p.000066: capabilities and the child’s or adolescent’s family situation.
p.000066:
p.000066: As adolescents near the age of majority, their agreement to participate in research may be ethically
p.000066: (though not legally) equivalent to consent. In this situation, parental consent is ethically best
p.000066: considered as “co-consent” but legally, the adolescent’s agreement remains assent. If child or adolescent
p.000066: participants reach the legal age of majority according to applicable law and become capable of independent informed
p.000066: consent during the research, their written informed consent to continued participation must be sought and their
p.000066: decision respected.
p.000066:
p.000066: Deliberate objection. Some children and adolescents who are too immature to give assent may be able to register a
p.000066: “deliberate objection,” meaning an expression of disapproval or refusal of a proposed procedure. The deliberate
p.000066: objection of an older child or adolescent, for example, is to be distinguished from the behaviour of an
p.000066: infant likely to cry or withdraw in response to almost any adverse stimulus. A deliberate objection by
p.000066: a child or adolescent to taking part in research must be respected even if the parents have given permission,
p.000066: unless the child or adolescent needs treatment that is not available outside the context of research, the research
p.000066: intervention has a clear prospect of clinical benefit, and the treating physician and the legally authorized
p.000066: representative consider the research intervention to be the best available medical option for the given
p.000066: child or adolescent. In such cases, particularly if the child is very young or immature, a parent or guardian may
p.000066: override the child`s objections. However, in some situations parents may press a researcher to persist with an
p.000066: investigational intervention against the child`s wishes. Sometimes this pressure is meant to serve the parents’
p.000066: interests rather than the child’s. In this case, the parents’ decision must be overridden if the researcher believes it
p.000066: is not in the child’s best clinical interest to enrol or continue study participation.
p.000066:
p.000066: Permission of a parent or legally authorized representative. The researcher must obtain the permission of
p.000066: at least one parent or guardian in writing, consistent with applicable laws and regulations. The age at
p.000066: which a child becomes legally capable to give consent differs substantially from one jurisdiction to another.
p.000066: Often children who have not yet reached the legally established age of consent can understand the implications
p.000066: of research participation and go through standard informed consent procedures; however, legally they can only assent to
p.000066: serve as research participants. Independent of its quality, assent is never sufficient to permit participation in
p.000066: research unless it is supplemented by the permission of a parent, legal guardian or other duly authorized
p.000066: representative. The decision to continue or discontinue participation by children or adolescents who become legally
p.000066: capable during the study trumps the decision of their parents or legal guardians.
p.000066:
p.000066: Waiver of parental permission. In certain circumstances, research ethics committees may waive parental permission. In
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
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p.000066: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000067: 67
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
p.000067: psychological and medical support for the participating children and adolescents is another special
p.000067: protection, though this may be difficult to realize in some communities. In such communities, the study
p.000067: personnel must be sufficiently qualified to help children and adolescents who need medical and psychological support.
p.000067:
p.000067: A research ethics committee may also allow a waiver of parental permission if the conditions set out in Guideline 10 –
p.000067: Modifications and waivers of informed consent - are satisfied.
p.000067:
p.000067: Observation of the study by a parent or guardian. A parent or legally appointed guardian who gives permission for a
p.000067: child or adolescent to participate in research must generally be given the opportunity, to a reasonable
p.000067: extent and without violating the privacy of other study participants, to observe the child’s participation as
p.000067: the study proceeds. This could enable the child to be withdrawn if the parent or guardian decides it is in the child’s
p.000067: best interests to do so.
p.000067:
p.000067: Emergency care situations in which the researcher anticipates that children and adolescents will participate. When
p.000067: children and adolescents participate in emergency care research, the principles of Guideline 16 – Research involving
p.000067: adults incapable of giving informed consent - apply.
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000068: 68
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: GUIDELINE 18:
p.000068: WOMEN AS RESEARCH PARTICIPANTS
p.000068:
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
p.000068: physiologies and health needs, they merit special consideration by researchers and research ethics committees. Only the
p.000068: informed consent of the woman herself should be required for her research participation. Since some societies lack
...
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
p.000070:
p.000070:
p.000070: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000071: 71
p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
p.000071: routine exclusion of pregnant women from clinical trials is their use of medications (both prescription and
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
p.000071: it is imperative to design research for pregnant and breastfeeding women to learn about the currently unknown
p.000071: risks and potential individual benefits to them, as well as to the fetus or nursing infant.
p.000071:
p.000071: A case in point is the thalidomide episode, in which about 10,000 babies around the world (many in Western Europe) were
p.000071: born with severely deformed limbs because their mothers had taken medication when pregnant. This tragedy is often cited
p.000071: as a reason for excluding pregnant women from health- related research, but the lesson to be learned is the opposite.
p.000071: Never having been tested in pregnant women, the drug came to market and was readily available for morning sickness, a
p.000071: relatively mild condition. Had the drug been tested in very few women in a clinical trial, the mutagenic effect would
p.000071: most likely have been discovered and the total number of babies born with deformities would have been much smaller.
p.000071:
...
p.000072: grounds for abortion in that jurisdiction. If they are not, pregnant women must not be recruited for research in which
p.000072: there is a realistic basis for concern that significant fetal abnormality may occur as a consequence of
p.000072: participation in research. At the same time, this rule might restrict potentially valuable research in
p.000072: countries where women cannot be guaranteed access to abortion. In such cases, research projects can be
p.000072: conducted only if a local research ethics committee determines that the research has compelling social value for
p.000072: pregnant women and the women are informed about existing restrictions on abortion and possible options for obtaining an
p.000072: abortion in another country.
p.000072:
p.000072: Breastfeeding women. The father may need to be consulted in research involving breastfeeding women, in accordance with
p.000072: Guideline 17 – Research involving children and adolescents. If a breast- fed infant may be exposed to an
p.000072: investigational product through the ingestion of breast milk (or it is unknown whether an infant would be exposed),
p.000072: such research should be conducted in accordance with Guideline 17 – Research involving children and adolescents.
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000073: 73
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073: GUIDELINE 20:
p.000073: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS
p.000073:
p.000073: Disasters arising from events such as earthquakes, tsunamis or military conflicts, and disease outbreaks, can
p.000073: have a sudden and devastating impact on the health of large affected populations. In order to identify effective ways
p.000073: of mitigating the health impact of disasters and disease outbreaks, health-related research should form an integral
p.000073: part of disaster response. However, the conduct of research must not unduly impact the response to the victims of a
p.000073: disaster.
p.000073:
p.000073: In the conduct of research in disasters and disease outbreaks, it is essential to uphold the ethical principles
p.000073: embodied in these Guidelines. Conducting research in these situations raises important challenges such as the
p.000073: need to generate knowledge quickly, maintain public trust, and overcome practical obstacles to implementing
p.000073: research. These challenges need to be carefully balanced with the need to ensure the scientific validity of the
p.000073: research and uphold ethical principles in its conduct.
p.000073:
p.000073: Researchers, sponsors, international organizations, research ethics committees and other relevant stakeholders should
p.000073: ensure that:
...
p.000079: therapeutic tool could confound the results of the research. Researchers would not be able to tell whether a new
p.000079: intervention is sufficiently effective if some health care workers refuse to participate and employ their usual
p.000079: procedures. A waiver of consent would then be an option (see Guideline 4 – Potential individual benefits and risks of
p.000079: research), but health care workers must nevertheless be notified that a study is taking place. If the
p.000079: interventions are directly carried out on patients, they would normally also be considered research subjects and their
p.000079: consent to receive the intervention would be required.
p.000079:
p.000079: Although in many CRTs participants cannot consent to being randomized, depending on the type of study design they may
p.000079: be able to give informed consent to receive the intervention. The intervention may be delivered at the individual level
p.000079: while the communities to which the individuals belong are randomized at the cluster level (for example, a vaccination
p.000079: campaign applied at the school level). These trials are called individual-cluster randomized trials. In some
p.000079: individual-cluster randomized trials, individuals may be able to consent to the intervention before it is administered
p.000079: in that cluster. For example, parents will not be able to consent to their children’s school being randomized to a
p.000079: vaccination programme or to being allocated to that cluster, but they could consent or refuse to consent to their
p.000079: child’s vaccination at school. In other CRTs, both the intervention and the community are randomized at the cluster
p.000079: level. These trials are called cluster-cluster randomized trials (for example, all the students in a school or
p.000079: all residents of a community). In cluster-cluster randomized trials, individual informed consent for receiving the
p.000079: intervention is typically difficult to obtain since it is almost impossible to avoid the intervention. At the same
p.000079: time, individual consent for data collection procedures is usually possible in both types of cluster randomized trials.
p.000079:
p.000079: Ethical acceptability of a no-intervention group. Some CRTs investigate interventions that have been proven
p.000079: to be effective elsewhere; this is termed implementation research. This type of research is often conducted in
p.000079: low-resource settings. An ethical question pertaining to this type of study is whether it is acceptable
p.000079: to withhold the proven intervention from a control group in a CRT. This situation is analogous to that of
p.000079: placebo controls in a randomized, controlled trial when an established, effective prevention or treatment exists. If
...
p.000098:
p.000098: 9. Name and address of the sponsor;
p.000098:
p.000098: 10. Names, addresses, institutional affiliations, qualifications and experience of the principal investigator
p.000098: and other investigators (Guideline 1);
p.000098:
p.000098: 11. The objectives of the trial or study, its hypotheses or research questions, its assumptions, and its
p.000098: variables (Guideline 1);
p.000098:
p.000098: 12. A detailed description of the design of the trial or study. In the case of controlled clinical trials the
p.000098: description should include, but not be limited to, whether assignment to treatment groups
p.000098:
p.000098:
p.000098: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: will be randomized (including the method of randomization), and whether the study will be blinded (single
p.000099: blind, double blind), or open (Guideline 5);
p.000099:
p.000099: 13. The number of research participants needed to achieve the study objective, and how this was statistically
p.000099: determined;
p.000099:
p.000099: 14. The criteria for inclusion or exclusion of potential participants, and justification for the exclusion of any
p.000099: groups on the basis of age, sex, social or economic factors, or for other reasons (Guideline 3);
p.000099:
p.000099: 15. The justification for involving as research participants children or adolescents, persons who are unable to give
p.000099: informed consent or vulnerable persons or groups, and a description of special measures to minimize risks to such
p.000099: persons (Guidelines 15, 16 and 17);
p.000099:
p.000099: 16. The process of recruitment, e.g. advertisements, and the steps to be taken to protect privacy and confidentiality
p.000099: during recruitment (Guideline 3);
p.000099:
p.000099: 17. Description and explanation of all interventions (the method of treatment administration, including
p.000099: route of administration, dose, dose interval and treatment period for investigational and comparator products used);
p.000099:
p.000099: 18. Plans and justification for withdrawing or withholding standard therapies in the course of the research, including
p.000099: any resulting risks to persons (Guidelines 4 and 5);
p.000099:
p.000099: 19. Any other treatment that may be given or permitted, or contraindicated, during the study (Guideline
p.000099: 6);
p.000099:
p.000099: 20. Clinical and laboratory tests and other tests that are to be carried out;
p.000099:
p.000099: 21. Samples of the standardized case-report forms to be used, the methods of recording therapeutic response
p.000099: (description and evaluation of methods and frequency of measurement), the follow-up procedures, and, if applicable, the
p.000099: measures proposed to determine the extent of compliance of persons with the treatment;
p.000099:
p.000099: 22. Rules or criteria according to which participants may be removed from the study or clinical trial, or (in a
p.000099: multi-centre study) a centre may be discontinued, or the study may be terminated;
p.000099:
...
p.000110:
p.000110: Carel IJsselmuiden, Council on Health Research for Development (COHRED)
p.000110: Carel is a physician, epidemiologist, public health practitioner, academic and social entrepreneur, with
p.000110: qualifications from universities in Belgium, Netherlands, South Africa and the United States. He spent 7
p.000110: years in rural medicine and public health, 4 years in peri-urban and urban health care, HIV/AIDS control and
p.000110: environmental services management as Deputy Medical Officer of Health for Johannesburg, South Africa. He
p.000110: was appointed as Professor and Head of Department of the department of community health at the University of
p.000110: Pretoria in 1995, where he became the founding Director of the School of Health Systems and Public Health in 1999. He
p.000110: held this position until his appointment as Executive Director at COHRED in 2004. As such, he is also member of the
p.000110: COHRED Board, President of COHRED USA and board member of COHRED Africa. He has published widely in applied research,
p.000110: nutrition, immunization, environmental health, research capacity building, global public health education and ethics of
p.000110: international collaborative health research. As part of community service, he was director of the Elim Care Group
p.000110: Project, a health and development NGO in the north of South Africa, served on the board of the Nokuthula
p.000110: Centre for Disabled Children in Alexandra township in South Africa and offers strategic research and innovation
p.000110: development support to low- and middle-income countries. Carel holds two nationalities – South African and Netherlands
p.000110: – and has worked and lived in Africa, Europe, the United States and the Caribbean.
p.000110:
p.000110: Observer
p.000110: Ingrid Callies
p.000110: Dr Ingrid Callies, PHD (University Paris Descartes), LLM (University of Virginia), a member of the New
p.000110: York Bar and a bioethicist, is Head of Ethics and Coordinator of the Code Authority and Ethics Committee (Codeem) for
p.000110: the pharmaceutical industry in France at Leem, the French federation of the pharmaceutical industry (www.leem.org).
p.000110: Previously, she was Ethics Advisor at the Institut Pasteur, worked for the French National Agency for Research on Aids
p.000110: and Viral Hepatitis, and practised law at Hogan & Hartson LLP, a law firm now called Hogan Lovells. Co-editor of the
p.000110: Ethics of Research Section in the Elsevier International Encyclopedia of the Social and Behavioural
p.000110: Sciences, Ingrid Callies has also participated in major research projects, including LeukoTreat (a
p.000110: collaborative European project on leukodystrophy) and Satori (Stakeholders Acting Together On the ethical impact
p.000110: assessment of Research and Innovation).
p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
p.000110: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000110:
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p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
...
Social / Elderly
Searching for indicator elderly:
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p.000105: in place (Guideline 22).
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
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p.000106: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000106:
p.000106:
p.000106:
p.000106:
p.000106:
p.000106: APPENDIX 3
p.000106: CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH INVOLVING
p.000106: HUMANS
p.000106:
p.000106: Chair
p.000106: Hans van Delden
p.000106: Johannes JM van Delden is professor of medical ethics at the medical school of Utrecht University, the Netherlands, and
p.000106: director of education at the Julius Center for health sciences. He has written more than two hundred articles in
p.000106: peer-reviewed scientific journals and (co)authored three books. He was secretary of the International Association of
p.000106: Bioethics. As a professor of medical ethics he has built a strong academic group within the University Medical Center
p.000106: Utrecht. The special fields of interest of this group are: research ethics, moral problems at the end of life and moral
p.000106: problems in the care for the elderly. He is currently the chair of the International Bioethics Committee at UNESCO and
p.000106: was president of CIOMS from 2011 to 2016.
p.000106:
p.000106: Secretary
p.000106: Rieke van der Graaf
p.000106: Rieke van der Graaf is an assistant professor of bioethics and employed at the University Medical Center Utrecht at the
p.000106: Julius Center, Department of Medical Humanities. Her current research interests are inclusion of “vulnerable
p.000106: populations” in clinical research, the integration of care and research, and the ethics of innovative research designs.
p.000106: She is teaching medical ethics at the UMC Utrecht and has been a member of the UMC Utrecht’s Hospital Ethics Committee
p.000106: for more than 10 years. She is a member of the Research Ethics Committee (REC) of the UMC Utrecht. She was the
p.000106: Secretary of the Working Group on the Revision of the CIOMS Guidelines.
p.000106:
p.000106: Members
p.000106: Anant Bhan
p.000106: Anant Bhan is trained as a medical doctor with a masters degree in bioethics from the University of Toronto. He is a
p.000106: researcher in the fields of Bioethics, Global Health and Health Policy based in India. He is also Adjunct
p.000106: Professor at Yenepoya University, Mangalore, India. In the past, he has worked for NGOs and a government
p.000106: public health training institution in India, as well as a consultant to a project on Ethical, Social and Cultural
...
Social / Ethnicity
Searching for indicator ethnic:
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p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
p.000057: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000058: 58
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
...
p.000058: engagement).
p.000058:
p.000058: Special protections. Special protections for these groups can include allowing no more than minimal risks for
p.000058: procedures that offer no potential individual benefits for participants; supplementing the participant’s agreement by
p.000058: the permission of family members, legal guardians, or other appropriate representatives; or requiring that the research
p.000058: be carried out only when it is targeted at conditions that affect these groups. Safeguards can be designed to promote
p.000058: voluntary decision-making, limit the potential for confidentiality breaches, and otherwise work to protect the
p.000058: interests of those at increased risk of harm. Research ethics committees need to be sensitive to not overly excluding
p.000058: people, and allow them to participate by requiring that special protections be put in place.
p.000058:
p.000058: Group vulnerability. Despite the importance of avoiding classification of entire groups as inherently vulnerable,
p.000058: circumstances exist that require research ethics committees to pay special attention to research involving
p.000058: certain groups. In some resource-limited countries or communities, lack of access to medical care,
p.000058: membership in ethnic and racial minorities, or other disadvantaged or marginalized groups can be factors
p.000058: that constitute vulnerability. As is true of the vulnerability of individuals, the judgment that groups
p.000058: are vulnerable is context dependent and requires empirical evidence to document the need for special
p.000058: protections.
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059: GUIDELINE 16:
p.000059: RESEARCH INVOLVING
p.000059: ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000059:
p.000059: Adults who are not capable of giving informed consent must be included in health-related research unless a good
p.000059: scientific reason justifies their exclusion. As adults who are not capable of giving informed consent
p.000059: have distinctive physiologies and health needs, they merit special consideration by researchers and research
...
Searching for indicator ethnicity:
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p.000005: can result in or exacerbate health disparities, the exclusion of groups in need of special protection must
p.000005: be justified. Groups that are unlikely to benefit from any knowledge gained from the research should not bear a
p.000005: disproportionate share of the risks and burdens of research participation. Groups that are under-represented
p.000005: in medical research should be provided appropriate access to participate.
p.000005:
p.000005:
p.000005: Commentary on Guideline 3
p.000005: General considerations. The equitable distribution of benefits and burdens in the selection of study
p.000005: populations requires that the benefits of research be distributed fairly and that no group or class of persons bears
p.000005: more than its fair share of the risks or burdens from research participation. When benefits or burdens of research are
p.000005: to be apportioned unequally among individuals or groups, the criteria for unequal distribution should be scientifically
p.000005: and ethically justified rather than arbitrarily or conveniently chosen. Situations where unequal distribution of
p.000005: benefits would be considered are those in which the research particularly affects the population under study.
p.000005: In general, equitable distribution requires that participants be drawn from the qualifying population in the
p.000005: geographic area of the study where the results can be applied (see Guideline 2 – Research conducted in low-resource
p.000005: settings). Inclusion and exclusion criteria should not be based upon potentially discriminatory criteria, such as race,
p.000005: ethnicity, economic status, age or sex, unless there is a sound ethical or scientific reason to do so. For example, in
p.000005: cases where the under-representation of particular groups results in or perpetuates health disparities, equity may
p.000005: require special efforts to include members of those populations in research (see Guideline 17 – Research involving
p.000005: children and adolescents, Guideline 18
p.000005: – Women as research participants, and Guideline 19 – Pregnant women and breastfeeding women as research participants).
p.000005:
p.000005:
p.000005:
p.000005: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: Fair distribution of research benefits. Equity in the distribution of the benefits of research requires
p.000007: that research not disproportionately focus on the health needs of a limited class of people, but instead
p.000007: aims to address diverse health needs across different classes or groups. In the past, groups considered vulnerable
p.000007: were excluded from participation in research because it was considered the most expedient way of protecting
...
Social / Fetus/Neonate
Searching for indicator fetus:
(return to top)
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
...
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000068: 68
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: GUIDELINE 18:
p.000068: WOMEN AS RESEARCH PARTICIPANTS
p.000068:
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
p.000068: physiologies and health needs, they merit special consideration by researchers and research ethics committees. Only the
p.000068: informed consent of the woman herself should be required for her research participation. Since some societies lack
p.000068: respect for women’s autonomy, in no case must the permission of another person replace the requirement of individual
p.000068: informed consent by the woman.
p.000068:
p.000068: Women of child-bearing potential must be informed in advance of the possibility of risks to the fetus
p.000068: should they become pregnant during their research participation. When participation in research might be
p.000068: hazardous to a fetus or a woman if she becomes pregnant, sponsors and researchers must guarantee access to pregnancy
p.000068: tests, effective contraceptive methods before and during the research and to safe, legal abortion.
p.000068:
p.000068:
p.000068: Commentary on Guideline 18
p.000068: General considerations. Women in many societies have been excluded from research. For example, most of the early
p.000068: cardiovascular disease studies have excluded women because these diseases were believed to be uncommon in women. In
p.000068: particular, women who are biologically capable of becoming pregnant have been traditionally excluded from clinical
p.000068: trials of drugs, vaccines and medical devices owing to concern about undetermined risks to the fetus (see
p.000068: Guideline 15 – Research involving vulnerable persons and groups). Although the presumption against including women
p.000068: has changed in recent years, they are still excluded in many cases without adequate justification. Much remains unknown
p.000068: about the safety and efficacy of most drugs, vaccines, or devices used by women in medical practice, and
p.000068: this lack of knowledge can be dangerous. For example, heart attacks in women are different from heart attacks in men,
p.000068: so research is necessary to determine the best means of diagnosis and treatment in women.
p.000068:
p.000068: Vulnerability of women. Despite the current general presumption that favours the inclusion of women in
p.000068: research, in many societies women remain socially vulnerable in the conduct of research. For example, they may
p.000068: suffer negligence or harm because of their submission to authority, their hesitancy or inability to ask
p.000068: questions, and a cultural tendency to deny or tolerate pain and suffering. When women in these situations are potential
...
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
p.000069: could include risks to the fetus if they become pregnant during the research (see Guideline 19 – Pregnant
p.000069: women and breastfeeding women as research participants). Access to a pregnancy test, to effective
p.000069: contraceptive methods and to safe, legal abortion must be guaranteed before exposure to a potential teratogenic or
p.000069: mutagenic intervention. When effective contraception and safe abortion are not available and alternative study sites
p.000069: are not feasible, the informed consent discussion must include information about the risk of unintended pregnancy, the
p.000069: legal grounds for abortion, and information about reducing harms from unsafe abortion and subsequent complications.
p.000069: Also, if the pregnancy is not terminated, participants must be guaranteed a medical follow-up for their own health and
p.000069: that of the infant and child.
p.000069:
p.000069: Women who become pregnant during research. Many biomedical protocols call for terminating the participation of women
p.000069: who become pregnant during the research. In cases where a drug or biological product is known to be mutagenic or
p.000069: teratogenic, pregnant women must be removed from the study, and followed up and provided care through
p.000069: the duration of their pregnancy and delivery. Access to diagnostic tests must be provided to reveal any fetal
p.000069: anomalies. If anomalies are detected, women who wish may be referred for an abortion. When there is no evidence on the
p.000069: basis of which a potential harm to the fetus can be assumed, women who become pregnant should not automatically be
p.000069: removed from the study, but must be offered the option to continue or end their participation. For instance, in some
p.000069: cases it may be appropriate for a woman to stay in the study for safety monitoring but removed from the study drug. If
p.000069: the woman opts for continued participation, researchers and sponsors must offer adequate monitoring and support.
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000070: 70
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: GUIDELINE 19:
p.000070: PREGNANT AND BREASTFEEDING WOMEN AS RESEARCH PARTICIPANTS
p.000070:
p.000070: Pregnant and breastfeeding women have distinctive physiologies and health needs. Research designed to obtain
p.000070: knowledge relevant to the health needs of the pregnant and breastfeeding woman must be promoted. Research in pregnant
p.000070: women must be initiated only after careful consideration of the best available relevant data.
p.000070:
p.000070: In no case must the permission of another person replace the requirement of individual informed consent by the pregnant
p.000070: or breastfeeding woman.
p.000070:
p.000070: For research interventions or procedures that have the potential to benefit either pregnant or breastfeeding women or
p.000070: their fetus or infant, risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000070:
p.000070: For research interventions or procedures that have no potential individual benefits for pregnant and
p.000070: breastfeeding women:
p.000070: f the risks must be minimized and no more than minimal; and
p.000070: f the purpose of the research must be to obtain knowledge relevant to the particular health needs of
p.000070: pregnant or breastfeeding women or their fetuses or infants.
p.000070:
p.000070: When the social value of the research for pregnant or breastfeeding women or their fetus or infant is compelling,
p.000070: and the research cannot be conducted in non-pregnant or non- breastfeeding women, a research ethics committee
p.000070: may permit a minor increase above minimal risk.
p.000070:
p.000070: Short-term and long‐term follow-up of the fetus and the child may be required in research involving pregnant and
p.000070: breastfeeding women depending upon the study intervention and its potential risks.
p.000070:
p.000070: As a general rule, health-related research involving pregnant women that has the potential for harm to the fetus should
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
p.000070:
p.000070:
p.000070: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000071: 71
p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
p.000071: routine exclusion of pregnant women from clinical trials is their use of medications (both prescription and
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
p.000071: it is imperative to design research for pregnant and breastfeeding women to learn about the currently unknown
p.000071: risks and potential individual benefits to them, as well as to the fetus or nursing infant.
p.000071:
p.000071: A case in point is the thalidomide episode, in which about 10,000 babies around the world (many in Western Europe) were
p.000071: born with severely deformed limbs because their mothers had taken medication when pregnant. This tragedy is often cited
p.000071: as a reason for excluding pregnant women from health- related research, but the lesson to be learned is the opposite.
p.000071: Never having been tested in pregnant women, the drug came to market and was readily available for morning sickness, a
p.000071: relatively mild condition. Had the drug been tested in very few women in a clinical trial, the mutagenic effect would
p.000071: most likely have been discovered and the total number of babies born with deformities would have been much smaller.
p.000071:
p.000071: Research designed to obtain knowledge relevant to the health needs of pregnant and breastfeeding women should be
p.000071: promoted in the following areas:
p.000071: f interventions for conditions resulting from pregnancy;
p.000071: f interventions for conditions that affect the general population and are reasonably expected to be used without
p.000071: adequate evidence during pregnancy (for example off-label use of medications); and
p.000071: f interventions for conditions that affect the developing fetus.
p.000071:
p.000071: Informed consent and risks and potential individual benefits. The involvement of pregnant women in
p.000071: research is complicated by the fact that it may present risks and potential individual benefits to the
p.000071: fetus as well as to the woman. Participation of breastfeeding women in biomedical research may similarly pose risks
p.000071: to the nursing infant. Research in pregnant and breastfeeding women must be initiated only after careful
p.000071: consideration of the best available data from preclinical research in pregnant animal models, research in non‐pregnant
p.000071: women, retrospective observational studies, and pregnancy registries.
p.000071:
p.000071: Researchers and research ethics committees must ensure that potential research participants are adequately
p.000071: informed about the risks to breastfeeding women and their infants, and about the risks to pregnant women (including
p.000071: future fertility), their pregnancies, their fetuses, and their future offspring. Information must also include steps
p.000071: taken to maximize potential individual benefits and minimize risks (see Guideline 4 – Potential individual benefits and
p.000071: risks of research). When evidence concerning risks is unknown or conflicting, this must be disclosed to the pregnant or
p.000071: breastfeeding woman as part of the informed consent process. She is the one to make the final decision about the
p.000071: acceptability of these risks to her and her fetus or infant. Women must also be informed that it is often difficult to
p.000071: determine causality in cases of fetal or infant abnormalities. Pregnant women may be recruited for research in which
p.000071: there is no prospect of potential individual benefit to them or the fetus only if the risks of the
p.000071: intervention are minimal. Examples include minimally invasive studies of new diagnostic techniques. In
p.000071: special circumstances, a minor increase above minimal risk may be acceptable.
p.000071:
p.000071: Some research involving pregnant women may be directed at the health of the fetus. In such cases, the role of the woman
p.000071: remains the same: she is the decision-maker for any interventions that affect her. This does not exclude the
p.000071: possibility of the woman consulting with the father of the fetus, if she wishes.
p.000071:
p.000071: Especially in communities or societies in which cultural beliefs accord more importance to the fetus than to the
p.000071: woman’s life or health, women may feel constrained to participate, or not to participate,
p.000071:
p.000071: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000072: 72
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: in research. Special safeguards must be established to prevent undue inducement to pregnant women to
p.000072: participate in research in which interventions hold out the prospect of potential individual benefit to the fetus but
p.000072: not to the woman herself.
p.000072:
p.000072: Researchers must include in protocols on research involving pregnant women a plan for monitoring the outcome of the
p.000072: pregnancy with regard to both the health of the woman and the short-term and long-term health of the infant and child.
p.000072: Adverse events associated with research in pregnancy and during lactation may not occur immediately.
p.000072:
p.000072: Potential individual benefits and risks. The potential individual benefits and risks of research with pregnant and
p.000072: breastfeeding women should be evaluated based on Guideline 4 – Potential individual benefits and risks of research, and
p.000072: Guideline 5 – Choice of control in clinical trials.
p.000072:
p.000072: Serious harm and access to abortion. Research with pregnant women must be conducted only in settings where
p.000072: these women can be guaranteed access to a safe, legal abortion. This rule serves to prevent women from having to carry
p.000072: an unwanted fetus to term and deliver an affected baby against their wishes. Before pregnant women are enrolled,
p.000072: researchers must, at a minimum, determine whether fetal impairment and mental health conditions are recognised as legal
p.000072: grounds for abortion in that jurisdiction. If they are not, pregnant women must not be recruited for research in which
p.000072: there is a realistic basis for concern that significant fetal abnormality may occur as a consequence of
p.000072: participation in research. At the same time, this rule might restrict potentially valuable research in
p.000072: countries where women cannot be guaranteed access to abortion. In such cases, research projects can be
p.000072: conducted only if a local research ethics committee determines that the research has compelling social value for
p.000072: pregnant women and the women are informed about existing restrictions on abortion and possible options for obtaining an
p.000072: abortion in another country.
p.000072:
...
p.000117: Compensation 13, 53 - 56, 96, 100, 104 Competent. See Capable of giving informed consent Comprehension 34
p.000117: Confidentiality 11, 13, 41, 42, 44, 47, 48, 50, 51, 57, 59, 70, 100, 101, 102, 104, 105
p.000117: Conflicts of interest 5, 30, 34, 78, 89, 92, 95 - 97, 102, 104
p.000117: Continued access 21 - 23, 101, 104
p.000117: Control 9, 12, 15 - 18, 22, 26, 45, 51, 62, 67, 73, 79, 80, 83, 85,
p.000117: Custodian 41, 43, 44, 47, 49, 50, 105
p.000117: D
p.000117: Databank 47 - 52
p.000117:
p.000117:
p.000117: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000117:
p.000119: 119
p.000119:
p.000119: Data mining 50
p.000119: Data sharing 29, 31, 51, 85, 92
p.000119: Deception, deceiving 33, 38, 57
p.000119: Deliberate objection 67
p.000119: Dependent relationship 26, 35, 36, 58, 96
p.000119: Digital 83, 106
p.000119: Disaster ix, 75 - 78, 106
p.000119: Disclosure 44, 45, 51, 84, 85, 91, 95, 97, 101, 103 - 105
p.000119: Disease outbreak ii, x, 19, 34, 41, 44, 47, 49, 83, 96, 97, 99, 103, 105
p.000119: Dissemination 2, 4, 25, 85, 92
p.000119: Dissent 62, 67
p.000119: E
p.000119: Education 2, 30, 57, 89, 97
p.000119: Emergency care 63, 68, 78
p.000119: Equitable distribution 4, 7, 42, 45, 47, 52, 75, 77
p.000119: Established effective intervention viii, 9, 12, 15 - 19
p.000119: Ethical review xii, 2, 29, 30, 39, 76 - 78, 87 - 90, 95, 97, 99, 102
p.000119: Externally sponsored research 87, 89
p.000119: F
p.000119: Fairness 2
p.000119: Fetus 58, 69, 70 - 73
p.000119: Free medical treatment 56
p.000119: G
p.000119: Gatekeeping 80
p.000119: Governance 41 - 43, 44, 47, 48, 50, 51, 78
p.000119: H
p.000119: Harms 10, 11, 12, 18, 54, 55, 56, 70, 72, 91, 105
p.000119: Health needs 2 - 4, 8, 17, 19, 21 - 23, 26, 55, 61, 65, 69, 71, 72, 75, 76, 104
p.000119: I
p.000119: Identifiable 38, 39, 51, 84
p.000119: Implementation research 80
p.000119: Incentives 10, 54, 92, 101
p.000119: Information leaflet 34
p.000119: Informed consent ix, 2, 9, 10, 21, 25, 26, 33 - 39, 41 - 45, 47 - 52, 54, 56, 58, 61 - 65, 67 - 72, 75,
p.000119: 76, 78 - 80, 89, 96, 97, 100, 101, 103, 105
p.000119: Informed opt-out /opt-in 41, 44, 47, 49, 83
p.000119: In-kind 54
p.000119: Interventions 1 - 4, 9 - 12, 15 - 19, 21 - 23, 26, 30, 53, 55, 56, 61 - 63, 65, 66, 71 - 73, 75 - 81, 84,
p.000119: 88, 91, 100, 101, 104
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000120: 120
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
p.000120: Low-resource settings viii, ix, 3 - 5, 7, 17, 19, 22, 23, 26, 45, 47, 52, 75 - 77, 80, 89, 92
p.000120: M
p.000120: Management (of risks) 8, 42, 45, 48, 51, 85, 95 - 97
p.000120: Material Transfer Agreement 41, 45
p.000120: Minimal risk 9, 13, 15, 16, 18, 38, 62, 65, 66, 71, 72, 80, 88, 100
...
Searching for indicator fetuses:
(return to top)
p.000070: women must be initiated only after careful consideration of the best available relevant data.
p.000070:
p.000070: In no case must the permission of another person replace the requirement of individual informed consent by the pregnant
p.000070: or breastfeeding woman.
p.000070:
p.000070: For research interventions or procedures that have the potential to benefit either pregnant or breastfeeding women or
p.000070: their fetus or infant, risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000070:
p.000070: For research interventions or procedures that have no potential individual benefits for pregnant and
p.000070: breastfeeding women:
p.000070: f the risks must be minimized and no more than minimal; and
p.000070: f the purpose of the research must be to obtain knowledge relevant to the particular health needs of
p.000070: pregnant or breastfeeding women or their fetuses or infants.
p.000070:
p.000070: When the social value of the research for pregnant or breastfeeding women or their fetus or infant is compelling,
p.000070: and the research cannot be conducted in non-pregnant or non- breastfeeding women, a research ethics committee
p.000070: may permit a minor increase above minimal risk.
p.000070:
p.000070: Short-term and long‐term follow-up of the fetus and the child may be required in research involving pregnant and
p.000070: breastfeeding women depending upon the study intervention and its potential risks.
p.000070:
p.000070: As a general rule, health-related research involving pregnant women that has the potential for harm to the fetus should
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
p.000070:
p.000070:
p.000070: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000071: 71
p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
p.000071: routine exclusion of pregnant women from clinical trials is their use of medications (both prescription and
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
p.000071: it is imperative to design research for pregnant and breastfeeding women to learn about the currently unknown
p.000071: risks and potential individual benefits to them, as well as to the fetus or nursing infant.
p.000071:
p.000071: A case in point is the thalidomide episode, in which about 10,000 babies around the world (many in Western Europe) were
p.000071: born with severely deformed limbs because their mothers had taken medication when pregnant. This tragedy is often cited
p.000071: as a reason for excluding pregnant women from health- related research, but the lesson to be learned is the opposite.
p.000071: Never having been tested in pregnant women, the drug came to market and was readily available for morning sickness, a
p.000071: relatively mild condition. Had the drug been tested in very few women in a clinical trial, the mutagenic effect would
...
p.000071: research is complicated by the fact that it may present risks and potential individual benefits to the
p.000071: fetus as well as to the woman. Participation of breastfeeding women in biomedical research may similarly pose risks
p.000071: to the nursing infant. Research in pregnant and breastfeeding women must be initiated only after careful
p.000071: consideration of the best available data from preclinical research in pregnant animal models, research in non‐pregnant
p.000071: women, retrospective observational studies, and pregnancy registries.
p.000071:
p.000071: Researchers and research ethics committees must ensure that potential research participants are adequately
p.000071: informed about the risks to breastfeeding women and their infants, and about the risks to pregnant women (including
p.000071: future fertility), their pregnancies, their fetuses, and their future offspring. Information must also include steps
p.000071: taken to maximize potential individual benefits and minimize risks (see Guideline 4 – Potential individual benefits and
p.000071: risks of research). When evidence concerning risks is unknown or conflicting, this must be disclosed to the pregnant or
p.000071: breastfeeding woman as part of the informed consent process. She is the one to make the final decision about the
p.000071: acceptability of these risks to her and her fetus or infant. Women must also be informed that it is often difficult to
p.000071: determine causality in cases of fetal or infant abnormalities. Pregnant women may be recruited for research in which
p.000071: there is no prospect of potential individual benefit to them or the fetus only if the risks of the
p.000071: intervention are minimal. Examples include minimally invasive studies of new diagnostic techniques. In
p.000071: special circumstances, a minor increase above minimal risk may be acceptable.
p.000071:
...
p.000104: be obtained, which should specify: the purpose of the biobank, the conditions and duration of storage; the rules of
p.000104: access to the biobank; the ways in which the donor can contact the biobank custodian and can remain informed about
p.000104: future use; the foreseeable uses of the materials, whether limited to an already fully defined study or extending to a
p.000104: number of wholly or partially undefined studies; the intended goal of such use, whether only for research, basic or
p.000104: applied, or also for commercial purposes, and whether the participant will receive monetary or other benefits from the
p.000104: development of commercial products developed from their biological specimens; the possibility of unsolicited findings
p.000104: and how they will be dealt with; the safeguards that will be taken to protect confidentiality as well as their
p.000104: limitations, whether it is planned that biological specimens collected in the research will be destroyed at its
p.000104: conclusion, and, if not, details about their storage (where, how, for how long, and final disposition) and possible
p.000104: future use, that participants have the right to decide about such future use, to refuse storage, and to have the
p.000104: material destroyed (Guidelines 11 and 12);
p.000104:
p.000104: 6. when women of childbearing potential are participating in health-related research, information about the
p.000104: possible risks, if they become pregnant during the research, to themselves (including future fertility), their
p.000104: pregnancies, their fetuses, and their future offspring; and the guaranteed access to a pregnancy test, to effective
p.000104: contraceptive methods and to safe, legal abortion before exposure to a potential teratogenic or mutagenic intervention.
p.000104: When effective contraception and/ or safe abortion are not available and alternative study sites are not feasible, the
p.000104: women must be given information about: the risk of unintended pregnancy; the legal grounds for abortion; reducing harms
p.000104: from unsafe abortion and subsequent complications; and, when pregnancy is not terminated, the guarantee for a medical
p.000104: follow-up for their own health and that of the infant and child and the information that it is often difficult to
p.000104: determine causality in cases of fetal or infant abnormalities (Guidelines 18 and 19);
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000104:
p.000105: 105
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: 7. when concerning pregnant and breastfeeding women, the risks of participation in health-related research to
p.000105: themselves, their pregnancies, their fetuses, and their future offspring, what has been done to maximize potential
p.000105: individual benefits and minimize risks, that evidence concerning risks may be unknown or controversial, and that
p.000105: it is often difficult to determine causality in cases of fetal or infant abnormalities (Guidelines 4 and 19);
p.000105:
p.000105: 8. when concerning disaster victims who mostly are under duress, the difference between research and humanitarian
p.000105: aid (Guideline 20); and
p.000105:
p.000105: 9. when research is done in the online environment and using online or digital tools that may
p.000105: involve potentially vulnerable persons, information about the privacy and security controls that will be used to
p.000105: protect their data; and the limitations of the measures used and the risks that may remain despite the safeguards put
p.000105: in place (Guideline 22).
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000106: 106
p.000106: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000106:
p.000106:
p.000106:
p.000106:
p.000106:
p.000106: APPENDIX 3
p.000106: CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH INVOLVING
p.000106: HUMANS
...
Social / Homeless Persons
Searching for indicator homeless:
(return to top)
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
p.000057: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000058: 58
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: stereotypes. One proposed mechanism that can be used to avoid stereotyping is consultation with relevant stakeholders,
...
Social / Incarcerated
Searching for indicator prison:
(return to top)
p.000034: should provide to the research ethics committee documentation of consent, certified either by the person
p.000034: obtaining consent or by a witness at the time consent is obtained.
p.000034:
p.000034: Renewing consent. When substantive changes occur in any aspect of a study, the researcher must again seek
p.000034: informed consent from the participants. For example, new information may have come to light, either from the study
p.000034: itself or other sources, about the risks or benefits of products being tested or about alternatives to them.
p.000034: Participants must be given such information promptly. In most clinical trials, interim results are not disclosed to
p.000034: researchers or participants until the study has been concluded. In long-term studies, the willingness of each
p.000034: participant to continue in the study must be ensured.
p.000034:
p.000034: Individual informed consent and access to research populations. In some circumstances, a researcher may
p.000034: enter a community or institution to conduct research or approach potential participants for their individual
p.000034: consent only after obtaining permission from an institution such as a school or a prison, or from a community leader, a
p.000034: council of elders, or another designated authority. Such institutional procedures or cultural customs should be
p.000034: respected. In no case, however, may the permission of a community leader or other authority substitute for individual
p.000034: informed consent. In some populations, the use of local languages may facilitate the communication of information to
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
...
Social / Infant
Searching for indicator infant:
(return to top)
p.000066: capabilities and the child’s or adolescent’s family situation.
p.000066:
p.000066: As adolescents near the age of majority, their agreement to participate in research may be ethically
p.000066: (though not legally) equivalent to consent. In this situation, parental consent is ethically best
p.000066: considered as “co-consent” but legally, the adolescent’s agreement remains assent. If child or adolescent
p.000066: participants reach the legal age of majority according to applicable law and become capable of independent informed
p.000066: consent during the research, their written informed consent to continued participation must be sought and their
p.000066: decision respected.
p.000066:
p.000066: Deliberate objection. Some children and adolescents who are too immature to give assent may be able to register a
p.000066: “deliberate objection,” meaning an expression of disapproval or refusal of a proposed procedure. The deliberate
p.000066: objection of an older child or adolescent, for example, is to be distinguished from the behaviour of an
p.000066: infant likely to cry or withdraw in response to almost any adverse stimulus. A deliberate objection by
p.000066: a child or adolescent to taking part in research must be respected even if the parents have given permission,
p.000066: unless the child or adolescent needs treatment that is not available outside the context of research, the research
p.000066: intervention has a clear prospect of clinical benefit, and the treating physician and the legally authorized
p.000066: representative consider the research intervention to be the best available medical option for the given
p.000066: child or adolescent. In such cases, particularly if the child is very young or immature, a parent or guardian may
p.000066: override the child`s objections. However, in some situations parents may press a researcher to persist with an
p.000066: investigational intervention against the child`s wishes. Sometimes this pressure is meant to serve the parents’
p.000066: interests rather than the child’s. In this case, the parents’ decision must be overridden if the researcher believes it
p.000066: is not in the child’s best clinical interest to enrol or continue study participation.
...
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
p.000069: could include risks to the fetus if they become pregnant during the research (see Guideline 19 – Pregnant
p.000069: women and breastfeeding women as research participants). Access to a pregnancy test, to effective
p.000069: contraceptive methods and to safe, legal abortion must be guaranteed before exposure to a potential teratogenic or
p.000069: mutagenic intervention. When effective contraception and safe abortion are not available and alternative study sites
p.000069: are not feasible, the informed consent discussion must include information about the risk of unintended pregnancy, the
p.000069: legal grounds for abortion, and information about reducing harms from unsafe abortion and subsequent complications.
p.000069: Also, if the pregnancy is not terminated, participants must be guaranteed a medical follow-up for their own health and
p.000069: that of the infant and child.
p.000069:
p.000069: Women who become pregnant during research. Many biomedical protocols call for terminating the participation of women
p.000069: who become pregnant during the research. In cases where a drug or biological product is known to be mutagenic or
p.000069: teratogenic, pregnant women must be removed from the study, and followed up and provided care through
p.000069: the duration of their pregnancy and delivery. Access to diagnostic tests must be provided to reveal any fetal
p.000069: anomalies. If anomalies are detected, women who wish may be referred for an abortion. When there is no evidence on the
p.000069: basis of which a potential harm to the fetus can be assumed, women who become pregnant should not automatically be
p.000069: removed from the study, but must be offered the option to continue or end their participation. For instance, in some
p.000069: cases it may be appropriate for a woman to stay in the study for safety monitoring but removed from the study drug. If
...
p.000070: 70
p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: GUIDELINE 19:
p.000070: PREGNANT AND BREASTFEEDING WOMEN AS RESEARCH PARTICIPANTS
p.000070:
p.000070: Pregnant and breastfeeding women have distinctive physiologies and health needs. Research designed to obtain
p.000070: knowledge relevant to the health needs of the pregnant and breastfeeding woman must be promoted. Research in pregnant
p.000070: women must be initiated only after careful consideration of the best available relevant data.
p.000070:
p.000070: In no case must the permission of another person replace the requirement of individual informed consent by the pregnant
p.000070: or breastfeeding woman.
p.000070:
p.000070: For research interventions or procedures that have the potential to benefit either pregnant or breastfeeding women or
p.000070: their fetus or infant, risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000070:
p.000070: For research interventions or procedures that have no potential individual benefits for pregnant and
p.000070: breastfeeding women:
p.000070: f the risks must be minimized and no more than minimal; and
p.000070: f the purpose of the research must be to obtain knowledge relevant to the particular health needs of
p.000070: pregnant or breastfeeding women or their fetuses or infants.
p.000070:
p.000070: When the social value of the research for pregnant or breastfeeding women or their fetus or infant is compelling,
p.000070: and the research cannot be conducted in non-pregnant or non- breastfeeding women, a research ethics committee
p.000070: may permit a minor increase above minimal risk.
p.000070:
p.000070: Short-term and long‐term follow-up of the fetus and the child may be required in research involving pregnant and
p.000070: breastfeeding women depending upon the study intervention and its potential risks.
p.000070:
p.000070: As a general rule, health-related research involving pregnant women that has the potential for harm to the fetus should
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
p.000070:
p.000070:
p.000070: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000071: 71
p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
p.000071: routine exclusion of pregnant women from clinical trials is their use of medications (both prescription and
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
p.000071: it is imperative to design research for pregnant and breastfeeding women to learn about the currently unknown
p.000071: risks and potential individual benefits to them, as well as to the fetus or nursing infant.
p.000071:
p.000071: A case in point is the thalidomide episode, in which about 10,000 babies around the world (many in Western Europe) were
p.000071: born with severely deformed limbs because their mothers had taken medication when pregnant. This tragedy is often cited
p.000071: as a reason for excluding pregnant women from health- related research, but the lesson to be learned is the opposite.
p.000071: Never having been tested in pregnant women, the drug came to market and was readily available for morning sickness, a
p.000071: relatively mild condition. Had the drug been tested in very few women in a clinical trial, the mutagenic effect would
p.000071: most likely have been discovered and the total number of babies born with deformities would have been much smaller.
p.000071:
p.000071: Research designed to obtain knowledge relevant to the health needs of pregnant and breastfeeding women should be
p.000071: promoted in the following areas:
p.000071: f interventions for conditions resulting from pregnancy;
p.000071: f interventions for conditions that affect the general population and are reasonably expected to be used without
p.000071: adequate evidence during pregnancy (for example off-label use of medications); and
p.000071: f interventions for conditions that affect the developing fetus.
p.000071:
p.000071: Informed consent and risks and potential individual benefits. The involvement of pregnant women in
p.000071: research is complicated by the fact that it may present risks and potential individual benefits to the
p.000071: fetus as well as to the woman. Participation of breastfeeding women in biomedical research may similarly pose risks
p.000071: to the nursing infant. Research in pregnant and breastfeeding women must be initiated only after careful
p.000071: consideration of the best available data from preclinical research in pregnant animal models, research in non‐pregnant
p.000071: women, retrospective observational studies, and pregnancy registries.
p.000071:
p.000071: Researchers and research ethics committees must ensure that potential research participants are adequately
p.000071: informed about the risks to breastfeeding women and their infants, and about the risks to pregnant women (including
p.000071: future fertility), their pregnancies, their fetuses, and their future offspring. Information must also include steps
p.000071: taken to maximize potential individual benefits and minimize risks (see Guideline 4 – Potential individual benefits and
p.000071: risks of research). When evidence concerning risks is unknown or conflicting, this must be disclosed to the pregnant or
p.000071: breastfeeding woman as part of the informed consent process. She is the one to make the final decision about the
p.000071: acceptability of these risks to her and her fetus or infant. Women must also be informed that it is often difficult to
p.000071: determine causality in cases of fetal or infant abnormalities. Pregnant women may be recruited for research in which
p.000071: there is no prospect of potential individual benefit to them or the fetus only if the risks of the
p.000071: intervention are minimal. Examples include minimally invasive studies of new diagnostic techniques. In
p.000071: special circumstances, a minor increase above minimal risk may be acceptable.
p.000071:
p.000071: Some research involving pregnant women may be directed at the health of the fetus. In such cases, the role of the woman
p.000071: remains the same: she is the decision-maker for any interventions that affect her. This does not exclude the
p.000071: possibility of the woman consulting with the father of the fetus, if she wishes.
p.000071:
p.000071: Especially in communities or societies in which cultural beliefs accord more importance to the fetus than to the
p.000071: woman’s life or health, women may feel constrained to participate, or not to participate,
p.000071:
p.000071: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000072: 72
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: in research. Special safeguards must be established to prevent undue inducement to pregnant women to
p.000072: participate in research in which interventions hold out the prospect of potential individual benefit to the fetus but
p.000072: not to the woman herself.
p.000072:
p.000072: Researchers must include in protocols on research involving pregnant women a plan for monitoring the outcome of the
p.000072: pregnancy with regard to both the health of the woman and the short-term and long-term health of the infant and child.
p.000072: Adverse events associated with research in pregnancy and during lactation may not occur immediately.
p.000072:
p.000072: Potential individual benefits and risks. The potential individual benefits and risks of research with pregnant and
p.000072: breastfeeding women should be evaluated based on Guideline 4 – Potential individual benefits and risks of research, and
p.000072: Guideline 5 – Choice of control in clinical trials.
p.000072:
p.000072: Serious harm and access to abortion. Research with pregnant women must be conducted only in settings where
p.000072: these women can be guaranteed access to a safe, legal abortion. This rule serves to prevent women from having to carry
p.000072: an unwanted fetus to term and deliver an affected baby against their wishes. Before pregnant women are enrolled,
p.000072: researchers must, at a minimum, determine whether fetal impairment and mental health conditions are recognised as legal
p.000072: grounds for abortion in that jurisdiction. If they are not, pregnant women must not be recruited for research in which
p.000072: there is a realistic basis for concern that significant fetal abnormality may occur as a consequence of
p.000072: participation in research. At the same time, this rule might restrict potentially valuable research in
p.000072: countries where women cannot be guaranteed access to abortion. In such cases, research projects can be
p.000072: conducted only if a local research ethics committee determines that the research has compelling social value for
p.000072: pregnant women and the women are informed about existing restrictions on abortion and possible options for obtaining an
p.000072: abortion in another country.
p.000072:
p.000072: Breastfeeding women. The father may need to be consulted in research involving breastfeeding women, in accordance with
p.000072: Guideline 17 – Research involving children and adolescents. If a breast- fed infant may be exposed to an
p.000072: investigational product through the ingestion of breast milk (or it is unknown whether an infant would be exposed),
p.000072: such research should be conducted in accordance with Guideline 17 – Research involving children and adolescents.
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000073: 73
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073: GUIDELINE 20:
p.000073: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS
p.000073:
p.000073: Disasters arising from events such as earthquakes, tsunamis or military conflicts, and disease outbreaks, can
p.000073: have a sudden and devastating impact on the health of large affected populations. In order to identify effective ways
p.000073: of mitigating the health impact of disasters and disease outbreaks, health-related research should form an integral
p.000073: part of disaster response. However, the conduct of research must not unduly impact the response to the victims of a
p.000073: disaster.
p.000073:
p.000073: In the conduct of research in disasters and disease outbreaks, it is essential to uphold the ethical principles
p.000073: embodied in these Guidelines. Conducting research in these situations raises important challenges such as the
p.000073: need to generate knowledge quickly, maintain public trust, and overcome practical obstacles to implementing
p.000073: research. These challenges need to be carefully balanced with the need to ensure the scientific validity of the
p.000073: research and uphold ethical principles in its conduct.
p.000073:
...
p.000104: and how they will be dealt with; the safeguards that will be taken to protect confidentiality as well as their
p.000104: limitations, whether it is planned that biological specimens collected in the research will be destroyed at its
p.000104: conclusion, and, if not, details about their storage (where, how, for how long, and final disposition) and possible
p.000104: future use, that participants have the right to decide about such future use, to refuse storage, and to have the
p.000104: material destroyed (Guidelines 11 and 12);
p.000104:
p.000104: 6. when women of childbearing potential are participating in health-related research, information about the
p.000104: possible risks, if they become pregnant during the research, to themselves (including future fertility), their
p.000104: pregnancies, their fetuses, and their future offspring; and the guaranteed access to a pregnancy test, to effective
p.000104: contraceptive methods and to safe, legal abortion before exposure to a potential teratogenic or mutagenic intervention.
p.000104: When effective contraception and/ or safe abortion are not available and alternative study sites are not feasible, the
p.000104: women must be given information about: the risk of unintended pregnancy; the legal grounds for abortion; reducing harms
p.000104: from unsafe abortion and subsequent complications; and, when pregnancy is not terminated, the guarantee for a medical
p.000104: follow-up for their own health and that of the infant and child and the information that it is often difficult to
p.000104: determine causality in cases of fetal or infant abnormalities (Guidelines 18 and 19);
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000104:
p.000105: 105
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: 7. when concerning pregnant and breastfeeding women, the risks of participation in health-related research to
p.000105: themselves, their pregnancies, their fetuses, and their future offspring, what has been done to maximize potential
p.000105: individual benefits and minimize risks, that evidence concerning risks may be unknown or controversial, and that
p.000105: it is often difficult to determine causality in cases of fetal or infant abnormalities (Guidelines 4 and 19);
p.000105:
p.000105: 8. when concerning disaster victims who mostly are under duress, the difference between research and humanitarian
p.000105: aid (Guideline 20); and
p.000105:
p.000105: 9. when research is done in the online environment and using online or digital tools that may
p.000105: involve potentially vulnerable persons, information about the privacy and security controls that will be used to
p.000105: protect their data; and the limitations of the measures used and the risks that may remain despite the safeguards put
p.000105: in place (Guideline 22).
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
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p.000106: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000106:
p.000106:
p.000106:
p.000106:
p.000106:
p.000106: APPENDIX 3
p.000106: CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH INVOLVING
p.000106: HUMANS
p.000106:
p.000106: Chair
p.000106: Hans van Delden
p.000106: Johannes JM van Delden is professor of medical ethics at the medical school of Utrecht University, the Netherlands, and
...
Social / Institutionalized
Searching for indicator institutionalized:
(return to top)
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
p.000057: Examples are medical and nursing students, subordinate hospital and laboratory personnel, workers in settings
p.000057: where research studies are conducted, and members of the armed forces or police. Their agreement to volunteer may be
p.000057: unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate
p.000057: in the study or by fear of disapproval or retaliation if they refuse (see also commentary on Guideline 9 – Individuals
p.000057: capable of giving informed consent). The research protocol must include a description of provisions to protect such
p.000057: individuals from being conscripted into research.
p.000057:
p.000057: Institutionalized persons. Residents of nursing homes, mental institutions, and prisons are often considered vulnerable
p.000057: because in a confined setting they have few options and are denied certain freedoms that non-institutionalized persons
p.000057: enjoy. For example, prisons have been described as “an inherently coercive environment.” Also, they may be in a
p.000057: dependent relationship with caregivers or guardians (see commentary on Guideline 9 – Individuals capable of giving
p.000057: informed consent, section on Dependent relationship).
p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
p.000057: committee when such proposals are under review (see commentary on Guideline 9 – Individuals capable of giving informed
p.000057: consent, section on Dependent relationship). Some individuals with this characteristic may also have diminished
p.000057: capacity to consent, and therefore require the additional protections noted earlier for participants who lack
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
...
Social / Laboratory Staff
Searching for indicator research staff:
(return to top)
p.000012: risks to groups, notably by maintaining confidentiality during and after the study and publishing the
p.000012: resulting data in a manner that is respectful of the interests of all concerned.
p.000012:
p.000012: Similarly, conducting research may disrupt or interfere with providing health care to the local community
p.000012: and thereby pose risks to the community. Research ethics committees must ensure, as part of evaluating the
p.000012: risks and potential individual benefits of research studies, that the interests of all who may be affected are given
p.000012: due consideration. For example, researchers and sponsors could contribute to the local health infrastructure in
p.000012: a way that compensates for any disruption caused by the research.
p.000012:
p.000012: In assessing the risks and potential individual benefits that a study presents to a population, research ethics
p.000012: committees should consider the potential harm that could result from forgoing the research or from failing to publish
p.000012: the results.
p.000012:
p.000012: Risks to researchers. In addition to participants, investigators themselves can be exposed to risks that result from
p.000012: research activities. For example, research involving radiation can expose researchers to risks and studies on
p.000012: infectious disease can pose risks to laboratory staff who are handling samples. Sponsors should carefully
p.000012: assess and minimize risks to researchers; specify and explain the risks of undertaking the research to investigators
p.000012: and other research staff; and provide adequate compensation in case any members of the research team incur harm as a
p.000012: result of the research.
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000013: 13
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: GUIDELINE 5:
p.000013: CHOICE OF CONTROL IN CLINICAL TRIALS
p.000013:
p.000013: As a general rule, the research ethics committee must ensure that research participants in the control group of a trial
p.000013: of a diagnostic, therapeutic, or preventive intervention receive an established effective intervention.
p.000013:
p.000013: Placebo may be used as a comparator when there is no established effective intervention for the condition under
p.000013: study, or when placebo is added on to an established effective intervention.
p.000013:
p.000013: When there is an established effective intervention, placebo may be used as a comparator without providing the
p.000013: established effective intervention to participants only if:
p.000013: f there are compelling scientific reasons for using placebo; and
p.000013: f delaying or withholding the established effective intervention will result in no more than a minor
...
Social / Linguistic Proficiency
Searching for indicator language:
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p.000031: pre-determined intervals that each participant is willing to stay in the study, even if there are no changes in the
p.000031: design or objectives of the research.
p.000031:
p.000031: It is the principal investigator’s responsibility to ensure that all personnel obtaining informed consent for a study
p.000031: comply with this Guideline.
p.000031:
p.000031:
p.000031: Commentary on Guideline 9
p.000031: General considerations. Informed consent is a process. The start of this process requires providing relevant
p.000031: information to a potential participant, ensuring that the person has adequately understood the material facts and
p.000031: has decided or refused to participate without having been subjected to coercion, undue influence, or
p.000031: deception.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Informed consent is based on the principle that individuals capable of giving informed consent have a right to choose
p.000033: freely whether to participate in research. Informed consent protects the individual’s freedom of choice and respects
p.000033: the individual’s autonomy.
p.000033:
p.000033: The information must be provided in plain language understandable by the potential participant. The person
p.000033: obtaining informed consent must be knowledgeable about the research and capable of answering any questions from
p.000033: potential participants. Researchers in charge of the study must make themselves available to answer questions at the
p.000033: request of participants. Participants should be offered the opportunity to ask questions and receive answers before or
p.000033: during the research. Researchers should make every effort to address those questions in a timely and comprehensive
p.000033: manner.
p.000033:
p.000033: This Guideline applies to individuals capable of giving informed consent. Requirements for research with individuals
p.000033: who are not capable of giving informed consent or with children and adolescents are set out in Guideline 16 –
p.000033: Research involving adults incapable of giving informed consent, and Guideline 17 – Research involving children
p.000033: and adolescents.
p.000033:
p.000033: Process. Informed consent is a two-way communicative process that begins when initial contact is made with a potential
p.000033: participant and ends when consent is provided and documented, but can be revisited later during the conduct of the
p.000033: study. Each individual must be given as much time as needed to reach a decision, including time for consultation with
p.000033: family members or others. Adequate time and resources must be provided for informed-consent procedures.
p.000033:
p.000033: Language of the information leaflet and recruitment material. All potential participants should be provided with a
p.000033: written information leaflet that they may take with them. Informing the individual participant must not be simply a
p.000033: ritual recitation of the contents of a written document. The wording of the leaflet and any recruitment material
p.000033: must be in language understandable by the potential participant and be approved by the research ethics
p.000033: committee. The wording of the leaflet must be short and preferably not exceed two or three pages. An oral presentation
p.000033: of information or the use of appropriate audiovisual aids, including pictographs and summary tables, are important to
p.000033: supplement written information documents to aid understanding. Information should also be appropriate for the
p.000033: participant group and specific individual, for example, in braille. Informed consent shall not include any language
p.000033: through which the subject is made to waive or appear to waive any of the participant’s legal rights, or releases or
p.000033: appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.
p.000033:
p.000033: Contents of the information leaflet. Throughout these Guidelines, elements that need to be included in the
p.000033: information leaflet are specified. Appendix 2 contains the details of information that must be provided, as well
p.000033: as possible supplementary information. This list mentions, but is not limited to, information about the aims,
p.000033: methods, sources of funding, possible conflicts of interest, institutional affiliations of the researcher, the
p.000033: anticipated benefits and potential risks of the study and the discomfort it may entail, post-trial access and
p.000033: any other relevant aspects of the study.
p.000033:
p.000033: Comprehension. The person obtaining consent must ensure that the potential participant has adequately
p.000033: understood the information provided. Researchers should use evidence-based methods for imparting information to ensure
p.000033: comprehension. The potential participant’s ability to understand the information depends, among other things, on the
p.000033: individual’s maturity, educational level and belief system. The participant’s understanding also depends on the
p.000033: researcher’s ability and willingness to communicate with patience and sensitivity, as well as the atmosphere, situation
p.000033: and location where the informed consent process takes place.
...
p.000097: study. Research ethics committees themselves must employ similar measures to identify, mitigate and manage the
p.000097: conflicts of interests of their own members. When necessary, research ethics committees may require members with a
p.000097: serious conflict to withdraw from deliberations of the research ethics committee and its decisions (see Guideline 23 –
p.000097: Requirements for establishing research ethics committees and for their review of protocols).
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097:
p.000097: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000098: 98
p.000098:
p.000098:
p.000098:
p.000098:
p.000098:
p.000098: APPENDIX 1
p.000098: ITEMS TO BE INCLUDED IN A PROTOCOL (OR ASSOCIATED
p.000098: DOCUMENTS) FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000098:
p.000098: (Include the items relevant to the study/project in question)
p.000098:
p.000098: 1. Title of the study;
p.000098:
p.000098: 2. A summary of the proposed research in lay/non-technical language;
p.000098:
p.000098: 3. A clear statement of the justification for the study, its significance in development and in meeting the needs
p.000098: of the country /population in which the research is carried out;
p.000098:
p.000098: 4. The investigators` views of the ethical issues and considerations raised by the study and, if
p.000098: appropriate, how it is proposed to deal with them;
p.000098:
p.000098: 5. Summary of all previous studies on the topic, including unpublished studies known to the
p.000098: investigators and sponsors, and information on previously published research on the topic, including the
p.000098: nature, extent and relevance of animal studies and other preclinical and clinical studies (Guideline 4);
p.000098:
p.000098: 6. A statement that the principles set out in these Guidelines will be implemented;
p.000098:
p.000098: 7. An account of previous submissions of the protocol for ethical review and their outcome;
p.000098:
p.000098: 8. A brief description of the site(s) where the research is to be conducted, including information about the
p.000098: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000098: epidemiological information about the country or region concerned;
p.000098:
p.000098: 9. Name and address of the sponsor;
p.000098:
p.000098: 10. Names, addresses, institutional affiliations, qualifications and experience of the principal investigator
p.000098: and other investigators (Guideline 1);
p.000098:
p.000098: 11. The objectives of the trial or study, its hypotheses or research questions, its assumptions, and its
p.000098: variables (Guideline 1);
p.000098:
p.000098: 12. A detailed description of the design of the trial or study. In the case of controlled clinical trials the
...
p.000101: appropriate, through publication or by reporting to the drug registration authority (Guideline 24);
p.000101:
p.000101: 47. Plans for publication of research results in certain fields (for example, epidemiology, genetics, sociology) that
p.000101: may present risks to the interests of communities, societies, families, or racially or ethnically defined groups and
p.000101: for minimizing risks to these groups, notably by maintaining confidentiality during and after the study and publishing
p.000101: the resulting data in a manner that is respectful of the interests of all concerned (Guideline 4); and
p.000101:
p.000101: 48. A statement that any proven evidence of falsification of data will be dealt with in accordance with the policy of
p.000101: the sponsor to take appropriate action against such unacceptable procedures.
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:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000102: 102
p.000102: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000102:
p.000102:
p.000102:
p.000102:
p.000102:
p.000102: APPENDIX 2
p.000102: OBTAINING INFORMED CONSENT: ESSENTIAL INFORMATION
p.000102: FOR PROSPECTIVE RESEARCH PARTICIPANTS
p.000102:
p.000102: Before requesting an individual’s consent to participate in research, the researcher must provide the
p.000102: following information, in language or another form of communication that the individual can understand (see
p.000102: also Guideline 9):
p.000102: 1. the purpose of the research, its methods, the procedures to be carried out by the researcher and the
p.000102: participant, and an explanation of how the research differs from routine medical care (Guideline 9);
p.000102:
p.000102: 2. that the individual is invited to participate in research, the reasons for considering the individual suitable
p.000102: for the research, and that participation is voluntary (Guideline 9);
p.000102:
p.000102: 3. that the individual is free to refuse to participate and will be free to withdraw from the research at any time
p.000102: without penalty or loss of benefits to which he or she would otherwise be entitled (Guideline 9);
p.000102:
p.000102: 4. the expected duration of the individual’s participation (including number and duration of visits to the
p.000102: research centre and the total time involved) and the possibility of early termination of the trial or of
p.000102: the individual’s participation in it;
p.000102:
p.000102: 5. whether money or other forms of material goods will be provided in return for the individual’s participation,
p.000102: and, if so, the kind and amount, and that the time spent on the research and other inconveniences resulting from study
p.000102: participation will be appropriately compensated, monetary or non-monetary (Guideline 13);
p.000102:
p.000102: 6. that, after the completion of the study, participants will be informed of the outcomes of the
p.000102: research in general, if they so wish;
p.000102:
p.000102: 7. that individual participants during or after a study or collection of their biological material and
p.000102: health-related data will be informed of life-saving information and data of immediate clinical utility
...
p.000103: or for complications associated with the research, the nature and duration of such care, the name of
p.000103: the medical service or organization that will provide the treatment, and whether there is any uncertainty
p.000103: regarding funding of such treatment (Guideline 14);
p.000103:
p.000103: 23. in what way, and by what organization, the participant or the participant’s family or dependants will be
p.000103: compensated for disability or death resulting from such injury (or, when indicated, that there are no plans
p.000103: to provide such compensation) (Guideline 14);
p.000103:
p.000103: 24. whether or not, in the country in which the prospective participant is invited to participate in research, the
p.000103: right to compensation is legally guaranteed;
p.000103:
p.000103:
p.000103:
p.000104: 104
p.000104: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000104:
p.000104:
p.000104:
p.000104:
p.000104:
p.000104: 25. that a research ethics committee has approved or cleared the research protocol (Guideline 23);
p.000104:
p.000104: 26. that they will be informed in case of protocol violations and how safety and welfare will be
p.000104: protected in such a case (Guideline 23).
p.000104:
p.000104: In specific cases, before requesting an individual’s consent to participate in research, the researcher must provide
p.000104: the following information, in language or another form of communication that the individual can understand:
p.000104: 1. for controlled trials, an explanation of features of the research design (e.g., randomization,
p.000104: double-blinding), that the participant will not be told of the assigned treatment until the study has been completed
p.000104: and the blind has been broken;
p.000104:
p.000104: 2. whether all essential information is disclosed and, if not, that they are asked to agree to receiving incomplete
p.000104: information and that full information will be provided before study results are analysed and participants are given
p.000104: the possibility to withdraw their data collected under the study (Guideline 10);
p.000104:
p.000104: 3. policy with regard to the use of results of genetic tests and familial genetic information, and the precautions
p.000104: in place to prevent disclosure of the results of a participant’s genetic tests to immediate family
p.000104: relatives or to others (e.g. insurance companies or employers) without the consent of the participant (Guideline 11);
p.000104:
p.000104: 4. the possible research uses, direct or secondary, of the participant`s medical records and of biological
p.000104: specimens taken in the course of clinical care;
p.000104:
p.000104: 5. for collection, storage and use of biological material and health-related data, that broad informed consent will
p.000104: be obtained, which should specify: the purpose of the biobank, the conditions and duration of storage; the rules of
...
Searching for indicator linguistic:
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p.000034: consent only after obtaining permission from an institution such as a school or a prison, or from a community leader, a
p.000034: council of elders, or another designated authority. Such institutional procedures or cultural customs should be
p.000034: respected. In no case, however, may the permission of a community leader or other authority substitute for individual
p.000034: informed consent. In some populations, the use of local languages may facilitate the communication of information to
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
p.000034: factors can be internal to participants, such as mental illness, whereas other influences can be external, such as a
p.000034: dependent relationship between participants and clinician-researchers. Circumstances such as severe illness or poverty
p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
p.000034: consent in these situations. Research ethics committees must determine for each individual protocol if influences on
p.000034: voluntary consent cross the threshold of being undue, and if so, which safeguards are appropriate.
p.000034:
p.000034: Dependent relationship. There are different forms of dependent relationships, such as those between
...
Social / Literacy
Searching for indicator illiterate:
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p.000056: Although research ethics committees can require special protections only for potential participants collectively for a
p.000056: particular project, researchers and others involved in research must take into account factors that render individual
p.000056: participants vulnerable and take appropriate steps to mitigate those factors.
p.000056:
p.000056: A traditional approach to vulnerability in research has been to label entire classes of individuals as vulnerable. The
p.000056: account of vulnerability in this Guideline seeks to avoid considering members of entire classes of
p.000056: individuals as vulnerable. However, it is useful to look at the specific characteristics that may render individuals
p.000056: vulnerable, as this can aid in identifying the special protections needed for persons who may have an increased
p.000056: likelihood of being wronged or of incurring additional harm as participants in research. Different characteristics
p.000056: may also co-exist, making some individuals more vulnerable than others. This is highly dependent on the context.
p.000056: For example, persons who are illiterate, marginalized by virtue of their social status or behaviour, or living in an
p.000056: authoritarian environment, may have multiple factors that make them vulnerable.
p.000056:
p.000056: Some characteristics can make it reasonable to assume that certain individuals are vulnerable, for example:
p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
p.000056:
p.000056: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
...
p.000087: affect the safety of participants, or other ethical matters that emerge during the course of the study.
p.000087: These further reviews include progress reports submitted by researchers and possible monitoring of researchers’
p.000087: compliance with approved protocols.
p.000087:
p.000087: Committee membership. The research ethics committee must be constituted according to a document that
p.000087: specifies the manner in which members and the chair will be appointed, reappointed, and replaced. Research ethics
p.000087: committees must have members capable of providing competent and thorough review of research proposals. Membership
p.000087: normally must include physicians, scientists and other professionals such as research coordinators, nurses,
p.000087: lawyers, and ethicists, as well as community members or representatives of patients’ groups who can represent
p.000087: the cultural and moral values of study participants. Ideally, one or more members should have experience as study
p.000087: participants since there is growing recognition that knowledge gained through personal experience as a participant can
p.000087: supplement the professional understanding of illness and medical care. Committees must include both men and women.
p.000087: When a proposed study involves vulnerable individuals or groups, as may be the case in research involving
p.000087: prisoners or illiterate persons, representatives of relevant advocacy groups should be invited to meetings where such
p.000087: protocols will be reviewed (see
p.000087:
p.000087:
p.000087: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000088: 88
p.000088:
p.000088:
p.000088:
p.000088:
p.000088:
p.000088: Guideline 15 – Research involving vulnerable persons and groups). Regular rotation of members is desirable for
p.000088: balancing the advantage of experience with that of fresh perspectives.
p.000088:
p.000088: Members of research ethics committees must regularly update their knowledge about the ethical conduct of health-related
p.000088: research. If committees do not have the relevant expertise to adequately review a protocol, they must consult
p.000088: with external persons with the proper skills or certification. Committees must keep records of their
p.000088: deliberations and decisions.
p.000088:
p.000088: Conflicts of interests on the part of committee members. Research ethics committees must provide independent ethical
p.000088: opinions. Pressure can be brought to bear from many different directions, not just financial. Research ethics
p.000088: committees must therefore have mechanisms to ensure the independence of their operations. In particular, they
p.000088: must avoid any undue influence and minimize and manage conflicts of interests. Research ethics committees must
p.000088: require that their members disclose to the committee any interests they may have that could constitute a conflict of
...
Searching for indicator literacy:
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p.000025: forums outside of the community in which they were implemented, as well as any data generation that could create social
p.000025: risks for participants.
p.000025:
p.000025: Engagement at the earliest opportunity. Before a study is initiated, the community from which participants will be
p.000025: recruited should, when feasible, be consulted about their research priorities, preferred trial designs,
p.000025: willingness to be involved in the preparation and conduct of the study. Engaging the community at the
p.000025: earliest stage promotes smooth study functioning and contributes to the community’s capacity to understand the research
p.000025: process. Community members should be encouraged to raise any concerns they may have at the outset and as the research
p.000025: proceeds. Failure to engage the community can compromise the social value of the research, as well as threaten the
p.000025: recruitment and retention of participants.
p.000025:
p.000025: Community engagement should be an ongoing process, with an established forum for communication between researchers and
p.000025: community members. This forum can facilitate the creation of educational materials, planning the necessary
p.000025: logistical arrangements for the conduct of the research, and providing information about the health beliefs,
p.000025: cultural norms, and practices of the community. Active engagement with community members is a mutually educative
p.000025: process, which both enables researchers to learn about communities’ cultures and understanding of research- related
p.000025: concepts, and contributes to research literacy by educating the community about key concepts critical for
p.000025: understanding the purpose and procedures of the research. Good-quality community engagement helps to ensure that
p.000025: existing community dynamics and power inequities are not allowed to derail the process of ensuring the
p.000025: comprehensive engagement of all relevant community stakeholders. Care should be taken to solicit the views of all
p.000025: sectors of the community proactively and sensitively. Community members should be invited to assist in the development
p.000025: of the informed consent process and documents to ensure that they are understandable and appropriate for potential
p.000025: participants.
p.000025:
p.000025: Confidence and trust. Engaging the community strengthens local ownership of the research and builds confidence in
p.000025: the ability of leaders to negotiate various aspects of the research, such as recruitment strategies, care
p.000025: for the health needs of study participants, site selection, data collection and sharing, ancillary care and post-trial
p.000025: availability of any developed interventions for populations and communities (see Guideline 2 – Research conducted in
p.000025: low-resource settings, and Guideline 6
p.000025: – Caring for participants’ health needs). An open and active process of community engagement is critical for building
p.000025: and maintaining trust among researchers, participants, and other members of the local community. An illustration of
p.000025: successful involvement of the community was a study in the Eliminate Dengue Program in Queensland, Australia. Previous
p.000025: introductions of genetically-modified strategies for dengue vector control had generated international controversy by
...
Searching for indicator literate:
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p.000065:
p.000065:
p.000065:
p.000065:
p.000065: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: Potential individual benefits and risks. The potential individual benefits and risks of research with
p.000066: children or adolescents should be evaluated based on Guideline 4 – Potential individual benefits and risks of research,
p.000066: and Guideline 5 – Choice of control in clinical trials.
p.000066:
p.000066: Assent. Children and adolescents who are legally minors cannot give legally valid informed consent, but they may be
p.000066: able to give assent. To give assent means that the child or adolescent is meaningfully engaged in the research
p.000066: discussion in accordance with his or her capacities. Assent must be considered as a process (see Guideline 9
p.000066: – Individuals capable of giving informed consent) and is not merely the absence of dissent. Furthermore, the researcher
p.000066: must involve the child or adolescent in the actual decision-making process and use age-appropriate information. It is
p.000066: of major importance to inform the child or adolescent and obtain assent as described above, preferably in
p.000066: writing for children who are literate. The process of obtaining assent must take into account not only the age of
p.000066: children, but also their individual circumstances, life experiences, emotional and psychological maturity, intellectual
p.000066: capabilities and the child’s or adolescent’s family situation.
p.000066:
p.000066: As adolescents near the age of majority, their agreement to participate in research may be ethically
p.000066: (though not legally) equivalent to consent. In this situation, parental consent is ethically best
p.000066: considered as “co-consent” but legally, the adolescent’s agreement remains assent. If child or adolescent
p.000066: participants reach the legal age of majority according to applicable law and become capable of independent informed
p.000066: consent during the research, their written informed consent to continued participation must be sought and their
p.000066: decision respected.
p.000066:
p.000066: Deliberate objection. Some children and adolescents who are too immature to give assent may be able to register a
p.000066: “deliberate objection,” meaning an expression of disapproval or refusal of a proposed procedure. The deliberate
...
Social / Marital Status
Searching for indicator married:
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p.000066: research unless it is supplemented by the permission of a parent, legal guardian or other duly authorized
p.000066: representative. The decision to continue or discontinue participation by children or adolescents who become legally
p.000066: capable during the study trumps the decision of their parents or legal guardians.
p.000066:
p.000066: Waiver of parental permission. In certain circumstances, research ethics committees may waive parental permission. In
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
p.000066:
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p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
...
Searching for indicator single:
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p.000044: would not qualify for communication to the participant. The research ethics committee should also evaluate whether
p.000044: individual counselling is necessary when returning particular genetic findings. Some cases may require making an
p.000044: ethically responsible management plan for returning (un)solicited findings.
p.000044:
p.000044: Children and adolescents. Children and adolescents who reach the age of maturity during the research
p.000044: project should be given the opportunity to give informed consent for the continued storage and use of their
p.000044: material and related data, and they should also be able to withdraw consent for future research. An
p.000044: informed, opt-out system in which such persons are alerted to their right to withdraw could also be
p.000044: acceptable.
p.000044:
p.000044: Material Transfer Agreement. The transfer of human biological materials must be covered by a material transfer
p.000044: agreement (MTA). This MTA must ensure that the biological materials are documented in such a way that they can be
p.000044: retrieved. The range and duration of use and what needs to happen at the end of the period of use must also be
p.000044: specified. All responsibilities concerning these elements of an MTA need to be clearly stated in the agreement. An MTA
p.000044: is also needed in multinational research projects in which one entity collects samples from persons in all
p.000044: participating countries and stores them in a single biobank.
p.000044:
p.000044: Closure of a biobank. In the event of closure of the biobank, plans for appropriate transfer or
p.000044: disposal of the biological material and data should be developed in collaboration with local health authorities.
p.000044:
p.000044: Storing and using material from low-resource settings in biobanks. Biobanks have become a global phenomenon.
p.000044: Nevertheless, some low-resource settings may be inexperienced in storing and using biological materials. In
p.000044: addition to what is stated in this Guideline, requirements for community engagement, capacity-building and
p.000044: equitable distribution of burdens and benefits of research as described in other guidelines also apply to biobank
p.000044: research in low-resource settings (see Guideline 3 – Equitable distribution of benefits and burdens in the selection of
p.000044: individuals and groups of participants in research, Guideline 7 – Community engagement, and Guideline 8 – Collaborative
p.000044: partnership and capacity building for research and review).
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
p.000044: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000045: 45
p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: GUIDELINE 12:
p.000045: COLLECTION, STORAGE AND USE OF DATA IN HEALTH-RELATED RESEARCH
p.000045:
p.000045: When data are stored, institutions must have a governance system to obtain authorization for future use of these data
p.000045: in research. Researchers must not adversely affect the rights and welfare of individuals from whom the data were
...
p.000088: require that their members disclose to the committee any interests they may have that could constitute a conflict of
p.000088: interest or otherwise bias their evaluation of a research proposal. Research ethics committees must evaluate each study
p.000088: in light of any disclosed interests and ensure that appropriate steps are taken to mitigate possible conflicts of
p.000088: interest (see Guideline 25 – Conflicts of interest). Research ethics committees may receive a fee for reviewing
p.000088: studies. However, this need not constitute a conflict of interest (see Guideline 25 – Conflicts of interest).
p.000088:
p.000088: National (centralized) or local review. Research ethics committees may be created under the aegis of national or local
p.000088: administrations, national (or centralized) medical research councils or other nationally representative bodies. In
p.000088: a highly centralized administration, a national, or centralized, review committee may be constituted for both
p.000088: scientific and ethical review of research protocols. In countries where medical research is not centrally
p.000088: administered, ethical review can also be undertaken at a local or regional level. Whether research is nationally
p.000088: or locally reviewed varies and may depend on the size of the country and the type of the research. The authority of a
p.000088: local research ethics committee may be confined to a single institution or may extend to all institutions in which
p.000088: health-related research is carried out within a defined geographical area or network.
p.000088:
p.000088: Externally sponsored research. Research may be externally sponsored, meaning that it is sponsored, financed,
p.000088: and sometimes wholly or partly carried out by an external organization with the collaboration or agreement of the
p.000088: appropriate authorities of the host community. External sponsors must collaborate with local partners (see Guideline 8
p.000088: – Collaborative partnership and capacity building for research and review). Researchers and sponsors who plan to
p.000088: perform research in settings where research ethics committees are absent or lack adequate training should
p.000088: help to establish such committees according to their ability before the research is initiated, and make provisions
p.000088: for their education in research ethics (see Guideline 8 – Collaborative partnership and capacity building for research
p.000088: and review).
p.000088:
p.000088: Externally sponsored research must be reviewed at the site of the sponsor as well as locally. The ethical standards
p.000088: should be no less stringent than they would be for research carried out in the country of the sponsoring organization
p.000088: (see also Guideline 2 – Research conducted in low-resource settings). Local committees must be fully empowered to
p.000088: disapprove a study that they believe to be unethical.
p.000088:
p.000088: Multi-centre research. Some research projects are designed to be conducted in a number of centres in
p.000088: different communities or countries. To ensure that the results are valid, the study must be conducted in a
p.000088: methodologically identical way at each centre. However, committees at individual centres must be authorized to adapt
p.000088: the informed consent document provided by the sponsor or the lead institution in the multi-centre trial in order to
p.000088: make it culturally appropriate.
p.000088:
p.000088: To avoid lengthy procedures, multi-centre research in a single jurisdiction (state or country) should be reviewed by
p.000088: only one research ethics committee. In cases of multi-centre research, if a local
p.000088:
p.000088:
p.000088: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000089: 89
p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089: review committee proposes changes to the original protocol that it believes are necessary to protect the research
p.000089: participants, these changes must be reported to the research institution or sponsor responsible for the whole research
p.000089: programme for consideration and possible action. This should ensure that all persons are protected and that the
p.000089: research will be valid across sites.
p.000089:
p.000089: Ideally, review procedures should be harmonized, which may decrease the time needed for review and accordingly, speed
p.000089: up the research process. In order to harmonize review processes and to maintain sufficient quality of these processes,
p.000089: ethics committees must develop quality indicators for ethical review. Appropriate review must be sensitive to increases
p.000089: in risk of harm or wrongs to local participants and populations.
p.000089:
p.000089: Exemptions from review. Some studies may be exempt from review. For example, when publicly available data are analysed
p.000089: or the data for the study are generated by observation of public behaviour, and data that could identify individual
...
p.000095: potentially exposing participants to excessive risks or compromising the scientific validity of the research.
p.000095: This situation is of particular concern when participants are dependent on a researcher who is also their clinician
p.000095: (see Guideline 9 – Individuals capable of giving informed consent, section on Dependent relationship), and when the
p.000095: salary of the clinician is considerably lower than what the researcher is paid. It may also lead researchers to
p.000095: pressure eligible participants to enrol, thus compromising or undermining participants’ voluntary consent. In addition,
p.000095: financial conflicts of interest can arise when researchers or senior members of the research team (or their close
p.000095: family members) have a financial stake in the company sponsoring the research, such as stock ownership.
p.000095:
p.000095: 2. Research institutions (universities, research centres, or pharmaceutical companies). Research institutions can
p.000095: have both reputational and financial conflicts of interests. For example, universities rely on the reputation of
p.000095: their research to attract faculty, students, or external funding. Some universities also patent the discoveries
p.000095: of their employees. Institutional conflicts of interest can also arise when a research centre derives substantial
p.000095: support (perhaps covering years of funding) from a single sponsor or a handful of sponsors. Pharmaceutical companies
p.000095: may feel pushed to accelerate a marketing authorization for getting a longer period of patent protection, or they may
p.000095: be tempted to downplay the side effects of new medicines to get broader prescription patterns.
p.000095:
p.000095: 3. Research ethics committees. Researchers often serve as members of research ethics committees and
p.000095: conflicts of interest can arise in this role. For example, a researcher may submit her own study protocol for review,
p.000095: or she may be reviewing the work of colleagues whom she knows personally, or whose work she considers critical for the
p.000095: success of her institution. Research ethics committees may also have financial interests when their members
p.000095: receive salaries or when they are directly funded by sponsors or serve an institution that depends significantly on
p.000095: support from a single sponsor or several sponsors.
p.000095: A fee paid to a research ethics committee (or the institution where it operates) for reviewing a study does not present
p.000095: an inherent conflict of interest, provided that the fee is established by a general policy, is reasonably related to
p.000095: the costs of conducting the review and is not dependent on the outcome of the review (see Guideline 23 – Requirements
p.000095: for establishing research ethics committees and for their review of protocols).
p.000095:
p.000095: In order to evaluate the seriousness of a conflict of interest, and to determine appropriate measures for its
p.000095: management, research ethics committees need to judge the risk that the sponsor’s or investigator’s
p.000095: conflicts of interest unduly compromise or undermine the ethical or scientific conduct of a study. This involves
p.000095: judging both the likelihood that a secondary interest might compromise the rights or welfare of participants
p.000095: or the scientific validity of the research, as well as judging the magnitude of the secondary interest relative to the
p.000095: stakeholder’s personal situation. For example, an early-career researcher with a modest salary might have more
p.000095: significant academic and financial conflicts of interest than an established senior member of the research
p.000095: team. Research ethics committees have to exercise their judgment when evaluating the seriousness of conflicts of
p.000095: interest.
p.000095:
p.000095:
...
p.000098: investigators and sponsors, and information on previously published research on the topic, including the
p.000098: nature, extent and relevance of animal studies and other preclinical and clinical studies (Guideline 4);
p.000098:
p.000098: 6. A statement that the principles set out in these Guidelines will be implemented;
p.000098:
p.000098: 7. An account of previous submissions of the protocol for ethical review and their outcome;
p.000098:
p.000098: 8. A brief description of the site(s) where the research is to be conducted, including information about the
p.000098: adequacy of facilities for the safe and appropriate conduct of the research, and relevant demographic and
p.000098: epidemiological information about the country or region concerned;
p.000098:
p.000098: 9. Name and address of the sponsor;
p.000098:
p.000098: 10. Names, addresses, institutional affiliations, qualifications and experience of the principal investigator
p.000098: and other investigators (Guideline 1);
p.000098:
p.000098: 11. The objectives of the trial or study, its hypotheses or research questions, its assumptions, and its
p.000098: variables (Guideline 1);
p.000098:
p.000098: 12. A detailed description of the design of the trial or study. In the case of controlled clinical trials the
p.000098: description should include, but not be limited to, whether assignment to treatment groups
p.000098:
p.000098:
p.000098: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099:
p.000099:
p.000099:
p.000099:
p.000099:
p.000099: will be randomized (including the method of randomization), and whether the study will be blinded (single
p.000099: blind, double blind), or open (Guideline 5);
p.000099:
p.000099: 13. The number of research participants needed to achieve the study objective, and how this was statistically
p.000099: determined;
p.000099:
p.000099: 14. The criteria for inclusion or exclusion of potential participants, and justification for the exclusion of any
p.000099: groups on the basis of age, sex, social or economic factors, or for other reasons (Guideline 3);
p.000099:
p.000099: 15. The justification for involving as research participants children or adolescents, persons who are unable to give
p.000099: informed consent or vulnerable persons or groups, and a description of special measures to minimize risks to such
p.000099: persons (Guidelines 15, 16 and 17);
p.000099:
p.000099: 16. The process of recruitment, e.g. advertisements, and the steps to be taken to protect privacy and confidentiality
p.000099: during recruitment (Guideline 3);
p.000099:
p.000099: 17. Description and explanation of all interventions (the method of treatment administration, including
p.000099: route of administration, dose, dose interval and treatment period for investigational and comparator products used);
p.000099:
p.000099: 18. Plans and justification for withdrawing or withholding standard therapies in the course of the research, including
p.000099: any resulting risks to persons (Guidelines 4 and 5);
p.000099:
...
Social / Mothers
Searching for indicator mothers:
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p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
p.000070:
p.000070:
p.000070: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000071: 71
p.000071:
p.000071:
p.000071:
p.000071:
p.000071:
p.000071: routine exclusion of pregnant women from clinical trials is their use of medications (both prescription and
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
p.000071: it is imperative to design research for pregnant and breastfeeding women to learn about the currently unknown
p.000071: risks and potential individual benefits to them, as well as to the fetus or nursing infant.
p.000071:
p.000071: A case in point is the thalidomide episode, in which about 10,000 babies around the world (many in Western Europe) were
p.000071: born with severely deformed limbs because their mothers had taken medication when pregnant. This tragedy is often cited
p.000071: as a reason for excluding pregnant women from health- related research, but the lesson to be learned is the opposite.
p.000071: Never having been tested in pregnant women, the drug came to market and was readily available for morning sickness, a
p.000071: relatively mild condition. Had the drug been tested in very few women in a clinical trial, the mutagenic effect would
p.000071: most likely have been discovered and the total number of babies born with deformities would have been much smaller.
p.000071:
p.000071: Research designed to obtain knowledge relevant to the health needs of pregnant and breastfeeding women should be
p.000071: promoted in the following areas:
p.000071: f interventions for conditions resulting from pregnancy;
p.000071: f interventions for conditions that affect the general population and are reasonably expected to be used without
p.000071: adequate evidence during pregnancy (for example off-label use of medications); and
p.000071: f interventions for conditions that affect the developing fetus.
p.000071:
...
Social / Police Officer
Searching for indicator officer:
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p.000107: education projects since 2007. Since 2015, he is Secretary General of the Swiss Academic Foundation on Education in
p.000107: Infectious Diseases SAFE-ID. He is work package co-leader and member of the Executive Committee in the EUPATI-IMI
p.000107: project and involved in a number of European and global research networks and research collaborations, including the
p.000107: ENCePP Steering Group. He is co-chair of the Patient and Consumer Working Party at the European Medicines Agency and
p.000107: has served the European AIDS Treatment Group EATG in various positions since 2004. David has been involved in HIV and
p.000107: HCV drug development since 2005 and has specific interests in the areas of Personalised Medicine, Risk Communication,
p.000107: Pharmacovigilance, Observational Studies, Biomedical Prevention and HIV Eradication Research. He is living with HIV
p.000107: since 1986.
p.000107:
p.000107: Bocar Kouyaté
p.000107: Bocar A. Kouyaté is Senior Advisor to the Minister of Health, Burkina Faso and researcher at the Centre national de
p.000107: recherché et de formation sur le paludisme (CNRFP), Burkina Faso. Dr Kouyaté is a physician by training and holds
p.000107: a PhD degree in public health. He has worked throughout all levels of the health system in Burkina Faso from
p.000107: district medical officer to the intermediary level as
p.000107:
p.000107:
p.000107:
p.000107:
p.000108: 108
p.000108: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108: Provincial Director of Health and to Secretary General of the Ministry of Health from 1983 to 1998. From 1989 to 2009,
p.000108: he was Director of two research centres in Burkina Faso (Centre de recherche en santé de Nouna and, later on, Centre
p.000108: national de recherche et de formation sur le paludisme). He served as member of the Comité national d’éthique
p.000108: pour la recherche en santé (CERS) from 2003–2007 and was the Chair of the CERS from 2008–2013. He has
p.000108: considerable experience in research, research administration, capacity development and training, particularly in health
p.000108: systems, research ethics and malaria. His special interest is in the development of sustainable capacity and
p.000108: appropriate environment for research and getting research into policy and practice.
p.000108:
p.000108: Alex London
p.000108: Alex John London, PhD., is Professor of Philosophy and Director of The Center for Ethics and Policy at Carnegie Mellon
p.000108: University. An elected fellow of the Hastings Center, he has written extensively on problems in bioethics and
p.000108: ethical theory relating to uncertainty, risk, fairness, equality and justice. He is co-editor of Ethical Issues
...
p.000110: University of Tuebingen. Director of the Institute of History of Medicine at the University of Tuebingen. 2004-2013
p.000110: Chair of the Central Ethics-Committee of the Federal Board of Physicians.
p.000110:
p.000110: Hans-Joerg Ehni (Alternate), World Medical Association
p.000110: Hans-Joerg Ehni is the deputy director of the Institute for the Ethics and History of Medicine,
p.000110: University of Tuebingen, with a background in philosophy. His research is focused on the ethics of biomedical research
p.000110: involving human subjects and on the ethics of aging, particularly on the ethics of new biomedical interventions
p.000110: into the ageing process and increased longevity and on policies promoting healthy ageing. He is a member of
p.000110: the Research Ethics Committee of the Federal Board of Physicians, Baden-Württemberg.
p.000110:
p.000110: Carel IJsselmuiden, Council on Health Research for Development (COHRED)
p.000110: Carel is a physician, epidemiologist, public health practitioner, academic and social entrepreneur, with
p.000110: qualifications from universities in Belgium, Netherlands, South Africa and the United States. He spent 7
p.000110: years in rural medicine and public health, 4 years in peri-urban and urban health care, HIV/AIDS control and
p.000110: environmental services management as Deputy Medical Officer of Health for Johannesburg, South Africa. He
p.000110: was appointed as Professor and Head of Department of the department of community health at the University of
p.000110: Pretoria in 1995, where he became the founding Director of the School of Health Systems and Public Health in 1999. He
p.000110: held this position until his appointment as Executive Director at COHRED in 2004. As such, he is also member of the
p.000110: COHRED Board, President of COHRED USA and board member of COHRED Africa. He has published widely in applied research,
p.000110: nutrition, immunization, environmental health, research capacity building, global public health education and ethics of
p.000110: international collaborative health research. As part of community service, he was director of the Elim Care Group
p.000110: Project, a health and development NGO in the north of South Africa, served on the board of the Nokuthula
p.000110: Centre for Disabled Children in Alexandra township in South Africa and offers strategic research and innovation
p.000110: development support to low- and middle-income countries. Carel holds two nationalities – South African and Netherlands
p.000110: – and has worked and lived in Africa, Europe, the United States and the Caribbean.
p.000110:
p.000110: Observer
p.000110: Ingrid Callies
p.000110: Dr Ingrid Callies, PHD (University Paris Descartes), LLM (University of Virginia), a member of the New
...
Searching for indicator police:
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p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
p.000056:
p.000056: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
p.000057: Examples are medical and nursing students, subordinate hospital and laboratory personnel, workers in settings
p.000057: where research studies are conducted, and members of the armed forces or police. Their agreement to volunteer may be
p.000057: unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate
p.000057: in the study or by fear of disapproval or retaliation if they refuse (see also commentary on Guideline 9 – Individuals
p.000057: capable of giving informed consent). The research protocol must include a description of provisions to protect such
p.000057: individuals from being conscripted into research.
p.000057:
p.000057: Institutionalized persons. Residents of nursing homes, mental institutions, and prisons are often considered vulnerable
p.000057: because in a confined setting they have few options and are denied certain freedoms that non-institutionalized persons
p.000057: enjoy. For example, prisons have been described as “an inherently coercive environment.” Also, they may be in a
p.000057: dependent relationship with caregivers or guardians (see commentary on Guideline 9 – Individuals capable of giving
p.000057: informed consent, section on Dependent relationship).
p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
...
Social / Property Ownership
Searching for indicator home:
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p.000068: assessment of risks and benefits, as well as the process of informed consent, to ensure that women have
p.000068: the necessary time and appropriate environment to make decisions based on information provided to them.
p.000068:
p.000068: Some women become vulnerable in research because of heightened psychological, social, physical, or legal risks.
p.000068: Examples include surveys and interviews regarding intimate partner violence and rape; social and behavioural
p.000068: research involving sex workers or women who inject drugs; and studies that solicit information about sexual behaviour.
p.000068: When the research involves household surveys or interviews, researchers must take special care to ensure that the women
p.000068: are interviewed in a private
p.000068:
p.000068:
p.000068: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000069: 69
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: place without the possibility of intrusion by other family members. In such studies, women must be given
p.000069: the option of conducting the interview in a setting of their choosing outside the home. Breach of
p.000069: confidentiality in these types of research could result in serious harms to women, even if the only information
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
...
Searching for indicator property:
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p.000003: but is not carried out in populations that are the intended beneficiaries of the research. As an exception
p.000003: to the general rule specified in this Guideline, such studies can be justified because the effort to generate
p.000003: information relevant to significant health needs of people in low- resource settings represents an important
p.000003: demonstration of solidarity with burdened populations. For example, during the Ebola outbreak of 2014, phase one
p.000003: studies on investigational Ebola vaccines were carried out in low-resource communities not experiencing an Ebola
p.000003: outbreak.
p.000003:
p.000003: Responsibilities and plans. When the research has important potential individual benefits to the population or
p.000003: community, the responsibility to make any intervention or product developed available to this population is shared
p.000003: among researchers, sponsors, governments, and civil society. For this reason, the negotiation among stakeholders must
p.000003: include representatives in the community or country, including, where appropriate, the national government, the health
p.000003: ministry, local health authorities, relevant scientific and ethics groups, as well as members of the communities from
p.000003: which persons are drawn, patent-holders if they are other than the sponsor, and nongovernmental organizations such as
p.000003: health advocacy groups. The negotiation must address the health-care infrastructure required for safe and
p.000003: appropriate use of any intervention or product developed. When applicable, it must also consider the likelihood and
p.000003: conditions of authorization for distribution, and decisions regarding payments, royalties, subsidies, technology and
p.000003: intellectual property, as well as distribution costs, when such information is not proprietary. A plan to ensure the
p.000003: availability and distribution of successful products can require engaging with international organizations, donor
p.000003: governments and bilateral agencies, civil society organizations, and the private sector. The ability of the local
p.000003: health- care infrastructure to be able to provide the intervention must be facilitated at the outset so that delivery
p.000003: is possible following the completion of the research.
p.000003:
p.000003: Post-trial availability for communities and populations. Even if research addresses a question that has social value
p.000003: for the community or population where it is carried out, the community or population will not benefit from
p.000003: successful research unless the knowledge and interventions that it produces are made available to them and products are
p.000003: reasonably priced. Post-trial access plans are of particular concern for research conducted in low-resource settings
p.000003: where governments lack the means or infrastructure to make such products widely available.
p.000003:
p.000003: An investigational drug is unlikely to be generally available to the community or population until
p.000003: sometime after the conclusion of the study, as it may be in short supply, and in most cases could not be made generally
p.000003: available before a drug regulatory authority has approved it. However, other successful outcomes of research that
p.000003: do not require approval by a regulatory agency should be implemented as soon as feasible. An example is the
...
p.000091: their work to the lay public. Ideally, researchers should take steps to promote and enhance public discussion.
p.000091: Knowledge resulting from the research should be made accessible to the communities in which the research was conducted,
p.000091: either through publication in scientific journals or through other channels (see Guideline 2 – Research conducted in
p.000091: low-resource settings).
p.000091:
p.000091: Data sharing. There are compelling reasons to share the data of health-related research. Responsible sharing of
p.000091: clinical trial data serves the public interest by strengthening the science that is the foundation of safe
p.000091: and effective clinical care and public health practice. Sharing also fosters sound regulatory decisions, generates new
p.000091: research hypotheses, and increases the scientific knowledge gained from the contributions of clinical trial
p.000091: participants, the efforts of clinical trial researchers, and the resources of clinical trial funders.
p.000091:
p.000091: Data sharing requires careful balancing of competing considerations. Sharing of study data presents risks, burdens, and
p.000091: challenges as well potential individual benefits for various stakeholders. When sharing data, researchers must respect
p.000091: the privacy and consent of study participants. Researchers want a fair opportunity to publish their analyses and
p.000091: receive credit for carrying out studies and collecting data. Other researchers want to analyse data that would
p.000091: otherwise not be published in a timely manner and to replicate the findings of a published paper. Sponsors want
p.000091: to protect their intellectual property and commercially confidential information and allow a quiet period to
p.000091: review marketing applications. All stakeholders want to reduce the risk of invalid analyses of shared data.
p.000091:
p.000091: It is crucial to create a culture of responsible data sharing and mutually reinforcing incentives for sharing. Funders
p.000091: and sponsors must require funded researchers to share study data and must provide appropriate support
p.000091: for sharing. Researchers and sponsors must share data and design and carry out future studies assuming that
p.000091: data will be shared. Research institutions and universities must encourage researchers to share data. In their review
p.000091: of protocols, research ethics committees should consider a researcher’s and sponsor’s record in reporting results.
p.000091: Medical journals should request that authors share the analytical data set supporting the publication of study results.
p.000091: Patient advocacy organizations should consider data sharing plans as a criterion for funding grants and
p.000091: promoting studies to their constituents. Regulatory agencies around the globe should harmonize requirements
p.000091: and practices for data sharing. The risks of data sharing may be mitigated by controlling with whom the data are
p.000091: shared and under what conditions, without compromising the scientific usefulness of the shared data.
p.000091: Organizations that share data should employ data use agreements,
p.000091:
p.000091:
p.000091: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000092:
p.000092:
p.000092:
p.000092:
p.000092:
...
Social / Racial Minority
Searching for indicator race:
(return to top)
p.000005: compromised social or economic position or their ease of manipulation. Because categorical exclusion from research
p.000005: can result in or exacerbate health disparities, the exclusion of groups in need of special protection must
p.000005: be justified. Groups that are unlikely to benefit from any knowledge gained from the research should not bear a
p.000005: disproportionate share of the risks and burdens of research participation. Groups that are under-represented
p.000005: in medical research should be provided appropriate access to participate.
p.000005:
p.000005:
p.000005: Commentary on Guideline 3
p.000005: General considerations. The equitable distribution of benefits and burdens in the selection of study
p.000005: populations requires that the benefits of research be distributed fairly and that no group or class of persons bears
p.000005: more than its fair share of the risks or burdens from research participation. When benefits or burdens of research are
p.000005: to be apportioned unequally among individuals or groups, the criteria for unequal distribution should be scientifically
p.000005: and ethically justified rather than arbitrarily or conveniently chosen. Situations where unequal distribution of
p.000005: benefits would be considered are those in which the research particularly affects the population under study.
p.000005: In general, equitable distribution requires that participants be drawn from the qualifying population in the
p.000005: geographic area of the study where the results can be applied (see Guideline 2 – Research conducted in low-resource
p.000005: settings). Inclusion and exclusion criteria should not be based upon potentially discriminatory criteria, such as race,
p.000005: ethnicity, economic status, age or sex, unless there is a sound ethical or scientific reason to do so. For example, in
p.000005: cases where the under-representation of particular groups results in or perpetuates health disparities, equity may
p.000005: require special efforts to include members of those populations in research (see Guideline 17 – Research involving
p.000005: children and adolescents, Guideline 18
p.000005: – Women as research participants, and Guideline 19 – Pregnant women and breastfeeding women as research participants).
p.000005:
p.000005:
p.000005:
p.000005: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: Fair distribution of research benefits. Equity in the distribution of the benefits of research requires
p.000007: that research not disproportionately focus on the health needs of a limited class of people, but instead
p.000007: aims to address diverse health needs across different classes or groups. In the past, groups considered vulnerable
p.000007: were excluded from participation in research because it was considered the most expedient way of protecting
...
Searching for indicator racial:
(return to top)
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
p.000057: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000058: 58
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
...
p.000058: procedures that offer no potential individual benefits for participants; supplementing the participant’s agreement by
p.000058: the permission of family members, legal guardians, or other appropriate representatives; or requiring that the research
p.000058: be carried out only when it is targeted at conditions that affect these groups. Safeguards can be designed to promote
p.000058: voluntary decision-making, limit the potential for confidentiality breaches, and otherwise work to protect the
p.000058: interests of those at increased risk of harm. Research ethics committees need to be sensitive to not overly excluding
p.000058: people, and allow them to participate by requiring that special protections be put in place.
p.000058:
p.000058: Group vulnerability. Despite the importance of avoiding classification of entire groups as inherently vulnerable,
p.000058: circumstances exist that require research ethics committees to pay special attention to research involving
p.000058: certain groups. In some resource-limited countries or communities, lack of access to medical care,
p.000058: membership in ethnic and racial minorities, or other disadvantaged or marginalized groups can be factors
p.000058: that constitute vulnerability. As is true of the vulnerability of individuals, the judgment that groups
p.000058: are vulnerable is context dependent and requires empirical evidence to document the need for special
p.000058: protections.
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000059: 59
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059: GUIDELINE 16:
p.000059: RESEARCH INVOLVING
p.000059: ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000059:
p.000059: Adults who are not capable of giving informed consent must be included in health-related research unless a good
p.000059: scientific reason justifies their exclusion. As adults who are not capable of giving informed consent
p.000059: have distinctive physiologies and health needs, they merit special consideration by researchers and research
...
Social / Religion
Searching for indicator belief:
(return to top)
p.000033: participant group and specific individual, for example, in braille. Informed consent shall not include any language
p.000033: through which the subject is made to waive or appear to waive any of the participant’s legal rights, or releases or
p.000033: appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.
p.000033:
p.000033: Contents of the information leaflet. Throughout these Guidelines, elements that need to be included in the
p.000033: information leaflet are specified. Appendix 2 contains the details of information that must be provided, as well
p.000033: as possible supplementary information. This list mentions, but is not limited to, information about the aims,
p.000033: methods, sources of funding, possible conflicts of interest, institutional affiliations of the researcher, the
p.000033: anticipated benefits and potential risks of the study and the discomfort it may entail, post-trial access and
p.000033: any other relevant aspects of the study.
p.000033:
p.000033: Comprehension. The person obtaining consent must ensure that the potential participant has adequately
p.000033: understood the information provided. Researchers should use evidence-based methods for imparting information to ensure
p.000033: comprehension. The potential participant’s ability to understand the information depends, among other things, on the
p.000033: individual’s maturity, educational level and belief system. The participant’s understanding also depends on the
p.000033: researcher’s ability and willingness to communicate with patience and sensitivity, as well as the atmosphere, situation
p.000033: and location where the informed consent process takes place.
p.000033:
p.000033: Documentation of consent. Consent may be indicated in a number of ways. The participant may express consent orally, or
p.000033: sign a consent form. As a general rule, the participant should sign a consent form, or, where the individual lacks
p.000033: decisional capacity, a legal guardian or other duly authorized
p.000033:
p.000033:
p.000033: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000034: 34
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: representative must do so (see Guideline 16 – Research involving individuals incapable of giving informed
p.000034: consent, and Guideline 17 – Research involving children and adolescents). The research ethics committee may approve a
p.000034: waiver of the requirement of a signed consent document under certain conditions (see Guideline 10 – Modifications and
...
Social / Soldier
Searching for indicator armed forces:
(return to top)
p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
p.000056:
p.000056: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
p.000057: Examples are medical and nursing students, subordinate hospital and laboratory personnel, workers in settings
p.000057: where research studies are conducted, and members of the armed forces or police. Their agreement to volunteer may be
p.000057: unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate
p.000057: in the study or by fear of disapproval or retaliation if they refuse (see also commentary on Guideline 9 – Individuals
p.000057: capable of giving informed consent). The research protocol must include a description of provisions to protect such
p.000057: individuals from being conscripted into research.
p.000057:
p.000057: Institutionalized persons. Residents of nursing homes, mental institutions, and prisons are often considered vulnerable
p.000057: because in a confined setting they have few options and are denied certain freedoms that non-institutionalized persons
p.000057: enjoy. For example, prisons have been described as “an inherently coercive environment.” Also, they may be in a
p.000057: dependent relationship with caregivers or guardians (see commentary on Guideline 9 – Individuals capable of giving
p.000057: informed consent, section on Dependent relationship).
p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
...
Searching for indicator military:
(return to top)
p.000072: abortion in another country.
p.000072:
p.000072: Breastfeeding women. The father may need to be consulted in research involving breastfeeding women, in accordance with
p.000072: Guideline 17 – Research involving children and adolescents. If a breast- fed infant may be exposed to an
p.000072: investigational product through the ingestion of breast milk (or it is unknown whether an infant would be exposed),
p.000072: such research should be conducted in accordance with Guideline 17 – Research involving children and adolescents.
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000073: 73
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073: GUIDELINE 20:
p.000073: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS
p.000073:
p.000073: Disasters arising from events such as earthquakes, tsunamis or military conflicts, and disease outbreaks, can
p.000073: have a sudden and devastating impact on the health of large affected populations. In order to identify effective ways
p.000073: of mitigating the health impact of disasters and disease outbreaks, health-related research should form an integral
p.000073: part of disaster response. However, the conduct of research must not unduly impact the response to the victims of a
p.000073: disaster.
p.000073:
p.000073: In the conduct of research in disasters and disease outbreaks, it is essential to uphold the ethical principles
p.000073: embodied in these Guidelines. Conducting research in these situations raises important challenges such as the
p.000073: need to generate knowledge quickly, maintain public trust, and overcome practical obstacles to implementing
p.000073: research. These challenges need to be carefully balanced with the need to ensure the scientific validity of the
p.000073: research and uphold ethical principles in its conduct.
p.000073:
p.000073: Researchers, sponsors, international organizations, research ethics committees and other relevant stakeholders should
p.000073: ensure that:
p.000073: f studies are designed so as to yield scientifically valid results under the challenging and often rapidly evolving
p.000073: conditions of disasters and disease outbreaks (see Guideline 1
p.000073: – Scientific and social value and respect for rights);
p.000073: f the research is responsive to the health needs or priorities of the disaster victims and affected
p.000073: communities and cannot be conducted outside a disaster situation (see Guideline 2 – Research conducted in low-resource
p.000073: settings);
p.000073: f participants are selected fairly and adequate justification is given when particular populations are
...
Social / Student
Searching for indicator student:
(return to top)
p.000052: medical insurance, educational materials, counselling or food supplies. Especially when the research poses low risks,
p.000052: providing compensation for participation should not raise concerns about undue inducement.
p.000052:
p.000052: Unacceptable compensation. Compensation is not meant to compensate for risk that participants agree to undertake but
p.000052: rather, for inconvenience and time. Therefore, the level of compensation
p.000052:
p.000052: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000053: 53
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: should not be related to the level of risk that participants agree to undertake. But especially as the
p.000053: risks of research procedures having no potential individual benefit for participants increase, so does the
p.000053: concern that compensation may constitute an undue inducement. Monetary or in-kind compensation for research
p.000053: participants must not be so large as to persuade them to volunteer against their better judgment or deeply
p.000053: held beliefs (“undue inducement”).
p.000053:
p.000053: It can be difficult to determine whether undue inducement exists, in part because the compensation that makes some
p.000053: people volunteer against their better judgment depends on their personal situation. An unemployed person or a student
p.000053: may view compensation differently from an employed person. Research ethics committees must evaluate monetary and other
p.000053: forms of compensation in light of the traditions and socio-economic context of the particular culture and population in
p.000053: order to determine whether the average participant expected to enrol in the study is likely to participate in the
p.000053: research against his or her better judgment because of the compensation offered. The appropriateness of compensation
p.000053: is likely better judged by local research ethics committees than by international ones. Consultation with
p.000053: the local community may help to ascertain this even in the case of research conducted in the researcher’s own
p.000053: community.
p.000053:
p.000053: Compensation for persons who are incapable of giving informed consent. Persons who are incapable of giving informed
p.000053: consent may be vulnerable to exploitation for financial gain by their guardians. A legally authorized
p.000053: representative asked to give permission on behalf of a person who is incapable of giving informed consent must be
p.000053: offered no compensation other than reimbursement for travel and other direct or indirect expenses. Where it would be
...
Social / Threat of Stigma
Searching for indicator stigma:
(return to top)
p.000043: destroyed or returned to the donor. Future use of the biological materials and related data is not permitted after the
p.000043: withdrawal of consent.
p.000043:
p.000043: Authorization for research with archived materials. When biological materials and data collected and stored in the past
p.000043: without specific or broad informed consent contain important and otherwise unobtainable data, a research ethics
p.000043: committee needs to decide whether the use of such materials is justified. The most common justification for using
p.000043: records or materials collected in the past without consent is that it would be impracticable or prohibitively
p.000043: expensive to locate the persons whose materials or records are to be examined. For example, this may happen when
p.000043: the study involves review of hospital records or performing new tests on blood collected at a time when consent to
p.000043: future research uses of such materials was not usually sought. In addition, the research must have important social
p.000043: value, and the research must pose no more than minimal risks to participants or to the group from which the participant
p.000043: originates.
p.000043:
p.000043: Confidentiality. An important aspect of storing human biological material is confidentiality guaranteed to the donor.
p.000043: The information resulting from analysis of the material could, if disclosed to third parties, cause harm,
p.000043: stigma or distress. Those responsible for biobanks must arrange to protect the confidentiality of such information
p.000043: by, for example, providing only anonymized or coded data to researchers and limiting access of the material of
p.000043: third parties. During the process of obtaining informed consent, those responsible for the biobank must inform
p.000043: the potential donors about the safeguards that will be taken to protect confidentiality as well as their
p.000043: limitations. Biological material stored in biobanks must be anonymized or coded. When researchers use coded materials
p.000043: obtained from biobanks in later studies, the key to the code must remain with the custodian of the biobank. Thus
p.000043: researchers can use only anonymized or coded material. It should be acknowledged that the possibility of complete
p.000043: anonymization is becoming increasingly illusory as the possibility of cross- matching large datasets improves. The
p.000043: more difficult it becomes to anonymize data, the more important it will be to retain the ability to remove
p.000043: personal data from a dataset. This is a crucial part of the governance system specified above.
p.000043:
p.000043: Return of results and disclosure of (un)solicited findings. Generally, biobanks store coded material in
p.000043: order to be able to link this material to health data. This means that research findings,
p.000043:
p.000043:
p.000043: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000044: 44
p.000044:
p.000044:
p.000044:
p.000044:
p.000044:
...
p.000049: also establish acceptable modalities for establishing contact with those participants or service users who
p.000049: are willing to be reached out to for the above-mentioned purposes.
p.000049:
p.000049: In cases where a researcher does plan to contact persons based on their inclusion in a health-related registry, the
p.000049: researcher must bear in mind that these persons may be unaware that their data were submitted to the registry or
p.000049: unfamiliar with the process by which researchers obtain access to the data. If researchers wish to
p.000049: contact persons included in a health registry to obtain additional information from them for new
p.000049: research, such studies require individual informed consent (see Guideline 9 – Individuals capable of giving
p.000049: informed consent).
p.000049:
p.000049: Data mining. Some entities collect data that may be “mined” for health-related research, even if they are not
p.000049: collecting health-related data deliberately (for example, queries in search engines, consumer choices on websites).
p.000049: Such entities must strive for governance structures and mechanisms to obtain authorization for future use of these data
p.000049: in research as discussed in this Guideline.
p.000049:
p.000049: Confidentiality. Health-related data may contain a very large range of information. Therefore, an important
p.000049: aspect of storing health-related data is confidentiality. The collection and storage of information could, if disclosed
p.000049: to third parties, cause harm, stigma or distress. Those responsible for databanks must arrange to protect the
p.000049: confidentiality of such information by, for example, providing only anonymized or coded data to
p.000049: researchers and limiting access of the data to third parties. During the process of obtaining informed consent,
p.000049: those responsible for the databank must inform the potential donors about the safeguards that will be taken to protect
p.000049: confidentiality as well as their limitations. Data stored in databanks must be anonymized or coded. When
p.000049: researchers use coded materials obtained from databanks in later studies, the key to the code must
p.000049: remain with the custodian of the databank. Thus researchers can only use anonymized or coded material. It should be
p.000049: acknowledged that the possibility of complete anonymization is becoming increasingly illusory as the possibility of
p.000049: cross-matching large datasets improves. The more difficult it becomes to anonymize data, the more important it will be
p.000049: to retain the ability to remove personal data from a dataset. This is a crucial part of the governance system specified
p.000049: above.
p.000049:
p.000049: When linked data are used, researchers customarily discard personal identifying information when consolidating data for
p.000049: purposes of statistical analysis; this also occurs when researchers have linked (or coded) different sets of data
p.000049: regarding individuals with the consent of individual participants. When project plans require personal
...
Searching for indicator stigmatized:
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p.000056: increased likelihood of being wronged or of incurring additional harm.” This implies that vulnerability involves
p.000056: judgments about both the probability and degree of physical, psychological, or social harm, as well as a greater
p.000056: susceptibility to deception or having confidentiality breached. It is important to recognize that vulnerability
p.000056: involves not only the ability to provide initial consent to participate in research, but also aspects of the ongoing
p.000056: participation in research studies. In some cases, persons are vulnerable because they are relatively (or
p.000056: absolutely) incapable of protecting their own interests. This may occur when persons have relative or absolute
p.000056: impairments in decisional capacity, education, resources, strength, or other attributes needed to protect their own
p.000056: interests. In other cases, persons can also be vulnerable because some feature of the circumstances (temporary or
p.000056: permanent) in which they live makes it less likely that others will be vigilant about, or sensitive to, their
p.000056: interests. This may happen when people are marginalized, stigmatized, or face social exclusion or prejudice
p.000056: that increases the likelihood that others place their interests at risk, whether intentionally or unintentionally.
p.000056: Although research ethics committees can require special protections only for potential participants collectively for a
p.000056: particular project, researchers and others involved in research must take into account factors that render individual
p.000056: participants vulnerable and take appropriate steps to mitigate those factors.
p.000056:
p.000056: A traditional approach to vulnerability in research has been to label entire classes of individuals as vulnerable. The
p.000056: account of vulnerability in this Guideline seeks to avoid considering members of entire classes of
p.000056: individuals as vulnerable. However, it is useful to look at the specific characteristics that may render individuals
p.000056: vulnerable, as this can aid in identifying the special protections needed for persons who may have an increased
p.000056: likelihood of being wronged or of incurring additional harm as participants in research. Different characteristics
p.000056: may also co-exist, making some individuals more vulnerable than others. This is highly dependent on the context.
...
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
p.000057: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000058: 58
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: stereotypes. One proposed mechanism that can be used to avoid stereotyping is consultation with relevant stakeholders,
p.000058: where feasible, before, during and after the conduct of the research (see Guideline 7 – Community
p.000058: engagement).
p.000058:
p.000058: Special protections. Special protections for these groups can include allowing no more than minimal risks for
...
Social / Threat of Violence
Searching for indicator violence:
(return to top)
p.000057: informed consent, section on Dependent relationship).
p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
p.000057: committee when such proposals are under review (see commentary on Guideline 9 – Individuals capable of giving informed
p.000057: consent, section on Dependent relationship). Some individuals with this characteristic may also have diminished
p.000057: capacity to consent, and therefore require the additional protections noted earlier for participants who lack
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
...
p.000066: capable during the study trumps the decision of their parents or legal guardians.
p.000066:
p.000066: Waiver of parental permission. In certain circumstances, research ethics committees may waive parental permission. In
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
p.000066:
p.000066: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000067: 67
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
p.000067: psychological and medical support for the participating children and adolescents is another special
p.000067: protection, though this may be difficult to realize in some communities. In such communities, the study
p.000067: personnel must be sufficiently qualified to help children and adolescents who need medical and psychological support.
p.000067:
...
p.000068:
p.000068: Vulnerability of women. Despite the current general presumption that favours the inclusion of women in
p.000068: research, in many societies women remain socially vulnerable in the conduct of research. For example, they may
p.000068: suffer negligence or harm because of their submission to authority, their hesitancy or inability to ask
p.000068: questions, and a cultural tendency to deny or tolerate pain and suffering. When women in these situations are potential
p.000068: participants in research, researchers, sponsors and ethics committees must take special care in the research design,
p.000068: assessment of risks and benefits, as well as the process of informed consent, to ensure that women have
p.000068: the necessary time and appropriate environment to make decisions based on information provided to them.
p.000068:
p.000068: Some women become vulnerable in research because of heightened psychological, social, physical, or legal risks.
p.000068: Examples include surveys and interviews regarding intimate partner violence and rape; social and behavioural
p.000068: research involving sex workers or women who inject drugs; and studies that solicit information about sexual behaviour.
p.000068: When the research involves household surveys or interviews, researchers must take special care to ensure that the women
p.000068: are interviewed in a private
p.000068:
p.000068:
p.000068: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000069: 69
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: place without the possibility of intrusion by other family members. In such studies, women must be given
p.000069: the option of conducting the interview in a setting of their choosing outside the home. Breach of
p.000069: confidentiality in these types of research could result in serious harms to women, even if the only information
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
p.000069: could include risks to the fetus if they become pregnant during the research (see Guideline 19 – Pregnant
...
Social / Unemployment
Searching for indicator unemployed:
(return to top)
p.000052: Compensation can be monetary or non-monetary and may include, for example, health services unrelated to the research,
p.000052: medical insurance, educational materials, counselling or food supplies. Especially when the research poses low risks,
p.000052: providing compensation for participation should not raise concerns about undue inducement.
p.000052:
p.000052: Unacceptable compensation. Compensation is not meant to compensate for risk that participants agree to undertake but
p.000052: rather, for inconvenience and time. Therefore, the level of compensation
p.000052:
p.000052: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000053: 53
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: should not be related to the level of risk that participants agree to undertake. But especially as the
p.000053: risks of research procedures having no potential individual benefit for participants increase, so does the
p.000053: concern that compensation may constitute an undue inducement. Monetary or in-kind compensation for research
p.000053: participants must not be so large as to persuade them to volunteer against their better judgment or deeply
p.000053: held beliefs (“undue inducement”).
p.000053:
p.000053: It can be difficult to determine whether undue inducement exists, in part because the compensation that makes some
p.000053: people volunteer against their better judgment depends on their personal situation. An unemployed person or a student
p.000053: may view compensation differently from an employed person. Research ethics committees must evaluate monetary and other
p.000053: forms of compensation in light of the traditions and socio-economic context of the particular culture and population in
p.000053: order to determine whether the average participant expected to enrol in the study is likely to participate in the
p.000053: research against his or her better judgment because of the compensation offered. The appropriateness of compensation
p.000053: is likely better judged by local research ethics committees than by international ones. Consultation with
p.000053: the local community may help to ascertain this even in the case of research conducted in the researcher’s own
p.000053: community.
p.000053:
p.000053: Compensation for persons who are incapable of giving informed consent. Persons who are incapable of giving informed
p.000053: consent may be vulnerable to exploitation for financial gain by their guardians. A legally authorized
p.000053: representative asked to give permission on behalf of a person who is incapable of giving informed consent must be
p.000053: offered no compensation other than reimbursement for travel and other direct or indirect expenses. Where it would be
...
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
...
Social / Victim of Abuse
Searching for indicator trauma:
(return to top)
p.000061: be sought. Surrogate decision-makers must evaluate to what extent study participation is consistent with the
p.000061: individual’s previously formed preferences and values (if any), and, in the case of research that offers participants a
p.000061: prospect of clinical benefit, to what extent study participation promotes the individual’s clinical interests.
p.000061: Previously stated preferences regarding the individual’s willingness to enrol in research or documented preferences in
p.000061: an advance directive should be respected. Researchers must recognize that surrogates may have their own
p.000061: interests that may call their permission into question. Furthermore, in situations where a legally
p.000061: authorized representative is not available to allow for timely enrolment, researchers may obtain the permission of a
p.000061: representative who is socially accepted but not formally recognized before the law.
p.000061:
p.000061: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000062: 62
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062: Emergency care situations in which the researcher anticipates that many participants will be unable to
p.000062: consent. Research protocols are sometimes designed to address conditions occurring suddenly and rendering the
p.000062: patients or participants incapable of giving informed consent. Examples are sepsis, head trauma, cardiopulmonary arrest
p.000062: and stroke. In such circumstances, it is often necessary to proceed with the research interventions very soon after the
p.000062: onset of the condition in order to evaluate an investigational treatment or develop the desired knowledge.
p.000062:
p.000062: If possible, an attempt must be made to identify a population that is likely to develop the condition to be studied.
p.000062: This can be done readily, for example, if the condition is one that recurs periodically in individuals, such as grand
p.000062: mal seizures and alcohol binges. In such cases, researchers should ideally contact potential participants while fully
p.000062: capable of informed consent, and obtain their agreement to be involved in the research during future periods of
p.000062: incapacitation, for example in an advance directive.
p.000062:
p.000062: If there is no opportunity to solicit informed consent of participants while fully capable of informed consent, plans
p.000062: to conduct emergency care research with incapacitated persons must be publicized within the community in which it will
p.000062: be carried out, where feasible. In the design and conduct of the research, the research ethics committee, the
p.000062: researchers and the sponsors must be responsive to the concerns of the community. The research must not be carried out
p.000062: if it does not have substantial support in the community concerned. (See commentary on Guideline 4 – Potential
...
p.000075: their studies do not unduly compromise the disaster response. Researchers and sponsors should also aim to contribute to
p.000075: the infrastructure for the humanitarian response and integrate their research activities with this response.
p.000075: Importantly, all studies must be responsive to the health needs or priorities of the affected populations, and it must
p.000075: not be possible to conduct the research outside a disaster situation.
p.000075:
p.000075: General challenges in disaster research. In infectious disease outbreaks, there can be considerable pressure to conduct
p.000075: research. This is especially the case for diseases that have a high mortality rate and where the treatment options
p.000075: are limited (for example during the 2014 Ebola outbreak). Conversely, in natural or man-made disasters,
p.000075: research can be met with great scepticism or even hostility, and researchers can be at risk of physical harm.
p.000075: Researchers and sponsors must be equipped to negotiate these pressures in what are typically fragile political and
p.000075: social situations. They must also have sufficient operational and security support in order to work effectively in such
p.000075: challenging environments. Acute disasters pose numerous challenges for conducting ethically responsible
p.000075: research. For example, potential study participants often suffer from serious physical or psychological
p.000075:
p.000075:
p.000075: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000076: 76
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000076: trauma that can make it difficult for them to protect their rights and interests. Limited or damaged health
p.000076: infrastructures can challenge implementation of preferred study designs and data collection. Moreover, efforts to make
p.000076: available as soon as possible any interventions or products developed from the research to the affected communities are
p.000076: often more challenging in acute disaster situations (see Guideline 2 – Research conducted in low-resource
p.000076: settings). Despite these challenges, it is essential that researchers and sponsors uphold the ethical principles
p.000076: embodied in these Guidelines, even if the standard ways of respecting these principles may need to be modified. In
p.000076: fact, an acute disaster situation can require modifying standard procedures so that ethical principles can be upheld in
p.000076: the most expedient way possible. For example, while ethical oversight is essential in all research, accelerated ethical
p.000076: review during disasters may be necessary to ensure that valuable studies can begin as soon as possible without
p.000076: compromising ethical requirements (see below).
p.000076:
p.000076: While all ethical principles in these Guidelines have to be upheld, some require special attention.
p.000076:
p.000076: Potential individual benefits and risks of investigational interventions and emergency use outside clinical trials.
p.000076: Especially when disasters are caused by infectious diseases that are highly contagious or serious (for example
p.000076: influenza, Ebola), there is great pressure to develop effective treatments and vaccines. When facing a serious,
p.000076: life-threatening infection, many people are willing to assume high risks and use unproven agents within or
...
Searching for indicator abuse:
(return to top)
p.000050: implication, efforts to de-identify data in order to safeguard confidentiality and the resulting trade-offs
p.000050: in the scientific value of the given data need to be carefully balanced.
p.000050:
p.000050: Limits of confidentiality. Donors must be informed of the limits to the ability of researchers to ensure
p.000050: strict confidentiality and of the potential adverse consequences of breaches of confidentiality. Confidentiality is
p.000050: limited for three reasons. First, even with good governance structures, there is some background risk that data are
p.000050: leaked or stolen and thus are obtained by unauthorized third parties. Second, data from different sources (for example,
p.000050: health records, employment records, etc.) may be linked due to technological advances, which increasingly enable
p.000050: researchers or others to identify individuals even when working with anonymized or coded data. Identification is also
p.000050: possible when the context in which the research is conducted is narrow (for example, small hospital) or very specific
p.000050: (for example, patients with rare diseases). Pooling data from a number of comparable sources may reduce but not
p.000050: completely eliminate the possibility of identifying individuals. In addition, genetic information derived
p.000050: through comprehensive technologies (for example, whole-genome sequencing) increasingly allows identifying individuals.
p.000050: Third, releasing confidential data can be required by law. For example, some jurisdictions require the reporting to
p.000050: appropriate agencies of certain communicable diseases or evidence of child abuse or neglect. Similarly, (health)
p.000050: authorities and research ethics committee accrediting agencies may have the legal right to inspect study records, and a
p.000050: sponsor’s compliance audit staff may require and obtain access to confidential data. These and similar limits to the
p.000050: ability to maintain confidentiality must be anticipated and disclosed to potential participants (see Guideline 9 –
p.000050: Individuals capable of giving informed consent). The more difficult it becomes to truly anonymize data, the
p.000050: more important it becomes for the participant to retain the ability to remove personal data from a dataset. Therefore,
p.000050: this is a crucial part of the governance system specified above.
p.000050:
p.000050: Mandatory population-based registries. Research projects using data from mandatory population- based registries must
p.000050: be submitted for review to a research ethics committee except for data analyses inherent to the internal
p.000050: institutional research activity of the registry.
p.000050:
p.000050: Return of results and (un)solicited findings. Especially in the context of data collections in which large data bases
p.000050: are combined (big data research), the informed consent must clearly stipulate whether return of
p.000050: information derived from analysis of the data is foreseen, if the donor wishes. The information given to
p.000050: the donor should clearly state that providing individual diagnoses is not the purpose of the databank or future
...
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
p.000066:
p.000066: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000067: 67
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
p.000067: psychological and medical support for the participating children and adolescents is another special
p.000067: protection, though this may be difficult to realize in some communities. In such communities, the study
p.000067: personnel must be sufficiently qualified to help children and adolescents who need medical and psychological support.
p.000067:
p.000067: A research ethics committee may also allow a waiver of parental permission if the conditions set out in Guideline 10 –
...
Social / Women
Searching for indicator women:
(return to top)
p.000007: GUIDELINE 8: COLLABORATIVE PARTNERSHIP AND CAPACITY-BUILDING
p.000007: FOR RESEARCH AND RESEARCH REVIEW 29
p.000007: GUIDELINE 9: INDIVIDUALS CAPABLE OF GIVING INFORMED CONSENT 33
p.000007: GUIDELINE 10: MODIFICATIONS AND WAIVERS OF INFORMED CONSENT 37
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: v
p.000007:
p.000007: GUIDELINE 11: COLLECTION, STORAGE AND USE OF BIOLOGICAL
p.000007: MATERIALS AND RELATED DATA 41
p.000007: GUIDELINE 12: COLLECTION, STORAGE AND USE OF DATA IN HEALTH- RELATED RESEARCH
p.000047: 47
p.000047: GUIDELINE 13: REIMBURSEMENT AND COMPENSATION FOR
p.000047: RESEARCH PARTICIPANTS 53
p.000047: GUIDELINE 14: TREATMENT AND COMPENSATION FOR RESEARCH-
p.000047: RELATED HARMS
p.000055: 55
p.000055: GUIDELINE 15: RESEARCH INVOLVING VULNERABLE PERSONS
p.000055: AND GROUPS
p.000057: 57
p.000057: GUIDELINE 16: RESEARCH INVOLVING ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000061: 61
p.000061: GUIDELINE 17: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS 65
p.000061: GUIDELINE 18: WOMEN AS RESEARCH PARTICIPANTS 69
p.000061: GUIDELINE 19: PREGNANT AND BREASTFEEDING WOMEN AS
p.000061: RESEARCH PARTICIPANTS 71
p.000061: GUIDELINE 20: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS 75
p.000061: GUIDELINE 21: CLUSTER RANDOMIZED TRIALS 79
p.000061: GUIDELINE 22: USE OF DATA OBTAINED FROM THE ONLINE
p.000061: ENVIRONMENT AND DIGITAL TOOLS IN HEALTH-RELATED RESEARCH 83
p.000061: GUIDELINE 23: REQUIREMENTS FOR ESTABLISHING RESEARCH ETHICS COMMITTEES AND FOR THEIR REVIEW OF PROTOCOLS
p.000087: 87
p.000087: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000087: vi
p.000087:
p.000087: GUIDELINE 24: PUBLIC ACCOUNTABILITY FOR HEALTH-RELATED RESEARCH 91
p.000087: GUIDELINE 25: CONFLICTS OF INTEREST 95
p.000087: APPENDIX 1 ITEMS TO BE INCLUDED IN A PROTOCOL (OR ASSOCIATED DOCUMENTS) FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099: APPENDIX 2 OBTAINING INFORMED CONSENT: ESSENTIAL
p.000099: INFORMATION FOR PROSPECTIVE RESEARCH PARTICIPANTS 103
p.000099: APPENDIX 3 CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH
p.000099: INVOLVING HUMANS
p.000107: 107
p.000107: APPENDIX 4 COMMENTATORS 113
p.000107: INDEX
p.000119: 119
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
...
p.000005:
p.000005:
p.000005: Commentary on Guideline 3
p.000005: General considerations. The equitable distribution of benefits and burdens in the selection of study
p.000005: populations requires that the benefits of research be distributed fairly and that no group or class of persons bears
p.000005: more than its fair share of the risks or burdens from research participation. When benefits or burdens of research are
p.000005: to be apportioned unequally among individuals or groups, the criteria for unequal distribution should be scientifically
p.000005: and ethically justified rather than arbitrarily or conveniently chosen. Situations where unequal distribution of
p.000005: benefits would be considered are those in which the research particularly affects the population under study.
p.000005: In general, equitable distribution requires that participants be drawn from the qualifying population in the
p.000005: geographic area of the study where the results can be applied (see Guideline 2 – Research conducted in low-resource
p.000005: settings). Inclusion and exclusion criteria should not be based upon potentially discriminatory criteria, such as race,
p.000005: ethnicity, economic status, age or sex, unless there is a sound ethical or scientific reason to do so. For example, in
p.000005: cases where the under-representation of particular groups results in or perpetuates health disparities, equity may
p.000005: require special efforts to include members of those populations in research (see Guideline 17 – Research involving
p.000005: children and adolescents, Guideline 18
p.000005: – Women as research participants, and Guideline 19 – Pregnant women and breastfeeding women as research participants).
p.000005:
p.000005:
p.000005:
p.000005: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007: 7
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: Fair distribution of research benefits. Equity in the distribution of the benefits of research requires
p.000007: that research not disproportionately focus on the health needs of a limited class of people, but instead
p.000007: aims to address diverse health needs across different classes or groups. In the past, groups considered vulnerable
p.000007: were excluded from participation in research because it was considered the most expedient way of protecting
p.000007: those groups (for example, children, women of reproductive age, pregnant women). As a consequence of such exclusions,
p.000007: information about the diagnosis, prevention and treatment of diseases that afflict such groups is limited. This has
p.000007: resulted in a serious injustice. Since information about the management of diseases is considered a benefit to society,
p.000007: it is unjust to intentionally deprive specific groups of that benefit. The need to redress these injustices by
p.000007: encouraging the participation of previously excluded groups in basic and applied biomedical research is widely
p.000007: recognized.
p.000007:
p.000007: Fair distribution of research burdens. Research with human participants typically requires that some persons or
p.000007: groups are exposed to risks and burdens in order to generate the knowledge needed to protect and promote
p.000007: people’s health (see Guideline 1 – Scientific and social value and respect for rights). Equity in the distribution of
p.000007: burdens of research requires special care to ensure that individuals, communities or populations that are already
p.000007: disadvantaged or marginalized are not over-represented in research. A disproportionate selection of disadvantaged or
p.000007: convenient populations is morally problematic for several reasons. First, it is unjust to selectively invite poor or
p.000007: marginalized individuals or groups to participate in research because this concentrates the risks and burdens of
p.000007: research on people who already experience increased risks and burdens from social and economic disadvantage. Second,
p.000007: these individuals and groups are also the most likely to be excluded from, or to have difficulty accessing, the
p.000007: benefits of research. Third, the broad inclusion of different social groups helps to ensure that research is conducted
...
p.000023: is also valuable for the contribution it can make to the successful conduct of research. In particular, community
p.000023: engagement is a means of ensuring the relevance of proposed research to the affected community, as well as
p.000023: its acceptance by the community. In addition, active community involvement helps to ensure the ethical and social
p.000023: value and outcome of proposed research. Community engagement is especially important when the research
p.000023: involves minorities or marginalized groups, including persons with stigmatizing diseases such as HIV, in order to
p.000023: address any potential discrimination.
p.000023:
p.000023: A community consists not only of people living in the geographic area where research is to be carried out; it also
p.000023: comprises different sectors of society that have a stake in the proposed research, as well as sub-populations from
p.000023: which research participants will be recruited. Stakeholders are individuals, groups, organizations, government bodies,
p.000023: or any others who can influence or are affected by the conduct or outcome of the research project. The process must be
p.000023: fully collaborative and transparent, involving a wide variety of participants, including patients and consumer
p.000023: organizations, community leaders and representatives, relevant NGOs and advocacy groups, regulatory authorities,
p.000023: government agencies and community advisory boards. Also, it is important to ensure diversity of views within the
p.000023: consultation process. For instance, when community leaders are men only, researchers should actively include the views
p.000023: of women, as well. There may also be value in consulting individuals who have previously participated in comparable
p.000023: studies.
p.000023:
p.000023: The research protocol or other documents submitted to the research ethics committee should include a
p.000023: description of the plan for community engagement, and identify resources allocated for the proposed activities. This
p.000023: documentation must specify what has been and will be done, when and by whom, to ensure that the community is clearly
p.000023: defined and can be proactively engaged throughout the research to ensure that it is relevant to the community and is
p.000023: accepted. The community should participate, when feasible, in the actual discussion and preparation of the
p.000023: research protocol and documents.
p.000023:
p.000023: Researchers, sponsors, health authorities and relevant institutions should take care that community engagement does
p.000023: not lead to pressure or undue influence on individual community members to participate (see commentary on
p.000023: Guideline 9 – Individuals capable of giving informed consent, section
p.000023:
p.000023:
p.000023:
p.000023: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000025: 25
p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: on Dependent relationship). In order to avoid such pressure, individual informed consent must always be sought by the
p.000025: researcher.
p.000025:
...
p.000057: because in a confined setting they have few options and are denied certain freedoms that non-institutionalized persons
p.000057: enjoy. For example, prisons have been described as “an inherently coercive environment.” Also, they may be in a
p.000057: dependent relationship with caregivers or guardians (see commentary on Guideline 9 – Individuals capable of giving
p.000057: informed consent, section on Dependent relationship).
p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
p.000057: committee when such proposals are under review (see commentary on Guideline 9 – Individuals capable of giving informed
p.000057: consent, section on Dependent relationship). Some individuals with this characteristic may also have diminished
p.000057: capacity to consent, and therefore require the additional protections noted earlier for participants who lack
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
...
p.000067: child or adolescent to participate in research must generally be given the opportunity, to a reasonable
p.000067: extent and without violating the privacy of other study participants, to observe the child’s participation as
p.000067: the study proceeds. This could enable the child to be withdrawn if the parent or guardian decides it is in the child’s
p.000067: best interests to do so.
p.000067:
p.000067: Emergency care situations in which the researcher anticipates that children and adolescents will participate. When
p.000067: children and adolescents participate in emergency care research, the principles of Guideline 16 – Research involving
p.000067: adults incapable of giving informed consent - apply.
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p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: GUIDELINE 18:
p.000068: WOMEN AS RESEARCH PARTICIPANTS
p.000068:
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
p.000068: physiologies and health needs, they merit special consideration by researchers and research ethics committees. Only the
p.000068: informed consent of the woman herself should be required for her research participation. Since some societies lack
p.000068: respect for women’s autonomy, in no case must the permission of another person replace the requirement of individual
p.000068: informed consent by the woman.
p.000068:
p.000068: Women of child-bearing potential must be informed in advance of the possibility of risks to the fetus
p.000068: should they become pregnant during their research participation. When participation in research might be
p.000068: hazardous to a fetus or a woman if she becomes pregnant, sponsors and researchers must guarantee access to pregnancy
p.000068: tests, effective contraceptive methods before and during the research and to safe, legal abortion.
p.000068:
p.000068:
p.000068: Commentary on Guideline 18
p.000068: General considerations. Women in many societies have been excluded from research. For example, most of the early
p.000068: cardiovascular disease studies have excluded women because these diseases were believed to be uncommon in women. In
p.000068: particular, women who are biologically capable of becoming pregnant have been traditionally excluded from clinical
p.000068: trials of drugs, vaccines and medical devices owing to concern about undetermined risks to the fetus (see
p.000068: Guideline 15 – Research involving vulnerable persons and groups). Although the presumption against including women
p.000068: has changed in recent years, they are still excluded in many cases without adequate justification. Much remains unknown
p.000068: about the safety and efficacy of most drugs, vaccines, or devices used by women in medical practice, and
p.000068: this lack of knowledge can be dangerous. For example, heart attacks in women are different from heart attacks in men,
p.000068: so research is necessary to determine the best means of diagnosis and treatment in women.
p.000068:
p.000068: Vulnerability of women. Despite the current general presumption that favours the inclusion of women in
p.000068: research, in many societies women remain socially vulnerable in the conduct of research. For example, they may
p.000068: suffer negligence or harm because of their submission to authority, their hesitancy or inability to ask
p.000068: questions, and a cultural tendency to deny or tolerate pain and suffering. When women in these situations are potential
p.000068: participants in research, researchers, sponsors and ethics committees must take special care in the research design,
p.000068: assessment of risks and benefits, as well as the process of informed consent, to ensure that women have
p.000068: the necessary time and appropriate environment to make decisions based on information provided to them.
p.000068:
p.000068: Some women become vulnerable in research because of heightened psychological, social, physical, or legal risks.
p.000068: Examples include surveys and interviews regarding intimate partner violence and rape; social and behavioural
p.000068: research involving sex workers or women who inject drugs; and studies that solicit information about sexual behaviour.
p.000068: When the research involves household surveys or interviews, researchers must take special care to ensure that the women
p.000068: are interviewed in a private
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p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: place without the possibility of intrusion by other family members. In such studies, women must be given
p.000069: the option of conducting the interview in a setting of their choosing outside the home. Breach of
p.000069: confidentiality in these types of research could result in serious harms to women, even if the only information
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
p.000069: could include risks to the fetus if they become pregnant during the research (see Guideline 19 – Pregnant
p.000069: women and breastfeeding women as research participants). Access to a pregnancy test, to effective
p.000069: contraceptive methods and to safe, legal abortion must be guaranteed before exposure to a potential teratogenic or
p.000069: mutagenic intervention. When effective contraception and safe abortion are not available and alternative study sites
p.000069: are not feasible, the informed consent discussion must include information about the risk of unintended pregnancy, the
p.000069: legal grounds for abortion, and information about reducing harms from unsafe abortion and subsequent complications.
p.000069: Also, if the pregnancy is not terminated, participants must be guaranteed a medical follow-up for their own health and
p.000069: that of the infant and child.
p.000069:
p.000069: Women who become pregnant during research. Many biomedical protocols call for terminating the participation of women
p.000069: who become pregnant during the research. In cases where a drug or biological product is known to be mutagenic or
p.000069: teratogenic, pregnant women must be removed from the study, and followed up and provided care through
p.000069: the duration of their pregnancy and delivery. Access to diagnostic tests must be provided to reveal any fetal
p.000069: anomalies. If anomalies are detected, women who wish may be referred for an abortion. When there is no evidence on the
p.000069: basis of which a potential harm to the fetus can be assumed, women who become pregnant should not automatically be
p.000069: removed from the study, but must be offered the option to continue or end their participation. For instance, in some
p.000069: cases it may be appropriate for a woman to stay in the study for safety monitoring but removed from the study drug. If
p.000069: the woman opts for continued participation, researchers and sponsors must offer adequate monitoring and support.
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p.000070:
p.000070:
p.000070:
p.000070:
p.000070:
p.000070: GUIDELINE 19:
p.000070: PREGNANT AND BREASTFEEDING WOMEN AS RESEARCH PARTICIPANTS
p.000070:
p.000070: Pregnant and breastfeeding women have distinctive physiologies and health needs. Research designed to obtain
p.000070: knowledge relevant to the health needs of the pregnant and breastfeeding woman must be promoted. Research in pregnant
p.000070: women must be initiated only after careful consideration of the best available relevant data.
p.000070:
p.000070: In no case must the permission of another person replace the requirement of individual informed consent by the pregnant
p.000070: or breastfeeding woman.
p.000070:
p.000070: For research interventions or procedures that have the potential to benefit either pregnant or breastfeeding women or
p.000070: their fetus or infant, risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000070:
p.000070: For research interventions or procedures that have no potential individual benefits for pregnant and
p.000070: breastfeeding women:
p.000070: f the risks must be minimized and no more than minimal; and
p.000070: f the purpose of the research must be to obtain knowledge relevant to the particular health needs of
p.000070: pregnant or breastfeeding women or their fetuses or infants.
p.000070:
p.000070: When the social value of the research for pregnant or breastfeeding women or their fetus or infant is compelling,
p.000070: and the research cannot be conducted in non-pregnant or non- breastfeeding women, a research ethics committee
p.000070: may permit a minor increase above minimal risk.
p.000070:
p.000070: Short-term and long‐term follow-up of the fetus and the child may be required in research involving pregnant and
p.000070: breastfeeding women depending upon the study intervention and its potential risks.
p.000070:
p.000070: As a general rule, health-related research involving pregnant women that has the potential for harm to the fetus should
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
p.000070: treatment includes medications that may have a prospect of serious harm to the fetus, such as radiation or
p.000070: chemotherapy for cancer. A direct consequence of the
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p.000071:
p.000071:
p.000071:
p.000071:
p.000071: routine exclusion of pregnant women from clinical trials is their use of medications (both prescription and
p.000071: non-prescription) lacking data from clinical trials about the potential individual benefits and harms to themselves,
p.000071: their fetuses and their future children. Therefore, after careful consideration of the best available relevant data,
p.000071: it is imperative to design research for pregnant and breastfeeding women to learn about the currently unknown
p.000071: risks and potential individual benefits to them, as well as to the fetus or nursing infant.
p.000071:
p.000071: A case in point is the thalidomide episode, in which about 10,000 babies around the world (many in Western Europe) were
p.000071: born with severely deformed limbs because their mothers had taken medication when pregnant. This tragedy is often cited
p.000071: as a reason for excluding pregnant women from health- related research, but the lesson to be learned is the opposite.
p.000071: Never having been tested in pregnant women, the drug came to market and was readily available for morning sickness, a
p.000071: relatively mild condition. Had the drug been tested in very few women in a clinical trial, the mutagenic effect would
p.000071: most likely have been discovered and the total number of babies born with deformities would have been much smaller.
p.000071:
p.000071: Research designed to obtain knowledge relevant to the health needs of pregnant and breastfeeding women should be
p.000071: promoted in the following areas:
p.000071: f interventions for conditions resulting from pregnancy;
p.000071: f interventions for conditions that affect the general population and are reasonably expected to be used without
p.000071: adequate evidence during pregnancy (for example off-label use of medications); and
p.000071: f interventions for conditions that affect the developing fetus.
p.000071:
p.000071: Informed consent and risks and potential individual benefits. The involvement of pregnant women in
p.000071: research is complicated by the fact that it may present risks and potential individual benefits to the
p.000071: fetus as well as to the woman. Participation of breastfeeding women in biomedical research may similarly pose risks
p.000071: to the nursing infant. Research in pregnant and breastfeeding women must be initiated only after careful
p.000071: consideration of the best available data from preclinical research in pregnant animal models, research in non‐pregnant
p.000071: women, retrospective observational studies, and pregnancy registries.
p.000071:
p.000071: Researchers and research ethics committees must ensure that potential research participants are adequately
p.000071: informed about the risks to breastfeeding women and their infants, and about the risks to pregnant women (including
p.000071: future fertility), their pregnancies, their fetuses, and their future offspring. Information must also include steps
p.000071: taken to maximize potential individual benefits and minimize risks (see Guideline 4 – Potential individual benefits and
p.000071: risks of research). When evidence concerning risks is unknown or conflicting, this must be disclosed to the pregnant or
p.000071: breastfeeding woman as part of the informed consent process. She is the one to make the final decision about the
p.000071: acceptability of these risks to her and her fetus or infant. Women must also be informed that it is often difficult to
p.000071: determine causality in cases of fetal or infant abnormalities. Pregnant women may be recruited for research in which
p.000071: there is no prospect of potential individual benefit to them or the fetus only if the risks of the
p.000071: intervention are minimal. Examples include minimally invasive studies of new diagnostic techniques. In
p.000071: special circumstances, a minor increase above minimal risk may be acceptable.
p.000071:
p.000071: Some research involving pregnant women may be directed at the health of the fetus. In such cases, the role of the woman
p.000071: remains the same: she is the decision-maker for any interventions that affect her. This does not exclude the
p.000071: possibility of the woman consulting with the father of the fetus, if she wishes.
p.000071:
p.000071: Especially in communities or societies in which cultural beliefs accord more importance to the fetus than to the
p.000071: woman’s life or health, women may feel constrained to participate, or not to participate,
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p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: in research. Special safeguards must be established to prevent undue inducement to pregnant women to
p.000072: participate in research in which interventions hold out the prospect of potential individual benefit to the fetus but
p.000072: not to the woman herself.
p.000072:
p.000072: Researchers must include in protocols on research involving pregnant women a plan for monitoring the outcome of the
p.000072: pregnancy with regard to both the health of the woman and the short-term and long-term health of the infant and child.
p.000072: Adverse events associated with research in pregnancy and during lactation may not occur immediately.
p.000072:
p.000072: Potential individual benefits and risks. The potential individual benefits and risks of research with pregnant and
p.000072: breastfeeding women should be evaluated based on Guideline 4 – Potential individual benefits and risks of research, and
p.000072: Guideline 5 – Choice of control in clinical trials.
p.000072:
p.000072: Serious harm and access to abortion. Research with pregnant women must be conducted only in settings where
p.000072: these women can be guaranteed access to a safe, legal abortion. This rule serves to prevent women from having to carry
p.000072: an unwanted fetus to term and deliver an affected baby against their wishes. Before pregnant women are enrolled,
p.000072: researchers must, at a minimum, determine whether fetal impairment and mental health conditions are recognised as legal
p.000072: grounds for abortion in that jurisdiction. If they are not, pregnant women must not be recruited for research in which
p.000072: there is a realistic basis for concern that significant fetal abnormality may occur as a consequence of
p.000072: participation in research. At the same time, this rule might restrict potentially valuable research in
p.000072: countries where women cannot be guaranteed access to abortion. In such cases, research projects can be
p.000072: conducted only if a local research ethics committee determines that the research has compelling social value for
p.000072: pregnant women and the women are informed about existing restrictions on abortion and possible options for obtaining an
p.000072: abortion in another country.
p.000072:
p.000072: Breastfeeding women. The father may need to be consulted in research involving breastfeeding women, in accordance with
p.000072: Guideline 17 – Research involving children and adolescents. If a breast- fed infant may be exposed to an
p.000072: investigational product through the ingestion of breast milk (or it is unknown whether an infant would be exposed),
p.000072: such research should be conducted in accordance with Guideline 17 – Research involving children and adolescents.
p.000072:
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p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073: GUIDELINE 20:
p.000073: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS
p.000073:
p.000073: Disasters arising from events such as earthquakes, tsunamis or military conflicts, and disease outbreaks, can
p.000073: have a sudden and devastating impact on the health of large affected populations. In order to identify effective ways
p.000073: of mitigating the health impact of disasters and disease outbreaks, health-related research should form an integral
p.000073: part of disaster response. However, the conduct of research must not unduly impact the response to the victims of a
p.000073: disaster.
p.000073:
p.000073: In the conduct of research in disasters and disease outbreaks, it is essential to uphold the ethical principles
...
p.000087: Further review. The research ethics committee must conduct further reviews of approved studies as necessary, in
p.000087: particular if there are significant changes in the protocol that require re-consent by participants,
p.000087: affect the safety of participants, or other ethical matters that emerge during the course of the study.
p.000087: These further reviews include progress reports submitted by researchers and possible monitoring of researchers’
p.000087: compliance with approved protocols.
p.000087:
p.000087: Committee membership. The research ethics committee must be constituted according to a document that
p.000087: specifies the manner in which members and the chair will be appointed, reappointed, and replaced. Research ethics
p.000087: committees must have members capable of providing competent and thorough review of research proposals. Membership
p.000087: normally must include physicians, scientists and other professionals such as research coordinators, nurses,
p.000087: lawyers, and ethicists, as well as community members or representatives of patients’ groups who can represent
p.000087: the cultural and moral values of study participants. Ideally, one or more members should have experience as study
p.000087: participants since there is growing recognition that knowledge gained through personal experience as a participant can
p.000087: supplement the professional understanding of illness and medical care. Committees must include both men and women.
p.000087: When a proposed study involves vulnerable individuals or groups, as may be the case in research involving
p.000087: prisoners or illiterate persons, representatives of relevant advocacy groups should be invited to meetings where such
p.000087: protocols will be reviewed (see
p.000087:
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p.000088:
p.000088:
p.000088:
p.000088:
p.000088:
p.000088: Guideline 15 – Research involving vulnerable persons and groups). Regular rotation of members is desirable for
p.000088: balancing the advantage of experience with that of fresh perspectives.
p.000088:
p.000088: Members of research ethics committees must regularly update their knowledge about the ethical conduct of health-related
p.000088: research. If committees do not have the relevant expertise to adequately review a protocol, they must consult
p.000088: with external persons with the proper skills or certification. Committees must keep records of their
p.000088: deliberations and decisions.
p.000088:
p.000088: Conflicts of interests on the part of committee members. Research ethics committees must provide independent ethical
p.000088: opinions. Pressure can be brought to bear from many different directions, not just financial. Research ethics
p.000088: committees must therefore have mechanisms to ensure the independence of their operations. In particular, they
...
p.000099: 23. Methods of recording and reporting adverse events or reactions, and provisions for dealing with
p.000099: complications (Guidelines 4 and 23);
p.000099:
p.000099: 24. The known or foreseen risks of adverse reactions, including the risks attached to each proposed intervention and
p.000099: to any drug, vaccine or procedure to be tested (Guideline 4);
p.000099:
p.000099: 25. The potential individual benefits of the research to participants and to others (Guideline 4);
p.000099:
p.000099: 26. The expected benefits of the research to the population, including new knowledge that the study might
p.000099: generate (Guidelines 1 and 4);
p.000099:
p.000099: 27. For research carrying more than minimal risk of physical injury, details of plans, including
p.000099: insurance coverage, to provide treatment for such injury, including the funding of treatment, and to provide
p.000099: compensation for research-related disability or death (Guideline 14);
p.000099:
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p.000100:
p.000100:
p.000100:
p.000100: 28. Provision for continued access to study interventions that have demonstrated significant benefit, indicating its
p.000100: modalities, the parties involved in continued care and the organization responsible for paying for it, and for how long
p.000100: it will continue (Guideline 6);
p.000100:
p.000100: 29. For research on pregnant women, a plan, if appropriate, for monitoring the outcome of the pregnancy
p.000100: with regard to both the health of the woman and the short-term and long-term health of the child (Guideline 19);
p.000100:
p.000100: 30. The means proposed to obtain individual informed consent and the procedure planned to communicate
p.000100: information to prospective participants, including the name and position of the person responsible for obtaining
p.000100: consent (Guideline 9);
p.000100:
p.000100: 31. When a prospective subject is not capable of informed consent, satisfactory assurance that permission will be
p.000100: obtained from a duly authorized person, or, in the case of a child who is sufficiently mature to
p.000100: understand the implications of informed consent but has not reached the legal age of consent, that knowing
p.000100: agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian or other duly
p.000100: authorized representative (Guidelines 16 and 17);
p.000100:
p.000100: 32. An account of any economic or other inducements or incentives to prospective participants to
p.000100: participate, such as offers of cash payments, gifts, or free services or facilities, and of any financial obligations
p.000100: assumed by the participants, such as payment for medical services;
p.000100:
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p.000104:
p.000104: 4. the possible research uses, direct or secondary, of the participant`s medical records and of biological
p.000104: specimens taken in the course of clinical care;
p.000104:
p.000104: 5. for collection, storage and use of biological material and health-related data, that broad informed consent will
p.000104: be obtained, which should specify: the purpose of the biobank, the conditions and duration of storage; the rules of
p.000104: access to the biobank; the ways in which the donor can contact the biobank custodian and can remain informed about
p.000104: future use; the foreseeable uses of the materials, whether limited to an already fully defined study or extending to a
p.000104: number of wholly or partially undefined studies; the intended goal of such use, whether only for research, basic or
p.000104: applied, or also for commercial purposes, and whether the participant will receive monetary or other benefits from the
p.000104: development of commercial products developed from their biological specimens; the possibility of unsolicited findings
p.000104: and how they will be dealt with; the safeguards that will be taken to protect confidentiality as well as their
p.000104: limitations, whether it is planned that biological specimens collected in the research will be destroyed at its
p.000104: conclusion, and, if not, details about their storage (where, how, for how long, and final disposition) and possible
p.000104: future use, that participants have the right to decide about such future use, to refuse storage, and to have the
p.000104: material destroyed (Guidelines 11 and 12);
p.000104:
p.000104: 6. when women of childbearing potential are participating in health-related research, information about the
p.000104: possible risks, if they become pregnant during the research, to themselves (including future fertility), their
p.000104: pregnancies, their fetuses, and their future offspring; and the guaranteed access to a pregnancy test, to effective
p.000104: contraceptive methods and to safe, legal abortion before exposure to a potential teratogenic or mutagenic intervention.
p.000104: When effective contraception and/ or safe abortion are not available and alternative study sites are not feasible, the
p.000104: women must be given information about: the risk of unintended pregnancy; the legal grounds for abortion; reducing harms
p.000104: from unsafe abortion and subsequent complications; and, when pregnancy is not terminated, the guarantee for a medical
p.000104: follow-up for their own health and that of the infant and child and the information that it is often difficult to
p.000104: determine causality in cases of fetal or infant abnormalities (Guidelines 18 and 19);
p.000104:
p.000104:
p.000104:
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p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105: 7. when concerning pregnant and breastfeeding women, the risks of participation in health-related research to
p.000105: themselves, their pregnancies, their fetuses, and their future offspring, what has been done to maximize potential
p.000105: individual benefits and minimize risks, that evidence concerning risks may be unknown or controversial, and that
p.000105: it is often difficult to determine causality in cases of fetal or infant abnormalities (Guidelines 4 and 19);
p.000105:
p.000105: 8. when concerning disaster victims who mostly are under duress, the difference between research and humanitarian
p.000105: aid (Guideline 20); and
p.000105:
p.000105: 9. when research is done in the online environment and using online or digital tools that may
p.000105: involve potentially vulnerable persons, information about the privacy and security controls that will be used to
p.000105: protect their data; and the limitations of the measures used and the risks that may remain despite the safeguards put
p.000105: in place (Guideline 22).
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
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p.000105:
p.000105:
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p.000106: 106
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p.000106:
p.000106:
p.000106:
p.000106:
p.000106:
p.000106: APPENDIX 3
...
p.000109: the three levels of the Organization. The function ensures ethical considerations are included in the elaboration and
p.000109: implementation of health policies and research activities and contributes to build global consensus on ethics topics
p.000109: and to harmonize ethical standards. Her role is to provide advice to WHO departments (Ethics Clinic), foster
p.000109: partnerships with other international organizations, in particular through the UN Inter-Agency Committee on Bioethics;
p.000109: with national ethics committees, serving as the permanent secretariat of the Global Summit of National Ethics
p.000109: Committees; with NGOs and all relevant partners. She supervises the development and dissemination of WHO ethics
p.000109: guidance and tools, the interaction with the WHO Global Network of Collaborating Centres on Bioethics, the
p.000109: Secretariat of the WHO Ethics Review Committee and the Public Health Ethics Consultative Group. For more
p.000109: information, please see http:// www.who.int/ethics/en/
p.000109:
p.000109: Dafna Feinholz Klip, UNESCO
p.000109: Dafna Feinholz has a PhD in Research Psychology (UIA Mexico) and a Master in Bioethics (Universidad Complutense,
p.000109: Madrid, Spain). She was the Head of the Reproductive Epidemiology Department at the Mexican National Institute of
p.000109: Perinatology, as well as the Research and Planning Director of the Women and Health Program, at the Ministry of Health
p.000109: (Mexico). She successively occupied the posts of Academic Coordinator of the National Commission of Human Genome at the
p.000109: Ministry of Health; and the Executive Director of the National Commission of Bioethics, achieving a more independent
p.000109: legal status for the National Bioethics Committees, drafting the first national guidelines for Research Ethics
p.000109: Committees and Clinical Bioethics Committees, training their members, and promoting the law at the parliament that is
p.000109: currently in force, to legally establish and differentiate both types of committees. She is the founder of FLACEIS
p.000109: (Latin American Forum of Ethics Committees in Health Research) and was the Chairperson (2000–2006). Invited member of
p.000109: the international expert group, TDR-WHO: Drafting and translating Operational Guidelines for Ethics Committees. She was
p.000109: Mexico´s representative at the meetings of the Intergovernmental Bioethics Committee to discuss the UNESCO Universal
p.000109: Declaration on Bioethics and Human Rights. Since September 2009, Dafna Feinholz is the Chief of the Bioethics Section,
p.000109: within UNESCO Social and Human Science Sector. In this capacity, she leads different activities aiming at reinforcing
p.000109: capacities of Member States to manage bioethical
p.000109:
p.000109:
p.000109:
p.000110: 110
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p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
p.000110: challenges and to identify the ethical, legal and social implications of cutting-edge science, emerging technologies
...
p.000113: Marianne
p.000113:
p.000113:
p.000113:
p.000113:
p.000114: 114
p.000114:
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p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114: Institution/Organization Country Surname First name
p.000114:
p.000114: 31 Novo Nordisk A/S, Copenhagen
p.000114: 32 Núcleo de Bioética de Londrina- Londrina, Parana
p.000114: Denmark Zdravkovic Milan
p.000114:
p.000114: Brazil Diniz Nilza
p.000114: 33 Nuffield Council on Bioethics United Kingdom Whittall Hugh
p.000114:
p.000114: 34 Pan American Health Organization, Regional Office for the Americas of the World Health Organization, Washington
p.000114: DC
p.000114: 35 Panamerican University, Mexico City
p.000114: United States Saenz Carla
p.000114:
p.000114:
p.000114:
p.000114:
p.000114: Mexico Casas Maria de la Luz
p.000114: 36 Peruvian IRB Network, Lima Peru Gil
p.000114: Ana Lescano A. Roxana
p.000114: Mestanza Miguel
p.000114: Quiroz Estela
p.000114: Sevilla Carlos
p.000114:
p.000114: 37 Red Latinoamericana y del Caribe de Bioética UNESCO
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114: 38 Sama, Resource group for women and health, New Delhi
p.000114: 39 Sense About Science/ AllTrials campaign, London
p.000114: 40 St. John’s Research Institute, Bangalore
p.000114: Fuentes Duilio
p.000114: Justo Luis
p.000114: Lorenzo Claudio
p.000114: Macías Andrea
p.000114: Maglio Ignacio
p.000114: Minaya Gabriela
p.000114: Pacheco Victor
p.000114: Penchaszadeh Victor
p.000114: Pfeiffer Maria Luisa Rocha de Cunha Thiago Verges Claude
p.000114: Vidal Susana
p.000114: India Sarojini N.
p.000114:
p.000114:
p.000114: United Kingdom Cockerill James
p.000114:
p.000114: India Vaz Manjulika
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
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p.000115: 115
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115: Institution/Organization Country Surname First name
p.000115:
p.000115: 41 Stellenbosch University, Stellenbosch
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115:
p.000115: 42 Swiss Academy of Medical Sciences (SAMS), Bern
p.000115: 43 Training and Resources in Research Ethics Evaluation (TRREE)
p.000115: 44 Universidad Peruana Cayetano Heredia, Lima
p.000115: 45 Universidad Autónoma de Querétaro, Santiago de Querétaro
...
p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
p.000120: Low-resource settings viii, ix, 3 - 5, 7, 17, 19, 22, 23, 26, 45, 47, 52, 75 - 77, 80, 89, 92
p.000120: M
p.000120: Management (of risks) 8, 42, 45, 48, 51, 85, 95 - 97
p.000120: Material Transfer Agreement 41, 45
p.000120: Minimal risk 9, 13, 15, 16, 18, 38, 62, 65, 66, 71, 72, 80, 88, 100
p.000120: Minor increase above minimal risk 13, 18
p.000120: Mitigation 11, 15, 76, 85, 95, 97
p.000120: Modification of informed consent 33, 37
p.000120: Money 54, 103
p.000120: Multi-centre research 87, 89
p.000120: O
p.000120: Observational ix, xii, 16, 53, 72, 78
p.000120: Online 27, 83 - 85, 106
p.000120: Opt-out/opt-in. See Informed opt-out/opt-in
p.000120: P
p.000120: Parent 65, 67, 68, 101
p.000120: Payment 54, 88, 101
p.000120: Permission 35, 38, 54, 58, 59, 61 - 63, 65, 67 - 71, 79, 80, 81, 83, 101
p.000120: Placebo 9, 15 - 19, 35, 78, 80
p.000120: Post-trial access. See Continued access
p.000120: Pregnant women 7, 8, 58, 70 - 73, 101
p.000120: Privacy 68, 83 - 85, 92, 93, 100, 101, 104, 106
p.000120: Procedures xi, 9 - 12, 15, 17, 19, 23, 26, 33 - 35, 37, 38, 42, 53 - 55, 59, 61, 62, 65 - 67, 71,
p.000120: 76 - 80, 87 - 90, 95, 97, 100 - 103
p.000120: Protocol 2, 12, 18, 23, 25, 35, 36, 43, 49, 55, 56, 58, 76, 83, 87 - 90, 92, 96, 99, 101, 102, 105
p.000120: Public accountability 11, 13, 29, 31, 51, 91
p.000120: Publication ii, 29, 31, 84, 91, 92, 95, 102
p.000120: R
p.000120: Registries 36, 38, 39, 47, 49, 51, 72, 91
p.000120: Rehabilitation 55, 104
p.000120: Reimbursement 53, 54
p.000120: Research ethics committee 2, 9, 10, 12, 15, 17, 18, 23, 25, 27, 33, 34 - 39, 41, 43 - 45, 47,
p.000120: 49 - 51, 53, 54, 56, 58, 61 - 63, 65, 68, 71, 73, 79, 85, 87 - 91, 95, 96, 98, 102, 103, 105
p.000120: Residual tissue 41, 43, 44
p.000120: Responsiveness 3, 4, 17, 19, 63, 75, 76
p.000120: Return of results 44, 45, 51
p.000120:
p.000120:
p.000120:
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p.000120:
p.000121: 121
p.000121:
p.000121: Risks 2, 5, 7 - 13, 15 - 19, 23, 26, 34 - 39, 41, 44, 47, 49, 50, 53, 54, 58, 59, 61 - 63, 65 - 67,
p.000121: 69 - 73, 75 - 77, 80, 81, 83 - 85, 88, 91, 92, 96, 100, 102, 104 - 106
p.000121: S
p.000121: Scientific value 2, 9 - 13, 51, 91
p.000121: Secondary use 49
p.000121: Social value 1 - 4, 8 - 11, 19, 25, 26, 30, 37, 38, 41, 44, 47, 50, 62, 65, 71, 73, 75, 77, 88, 91
p.000121: Specific informed consent 41 - 44, 47, 48, 49
p.000121: Storage 36, 41, 43, 45, 47 - 50, 52, 105
p.000121: U
p.000121: (Un)solicited findings xi, 44, 45, 51
p.000121: Undue inducement 53, 54, 73
p.000121: Use of biological material 44, 105
p.000121: V
p.000121: Voluntary, voluntariness 10, 35, 36, 39, 58, 59, 78, 96, 103
p.000121: Vulnerable viii, ix, xi, 3, 8, 54, 57 - 59, 69, 77, 84, 88, 89, 100, 106
p.000121: W
p.000121: Waivers of informed consent 33, 35 - 37, 43, 49, 63, 68, 76, 78, 79
p.000121: Withdrawal 44, 49, 50, 54, 63
p.000121: Women 7, 8, 25, 58, 69, 70 - 73, 88, 101, 105, 106
p.000121:
p.000121:
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p.000121:
p.000122: 122
p.000122: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000122:
p.000122: CIOMS, in association with the World Health Organization, started its work on ethics in health-related
p.000122: research in the late 1970s. Accordingly, CIOMS set out, in cooperation with WHO, to prepare guidelines
p.000122: to indicate how the ethical principles set forth in the Declaration of Helsinki of the World Medical
p.000122: Association, could be effectively applied, particularly in low-resource settings, given their socio-economic
p.000122: circumstances, laws and regulations, and executive and administrative arrangements. Since then revised editions of
p.000122: the CIOMS ethical guidelines were published in 1993 and 2002. New developments in research have prompted
p.000122: CIOMS to again revise their ethical guidelines. The result is now available in this new publication.
p.000122:
p.000122: In the new 2016 version of the ethical guidelines, CIOMS provides answers to a number of pressing issues in research
...
Social / Youth/Minors
Searching for indicator minor:
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p.000119: Association of Bioethics (IAB) in Mexico City during which key issues were presented and opened for discussion.
p.000119: This session served as one element of the international consultation process for the proposed revision of the
p.000119: CIOMS Guidelines. In November 2014 the draft revision was discussed at the Forum of Ethical Review Committees in the
p.000119: Asian & Western Pacific Region (FERCAP) in Manila in a plenary session with more than 800 attendees. The revision was
p.000119: also discussed at the Advancing Research Ethics Training in Southern Africa (ARESA) Seminar on 17—18 September 2015 in
p.000119: Cape Town and at CENTRES (Clinical Ethics Network & Research Ethics Support), in Singapore in November 2015.
p.000119:
p.000119: Specific feedback was sought from the member organizations of CIOMS and from members of National Ethics
p.000119: Committees participating in the Global Summit of National Ethics Committees (2014).
p.000119:
p.000119: At the end of September 2015 the Working Group opened its draft guidelines for public comments until 1 March 2016.
p.000119: The Working Group received comments from 57 different institutions and organizations. In many cases these
p.000119: comments were prepared by several persons from one institution. The commentators represented all parts of the world
p.000119: (see Appendix 4). The Working Group received over 250 pages of comments, ranging from minor editorial issues to
p.000119: in-depth, detailed comments. In June 2016 the Working Group met a final time.
p.000119:
p.000119: The close cooperation with the World Medical Association during the revision process ensured that the final draft was
p.000119: in line with the Declaration of Helsinki.
p.000119:
p.000119: At the beginning of October 2016 the final draft was submitted to the CIOMS Executive Committee, which approved the
p.000119: text at its General Assembly meeting in Geneva in November 2016.
p.000119:
p.000119: The final draft replaces all previous versions of the CIOMS ethical guidelines, both in the domain of
p.000119: biomedical and epidemiological research. At the same time, research projects that have been ethically
p.000119: assessed on the basis of previous versions of the guidelines may be continued on the terms and conditions as set out in
p.000119: those previous versions.
p.000119:
p.000119: Reactions to the Guidelines are welcome and should be addressed to the Secretary-General, Council for International
p.000119: Organizations of Medical Sciences, P.O. Box 2100, CH-1211 Geneva 2, Switzerland; or by email to info@cioms.ch.
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119: x
p.000119:
p.000119: EVIDENCE RETRIEVAL AND SYNTHESIS
p.000119: In the revision process, literature reviews were used as sources for further ethical deliberation.
p.000119: Authoritative declarations, reports and guidance documents have had a prominent role in these discussions,
...
p.000008:
p.000008: The potential individual benefits and risks of research must be evaluated in a two-step process. First,
p.000008: the potential individual benefits and risks of each individual research intervention or procedure in the study
p.000008: must be evaluated.
p.000008: f For research interventions or procedures that have the potential to benefit participants, risks are acceptable if
p.000008: they are minimized and outweighed by the prospect of potential individual benefit and the available evidence suggests
p.000008: that the intervention will be at least as advantageous, in the light of foreseeable risks and benefits, as any
p.000008: established effective alternative. Therefore, as a general rule, participants in the control group of a trial must
p.000008: receive an established effective intervention. The conditions under which a placebo may be used are spelled out in
p.000008: Guideline 5 – Choice of control in clinical trials.
p.000008: f For research interventions or procedures that offer no potential individual benefits to participants, the risks
p.000008: must be minimized and appropriate in relation to the social and scientific value of the knowledge to be gained
p.000008: (expected benefits to society from the generalizable knowledge).
p.000008: f In general, when it is not possible or feasible to obtain the informed consent of participants,
p.000008: research interventions or procedures that offer no potential individual benefits must pose no more than minimal
p.000008: risks. However, a research ethics committee may permit a minor increase above minimal risk when it is not possible to
p.000008: gather the necessary data in another population or in a less risky or burdensome manner, and the social and scientific
p.000008: value of the research is compelling (see Guideline 16 – Research involving adults incapable of giving informed
p.000008: consent, and Guideline 17 – Research involving children and adolescents).
p.000008:
p.000008: In a second step, the aggregate risks and potential individual benefits of the entire study must be assessed and must
p.000008: be considered appropriate.
p.000008: f The aggregate risks of all research interventions or procedures in a study must be considered
p.000008: appropriate in light of the potential individual benefits to participants and the scientific social value of the
p.000008: research.
p.000008: f The researcher, sponsor and research ethics committee must also consider risks to groups and
p.000008: populations, including strategies to minimize these risks.
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: f The potential individual benefits and risks of research studies must be evaluated in consultation with
p.000009: the communities to be involved in the research (see Guideline 7 – Community engagement).
p.000009:
p.000009:
p.000009: Commentary on Guideline 4
...
p.000011: being exposed to greater risks in research merely because they are poor, members of disadvantaged groups or
p.000011: because their environment exposes them to greater risks in their daily lives (for example, poor road safety).
p.000011: Research ethics committees must be similarly vigilant about not permitting greater research risks in
p.000011: populations of patients who routinely undergo risky treatments or diagnostic procedures (for example, cancer patients).
p.000011: Rather, risks in research must be compared to risks that an average, normal, healthy individual
p.000011: experiences in daily life or during routine examinations. Furthermore, risk comparisons must not be made to
p.000011: activities that pose unacceptable risks themselves, or in which people choose to participate because of the associated
p.000011: benefits (some sporting activities, for example, are thrilling precisely because they involve an elevated risk of
p.000011: harm).
p.000011:
p.000011:
p.000011: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000012: 12
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: When the risks of a research procedure are judged to be minimal, there is no requirement for special protective
p.000012: measures apart from those generally required for all research involving members of the particular class of persons.
p.000012:
p.000012: Minor increase above minimal risk. While there is no precise definition of a “minor increase” above
p.000012: minimal risk, the increment in risk must only be a fraction above the minimal risk threshold and considered acceptable
p.000012: by a reasonable person. It is imperative that judgments about a minor increase above minimal risk pay careful attention
p.000012: to context. Thus, research ethics committees need to determine the meaning of a minor increase above minimal risk in
p.000012: light of the particular aspects of the study they are reviewing.
p.000012:
p.000012: Risks to groups. In order to achieve the social and scientific value of research, results must be made public (see
p.000012: Guideline 24 – Public accountability for health-related research). However, research results in certain fields (for
p.000012: example, epidemiology, genetics, and sociology) may present risks to the interests of communities, societies, families,
p.000012: or racially or ethnically defined groups. For example, results could indicate – rightly or wrongly – that a group has a
p.000012: higher than average prevalence of alcoholism, mental illness or sexually transmitted disease, or that it is
p.000012: particularly susceptible to certain genetic disorders. Research results could therefore stigmatize a group or expose
p.000012: its members to discrimination. Plans to conduct such research should be sensitive to these considerations and minimize
p.000012: risks to groups, notably by maintaining confidentiality during and after the study and publishing the
p.000012: resulting data in a manner that is respectful of the interests of all concerned.
p.000012:
p.000012: Similarly, conducting research may disrupt or interfere with providing health care to the local community
p.000012: and thereby pose risks to the community. Research ethics committees must ensure, as part of evaluating the
p.000012: risks and potential individual benefits of research studies, that the interests of all who may be affected are given
...
p.000012: result of the research.
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
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p.000012: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000013: 13
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: GUIDELINE 5:
p.000013: CHOICE OF CONTROL IN CLINICAL TRIALS
p.000013:
p.000013: As a general rule, the research ethics committee must ensure that research participants in the control group of a trial
p.000013: of a diagnostic, therapeutic, or preventive intervention receive an established effective intervention.
p.000013:
p.000013: Placebo may be used as a comparator when there is no established effective intervention for the condition under
p.000013: study, or when placebo is added on to an established effective intervention.
p.000013:
p.000013: When there is an established effective intervention, placebo may be used as a comparator without providing the
p.000013: established effective intervention to participants only if:
p.000013: f there are compelling scientific reasons for using placebo; and
p.000013: f delaying or withholding the established effective intervention will result in no more than a minor
p.000013: increase above minimal risk to the participant and risks are minimized, including through the use of effective
p.000013: mitigation procedures.
p.000013:
p.000013: Risks and benefits of other study interventions and procedures should be evaluated according to the criteria set out in
p.000013: Guideline 4 – Potential individual benefits and risks of research.
p.000013:
p.000013:
p.000013: Commentary on Guideline 5
p.000013: General considerations for controlled clinical trials. The conduct of controlled clinical trials is
p.000013: methodologically essential in order to test the relative merits of investigational interventions. To obtain
p.000013: valid results in a controlled trial, researchers must compare the effects of an experimental intervention on
p.000013: participants assigned to the investigational arm (or arms) of a trial with the effects that a control intervention
p.000013: produces in persons drawn from the same population. Randomization is the preferred method for assigning
p.000013: participants to the arms of controlled trials. Assignment to treatment arms by randomization tends to produce study
p.000013: groups comparable with respect to factors that might influence study outcomes, removes researcher bias in the
p.000013: allocation of participants, and helps to ensure that the study results reflect the effects of administered
p.000013: interventions and not the influence of extraneous factors.
p.000013:
p.000013: The use of placebo controls in clinical trials creates the potential for conflict between the demands of sound
p.000013: science and the obligation to safeguard the health and welfare of study participants. In general, studies
p.000013: must be designed to generate accurate scientific information without delaying or withholding established effective
p.000013: interventions from participants. Researchers and sponsors may deviate from this rule when withholding such
p.000013: interventions is methodologically necessary and exposes participants to no more than a minor increase above minimal
p.000013: risk.
p.000013:
p.000013:
p.000013:
p.000013: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000015: 15
p.000015:
p.000015:
p.000015:
p.000015:
p.000015:
p.000015: Although conventional randomized controlled clinical trials are often considered the gold standard, other study
p.000015: designs such as response-adaptive trial designs, observational studies, or historical comparisons can also
p.000015: yield valid research results. Researchers and sponsors must carefully consider whether the research question
p.000015: can be answered with an alternative design, and whether the risk-benefit profile of alternative designs is more
p.000015: favourable when compared to a conventional randomized controlled trial.
p.000015:
p.000015: Established effective intervention. An established effective intervention for the condition under study exists when it
p.000015: is part of the medical professional standard. The professional standard includes, but is not limited to, the best
p.000015: proven intervention for treating, diagnosing or preventing the given condition. In addition, the professional
p.000015: standard includes interventions that may not be the very best when compared to available alternatives, but are
p.000015: nonetheless professionally recognized as a reasonable option (for example, as evidenced in treatment guidelines).
p.000015:
p.000015: Yet established effective interventions may need further testing, especially when their merits are subject
p.000015: to reasonable disagreement among medical professionals and other knowledgeable persons. Clinical trials may be
...
p.000015: favourable, such that patients might reasonably forgo the usual intervention for the condition (for example, antibiotic
p.000015: treatment for otitis media in children, or arthroscopic knee surgery). When there are several treatment
p.000015: options but it remains unknown which treatment works best for whom, comparative effectiveness research may help to
p.000015: further determine the effectiveness of an intervention or procedure for specific groups. This may include testing an
p.000015: established effective intervention against a placebo, provided the conditions of this Guideline are met.
p.000015:
p.000015: Some people contend that it is never acceptable for researchers to withhold or withdraw established effective
p.000015: interventions. Others argue that it may be acceptable, provided that the risks of withholding an established
p.000015: intervention are acceptable, and withholding the established effective intervention is necessary to ensure that
p.000015: the results are interpretable and valid. In such cases, an intervention known to be inferior, a placebo (see below) or
p.000015: no intervention may be substituted for the established intervention. This Guideline takes a middle stance on
p.000015: this issue. The preferred option is to test potential new interventions against an established effective
p.000015: intervention. When researchers propose to deviate from this option, they must provide a compelling methodological
p.000015: justification and evidence that the risks from withholding or delaying the established intervention are no greater than
p.000015: a minor increase above minimal risk.
p.000015:
p.000015: These principles on the use of placebo also apply to the use of control groups who receive no treatment or who
p.000015: receive a treatment that is known to be inferior to an established treatment. Sponsors, researchers, and
p.000015: research ethics committees should evaluate the risks of providing no treatment (and no placebo) or an inferior
p.000015: treatment, compared to the risks and potential individual benefits of providing an established treatment, and apply the
p.000015: criteria for placebo use in this Guideline. In sum, when an established effective intervention exists, it may be
p.000015: withheld or substituted with an inferior intervention only if there are compelling scientific reasons for doing so; the
p.000015: risks of withholding the established intervention or substituting it with an inferior one will result in no
p.000015: more than a minor increase above minimal risk to participants; and the risks to participants are minimized.
p.000015:
p.000015: Placebo. An inert substance or sham procedure is provided to research participants with the aim of making it impossible
p.000015: for them, and usually the researchers themselves, to know who is receiving an active or inactive intervention. Placebo
p.000015: interventions are methodological tools used with the goal of isolating the clinical effects of the investigational drug
p.000015: or intervention. This enables researchers to treat participants in the study arm and the control arm in exactly the
p.000015: same way, except that the
p.000015:
p.000015:
p.000015:
p.000015: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000016: 16
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: study group receives an active substance and the control group does not. The risks of the placebo intervention itself
p.000016: are typically very low or non-existent (for example, ingestion of an inert substance).
p.000016:
p.000016: In some fields, such as surgery and anaesthesia, testing the effectiveness of interventions may require the use of sham
p.000016: interventions. For example, the participants in the active arm of a surgery trial may receive arthroscopic surgery
p.000016: on their knees, while participants in the control group may receive only a minor skin incision. In other
p.000016: cases, both groups may receive an invasive procedure, such as inserting a catheter into a person’s artery. The catheter
p.000016: is threaded into the heart of participants in the active arm, but stopped short of the heart in participants in the
p.000016: control arm. The risks of sham procedures can be considerable (for example, surgical incision under general
p.000016: anaesthesia) and must be carefully considered by a research ethics committee.
p.000016:
p.000016: Placebo controls. The use of placebo is usually uncontroversial in the absence of an established effective
p.000016: intervention. As a general rule, when an established effective intervention exists for the condition under
p.000016: investigation, study participants must receive that intervention within the trial. This does not preclude
p.000016: comparing the effects of potential new interventions against a placebo control in cases where all participants receive
p.000016: the established effective intervention and are then randomized to the investigational intervention or placebo. Such
p.000016: add-on designs are common in oncology where all participants receive an established effective treatment, and are then
p.000016: randomized to placebo or the investigational intervention.
p.000016:
p.000016: Alternatively, when there is credible uncertainty about the superiority of an established effective
p.000016: intervention over an investigational agent (“this is known as clinical equipoise”), it is permissible to compare its
...
p.000017: following conditions apply to placebo-controlled trials.
p.000017:
p.000017: First, researchers must decrease the period of placebo use to the shortest possible time consistent with achieving
p.000017: the scientific aims of the study. Risks in the placebo arm may be further reduced by permitting a change
p.000017: to active treatment (“escape treatment”). The protocol should establish a threshold beyond which the participant should
p.000017: be offered the active treatment.
p.000017:
p.000017: Second, as discussed in Guideline 4 – Commentary, the researcher must minimize harmful effects of placebo-controlled
p.000017: studies by providing safety monitoring of research data during the trial.
p.000017:
p.000017: Minimal risks of receiving placebo. Risks of receiving placebo count as minimal when the risk of serious harm is
p.000017: very unlikely and the potential harms associated with more common adverse events are small, as described in
p.000017: Guideline 4 – Potential individual benefits and risks of research. For example, when the investigational intervention
p.000017: is aimed at a relatively trivial condition, such as the common cold in an otherwise healthy person, or hair loss, and
p.000017: using a placebo for the duration of a trial would deprive control groups of only minor benefits, the risks of using a
p.000017: placebo-control design are minimal. The risks of receiving placebo in the presence of an established effective
p.000017: intervention must be compared with the risks that an average, normal, healthy individual experiences in
p.000017: daily life or during routine examinations.
p.000017:
p.000017: Minor increase above minimal risk. Consistent with Guideline 4 – Potential individual benefits and risks of
p.000017: research, the minor increase above minimal risk standard also applies to placebo- controlled trials.
p.000017:
p.000017: Placebo control in a low-resource setting when an established effective intervention cannot be made available
p.000017: for economic or logistic reasons. In some cases, an established effective intervention for the condition under study
p.000017: exists, but for economic or logistic reasons this intervention may not be possible to implement or made available in
p.000017: the country where the study is conducted. In this situation, a trial may seek to develop an intervention that could be
p.000017: made available, given the finances and infrastructure of the country (for example, a shorter or less complex course of
p.000017: treatment for a disease). This can involve testing an intervention that is expected or even known to be inferior to the
p.000017: established effective intervention, but may nonetheless be the only feasible or cost-effective and beneficial option
p.000017: in the circumstances. Considerable controversy exists in this situation regarding which trial design is
p.000017: both ethically acceptable and necessary to address the research question. Some argue that such studies should be
p.000017: conducted with a non-inferiority design that compares the study intervention with an established effective
p.000017: method. Others argue that a superiority design using a placebo can be acceptable.
p.000017:
p.000017: The use of placebo controls in these situations is ethically controversial for several reasons:
...
p.000021: for a certain period of time, possibly for research purposes, and then transfer care to an appropriate provider. The
p.000021: obligation to provide transition to care following the research applies to both participants in the control arm and the
p.000021: intervention arm.
p.000021:
p.000021: Continued access to beneficial interventions. As part of their obligation to transition to care after research,
p.000021: researchers and sponsors may have to provide continued access to interventions that have demonstrated significant
p.000021: benefit in the study or to established effective interventions that were provided as part of the
p.000021: standard of care or prevention to all participants during the research. Access should also be provided, when
p.000021: pertinent, in the interval between the end of the individual’s participation and the end of the study. In this
p.000021: situation, access could be arranged by an extension study or by compassionate use. This obligation depends on several
p.000021: factors. For example, if discontinuing an intervention will deprive participants of basic capabilities, such as the
p.000021: ability to
p.000021:
p.000021:
p.000021: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000022: 22
p.000022:
p.000022:
p.000022:
p.000022:
p.000022:
p.000022: communicate or function independently, or significantly reduce a quality of life they had attained during
p.000022: the study, then the obligation will be greater than if the intervention provides relief for a minor or
p.000022: transient condition. Similarly, the obligation will be greater when participants are not able to access the needed care
p.000022: or prevention within the local health system than in cases where this is readily available. The obligation may also be
p.000022: greater when there are no available alternatives with clinical effectiveness similar to the intervention that
p.000022: has demonstrated significant benefit than in cases where such alternatives exist. However, the obligation
p.000022: may not be able to be completely met if the total number of qualifying individuals is very large.
p.000022: Continued access to interventions that have demonstrated significant benefit but await regulatory approval should be
p.000022: consistent with the relevant regulatory requirements for pre-licensure access and should not delay the process of
p.000022: obtaining regulatory approval.
p.000022:
p.000022: Providing continued access to a beneficial study intervention can create several dilemmas:
p.000022: f In the case of blinded controlled trials, it may take time to unblind the results and find out who has received
p.000022: which intervention. Researchers and sponsors should make provisions for this transition period and inform
p.000022: participants if they will be temporarily receiving the current standard of care before the study intervention can be
p.000022: administered.
p.000022: f A research ethics committee may discuss whether researchers and sponsors are under an obligation to
...
p.000059:
p.000059: For research interventions or procedures that have the potential to benefit adults who are incapable of
p.000059: giving informed consent, the risks must be minimized and outweighed by the prospect of potential individual
p.000059: benefit. For research interventions or procedures that have no potential individual benefits for participants, two
p.000059: conditions apply:
p.000059: f the interventions and procedures should be studied first in persons who can give consent when these interventions
p.000059: and procedures target conditions that affect persons who are not capable of giving informed consent as well as those
p.000059: who are capable, unless the necessary data cannot be obtained without participation of persons who are incapable of
p.000059: giving informed consent; and
p.000059:
p.000059:
p.000059: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000061: 61
p.000061:
p.000061:
p.000061:
p.000061:
p.000061:
p.000061: f the risks must be minimized and no more than minimal.
p.000061:
p.000061: When the social value of the studies with such research interventions and procedures is compelling, and these
p.000061: studies cannot be conducted in persons who can give informed consent, a research ethics committee may permit a
p.000061: minor increase above minimal risk.
p.000061:
p.000061:
p.000061: Commentary on Guideline 16
p.000061: General considerations. In general, competence or decisional capacity is determined by the ability to
p.000061: understand material information, appreciate the situation and its consequences, consider the treatment options, and
p.000061: communicate a choice. Persons should be considered capable of giving informed consent unless it is proven otherwise. A
p.000061: person may be incapable to give informed consent for a variety of reasons (for example, dementia, some psychiatric
p.000061: conditions and accidents). Persons can become capable of giving informed consent after a certain period, or they can be
p.000061: incapable to decide whether they should be treated for a certain disease but capable to decide whether they want to
p.000061: enjoy a meal. This illustrates that a lack of decisional capacity is time-, task- and context-specific.
p.000061:
p.000061: When researchers have reason to believe that potential or current participants are incapacitated, the participant’s
p.000061: decisional capacity must be adequately assessed. In cases where incapacity to give informed consent might reasonably be
...
p.000063: obtained.
p.000063:
p.000063: In general, the refusal of a child or adolescent to participate or continue in the research must be respected,
p.000063: unless, in exceptional circumstances, research participation is considered the best medical option for a child or
p.000063: adolescent.
p.000063:
p.000063: For research interventions or procedures that have the potential to benefit children or adolescents, the
p.000063: risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000063:
p.000063: For research interventions or procedures that have no potential individual benefits for participants, two
p.000063: conditions apply:
p.000063: f the interventions and procedures should be studied in adults first, when these interventions and
p.000063: procedures target conditions that affect adults as well as children and adolescents, unless the necessary data
p.000063: cannot be obtained without participation of children or adolescents; and
p.000063: f the risks must be minimized and no more than minimal.
p.000063:
p.000063: When the social value of the studies with such research interventions and procedures is compelling, and these studies
p.000063: cannot be conducted in adults, a research ethics committee may permit a minor increase above minimal risk.
p.000063:
p.000063:
p.000063: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000065: 65
p.000065:
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: Commentary on Guideline 17
p.000065: Justification of the involvement of children and adolescents in health-related research. The participation of
p.000065: children and adolescents is indispensable for research into diseases of childhood and conditions to which they are
p.000065: particularly susceptible, as well as for clinical trials of drugs that will be used for children and adolescents as
p.000065: well as adults. In the past, many new products were not tested in children or adolescents although they were
p.000065: directed at diseases also occurring in childhood. In some cases, this resulted in children or adolescents being
p.000065: exposed to interventions that were either not effective or were harmful. In general, this lack of information results
p.000065: in higher risks for children and adolescents from being exposed to interventions where little is known about their
p.000065: specific effects or safety in this population. Therefore, it is imperative to involve children and adolescents in
p.000065: research to study both investigational interventions for childhood conditions and established interventions in
...
p.000065: be tenable in pediatric research since children and adolescents face distinctive health problems. In the case
p.000065: of childhood-specific conditions, studies in adults would not be feasible or their results meaningful. Moreover, in
p.000065: rare cases (for example, when a disease affects large numbers of people, including children and adolescents, the
p.000065: available treatment options are limited, and an investigational agent shows great promise), waiting for conclusive
p.000065: results from research in adults before initiating pediatric studies can significantly delay the acquisition of relevant
p.000065: data and the development of beneficial interventions for children.
p.000065:
p.000065: The current Guidelines do not require that research first be conducted in adults if the research
p.000065: includes interventions that have a prospect for potential individual benefit for children and adolescents. This
p.000065: prospect is sufficient to justify the risks associated with the interventions and procedures, provided that
p.000065: the cumulative risk of all study interventions and procedures that do not have a prospect of potential individual
p.000065: benefit are no more than minimal. If research meets these conditions but the cumulative risk of all study interventions
p.000065: and procedures that do not have a prospect of potential individual benefit is only a minor increment above
p.000065: minimal risk, then research ethics committees must be convinced that the research is of special relevance to
p.000065: children or adolescents and could not be carried out equally well in an adult population. In such cases, older children
p.000065: who are more capable of giving assent must be selected before younger children or infants, unless there are sound
p.000065: scientific reasons for performing the research in younger children first.
p.000065:
p.000065: Research must always be conducted in adults before it is conducted in children when exploring the possible toxicity of
p.000065: new drugs. First exploring the possible toxicity of new drugs in adult populations represents a way of reducing risk
p.000065: for children and adolescents who might be involved in subsequent investigations of the same intervention.
p.000065:
p.000065:
p.000065:
p.000065:
p.000065: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000066: 66
p.000066:
p.000066:
p.000066:
p.000066:
p.000066:
p.000066: Potential individual benefits and risks. The potential individual benefits and risks of research with
p.000066: children or adolescents should be evaluated based on Guideline 4 – Potential individual benefits and risks of research,
...
p.000070: their fetus or infant, risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000070:
p.000070: For research interventions or procedures that have no potential individual benefits for pregnant and
p.000070: breastfeeding women:
p.000070: f the risks must be minimized and no more than minimal; and
p.000070: f the purpose of the research must be to obtain knowledge relevant to the particular health needs of
p.000070: pregnant or breastfeeding women or their fetuses or infants.
p.000070:
p.000070: When the social value of the research for pregnant or breastfeeding women or their fetus or infant is compelling,
p.000070: and the research cannot be conducted in non-pregnant or non- breastfeeding women, a research ethics committee
p.000070: may permit a minor increase above minimal risk.
p.000070:
p.000070: Short-term and long‐term follow-up of the fetus and the child may be required in research involving pregnant and
p.000070: breastfeeding women depending upon the study intervention and its potential risks.
p.000070:
p.000070: As a general rule, health-related research involving pregnant women that has the potential for harm to the fetus should
p.000070: be conducted only in settings where women can be guaranteed access to a safe, timely and legal abortion in the event
p.000070: that participation in the research makes the pregnancy unwanted.
p.000070:
p.000070:
p.000070: Commentary on Guideline 19
p.000070: General considerations. Physicians prescribe medications for pregnant and breastfeeding women, but most often do so in
p.000070: the absence of studies involving such women and without adequate evidence of safety and efficacy. Such routine
...
p.000071: future fertility), their pregnancies, their fetuses, and their future offspring. Information must also include steps
p.000071: taken to maximize potential individual benefits and minimize risks (see Guideline 4 – Potential individual benefits and
p.000071: risks of research). When evidence concerning risks is unknown or conflicting, this must be disclosed to the pregnant or
p.000071: breastfeeding woman as part of the informed consent process. She is the one to make the final decision about the
p.000071: acceptability of these risks to her and her fetus or infant. Women must also be informed that it is often difficult to
p.000071: determine causality in cases of fetal or infant abnormalities. Pregnant women may be recruited for research in which
p.000071: there is no prospect of potential individual benefit to them or the fetus only if the risks of the
p.000071: intervention are minimal. Examples include minimally invasive studies of new diagnostic techniques. In
p.000071: special circumstances, a minor increase above minimal risk may be acceptable.
p.000071:
p.000071: Some research involving pregnant women may be directed at the health of the fetus. In such cases, the role of the woman
p.000071: remains the same: she is the decision-maker for any interventions that affect her. This does not exclude the
p.000071: possibility of the woman consulting with the father of the fetus, if she wishes.
p.000071:
p.000071: Especially in communities or societies in which cultural beliefs accord more importance to the fetus than to the
p.000071: woman’s life or health, women may feel constrained to participate, or not to participate,
p.000071:
p.000071: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: in research. Special safeguards must be established to prevent undue inducement to pregnant women to
p.000072: participate in research in which interventions hold out the prospect of potential individual benefit to the fetus but
p.000072: not to the woman herself.
p.000072:
...
p.000079: vaccination programme or to being allocated to that cluster, but they could consent or refuse to consent to their
p.000079: child’s vaccination at school. In other CRTs, both the intervention and the community are randomized at the cluster
p.000079: level. These trials are called cluster-cluster randomized trials (for example, all the students in a school or
p.000079: all residents of a community). In cluster-cluster randomized trials, individual informed consent for receiving the
p.000079: intervention is typically difficult to obtain since it is almost impossible to avoid the intervention. At the same
p.000079: time, individual consent for data collection procedures is usually possible in both types of cluster randomized trials.
p.000079:
p.000079: Ethical acceptability of a no-intervention group. Some CRTs investigate interventions that have been proven
p.000079: to be effective elsewhere; this is termed implementation research. This type of research is often conducted in
p.000079: low-resource settings. An ethical question pertaining to this type of study is whether it is acceptable
p.000079: to withhold the proven intervention from a control group in a CRT. This situation is analogous to that of
p.000079: placebo controls in a randomized, controlled trial when an established, effective prevention or treatment exists. If
p.000079: withholding the proven intervention from the control cluster would expose participants to more than a minor
p.000079: increase above minimal risk, it would be unethical to use that study design. An example would be the introduction of
p.000079: sterilizing equipment or disposable needles in a resource-poor health centre with a high infection rate among the
p.000079: patients. In the implementation CRT, health care workers would have to be educated in the use of the new equipment
p.000079: and instructed to throw away the disposable needles. Since the reuse of needles without sterilization would
p.000079: expose patients to more than a minor increase above minimal risk, it would be unethical for the control cluster to
p.000079: continue the usual practice. In such cases, it is necessary for researchers to explore an alternative design, such as
p.000079: using historical controls from the same facility. Research ethics committees have the responsibility to
p.000079: determine whether the proposed research is ethically acceptable when the methodology calls for withholding an
p.000079: established effective treatment from the control cluster.
p.000079:
p.000079: Gatekeeping in cluster randomized trials. When a CRT substantially affects cluster or organizational
p.000079: interests, and a gatekeeper (for example, a community leader, headmaster, or local health council) possesses the
p.000079: legitimate authority to make decisions on the cluster or organization’s behalf, the researcher must obtain the
p.000079: gatekeeper’s permission to enrol the cluster or organization in the trial. Such permission does not replace the need to
p.000079: obtain individual informed consent where
p.000079:
p.000079:
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p.000080: 80
p.000080:
p.000080:
p.000080:
p.000080:
p.000080:
p.000080: this is required. Although a gatekeeper may not have been appointed or elected for the specific purpose
p.000080: of giving permission for the cluster to participate in research, the scope of authority must encompass interventions of
p.000080: the type in question when provided outside a research project. Moreover, the decision-maker must ensure that the risks
...
p.000095: interest.
p.000095:
p.000095:
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p.000096:
p.000096:
p.000096:
p.000096:
p.000096:
p.000096: As a general rule, a potential serious conflict of interest exists when there is a significant possibility that the
p.000096: actions of an investigator resulting from professional, academic, or financial interests will result in biased study
p.000096: results or cause harm or wrong to participants.
p.000096:
p.000096: Conflicts of interests can influence researchers subconsciously. For example, researchers with a financial
p.000096: stake in a study may not intentionally manipulate the research findings. However, their financial interests may
p.000096: subconsciously influence their analysis and interpretation of the research data.
p.000096:
p.000096: Management of conflicts of interest. All stakeholders in research share responsibility for developing and implementing
p.000096: policies and procedures to identify, mitigate, eliminate, or otherwise manage conflicts of interest.
p.000096: Although this is a joint responsibility, research institutions play a critical role in creating an
p.000096: institutional culture that takes conflicts of interest seriously and adopts appropriate measures for their management.
p.000096: Measures for managing conflicts of interest must be proportional to their seriousness. For example, a minor
p.000096: conflict of interest may be appropriately managed by disclosure, while a potential serious conflict can, in some
p.000096: cases, justify excluding a researcher from the study team. Policies and measures for managing conflicts of interest
p.000096: must be transparent and actively communicated to those affected.
p.000096:
p.000096: 1. Education of researchers and research ethics committees. Raising awareness of conflicts of interest, as well as
p.000096: the importance of managing such conflicts, is essential for making procedures and policies effective.
p.000096:
p.000096: 2. Disclosure of interests to research ethics committees. Researchers must disclose conflicts of interest on their
p.000096: part to the ethical review committee or to other institutional committees designed to evaluate and manage
p.000096: such conflicts. Researchers will most likely come to recognize conflicts of interest if they are prompted to
p.000096: scrutinize these conflicts as an expected part of preparing a description of their projects for ethical review.
p.000096: The development of a standardized disclosure form and related educational and explanatory materials may help
p.000096: to ensure that researchers understand conflicts of interest and routinely report relevant facts about their own
p.000096: situation to research ethics committees reviewing their protocols. Disclosure forms should provide a definition of
p.000096: conflicts of interest, along with some examples, and help researchers understand that a conflict of interest is not
...
p.000119: Fetus 58, 69, 70 - 73
p.000119: Free medical treatment 56
p.000119: G
p.000119: Gatekeeping 80
p.000119: Governance 41 - 43, 44, 47, 48, 50, 51, 78
p.000119: H
p.000119: Harms 10, 11, 12, 18, 54, 55, 56, 70, 72, 91, 105
p.000119: Health needs 2 - 4, 8, 17, 19, 21 - 23, 26, 55, 61, 65, 69, 71, 72, 75, 76, 104
p.000119: I
p.000119: Identifiable 38, 39, 51, 84
p.000119: Implementation research 80
p.000119: Incentives 10, 54, 92, 101
p.000119: Information leaflet 34
p.000119: Informed consent ix, 2, 9, 10, 21, 25, 26, 33 - 39, 41 - 45, 47 - 52, 54, 56, 58, 61 - 65, 67 - 72, 75,
p.000119: 76, 78 - 80, 89, 96, 97, 100, 101, 103, 105
p.000119: Informed opt-out /opt-in 41, 44, 47, 49, 83
p.000119: In-kind 54
p.000119: Interventions 1 - 4, 9 - 12, 15 - 19, 21 - 23, 26, 30, 53, 55, 56, 61 - 63, 65, 66, 71 - 73, 75 - 81, 84,
p.000119: 88, 91, 100, 101, 104
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000120: 120
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
p.000120: Low-resource settings viii, ix, 3 - 5, 7, 17, 19, 22, 23, 26, 45, 47, 52, 75 - 77, 80, 89, 92
p.000120: M
p.000120: Management (of risks) 8, 42, 45, 48, 51, 85, 95 - 97
p.000120: Material Transfer Agreement 41, 45
p.000120: Minimal risk 9, 13, 15, 16, 18, 38, 62, 65, 66, 71, 72, 80, 88, 100
p.000120: Minor increase above minimal risk 13, 18
p.000120: Mitigation 11, 15, 76, 85, 95, 97
p.000120: Modification of informed consent 33, 37
p.000120: Money 54, 103
p.000120: Multi-centre research 87, 89
p.000120: O
p.000120: Observational ix, xii, 16, 53, 72, 78
p.000120: Online 27, 83 - 85, 106
p.000120: Opt-out/opt-in. See Informed opt-out/opt-in
p.000120: P
p.000120: Parent 65, 67, 68, 101
p.000120: Payment 54, 88, 101
p.000120: Permission 35, 38, 54, 58, 59, 61 - 63, 65, 67 - 71, 79, 80, 81, 83, 101
p.000120: Placebo 9, 15 - 19, 35, 78, 80
p.000120: Post-trial access. See Continued access
p.000120: Pregnant women 7, 8, 58, 70 - 73, 101
p.000120: Privacy 68, 83 - 85, 92, 93, 100, 101, 104, 106
p.000120: Procedures xi, 9 - 12, 15, 17, 19, 23, 26, 33 - 35, 37, 38, 42, 53 - 55, 59, 61, 62, 65 - 67, 71,
p.000120: 76 - 80, 87 - 90, 95, 97, 100 - 103
p.000120: Protocol 2, 12, 18, 23, 25, 35, 36, 43, 49, 55, 56, 58, 76, 83, 87 - 90, 92, 96, 99, 101, 102, 105
p.000120: Public accountability 11, 13, 29, 31, 51, 91
p.000120: Publication ii, 29, 31, 84, 91, 92, 95, 102
p.000120: R
p.000120: Registries 36, 38, 39, 47, 49, 51, 72, 91
p.000120: Rehabilitation 55, 104
p.000120: Reimbursement 53, 54
p.000120: Research ethics committee 2, 9, 10, 12, 15, 17, 18, 23, 25, 27, 33, 34 - 39, 41, 43 - 45, 47,
...
Social / education
Searching for indicator education:
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p.000001: sponsors and others) rely on the information that research generates to make decisions that have
p.000001: important consequences for individual and public health. For example, evidence produced in early phase research
p.000001: provides the foundation for subsequent studies, and methodological shortcomings can derail promising avenues of
p.000001: research and squander valuable resources. Many other forms of research, such as clinical trials, health systems
p.000001: research, epidemiological studies or post-marketing studies, generate data that are relevant for clinical
p.000001: decision-making, health and social policy, or resource allocation. Ensuring that studies uphold high scientific
p.000001: standards is essential for maintaining the integrity of the research enterprise and its ability to fulfil its social
p.000001: function.
p.000001:
p.000001: Although the quality of the information produced by research depends critically on the scientific value of
p.000001: a study, scientific value alone does not make a study socially valuable. For example, a study can be rigorously
p.000001: designed but lack social value when the research question has been successfully addressed in prior research. However, a
p.000001: study cannot be socially valuable without appropriate and rigorous research methods to address the question at
p.000001: hand. In other words, scientific value is a necessary but not a sufficient condition for the social value of
p.000001: health research.
p.000001:
p.000001: Qualification of research personnel. Sponsors, researchers, and research ethics committees must ensure that all
p.000001: research personnel are qualified by virtue of their education and experience to perform competently and
p.000001: with integrity. This includes receiving appropriate ethics education and training. Qualifications of
p.000001: research personnel must be adequately described in the materials submitted to the research ethics committee
p.000001: (Appendix I).
p.000001:
p.000001: Respect for rights and welfare. Although the social value of research is a necessary condition for its ethical
p.000001: acceptability, it is not sufficient. All research with humans must be carried out in ways that show respect and concern
p.000001: for the rights and welfare of individual participants and the communities in which research is carried out. This
p.000001: respect and concern is manifest in requirements for informed consent, ensuring that risks are minimized and are
p.000001: reasonable in light of the importance of the research, and other requirements discussed in this document. Research must
p.000001: also be sensitive to issues of justice and fairness. This concern is manifest in choosing whose health needs
p.000001: are investigated; how risks, burdens, and anticipated benefits of individual studies are distributed; and who will
p.000001: have access to any resulting knowledge and interventions. These and other ethical aspects of research are discussed in
p.000001: the following guidelines and commentaries. The research protocol submitted for ethical review must include, when
p.000001: relevant, the items specified in Appendix I, and must be carefully followed in conducting the research.
p.000001:
...
p.000029: component of the country’s health system, and optimize its sustainability for further generation of new knowledge.
p.000029: Local principal investigators should be involved in the research project.
p.000029:
p.000029: Capacity-building and conflicts of interest. Capacity-building may give rise to conflicts of interests. The
p.000029: following interests may conflict: the desire of the sponsor to conduct the research; the wishes of potential
p.000029: participants regarding their enrolment; the desire of investigators to access the latest medications for their patients
p.000029: and contribute to knowledge; and the commitment of local community leaders to compensate for inadequate research
p.000029: funding by bringing in sponsored research to build their infrastructure. Research ethics committees should evaluate
p.000029: whether capacity-building efforts may involve such conflicts of interests and seek ways to mitigate them (see Guideline
p.000029: 25 – Conflicts of interest).
p.000029:
p.000029: Strengthening ethical review. Researchers and sponsors who plan to perform research in settings where research ethics
p.000029: committees are absent or lack adequate training should help to establish such committees, to the extent
p.000029: reasonably possible, before the research is initiated and make provisions for their education in research
p.000029: ethics. To avoid conflicts of interest and safeguard the independence of review committees, financial
p.000029: assistance from researchers and sponsors must not be provided directly and must never be tied to the committee’s
p.000029: decision about specific protocols (see Guideline 25 – Conflicts of interest). Rather, funds must be made
p.000029: available specifically for research ethics capacity-building. It is in everyone’s interest to have truly independent
p.000029: scientific and ethical review.
p.000029:
p.000029: Education of research personnel. Sponsors are expected to employ and, if necessary, educate individuals to function
p.000029: as researchers, research assistants and coordinators and data managers, for example, and to provide, as
p.000029: necessary, reasonable amounts of financial, educational and other assistance for capacity-building.
p.000029:
p.000029: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000030: 30
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p.000030:
p.000030:
p.000030: Joint publication and data sharing. Collaborative research should lead to jointly (external and in-country)
p.000030: authored, open-access publications (see Guideline 24 – Public accountability for health- related research). Researchers
p.000030: and sponsors must provide fair opportunities to enable joint authorship consistent with recognized authorship
p.000030: requirements, such as those of the International Committee of Medical Journal Editors (ICMJE).
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p.000030: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000031: 31
p.000031:
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p.000031:
p.000031:
p.000031: GUIDELINE 9:
...
p.000056: ethics committees must ensure that specific protections are in place to safeguard the rights and welfare of these
p.000056: individuals and groups in the conduct of the research.
p.000056:
p.000056:
p.000056: Commentary on Guideline 15
p.000056: General considerations. According to the Declaration of Helsinki, vulnerable groups and individuals “may have an
p.000056: increased likelihood of being wronged or of incurring additional harm.” This implies that vulnerability involves
p.000056: judgments about both the probability and degree of physical, psychological, or social harm, as well as a greater
p.000056: susceptibility to deception or having confidentiality breached. It is important to recognize that vulnerability
p.000056: involves not only the ability to provide initial consent to participate in research, but also aspects of the ongoing
p.000056: participation in research studies. In some cases, persons are vulnerable because they are relatively (or
p.000056: absolutely) incapable of protecting their own interests. This may occur when persons have relative or absolute
p.000056: impairments in decisional capacity, education, resources, strength, or other attributes needed to protect their own
p.000056: interests. In other cases, persons can also be vulnerable because some feature of the circumstances (temporary or
p.000056: permanent) in which they live makes it less likely that others will be vigilant about, or sensitive to, their
p.000056: interests. This may happen when people are marginalized, stigmatized, or face social exclusion or prejudice
p.000056: that increases the likelihood that others place their interests at risk, whether intentionally or unintentionally.
p.000056: Although research ethics committees can require special protections only for potential participants collectively for a
p.000056: particular project, researchers and others involved in research must take into account factors that render individual
p.000056: participants vulnerable and take appropriate steps to mitigate those factors.
p.000056:
p.000056: A traditional approach to vulnerability in research has been to label entire classes of individuals as vulnerable. The
p.000056: account of vulnerability in this Guideline seeks to avoid considering members of entire classes of
p.000056: individuals as vulnerable. However, it is useful to look at the specific characteristics that may render individuals
...
p.000088: a highly centralized administration, a national, or centralized, review committee may be constituted for both
p.000088: scientific and ethical review of research protocols. In countries where medical research is not centrally
p.000088: administered, ethical review can also be undertaken at a local or regional level. Whether research is nationally
p.000088: or locally reviewed varies and may depend on the size of the country and the type of the research. The authority of a
p.000088: local research ethics committee may be confined to a single institution or may extend to all institutions in which
p.000088: health-related research is carried out within a defined geographical area or network.
p.000088:
p.000088: Externally sponsored research. Research may be externally sponsored, meaning that it is sponsored, financed,
p.000088: and sometimes wholly or partly carried out by an external organization with the collaboration or agreement of the
p.000088: appropriate authorities of the host community. External sponsors must collaborate with local partners (see Guideline 8
p.000088: – Collaborative partnership and capacity building for research and review). Researchers and sponsors who plan to
p.000088: perform research in settings where research ethics committees are absent or lack adequate training should
p.000088: help to establish such committees according to their ability before the research is initiated, and make provisions
p.000088: for their education in research ethics (see Guideline 8 – Collaborative partnership and capacity building for research
p.000088: and review).
p.000088:
p.000088: Externally sponsored research must be reviewed at the site of the sponsor as well as locally. The ethical standards
p.000088: should be no less stringent than they would be for research carried out in the country of the sponsoring organization
p.000088: (see also Guideline 2 – Research conducted in low-resource settings). Local committees must be fully empowered to
p.000088: disapprove a study that they believe to be unethical.
p.000088:
p.000088: Multi-centre research. Some research projects are designed to be conducted in a number of centres in
p.000088: different communities or countries. To ensure that the results are valid, the study must be conducted in a
p.000088: methodologically identical way at each centre. However, committees at individual centres must be authorized to adapt
p.000088: the informed consent document provided by the sponsor or the lead institution in the multi-centre trial in order to
p.000088: make it culturally appropriate.
p.000088:
p.000088: To avoid lengthy procedures, multi-centre research in a single jurisdiction (state or country) should be reviewed by
p.000088: only one research ethics committee. In cases of multi-centre research, if a local
p.000088:
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...
p.000096: actions of an investigator resulting from professional, academic, or financial interests will result in biased study
p.000096: results or cause harm or wrong to participants.
p.000096:
p.000096: Conflicts of interests can influence researchers subconsciously. For example, researchers with a financial
p.000096: stake in a study may not intentionally manipulate the research findings. However, their financial interests may
p.000096: subconsciously influence their analysis and interpretation of the research data.
p.000096:
p.000096: Management of conflicts of interest. All stakeholders in research share responsibility for developing and implementing
p.000096: policies and procedures to identify, mitigate, eliminate, or otherwise manage conflicts of interest.
p.000096: Although this is a joint responsibility, research institutions play a critical role in creating an
p.000096: institutional culture that takes conflicts of interest seriously and adopts appropriate measures for their management.
p.000096: Measures for managing conflicts of interest must be proportional to their seriousness. For example, a minor
p.000096: conflict of interest may be appropriately managed by disclosure, while a potential serious conflict can, in some
p.000096: cases, justify excluding a researcher from the study team. Policies and measures for managing conflicts of interest
p.000096: must be transparent and actively communicated to those affected.
p.000096:
p.000096: 1. Education of researchers and research ethics committees. Raising awareness of conflicts of interest, as well as
p.000096: the importance of managing such conflicts, is essential for making procedures and policies effective.
p.000096:
p.000096: 2. Disclosure of interests to research ethics committees. Researchers must disclose conflicts of interest on their
p.000096: part to the ethical review committee or to other institutional committees designed to evaluate and manage
p.000096: such conflicts. Researchers will most likely come to recognize conflicts of interest if they are prompted to
p.000096: scrutinize these conflicts as an expected part of preparing a description of their projects for ethical review.
p.000096: The development of a standardized disclosure form and related educational and explanatory materials may help
p.000096: to ensure that researchers understand conflicts of interest and routinely report relevant facts about their own
p.000096: situation to research ethics committees reviewing their protocols. Disclosure forms should provide a definition of
p.000096: conflicts of interest, along with some examples, and help researchers understand that a conflict of interest is not
p.000096: necessarily disqualifying, but may be managed. When research ethics committees have credible evidence about serious
p.000096: conflicts of interest related to a study that are not disclosed in the materials submitted to the committee, the member
p.000096: of the research team with the apparent conflict should be contacted for further information. Research
...
p.000105:
p.000105: 8. when concerning disaster victims who mostly are under duress, the difference between research and humanitarian
p.000105: aid (Guideline 20); and
p.000105:
p.000105: 9. when research is done in the online environment and using online or digital tools that may
p.000105: involve potentially vulnerable persons, information about the privacy and security controls that will be used to
p.000105: protect their data; and the limitations of the measures used and the risks that may remain despite the safeguards put
p.000105: in place (Guideline 22).
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p.000106: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000106:
p.000106: APPENDIX 3
p.000106: CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH INVOLVING
p.000106: HUMANS
p.000106:
p.000106: Chair
p.000106: Hans van Delden
p.000106: Johannes JM van Delden is professor of medical ethics at the medical school of Utrecht University, the Netherlands, and
p.000106: director of education at the Julius Center for health sciences. He has written more than two hundred articles in
p.000106: peer-reviewed scientific journals and (co)authored three books. He was secretary of the International Association of
p.000106: Bioethics. As a professor of medical ethics he has built a strong academic group within the University Medical Center
p.000106: Utrecht. The special fields of interest of this group are: research ethics, moral problems at the end of life and moral
p.000106: problems in the care for the elderly. He is currently the chair of the International Bioethics Committee at UNESCO and
p.000106: was president of CIOMS from 2011 to 2016.
p.000106:
p.000106: Secretary
p.000106: Rieke van der Graaf
p.000106: Rieke van der Graaf is an assistant professor of bioethics and employed at the University Medical Center Utrecht at the
p.000106: Julius Center, Department of Medical Humanities. Her current research interests are inclusion of “vulnerable
p.000106: populations” in clinical research, the integration of care and research, and the ethics of innovative research designs.
p.000106: She is teaching medical ethics at the UMC Utrecht and has been a member of the UMC Utrecht’s Hospital Ethics Committee
p.000106: for more than 10 years. She is a member of the Research Ethics Committee (REC) of the UMC Utrecht. She was the
...
p.000107:
p.000107: Dirceu Greco
p.000107: Dirceu Greco is full professor of Infectious Diseases and Bioethics at the School of Medicine, Federal University of
p.000107: Minas Gerais (UFMG), Belo Horizonte, Brazil. He received his MD degree and this PhD from UFMG. Chief, Infectious and
p.000107: Parasitic Diseases Service (2009-2011), Coordinator of UFMG University Hospital Centre for Clinical Research
p.000107: (2005-2010), member (2007-2010), Brazilian Research Ethics Commission (CONEP); member, Brazilian AIDS Commission
p.000107: (Ministry of Health-MoH). Main topics of interest include Infectious and Parasitic Illnesses, bioethics, public health
p.000107: and clinical immunology. He has participated in several working groups that gave rise to
p.000107: national/international guidelines related to ethics, prevention, care and treatment of HIV/AIDS and TB. He has
p.000107: frequently acted as temporary advisor to many national/international institutions, such as the Brazilian AIDS
p.000107: Programme, WHO, UNITAID, UNAIDS, CIOMS and WMA. From 2010 to 2013 he directed the Department of STD, AIDS and Viral
p.000107: Hepatitis (Secretary of Health Surveillance, MoH, Brazil).
p.000107:
p.000107: David Haerry
p.000107: David Haerry is a treatment writer and conference reporter since 1996. He is co-authoring a database on travel &
p.000107: residency restrictions for people living with HIV. David Haerry has been involved in health care professionals
p.000107: education projects since 2007. Since 2015, he is Secretary General of the Swiss Academic Foundation on Education in
p.000107: Infectious Diseases SAFE-ID. He is work package co-leader and member of the Executive Committee in the EUPATI-IMI
p.000107: project and involved in a number of European and global research networks and research collaborations, including the
p.000107: ENCePP Steering Group. He is co-chair of the Patient and Consumer Working Party at the European Medicines Agency and
p.000107: has served the European AIDS Treatment Group EATG in various positions since 2004. David has been involved in HIV and
p.000107: HCV drug development since 2005 and has specific interests in the areas of Personalised Medicine, Risk Communication,
p.000107: Pharmacovigilance, Observational Studies, Biomedical Prevention and HIV Eradication Research. He is living with HIV
p.000107: since 1986.
p.000107:
p.000107: Bocar Kouyaté
p.000107: Bocar A. Kouyaté is Senior Advisor to the Minister of Health, Burkina Faso and researcher at the Centre national de
p.000107: recherché et de formation sur le paludisme (CNRFP), Burkina Faso. Dr Kouyaté is a physician by training and holds
p.000107: a PhD degree in public health. He has worked throughout all levels of the health system in Burkina Faso from
p.000107: district medical officer to the intermediary level as
p.000107:
p.000107:
p.000107:
p.000107:
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p.000108:
p.000108:
p.000108:
p.000108:
...
p.000110: involving human subjects and on the ethics of aging, particularly on the ethics of new biomedical interventions
p.000110: into the ageing process and increased longevity and on policies promoting healthy ageing. He is a member of
p.000110: the Research Ethics Committee of the Federal Board of Physicians, Baden-Württemberg.
p.000110:
p.000110: Carel IJsselmuiden, Council on Health Research for Development (COHRED)
p.000110: Carel is a physician, epidemiologist, public health practitioner, academic and social entrepreneur, with
p.000110: qualifications from universities in Belgium, Netherlands, South Africa and the United States. He spent 7
p.000110: years in rural medicine and public health, 4 years in peri-urban and urban health care, HIV/AIDS control and
p.000110: environmental services management as Deputy Medical Officer of Health for Johannesburg, South Africa. He
p.000110: was appointed as Professor and Head of Department of the department of community health at the University of
p.000110: Pretoria in 1995, where he became the founding Director of the School of Health Systems and Public Health in 1999. He
p.000110: held this position until his appointment as Executive Director at COHRED in 2004. As such, he is also member of the
p.000110: COHRED Board, President of COHRED USA and board member of COHRED Africa. He has published widely in applied research,
p.000110: nutrition, immunization, environmental health, research capacity building, global public health education and ethics of
p.000110: international collaborative health research. As part of community service, he was director of the Elim Care Group
p.000110: Project, a health and development NGO in the north of South Africa, served on the board of the Nokuthula
p.000110: Centre for Disabled Children in Alexandra township in South Africa and offers strategic research and innovation
p.000110: development support to low- and middle-income countries. Carel holds two nationalities – South African and Netherlands
p.000110: – and has worked and lived in Africa, Europe, the United States and the Caribbean.
p.000110:
p.000110: Observer
p.000110: Ingrid Callies
p.000110: Dr Ingrid Callies, PHD (University Paris Descartes), LLM (University of Virginia), a member of the New
p.000110: York Bar and a bioethicist, is Head of Ethics and Coordinator of the Code Authority and Ethics Committee (Codeem) for
p.000110: the pharmaceutical industry in France at Leem, the French federation of the pharmaceutical industry (www.leem.org).
p.000110: Previously, she was Ethics Advisor at the Institut Pasteur, worked for the French National Agency for Research on Aids
p.000110: and Viral Hepatitis, and practised law at Hogan & Hartson LLP, a law firm now called Hogan Lovells. Co-editor of the
p.000110: Ethics of Research Section in the Elsevier International Encyclopedia of the Social and Behavioural
...
p.000117: Cluster randomized trials 79, 80
p.000117: Coding 41, 44, 47, 50, 51, 90
p.000117: Collaborative partnership 27, 29, 30, 42, 45, 47, 52, 89
p.000117: Collection, collecting 26, 36, 39, 41 - 43, 47 - 50, 77, 80, 83 - 85, 92, 103, 105
p.000117: Community engagement ix, xi, 5, 10, 23, 25, 26, 29, 30, 42, 45, 47, 52, 59, 63, 75, 78, 102
p.000117: Comparative effectiveness research 16, 19
p.000117: Compassionate use 22
p.000117: Compelling scientific reasons 15 - 18
p.000117: Compensation 13, 53 - 56, 96, 100, 104 Competent. See Capable of giving informed consent Comprehension 34
p.000117: Confidentiality 11, 13, 41, 42, 44, 47, 48, 50, 51, 57, 59, 70, 100, 101, 102, 104, 105
p.000117: Conflicts of interest 5, 30, 34, 78, 89, 92, 95 - 97, 102, 104
p.000117: Continued access 21 - 23, 101, 104
p.000117: Control 9, 12, 15 - 18, 22, 26, 45, 51, 62, 67, 73, 79, 80, 83, 85,
p.000117: Custodian 41, 43, 44, 47, 49, 50, 105
p.000117: D
p.000117: Databank 47 - 52
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p.000119: 119
p.000119:
p.000119: Data mining 50
p.000119: Data sharing 29, 31, 51, 85, 92
p.000119: Deception, deceiving 33, 38, 57
p.000119: Deliberate objection 67
p.000119: Dependent relationship 26, 35, 36, 58, 96
p.000119: Digital 83, 106
p.000119: Disaster ix, 75 - 78, 106
p.000119: Disclosure 44, 45, 51, 84, 85, 91, 95, 97, 101, 103 - 105
p.000119: Disease outbreak ii, x, 19, 34, 41, 44, 47, 49, 83, 96, 97, 99, 103, 105
p.000119: Dissemination 2, 4, 25, 85, 92
p.000119: Dissent 62, 67
p.000119: E
p.000119: Education 2, 30, 57, 89, 97
p.000119: Emergency care 63, 68, 78
p.000119: Equitable distribution 4, 7, 42, 45, 47, 52, 75, 77
p.000119: Established effective intervention viii, 9, 12, 15 - 19
p.000119: Ethical review xii, 2, 29, 30, 39, 76 - 78, 87 - 90, 95, 97, 99, 102
p.000119: Externally sponsored research 87, 89
p.000119: F
p.000119: Fairness 2
p.000119: Fetus 58, 69, 70 - 73
p.000119: Free medical treatment 56
p.000119: G
p.000119: Gatekeeping 80
p.000119: Governance 41 - 43, 44, 47, 48, 50, 51, 78
p.000119: H
p.000119: Harms 10, 11, 12, 18, 54, 55, 56, 70, 72, 91, 105
p.000119: Health needs 2 - 4, 8, 17, 19, 21 - 23, 26, 55, 61, 65, 69, 71, 72, 75, 76, 104
p.000119: I
p.000119: Identifiable 38, 39, 51, 84
p.000119: Implementation research 80
p.000119: Incentives 10, 54, 92, 101
p.000119: Information leaflet 34
p.000119: Informed consent ix, 2, 9, 10, 21, 25, 26, 33 - 39, 41 - 45, 47 - 52, 54, 56, 58, 61 - 65, 67 - 72, 75,
p.000119: 76, 78 - 80, 89, 96, 97, 100, 101, 103, 105
p.000119: Informed opt-out /opt-in 41, 44, 47, 49, 83
p.000119: In-kind 54
p.000119: Interventions 1 - 4, 9 - 12, 15 - 19, 21 - 23, 26, 30, 53, 55, 56, 61 - 63, 65, 66, 71 - 73, 75 - 81, 84,
p.000119: 88, 91, 100, 101, 104
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p.000120: 120
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p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
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p.000099: INFORMATION FOR PROSPECTIVE RESEARCH PARTICIPANTS 103
p.000099: APPENDIX 3 CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH
p.000099: INVOLVING HUMANS
p.000107: 107
p.000107: APPENDIX 4 COMMENTATORS 113
p.000107: INDEX
p.000119: 119
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p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000119: vii
p.000119:
p.000119: PREFACE
p.000119: About CIOMS
p.000119: The Council for International Organizations of Medical Sciences (CIOMS) is an international nongovernmental
p.000119: organization in official relationship with World Health Organization (WHO). It was founded under the auspices of WHO
p.000119: and the United Nations Educational, Scientific and Cultural and Organization (UNESCO) in 1949. Among its mandates is
p.000119: maintaining collaborative relations with the United Nations and its specialized agencies, especially UNESCO and WHO.
p.000119:
p.000119: The first version of the CIOMS Guidelines (1982)
p.000119: CIOMS, in association with WHO, undertook its work on ethics in biomedical research in the late 1970s.
p.000119: Accordingly, CIOMS set out, in cooperation with WHO, to prepare guidelines. The aim of the guidelines was (and still
p.000119: is) to provide internationally vetted ethical principles and detailed commentary on how universal ethical principles
p.000119: should be applied, with particular attention to conducting research in low-resource settings. The outcome of the
p.000119: CIOMS/WHO collaboration was entitled Proposed International Ethical Guidelines for Biomedical Research Involving
p.000119: Human Subjects.
p.000119:
p.000119: The second version of the CIOMS Guidelines (1993)
p.000119: The period that followed saw the outbreak of the HIV/AIDS pandemic and proposals for large-scale trials of prevention
p.000119: and treatment for the disease. These developments raised new ethical issues that had not been considered in the
p.000119: preparation of the Proposed Guidelines. There were other factors also – rapid advances in medicine and
...
p.000025: researcher.
p.000025:
p.000025: Researchers and research ethics committees should be cognizant of the point at which the process of community
p.000025: engagement becomes a stage of formative research that itself requires ethics review. Examples of community engagement
p.000025: processes that may require ethics review include systematic data collection that can be generalized and disseminated in
p.000025: forums outside of the community in which they were implemented, as well as any data generation that could create social
p.000025: risks for participants.
p.000025:
p.000025: Engagement at the earliest opportunity. Before a study is initiated, the community from which participants will be
p.000025: recruited should, when feasible, be consulted about their research priorities, preferred trial designs,
p.000025: willingness to be involved in the preparation and conduct of the study. Engaging the community at the
p.000025: earliest stage promotes smooth study functioning and contributes to the community’s capacity to understand the research
p.000025: process. Community members should be encouraged to raise any concerns they may have at the outset and as the research
p.000025: proceeds. Failure to engage the community can compromise the social value of the research, as well as threaten the
p.000025: recruitment and retention of participants.
p.000025:
p.000025: Community engagement should be an ongoing process, with an established forum for communication between researchers and
p.000025: community members. This forum can facilitate the creation of educational materials, planning the necessary
p.000025: logistical arrangements for the conduct of the research, and providing information about the health beliefs,
p.000025: cultural norms, and practices of the community. Active engagement with community members is a mutually educative
p.000025: process, which both enables researchers to learn about communities’ cultures and understanding of research- related
p.000025: concepts, and contributes to research literacy by educating the community about key concepts critical for
p.000025: understanding the purpose and procedures of the research. Good-quality community engagement helps to ensure that
p.000025: existing community dynamics and power inequities are not allowed to derail the process of ensuring the
p.000025: comprehensive engagement of all relevant community stakeholders. Care should be taken to solicit the views of all
p.000025: sectors of the community proactively and sensitively. Community members should be invited to assist in the development
p.000025: of the informed consent process and documents to ensure that they are understandable and appropriate for potential
p.000025: participants.
p.000025:
p.000025: Confidence and trust. Engaging the community strengthens local ownership of the research and builds confidence in
p.000025: the ability of leaders to negotiate various aspects of the research, such as recruitment strategies, care
p.000025: for the health needs of study participants, site selection, data collection and sharing, ancillary care and post-trial
p.000025: availability of any developed interventions for populations and communities (see Guideline 2 – Research conducted in
p.000025: low-resource settings, and Guideline 6
...
p.000029: 25 – Conflicts of interest).
p.000029:
p.000029: Strengthening ethical review. Researchers and sponsors who plan to perform research in settings where research ethics
p.000029: committees are absent or lack adequate training should help to establish such committees, to the extent
p.000029: reasonably possible, before the research is initiated and make provisions for their education in research
p.000029: ethics. To avoid conflicts of interest and safeguard the independence of review committees, financial
p.000029: assistance from researchers and sponsors must not be provided directly and must never be tied to the committee’s
p.000029: decision about specific protocols (see Guideline 25 – Conflicts of interest). Rather, funds must be made
p.000029: available specifically for research ethics capacity-building. It is in everyone’s interest to have truly independent
p.000029: scientific and ethical review.
p.000029:
p.000029: Education of research personnel. Sponsors are expected to employ and, if necessary, educate individuals to function
p.000029: as researchers, research assistants and coordinators and data managers, for example, and to provide, as
p.000029: necessary, reasonable amounts of financial, educational and other assistance for capacity-building.
p.000029:
p.000029: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000030:
p.000030:
p.000030:
p.000030:
p.000030:
p.000030: Joint publication and data sharing. Collaborative research should lead to jointly (external and in-country)
p.000030: authored, open-access publications (see Guideline 24 – Public accountability for health- related research). Researchers
p.000030: and sponsors must provide fair opportunities to enable joint authorship consistent with recognized authorship
p.000030: requirements, such as those of the International Committee of Medical Journal Editors (ICMJE).
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p.000030: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: GUIDELINE 9:
p.000031: INDIVIDUALS CAPABLE OF GIVING INFORMED CONSENT
p.000031:
p.000031: Researchers have a duty to provide potential research participants with the information and the opportunity to give
...
p.000033: supplement written information documents to aid understanding. Information should also be appropriate for the
p.000033: participant group and specific individual, for example, in braille. Informed consent shall not include any language
p.000033: through which the subject is made to waive or appear to waive any of the participant’s legal rights, or releases or
p.000033: appears to release the investigator, the sponsor, the institution, or its agents from liability for negligence.
p.000033:
p.000033: Contents of the information leaflet. Throughout these Guidelines, elements that need to be included in the
p.000033: information leaflet are specified. Appendix 2 contains the details of information that must be provided, as well
p.000033: as possible supplementary information. This list mentions, but is not limited to, information about the aims,
p.000033: methods, sources of funding, possible conflicts of interest, institutional affiliations of the researcher, the
p.000033: anticipated benefits and potential risks of the study and the discomfort it may entail, post-trial access and
p.000033: any other relevant aspects of the study.
p.000033:
p.000033: Comprehension. The person obtaining consent must ensure that the potential participant has adequately
p.000033: understood the information provided. Researchers should use evidence-based methods for imparting information to ensure
p.000033: comprehension. The potential participant’s ability to understand the information depends, among other things, on the
p.000033: individual’s maturity, educational level and belief system. The participant’s understanding also depends on the
p.000033: researcher’s ability and willingness to communicate with patience and sensitivity, as well as the atmosphere, situation
p.000033: and location where the informed consent process takes place.
p.000033:
p.000033: Documentation of consent. Consent may be indicated in a number of ways. The participant may express consent orally, or
p.000033: sign a consent form. As a general rule, the participant should sign a consent form, or, where the individual lacks
p.000033: decisional capacity, a legal guardian or other duly authorized
p.000033:
p.000033:
p.000033: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000034: 34
p.000034:
p.000034:
p.000034:
p.000034:
p.000034:
p.000034: representative must do so (see Guideline 16 – Research involving individuals incapable of giving informed
p.000034: consent, and Guideline 17 – Research involving children and adolescents). The research ethics committee may approve a
p.000034: waiver of the requirement of a signed consent document under certain conditions (see Guideline 10 – Modifications and
...
p.000051: Nevertheless, some low-resource settings may be inexperienced in storing and using biological materials. In addition to
p.000051: what is stated in this Guideline, requirements for community engagement, capacity-building and equitable
p.000051: distribution of burdens and benefits of research as described in other guidelines also apply to databank
p.000051: research in low-resource settings (see Guideline 3 – Equitable distribution of benefits and burdens in the
p.000051: selection of individuals and groups of participants in research, Guideline 7 – Community engagement, and Guideline 8 –
p.000051: Collaborative partnership and capacity building for research and review).
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p.000051: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000052: 52
p.000052:
p.000052:
p.000052:
p.000052:
p.000052:
p.000052: GUIDELINE 13:
p.000052: REIMBURSEMENT AND
p.000052: COMPENSATION FOR RESEARCH PARTICIPANTS
p.000052:
p.000052: Research participants should be reasonably reimbursed for costs directly incurred during the research, such as travel
p.000052: costs, and compensated reasonably for their inconvenience and time spent. Compensation can be monetary or non-monetary.
p.000052: The latter might include free health services unrelated to the research, medical insurance, educational materials, or
p.000052: other benefits.
p.000052:
p.000052: Compensation must not be so large as to induce potential participants to consent to participate in the
p.000052: research against their better judgment (“undue inducement”). A local research ethics committee must approve
p.000052: reimbursement and compensation for research participants.
p.000052:
p.000052:
p.000052: Commentary on Guideline 13
p.000052: General considerations. Both in observational studies and intervention research, participants should not have to pay
p.000052: for making a contribution to the social good of research, whether in the form of direct expenses (for
p.000052: example, transportation costs), and must therefore be reasonably reimbursed for such expenses. In addition,
p.000052: participants must be appropriately compensated for the time spent and other inconveniences resulting from study
p.000052: participation. The amount of compensation should be proportional to the time spent for research purposes and for travel
p.000052: to the research site. This amount should be calculated using the minimum hourly wage in the region or country as a
p.000052: reference value. The obligation to reasonably reimburse and compensate participants arises even when study
p.000052: enrolment offers participants potential individual benefits (for example, an investigational drug). This is
p.000052: because the vast majority of clinical research studies involve research procedures that have no potential individual
p.000052: benefits for participants but are performed for research purposes, such as additional blood draws, extra hospital
p.000052: visits and overnight stays. Moreover, it cannot be known before the research that investigational interventions
p.000052: will benefit participants. Indeed, some research interventions may cause more harm than good.
p.000052:
p.000052: Appropriate compensation. Participants must also be reasonably compensated for their inconvenience and time
p.000052: spent participating in research according to monetary value of the country in which the research is conducted.
p.000052: Compensation can be monetary or non-monetary and may include, for example, health services unrelated to the research,
p.000052: medical insurance, educational materials, counselling or food supplies. Especially when the research poses low risks,
p.000052: providing compensation for participation should not raise concerns about undue inducement.
p.000052:
p.000052: Unacceptable compensation. Compensation is not meant to compensate for risk that participants agree to undertake but
p.000052: rather, for inconvenience and time. Therefore, the level of compensation
p.000052:
p.000052: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000053: 53
p.000053:
p.000053:
p.000053:
p.000053:
p.000053:
p.000053: should not be related to the level of risk that participants agree to undertake. But especially as the
p.000053: risks of research procedures having no potential individual benefit for participants increase, so does the
p.000053: concern that compensation may constitute an undue inducement. Monetary or in-kind compensation for research
p.000053: participants must not be so large as to persuade them to volunteer against their better judgment or deeply
p.000053: held beliefs (“undue inducement”).
p.000053:
p.000053: It can be difficult to determine whether undue inducement exists, in part because the compensation that makes some
p.000053: people volunteer against their better judgment depends on their personal situation. An unemployed person or a student
p.000053: may view compensation differently from an employed person. Research ethics committees must evaluate monetary and other
...
p.000096: Although this is a joint responsibility, research institutions play a critical role in creating an
p.000096: institutional culture that takes conflicts of interest seriously and adopts appropriate measures for their management.
p.000096: Measures for managing conflicts of interest must be proportional to their seriousness. For example, a minor
p.000096: conflict of interest may be appropriately managed by disclosure, while a potential serious conflict can, in some
p.000096: cases, justify excluding a researcher from the study team. Policies and measures for managing conflicts of interest
p.000096: must be transparent and actively communicated to those affected.
p.000096:
p.000096: 1. Education of researchers and research ethics committees. Raising awareness of conflicts of interest, as well as
p.000096: the importance of managing such conflicts, is essential for making procedures and policies effective.
p.000096:
p.000096: 2. Disclosure of interests to research ethics committees. Researchers must disclose conflicts of interest on their
p.000096: part to the ethical review committee or to other institutional committees designed to evaluate and manage
p.000096: such conflicts. Researchers will most likely come to recognize conflicts of interest if they are prompted to
p.000096: scrutinize these conflicts as an expected part of preparing a description of their projects for ethical review.
p.000096: The development of a standardized disclosure form and related educational and explanatory materials may help
p.000096: to ensure that researchers understand conflicts of interest and routinely report relevant facts about their own
p.000096: situation to research ethics committees reviewing their protocols. Disclosure forms should provide a definition of
p.000096: conflicts of interest, along with some examples, and help researchers understand that a conflict of interest is not
p.000096: necessarily disqualifying, but may be managed. When research ethics committees have credible evidence about serious
p.000096: conflicts of interest related to a study that are not disclosed in the materials submitted to the committee, the member
p.000096: of the research team with the apparent conflict should be contacted for further information. Research
p.000096: ethics committees may also consult with the Conflict of Interest Coordinator in their institution.
p.000096:
p.000096: 3. Disclosure of interests to participants. Research ethics committees may require that conflicts of interest be
p.000096: disclosed to potential study participants in the informed consent discussion and documents (for example, stock
p.000096: ownership). The disclosure must allow potential participants to judge the seriousness of the conflict of interest. This
p.000096: goes beyond describing “the nature and sources of funding for the research,” which is an element of informed consent
p.000096: (see Appendix 2). In the case of serious conflicts of interest, studies suggest that disclosure works best when it is
...
p.000106: She is teaching medical ethics at the UMC Utrecht and has been a member of the UMC Utrecht’s Hospital Ethics Committee
p.000106: for more than 10 years. She is a member of the Research Ethics Committee (REC) of the UMC Utrecht. She was the
p.000106: Secretary of the Working Group on the Revision of the CIOMS Guidelines.
p.000106:
p.000106: Members
p.000106: Anant Bhan
p.000106: Anant Bhan is trained as a medical doctor with a masters degree in bioethics from the University of Toronto. He is a
p.000106: researcher in the fields of Bioethics, Global Health and Health Policy based in India. He is also Adjunct
p.000106: Professor at Yenepoya University, Mangalore, India. In the past, he has worked for NGOs and a government
p.000106: public health training institution in India, as well as a consultant to a project on Ethical, Social and Cultural
p.000106: issues in health biotechnology based at the University of Toronto. Anant has published extensively in various national
p.000106: and international medical journals in the field of global/public health and bioethics, as well as contributed to
p.000106: popular mass media. Anant has been a resource person for trainings in global health, research methodology, research
p.000106: ethics and public health ethics, and also serves as guest faculty in various educational institutions in India and
p.000106: abroad. He is on the Editorial Board of ‘Public Health Ethics’ (www.phe.oxfordjournals.org),
p.000106:
p.000106:
p.000106: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000106:
p.000107: 107
p.000107:
p.000107:
p.000107:
p.000107:
p.000107:
p.000107: a quarterly journal of Oxford University Press and also serves on the International Advisory Board of the Asian
p.000107: Bioethics Review (http://www.asianbioethicsreview.com). He is also a member of the Ethics Working Group of the US
p.000107: NIH‐funded HIV Prevention Trials Network (http://www.hptn.org/hptnresearchethics.htm). He currently is a member of four
p.000107: ethics committees in India (in two of which he also serves as the chairperson), and has been as a reviewer for multiple
p.000107: journals, conference scientific committees and international grant competitions. Anant is also a member of
p.000107: the Steering Committee of the Global Forum on Bioethics in Research. He is also a member of the Board of
p.000107: the International Association of Bioethics.
p.000107:
p.000107: Eugenijus Gefenas
p.000107: Eugenijus Gefenas is a professor and director of the Department of Medical History and Ethics at the Medical Faculty of
p.000107: Vilnius University. He is also a director of the Lithuanian Bioethics Committee. Eugenijus Gefenas graduated from the
...
p.000108: Provincial Director of Health and to Secretary General of the Ministry of Health from 1983 to 1998. From 1989 to 2009,
p.000108: he was Director of two research centres in Burkina Faso (Centre de recherche en santé de Nouna and, later on, Centre
p.000108: national de recherche et de formation sur le paludisme). He served as member of the Comité national d’éthique
p.000108: pour la recherche en santé (CERS) from 2003–2007 and was the Chair of the CERS from 2008–2013. He has
p.000108: considerable experience in research, research administration, capacity development and training, particularly in health
p.000108: systems, research ethics and malaria. His special interest is in the development of sustainable capacity and
p.000108: appropriate environment for research and getting research into policy and practice.
p.000108:
p.000108: Alex London
p.000108: Alex John London, PhD., is Professor of Philosophy and Director of The Center for Ethics and Policy at Carnegie Mellon
p.000108: University. An elected fellow of the Hastings Center, he has written extensively on problems in bioethics and
p.000108: ethical theory relating to uncertainty, risk, fairness, equality and justice. He is co-editor of Ethical Issues
p.000108: in Modern Medicine, one of the most widely used textbooks in medical ethics and recipient of the Elliott Dunlap
p.000108: Smith Award for Distinguished Teaching and Educational Service in the Dietrich College of Humanities and Social
p.000108: Sciences at Carnegie Mellon University. In 2016 Professor London was appointed to the U.S. National Academies of
p.000108: Sciences, Engineering and Medicine (formerly the Institute of Medicine) Committee on Clinical Trials During
p.000108: the 2014–2015 Ebola Outbreak. Since 2007 he has served as a member of the Ethics Working Group of the
p.000108: HIV Prevention Trials Network. He has served as an ethics expert in consultations with numerous national and
p.000108: international organizations including the U.S. National Institutes of Health, the World Health Organization,
p.000108: the World Medical Association and the World Bank.
p.000108:
p.000108: Ruth Macklin
p.000108: Ruth Macklin is Distinguished University Professor Emerita (Bioethics) in the Department of Epidemiology and Population
p.000108: Health at Albert Einstein College of Medicine in the Bronx, New York, USA. She has more than two hundred and
p.000108: seventy publications in professional journals and scholarly books in bioethics, law, medicine, philosophy, and
p.000108: the social sciences, in addition to articles in magazines and newspapers for general audiences. She is author or editor
p.000108: of thirteen books, including Mortal Choices (1988), Against Relativism (1999) and Double Standards in Medical Research
p.000108: in Developing Countries (2004). Dr Macklin is an elected member of the U.S. National Academy of Medicine and was
p.000108: president of the International Association of Bioethics from 1999–2001. She has served as consultant or
...
Social / employees
Searching for indicator employees:
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p.000095: compensation for their time spent on recruitment, it does not present an inherent conflict of interest. However, a
p.000095: salary or “finder’s fee” may lead researchers
p.000095: – intentionally or unintentionally – to interpret the inclusion or exclusion criteria of a study too flexibly, thereby
p.000095: potentially exposing participants to excessive risks or compromising the scientific validity of the research.
p.000095: This situation is of particular concern when participants are dependent on a researcher who is also their clinician
p.000095: (see Guideline 9 – Individuals capable of giving informed consent, section on Dependent relationship), and when the
p.000095: salary of the clinician is considerably lower than what the researcher is paid. It may also lead researchers to
p.000095: pressure eligible participants to enrol, thus compromising or undermining participants’ voluntary consent. In addition,
p.000095: financial conflicts of interest can arise when researchers or senior members of the research team (or their close
p.000095: family members) have a financial stake in the company sponsoring the research, such as stock ownership.
p.000095:
p.000095: 2. Research institutions (universities, research centres, or pharmaceutical companies). Research institutions can
p.000095: have both reputational and financial conflicts of interests. For example, universities rely on the reputation of
p.000095: their research to attract faculty, students, or external funding. Some universities also patent the discoveries
p.000095: of their employees. Institutional conflicts of interest can also arise when a research centre derives substantial
p.000095: support (perhaps covering years of funding) from a single sponsor or a handful of sponsors. Pharmaceutical companies
p.000095: may feel pushed to accelerate a marketing authorization for getting a longer period of patent protection, or they may
p.000095: be tempted to downplay the side effects of new medicines to get broader prescription patterns.
p.000095:
p.000095: 3. Research ethics committees. Researchers often serve as members of research ethics committees and
p.000095: conflicts of interest can arise in this role. For example, a researcher may submit her own study protocol for review,
p.000095: or she may be reviewing the work of colleagues whom she knows personally, or whose work she considers critical for the
p.000095: success of her institution. Research ethics committees may also have financial interests when their members
p.000095: receive salaries or when they are directly funded by sponsors or serve an institution that depends significantly on
p.000095: support from a single sponsor or several sponsors.
p.000095: A fee paid to a research ethics committee (or the institution where it operates) for reviewing a study does not present
p.000095: an inherent conflict of interest, provided that the fee is established by a general policy, is reasonably related to
...
Social / gender
Searching for indicator gender:
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p.000007: International Organizations of Medical Sciences (CIOMS); 2016.
p.000007: The authors alone are responsible for the views expressed in this publication and those views do not necessarily
p.000007: represent the decisions, policies or views of their respective institutions or companies.
p.000007: Design and Layout: Paprika (Annecy, France)
p.000007:
p.000007: ACKNOWLEDGEMENTS
p.000007: The Council for International Organizations of Medical Sciences (CIOMS) acknowledges the contribution of the Working
p.000007: Group for the revision of the CIOMS Ethical Guidelines. In 2011, the Executive Committee of CIOMS decided
p.000007: to set up a Working Group to revise the CIOMS Guidelines. The Working Group consisted of 10 members (Anant Bhan,
p.000007: Eugenijus Gefenas, Dirceu Greco, David Haerry, Bocar Kouyate, Alex John London, Ruth Macklin, Annette Rid, Rodolfo
p.000007: Saracci, Aissatou Touré, one chair (Hans van Delden), four advisers, from WHO (Marie-Charlotte Bouësseau and later Abha
p.000007: Saxena), UNESCO (Dafna Feinholz), COHRED (Carel Ijsselmuiden) and WMA (Urban Wiesing and Hans-Joerg Ehni) and one
p.000007: scientific secretary (Rieke van der Graaf). All members of the Working Group were internationally
p.000007: recognized for their expertise in research. The composition of the Working Group ensured that different
p.000007: cultural perspectives were present, members varied in experience and expertise, and gender balance was
p.000007: achieved. One of the members represented the perspective of research participants. Their affiliations are indicated in
p.000007: Appendix 3.
p.000007:
p.000007: CIOMS is grateful for the valuable contributions of many commentators on its first draft from individual persons and
p.000007: institutions (see Appendix 4). Their detailed review and comments have greatly helped to shape the final document.
p.000007:
p.000007: A number of institutions and organizations made valuable contributions by providing hospitality to host meetings of the
p.000007: Working Group (Utrecht University, Netherlands; Vilnius University, Lithuania; and UNESCO, Paris, France).
p.000007:
p.000007: Special thanks are due to Carla Saenz and Tania Flores at PAHO, who at no cost translated comments submitted by
p.000007: Spanish-speaking persons and organizations into English. Their work has been tremendously helpful in ensuring
p.000007: meaningful global involvement in the revision process.
p.000007:
p.000007: The revision of these Guidelines has been carried out in collaboration with World Health Organization (WHO), the
p.000007: facilitation of which was led by Abha Saxena. As a result of this collaboration, the guideline development process is
p.000007: consistent with the standards and policies of WHO. The organization-wide review by WHO especially by the Ethics
p.000007: Review Committee was coordinated by Maria Magdalena Guraiib and Vânia de la Fuente Nunez. Ronald Johnson, Melba
p.000007: Gomes, Joan Dzenowagis and Sheryl VanderPoel have provided substantial inputs to the draft document.
p.000007:
p.000007: At CIOMS, Sev Fluss edited the draft document and provided constructive comments, and Gunilla Sjölin-Forsberg, the
...
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
p.000057: judgments regarding the exclusion of such groups based on
p.000057:
p.000057:
p.000057: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000058: 58
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: stereotypes. One proposed mechanism that can be used to avoid stereotyping is consultation with relevant stakeholders,
p.000058: where feasible, before, during and after the conduct of the research (see Guideline 7 – Community
p.000058: engagement).
p.000058:
p.000058: Special protections. Special protections for these groups can include allowing no more than minimal risks for
p.000058: procedures that offer no potential individual benefits for participants; supplementing the participant’s agreement by
p.000058: the permission of family members, legal guardians, or other appropriate representatives; or requiring that the research
p.000058: be carried out only when it is targeted at conditions that affect these groups. Safeguards can be designed to promote
...
p.000068:
p.000068: Some women become vulnerable in research because of heightened psychological, social, physical, or legal risks.
p.000068: Examples include surveys and interviews regarding intimate partner violence and rape; social and behavioural
p.000068: research involving sex workers or women who inject drugs; and studies that solicit information about sexual behaviour.
p.000068: When the research involves household surveys or interviews, researchers must take special care to ensure that the women
p.000068: are interviewed in a private
p.000068:
p.000068:
p.000068: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000069: 69
p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: place without the possibility of intrusion by other family members. In such studies, women must be given
p.000069: the option of conducting the interview in a setting of their choosing outside the home. Breach of
p.000069: confidentiality in these types of research could result in serious harms to women, even if the only information
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
p.000069: women to participate. This authorization must not be used as a substitute for individual informed consent. The women
p.000069: must have adequate time and a proper environment in which to decide to enrol.
p.000069:
p.000069: Inclusion of women of child-bearing potential. A general policy of excluding from clinical studies women who are
p.000069: biologically capable of becoming pregnant is unjust in that it deprives them of the benefits of new knowledge
p.000069: derived from these studies. It is also an affront to their right to self- determination. Although women of
p.000069: child-bearing age must be given the opportunity to participate in research, they must be informed that the research
...
Social / parents
Searching for indicator parent:
(return to top)
p.000063: 63
p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063: GUIDELINE 17:
p.000063: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS
p.000063:
p.000063: Children and adolescents must be included in health-related research unless a good scientific reason justifies their
p.000063: exclusion. As children and adolescents have distinctive physiologies and health needs, they merit special
p.000063: consideration by researchers and research ethics committees. However, their distinctive physiologies and
p.000063: emotional development may also place children and adolescents at increased risk of being harmed in the conduct of
p.000063: research. Moreover, without appropriate support, they may not be able to protect their own interests due to
p.000063: their evolving capacity to give informed consent. Specific protections to safeguard children’s rights and welfare in
p.000063: the research are therefore necessary.
p.000063:
p.000063: Before undertaking research involving children and adolescents, the researcher and the research ethics committee must
p.000063: ensure that:
p.000063: f a parent or a legally authorized representative of the child or adolescent has given permission; and
p.000063: f the agreement (assent) of the child or adolescent has been obtained in keeping with the child’s or adolescent’s
p.000063: capacity, after having been provided with adequate information about the research tailored to the child’s or
p.000063: adolescent’s level of maturity.
p.000063:
p.000063: If children reach the legal age of maturity during the research, their consent to continued participation should be
p.000063: obtained.
p.000063:
p.000063: In general, the refusal of a child or adolescent to participate or continue in the research must be respected,
p.000063: unless, in exceptional circumstances, research participation is considered the best medical option for a child or
p.000063: adolescent.
p.000063:
p.000063: For research interventions or procedures that have the potential to benefit children or adolescents, the
p.000063: risks must be minimized and outweighed by the prospect of potential individual benefit.
p.000063:
p.000063: For research interventions or procedures that have no potential individual benefits for participants, two
p.000063: conditions apply:
...
p.000066: decision respected.
p.000066:
p.000066: Deliberate objection. Some children and adolescents who are too immature to give assent may be able to register a
p.000066: “deliberate objection,” meaning an expression of disapproval or refusal of a proposed procedure. The deliberate
p.000066: objection of an older child or adolescent, for example, is to be distinguished from the behaviour of an
p.000066: infant likely to cry or withdraw in response to almost any adverse stimulus. A deliberate objection by
p.000066: a child or adolescent to taking part in research must be respected even if the parents have given permission,
p.000066: unless the child or adolescent needs treatment that is not available outside the context of research, the research
p.000066: intervention has a clear prospect of clinical benefit, and the treating physician and the legally authorized
p.000066: representative consider the research intervention to be the best available medical option for the given
p.000066: child or adolescent. In such cases, particularly if the child is very young or immature, a parent or guardian may
p.000066: override the child`s objections. However, in some situations parents may press a researcher to persist with an
p.000066: investigational intervention against the child`s wishes. Sometimes this pressure is meant to serve the parents’
p.000066: interests rather than the child’s. In this case, the parents’ decision must be overridden if the researcher believes it
p.000066: is not in the child’s best clinical interest to enrol or continue study participation.
p.000066:
p.000066: Permission of a parent or legally authorized representative. The researcher must obtain the permission of
p.000066: at least one parent or guardian in writing, consistent with applicable laws and regulations. The age at
p.000066: which a child becomes legally capable to give consent differs substantially from one jurisdiction to another.
p.000066: Often children who have not yet reached the legally established age of consent can understand the implications
p.000066: of research participation and go through standard informed consent procedures; however, legally they can only assent to
p.000066: serve as research participants. Independent of its quality, assent is never sufficient to permit participation in
p.000066: research unless it is supplemented by the permission of a parent, legal guardian or other duly authorized
p.000066: representative. The decision to continue or discontinue participation by children or adolescents who become legally
p.000066: capable during the study trumps the decision of their parents or legal guardians.
p.000066:
p.000066: Waiver of parental permission. In certain circumstances, research ethics committees may waive parental permission. In
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
p.000066:
p.000066: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000067: 67
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
p.000067: psychological and medical support for the participating children and adolescents is another special
p.000067: protection, though this may be difficult to realize in some communities. In such communities, the study
p.000067: personnel must be sufficiently qualified to help children and adolescents who need medical and psychological support.
p.000067:
p.000067: A research ethics committee may also allow a waiver of parental permission if the conditions set out in Guideline 10 –
p.000067: Modifications and waivers of informed consent - are satisfied.
p.000067:
p.000067: Observation of the study by a parent or guardian. A parent or legally appointed guardian who gives permission for a
p.000067: child or adolescent to participate in research must generally be given the opportunity, to a reasonable
p.000067: extent and without violating the privacy of other study participants, to observe the child’s participation as
p.000067: the study proceeds. This could enable the child to be withdrawn if the parent or guardian decides it is in the child’s
p.000067: best interests to do so.
p.000067:
p.000067: Emergency care situations in which the researcher anticipates that children and adolescents will participate. When
p.000067: children and adolescents participate in emergency care research, the principles of Guideline 16 – Research involving
p.000067: adults incapable of giving informed consent - apply.
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000068: 68
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: GUIDELINE 18:
p.000068: WOMEN AS RESEARCH PARTICIPANTS
p.000068:
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
...
p.000100: modalities, the parties involved in continued care and the organization responsible for paying for it, and for how long
p.000100: it will continue (Guideline 6);
p.000100:
p.000100: 29. For research on pregnant women, a plan, if appropriate, for monitoring the outcome of the pregnancy
p.000100: with regard to both the health of the woman and the short-term and long-term health of the child (Guideline 19);
p.000100:
p.000100: 30. The means proposed to obtain individual informed consent and the procedure planned to communicate
p.000100: information to prospective participants, including the name and position of the person responsible for obtaining
p.000100: consent (Guideline 9);
p.000100:
p.000100: 31. When a prospective subject is not capable of informed consent, satisfactory assurance that permission will be
p.000100: obtained from a duly authorized person, or, in the case of a child who is sufficiently mature to
p.000100: understand the implications of informed consent but has not reached the legal age of consent, that knowing
p.000100: agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian or other duly
p.000100: authorized representative (Guidelines 16 and 17);
p.000100:
p.000100: 32. An account of any economic or other inducements or incentives to prospective participants to
p.000100: participate, such as offers of cash payments, gifts, or free services or facilities, and of any financial obligations
p.000100: assumed by the participants, such as payment for medical services;
p.000100:
p.000100: 33. Plans and procedures, and the persons responsible, for communicating to participants information arising from the
p.000100: study (on harm or benefit, for example), or from other research on the same topic, that could affect participants’
p.000100: willingness to continue in the study (Guideline 9);
p.000100:
p.000100: 34. Plans to inform participants about the results of the study;
p.000100:
p.000100: 35. The provisions for protecting the confidentiality of personal data, and respecting the privacy of persons,
p.000100: including the precautions that are in place to prevent disclosure of the results of a subject’s genetic
p.000100: tests to immediate family relatives without the consent of the subject (Guidelines 4, 11, 12 and 24);
p.000100:
p.000100: 36. Information about how the code, if any, for the persons’ identity is established, where it will be kept and when,
p.000100: how and by whom it can be broken in the event of an emergency (Guidelines 11 and 12);
p.000100:
p.000100: 37. Any foreseen further uses of personal data or biological materials (Guidelines 11 and 12);
p.000100:
...
p.000119: Informed consent ix, 2, 9, 10, 21, 25, 26, 33 - 39, 41 - 45, 47 - 52, 54, 56, 58, 61 - 65, 67 - 72, 75,
p.000119: 76, 78 - 80, 89, 96, 97, 100, 101, 103, 105
p.000119: Informed opt-out /opt-in 41, 44, 47, 49, 83
p.000119: In-kind 54
p.000119: Interventions 1 - 4, 9 - 12, 15 - 19, 21 - 23, 26, 30, 53, 55, 56, 61 - 63, 65, 66, 71 - 73, 75 - 81, 84,
p.000119: 88, 91, 100, 101, 104
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000120: 120
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
p.000120: Low-resource settings viii, ix, 3 - 5, 7, 17, 19, 22, 23, 26, 45, 47, 52, 75 - 77, 80, 89, 92
p.000120: M
p.000120: Management (of risks) 8, 42, 45, 48, 51, 85, 95 - 97
p.000120: Material Transfer Agreement 41, 45
p.000120: Minimal risk 9, 13, 15, 16, 18, 38, 62, 65, 66, 71, 72, 80, 88, 100
p.000120: Minor increase above minimal risk 13, 18
p.000120: Mitigation 11, 15, 76, 85, 95, 97
p.000120: Modification of informed consent 33, 37
p.000120: Money 54, 103
p.000120: Multi-centre research 87, 89
p.000120: O
p.000120: Observational ix, xii, 16, 53, 72, 78
p.000120: Online 27, 83 - 85, 106
p.000120: Opt-out/opt-in. See Informed opt-out/opt-in
p.000120: P
p.000120: Parent 65, 67, 68, 101
p.000120: Payment 54, 88, 101
p.000120: Permission 35, 38, 54, 58, 59, 61 - 63, 65, 67 - 71, 79, 80, 81, 83, 101
p.000120: Placebo 9, 15 - 19, 35, 78, 80
p.000120: Post-trial access. See Continued access
p.000120: Pregnant women 7, 8, 58, 70 - 73, 101
p.000120: Privacy 68, 83 - 85, 92, 93, 100, 101, 104, 106
p.000120: Procedures xi, 9 - 12, 15, 17, 19, 23, 26, 33 - 35, 37, 38, 42, 53 - 55, 59, 61, 62, 65 - 67, 71,
p.000120: 76 - 80, 87 - 90, 95, 97, 100 - 103
p.000120: Protocol 2, 12, 18, 23, 25, 35, 36, 43, 49, 55, 56, 58, 76, 83, 87 - 90, 92, 96, 99, 101, 102, 105
p.000120: Public accountability 11, 13, 29, 31, 51, 91
p.000120: Publication ii, 29, 31, 84, 91, 92, 95, 102
p.000120: R
p.000120: Registries 36, 38, 39, 47, 49, 51, 72, 91
p.000120: Rehabilitation 55, 104
p.000120: Reimbursement 53, 54
p.000120: Research ethics committee 2, 9, 10, 12, 15, 17, 18, 23, 25, 27, 33, 34 - 39, 41, 43 - 45, 47,
p.000120: 49 - 51, 53, 54, 56, 58, 61 - 63, 65, 68, 71, 73, 79, 85, 87 - 91, 95, 96, 98, 102, 103, 105
p.000120: Residual tissue 41, 43, 44
p.000120: Responsiveness 3, 4, 17, 19, 63, 75, 76
p.000120: Return of results 44, 45, 51
p.000120:
p.000120:
p.000120:
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000121: 121
p.000121:
p.000121: Risks 2, 5, 7 - 13, 15 - 19, 23, 26, 34 - 39, 41, 44, 47, 49, 50, 53, 54, 58, 59, 61 - 63, 65 - 67,
p.000121: 69 - 73, 75 - 77, 80, 81, 83 - 85, 88, 91, 92, 96, 100, 102, 104 - 106
...
Searching for indicator parents:
(return to top)
p.000066: (though not legally) equivalent to consent. In this situation, parental consent is ethically best
p.000066: considered as “co-consent” but legally, the adolescent’s agreement remains assent. If child or adolescent
p.000066: participants reach the legal age of majority according to applicable law and become capable of independent informed
p.000066: consent during the research, their written informed consent to continued participation must be sought and their
p.000066: decision respected.
p.000066:
p.000066: Deliberate objection. Some children and adolescents who are too immature to give assent may be able to register a
p.000066: “deliberate objection,” meaning an expression of disapproval or refusal of a proposed procedure. The deliberate
p.000066: objection of an older child or adolescent, for example, is to be distinguished from the behaviour of an
p.000066: infant likely to cry or withdraw in response to almost any adverse stimulus. A deliberate objection by
p.000066: a child or adolescent to taking part in research must be respected even if the parents have given permission,
p.000066: unless the child or adolescent needs treatment that is not available outside the context of research, the research
p.000066: intervention has a clear prospect of clinical benefit, and the treating physician and the legally authorized
p.000066: representative consider the research intervention to be the best available medical option for the given
p.000066: child or adolescent. In such cases, particularly if the child is very young or immature, a parent or guardian may
p.000066: override the child`s objections. However, in some situations parents may press a researcher to persist with an
p.000066: investigational intervention against the child`s wishes. Sometimes this pressure is meant to serve the parents’
p.000066: interests rather than the child’s. In this case, the parents’ decision must be overridden if the researcher believes it
p.000066: is not in the child’s best clinical interest to enrol or continue study participation.
p.000066:
p.000066: Permission of a parent or legally authorized representative. The researcher must obtain the permission of
p.000066: at least one parent or guardian in writing, consistent with applicable laws and regulations. The age at
p.000066: which a child becomes legally capable to give consent differs substantially from one jurisdiction to another.
p.000066: Often children who have not yet reached the legally established age of consent can understand the implications
p.000066: of research participation and go through standard informed consent procedures; however, legally they can only assent to
p.000066: serve as research participants. Independent of its quality, assent is never sufficient to permit participation in
p.000066: research unless it is supplemented by the permission of a parent, legal guardian or other duly authorized
p.000066: representative. The decision to continue or discontinue participation by children or adolescents who become legally
p.000066: capable during the study trumps the decision of their parents or legal guardians.
p.000066:
p.000066: Waiver of parental permission. In certain circumstances, research ethics committees may waive parental permission. In
p.000066: such cases, special protections must be devised to ensure that the best interests of these children or
p.000066: adolescents are being served. These circumstances might include cases in which permission of a parent is not
p.000066: feasible or is undesirable. In some jurisdictions, certain
p.000066:
p.000066:
p.000066: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000067: 67
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: individuals who are below the general age of consent are regarded as “emancipated” or “mature” minors and are
p.000067: authorized to consent without the agreement or even the awareness of their parents or guardians. They may be married,
p.000067: pregnant or be parents themselves, or they may live independently. In other cases, studies involve investigation of
p.000067: adolescents’ beliefs and behaviour regarding sexuality or use of recreational drugs. Research may also address domestic
p.000067: violence, sexually transmitted diseases, pregnancy, abortion, or child abuse. In these cases, parental knowledge of the
p.000067: topic of the research may place the children or adolescents at risk of questioning, intimidation, or even
p.000067: physical harm by their parents.
p.000067:
p.000067: In such cases, special protections to promote the best interests of these children or adolescents should include the
p.000067: involvement of independent child advocates. A child may also be asked to choose a relative, trusted friend, or family
p.000067: physician who is not involved in the research project who might then represent the child. Independent
p.000067: psychological and medical support for the participating children and adolescents is another special
p.000067: protection, though this may be difficult to realize in some communities. In such communities, the study
p.000067: personnel must be sufficiently qualified to help children and adolescents who need medical and psychological support.
p.000067:
p.000067: A research ethics committee may also allow a waiver of parental permission if the conditions set out in Guideline 10 –
p.000067: Modifications and waivers of informed consent - are satisfied.
p.000067:
p.000067: Observation of the study by a parent or guardian. A parent or legally appointed guardian who gives permission for a
...
p.000079: When health care workers are the subjects, the refusal of some workers to be observed or to apply a new diagnostic or
p.000079: therapeutic tool could confound the results of the research. Researchers would not be able to tell whether a new
p.000079: intervention is sufficiently effective if some health care workers refuse to participate and employ their usual
p.000079: procedures. A waiver of consent would then be an option (see Guideline 4 – Potential individual benefits and risks of
p.000079: research), but health care workers must nevertheless be notified that a study is taking place. If the
p.000079: interventions are directly carried out on patients, they would normally also be considered research subjects and their
p.000079: consent to receive the intervention would be required.
p.000079:
p.000079: Although in many CRTs participants cannot consent to being randomized, depending on the type of study design they may
p.000079: be able to give informed consent to receive the intervention. The intervention may be delivered at the individual level
p.000079: while the communities to which the individuals belong are randomized at the cluster level (for example, a vaccination
p.000079: campaign applied at the school level). These trials are called individual-cluster randomized trials. In some
p.000079: individual-cluster randomized trials, individuals may be able to consent to the intervention before it is administered
p.000079: in that cluster. For example, parents will not be able to consent to their children’s school being randomized to a
p.000079: vaccination programme or to being allocated to that cluster, but they could consent or refuse to consent to their
p.000079: child’s vaccination at school. In other CRTs, both the intervention and the community are randomized at the cluster
p.000079: level. These trials are called cluster-cluster randomized trials (for example, all the students in a school or
p.000079: all residents of a community). In cluster-cluster randomized trials, individual informed consent for receiving the
p.000079: intervention is typically difficult to obtain since it is almost impossible to avoid the intervention. At the same
p.000079: time, individual consent for data collection procedures is usually possible in both types of cluster randomized trials.
p.000079:
p.000079: Ethical acceptability of a no-intervention group. Some CRTs investigate interventions that have been proven
p.000079: to be effective elsewhere; this is termed implementation research. This type of research is often conducted in
p.000079: low-resource settings. An ethical question pertaining to this type of study is whether it is acceptable
p.000079: to withhold the proven intervention from a control group in a CRT. This situation is analogous to that of
p.000079: placebo controls in a randomized, controlled trial when an established, effective prevention or treatment exists. If
...
Social / philosophical differences/differences of opinion
Searching for indicator opinion:
(return to top)
p.000017: method. Others argue that a superiority design using a placebo can be acceptable.
p.000017:
p.000017: The use of placebo controls in these situations is ethically controversial for several reasons:
p.000017: 1. Researchers and sponsors knowingly withhold an established effective intervention from participants in the control
p.000017: arm. However, when researchers and sponsors are in a position to provide an intervention that would
p.000017: prevent or treat a serious disease, it is difficult to see why they are under no obligation to provide it. They could
p.000017: design the trial as an equivalency trial to determine whether the experimental intervention is as good or almost as
p.000017: good as the established effective intervention.
p.000017:
p.000017:
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p.000018:
p.000018:
p.000018:
p.000018:
p.000018:
p.000018: 2. Some argue that it is not necessary to conduct clinical trials in populations in low-resource settings in order to
p.000018: develop affordable interventions that are substandard compared to the available interventions in other
p.000018: countries. Instead, they argue that drug prices for established treatments should be negotiated and increased funding
p.000018: from international agencies should be sought.
p.000018:
p.000018: When controversial, placebo-controlled trials are planned, research ethics committees in the host country must:
p.000018: 1. seek expert opinion, if not available within the committee, as to whether use of placebo may lead to
p.000018: results that are responsive to the needs or priorities of the host country (see Guideline 2
p.000018: – Research conducted in low-resource settings); and
p.000018:
p.000018: 2. ascertain whether arrangements have been made for the transition to care after research for study
p.000018: participants (see Guideline 6 – Caring for participants’ health needs), including post-trial arrangements
p.000018: for implementing any positive trial results, taking into consideration the regulatory and health care policy framework
p.000018: in the country.
p.000018:
p.000018: Comparative effectiveness and standard of care trials. For many conditions and diseases, one or more
p.000018: established effective treatments exist. Physicians and hospitals may then use different treatments for the same
p.000018: condition. Yet often the relative merits of these treatments are unknown. Comparative effectiveness research, as well
p.000018: as systematic reviews, have received growing attention over the past few years. In comparative effectiveness research,
p.000018: two or more interventions regarded as standards of care are directly compared. Comparative effectiveness
p.000018: research may help to determine which standard of care has better outcomes or more acceptable risks. Research ethics
p.000018: committees should carefully distinguish between marketing studies that aim to position a product (sometimes called
p.000018: seeding trials) and comparative effectiveness studies in which scientific and public health perspectives are the
...
Searching for indicator philosophy:
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p.000119: the Universal Declaration on Bioethics and Human Rights of UNESCO (2005), the UNAIDS/WHO Ethical
p.000119: Considerations in Biomedical HIV Prevention Trials (2007/2012), Standards and operational guidance for
p.000119: ethics review of health-related research with human participants of the WHO (2011), and the Declaration of Helsinki of
p.000119: the World Medical Association (2013). Some of these guidelines have been extensively used, in particular the UNAIDS/WHO
p.000119: document (2012) for Guideline 7 on community engagement.
p.000119:
p.000119: Textbooks, existing ethical frameworks for human subjects research and reports on research involving human beings
p.000119: were also valuable sources of information. The Working Group reviewed papers in major ethics journals (in
p.000119: alphabetical order) such as the American Journal of Bioethics, Bioethics, BMC Medical Ethics, the Cambridge
p.000119: Quarterly of Healthcare Ethics, Developing World Bioethics, the Hastings Center Report, the Journal of Bioethical
p.000119: Inquiry, the Journal of Empirical Research on Human Research Ethics, the Journal of Law, Medicine and Ethics,
p.000119: the Journal of Medical Ethics, the Journal of Medicine and Philosophy, Medicine, Health Care and Philosophy, as
p.000119: well as articles in leading medical or scientific journals, such as BMJ, The Lancet, the New England
p.000119: Journal of Medicine and Science.
p.000119:
p.000119: Literature reviews were used in three ways. First, we searched main ethical guidelines on research with humans and
p.000119: textbooks on research ethics to identify new topics or viewpoints in existing debates. For instance, many guidelines
p.000119: have included statements on biobanking which was one of the reasons to merge the CIOMS guidelines for epidemiological
p.000119: research with those for biomedical research.
p.000119:
p.000119: We performed searches in Embase and Medline on review papers and papers with strong positions on certain topics. For
p.000119: example, component analysis and the net risk test are two recent approaches to making risk-benefit assessments. There
p.000119: is no agreement among bioethicists on which of these approaches is preferable. The Working Group read relevant papers
p.000119: on these approaches and developed a middle ground. A similar process was adopted for vulnerability. A consensus emerged
p.000119: in recent publications that vulnerability can no longer be applied to entire groups. As a result, the
p.000119: Working Group eliminated the group approach. Instead, the Guidelines focus on characteristics that lead to considering
p.000119: certain groups as vulnerable and on the specific protections that are needed in those situations.
p.000119:
...
p.000106: abroad. He is on the Editorial Board of ‘Public Health Ethics’ (www.phe.oxfordjournals.org),
p.000106:
p.000106:
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p.000107:
p.000107:
p.000107:
p.000107:
p.000107:
p.000107: a quarterly journal of Oxford University Press and also serves on the International Advisory Board of the Asian
p.000107: Bioethics Review (http://www.asianbioethicsreview.com). He is also a member of the Ethics Working Group of the US
p.000107: NIH‐funded HIV Prevention Trials Network (http://www.hptn.org/hptnresearchethics.htm). He currently is a member of four
p.000107: ethics committees in India (in two of which he also serves as the chairperson), and has been as a reviewer for multiple
p.000107: journals, conference scientific committees and international grant competitions. Anant is also a member of
p.000107: the Steering Committee of the Global Forum on Bioethics in Research. He is also a member of the Board of
p.000107: the International Association of Bioethics.
p.000107:
p.000107: Eugenijus Gefenas
p.000107: Eugenijus Gefenas is a professor and director of the Department of Medical History and Ethics at the Medical Faculty of
p.000107: Vilnius University. He is also a director of the Lithuanian Bioethics Committee. Eugenijus Gefenas graduated from the
p.000107: Medical Faculty of Vilnius University in 1983 and obtained his PhD in medical ethics from the Institute of Philosophy,
p.000107: Sociology and Law in 1993. E. Gefenas teaches bioethics at the Medical Faculty of Vilnius University and
p.000107: together with colleagues from Clarkson University (USA) co-directs the Advanced Certificate Program in Research
p.000107: Ethics in Central and Eastern Europe. E. Gefenas is a member of the Council of Europe Committee on
p.000107: Bioethics; he was the chair of this Committee from 2011–2012. He was elected as the chairman of the
p.000107: Intergovernmental Bioethics Committee (IGBC) of UNESCO in 2015. The areas of his professional interest include
p.000107: ethical and policy-making issues related to human research and health care in transition societies.
p.000107:
p.000107: Dirceu Greco
p.000107: Dirceu Greco is full professor of Infectious Diseases and Bioethics at the School of Medicine, Federal University of
p.000107: Minas Gerais (UFMG), Belo Horizonte, Brazil. He received his MD degree and this PhD from UFMG. Chief, Infectious and
p.000107: Parasitic Diseases Service (2009-2011), Coordinator of UFMG University Hospital Centre for Clinical Research
p.000107: (2005-2010), member (2007-2010), Brazilian Research Ethics Commission (CONEP); member, Brazilian AIDS Commission
p.000107: (Ministry of Health-MoH). Main topics of interest include Infectious and Parasitic Illnesses, bioethics, public health
p.000107: and clinical immunology. He has participated in several working groups that gave rise to
p.000107: national/international guidelines related to ethics, prevention, care and treatment of HIV/AIDS and TB. He has
...
p.000107: since 1986.
p.000107:
p.000107: Bocar Kouyaté
p.000107: Bocar A. Kouyaté is Senior Advisor to the Minister of Health, Burkina Faso and researcher at the Centre national de
p.000107: recherché et de formation sur le paludisme (CNRFP), Burkina Faso. Dr Kouyaté is a physician by training and holds
p.000107: a PhD degree in public health. He has worked throughout all levels of the health system in Burkina Faso from
p.000107: district medical officer to the intermediary level as
p.000107:
p.000107:
p.000107:
p.000107:
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p.000108:
p.000108:
p.000108:
p.000108:
p.000108:
p.000108: Provincial Director of Health and to Secretary General of the Ministry of Health from 1983 to 1998. From 1989 to 2009,
p.000108: he was Director of two research centres in Burkina Faso (Centre de recherche en santé de Nouna and, later on, Centre
p.000108: national de recherche et de formation sur le paludisme). He served as member of the Comité national d’éthique
p.000108: pour la recherche en santé (CERS) from 2003–2007 and was the Chair of the CERS from 2008–2013. He has
p.000108: considerable experience in research, research administration, capacity development and training, particularly in health
p.000108: systems, research ethics and malaria. His special interest is in the development of sustainable capacity and
p.000108: appropriate environment for research and getting research into policy and practice.
p.000108:
p.000108: Alex London
p.000108: Alex John London, PhD., is Professor of Philosophy and Director of The Center for Ethics and Policy at Carnegie Mellon
p.000108: University. An elected fellow of the Hastings Center, he has written extensively on problems in bioethics and
p.000108: ethical theory relating to uncertainty, risk, fairness, equality and justice. He is co-editor of Ethical Issues
p.000108: in Modern Medicine, one of the most widely used textbooks in medical ethics and recipient of the Elliott Dunlap
p.000108: Smith Award for Distinguished Teaching and Educational Service in the Dietrich College of Humanities and Social
p.000108: Sciences at Carnegie Mellon University. In 2016 Professor London was appointed to the U.S. National Academies of
p.000108: Sciences, Engineering and Medicine (formerly the Institute of Medicine) Committee on Clinical Trials During
p.000108: the 2014–2015 Ebola Outbreak. Since 2007 he has served as a member of the Ethics Working Group of the
p.000108: HIV Prevention Trials Network. He has served as an ethics expert in consultations with numerous national and
p.000108: international organizations including the U.S. National Institutes of Health, the World Health Organization,
p.000108: the World Medical Association and the World Bank.
p.000108:
p.000108: Ruth Macklin
p.000108: Ruth Macklin is Distinguished University Professor Emerita (Bioethics) in the Department of Epidemiology and Population
p.000108: Health at Albert Einstein College of Medicine in the Bronx, New York, USA. She has more than two hundred and
p.000108: seventy publications in professional journals and scholarly books in bioethics, law, medicine, philosophy, and
p.000108: the social sciences, in addition to articles in magazines and newspapers for general audiences. She is author or editor
p.000108: of thirteen books, including Mortal Choices (1988), Against Relativism (1999) and Double Standards in Medical Research
p.000108: in Developing Countries (2004). Dr Macklin is an elected member of the U.S. National Academy of Medicine and was
p.000108: president of the International Association of Bioethics from 1999–2001. She has served as consultant or
p.000108: adviser to the World Health Organization and UNAIDS, and chaired the external ethics committee of the Centers for
p.000108: Disease Control and Prevention from 2005 to 2008.
p.000108:
p.000108: Annette Rid
p.000108: Annette Rid is a Senior Lecturer in Bioethics and Society in the Department of Global Health & Social Medicine, King’s
p.000108: College London, and an Elected Fellow of the Hastings Center. Trained in medicine, philosophy and bioethics in Germany,
p.000108: Switzerland and the United States, Annette’s research interests span research ethics, clinical ethics and justice
p.000108: in health and health care. Annette has published widely in medical journals (e.g. Lancet, JAMA) and bioethics
p.000108: journals (e.g. Journal of Medical Ethics, Bioethics). She has served as an advisor, among others, for the World Health
p.000108: Organization and the World Medical Association, and sits on numerous scientific and advisory boards. At King’s, Annette
p.000108: has led the new Masters in Bioethics & Society as one of its inaugural co-directors.
p.000108:
p.000108: Rodolfo Saracci
p.000108: Rodolfo Saracci qualified as an MD and holds specialist degrees in internal medicine and in medical statistics. He is a
p.000108: Fellow of the UK Faculty of Public Health. His career as a research epidemiologist in the field of chronic
p.000108: diseases, particularly cancer, has been principally developed at the WHO International Agency for Research on
p.000108: Cancer (IARC) in Lyon as a staff member and Chief of the Unit of Analytical Epidemiology. From 1982 to 2005 he chaired
p.000108: the Ethics Review Committee of IARC and has taken an active part in the CIOMS projects in biomedical ethics as a member
p.000108: of the drafting
p.000108:
p.000108:
p.000108:
p.000108:
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p.000109: 109
p.000109:
p.000109:
p.000109:
p.000109:
...
p.000109: legal status for the National Bioethics Committees, drafting the first national guidelines for Research Ethics
p.000109: Committees and Clinical Bioethics Committees, training their members, and promoting the law at the parliament that is
p.000109: currently in force, to legally establish and differentiate both types of committees. She is the founder of FLACEIS
p.000109: (Latin American Forum of Ethics Committees in Health Research) and was the Chairperson (2000–2006). Invited member of
p.000109: the international expert group, TDR-WHO: Drafting and translating Operational Guidelines for Ethics Committees. She was
p.000109: Mexico´s representative at the meetings of the Intergovernmental Bioethics Committee to discuss the UNESCO Universal
p.000109: Declaration on Bioethics and Human Rights. Since September 2009, Dafna Feinholz is the Chief of the Bioethics Section,
p.000109: within UNESCO Social and Human Science Sector. In this capacity, she leads different activities aiming at reinforcing
p.000109: capacities of Member States to manage bioethical
p.000109:
p.000109:
p.000109:
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p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
p.000110: challenges and to identify the ethical, legal and social implications of cutting-edge science, emerging technologies
p.000110: and their application for sustainable development.
p.000110:
p.000110: Urban Wiesing, World Medical Association
p.000110: Born 1958 in Ahlen/Westf, studied medicine, philosophy, sociology and history of medicine in Muenster and
p.000110: Berlin. Dr. med. 1987, Dr. phil. 1995, 1985-1988 Physician in anaesthesiology and internal medicine. 1988–1998
p.000110: assistant at the Institute of Theory and History of Medicine at the University of Muenster. “Habilitation”
p.000110: and lecturer for theory and history of medicine in 1993. Since 1998 Professor and Chair of Medical Ethics at the
p.000110: University of Tuebingen. Director of the Institute of History of Medicine at the University of Tuebingen. 2004-2013
p.000110: Chair of the Central Ethics-Committee of the Federal Board of Physicians.
p.000110:
p.000110: Hans-Joerg Ehni (Alternate), World Medical Association
p.000110: Hans-Joerg Ehni is the deputy director of the Institute for the Ethics and History of Medicine,
p.000110: University of Tuebingen, with a background in philosophy. His research is focused on the ethics of biomedical research
p.000110: involving human subjects and on the ethics of aging, particularly on the ethics of new biomedical interventions
p.000110: into the ageing process and increased longevity and on policies promoting healthy ageing. He is a member of
p.000110: the Research Ethics Committee of the Federal Board of Physicians, Baden-Württemberg.
p.000110:
p.000110: Carel IJsselmuiden, Council on Health Research for Development (COHRED)
p.000110: Carel is a physician, epidemiologist, public health practitioner, academic and social entrepreneur, with
p.000110: qualifications from universities in Belgium, Netherlands, South Africa and the United States. He spent 7
p.000110: years in rural medicine and public health, 4 years in peri-urban and urban health care, HIV/AIDS control and
p.000110: environmental services management as Deputy Medical Officer of Health for Johannesburg, South Africa. He
p.000110: was appointed as Professor and Head of Department of the department of community health at the University of
p.000110: Pretoria in 1995, where he became the founding Director of the School of Health Systems and Public Health in 1999. He
p.000110: held this position until his appointment as Executive Director at COHRED in 2004. As such, he is also member of the
p.000110: COHRED Board, President of COHRED USA and board member of COHRED Africa. He has published widely in applied research,
...
Social / sex worker
Searching for indicator prostitution:
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p.000010: research can pose risks to participants, especially when adequate safeguards to protect confidentiality are not in
p.000010: place.
p.000010:
p.000010: Risks to research participants. To evaluate the acceptability of risks in a given study, researchers, sponsors and
p.000010: research ethics committees must begin by ensuring that the study poses a socially valuable research question and
p.000010: employs sound scientific methods for addressing this question. They must then determine for each
p.000010: intervention and procedure in the study that the associated risks to participants are minimized and that
p.000010: mitigation procedures are in place. This can involve ensuring that plans and procedures exist to adequately
p.000010: manage and reduce risks, for example by:
p.000010: f monitoring the study and providing mechanisms for responding to adverse events;
p.000010: f establishing a Data Safety and Monitoring Committee (DSMC) to review and decide on data on harms and benefits as a
p.000010: study progresses;
p.000010: f instituting clear criteria for stopping a study;
p.000010: f installing safeguards to protect the confidentiality of sensitive personal data;
p.000010: f seeking exemptions, where possible, from requirements to report information about illegal activities of study
p.000010: participants (such as sex work in countries where prostitution is forbidden by law);
p.000010: f avoiding unnecessary procedures (for example, by performing laboratory tests on existing blood samples instead of
p.000010: drawing new blood, where scientifically appropriate); and
p.000010: f excluding participants who are at a significantly increased risk of being harmed from an intervention
p.000010: or procedure.
p.000010:
p.000010: Measures to minimize risks need to be carefully balanced with competing considerations regarding the scientific and
p.000010: value of research and fair subject selection. For example, decisions to stop a trial due to early,
p.000010: significant findings have to be balanced with the need to collect robust data on investigational interventions that are
p.000010: adequate to guide clinical practice.
p.000010:
p.000010: Researchers, sponsors and research ethics committees must then ensure that the risks of each intervention
p.000010: and procedure, once minimized, are appropriately balanced in relation to the intervention’s prospect of benefit for the
p.000010: individual participant and the social and scientific value of the research. For interventions that have a prospect of
p.000010: potential individual benefit, risks are acceptable if they are outweighed by the potential individual benefits for the
p.000010: individual participant and the intervention’s risk- benefit profile is at least as advantageous as any established
p.000010: effective alternative. Participants in the
p.000010:
p.000010: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
...
Searching for indicator sex work:
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p.000010: benefits need to be carefully balanced with competing considerations. For example, sharing data or specimens for future
p.000010: research can pose risks to participants, especially when adequate safeguards to protect confidentiality are not in
p.000010: place.
p.000010:
p.000010: Risks to research participants. To evaluate the acceptability of risks in a given study, researchers, sponsors and
p.000010: research ethics committees must begin by ensuring that the study poses a socially valuable research question and
p.000010: employs sound scientific methods for addressing this question. They must then determine for each
p.000010: intervention and procedure in the study that the associated risks to participants are minimized and that
p.000010: mitigation procedures are in place. This can involve ensuring that plans and procedures exist to adequately
p.000010: manage and reduce risks, for example by:
p.000010: f monitoring the study and providing mechanisms for responding to adverse events;
p.000010: f establishing a Data Safety and Monitoring Committee (DSMC) to review and decide on data on harms and benefits as a
p.000010: study progresses;
p.000010: f instituting clear criteria for stopping a study;
p.000010: f installing safeguards to protect the confidentiality of sensitive personal data;
p.000010: f seeking exemptions, where possible, from requirements to report information about illegal activities of study
p.000010: participants (such as sex work in countries where prostitution is forbidden by law);
p.000010: f avoiding unnecessary procedures (for example, by performing laboratory tests on existing blood samples instead of
p.000010: drawing new blood, where scientifically appropriate); and
p.000010: f excluding participants who are at a significantly increased risk of being harmed from an intervention
p.000010: or procedure.
p.000010:
p.000010: Measures to minimize risks need to be carefully balanced with competing considerations regarding the scientific and
p.000010: value of research and fair subject selection. For example, decisions to stop a trial due to early,
p.000010: significant findings have to be balanced with the need to collect robust data on investigational interventions that are
p.000010: adequate to guide clinical practice.
p.000010:
p.000010: Researchers, sponsors and research ethics committees must then ensure that the risks of each intervention
p.000010: and procedure, once minimized, are appropriately balanced in relation to the intervention’s prospect of benefit for the
p.000010: individual participant and the social and scientific value of the research. For interventions that have a prospect of
p.000010: potential individual benefit, risks are acceptable if they are outweighed by the potential individual benefits for the
p.000010: individual participant and the intervention’s risk- benefit profile is at least as advantageous as any established
p.000010: effective alternative. Participants in the
p.000010:
p.000010: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000011: 11
...
Searching for indicator sex workers:
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p.000057: informed consent, section on Dependent relationship).
p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
p.000057: committee when such proposals are under review (see commentary on Guideline 9 – Individuals capable of giving informed
p.000057: consent, section on Dependent relationship). Some individuals with this characteristic may also have diminished
p.000057: capacity to consent, and therefore require the additional protections noted earlier for participants who lack
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
...
p.000068: research, in many societies women remain socially vulnerable in the conduct of research. For example, they may
p.000068: suffer negligence or harm because of their submission to authority, their hesitancy or inability to ask
p.000068: questions, and a cultural tendency to deny or tolerate pain and suffering. When women in these situations are potential
p.000068: participants in research, researchers, sponsors and ethics committees must take special care in the research design,
p.000068: assessment of risks and benefits, as well as the process of informed consent, to ensure that women have
p.000068: the necessary time and appropriate environment to make decisions based on information provided to them.
p.000068:
p.000068: Some women become vulnerable in research because of heightened psychological, social, physical, or legal risks.
p.000068: Examples include surveys and interviews regarding intimate partner violence and rape; social and behavioural
p.000068: research involving sex workers or women who inject drugs; and studies that solicit information about sexual behaviour.
p.000068: When the research involves household surveys or interviews, researchers must take special care to ensure that the women
p.000068: are interviewed in a private
p.000068:
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p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
p.000069: place without the possibility of intrusion by other family members. In such studies, women must be given
p.000069: the option of conducting the interview in a setting of their choosing outside the home. Breach of
p.000069: confidentiality in these types of research could result in serious harms to women, even if the only information
p.000069: disclosed is their participation in the research. In studies involving women who have experienced gender-based
p.000069: violence, participation in interviews may cause emotional distress. Researchers must be prepared with referrals for
p.000069: psychological counselling if the need arises.
p.000069:
p.000069: Informed consent and authorization. In some cultures, spouses or community leaders typically grant permission to invite
...
Economic / Economic/Poverty
Searching for indicator poor:
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p.000119: epidemiological studies should be updated. Intending to ensure that ethical principles are consistently applied to all
p.000119: types of research, the core group decided to prepare a Supplement to the 2002 document that would address the special
p.000119: features of epidemiological studies. In February 2006, a draft of the supplement was posted on the CIOMS website and
p.000119: opened to comment from interested parties. The response from groups and individuals involved in biomedical research was
p.000119: largely positive, but many objected that epidemiologists were not necessarily conversant with the 2002 Guidelines and
p.000119: would therefore find it burdensome to have to switch back and forth between the epidemiology supplement and the
p.000119: biomedical research document. Eventually, therefore, the final version of the Guidelines (2009) combined both
p.000119: documents.
p.000119:
p.000119: The fourth version of the CIOMS Guidelines (2016)
p.000119: During its annual meeting in 2009 the Executive Committee of CIOMS considered the desirability of a revision of the
p.000119: CIOMS Ethical Guidelines for Biomedical Research. Since 2002 several developments had taken place including: a
p.000119: heightened emphasis on the importance of translational research, a felt need to clarify what counts as fair research in
p.000119: low-resource settings, more emphasis on community engagement in research, the awareness that exclusion of
p.000119: potentially vulnerable groups in many cases has resulted in a poor evidence base, and the increase of big data
p.000119: research. Moreover the Declaration of Helsinki of 2008 was revised again at that moment. The Executive Committee
p.000119: therefore decided to first explore the desirability of such a revision.
p.000119:
p.000119: The revision process of the 2002 version
p.000119: In 2011, the CIOMS Executive Committee decided to set up a Working Group to revise the CIOMS Guidelines
p.000119: and fund the work from internal means. This Group met three times each year from September 2012 until September
p.000119: 2015. Virtually all Guidelines underwent major revisions. Some Guidelines were merged (for example, 2002
p.000119: Guidelines 4 and 6 both dealt with informed consent), and others were newly created (for example,
p.000119: Guideline 20 on research in disaster and disease outbreaks). Furthermore, the Working Group decided to merge the
p.000119: CIOMS Guidelines for Biomedical Research with the CIOMS Guidelines for Epidemiological Research. At the same time, in
p.000119: order to ensure the epidemiological dimension, an epidemiologist, who was also a member of the Working Group, closely
p.000119: read the revisions from an epidemiological perspective.
p.000119:
p.000119: Scope of the 2016 version
p.000119: The Working Group decided to broaden the scope of the 2002 Guidelines from “biomedical research” to “health-related
p.000119: research”. The Working Group considered biomedical research too narrow since that term would not cover research with
...
p.000003: community about the form such dissemination
p.000003:
p.000003:
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p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: should take. One example might be a study that learns why a health condition such as neural tube defects is prevalent
p.000004: in a particular population. Another example could be a study that results in knowledge to educate the
p.000004: population about foods to eat or avoid in order to promote or maintain health.
p.000004:
p.000004: These requirements for post-trial availability to communities and populations must not be construed as precluding
p.000004: studies designed to evaluate novel therapeutic concepts. An example might be research designed to obtain
p.000004: preliminary evidence that a drug or a class of drugs is beneficial in treating a disease that occurs only
p.000004: in low-resource settings, when the research could not be carried out reasonably well in more developed
p.000004: communities. Such preliminary research may be justified ethically even if there will not be a specific product
p.000004: that could be made available to the population of the host country or community at the conclusion of the
p.000004: preliminary phase of its development. If the concept is found to be valid, subsequent phases of the research could
p.000004: result in a product that would be made reasonably available at its conclusion.
p.000004:
p.000004: Additional benefits to the population or community. Benefits other than those associated with study
p.000004: participation may accrue to the community or population, especially in resource-poor settings. Such benefits
p.000004: can include improving the health infrastructure, training laboratory personnel, and educating the public about the
p.000004: nature of research and the benefits resulting from a particular study. Whereas capacity-building should be a part of
p.000004: any research conducted in low-resource settings, other types of benefits will depend on the circumstances of the
p.000004: research and environment in which it is carried out. These additional benefits must be determined in consultation with
p.000004: the communities or the local population. Additional benefits may also include contributions that research or research
p.000004: partnerships make to the overall scientific environment of such countries and communities.
p.000004:
p.000004: Community engagement. From the inception of research planning, it is important to ensure full participation of
p.000004: communities in all steps of the project, including discussions of the relevance of the research for the
p.000004: community, its risks and potential individual benefits, and how any successful products and possible financial gain
p.000004: will be distributed, for example through a benefit-sharing agreement. This consultation should be an open,
p.000004: collaborative process that involves a wide variety of participants, including community advisory boards, community
p.000004: representatives, and members of the population from which research participants will be recruited. Research ethics
p.000004: committees should require community members to disclose any conflicts of interests (see Guideline 25 – Conflicts of
p.000004: interest). Active community involvement helps to ensure the ethical and scientific quality and successful completion of
...
p.000007: were excluded from participation in research because it was considered the most expedient way of protecting
p.000007: those groups (for example, children, women of reproductive age, pregnant women). As a consequence of such exclusions,
p.000007: information about the diagnosis, prevention and treatment of diseases that afflict such groups is limited. This has
p.000007: resulted in a serious injustice. Since information about the management of diseases is considered a benefit to society,
p.000007: it is unjust to intentionally deprive specific groups of that benefit. The need to redress these injustices by
p.000007: encouraging the participation of previously excluded groups in basic and applied biomedical research is widely
p.000007: recognized.
p.000007:
p.000007: Fair distribution of research burdens. Research with human participants typically requires that some persons or
p.000007: groups are exposed to risks and burdens in order to generate the knowledge needed to protect and promote
p.000007: people’s health (see Guideline 1 – Scientific and social value and respect for rights). Equity in the distribution of
p.000007: burdens of research requires special care to ensure that individuals, communities or populations that are already
p.000007: disadvantaged or marginalized are not over-represented in research. A disproportionate selection of disadvantaged or
p.000007: convenient populations is morally problematic for several reasons. First, it is unjust to selectively invite poor or
p.000007: marginalized individuals or groups to participate in research because this concentrates the risks and burdens of
p.000007: research on people who already experience increased risks and burdens from social and economic disadvantage. Second,
p.000007: these individuals and groups are also the most likely to be excluded from, or to have difficulty accessing, the
p.000007: benefits of research. Third, the broad inclusion of different social groups helps to ensure that research is conducted
p.000007: in a socially and ethically acceptable manner. When research is concentrated in disadvantaged or marginalized groups,
p.000007: it may be easier to expose participants to unreasonable risks or undignified treatment. Furthermore, research results
p.000007: obtained from disadvantaged populations may not be appropriately extrapolated to the general population.
p.000007:
p.000007: In the past, certain groups have been over-used as research subjects. In some cases, this has been based on the easy
p.000007: availability of the populations. For example, in the United States prisoners were considered ideal persons for Phase I
p.000007: drug studies in the past. Other populations that may be over- represented in research because of their easy
p.000007: availability include students in researchers’ classes, residents of long-term care facilities and subordinate members
p.000007: of hierarchical organizations. In other cases, impoverished groups have been over-used because of their willingness to
p.000007: serve as subjects in exchange for relatively small stipends, their desire to access medical care, or because research
p.000007: hospitals are often located in places where members of the lowest socio-economic classes reside.
p.000007:
...
p.000011: performance of routine physical or psychological examinations or tests. The purpose of these comparisons is to
p.000011: determine the level of acceptable research risk by analogy with the risks of activities in other areas of life: when
p.000011: the risks of an activity are considered acceptable for the population in question, and the activity is relatively
p.000011: similar to participating in research, then the same level of risk should be considered acceptable in the
p.000011: research context. These comparisons typically imply that research risks are minimal when the risk of serious harm is
p.000011: very unlikely and the potential harms associated with more common adverse events are small.
p.000011:
p.000011: One difficulty with these risk comparisons, however, is that different populations can experience dramatic differences
p.000011: in the risks of daily life or in routine clinical examinations and testing. Such differences in background risk can
p.000011: stem from inequalities in health, wealth, social status, or social determinants of health. Therefore, research ethics
p.000011: committees must be careful not to make such comparisons in ways that permit participants or groups of participants from
p.000011: being exposed to greater risks in research merely because they are poor, members of disadvantaged groups or
p.000011: because their environment exposes them to greater risks in their daily lives (for example, poor road safety).
p.000011: Research ethics committees must be similarly vigilant about not permitting greater research risks in
p.000011: populations of patients who routinely undergo risky treatments or diagnostic procedures (for example, cancer patients).
p.000011: Rather, risks in research must be compared to risks that an average, normal, healthy individual
p.000011: experiences in daily life or during routine examinations. Furthermore, risk comparisons must not be made to
p.000011: activities that pose unacceptable risks themselves, or in which people choose to participate because of the associated
p.000011: benefits (some sporting activities, for example, are thrilling precisely because they involve an elevated risk of
p.000011: harm).
p.000011:
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p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: When the risks of a research procedure are judged to be minimal, there is no requirement for special protective
p.000012: measures apart from those generally required for all research involving members of the particular class of persons.
p.000012:
p.000012: Minor increase above minimal risk. While there is no precise definition of a “minor increase” above
...
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
p.000057: care (see Guideline 18 – Women as research participants).
p.000057:
p.000057: Pregnant women. Pregnant women must not be considered vulnerable simply because they are pregnant. Specific
p.000057: circumstances, such as risks to the fetus, may require special protections, as set out in Guideline 19 – Pregnant women
p.000057: and breastfeeding women as research participants.
p.000057:
p.000057: Other potentially vulnerable individuals. Among members of groups that have traditionally been considered vulnerable,
p.000057: the following are frequently mentioned: people receiving welfare benefits or social assistance and other poor people
p.000057: and the unemployed; people who perceive participation as the only means of accessing medical care; some ethnic and
p.000057: racial minorities; homeless persons, nomads, refugees or displaced persons; people living with disabilities;
p.000057: people with incurable or stigmatized conditions or diseases; people faced with physical frailty, for example because
p.000057: of age and co-morbidities, individuals who are politically powerless; and members of communities unfamiliar with
p.000057: modern medical concepts. Furthermore, in some contexts vulnerability might be related to gender, sexuality
p.000057: and age.
p.000057:
p.000057: To the extent that these and other people have one or more of the characteristics discussed above,
p.000057: research ethics committees must review the need for special protection of their rights and welfare, and
p.000057: include such protections when necessary. However, researchers and research ethics committees must avoid making
...
p.000079: level. These trials are called cluster-cluster randomized trials (for example, all the students in a school or
p.000079: all residents of a community). In cluster-cluster randomized trials, individual informed consent for receiving the
p.000079: intervention is typically difficult to obtain since it is almost impossible to avoid the intervention. At the same
p.000079: time, individual consent for data collection procedures is usually possible in both types of cluster randomized trials.
p.000079:
p.000079: Ethical acceptability of a no-intervention group. Some CRTs investigate interventions that have been proven
p.000079: to be effective elsewhere; this is termed implementation research. This type of research is often conducted in
p.000079: low-resource settings. An ethical question pertaining to this type of study is whether it is acceptable
p.000079: to withhold the proven intervention from a control group in a CRT. This situation is analogous to that of
p.000079: placebo controls in a randomized, controlled trial when an established, effective prevention or treatment exists. If
p.000079: withholding the proven intervention from the control cluster would expose participants to more than a minor
p.000079: increase above minimal risk, it would be unethical to use that study design. An example would be the introduction of
p.000079: sterilizing equipment or disposable needles in a resource-poor health centre with a high infection rate among the
p.000079: patients. In the implementation CRT, health care workers would have to be educated in the use of the new equipment
p.000079: and instructed to throw away the disposable needles. Since the reuse of needles without sterilization would
p.000079: expose patients to more than a minor increase above minimal risk, it would be unethical for the control cluster to
p.000079: continue the usual practice. In such cases, it is necessary for researchers to explore an alternative design, such as
p.000079: using historical controls from the same facility. Research ethics committees have the responsibility to
p.000079: determine whether the proposed research is ethically acceptable when the methodology calls for withholding an
p.000079: established effective treatment from the control cluster.
p.000079:
p.000079: Gatekeeping in cluster randomized trials. When a CRT substantially affects cluster or organizational
p.000079: interests, and a gatekeeper (for example, a community leader, headmaster, or local health council) possesses the
p.000079: legitimate authority to make decisions on the cluster or organization’s behalf, the researcher must obtain the
p.000079: gatekeeper’s permission to enrol the cluster or organization in the trial. Such permission does not replace the need to
p.000079: obtain individual informed consent where
p.000079:
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p.000079: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000080:
p.000080:
p.000080:
p.000080:
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p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
p.000034: factors can be internal to participants, such as mental illness, whereas other influences can be external, such as a
p.000034: dependent relationship between participants and clinician-researchers. Circumstances such as severe illness or poverty
p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
p.000034: consent in these situations. Research ethics committees must determine for each individual protocol if influences on
p.000034: voluntary consent cross the threshold of being undue, and if so, which safeguards are appropriate.
p.000034:
p.000034: Dependent relationship. There are different forms of dependent relationships, such as those between
p.000034: teachers and students, and guards and prisoners. In the context of clinical research, dependent
p.000034: relationships can result from pre-existing relationships between a treating physician and a patient, who
p.000034: becomes a potential participant when his or her treating physician assumes the role of researcher. The
p.000034: dependent relationship between patients and clinician-researchers may compromise the voluntariness of informed
p.000034: consent, since potential participants who are patients depend on the clinician-researcher for medical care and
p.000034: may be reluctant to refuse an invitation to enrol in research in which the treating clinician is involved. Therefore,
...
Searching for indicator social status:
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p.000011: with an overall judgment about the risks and potential individual benefits of the given study.
p.000011:
p.000011: The minimal-risk standard. The minimal-risk standard is often defined by comparing the probability and magnitude of
p.000011: anticipated harms with the probability and magnitude of harms ordinarily encountered in daily life or during the
p.000011: performance of routine physical or psychological examinations or tests. The purpose of these comparisons is to
p.000011: determine the level of acceptable research risk by analogy with the risks of activities in other areas of life: when
p.000011: the risks of an activity are considered acceptable for the population in question, and the activity is relatively
p.000011: similar to participating in research, then the same level of risk should be considered acceptable in the
p.000011: research context. These comparisons typically imply that research risks are minimal when the risk of serious harm is
p.000011: very unlikely and the potential harms associated with more common adverse events are small.
p.000011:
p.000011: One difficulty with these risk comparisons, however, is that different populations can experience dramatic differences
p.000011: in the risks of daily life or in routine clinical examinations and testing. Such differences in background risk can
p.000011: stem from inequalities in health, wealth, social status, or social determinants of health. Therefore, research ethics
p.000011: committees must be careful not to make such comparisons in ways that permit participants or groups of participants from
p.000011: being exposed to greater risks in research merely because they are poor, members of disadvantaged groups or
p.000011: because their environment exposes them to greater risks in their daily lives (for example, poor road safety).
p.000011: Research ethics committees must be similarly vigilant about not permitting greater research risks in
p.000011: populations of patients who routinely undergo risky treatments or diagnostic procedures (for example, cancer patients).
p.000011: Rather, risks in research must be compared to risks that an average, normal, healthy individual
p.000011: experiences in daily life or during routine examinations. Furthermore, risk comparisons must not be made to
p.000011: activities that pose unacceptable risks themselves, or in which people choose to participate because of the associated
p.000011: benefits (some sporting activities, for example, are thrilling precisely because they involve an elevated risk of
p.000011: harm).
p.000011:
p.000011:
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p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
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p.000056: Although research ethics committees can require special protections only for potential participants collectively for a
p.000056: particular project, researchers and others involved in research must take into account factors that render individual
p.000056: participants vulnerable and take appropriate steps to mitigate those factors.
p.000056:
p.000056: A traditional approach to vulnerability in research has been to label entire classes of individuals as vulnerable. The
p.000056: account of vulnerability in this Guideline seeks to avoid considering members of entire classes of
p.000056: individuals as vulnerable. However, it is useful to look at the specific characteristics that may render individuals
p.000056: vulnerable, as this can aid in identifying the special protections needed for persons who may have an increased
p.000056: likelihood of being wronged or of incurring additional harm as participants in research. Different characteristics
p.000056: may also co-exist, making some individuals more vulnerable than others. This is highly dependent on the context.
p.000056: For example, persons who are illiterate, marginalized by virtue of their social status or behaviour, or living in an
p.000056: authoritarian environment, may have multiple factors that make them vulnerable.
p.000056:
p.000056: Some characteristics can make it reasonable to assume that certain individuals are vulnerable, for example:
p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
p.000056:
p.000056: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
...
General/Other / Dependent
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p.000119: Guidelines have cross references to other Guidelines. The purpose of these cross references is to help the reader
p.000119: navigate through the Guidelines. However, absence of cross references to other Guidelines does not imply that other
p.000119: Guidelines may not be applicable.
p.000119:
p.000119: Although the Guidelines focus primarily on rules and principles to protect humans in research, both
p.000119: virtues and protections are essential to reliably safeguard the rights and welfare of humans.
p.000119:
p.000119: As a general rule, “must” has been used to attach greater moral weight to requirements when compared to
p.000119: “should”.
p.000119:
p.000119: The term “health-related research” in these Guidelines refers to activities designed to develop or
p.000119: contribute to generalizable health knowledge within the more classic realm of research with humans, such as
p.000119: observational research, clinical trials, biobanking and epidemiological studies. Generalizable health knowledge
p.000119: consists of theories, principles or relationships, or the accumulation of information on which they are based related
p.000119: to health, which can be corroborated by accepted scientific methods of observation and inference.
p.000119:
p.000119: These Guidelines address research involving humans. Usage in the bioethics literature varies. In this
p.000119: document, the terms “human beings”, “research participants”, and “human subjects” are used interchangeably.
p.000119:
p.000119: Progress towards a world where all can enjoy optimal health and health care is crucially dependent on all kinds of
p.000119: research including research involving humans.
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
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p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000119:
p.000119:
p.000119: GUIDELINE 1:
p.000119: SCIENTIFIC AND SOCIAL VALUE AND RESPECT FOR RIGHTS
p.000119:
p.000119: The ethical justification for undertaking health-related research involving humans is its scientific and
p.000119: social value: the prospect of generating the knowledge and the means necessary to protect and promote
p.000119: people’s health. Patients, health professionals, researchers, policy-makers, public health officials, pharmaceutical
p.000119: companies and others rely on the results of research for activities and decisions that impact individual and
p.000119: public health, welfare, and the use of limited resources. Therefore, researchers, sponsors, research ethics
p.000119: committees, and health authorities, must ensure that proposed studies are scientifically sound, build on an
p.000119: adequate prior knowledge base, and are likely to generate valuable information.
p.000119:
p.000119: Although scientific and social value are the fundamental justification for undertaking research, researchers,
...
p.000023: government agencies and community advisory boards. Also, it is important to ensure diversity of views within the
p.000023: consultation process. For instance, when community leaders are men only, researchers should actively include the views
p.000023: of women, as well. There may also be value in consulting individuals who have previously participated in comparable
p.000023: studies.
p.000023:
p.000023: The research protocol or other documents submitted to the research ethics committee should include a
p.000023: description of the plan for community engagement, and identify resources allocated for the proposed activities. This
p.000023: documentation must specify what has been and will be done, when and by whom, to ensure that the community is clearly
p.000023: defined and can be proactively engaged throughout the research to ensure that it is relevant to the community and is
p.000023: accepted. The community should participate, when feasible, in the actual discussion and preparation of the
p.000023: research protocol and documents.
p.000023:
p.000023: Researchers, sponsors, health authorities and relevant institutions should take care that community engagement does
p.000023: not lead to pressure or undue influence on individual community members to participate (see commentary on
p.000023: Guideline 9 – Individuals capable of giving informed consent, section
p.000023:
p.000023:
p.000023:
p.000023: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000025:
p.000025:
p.000025:
p.000025:
p.000025:
p.000025: on Dependent relationship). In order to avoid such pressure, individual informed consent must always be sought by the
p.000025: researcher.
p.000025:
p.000025: Researchers and research ethics committees should be cognizant of the point at which the process of community
p.000025: engagement becomes a stage of formative research that itself requires ethics review. Examples of community engagement
p.000025: processes that may require ethics review include systematic data collection that can be generalized and disseminated in
p.000025: forums outside of the community in which they were implemented, as well as any data generation that could create social
p.000025: risks for participants.
p.000025:
p.000025: Engagement at the earliest opportunity. Before a study is initiated, the community from which participants will be
p.000025: recruited should, when feasible, be consulted about their research priorities, preferred trial designs,
p.000025: willingness to be involved in the preparation and conduct of the study. Engaging the community at the
p.000025: earliest stage promotes smooth study functioning and contributes to the community’s capacity to understand the research
p.000025: process. Community members should be encouraged to raise any concerns they may have at the outset and as the research
p.000025: proceeds. Failure to engage the community can compromise the social value of the research, as well as threaten the
p.000025: recruitment and retention of participants.
p.000025:
p.000025: Community engagement should be an ongoing process, with an established forum for communication between researchers and
...
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
p.000034: factors can be internal to participants, such as mental illness, whereas other influences can be external, such as a
p.000034: dependent relationship between participants and clinician-researchers. Circumstances such as severe illness or poverty
p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
p.000034: consent in these situations. Research ethics committees must determine for each individual protocol if influences on
p.000034: voluntary consent cross the threshold of being undue, and if so, which safeguards are appropriate.
p.000034:
p.000034: Dependent relationship. There are different forms of dependent relationships, such as those between
p.000034: teachers and students, and guards and prisoners. In the context of clinical research, dependent
p.000034: relationships can result from pre-existing relationships between a treating physician and a patient, who
p.000034: becomes a potential participant when his or her treating physician assumes the role of researcher. The
p.000034: dependent relationship between patients and clinician-researchers may compromise the voluntariness of informed
p.000034: consent, since potential participants who are patients depend on the clinician-researcher for medical care and
p.000034: may be reluctant to refuse an invitation to enrol in research in which the treating clinician is involved. Therefore,
p.000034: in principle, in the case of a dependent relationship a neutral third party such as a research nurse or a
p.000034: qualified collaborator,
p.000034:
p.000034:
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p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: should obtain informed consent. However, in some situations of dependency, it is preferable that the clinician provide
p.000035: the patient with information since he or she is most knowledgeable about the condition of the patient. However, to
p.000035: minimize the influence of the dependent relationship, several protective measures must be taken. Clinicians engaged in
p.000035: research must acknowledge and inform patients that they have a dual role as the treating clinician and researcher. They
p.000035: must emphasize the voluntary nature of participation and the right to refuse or withdraw from the research. They must
p.000035: also assure patients that their decision whether to enrol or refuse participation will not affect the therapeutic
p.000035: relationship or other benefits to which they are entitled. In cases where it is necessary for the treating clinician to
p.000035: explain the details of the study protocol, the research ethics committee must consider whether the informed consent
p.000035: document must be signed in the presence of a neutral third party.
p.000035:
p.000035: Risks. Researchers must be completely objective in discussing the details of the experimental intervention,
p.000035: the pain or discomfort it may entail, and known risks and possible hazards. In some types of prevention research,
p.000035: potential participants must receive counselling about risks of acquiring a disease and steps they can take to reduce
p.000035: those risks. This is especially true of preventive research on communicable diseases, such as HIV/AIDS.
p.000035:
p.000035: Who obtains consent. Informed consent must be obtained by a member of the research team. Delegation of obtaining
p.000035: consent, for instance to a research nurse or another member of the research team, for instance in the case of a
p.000035: dependent relationship, is permissible as long as the person who obtains consent is duly qualified and has
p.000035: prior experience in obtaining consent. The principal investigator is responsible for ensuring that all personnel
p.000035: working on the project comply with this Guideline.
p.000035:
p.000035: Special considerations regarding informed consent for the use of data in health registries. The requirement to obtain
p.000035: informed consent for research on data in health-related registries may be waived, provided the conditions in Guideline
p.000035: 10 – Modifications and waivers of informed consent - are met. When a researcher plans to contact persons based on their
p.000035: inclusion in a health-related registry, the researcher must bear in mind that these persons may be unaware that their
p.000035: data were submitted to the registry or unfamiliar with the process by which researchers obtain access to the data (see
p.000035: Guideline 12 – Collection, storage and use of data in health-related research). If researchers wish to contact persons
p.000035: included in a health registry to obtain additional information from them for new research, such studies require
p.000035: informed consent.
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000056: that increases the likelihood that others place their interests at risk, whether intentionally or unintentionally.
p.000056: Although research ethics committees can require special protections only for potential participants collectively for a
p.000056: particular project, researchers and others involved in research must take into account factors that render individual
p.000056: participants vulnerable and take appropriate steps to mitigate those factors.
p.000056:
p.000056: A traditional approach to vulnerability in research has been to label entire classes of individuals as vulnerable. The
p.000056: account of vulnerability in this Guideline seeks to avoid considering members of entire classes of
p.000056: individuals as vulnerable. However, it is useful to look at the specific characteristics that may render individuals
p.000056: vulnerable, as this can aid in identifying the special protections needed for persons who may have an increased
p.000056: likelihood of being wronged or of incurring additional harm as participants in research. Different characteristics
p.000056: may also co-exist, making some individuals more vulnerable than others. This is highly dependent on the context.
p.000056: For example, persons who are illiterate, marginalized by virtue of their social status or behaviour, or living in an
p.000056: authoritarian environment, may have multiple factors that make them vulnerable.
p.000056:
p.000056: Some characteristics can make it reasonable to assume that certain individuals are vulnerable, for example:
p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
p.000056:
p.000056: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
p.000057: Examples are medical and nursing students, subordinate hospital and laboratory personnel, workers in settings
p.000057: where research studies are conducted, and members of the armed forces or police. Their agreement to volunteer may be
p.000057: unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate
p.000057: in the study or by fear of disapproval or retaliation if they refuse (see also commentary on Guideline 9 – Individuals
p.000057: capable of giving informed consent). The research protocol must include a description of provisions to protect such
p.000057: individuals from being conscripted into research.
p.000057:
p.000057: Institutionalized persons. Residents of nursing homes, mental institutions, and prisons are often considered vulnerable
p.000057: because in a confined setting they have few options and are denied certain freedoms that non-institutionalized persons
p.000057: enjoy. For example, prisons have been described as “an inherently coercive environment.” Also, they may be in a
p.000057: dependent relationship with caregivers or guardians (see commentary on Guideline 9 – Individuals capable of giving
p.000057: informed consent, section on Dependent relationship).
p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
p.000057: committee when such proposals are under review (see commentary on Guideline 9 – Individuals capable of giving informed
p.000057: consent, section on Dependent relationship). Some individuals with this characteristic may also have diminished
p.000057: capacity to consent, and therefore require the additional protections noted earlier for participants who lack
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
...
p.000058: voluntary decision-making, limit the potential for confidentiality breaches, and otherwise work to protect the
p.000058: interests of those at increased risk of harm. Research ethics committees need to be sensitive to not overly excluding
p.000058: people, and allow them to participate by requiring that special protections be put in place.
p.000058:
p.000058: Group vulnerability. Despite the importance of avoiding classification of entire groups as inherently vulnerable,
p.000058: circumstances exist that require research ethics committees to pay special attention to research involving
p.000058: certain groups. In some resource-limited countries or communities, lack of access to medical care,
p.000058: membership in ethnic and racial minorities, or other disadvantaged or marginalized groups can be factors
p.000058: that constitute vulnerability. As is true of the vulnerability of individuals, the judgment that groups
p.000058: are vulnerable is context dependent and requires empirical evidence to document the need for special
p.000058: protections.
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058:
p.000058: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000059: 59
p.000059:
p.000059:
p.000059:
p.000059:
p.000059:
p.000059: GUIDELINE 16:
p.000059: RESEARCH INVOLVING
p.000059: ADULTS INCAPABLE OF GIVING INFORMED CONSENT
p.000059:
p.000059: Adults who are not capable of giving informed consent must be included in health-related research unless a good
p.000059: scientific reason justifies their exclusion. As adults who are not capable of giving informed consent
p.000059: have distinctive physiologies and health needs, they merit special consideration by researchers and research
p.000059: ethics committees. At the same time, they may not be able to protect their own interests due to their lack of capacity
p.000059: to provide informed consent. Specific protections to safeguard the rights and welfare of these persons in research are
p.000059: therefore necessary.
p.000059:
...
p.000075: health professionals conducting research in a disaster context. Sponsors should include in the protocol a plan for
p.000075: mitigating adverse events. Furthermore, appropriate resources for mitigation measures should be included in the
p.000075: protocol budget.
p.000075:
p.000075:
p.000075: Commentary on Guideline 20
p.000075: Humanitarian response and research in the acute phase of disasters and diseases outbreaks. Disasters are sudden events
p.000075: that cause great suffering or loss of life. Disease and illness can either be the cause or a result of disasters. For
p.000075: example, epidemics can lead to disasters and destabilize political institutions or undermine economic activity.
p.000075: Conversely, natural and man-made disasters, such as earthquakes and war, can weaken or destroy health systems and have
p.000075: a devastating impact on individual and population health. The first and foremost obligation in acute
p.000075: disaster situations is to respond to the needs of those affected. At the same time, an obligation
p.000075: exists to conduct health-related research because disasters can be difficult to prevent, and the evidence
p.000075: base for effectively preventing or mitigating their public health impact is limited. These two obligations can come
p.000075: into conflict. This is because humanitarian response and health-related research often rely on the same infrastructure
p.000075: and the same personnel, so priorities between the two may need to be set. If nurses and physicians become
p.000075: researchers, this may also create dependent relationships (see Guideline 9 – Individuals capable of giving
p.000075: informed consent). Humanitarian workers, researchers and sponsors must be aware of these conflicts and ensure that
p.000075: their studies do not unduly compromise the disaster response. Researchers and sponsors should also aim to contribute to
p.000075: the infrastructure for the humanitarian response and integrate their research activities with this response.
p.000075: Importantly, all studies must be responsive to the health needs or priorities of the affected populations, and it must
p.000075: not be possible to conduct the research outside a disaster situation.
p.000075:
p.000075: General challenges in disaster research. In infectious disease outbreaks, there can be considerable pressure to conduct
p.000075: research. This is especially the case for diseases that have a high mortality rate and where the treatment options
p.000075: are limited (for example during the 2014 Ebola outbreak). Conversely, in natural or man-made disasters,
p.000075: research can be met with great scepticism or even hostility, and researchers can be at risk of physical harm.
p.000075: Researchers and sponsors must be equipped to negotiate these pressures in what are typically fragile political and
p.000075: social situations. They must also have sufficient operational and security support in order to work effectively in such
p.000075: challenging environments. Acute disasters pose numerous challenges for conducting ethically responsible
p.000075: research. For example, potential study participants often suffer from serious physical or psychological
p.000075:
p.000075:
...
p.000093:
p.000093: Conflicts of interest. Different stakeholders in research can have different types of conflicts of
p.000093: interest.
p.000093:
p.000093:
p.000093:
p.000093: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000095: 95
p.000095:
p.000095:
p.000095:
p.000095:
p.000095:
p.000095: 1. Researchers. Academic conflicts of interest can arise when researchers or senior members of a research team become
p.000095: overly invested in their own ideas. For example, a researcher who has worked for decades on an investigational HIV drug
p.000095: may find it difficult to stop a trial early when interim results clearly recommend this course of action. Furthermore,
p.000095: researchers’ careers depend on publishing interesting results, for example, when applying for research
p.000095: funding or promotion. This can create professional conflicts of interests.
p.000095: Some researchers also have personal financial conflicts of interest. For example, researchers sometimes receive part
p.000095: of their salary or a “finder’s fee” for recruiting research participants. When this income reflects a fair
p.000095: compensation for their time spent on recruitment, it does not present an inherent conflict of interest. However, a
p.000095: salary or “finder’s fee” may lead researchers
p.000095: – intentionally or unintentionally – to interpret the inclusion or exclusion criteria of a study too flexibly, thereby
p.000095: potentially exposing participants to excessive risks or compromising the scientific validity of the research.
p.000095: This situation is of particular concern when participants are dependent on a researcher who is also their clinician
p.000095: (see Guideline 9 – Individuals capable of giving informed consent, section on Dependent relationship), and when the
p.000095: salary of the clinician is considerably lower than what the researcher is paid. It may also lead researchers to
p.000095: pressure eligible participants to enrol, thus compromising or undermining participants’ voluntary consent. In addition,
p.000095: financial conflicts of interest can arise when researchers or senior members of the research team (or their close
p.000095: family members) have a financial stake in the company sponsoring the research, such as stock ownership.
p.000095:
p.000095: 2. Research institutions (universities, research centres, or pharmaceutical companies). Research institutions can
p.000095: have both reputational and financial conflicts of interests. For example, universities rely on the reputation of
p.000095: their research to attract faculty, students, or external funding. Some universities also patent the discoveries
p.000095: of their employees. Institutional conflicts of interest can also arise when a research centre derives substantial
p.000095: support (perhaps covering years of funding) from a single sponsor or a handful of sponsors. Pharmaceutical companies
p.000095: may feel pushed to accelerate a marketing authorization for getting a longer period of patent protection, or they may
p.000095: be tempted to downplay the side effects of new medicines to get broader prescription patterns.
p.000095:
p.000095: 3. Research ethics committees. Researchers often serve as members of research ethics committees and
p.000095: conflicts of interest can arise in this role. For example, a researcher may submit her own study protocol for review,
p.000095: or she may be reviewing the work of colleagues whom she knows personally, or whose work she considers critical for the
p.000095: success of her institution. Research ethics committees may also have financial interests when their members
p.000095: receive salaries or when they are directly funded by sponsors or serve an institution that depends significantly on
p.000095: support from a single sponsor or several sponsors.
p.000095: A fee paid to a research ethics committee (or the institution where it operates) for reviewing a study does not present
p.000095: an inherent conflict of interest, provided that the fee is established by a general policy, is reasonably related to
p.000095: the costs of conducting the review and is not dependent on the outcome of the review (see Guideline 23 – Requirements
p.000095: for establishing research ethics committees and for their review of protocols).
p.000095:
p.000095: In order to evaluate the seriousness of a conflict of interest, and to determine appropriate measures for its
p.000095: management, research ethics committees need to judge the risk that the sponsor’s or investigator’s
p.000095: conflicts of interest unduly compromise or undermine the ethical or scientific conduct of a study. This involves
p.000095: judging both the likelihood that a secondary interest might compromise the rights or welfare of participants
p.000095: or the scientific validity of the research, as well as judging the magnitude of the secondary interest relative to the
p.000095: stakeholder’s personal situation. For example, an early-career researcher with a modest salary might have more
p.000095: significant academic and financial conflicts of interest than an established senior member of the research
p.000095: team. Research ethics committees have to exercise their judgment when evaluating the seriousness of conflicts of
p.000095: interest.
p.000095:
p.000095:
p.000095: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000096: 96
p.000096:
p.000096:
p.000096:
p.000096:
p.000096:
p.000096: As a general rule, a potential serious conflict of interest exists when there is a significant possibility that the
p.000096: actions of an investigator resulting from professional, academic, or financial interests will result in biased study
...
p.000117: C
p.000117: Capable of giving informed consent 10, 25, 33, 34, 37, 38, 41, 43, 47, 49, 50, 51, 56, 58,
p.000117: 61 - 63, 67, 76, 78, 96
p.000117: Capacity-building 5, 27, 29, 30, 45, 52, 102
p.000117: Cluster randomized trials 79, 80
p.000117: Coding 41, 44, 47, 50, 51, 90
p.000117: Collaborative partnership 27, 29, 30, 42, 45, 47, 52, 89
p.000117: Collection, collecting 26, 36, 39, 41 - 43, 47 - 50, 77, 80, 83 - 85, 92, 103, 105
p.000117: Community engagement ix, xi, 5, 10, 23, 25, 26, 29, 30, 42, 45, 47, 52, 59, 63, 75, 78, 102
p.000117: Comparative effectiveness research 16, 19
p.000117: Compassionate use 22
p.000117: Compelling scientific reasons 15 - 18
p.000117: Compensation 13, 53 - 56, 96, 100, 104 Competent. See Capable of giving informed consent Comprehension 34
p.000117: Confidentiality 11, 13, 41, 42, 44, 47, 48, 50, 51, 57, 59, 70, 100, 101, 102, 104, 105
p.000117: Conflicts of interest 5, 30, 34, 78, 89, 92, 95 - 97, 102, 104
p.000117: Continued access 21 - 23, 101, 104
p.000117: Control 9, 12, 15 - 18, 22, 26, 45, 51, 62, 67, 73, 79, 80, 83, 85,
p.000117: Custodian 41, 43, 44, 47, 49, 50, 105
p.000117: D
p.000117: Databank 47 - 52
p.000117:
p.000117:
p.000117: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000117:
p.000119: 119
p.000119:
p.000119: Data mining 50
p.000119: Data sharing 29, 31, 51, 85, 92
p.000119: Deception, deceiving 33, 38, 57
p.000119: Deliberate objection 67
p.000119: Dependent relationship 26, 35, 36, 58, 96
p.000119: Digital 83, 106
p.000119: Disaster ix, 75 - 78, 106
p.000119: Disclosure 44, 45, 51, 84, 85, 91, 95, 97, 101, 103 - 105
p.000119: Disease outbreak ii, x, 19, 34, 41, 44, 47, 49, 83, 96, 97, 99, 103, 105
p.000119: Dissemination 2, 4, 25, 85, 92
p.000119: Dissent 62, 67
p.000119: E
p.000119: Education 2, 30, 57, 89, 97
p.000119: Emergency care 63, 68, 78
p.000119: Equitable distribution 4, 7, 42, 45, 47, 52, 75, 77
p.000119: Established effective intervention viii, 9, 12, 15 - 19
p.000119: Ethical review xii, 2, 29, 30, 39, 76 - 78, 87 - 90, 95, 97, 99, 102
p.000119: Externally sponsored research 87, 89
p.000119: F
p.000119: Fairness 2
p.000119: Fetus 58, 69, 70 - 73
p.000119: Free medical treatment 56
p.000119: G
p.000119: Gatekeeping 80
p.000119: Governance 41 - 43, 44, 47, 48, 50, 51, 78
p.000119: H
p.000119: Harms 10, 11, 12, 18, 54, 55, 56, 70, 72, 91, 105
p.000119: Health needs 2 - 4, 8, 17, 19, 21 - 23, 26, 55, 61, 65, 69, 71, 72, 75, 76, 104
p.000119: I
p.000119: Identifiable 38, 39, 51, 84
p.000119: Implementation research 80
p.000119: Incentives 10, 54, 92, 101
p.000119: Information leaflet 34
p.000119: Informed consent ix, 2, 9, 10, 21, 25, 26, 33 - 39, 41 - 45, 47 - 52, 54, 56, 58, 61 - 65, 67 - 72, 75,
p.000119: 76, 78 - 80, 89, 96, 97, 100, 101, 103, 105
p.000119: Informed opt-out /opt-in 41, 44, 47, 49, 83
p.000119: In-kind 54
p.000119: Interventions 1 - 4, 9 - 12, 15 - 19, 21 - 23, 26, 30, 53, 55, 56, 61 - 63, 65, 66, 71 - 73, 75 - 81, 84,
p.000119: 88, 91, 100, 101, 104
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000120: 120
...
General/Other / Developing Country
Searching for indicator underdeveloped:
(return to top)
p.000027: for establishing research ethics committees and for their review of protocols);
p.000027: f developing technologies appropriate to health care and health-related research;
p.000027: f educating research and health-care personnel and making arrangements to avoid undue displacement of health
p.000027: care personnel;
p.000027: f engaging with the community from which research participants will be drawn (see Guideline 7 – Community
p.000027: engagement);
p.000027: f arranging for joint publication consistent with recognized authorship requirements and data sharing (see Guideline
p.000027: 24 – Public accountability for health-related research); and
p.000027: f preparing a benefit-sharing agreement to distribute eventual economic gains from the research.
p.000027:
p.000027:
p.000027: Commentary on Guideline 8
p.000027: General considerations. Governmental authorities in charge of health-related research involving human participants
p.000027: have to ensure that such research is reviewed ethically and scientifically by competent and independent
p.000027: research ethics committees and is conducted by competent research teams (see Guideline 23 – Requirements for
p.000027: establishing research ethics committees and for their review of protocols). Where research capacity is
p.000027: lacking or underdeveloped, sponsors and researchers have an ethical obligation to contribute to a host
p.000027: country’s sustainable capacity for
p.000027:
p.000027: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000029: 29
p.000029:
p.000029:
p.000029:
p.000029:
p.000029:
p.000029: health-related research and ethical review. Before undertaking research in a community with little or no such
p.000029: capacities, sponsors and researchers should have a plan that describes how the research can contribute to local
p.000029: capacity. The kind and amount of capacity-building reasonably required should be proportional to the magnitude of
p.000029: the research project. A brief epidemiological study involving only review of medical records, for example, would
p.000029: require relatively little, if any, such development, whereas a considerable contribution is to be expected of a sponsor
p.000029: of a large-scale vaccine trial intended to last several years. The conduct of research must not destabilize health care
p.000029: systems, and ideally should contribute to them.
p.000029:
p.000029: Collaborative partnership. The development and testing of biomedical interventions frequently require
p.000029: international cooperative research. Real or perceived disparities in power or expertise should be resolved in a way
p.000029: that ensures equity in decision-making and action. The desired relationship is one of equal partners whose common aim
p.000029: is to develop a long-term collaboration through South- South and North-South cooperation that sustains site research
...
General/Other / Diminished Autonomy
Searching for indicator diminished:
(return to top)
p.000056: authoritarian environment, may have multiple factors that make them vulnerable.
p.000056:
p.000056: Some characteristics can make it reasonable to assume that certain individuals are vulnerable, for example:
p.000056: Capacity to consent. One widely accepted criterion of vulnerability is limited capacity to consent or decline to
p.000056: consent to research participation. Individuals with this characteristic are discussed in
p.000056:
p.000056: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000057: 57
p.000057:
p.000057:
p.000057:
p.000057:
p.000057:
p.000057: other guidelines in this document (see Guideline 16 – Research involving adults incapable of giving informed consent,
p.000057: and Guideline 17 – Research involving children and adolescents).
p.000057:
p.000057: Individuals in hierarchical relationships. The characteristic of vulnerability in this case is the
p.000057: possibility of diminished voluntariness of the consent of potential participants who are in a subordinate relationship.
p.000057: Examples are medical and nursing students, subordinate hospital and laboratory personnel, workers in settings
p.000057: where research studies are conducted, and members of the armed forces or police. Their agreement to volunteer may be
p.000057: unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree to participate
p.000057: in the study or by fear of disapproval or retaliation if they refuse (see also commentary on Guideline 9 – Individuals
p.000057: capable of giving informed consent). The research protocol must include a description of provisions to protect such
p.000057: individuals from being conscripted into research.
p.000057:
p.000057: Institutionalized persons. Residents of nursing homes, mental institutions, and prisons are often considered vulnerable
p.000057: because in a confined setting they have few options and are denied certain freedoms that non-institutionalized persons
p.000057: enjoy. For example, prisons have been described as “an inherently coercive environment.” Also, they may be in a
p.000057: dependent relationship with caregivers or guardians (see commentary on Guideline 9 – Individuals capable of giving
p.000057: informed consent, section on Dependent relationship).
p.000057:
p.000057: One protection for institutionalized individuals is the appointment of an advocate of some sort to the research ethics
p.000057: committee when such proposals are under review (see commentary on Guideline 9 – Individuals capable of giving informed
p.000057: consent, section on Dependent relationship). Some individuals with this characteristic may also have diminished
p.000057: capacity to consent, and therefore require the additional protections noted earlier for participants who lack
p.000057: decisional capacity.
p.000057:
p.000057: Women. Although women in general must not be considered vulnerable, specific circumstances in which women
p.000057: could be vulnerable in research include: studies with female or transsexual sex workers; research on sexual
p.000057: and intimate partner violence; studies with trafficked women, refugees and asylum seekers; studies of abortion in
p.000057: jurisdictions where abortion is illegal; and research with women who live in a cultural context where they are not
p.000057: permitted to consent on their own behalf for participation in research, but require permission from a spouse or male
p.000057: relative. When women in such situations are potential participants in research, researchers need to exercise special
...
General/Other / Impaired Autonomy
Searching for indicator autonomy:
(return to top)
p.000031: that could affect the willingness of participants to continue. In long-term studies, researchers should ensure at
p.000031: pre-determined intervals that each participant is willing to stay in the study, even if there are no changes in the
p.000031: design or objectives of the research.
p.000031:
p.000031: It is the principal investigator’s responsibility to ensure that all personnel obtaining informed consent for a study
p.000031: comply with this Guideline.
p.000031:
p.000031:
p.000031: Commentary on Guideline 9
p.000031: General considerations. Informed consent is a process. The start of this process requires providing relevant
p.000031: information to a potential participant, ensuring that the person has adequately understood the material facts and
p.000031: has decided or refused to participate without having been subjected to coercion, undue influence, or
p.000031: deception.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Informed consent is based on the principle that individuals capable of giving informed consent have a right to choose
p.000033: freely whether to participate in research. Informed consent protects the individual’s freedom of choice and respects
p.000033: the individual’s autonomy.
p.000033:
p.000033: The information must be provided in plain language understandable by the potential participant. The person
p.000033: obtaining informed consent must be knowledgeable about the research and capable of answering any questions from
p.000033: potential participants. Researchers in charge of the study must make themselves available to answer questions at the
p.000033: request of participants. Participants should be offered the opportunity to ask questions and receive answers before or
p.000033: during the research. Researchers should make every effort to address those questions in a timely and comprehensive
p.000033: manner.
p.000033:
p.000033: This Guideline applies to individuals capable of giving informed consent. Requirements for research with individuals
p.000033: who are not capable of giving informed consent or with children and adolescents are set out in Guideline 16 –
p.000033: Research involving adults incapable of giving informed consent, and Guideline 17 – Research involving children
p.000033: and adolescents.
p.000033:
p.000033: Process. Informed consent is a two-way communicative process that begins when initial contact is made with a potential
p.000033: participant and ends when consent is provided and documented, but can be revisited later during the conduct of the
...
p.000067: adults incapable of giving informed consent - apply.
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000068: 68
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: GUIDELINE 18:
p.000068: WOMEN AS RESEARCH PARTICIPANTS
p.000068:
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
p.000068: physiologies and health needs, they merit special consideration by researchers and research ethics committees. Only the
p.000068: informed consent of the woman herself should be required for her research participation. Since some societies lack
p.000068: respect for women’s autonomy, in no case must the permission of another person replace the requirement of individual
p.000068: informed consent by the woman.
p.000068:
p.000068: Women of child-bearing potential must be informed in advance of the possibility of risks to the fetus
p.000068: should they become pregnant during their research participation. When participation in research might be
p.000068: hazardous to a fetus or a woman if she becomes pregnant, sponsors and researchers must guarantee access to pregnancy
p.000068: tests, effective contraceptive methods before and during the research and to safe, legal abortion.
p.000068:
p.000068:
p.000068: Commentary on Guideline 18
p.000068: General considerations. Women in many societies have been excluded from research. For example, most of the early
p.000068: cardiovascular disease studies have excluded women because these diseases were believed to be uncommon in women. In
p.000068: particular, women who are biologically capable of becoming pregnant have been traditionally excluded from clinical
...
General/Other / Incapacitated
Searching for indicator incapacitated:
(return to top)
p.000061: studies cannot be conducted in persons who can give informed consent, a research ethics committee may permit a
p.000061: minor increase above minimal risk.
p.000061:
p.000061:
p.000061: Commentary on Guideline 16
p.000061: General considerations. In general, competence or decisional capacity is determined by the ability to
p.000061: understand material information, appreciate the situation and its consequences, consider the treatment options, and
p.000061: communicate a choice. Persons should be considered capable of giving informed consent unless it is proven otherwise. A
p.000061: person may be incapable to give informed consent for a variety of reasons (for example, dementia, some psychiatric
p.000061: conditions and accidents). Persons can become capable of giving informed consent after a certain period, or they can be
p.000061: incapable to decide whether they should be treated for a certain disease but capable to decide whether they want to
p.000061: enjoy a meal. This illustrates that a lack of decisional capacity is time-, task- and context-specific.
p.000061:
p.000061: When researchers have reason to believe that potential or current participants are incapacitated, the participant’s
p.000061: decisional capacity must be adequately assessed. In cases where incapacity to give informed consent might reasonably be
p.000061: expected, participants must be routinely screened. However, it is important to note that diagnosis of a mental or
p.000061: behavioural disorder does not necessarily imply that individuals are incapable of giving informed consent.
p.000061:
p.000061: Potential individual benefits and risks. The potential individual benefits and risks of research with adults incapable
p.000061: of giving informed consent should be evaluated based on Guideline 4 – Potential individual benefits and risks of
p.000061: research, and Guideline 5 – Choice of control in clinical trials.
p.000061:
p.000061: Assent and dissent. If participants cannot consent because they are incapacitated due to mental or behavioural
p.000061: disorders, they must be engaged in the research discussion at the level of their capacity to understand, and they must
p.000061: be given a fair opportunity to agree to or to decline participation in the study. This can also be called
p.000061: obtaining the participant’s assent or dissent. Assent must be considered as a process (see Guideline 9 –
p.000061: Individuals capable of giving informed consent) that responds to changes in the person’s cognitive status and is
p.000061: not merely the absence of dissent.
p.000061:
p.000061: Any explicit objection by persons who are incapable to give informed consent must be respected even if the legally
p.000061: authorized representative has given permission. An explicit objection may be overruled if the incapacitated person
p.000061: needs treatment that is not available outside the context of research, prior research has demonstrated a significant
p.000061: benefit (see Guideline 4 – Potential individual benefits and risks of research), and the treating physician and the
p.000061: legally authorized representative consider the research intervention to be the best available medical option for the
p.000061: person lacking capacity.
p.000061:
p.000061: Permission of a legally authorized representative. In accordance with relevant national regulations, the
p.000061: permission of an immediate family member or other person with a close personal relationship with the individual must
p.000061: be sought. Surrogate decision-makers must evaluate to what extent study participation is consistent with the
p.000061: individual’s previously formed preferences and values (if any), and, in the case of research that offers participants a
p.000061: prospect of clinical benefit, to what extent study participation promotes the individual’s clinical interests.
p.000061: Previously stated preferences regarding the individual’s willingness to enrol in research or documented preferences in
p.000061: an advance directive should be respected. Researchers must recognize that surrogates may have their own
p.000061: interests that may call their permission into question. Furthermore, in situations where a legally
p.000061: authorized representative is not available to allow for timely enrolment, researchers may obtain the permission of a
p.000061: representative who is socially accepted but not formally recognized before the law.
p.000061:
p.000061: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000062: 62
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
...
p.000062: consent. Research protocols are sometimes designed to address conditions occurring suddenly and rendering the
p.000062: patients or participants incapable of giving informed consent. Examples are sepsis, head trauma, cardiopulmonary arrest
p.000062: and stroke. In such circumstances, it is often necessary to proceed with the research interventions very soon after the
p.000062: onset of the condition in order to evaluate an investigational treatment or develop the desired knowledge.
p.000062:
p.000062: If possible, an attempt must be made to identify a population that is likely to develop the condition to be studied.
p.000062: This can be done readily, for example, if the condition is one that recurs periodically in individuals, such as grand
p.000062: mal seizures and alcohol binges. In such cases, researchers should ideally contact potential participants while fully
p.000062: capable of informed consent, and obtain their agreement to be involved in the research during future periods of
p.000062: incapacitation, for example in an advance directive.
p.000062:
p.000062: If there is no opportunity to solicit informed consent of participants while fully capable of informed consent, plans
p.000062: to conduct emergency care research with incapacitated persons must be publicized within the community in which it will
p.000062: be carried out, where feasible. In the design and conduct of the research, the research ethics committee, the
p.000062: researchers and the sponsors must be responsive to the concerns of the community. The research must not be carried out
p.000062: if it does not have substantial support in the community concerned. (See commentary on Guideline 4 – Potential
p.000062: individual benefits and risks of research, section on Risks to groups of persons, and Guideline 7 – Community
p.000062: engagement).
p.000062:
p.000062: Before proceeding without prior informed consent, the researcher must make reasonable efforts to locate a legally
p.000062: authorized representative to give permission on behalf of an incapacitated patient in need of emergency care. If such a
p.000062: person can be located and refuses to give permission, the patient may not be enrolled as a participant.
p.000062:
p.000062: The researcher and the research ethics committee should agree to a maximum time of involvement of an individual without
p.000062: obtaining either the individual’s own informed consent or surrogate consent if the person continues to be unable to
p.000062: give consent. If, by that time, there is no individual or surrogate consent, the participant should be withdrawn from
p.000062: the study provided that withdrawal will not make the participant worse off. The participant or the surrogate should be
p.000062: offered an opportunity to object to the use of data derived from participation of the patient without consent or
p.000062: permission.
p.000062:
p.000062: When there are no advance directives for research participation for the period of incapacitation,
p.000062: permission of a legally authorized representative must be sought. This permission must take account of the
p.000062: participant’s previously expressed preferences and values, if any.
p.000062:
p.000062: In all cases in which research has been approved to begin without prior consent of incapacitated persons because of
p.000062: suddenly occurring conditions, they must be given all relevant information as soon as they regain capacity, and their
p.000062: consent to remain in the study must be obtained as soon as reasonably possible. In addition, they must be given the
p.000062: opportunity to opt out of the study.
p.000062:
p.000062: Waivers of the permission by a legally authorized representative. Research ethics committees may waive the
p.000062: requirement to obtain permission from a legally authorized representative if the conditions for waiving
p.000062: informed consent in research with participants who are capable of giving informed consent are satisfied
p.000062: (Guideline 10 – Modifications and waivers of informed consent).
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000063:
p.000063:
p.000063:
p.000063:
p.000063:
p.000063: GUIDELINE 17:
p.000063: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS
p.000063:
p.000063: Children and adolescents must be included in health-related research unless a good scientific reason justifies their
p.000063: exclusion. As children and adolescents have distinctive physiologies and health needs, they merit special
...
Searching for indicator incapacity:
(return to top)
p.000061: minor increase above minimal risk.
p.000061:
p.000061:
p.000061: Commentary on Guideline 16
p.000061: General considerations. In general, competence or decisional capacity is determined by the ability to
p.000061: understand material information, appreciate the situation and its consequences, consider the treatment options, and
p.000061: communicate a choice. Persons should be considered capable of giving informed consent unless it is proven otherwise. A
p.000061: person may be incapable to give informed consent for a variety of reasons (for example, dementia, some psychiatric
p.000061: conditions and accidents). Persons can become capable of giving informed consent after a certain period, or they can be
p.000061: incapable to decide whether they should be treated for a certain disease but capable to decide whether they want to
p.000061: enjoy a meal. This illustrates that a lack of decisional capacity is time-, task- and context-specific.
p.000061:
p.000061: When researchers have reason to believe that potential or current participants are incapacitated, the participant’s
p.000061: decisional capacity must be adequately assessed. In cases where incapacity to give informed consent might reasonably be
p.000061: expected, participants must be routinely screened. However, it is important to note that diagnosis of a mental or
p.000061: behavioural disorder does not necessarily imply that individuals are incapable of giving informed consent.
p.000061:
p.000061: Potential individual benefits and risks. The potential individual benefits and risks of research with adults incapable
p.000061: of giving informed consent should be evaluated based on Guideline 4 – Potential individual benefits and risks of
p.000061: research, and Guideline 5 – Choice of control in clinical trials.
p.000061:
p.000061: Assent and dissent. If participants cannot consent because they are incapacitated due to mental or behavioural
p.000061: disorders, they must be engaged in the research discussion at the level of their capacity to understand, and they must
p.000061: be given a fair opportunity to agree to or to decline participation in the study. This can also be called
p.000061: obtaining the participant’s assent or dissent. Assent must be considered as a process (see Guideline 9 –
p.000061: Individuals capable of giving informed consent) that responds to changes in the person’s cognitive status and is
p.000061: not merely the absence of dissent.
p.000061:
...
General/Other / Manipulable
Searching for indicator manipulate:
(return to top)
p.000095: conflicts of interest unduly compromise or undermine the ethical or scientific conduct of a study. This involves
p.000095: judging both the likelihood that a secondary interest might compromise the rights or welfare of participants
p.000095: or the scientific validity of the research, as well as judging the magnitude of the secondary interest relative to the
p.000095: stakeholder’s personal situation. For example, an early-career researcher with a modest salary might have more
p.000095: significant academic and financial conflicts of interest than an established senior member of the research
p.000095: team. Research ethics committees have to exercise their judgment when evaluating the seriousness of conflicts of
p.000095: interest.
p.000095:
p.000095:
p.000095: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000096: 96
p.000096:
p.000096:
p.000096:
p.000096:
p.000096:
p.000096: As a general rule, a potential serious conflict of interest exists when there is a significant possibility that the
p.000096: actions of an investigator resulting from professional, academic, or financial interests will result in biased study
p.000096: results or cause harm or wrong to participants.
p.000096:
p.000096: Conflicts of interests can influence researchers subconsciously. For example, researchers with a financial
p.000096: stake in a study may not intentionally manipulate the research findings. However, their financial interests may
p.000096: subconsciously influence their analysis and interpretation of the research data.
p.000096:
p.000096: Management of conflicts of interest. All stakeholders in research share responsibility for developing and implementing
p.000096: policies and procedures to identify, mitigate, eliminate, or otherwise manage conflicts of interest.
p.000096: Although this is a joint responsibility, research institutions play a critical role in creating an
p.000096: institutional culture that takes conflicts of interest seriously and adopts appropriate measures for their management.
p.000096: Measures for managing conflicts of interest must be proportional to their seriousness. For example, a minor
p.000096: conflict of interest may be appropriately managed by disclosure, while a potential serious conflict can, in some
p.000096: cases, justify excluding a researcher from the study team. Policies and measures for managing conflicts of interest
p.000096: must be transparent and actively communicated to those affected.
p.000096:
p.000096: 1. Education of researchers and research ethics committees. Raising awareness of conflicts of interest, as well as
p.000096: the importance of managing such conflicts, is essential for making procedures and policies effective.
p.000096:
p.000096: 2. Disclosure of interests to research ethics committees. Researchers must disclose conflicts of interest on their
...
General/Other / Other Country
Searching for indicator another country:
(return to top)
p.000072: an unwanted fetus to term and deliver an affected baby against their wishes. Before pregnant women are enrolled,
p.000072: researchers must, at a minimum, determine whether fetal impairment and mental health conditions are recognised as legal
p.000072: grounds for abortion in that jurisdiction. If they are not, pregnant women must not be recruited for research in which
p.000072: there is a realistic basis for concern that significant fetal abnormality may occur as a consequence of
p.000072: participation in research. At the same time, this rule might restrict potentially valuable research in
p.000072: countries where women cannot be guaranteed access to abortion. In such cases, research projects can be
p.000072: conducted only if a local research ethics committee determines that the research has compelling social value for
p.000072: pregnant women and the women are informed about existing restrictions on abortion and possible options for obtaining an
p.000072: abortion in another country.
p.000072:
p.000072: Breastfeeding women. The father may need to be consulted in research involving breastfeeding women, in accordance with
p.000072: Guideline 17 – Research involving children and adolescents. If a breast- fed infant may be exposed to an
p.000072: investigational product through the ingestion of breast milk (or it is unknown whether an infant would be exposed),
p.000072: such research should be conducted in accordance with Guideline 17 – Research involving children and adolescents.
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072:
p.000072: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000073: 73
p.000073:
p.000073:
p.000073:
p.000073:
p.000073:
p.000073: GUIDELINE 20:
p.000073: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS
p.000073:
p.000073: Disasters arising from events such as earthquakes, tsunamis or military conflicts, and disease outbreaks, can
p.000073: have a sudden and devastating impact on the health of large affected populations. In order to identify effective ways
p.000073: of mitigating the health impact of disasters and disease outbreaks, health-related research should form an integral
...
General/Other / Public Emergency
Searching for indicator emergency:
(return to top)
p.000061: benefit (see Guideline 4 – Potential individual benefits and risks of research), and the treating physician and the
p.000061: legally authorized representative consider the research intervention to be the best available medical option for the
p.000061: person lacking capacity.
p.000061:
p.000061: Permission of a legally authorized representative. In accordance with relevant national regulations, the
p.000061: permission of an immediate family member or other person with a close personal relationship with the individual must
p.000061: be sought. Surrogate decision-makers must evaluate to what extent study participation is consistent with the
p.000061: individual’s previously formed preferences and values (if any), and, in the case of research that offers participants a
p.000061: prospect of clinical benefit, to what extent study participation promotes the individual’s clinical interests.
p.000061: Previously stated preferences regarding the individual’s willingness to enrol in research or documented preferences in
p.000061: an advance directive should be respected. Researchers must recognize that surrogates may have their own
p.000061: interests that may call their permission into question. Furthermore, in situations where a legally
p.000061: authorized representative is not available to allow for timely enrolment, researchers may obtain the permission of a
p.000061: representative who is socially accepted but not formally recognized before the law.
p.000061:
p.000061: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000062: 62
p.000062:
p.000062:
p.000062:
p.000062:
p.000062:
p.000062: Emergency care situations in which the researcher anticipates that many participants will be unable to
p.000062: consent. Research protocols are sometimes designed to address conditions occurring suddenly and rendering the
p.000062: patients or participants incapable of giving informed consent. Examples are sepsis, head trauma, cardiopulmonary arrest
p.000062: and stroke. In such circumstances, it is often necessary to proceed with the research interventions very soon after the
p.000062: onset of the condition in order to evaluate an investigational treatment or develop the desired knowledge.
p.000062:
p.000062: If possible, an attempt must be made to identify a population that is likely to develop the condition to be studied.
p.000062: This can be done readily, for example, if the condition is one that recurs periodically in individuals, such as grand
p.000062: mal seizures and alcohol binges. In such cases, researchers should ideally contact potential participants while fully
p.000062: capable of informed consent, and obtain their agreement to be involved in the research during future periods of
p.000062: incapacitation, for example in an advance directive.
p.000062:
p.000062: If there is no opportunity to solicit informed consent of participants while fully capable of informed consent, plans
p.000062: to conduct emergency care research with incapacitated persons must be publicized within the community in which it will
p.000062: be carried out, where feasible. In the design and conduct of the research, the research ethics committee, the
p.000062: researchers and the sponsors must be responsive to the concerns of the community. The research must not be carried out
p.000062: if it does not have substantial support in the community concerned. (See commentary on Guideline 4 – Potential
p.000062: individual benefits and risks of research, section on Risks to groups of persons, and Guideline 7 – Community
p.000062: engagement).
p.000062:
p.000062: Before proceeding without prior informed consent, the researcher must make reasonable efforts to locate a legally
p.000062: authorized representative to give permission on behalf of an incapacitated patient in need of emergency care. If such a
p.000062: person can be located and refuses to give permission, the patient may not be enrolled as a participant.
p.000062:
p.000062: The researcher and the research ethics committee should agree to a maximum time of involvement of an individual without
p.000062: obtaining either the individual’s own informed consent or surrogate consent if the person continues to be unable to
p.000062: give consent. If, by that time, there is no individual or surrogate consent, the participant should be withdrawn from
p.000062: the study provided that withdrawal will not make the participant worse off. The participant or the surrogate should be
p.000062: offered an opportunity to object to the use of data derived from participation of the patient without consent or
p.000062: permission.
p.000062:
p.000062: When there are no advance directives for research participation for the period of incapacitation,
p.000062: permission of a legally authorized representative must be sought. This permission must take account of the
p.000062: participant’s previously expressed preferences and values, if any.
p.000062:
p.000062: In all cases in which research has been approved to begin without prior consent of incapacitated persons because of
p.000062: suddenly occurring conditions, they must be given all relevant information as soon as they regain capacity, and their
...
p.000067: psychological and medical support for the participating children and adolescents is another special
p.000067: protection, though this may be difficult to realize in some communities. In such communities, the study
p.000067: personnel must be sufficiently qualified to help children and adolescents who need medical and psychological support.
p.000067:
p.000067: A research ethics committee may also allow a waiver of parental permission if the conditions set out in Guideline 10 –
p.000067: Modifications and waivers of informed consent - are satisfied.
p.000067:
p.000067: Observation of the study by a parent or guardian. A parent or legally appointed guardian who gives permission for a
p.000067: child or adolescent to participate in research must generally be given the opportunity, to a reasonable
p.000067: extent and without violating the privacy of other study participants, to observe the child’s participation as
p.000067: the study proceeds. This could enable the child to be withdrawn if the parent or guardian decides it is in the child’s
p.000067: best interests to do so.
p.000067:
p.000067: Emergency care situations in which the researcher anticipates that children and adolescents will participate. When
p.000067: children and adolescents participate in emergency care research, the principles of Guideline 16 – Research involving
p.000067: adults incapable of giving informed consent - apply.
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067:
p.000067: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000068: 68
p.000068:
p.000068:
p.000068:
p.000068:
p.000068:
p.000068: GUIDELINE 18:
p.000068: WOMEN AS RESEARCH PARTICIPANTS
p.000068:
p.000068: Women must be included in health-related research unless a good scientific reason justifies their exclusion. Women have
p.000068: been excluded from much health-related research because of their child-bearing potential. As women have distinctive
p.000068: physiologies and health needs, they merit special consideration by researchers and research ethics committees. Only the
p.000068: informed consent of the woman herself should be required for her research participation. Since some societies lack
p.000068: respect for women’s autonomy, in no case must the permission of another person replace the requirement of individual
...
p.000075: research. For example, potential study participants often suffer from serious physical or psychological
p.000075:
p.000075:
p.000075: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000076: 76
p.000076:
p.000076:
p.000076:
p.000076:
p.000076:
p.000076: trauma that can make it difficult for them to protect their rights and interests. Limited or damaged health
p.000076: infrastructures can challenge implementation of preferred study designs and data collection. Moreover, efforts to make
p.000076: available as soon as possible any interventions or products developed from the research to the affected communities are
p.000076: often more challenging in acute disaster situations (see Guideline 2 – Research conducted in low-resource
p.000076: settings). Despite these challenges, it is essential that researchers and sponsors uphold the ethical principles
p.000076: embodied in these Guidelines, even if the standard ways of respecting these principles may need to be modified. In
p.000076: fact, an acute disaster situation can require modifying standard procedures so that ethical principles can be upheld in
p.000076: the most expedient way possible. For example, while ethical oversight is essential in all research, accelerated ethical
p.000076: review during disasters may be necessary to ensure that valuable studies can begin as soon as possible without
p.000076: compromising ethical requirements (see below).
p.000076:
p.000076: While all ethical principles in these Guidelines have to be upheld, some require special attention.
p.000076:
p.000076: Potential individual benefits and risks of investigational interventions and emergency use outside clinical trials.
p.000076: Especially when disasters are caused by infectious diseases that are highly contagious or serious (for example
p.000076: influenza, Ebola), there is great pressure to develop effective treatments and vaccines. When facing a serious,
p.000076: life-threatening infection, many people are willing to assume high risks and use unproven agents within or
p.000076: outside of clinical trials. However, it is essential that researchers and sponsors realistically assess
p.000076: the potential individual benefits and risks of experimental interventions and communicate these clearly to
p.000076: potential participants and individuals at risk. Even in ordinary circumstances, many promising experimental agents
p.000076: may not be safe and effective, and experimental interventions must be systematically evaluated in clinical trials.
p.000076: Moreover, emergency use can compromise recruitment of research participants and therefore undermine the conclusion of
p.000076: trials. Widespread emergency use with inadequate data collection about patient outcomes must therefore be avoided.
p.000076:
p.000076: Equitable distribution of risks and benefits. Because experimental interventions are often limited in disaster
p.000076: situations, fair selection of participants is essential (Guideline 3 – Equitable distribution of benefits and burdens
p.000076: in the selection of individuals and groups of participants in research). Especially in dire emergencies, well-off and
p.000076: well-connected patients must not be further privileged (for example, community leaders). Moreover, the exclusion of
p.000076: especially vulnerable populations must be justified (Guideline 15 – Research involving vulnerable persons and groups).
p.000076: It may be acceptable to prioritize certain populations in study enrolment. For example, front line workers often put
p.000076: themselves at risk during a disaster such as an epidemic, and if experimental interventions are effective, these
p.000076: workers would be able to help more patients. The principles of reciprocity and helping the largest number of people
p.000076: could therefore justify their prioritization. Researchers, sponsors, and research ethics committees also need
p.000076: to ensure that burdens and benefits of participation are equitably distributed (see Guideline 3 – Equitable
p.000076: distribution of benefits and burdens in the selection of individuals and groups of participants in research).
p.000076:
p.000076: Scientific validity and alternative trial designs. Disasters unfold quickly and study designs need to be
...
p.000077: disaster. However, reviewing generic research protocols in advance cannot substitute for the ethical review of specific
p.000077: research protocols in a disaster. Local ethics review should be carried out whenever possible.
p.000077:
p.000077: Informed consent. Even though most disaster victims are under duress, it is important to obtain their informed consent
p.000077: for study participation and especially to emphasize the difference between research and humanitarian aid. To
p.000077: explain the difference is especially important in the context of clinical trials that test experimental
p.000077: interventions in the early phases of development. The fact that potential participants are under duress does not
p.000077: prevent them from making a voluntary decision (Guideline 9 – Individuals capable of giving informed consent). The
p.000077: informed consent process must be designed in a way that is comprehensible and sensitive to persons who are under
p.000077: duress.
p.000077:
p.000077: Special protections for individuals incapable of giving informed consent may apply, as described in
p.000077: Guideline 16 – Research involving adults incapable of giving informed consent, in the section on Emergency care
p.000077: situations in which the researcher anticipates that many participants will be unable to consent.
p.000077:
p.000077: Individual informed consent may be waived for the sharing and analysis of surveillance data provided that the
p.000077: conditions of Guideline 10 – Modifications and waivers of informed consent - are met and appropriate governance systems
p.000077: for these data are put in place.
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000078:
p.000078:
p.000078:
p.000078:
p.000078:
p.000078: GUIDELINE 21:
p.000078: CLUSTER RANDOMIZED TRIALS
p.000078:
p.000078: In advance of initiating a cluster randomized trial, researchers, sponsors, relevant authorities, and
p.000078: research ethics committees should:
p.000078: f determine who are the research participants and what other individuals or groups are affected, even though they are
p.000078: not directly targeted;
p.000078: f determine whether it is required or feasible to obtain informed consent from patients, health care workers, or
p.000078: community members in certain studies;
p.000078: f determine whether requiring informed consent and allowing refusal to consent may invalidate or compromise
p.000078: the research results;
...
p.000100: agreement, or assent, will be obtained, as well as the permission of a parent, or a legal guardian or other duly
p.000100: authorized representative (Guidelines 16 and 17);
p.000100:
p.000100: 32. An account of any economic or other inducements or incentives to prospective participants to
p.000100: participate, such as offers of cash payments, gifts, or free services or facilities, and of any financial obligations
p.000100: assumed by the participants, such as payment for medical services;
p.000100:
p.000100: 33. Plans and procedures, and the persons responsible, for communicating to participants information arising from the
p.000100: study (on harm or benefit, for example), or from other research on the same topic, that could affect participants’
p.000100: willingness to continue in the study (Guideline 9);
p.000100:
p.000100: 34. Plans to inform participants about the results of the study;
p.000100:
p.000100: 35. The provisions for protecting the confidentiality of personal data, and respecting the privacy of persons,
p.000100: including the precautions that are in place to prevent disclosure of the results of a subject’s genetic
p.000100: tests to immediate family relatives without the consent of the subject (Guidelines 4, 11, 12 and 24);
p.000100:
p.000100: 36. Information about how the code, if any, for the persons’ identity is established, where it will be kept and when,
p.000100: how and by whom it can be broken in the event of an emergency (Guidelines 11 and 12);
p.000100:
p.000100: 37. Any foreseen further uses of personal data or biological materials (Guidelines 11 and 12);
p.000100:
p.000100: 38. A description of the plans for statistical analysis of the study, including plans for interim analyses, if any,
p.000100: and criteria for prematurely terminating the study as a whole if necessary (Guideline 4);
p.000100:
p.000100: 39. Plans for monitoring the continuing safety of drugs or other interventions administered for purposes
p.000100: of the study or trial and, if appropriate, the appointment for this purpose of an independent
p.000100: data-monitoring (data and safety monitoring) committee (Guideline 4);
p.000100:
p.000100: 40. A list of the references cited in the protocol;
p.000100:
p.000100: 41. The source and amount of funding of the research: the organization that is sponsoring the research
p.000100: and a detailed account of the sponsor’s financial commitments to the research institution, the
p.000100: investigators, the research participants, and, when relevant, the community (Guideline 25);
p.000100:
p.000100:
p.000100:
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p.000101: 101
p.000101:
p.000101:
p.000101:
p.000101:
p.000101:
p.000101: 42. The arrangements for dealing with financial or other conflicts of interest that might affect the judgement of
p.000101: investigators or other research personnel: informing the institutional conflict-of-interest committee of such conflicts
p.000101: of interest; the communication by that committee of the pertinent details of the information to the ethical review
p.000101: committee; and the transmission by that committee to the research participants of the parts of the information that it
p.000101: decides should be passed on to them (Guideline 25);
...
p.000117: Collaborative partnership 27, 29, 30, 42, 45, 47, 52, 89
p.000117: Collection, collecting 26, 36, 39, 41 - 43, 47 - 50, 77, 80, 83 - 85, 92, 103, 105
p.000117: Community engagement ix, xi, 5, 10, 23, 25, 26, 29, 30, 42, 45, 47, 52, 59, 63, 75, 78, 102
p.000117: Comparative effectiveness research 16, 19
p.000117: Compassionate use 22
p.000117: Compelling scientific reasons 15 - 18
p.000117: Compensation 13, 53 - 56, 96, 100, 104 Competent. See Capable of giving informed consent Comprehension 34
p.000117: Confidentiality 11, 13, 41, 42, 44, 47, 48, 50, 51, 57, 59, 70, 100, 101, 102, 104, 105
p.000117: Conflicts of interest 5, 30, 34, 78, 89, 92, 95 - 97, 102, 104
p.000117: Continued access 21 - 23, 101, 104
p.000117: Control 9, 12, 15 - 18, 22, 26, 45, 51, 62, 67, 73, 79, 80, 83, 85,
p.000117: Custodian 41, 43, 44, 47, 49, 50, 105
p.000117: D
p.000117: Databank 47 - 52
p.000117:
p.000117:
p.000117: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000117:
p.000119: 119
p.000119:
p.000119: Data mining 50
p.000119: Data sharing 29, 31, 51, 85, 92
p.000119: Deception, deceiving 33, 38, 57
p.000119: Deliberate objection 67
p.000119: Dependent relationship 26, 35, 36, 58, 96
p.000119: Digital 83, 106
p.000119: Disaster ix, 75 - 78, 106
p.000119: Disclosure 44, 45, 51, 84, 85, 91, 95, 97, 101, 103 - 105
p.000119: Disease outbreak ii, x, 19, 34, 41, 44, 47, 49, 83, 96, 97, 99, 103, 105
p.000119: Dissemination 2, 4, 25, 85, 92
p.000119: Dissent 62, 67
p.000119: E
p.000119: Education 2, 30, 57, 89, 97
p.000119: Emergency care 63, 68, 78
p.000119: Equitable distribution 4, 7, 42, 45, 47, 52, 75, 77
p.000119: Established effective intervention viii, 9, 12, 15 - 19
p.000119: Ethical review xii, 2, 29, 30, 39, 76 - 78, 87 - 90, 95, 97, 99, 102
p.000119: Externally sponsored research 87, 89
p.000119: F
p.000119: Fairness 2
p.000119: Fetus 58, 69, 70 - 73
p.000119: Free medical treatment 56
p.000119: G
p.000119: Gatekeeping 80
p.000119: Governance 41 - 43, 44, 47, 48, 50, 51, 78
p.000119: H
p.000119: Harms 10, 11, 12, 18, 54, 55, 56, 70, 72, 91, 105
p.000119: Health needs 2 - 4, 8, 17, 19, 21 - 23, 26, 55, 61, 65, 69, 71, 72, 75, 76, 104
p.000119: I
p.000119: Identifiable 38, 39, 51, 84
p.000119: Implementation research 80
p.000119: Incentives 10, 54, 92, 101
p.000119: Information leaflet 34
p.000119: Informed consent ix, 2, 9, 10, 21, 25, 26, 33 - 39, 41 - 45, 47 - 52, 54, 56, 58, 61 - 65, 67 - 72, 75,
p.000119: 76, 78 - 80, 89, 96, 97, 100, 101, 103, 105
p.000119: Informed opt-out /opt-in 41, 44, 47, 49, 83
p.000119: In-kind 54
p.000119: Interventions 1 - 4, 9 - 12, 15 - 19, 21 - 23, 26, 30, 53, 55, 56, 61 - 63, 65, 66, 71 - 73, 75 - 81, 84,
p.000119: 88, 91, 100, 101, 104
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000120: 120
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
p.000120: Low-resource settings viii, ix, 3 - 5, 7, 17, 19, 22, 23, 26, 45, 47, 52, 75 - 77, 80, 89, 92
p.000120: M
...
General/Other / Relationship to Authority
Searching for indicator authority:
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p.000001: reasonable in light of the importance of the research, and other requirements discussed in this document. Research must
p.000001: also be sensitive to issues of justice and fairness. This concern is manifest in choosing whose health needs
p.000001: are investigated; how risks, burdens, and anticipated benefits of individual studies are distributed; and who will
p.000001: have access to any resulting knowledge and interventions. These and other ethical aspects of research are discussed in
p.000001: the following guidelines and commentaries. The research protocol submitted for ethical review must include, when
p.000001: relevant, the items specified in Appendix I, and must be carefully followed in conducting the research.
p.000001:
p.000001: Dissemination of results of research. Dissemination is essential to achieving social value. The importance
p.000001: of disseminating scientific information, including negative findings, is discussed in Guideline 23 – Requirements
p.000001: for establishing research ethics committees and for their review of protocols.
p.000001:
p.000001:
p.000001: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000002: 2
p.000002:
p.000002:
p.000002:
p.000002:
p.000002:
p.000002: GUIDELINE 2:
p.000002: RESEARCH CONDUCTED IN LOW-RESOURCE SETTINGS
p.000002:
p.000002:
p.000002: Before instituting a plan to undertake research in a population or community in low-resource settings, the sponsor,
p.000002: researchers, and relevant public health authority must ensure that the research is responsive to the health needs or
p.000002: priorities of the communities or populations where the research will be conducted.
p.000002:
p.000002: As part of their obligation, sponsors, and researchers must also:
p.000002: f make every effort, in cooperation with government and other relevant stakeholders, to make available as soon
p.000002: as possible any intervention or product developed, and knowledge generated, for the population or community in
p.000002: which the research is carried out, and to assist in building local research capacity. In some cases, in order to
p.000002: ensure an overall fair distribution of the benefits and burdens of the research, additional benefits such
p.000002: as investments in the local health infrastructure should be provided to the population or community; and
p.000002: f consult with and engage communities in making plans for any intervention or product developed available, including
p.000002: the responsibilities of all relevant stakeholders.
p.000002:
p.000002:
p.000002: Commentary on Guideline 2
p.000002: General considerations. This Guideline pertains to settings in which resources are so limited that the
p.000002: population may be vulnerable to exploitation by sponsors and investigators from wealthier countries and communities.
p.000002: The ethical standards applied should be no less stringent than they would be for research carried out in
p.000002: high-resource settings. To ensure that people in low-resource settings receive equitable benefit from their
p.000002: participation in health-related research, this Guideline demands that local social value be created. Low-resource
...
p.000003: conditions of authorization for distribution, and decisions regarding payments, royalties, subsidies, technology and
p.000003: intellectual property, as well as distribution costs, when such information is not proprietary. A plan to ensure the
p.000003: availability and distribution of successful products can require engaging with international organizations, donor
p.000003: governments and bilateral agencies, civil society organizations, and the private sector. The ability of the local
p.000003: health- care infrastructure to be able to provide the intervention must be facilitated at the outset so that delivery
p.000003: is possible following the completion of the research.
p.000003:
p.000003: Post-trial availability for communities and populations. Even if research addresses a question that has social value
p.000003: for the community or population where it is carried out, the community or population will not benefit from
p.000003: successful research unless the knowledge and interventions that it produces are made available to them and products are
p.000003: reasonably priced. Post-trial access plans are of particular concern for research conducted in low-resource settings
p.000003: where governments lack the means or infrastructure to make such products widely available.
p.000003:
p.000003: An investigational drug is unlikely to be generally available to the community or population until
p.000003: sometime after the conclusion of the study, as it may be in short supply, and in most cases could not be made generally
p.000003: available before a drug regulatory authority has approved it. However, other successful outcomes of research that
p.000003: do not require approval by a regulatory agency should be implemented as soon as feasible. An example is the
p.000003: introduction of male circumcision in countries with a high burden of HIV disease. Research demonstrated a significant
p.000003: preventive effect of male circumcision, following which, programmes to offer male circumcision were introduced in
p.000003: several countries.
p.000003:
p.000003: When the outcome is scientific knowledge rather than a commercial product, complex planning or negotiation among
p.000003: relevant stakeholders may not be needed. There must be assurance, however, that the scientific knowledge gained will be
p.000003: distributed and available for the benefit of the population. To that end, agreement must be reached with the local
p.000003: community about the form such dissemination
p.000003:
p.000003:
p.000003: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000004: 4
p.000004:
p.000004:
p.000004:
p.000004:
p.000004:
p.000004: should take. One example might be a study that learns why a health condition such as neural tube defects is prevalent
p.000004: in a particular population. Another example could be a study that results in knowledge to educate the
p.000004: population about foods to eat or avoid in order to promote or maintain health.
p.000004:
p.000004: These requirements for post-trial availability to communities and populations must not be construed as precluding
p.000004: studies designed to evaluate novel therapeutic concepts. An example might be research designed to obtain
...
p.000025: of the informed consent process and documents to ensure that they are understandable and appropriate for potential
p.000025: participants.
p.000025:
p.000025: Confidence and trust. Engaging the community strengthens local ownership of the research and builds confidence in
p.000025: the ability of leaders to negotiate various aspects of the research, such as recruitment strategies, care
p.000025: for the health needs of study participants, site selection, data collection and sharing, ancillary care and post-trial
p.000025: availability of any developed interventions for populations and communities (see Guideline 2 – Research conducted in
p.000025: low-resource settings, and Guideline 6
p.000025: – Caring for participants’ health needs). An open and active process of community engagement is critical for building
p.000025: and maintaining trust among researchers, participants, and other members of the local community. An illustration of
p.000025: successful involvement of the community was a study in the Eliminate Dengue Program in Queensland, Australia. Previous
p.000025: introductions of genetically-modified strategies for dengue vector control had generated international controversy by
p.000025: inadequately engaging host communities. This successful episode used well-established techniques in social
p.000025: science to understand the community’s concerns and gain their support for conducting the trial.
p.000025:
p.000025: Roles and responsibilities. Any disagreements that may arise regarding the design or conduct of the research must be
p.000025: subject to negotiation between community leaders and the researchers. The process must ensure that all voices are
p.000025: heard, and that pressure is not exerted by community members or groups with greater power or authority. In cases of
p.000025: irreconcilable differences between the community and researchers, it is important to specify in advance who
p.000025: will have the final say. The community must not be permitted to insist on including or omitting certain
p.000025: procedures that could threaten the scientific validity of the research. At the same time, the research team must be
p.000025: sensitive to cultural norms of communities in order to support collaborative partnerships, preserve
p.000025:
p.000025:
p.000025: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000026: 26
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026: trust, and ensure relevance. The value of beginning community involvement at the earliest opportunity is that any such
p.000026: disagreements can be aired, and if unable to be resolved, the research may have to be forgone (see Guideline 8 –
p.000026: Collaborative partnership and capacity-building for research and research review). If a research ethics committee is
p.000026: confronted with a severe split in the community about the design or conduct of a proposed study, the committee should
p.000026: urge the researchers to conduct the study in another community.
p.000026:
p.000026: Engagement by communities or groups. In some cases, communities or groups themselves initiate or conduct
p.000026: research projects. For example, patients with rare diseases may connect on online platforms and decide to collectively
p.000026: alter their treatment regimen while documenting the resulting clinical effects. Researchers should engage with these
...
p.000034: obtaining consent or by a witness at the time consent is obtained.
p.000034:
p.000034: Renewing consent. When substantive changes occur in any aspect of a study, the researcher must again seek
p.000034: informed consent from the participants. For example, new information may have come to light, either from the study
p.000034: itself or other sources, about the risks or benefits of products being tested or about alternatives to them.
p.000034: Participants must be given such information promptly. In most clinical trials, interim results are not disclosed to
p.000034: researchers or participants until the study has been concluded. In long-term studies, the willingness of each
p.000034: participant to continue in the study must be ensured.
p.000034:
p.000034: Individual informed consent and access to research populations. In some circumstances, a researcher may
p.000034: enter a community or institution to conduct research or approach potential participants for their individual
p.000034: consent only after obtaining permission from an institution such as a school or a prison, or from a community leader, a
p.000034: council of elders, or another designated authority. Such institutional procedures or cultural customs should be
p.000034: respected. In no case, however, may the permission of a community leader or other authority substitute for individual
p.000034: informed consent. In some populations, the use of local languages may facilitate the communication of information to
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
...
p.000038: creation and maintenance of health-related registries (for example, cancer registries and databanks of genetic and
p.000038: other anomalies in newborn babies) provide a major resource for many public health and epidemiological research
p.000038: activities, ranging from disease prevention to resource allocation. Several considerations support the common practice
p.000038: of requiring that all practitioners submit relevant data to such registries: the importance of having
p.000038: comprehensive and accurate information about an entire population; the scientific need to include all
p.000038: cases in order to avoid undetectable selection bias; and the ethical principle that burdens and benefits must be
p.000038: distributed equitably across the population. Hence, registries established as mandatory by governmental
p.000038: authorities usually involve obligatory rather than voluntary collection of data.
p.000038:
p.000038: When a study is performed under a public health mandate or by public health authorities, such as disease surveillance,
p.000038: normally neither ethical review nor a waiver of consent is needed because the activity is mandated by law. At the same
p.000038: time, consent cannot be waived when public health authorities conduct studies in which data in the registries are
p.000038: combined with new activities that involve direct contact with persons, such as studies in which they obtain
p.000038: information from individuals by using questionnaires. Although the extent and limits of data collection are
p.000038: determined by law, researchers must still consider whether, in a given case, it is ethical to use their authority to
p.000038: access personal data for research purposes. When the use of such data does not constitute (or no longer clearly
p.000038: constitutes) a public health activity, the researcher must seek individual consent for the use of the data or
p.000038: demonstrate that the research meets the conditions for waiving informed consent, as set out in this Guideline. Research
p.000038: projects using data from one or more mandatory population-based registries should be submitted to a research ethics
p.000038: committee, except for data analyses involving internal institutional activity of a registry.
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
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p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
p.000038:
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p.000038: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: GUIDELINE 11:
p.000039: COLLECTION, STORAGE AND USE OF BIOLOGICAL MATERIALS AND RELATED DATA
p.000039:
p.000039: When biological materials and related data, such as health or employment records, are collected and stored,
p.000039: institutions must have a governance system to obtain authorization for future use of these materials in research.
p.000039: Researchers must not adversely affect the rights and welfare of individuals from whom the materials were collected.
p.000039:
...
p.000068: trials of drugs, vaccines and medical devices owing to concern about undetermined risks to the fetus (see
p.000068: Guideline 15 – Research involving vulnerable persons and groups). Although the presumption against including women
p.000068: has changed in recent years, they are still excluded in many cases without adequate justification. Much remains unknown
p.000068: about the safety and efficacy of most drugs, vaccines, or devices used by women in medical practice, and
p.000068: this lack of knowledge can be dangerous. For example, heart attacks in women are different from heart attacks in men,
p.000068: so research is necessary to determine the best means of diagnosis and treatment in women.
p.000068:
p.000068: Vulnerability of women. Despite the current general presumption that favours the inclusion of women in
p.000068: research, in many societies women remain socially vulnerable in the conduct of research. For example, they may
p.000068: suffer negligence or harm because of their submission to authority, their hesitancy or inability to ask
p.000068: questions, and a cultural tendency to deny or tolerate pain and suffering. When women in these situations are potential
p.000068: participants in research, researchers, sponsors and ethics committees must take special care in the research design,
p.000068: assessment of risks and benefits, as well as the process of informed consent, to ensure that women have
p.000068: the necessary time and appropriate environment to make decisions based on information provided to them.
p.000068:
p.000068: Some women become vulnerable in research because of heightened psychological, social, physical, or legal risks.
p.000068: Examples include surveys and interviews regarding intimate partner violence and rape; social and behavioural
p.000068: research involving sex workers or women who inject drugs; and studies that solicit information about sexual behaviour.
p.000068: When the research involves household surveys or interviews, researchers must take special care to ensure that the women
p.000068: are interviewed in a private
p.000068:
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p.000069:
p.000069:
p.000069:
p.000069:
p.000069:
...
p.000076:
p.000076:
p.000076: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077: a variation in critical background factors (for example mortality and infection rates), and measurement of outcomes,
p.000077: among others. Researchers and sponsors must carefully evaluate the relative merits of different designs (for example
p.000077: observational or placebo-controlled) based on these factors.
p.000077:
p.000077: Community engagement. Because disasters often lead to vulnerability and fragile political and social situations,
p.000077: engaging local communities about the research at an early stage is essential for maintaining public trust and ensuring
p.000077: that studies are conducted in a culturally sensitive manner (see Guideline 7 – Community engagement). Researchers and
p.000077: sponsors can use creative mechanisms to expedite and facilitate community engagement in a disaster situation (for
p.000077: example, by using social media). Fostering community leadership will often be important to address distrust and
p.000077: communicate effectively in order to gain support for the study design. In engaging with communities, researchers,
p.000077: sponsors and research ethics committees should be aware of potential conflicts of interest vis-à-vis the proposed
p.000077: research. For example, community leaders might seek to reassert their own authority by providing services to their
p.000077: communities through research.
p.000077:
p.000077: Ethical review and oversight. The standard mechanism for ethical review will often be too time-consuming
p.000077: to enable full research protocols to be prepared and reviewed at the outset of a disaster. Procedures
p.000077: should be developed to facilitate and accelerate ethical review in a situation of crisis. For example, research ethics
p.000077: committees or a specialist ethics committee (perhaps on a national or regional level) may conduct an initial
p.000077: accelerated review of study protocols and continue oversight if studies raise significant ethical concerns. Research in
p.000077: disaster situations should ideally be planned in advance. This can involve, among other things, submitting partial
p.000077: study protocols for ethical “pre-screening” and drafting arrangements for data and sample sharing among collaborators.
p.000077: Health officials might also create an international network of specialists that could assist local review during a
p.000077: disaster. However, reviewing generic research protocols in advance cannot substitute for the ethical review of specific
p.000077: research protocols in a disaster. Local ethics review should be carried out whenever possible.
p.000077:
p.000077: Informed consent. Even though most disaster victims are under duress, it is important to obtain their informed consent
p.000077: for study participation and especially to emphasize the difference between research and humanitarian aid. To
...
p.000079: withholding the proven intervention from the control cluster would expose participants to more than a minor
p.000079: increase above minimal risk, it would be unethical to use that study design. An example would be the introduction of
p.000079: sterilizing equipment or disposable needles in a resource-poor health centre with a high infection rate among the
p.000079: patients. In the implementation CRT, health care workers would have to be educated in the use of the new equipment
p.000079: and instructed to throw away the disposable needles. Since the reuse of needles without sterilization would
p.000079: expose patients to more than a minor increase above minimal risk, it would be unethical for the control cluster to
p.000079: continue the usual practice. In such cases, it is necessary for researchers to explore an alternative design, such as
p.000079: using historical controls from the same facility. Research ethics committees have the responsibility to
p.000079: determine whether the proposed research is ethically acceptable when the methodology calls for withholding an
p.000079: established effective treatment from the control cluster.
p.000079:
p.000079: Gatekeeping in cluster randomized trials. When a CRT substantially affects cluster or organizational
p.000079: interests, and a gatekeeper (for example, a community leader, headmaster, or local health council) possesses the
p.000079: legitimate authority to make decisions on the cluster or organization’s behalf, the researcher must obtain the
p.000079: gatekeeper’s permission to enrol the cluster or organization in the trial. Such permission does not replace the need to
p.000079: obtain individual informed consent where
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p.000080:
p.000080:
p.000080:
p.000080:
p.000080:
p.000080: this is required. Although a gatekeeper may not have been appointed or elected for the specific purpose
p.000080: of giving permission for the cluster to participate in research, the scope of authority must encompass interventions of
p.000080: the type in question when provided outside a research project. Moreover, the decision-maker must ensure that the risks
p.000080: of participation in the study and the randomisation are commensurate with the benefits for the cluster or for
p.000080: society. The gatekeeper may choose to consult a wider group of community representatives or advisers
p.000080: before taking the decision to permit the study.
p.000080:
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p.000081:
p.000081:
p.000081:
p.000081:
p.000081:
p.000081: GUIDELINE 22:
p.000081: USE OF DATA OBTAINED FROM THE ONLINE ENVIRONMENT AND
p.000081: DIGITAL TOOLS IN HEALTH-RELATED RESEARCH
p.000081:
p.000081: When researchers use the online environment and digital tools to obtain data for health- related research they should
p.000081: use privacy-protective measures to protect individuals from the possibility that their personal information is
p.000081: directly revealed or otherwise inferred when datasets are published, shared, combined or linked. Researchers should
p.000081: assess the privacy risks of their research, mitigate these risks as much as possible and describe the remaining risks
...
p.000085:
p.000085: Research ethics committees must be formally established and given adequate mandate and support to ensure timely and
p.000085: competent review according to clear and transparent procedures. Committees must include multidisciplinary membership in
p.000085: order to competently review the proposed research. Committee members must be duly qualified and regularly update their
p.000085: knowledge of ethical aspects of health-related research. Research ethics committees must have mechanisms to
p.000085: ensure independence of their operations.
p.000085:
p.000085: Research ethics committees from different institutions or countries should establish efficient communication
p.000085: in cases of externally sponsored and multi-centre research. In externally sponsored research, ethical review
p.000085: must take place in both the host and the sponsoring institution.
p.000085:
p.000085: Research ethics committees should have a clear procedure for researchers or sponsors to make legitimate appeals against
p.000085: the decisions of research ethics committees.
p.000085:
p.000085:
p.000085: Commentary on Guideline 23
p.000085: General considerations. Research ethics committees may function at the institutional, local, regional, or
p.000085: national levels, and in some cases at the international level. They must be established in accordance with rules set by
p.000085: a national or other recognized authority. Regulatory or other governmental authorities must promote uniform standards
p.000085: for committees within a country. Research institutions and governments must allocate sufficient resources for the
p.000085: ethical review process. Contributions of study sponsors to institutions or governments to support ethics
p.000085: review must be transparent.
p.000085:
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p.000087:
p.000087:
p.000087:
p.000087:
p.000087:
p.000087: Under no circumstances may payment be offered or accepted to procure a committee’s approval or clearance of a protocol.
p.000087:
p.000087: Scientific and ethical review. Although in some instances scientific review precedes ethical review,
p.000087: research ethics committees must always have the opportunity to combine scientific and ethical review in
p.000087: order to ensure the social value of the research (see Guideline 1 – Scientific and social value and respect for
p.000087: rights). The ethical review must consider, among other aspects: the study design; provisions for minimizing
p.000087: risk; an appropriate balance of risks in relation to potential individual benefits for participants and the
p.000087: social value of the research; safety of the study site, medical interventions, and monitoring safety during
p.000087: the study; and the feasibility of the research. Scientifically unsound research involving humans is unethical in that
...
p.000088: must avoid any undue influence and minimize and manage conflicts of interests. Research ethics committees must
p.000088: require that their members disclose to the committee any interests they may have that could constitute a conflict of
p.000088: interest or otherwise bias their evaluation of a research proposal. Research ethics committees must evaluate each study
p.000088: in light of any disclosed interests and ensure that appropriate steps are taken to mitigate possible conflicts of
p.000088: interest (see Guideline 25 – Conflicts of interest). Research ethics committees may receive a fee for reviewing
p.000088: studies. However, this need not constitute a conflict of interest (see Guideline 25 – Conflicts of interest).
p.000088:
p.000088: National (centralized) or local review. Research ethics committees may be created under the aegis of national or local
p.000088: administrations, national (or centralized) medical research councils or other nationally representative bodies. In
p.000088: a highly centralized administration, a national, or centralized, review committee may be constituted for both
p.000088: scientific and ethical review of research protocols. In countries where medical research is not centrally
p.000088: administered, ethical review can also be undertaken at a local or regional level. Whether research is nationally
p.000088: or locally reviewed varies and may depend on the size of the country and the type of the research. The authority of a
p.000088: local research ethics committee may be confined to a single institution or may extend to all institutions in which
p.000088: health-related research is carried out within a defined geographical area or network.
p.000088:
p.000088: Externally sponsored research. Research may be externally sponsored, meaning that it is sponsored, financed,
p.000088: and sometimes wholly or partly carried out by an external organization with the collaboration or agreement of the
p.000088: appropriate authorities of the host community. External sponsors must collaborate with local partners (see Guideline 8
p.000088: – Collaborative partnership and capacity building for research and review). Researchers and sponsors who plan to
p.000088: perform research in settings where research ethics committees are absent or lack adequate training should
p.000088: help to establish such committees according to their ability before the research is initiated, and make provisions
p.000088: for their education in research ethics (see Guideline 8 – Collaborative partnership and capacity building for research
p.000088: and review).
p.000088:
p.000088: Externally sponsored research must be reviewed at the site of the sponsor as well as locally. The ethical standards
p.000088: should be no less stringent than they would be for research carried out in the country of the sponsoring organization
p.000088: (see also Guideline 2 – Research conducted in low-resource settings). Local committees must be fully empowered to
...
p.000089: committee containing a summary of the study’s findings and conclusions.
p.000089:
p.000089: Protocol amendments, deviations, violations and sanctions. During the study, deviations from the original
p.000089: study might occur, such as changes in the sample size or analysis of the data as described in the protocol. Deviations
p.000089: must be reported to research ethics committees. In the case of permanent deviations, researchers may write an
p.000089: amendment. The research ethics committee must decide whether a deviation is legitimate or illegitimate. Protocol
p.000089: violations are deviations from the original protocol that significantly affect the rights or interests of
p.000089: research participants and significantly impact the scientific validity of the data. In the case of
p.000089: protocol violations, research ethics committees should ensure that study participants will be informed and provision
p.000089: will be made for the protection of their safety and welfare.
p.000089:
p.000089: A researcher may fail to submit a protocol to a research ethics committee for prospective review. This omission is a
p.000089: clear and serious violation of ethical standards, unless applicable regulations specify conditions for
p.000089: exemptions from review.
p.000089:
p.000089: Research ethics committees generally do not have the authority to impose sanctions on researchers for protocol
p.000089: violations or violations of ethical standards in the conduct of research involving humans. However, committees may halt
p.000089: the continuation of a previously approved protocol if it finds protocol violations or other misconduct on the part of
p.000089: researchers. Committees must report to the sponsor and institutional or governmental authorities any serious or
p.000089: continuing non-compliance with ethical standards in the conduct of previously approved research projects.
p.000089:
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p.000090:
p.000090:
p.000090:
p.000090:
p.000090:
p.000090: GUIDELINE 24:
p.000090: PUBLIC ACCOUNTABILITY FOR HEALTH-RELATED RESEARCH
p.000090:
p.000090: Public accountability is necessary for realizing the social and scientific value of health- related
p.000090: research. Therefore, researchers, sponsors, research ethics committees, funders, editors and publishers have an
p.000090: obligation to comply with recognized publication ethics for research and its results.
p.000090:
p.000090: Researchers should prospectively register their studies, publish the results and share the data on which these results
p.000090: are based in a timely manner. Negative and inconclusive as well as positive results of all studies should be published
p.000090: or otherwise be made publicly available. Any publication or report resulting from a research study should indicate
p.000090: which research ethics committee has authorized the study.
p.000090:
...
p.000101: capacity-building for scientific and ethical review and for health-related research in the host country, and an
p.000101: assurance that the capacity-building objectives are in keeping with the values and expectations of the participants and
p.000101: their communities (Guideline 8);
p.000101:
p.000101: 44. The research protocol or documents send to the research ethics committee should include a description of the plan
p.000101: for (continued) community engagement, and present resources allocated for the community engagement activities. This
p.000101: documentation must clarify what has been and will be done, when and by whom to ensure that the community is clearly
p.000101: mapped and defined and can be proactively engaged throughout the research to ensure that the research is relevant to
p.000101: the community and is accepted. The community should participate, when feasible, in the actual discussion
p.000101: and preparation of the research protocol and documents (Guideline 7);
p.000101:
p.000101: 45. Particularly in the case of an industrial sponsor, a contract stipulating who possesses the right to publish the
p.000101: results of the study, and a mandatory obligation to prepare with, and submit to, the principal investigators the draft
p.000101: of the text reporting the results (Guideline 24);
p.000101:
p.000101: 46. In the case of a negative outcome, an assurance that the results will be made available, as
p.000101: appropriate, through publication or by reporting to the drug registration authority (Guideline 24);
p.000101:
p.000101: 47. Plans for publication of research results in certain fields (for example, epidemiology, genetics, sociology) that
p.000101: may present risks to the interests of communities, societies, families, or racially or ethnically defined groups and
p.000101: for minimizing risks to these groups, notably by maintaining confidentiality during and after the study and publishing
p.000101: the resulting data in a manner that is respectful of the interests of all concerned (Guideline 4); and
p.000101:
p.000101: 48. A statement that any proven evidence of falsification of data will be dealt with in accordance with the policy of
p.000101: the sponsor to take appropriate action against such unacceptable procedures.
p.000101:
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p.000102:
p.000102:
p.000102:
p.000102:
p.000102: APPENDIX 2
p.000102: OBTAINING INFORMED CONSENT: ESSENTIAL INFORMATION
p.000102: FOR PROSPECTIVE RESEARCH PARTICIPANTS
p.000102:
p.000102: Before requesting an individual’s consent to participate in research, the researcher must provide the
p.000102: following information, in language or another form of communication that the individual can understand (see
p.000102: also Guideline 9):
p.000102: 1. the purpose of the research, its methods, the procedures to be carried out by the researcher and the
...
p.000110: was appointed as Professor and Head of Department of the department of community health at the University of
p.000110: Pretoria in 1995, where he became the founding Director of the School of Health Systems and Public Health in 1999. He
p.000110: held this position until his appointment as Executive Director at COHRED in 2004. As such, he is also member of the
p.000110: COHRED Board, President of COHRED USA and board member of COHRED Africa. He has published widely in applied research,
p.000110: nutrition, immunization, environmental health, research capacity building, global public health education and ethics of
p.000110: international collaborative health research. As part of community service, he was director of the Elim Care Group
p.000110: Project, a health and development NGO in the north of South Africa, served on the board of the Nokuthula
p.000110: Centre for Disabled Children in Alexandra township in South Africa and offers strategic research and innovation
p.000110: development support to low- and middle-income countries. Carel holds two nationalities – South African and Netherlands
p.000110: – and has worked and lived in Africa, Europe, the United States and the Caribbean.
p.000110:
p.000110: Observer
p.000110: Ingrid Callies
p.000110: Dr Ingrid Callies, PHD (University Paris Descartes), LLM (University of Virginia), a member of the New
p.000110: York Bar and a bioethicist, is Head of Ethics and Coordinator of the Code Authority and Ethics Committee (Codeem) for
p.000110: the pharmaceutical industry in France at Leem, the French federation of the pharmaceutical industry (www.leem.org).
p.000110: Previously, she was Ethics Advisor at the Institut Pasteur, worked for the French National Agency for Research on Aids
p.000110: and Viral Hepatitis, and practised law at Hogan & Hartson LLP, a law firm now called Hogan Lovells. Co-editor of the
p.000110: Ethics of Research Section in the Elsevier International Encyclopedia of the Social and Behavioural
p.000110: Sciences, Ingrid Callies has also participated in major research projects, including LeukoTreat (a
p.000110: collaborative European project on leukodystrophy) and Satori (Stakeholders Acting Together On the ethical impact
p.000110: assessment of Research and Innovation).
p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
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p.000111:
p.000111:
p.000111:
p.000111:
p.000111: APPENDIX 4
p.000111: COMMENTATORS
p.000111:
p.000111:
p.000111:
p.000111: Institution/Organization Country Surname First name
p.000111: 1 Brazil Neto
p.000111: Sodre
p.000111: 2 Areteva, Nottingham United Kingdom Corfield Julie
p.000111:
p.000111: 3 Association of Clinical Research Professionals, Alexandria, VA
p.000111: 4 Caribbean Public Health Agency Research Ethics Committee
...
p.000113: 18 Facultad de Ciencias Médicas, Universidad Nacionalde Rosario, Rosario
p.000113: 19 Faculty of Medicine Benha University, Banha
p.000113: 20 Faculty of Pharmaceutical Medicine, London
p.000113: 21 FLACSO Argentina, Buenos Aires
p.000113: India Gopichandran Vijayaprasad
p.000113:
p.000113:
p.000113:
p.000113: United Kingdom Chiumento Anna
p.000113:
p.000113:
p.000113:
p.000113: Belgium Doppelfeld Elmar
p.000113:
p.000113:
p.000113: Argentina Diaz María del Carmen
p.000113:
p.000113: Egypt Elgndy Ibrahim
p.000113:
p.000113: United Kingdom Cottam Ben
p.000113:
p.000113: Argentina Luna Florencia Mastroleo Ignacio
p.000113: Melamed Irene
p.000113: 22 GADOR SA, Buenos Aires Argentina Roldán Emilio
p.000113:
p.000113: 23 Indian Council Medical Research (formerly Deputy DG), New Delhi
p.000113: 24 International Society for Biological and Environmental Repositories (ISBER), Vancouver
p.000113: 25 Médecins Sans Frontières, Ethics Review Board, Geneva
p.000113: 26 Nagasaki University, Nagasaki
p.000113: 27 National Bioethics Commission on Health
p.000113: 28 National Institute of Radiological Sciences, Fuji Toranomon Orthopedic Hospital
p.000113: 29 NHS Health Research Authority, London
p.000113: India Kumar Nandini
p.000113:
p.000113:
p.000113: Canada Terris Adam
p.000113:
p.000113:
p.000113:
p.000113: Switzerland Schopper Doris Japan Koonrungsesomboon
p.000113: Nut
p.000113: Ecuador Pacheco-Bastidas Víctor
p.000113:
p.000113: Japan Kurihara Chieko
p.000113:
p.000113:
p.000113: Saio Takeo
p.000113: United Kingdom Collett Clive
p.000113: 30 Novartis Switzerland Maman
p.000113: Marianne
p.000113:
p.000113:
p.000113:
p.000113:
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p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114:
p.000114: Institution/Organization Country Surname First name
p.000114:
p.000114: 31 Novo Nordisk A/S, Copenhagen
p.000114: 32 Núcleo de Bioética de Londrina- Londrina, Parana
p.000114: Denmark Zdravkovic Milan
p.000114:
p.000114: Brazil Diniz Nilza
p.000114: 33 Nuffield Council on Bioethics United Kingdom Whittall Hugh
p.000114:
p.000114: 34 Pan American Health Organization, Regional Office for the Americas of the World Health Organization, Washington
p.000114: DC
p.000114: 35 Panamerican University, Mexico City
p.000114: United States Saenz Carla
p.000114:
p.000114:
p.000114:
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General/Other / Undue Influence
Searching for indicator undue influence:
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p.000021: country’s health systems. Nevertheless, research with humans often involves interactions that enable researchers to
p.000021: detect or diagnose health problems during recruitment and the conduct of research. Similarly, clinical research
p.000021: often involves care and preventive measures in addition to the experimental interventions. In some cases,
p.000021: participants may continue to need the care or prevention provided during the research after their participation
p.000021: in the study has ended. This may include access to an investigational intervention that has demonstrated
p.000021: significant benefit. In all these situations, researchers and sponsors must show care and concern for the health and
p.000021: welfare of study participants. This is justified by the principle of beneficence, which requires researchers and
p.000021: sponsors to safeguard the health of participants when it is in their power to do so. It is also supported by the
p.000021: principle of reciprocity; participants assist researchers in generating valuable data and, in return,
p.000021: researchers should ensure that participants receive needed care or preventive measures to safeguard their health.
p.000021: Importantly, the obligation to care for participants’ health needs is not limited to research in countries with limited
p.000021: resources (see Guideline 2 – Research conducted in low-resource settings) but is a universal ethical requirement in
p.000021: research. Furthermore, even though the provision of care during and after the trial may be an incentive for people in
p.000021: low-resource settings to enrol, it should not be considered an undue influence.
p.000021:
p.000021: Ancillary care. Sponsors are, in general, not obliged to finance interventions or to provide health-care services
p.000021: beyond that which is necessary for the safe and ethical conduct of research. Nevertheless, when prospective
p.000021: participants cannot be enrolled in a study because they do not meet the inclusion criteria, or enrolled participants
p.000021: are found to have diseases unrelated to the research, researchers should advise them to obtain or refer them for
p.000021: medical care. In some circumstances, it may be relatively easy for researchers to treat the condition or refer
p.000021: participants to a centre where treatment can be provided. In other cases, researchers may not have the expertise to
p.000021: treat the condition effectively, and appropriate treatment may not be available locally as part of the public health
p.000021: system. How to provide ancillary care in this situation is a complex issue and decisions will need to be made on a
p.000021: case-by-case basis following discussion with research ethics committees, clinicians, researchers and
p.000021: representatives of government and health authorities in the host country. Accordingly, before research begins agreement
p.000021: must be reached on how to provide care to participants who already have, or who develop, diseases or conditions other
p.000021: than those being studied (for example, whether care will be provided for health conditions that are readily treated in
p.000021: the local health-care system).
p.000021:
p.000021: Transition to care or preventive measures after research. Because gaps in care and prevention can have significant
p.000021: impact on the welfare of participants, researchers and sponsors must make arrangements to transition participants to
...
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p.000031: 31
p.000031:
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: GUIDELINE 9:
p.000031: INDIVIDUALS CAPABLE OF GIVING INFORMED CONSENT
p.000031:
p.000031: Researchers have a duty to provide potential research participants with the information and the opportunity to give
p.000031: their free and informed consent to participate in research, or to decline to do so, unless a research ethics committee
p.000031: has approved a waiver or modification of informed consent (see Guideline 10 – Modifications and waivers of informed
p.000031: consent). Informed consent should be understood as a process, and participants have a right to withdraw at
p.000031: any point in the study without retribution.
p.000031:
p.000031: Researchers have a duty to:
p.000031: f seek and obtain consent, but only after providing relevant information about the research and
p.000031: ascertaining that the potential participant has adequate understanding of the material facts;
p.000031: f refrain from unjustified deception or withholding of relevant information, undue influence, or coercion (see
p.000031: Guideline 10 – Modifications and waivers of informed consent);
p.000031: f ensure that the potential participant has been given sufficient opportunity and time to consider whether to
p.000031: participate; and
p.000031: f as a general rule, obtain from each potential participant a signed form as evidence of informed
p.000031: consent. Researchers must justify any exceptions to this general rule and seek the approval of the research ethics
p.000031: committee.
p.000031:
p.000031: With the approval of the research ethics committee, researchers must renew the informed consent of each participant if
p.000031: there is a substantive change in the conditions or procedures of the research, or if new information becomes available
p.000031: that could affect the willingness of participants to continue. In long-term studies, researchers should ensure at
p.000031: pre-determined intervals that each participant is willing to stay in the study, even if there are no changes in the
p.000031: design or objectives of the research.
p.000031:
p.000031: It is the principal investigator’s responsibility to ensure that all personnel obtaining informed consent for a study
p.000031: comply with this Guideline.
p.000031:
p.000031:
p.000031: Commentary on Guideline 9
p.000031: General considerations. Informed consent is a process. The start of this process requires providing relevant
p.000031: information to a potential participant, ensuring that the person has adequately understood the material facts and
p.000031: has decided or refused to participate without having been subjected to coercion, undue influence, or
p.000031: deception.
p.000031:
p.000031:
p.000031:
p.000031:
p.000031: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000033: 33
p.000033:
p.000033:
p.000033:
p.000033:
p.000033:
p.000033: Informed consent is based on the principle that individuals capable of giving informed consent have a right to choose
p.000033: freely whether to participate in research. Informed consent protects the individual’s freedom of choice and respects
p.000033: the individual’s autonomy.
p.000033:
p.000033: The information must be provided in plain language understandable by the potential participant. The person
p.000033: obtaining informed consent must be knowledgeable about the research and capable of answering any questions from
p.000033: potential participants. Researchers in charge of the study must make themselves available to answer questions at the
p.000033: request of participants. Participants should be offered the opportunity to ask questions and receive answers before or
p.000033: during the research. Researchers should make every effort to address those questions in a timely and comprehensive
p.000033: manner.
p.000033:
p.000033: This Guideline applies to individuals capable of giving informed consent. Requirements for research with individuals
...
p.000034: respected. In no case, however, may the permission of a community leader or other authority substitute for individual
p.000034: informed consent. In some populations, the use of local languages may facilitate the communication of information to
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
p.000034: factors can be internal to participants, such as mental illness, whereas other influences can be external, such as a
p.000034: dependent relationship between participants and clinician-researchers. Circumstances such as severe illness or poverty
p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
p.000034: consent in these situations. Research ethics committees must determine for each individual protocol if influences on
p.000034: voluntary consent cross the threshold of being undue, and if so, which safeguards are appropriate.
p.000034:
p.000034: Dependent relationship. There are different forms of dependent relationships, such as those between
p.000034: teachers and students, and guards and prisoners. In the context of clinical research, dependent
p.000034: relationships can result from pre-existing relationships between a treating physician and a patient, who
p.000034: becomes a potential participant when his or her treating physician assumes the role of researcher. The
...
p.000087: prisoners or illiterate persons, representatives of relevant advocacy groups should be invited to meetings where such
p.000087: protocols will be reviewed (see
p.000087:
p.000087:
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p.000088: 88
p.000088:
p.000088:
p.000088:
p.000088:
p.000088:
p.000088: Guideline 15 – Research involving vulnerable persons and groups). Regular rotation of members is desirable for
p.000088: balancing the advantage of experience with that of fresh perspectives.
p.000088:
p.000088: Members of research ethics committees must regularly update their knowledge about the ethical conduct of health-related
p.000088: research. If committees do not have the relevant expertise to adequately review a protocol, they must consult
p.000088: with external persons with the proper skills or certification. Committees must keep records of their
p.000088: deliberations and decisions.
p.000088:
p.000088: Conflicts of interests on the part of committee members. Research ethics committees must provide independent ethical
p.000088: opinions. Pressure can be brought to bear from many different directions, not just financial. Research ethics
p.000088: committees must therefore have mechanisms to ensure the independence of their operations. In particular, they
p.000088: must avoid any undue influence and minimize and manage conflicts of interests. Research ethics committees must
p.000088: require that their members disclose to the committee any interests they may have that could constitute a conflict of
p.000088: interest or otherwise bias their evaluation of a research proposal. Research ethics committees must evaluate each study
p.000088: in light of any disclosed interests and ensure that appropriate steps are taken to mitigate possible conflicts of
p.000088: interest (see Guideline 25 – Conflicts of interest). Research ethics committees may receive a fee for reviewing
p.000088: studies. However, this need not constitute a conflict of interest (see Guideline 25 – Conflicts of interest).
p.000088:
p.000088: National (centralized) or local review. Research ethics committees may be created under the aegis of national or local
p.000088: administrations, national (or centralized) medical research councils or other nationally representative bodies. In
p.000088: a highly centralized administration, a national, or centralized, review committee may be constituted for both
p.000088: scientific and ethical review of research protocols. In countries where medical research is not centrally
p.000088: administered, ethical review can also be undertaken at a local or regional level. Whether research is nationally
p.000088: or locally reviewed varies and may depend on the size of the country and the type of the research. The authority of a
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p.000119: in line with the Declaration of Helsinki.
p.000119:
p.000119: At the beginning of October 2016 the final draft was submitted to the CIOMS Executive Committee, which approved the
p.000119: text at its General Assembly meeting in Geneva in November 2016.
p.000119:
p.000119: The final draft replaces all previous versions of the CIOMS ethical guidelines, both in the domain of
p.000119: biomedical and epidemiological research. At the same time, research projects that have been ethically
p.000119: assessed on the basis of previous versions of the guidelines may be continued on the terms and conditions as set out in
p.000119: those previous versions.
p.000119:
p.000119: Reactions to the Guidelines are welcome and should be addressed to the Secretary-General, Council for International
p.000119: Organizations of Medical Sciences, P.O. Box 2100, CH-1211 Geneva 2, Switzerland; or by email to info@cioms.ch.
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119: x
p.000119:
p.000119: EVIDENCE RETRIEVAL AND SYNTHESIS
p.000119: In the revision process, literature reviews were used as sources for further ethical deliberation.
p.000119: Authoritative declarations, reports and guidance documents have had a prominent role in these discussions,
p.000119: such as the Nuremberg Code (1947), the Universal Declaration of Human Rights of the United Nations (1948), the
p.000119: International Covenant on Civil and Political Rights of the United Nations (1966), the Belmont Report (1979), the
p.000119: Guideline on Good Clinical Practice (GCP) of the International Conference on Harmonisation of Technical Requirements
p.000119: for Registration of Pharmaceuticals for Human Use (ICH) (1996), the Oviedo Convention of the Council of Europe (1997),
p.000119: the Universal Declaration on Bioethics and Human Rights of UNESCO (2005), the UNAIDS/WHO Ethical
p.000119: Considerations in Biomedical HIV Prevention Trials (2007/2012), Standards and operational guidance for
p.000119: ethics review of health-related research with human participants of the WHO (2011), and the Declaration of Helsinki of
p.000119: the World Medical Association (2013). Some of these guidelines have been extensively used, in particular the UNAIDS/WHO
p.000119: document (2012) for Guideline 7 on community engagement.
p.000119:
p.000119: Textbooks, existing ethical frameworks for human subjects research and reports on research involving human beings
p.000119: were also valuable sources of information. The Working Group reviewed papers in major ethics journals (in
p.000119: alphabetical order) such as the American Journal of Bioethics, Bioethics, BMC Medical Ethics, the Cambridge
p.000119: Quarterly of Healthcare Ethics, Developing World Bioethics, the Hastings Center Report, the Journal of Bioethical
...
General/Other / cioms guidelines
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p.000007:
p.000007: International Ethical Guidelines for
p.000007: Health-related Research Involving Humans
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p.000007:
p.000007:
p.000007: Prepared by the Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the
p.000007: World Health Organization (WHO)
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p.000007: Geneva 2016
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p.000007:
p.000007:
p.000007:
p.000007: International Ethical Guidelines for
p.000007: Health-related Research Involving Humans
p.000007:
p.000007:
p.000007:
p.000007: Prepared by the Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the
p.000007: World Health Organization (WHO)
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p.000007: Geneva 2014
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p.000007:
p.000007:
p.000007: Copyright © 2016 by the Council for International Organizations of Medical Sciences (CIOMS) ISBN 978-929036088-9
p.000007:
p.000007:
p.000007:
p.000007: All rights reserved. CIOMS publications may be obtained directly from:
p.000007: CIOMS, P.O. Box 2100, CH-1211 Geneva 2, Switzerland, tel.: +41 22 791 6497, www.cioms.ch, e-mail: info@cioms.ch.
p.000007: CIOMS publications are also available through the World Health Organization, WHO Press, 20 Avenue Appia, CH-1211 Geneva
p.000007: 27, Switzerland.
p.000007: Citation for this document:
p.000007: International Ethical Guidelines for Health-related Research Involving Humans, Fourth Edition. Geneva. Council for
p.000007: International Organizations of Medical Sciences (CIOMS); 2016.
p.000007: The authors alone are responsible for the views expressed in this publication and those views do not necessarily
p.000007: represent the decisions, policies or views of their respective institutions or companies.
p.000007: Design and Layout: Paprika (Annecy, France)
p.000007:
p.000007: ACKNOWLEDGEMENTS
p.000007: The Council for International Organizations of Medical Sciences (CIOMS) acknowledges the contribution of the Working
p.000007: Group for the revision of the CIOMS Ethical Guidelines. In 2011, the Executive Committee of CIOMS decided
p.000007: to set up a Working Group to revise the CIOMS Guidelines. The Working Group consisted of 10 members (Anant Bhan,
p.000007: Eugenijus Gefenas, Dirceu Greco, David Haerry, Bocar Kouyate, Alex John London, Ruth Macklin, Annette Rid, Rodolfo
p.000007: Saracci, Aissatou Touré, one chair (Hans van Delden), four advisers, from WHO (Marie-Charlotte Bouësseau and later Abha
p.000007: Saxena), UNESCO (Dafna Feinholz), COHRED (Carel Ijsselmuiden) and WMA (Urban Wiesing and Hans-Joerg Ehni) and one
p.000007: scientific secretary (Rieke van der Graaf). All members of the Working Group were internationally
p.000007: recognized for their expertise in research. The composition of the Working Group ensured that different
p.000007: cultural perspectives were present, members varied in experience and expertise, and gender balance was
p.000007: achieved. One of the members represented the perspective of research participants. Their affiliations are indicated in
p.000007: Appendix 3.
p.000007:
p.000007: CIOMS is grateful for the valuable contributions of many commentators on its first draft from individual persons and
p.000007: institutions (see Appendix 4). Their detailed review and comments have greatly helped to shape the final document.
p.000007:
p.000007: A number of institutions and organizations made valuable contributions by providing hospitality to host meetings of the
p.000007: Working Group (Utrecht University, Netherlands; Vilnius University, Lithuania; and UNESCO, Paris, France).
p.000007:
p.000007: Special thanks are due to Carla Saenz and Tania Flores at PAHO, who at no cost translated comments submitted by
p.000007: Spanish-speaking persons and organizations into English. Their work has been tremendously helpful in ensuring
p.000007: meaningful global involvement in the revision process.
p.000007:
p.000007: The revision of these Guidelines has been carried out in collaboration with World Health Organization (WHO), the
p.000007: facilitation of which was led by Abha Saxena. As a result of this collaboration, the guideline development process is
p.000007: consistent with the standards and policies of WHO. The organization-wide review by WHO especially by the Ethics
p.000007: Review Committee was coordinated by Maria Magdalena Guraiib and Vânia de la Fuente Nunez. Ronald Johnson, Melba
p.000007: Gomes, Joan Dzenowagis and Sheryl VanderPoel have provided substantial inputs to the draft document.
p.000007:
p.000007: At CIOMS, Sev Fluss edited the draft document and provided constructive comments, and Gunilla Sjölin-Forsberg, the
p.000007: Secretary-General (SG) of CIOMS until the end of 2015, attended many meetings of the Working Group and contributed her
p.000007: experience from the many other Working Groups in which she has participated. Lembit Rägo has supported the revision
p.000007: work after becoming the new SG in April 2016. Finally, Caprice Fraiha and Sue le Roux have helpfully provided
p.000007: administrative support for the revision process.
p.000007:
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p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000007:
p.000007: iii
p.000007:
p.000007: CONTENTS
p.000007: ACKNOWLEDGEMENTS
p.000007: III
p.000007: PREFACE
p.000007: VIII
p.000007: EVIDENCE RETRIEVAL AND SYNTHESIS XI
p.000007: PREAMBLE
p.000007: XII
p.000007: GUIDELINE 1: SCIENTIFIC AND SOCIAL VALUE AND RESPECT FOR RIGHTS 1
p.000007: GUIDELINE 2: RESEARCH CONDUCTED IN LOW-RESOURCE SETTINGS 3
p.000007: GUIDELINE 3: EQUITABLE DISTRIBUTION OF BENEFITS AND BURDENS IN THE SELECTION OF INDIVIDUALS AND GROUPS OF PARTICIPANTS
p.000007: IN RESEARCH
p.000007: 7
p.000007: GUIDELINE 4: POTENTIAL INDIVIDUAL BENEFITS AND RISKS OF RESEARCH 9
p.000007: GUIDELINE 5: CHOICE OF CONTROL IN CLINICAL TRIALS 15
p.000007: GUIDELINE 6: CARING FOR PARTICIPANTS’ HEALTH NEEDS 21
p.000007: GUIDELINE 7: COMMUNITY ENGAGEMENT 25
p.000007: GUIDELINE 8: COLLABORATIVE PARTNERSHIP AND CAPACITY-BUILDING
p.000007: FOR RESEARCH AND RESEARCH REVIEW 29
...
p.000061: 61
p.000061: GUIDELINE 17: RESEARCH INVOLVING CHILDREN AND ADOLESCENTS 65
p.000061: GUIDELINE 18: WOMEN AS RESEARCH PARTICIPANTS 69
p.000061: GUIDELINE 19: PREGNANT AND BREASTFEEDING WOMEN AS
p.000061: RESEARCH PARTICIPANTS 71
p.000061: GUIDELINE 20: RESEARCH IN DISASTERS AND DISEASE OUTBREAKS 75
p.000061: GUIDELINE 21: CLUSTER RANDOMIZED TRIALS 79
p.000061: GUIDELINE 22: USE OF DATA OBTAINED FROM THE ONLINE
p.000061: ENVIRONMENT AND DIGITAL TOOLS IN HEALTH-RELATED RESEARCH 83
p.000061: GUIDELINE 23: REQUIREMENTS FOR ESTABLISHING RESEARCH ETHICS COMMITTEES AND FOR THEIR REVIEW OF PROTOCOLS
p.000087: 87
p.000087: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000087: vi
p.000087:
p.000087: GUIDELINE 24: PUBLIC ACCOUNTABILITY FOR HEALTH-RELATED RESEARCH 91
p.000087: GUIDELINE 25: CONFLICTS OF INTEREST 95
p.000087: APPENDIX 1 ITEMS TO BE INCLUDED IN A PROTOCOL (OR ASSOCIATED DOCUMENTS) FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000099: 99
p.000099: APPENDIX 2 OBTAINING INFORMED CONSENT: ESSENTIAL
p.000099: INFORMATION FOR PROSPECTIVE RESEARCH PARTICIPANTS 103
p.000099: APPENDIX 3 CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH
p.000099: INVOLVING HUMANS
p.000107: 107
p.000107: APPENDIX 4 COMMENTATORS 113
p.000107: INDEX
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p.000119: vii
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p.000119: PREFACE
p.000119: About CIOMS
p.000119: The Council for International Organizations of Medical Sciences (CIOMS) is an international nongovernmental
p.000119: organization in official relationship with World Health Organization (WHO). It was founded under the auspices of WHO
p.000119: and the United Nations Educational, Scientific and Cultural and Organization (UNESCO) in 1949. Among its mandates is
p.000119: maintaining collaborative relations with the United Nations and its specialized agencies, especially UNESCO and WHO.
p.000119:
p.000119: The first version of the CIOMS Guidelines (1982)
p.000119: CIOMS, in association with WHO, undertook its work on ethics in biomedical research in the late 1970s.
p.000119: Accordingly, CIOMS set out, in cooperation with WHO, to prepare guidelines. The aim of the guidelines was (and still
p.000119: is) to provide internationally vetted ethical principles and detailed commentary on how universal ethical principles
p.000119: should be applied, with particular attention to conducting research in low-resource settings. The outcome of the
p.000119: CIOMS/WHO collaboration was entitled Proposed International Ethical Guidelines for Biomedical Research Involving
p.000119: Human Subjects.
p.000119:
p.000119: The second version of the CIOMS Guidelines (1993)
p.000119: The period that followed saw the outbreak of the HIV/AIDS pandemic and proposals for large-scale trials of prevention
p.000119: and treatment for the disease. These developments raised new ethical issues that had not been considered in the
p.000119: preparation of the Proposed Guidelines. There were other factors also – rapid advances in medicine and
p.000119: biotechnology, changing research practices such as multinational field trials, experimentation involving
p.000119: vulnerable population groups, and also a new perspective in both high- and low-resource settings, that research
p.000119: involving humans could be beneficial to participants rather than threatening. The World Medical Association’s
p.000119: Declaration of Helsinki was revised twice in the 1980s – in 1983 and 1989. It was timely to revise and update the 1982
p.000119: Guidelines, and CIOMS, with the collaboration of WHO and its Global Programme on AIDS, undertook the
p.000119: task. The outcome was the issue of two sets of guidelines: International Guidelines for Ethical Review of
p.000119: Epidemiological Studies in 1991, and International Ethical Guidelines for Biomedical Research Involving Human Subjects
p.000119: in 1993.
p.000119:
p.000119: The third version of the CIOMS Guidelines (2002)
p.000119: After 1993, ethical issues arose for which the 1993 CIOMS Guidelines had no specific provisions. They related mainly
p.000119: to externally sponsored clinical trials carried out in low-resource settings. In particular, the use of
p.000119: comparators other than an established effective intervention used in low- resource settings became a concern.
p.000119: Commentators took opposing sides on this issue. This debate necessitated the revision and updating of the 1993
p.000119: Guidelines. CIOMS organized a consultation meeting with eight commissioned papers. After this meeting, a WG was set
p.000119: up that laboured over a period of two years during which there was a public posting of a draft with a request for
p.000119: comments. The revision process was finished in 2002.
p.000119:
p.000119: Epidemiological Guidelines (2009)
p.000119: The process of revising the 1993 version of the biomedical research Guidelines made clear that
p.000119: developments in the ethical analysis of all types of research using human subjects had potential
p.000119: implications for the 1991 Guidelines for epidemiological studies. Furthermore, the growing recognition of the
p.000119: importance of epidemiological research to improving the health of the public highlighted the
p.000119:
p.000119:
p.000119:
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p.000119:
p.000119: importance of bringing the 1991 Guidelines into line with current thinking on ethics and human rights.
p.000119: Therefore, in 2003 CIOMS constituted a core group to consider how the existing ethical guidance for
p.000119: epidemiological studies should be updated. Intending to ensure that ethical principles are consistently applied to all
p.000119: types of research, the core group decided to prepare a Supplement to the 2002 document that would address the special
p.000119: features of epidemiological studies. In February 2006, a draft of the supplement was posted on the CIOMS website and
p.000119: opened to comment from interested parties. The response from groups and individuals involved in biomedical research was
p.000119: largely positive, but many objected that epidemiologists were not necessarily conversant with the 2002 Guidelines and
p.000119: would therefore find it burdensome to have to switch back and forth between the epidemiology supplement and the
p.000119: biomedical research document. Eventually, therefore, the final version of the Guidelines (2009) combined both
p.000119: documents.
p.000119:
p.000119: The fourth version of the CIOMS Guidelines (2016)
p.000119: During its annual meeting in 2009 the Executive Committee of CIOMS considered the desirability of a revision of the
p.000119: CIOMS Ethical Guidelines for Biomedical Research. Since 2002 several developments had taken place including: a
p.000119: heightened emphasis on the importance of translational research, a felt need to clarify what counts as fair research in
p.000119: low-resource settings, more emphasis on community engagement in research, the awareness that exclusion of
p.000119: potentially vulnerable groups in many cases has resulted in a poor evidence base, and the increase of big data
p.000119: research. Moreover the Declaration of Helsinki of 2008 was revised again at that moment. The Executive Committee
p.000119: therefore decided to first explore the desirability of such a revision.
p.000119:
p.000119: The revision process of the 2002 version
p.000119: In 2011, the CIOMS Executive Committee decided to set up a Working Group to revise the CIOMS Guidelines
p.000119: and fund the work from internal means. This Group met three times each year from September 2012 until September
p.000119: 2015. Virtually all Guidelines underwent major revisions. Some Guidelines were merged (for example, 2002
p.000119: Guidelines 4 and 6 both dealt with informed consent), and others were newly created (for example,
p.000119: Guideline 20 on research in disaster and disease outbreaks). Furthermore, the Working Group decided to merge the
p.000119: CIOMS Guidelines for Biomedical Research with the CIOMS Guidelines for Epidemiological Research. At the same time, in
p.000119: order to ensure the epidemiological dimension, an epidemiologist, who was also a member of the Working Group, closely
p.000119: read the revisions from an epidemiological perspective.
p.000119:
p.000119: Scope of the 2016 version
p.000119: The Working Group decided to broaden the scope of the 2002 Guidelines from “biomedical research” to “health-related
p.000119: research”. The Working Group considered biomedical research too narrow since that term would not cover research with
p.000119: health-related data, for example. At the same time, the Working Group acknowledged that this new scope also had
p.000119: limits. For example, new developments such as the idea of the Learning Healthcare System that tries to integrate
p.000119: forms of research and care, were beyond the scope of the draft of the Working Group. The Working Group also
p.000119: acknowledged that there is no clear distinction between the ethics of social science research, behavioural studies,
p.000119: public health surveillance and the ethics of other research activities. The current scope is confined to the classic
p.000119: activities that fall under health-related research with humans, such as observational research, clinical trials,
p.000119: biobanking and epidemiological studies.
p.000119:
p.000119: Collaboration with WHO
p.000119: The CIOMS Guidelines have always been written in collaboration with WHO. For the current Guidelines, the
p.000119: nature and scope of this collaboration were better defined with a joint decision
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000119:
p.000119: to follow recommendations of the WHO Guidelines Review Committee (GRC). This includes (i) a description of
p.000119: the process of revision, prior to revision; (ii) ensuring that the Working Group is global in representation, and
p.000119: includes regional balance and representation of all stakeholders, with a clear process for reporting and managing
p.000119: conflicts of interests; (iv) providing information on the process of evidence retrieval and synthesis for the revision
p.000119: of the Guidelines; and (v) ensuring an independent external peer review of the final product. The GRC acknowledged that
p.000119: many of the “review questions” may not require a full “systematic review” and quality assessment but the
p.000119: process of retrieving information needed to be documented.
p.000119:
p.000119: The process of development and revision of these Guidelines was discussed with, and approved by, the WHO
p.000119: GRC. The final draft of these Guidelines was reviewed by the Secretariat of the GRC, which concluded that since these
p.000119: Guidelines are related to values and moral principles, they were exempted from GRC review. Collaboration with WHO has
p.000119: included a review of the draft Guidelines by all WHO offices (Regional Offices and Headquarters) and the network of WHO
p.000119: Collaborating Centres on Bioethics. Members of the WHO Research Ethics Review Committee reviewed the entire document in
p.000119: two half-day meetings and provided extensive comments on the 2015 draft version of the document.
p.000119:
p.000119: International consultation and peer review
p.000119: In June 2014 the Working Group organized a symposium during the 12th World Congress of the International
p.000119: Association of Bioethics (IAB) in Mexico City during which key issues were presented and opened for discussion.
p.000119: This session served as one element of the international consultation process for the proposed revision of the
p.000119: CIOMS Guidelines. In November 2014 the draft revision was discussed at the Forum of Ethical Review Committees in the
p.000119: Asian & Western Pacific Region (FERCAP) in Manila in a plenary session with more than 800 attendees. The revision was
p.000119: also discussed at the Advancing Research Ethics Training in Southern Africa (ARESA) Seminar on 17—18 September 2015 in
p.000119: Cape Town and at CENTRES (Clinical Ethics Network & Research Ethics Support), in Singapore in November 2015.
p.000119:
p.000119: Specific feedback was sought from the member organizations of CIOMS and from members of National Ethics
p.000119: Committees participating in the Global Summit of National Ethics Committees (2014).
p.000119:
p.000119: At the end of September 2015 the Working Group opened its draft guidelines for public comments until 1 March 2016.
p.000119: The Working Group received comments from 57 different institutions and organizations. In many cases these
p.000119: comments were prepared by several persons from one institution. The commentators represented all parts of the world
p.000119: (see Appendix 4). The Working Group received over 250 pages of comments, ranging from minor editorial issues to
p.000119: in-depth, detailed comments. In June 2016 the Working Group met a final time.
p.000119:
p.000119: The close cooperation with the World Medical Association during the revision process ensured that the final draft was
p.000119: in line with the Declaration of Helsinki.
p.000119:
p.000119: At the beginning of October 2016 the final draft was submitted to the CIOMS Executive Committee, which approved the
p.000119: text at its General Assembly meeting in Geneva in November 2016.
p.000119:
p.000119: The final draft replaces all previous versions of the CIOMS ethical guidelines, both in the domain of
p.000119: biomedical and epidemiological research. At the same time, research projects that have been ethically
p.000119: assessed on the basis of previous versions of the guidelines may be continued on the terms and conditions as set out in
p.000119: those previous versions.
p.000119:
p.000119: Reactions to the Guidelines are welcome and should be addressed to the Secretary-General, Council for International
p.000119: Organizations of Medical Sciences, P.O. Box 2100, CH-1211 Geneva 2, Switzerland; or by email to info@cioms.ch.
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119: x
p.000119:
p.000119: EVIDENCE RETRIEVAL AND SYNTHESIS
p.000119: In the revision process, literature reviews were used as sources for further ethical deliberation.
p.000119: Authoritative declarations, reports and guidance documents have had a prominent role in these discussions,
p.000119: such as the Nuremberg Code (1947), the Universal Declaration of Human Rights of the United Nations (1948), the
p.000119: International Covenant on Civil and Political Rights of the United Nations (1966), the Belmont Report (1979), the
p.000119: Guideline on Good Clinical Practice (GCP) of the International Conference on Harmonisation of Technical Requirements
p.000119: for Registration of Pharmaceuticals for Human Use (ICH) (1996), the Oviedo Convention of the Council of Europe (1997),
p.000119: the Universal Declaration on Bioethics and Human Rights of UNESCO (2005), the UNAIDS/WHO Ethical
p.000119: Considerations in Biomedical HIV Prevention Trials (2007/2012), Standards and operational guidance for
p.000119: ethics review of health-related research with human participants of the WHO (2011), and the Declaration of Helsinki of
p.000119: the World Medical Association (2013). Some of these guidelines have been extensively used, in particular the UNAIDS/WHO
p.000119: document (2012) for Guideline 7 on community engagement.
p.000119:
p.000119: Textbooks, existing ethical frameworks for human subjects research and reports on research involving human beings
p.000119: were also valuable sources of information. The Working Group reviewed papers in major ethics journals (in
p.000119: alphabetical order) such as the American Journal of Bioethics, Bioethics, BMC Medical Ethics, the Cambridge
p.000119: Quarterly of Healthcare Ethics, Developing World Bioethics, the Hastings Center Report, the Journal of Bioethical
p.000119: Inquiry, the Journal of Empirical Research on Human Research Ethics, the Journal of Law, Medicine and Ethics,
p.000119: the Journal of Medical Ethics, the Journal of Medicine and Philosophy, Medicine, Health Care and Philosophy, as
p.000119: well as articles in leading medical or scientific journals, such as BMJ, The Lancet, the New England
p.000119: Journal of Medicine and Science.
p.000119:
p.000119: Literature reviews were used in three ways. First, we searched main ethical guidelines on research with humans and
p.000119: textbooks on research ethics to identify new topics or viewpoints in existing debates. For instance, many guidelines
p.000119: have included statements on biobanking which was one of the reasons to merge the CIOMS guidelines for epidemiological
p.000119: research with those for biomedical research.
p.000119:
p.000119: We performed searches in Embase and Medline on review papers and papers with strong positions on certain topics. For
p.000119: example, component analysis and the net risk test are two recent approaches to making risk-benefit assessments. There
p.000119: is no agreement among bioethicists on which of these approaches is preferable. The Working Group read relevant papers
p.000119: on these approaches and developed a middle ground. A similar process was adopted for vulnerability. A consensus emerged
p.000119: in recent publications that vulnerability can no longer be applied to entire groups. As a result, the
p.000119: Working Group eliminated the group approach. Instead, the Guidelines focus on characteristics that lead to considering
p.000119: certain groups as vulnerable and on the specific protections that are needed in those situations.
p.000119:
p.000119: Third, literature reviews were performed to address relatively new topics, such as opt-out procedures in biobanking or
p.000119: informing research participants of (un)solicited findings. The Working Group reviewed relevant papers on these topics
p.000119: and accordingly took a position.
p.000119:
p.000119: It is important to emphasize that the literature was used as a starting point for further discussion. Ultimately, the
p.000119: validity of the ethical positions in these Guidelines hinge on the strength of the arguments, not on the
p.000119: frequency of an ethical standpoint in the literature.
p.000119:
...
p.000105: themselves, their pregnancies, their fetuses, and their future offspring, what has been done to maximize potential
p.000105: individual benefits and minimize risks, that evidence concerning risks may be unknown or controversial, and that
p.000105: it is often difficult to determine causality in cases of fetal or infant abnormalities (Guidelines 4 and 19);
p.000105:
p.000105: 8. when concerning disaster victims who mostly are under duress, the difference between research and humanitarian
p.000105: aid (Guideline 20); and
p.000105:
p.000105: 9. when research is done in the online environment and using online or digital tools that may
p.000105: involve potentially vulnerable persons, information about the privacy and security controls that will be used to
p.000105: protect their data; and the limitations of the measures used and the risks that may remain despite the safeguards put
p.000105: in place (Guideline 22).
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
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p.000105:
p.000105:
p.000105:
p.000105:
p.000105:
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p.000106:
p.000106:
p.000106:
p.000106:
p.000106: APPENDIX 3
p.000106: CIOMS WORKING GROUP ON THE REVISION OF THE 2002 INTERNATIONAL GUIDELINES FOR BIOMEDICAL RESEARCH INVOLVING
p.000106: HUMANS
p.000106:
p.000106: Chair
p.000106: Hans van Delden
p.000106: Johannes JM van Delden is professor of medical ethics at the medical school of Utrecht University, the Netherlands, and
p.000106: director of education at the Julius Center for health sciences. He has written more than two hundred articles in
p.000106: peer-reviewed scientific journals and (co)authored three books. He was secretary of the International Association of
p.000106: Bioethics. As a professor of medical ethics he has built a strong academic group within the University Medical Center
p.000106: Utrecht. The special fields of interest of this group are: research ethics, moral problems at the end of life and moral
p.000106: problems in the care for the elderly. He is currently the chair of the International Bioethics Committee at UNESCO and
p.000106: was president of CIOMS from 2011 to 2016.
p.000106:
p.000106: Secretary
p.000106: Rieke van der Graaf
p.000106: Rieke van der Graaf is an assistant professor of bioethics and employed at the University Medical Center Utrecht at the
p.000106: Julius Center, Department of Medical Humanities. Her current research interests are inclusion of “vulnerable
p.000106: populations” in clinical research, the integration of care and research, and the ethics of innovative research designs.
p.000106: She is teaching medical ethics at the UMC Utrecht and has been a member of the UMC Utrecht’s Hospital Ethics Committee
p.000106: for more than 10 years. She is a member of the Research Ethics Committee (REC) of the UMC Utrecht. She was the
p.000106: Secretary of the Working Group on the Revision of the CIOMS Guidelines.
p.000106:
p.000106: Members
p.000106: Anant Bhan
p.000106: Anant Bhan is trained as a medical doctor with a masters degree in bioethics from the University of Toronto. He is a
p.000106: researcher in the fields of Bioethics, Global Health and Health Policy based in India. He is also Adjunct
p.000106: Professor at Yenepoya University, Mangalore, India. In the past, he has worked for NGOs and a government
p.000106: public health training institution in India, as well as a consultant to a project on Ethical, Social and Cultural
p.000106: issues in health biotechnology based at the University of Toronto. Anant has published extensively in various national
p.000106: and international medical journals in the field of global/public health and bioethics, as well as contributed to
p.000106: popular mass media. Anant has been a resource person for trainings in global health, research methodology, research
p.000106: ethics and public health ethics, and also serves as guest faculty in various educational institutions in India and
p.000106: abroad. He is on the Editorial Board of ‘Public Health Ethics’ (www.phe.oxfordjournals.org),
p.000106:
p.000106:
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p.000107: 107
p.000107:
p.000107:
p.000107:
p.000107:
p.000107:
p.000107: a quarterly journal of Oxford University Press and also serves on the International Advisory Board of the Asian
...
p.000107: together with colleagues from Clarkson University (USA) co-directs the Advanced Certificate Program in Research
p.000107: Ethics in Central and Eastern Europe. E. Gefenas is a member of the Council of Europe Committee on
p.000107: Bioethics; he was the chair of this Committee from 2011–2012. He was elected as the chairman of the
p.000107: Intergovernmental Bioethics Committee (IGBC) of UNESCO in 2015. The areas of his professional interest include
p.000107: ethical and policy-making issues related to human research and health care in transition societies.
p.000107:
p.000107: Dirceu Greco
p.000107: Dirceu Greco is full professor of Infectious Diseases and Bioethics at the School of Medicine, Federal University of
p.000107: Minas Gerais (UFMG), Belo Horizonte, Brazil. He received his MD degree and this PhD from UFMG. Chief, Infectious and
p.000107: Parasitic Diseases Service (2009-2011), Coordinator of UFMG University Hospital Centre for Clinical Research
p.000107: (2005-2010), member (2007-2010), Brazilian Research Ethics Commission (CONEP); member, Brazilian AIDS Commission
p.000107: (Ministry of Health-MoH). Main topics of interest include Infectious and Parasitic Illnesses, bioethics, public health
p.000107: and clinical immunology. He has participated in several working groups that gave rise to
p.000107: national/international guidelines related to ethics, prevention, care and treatment of HIV/AIDS and TB. He has
p.000107: frequently acted as temporary advisor to many national/international institutions, such as the Brazilian AIDS
p.000107: Programme, WHO, UNITAID, UNAIDS, CIOMS and WMA. From 2010 to 2013 he directed the Department of STD, AIDS and Viral
p.000107: Hepatitis (Secretary of Health Surveillance, MoH, Brazil).
p.000107:
p.000107: David Haerry
p.000107: David Haerry is a treatment writer and conference reporter since 1996. He is co-authoring a database on travel &
p.000107: residency restrictions for people living with HIV. David Haerry has been involved in health care professionals
p.000107: education projects since 2007. Since 2015, he is Secretary General of the Swiss Academic Foundation on Education in
p.000107: Infectious Diseases SAFE-ID. He is work package co-leader and member of the Executive Committee in the EUPATI-IMI
p.000107: project and involved in a number of European and global research networks and research collaborations, including the
p.000107: ENCePP Steering Group. He is co-chair of the Patient and Consumer Working Party at the European Medicines Agency and
p.000107: has served the European AIDS Treatment Group EATG in various positions since 2004. David has been involved in HIV and
p.000107: HCV drug development since 2005 and has specific interests in the areas of Personalised Medicine, Risk Communication,
p.000107: Pharmacovigilance, Observational Studies, Biomedical Prevention and HIV Eradication Research. He is living with HIV
p.000107: since 1986.
p.000107:
p.000107: Bocar Kouyaté
...
p.000108:
p.000108: Annette Rid
p.000108: Annette Rid is a Senior Lecturer in Bioethics and Society in the Department of Global Health & Social Medicine, King’s
p.000108: College London, and an Elected Fellow of the Hastings Center. Trained in medicine, philosophy and bioethics in Germany,
p.000108: Switzerland and the United States, Annette’s research interests span research ethics, clinical ethics and justice
p.000108: in health and health care. Annette has published widely in medical journals (e.g. Lancet, JAMA) and bioethics
p.000108: journals (e.g. Journal of Medical Ethics, Bioethics). She has served as an advisor, among others, for the World Health
p.000108: Organization and the World Medical Association, and sits on numerous scientific and advisory boards. At King’s, Annette
p.000108: has led the new Masters in Bioethics & Society as one of its inaugural co-directors.
p.000108:
p.000108: Rodolfo Saracci
p.000108: Rodolfo Saracci qualified as an MD and holds specialist degrees in internal medicine and in medical statistics. He is a
p.000108: Fellow of the UK Faculty of Public Health. His career as a research epidemiologist in the field of chronic
p.000108: diseases, particularly cancer, has been principally developed at the WHO International Agency for Research on
p.000108: Cancer (IARC) in Lyon as a staff member and Chief of the Unit of Analytical Epidemiology. From 1982 to 2005 he chaired
p.000108: the Ethics Review Committee of IARC and has taken an active part in the CIOMS projects in biomedical ethics as a member
p.000108: of the drafting
p.000108:
p.000108:
p.000108:
p.000108:
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p.000109: 109
p.000109:
p.000109:
p.000109:
p.000109:
p.000109:
p.000109: group of the 2002 International Ethical Guidelines for Biomedical Research Involving Human Subjects and as
p.000109: co-rapporteur of the 2009 International Ethical Guidelines for Epidemiological Studies.
p.000109:
p.000109: Aissatou Toure
p.000109: Dr Aissatou Toure is a researcher at the Pasteur Institute in Dakar where she heads the Unit of
p.000109: Immunology and conducts research in the area of immunology of malaria. In parallel to her scientific activities as
p.000109: researcher in malaria, Dr Toure has different activities in the field of ethics, which represents for her
p.000109: a major area of interest. Dr Toure is member of the Senegalese National Ethics Committee for Health Research since
p.000109: 2003. Since 2012 Dr Toure is member of the Working Group on the Revision of CIOMS 2002 International Ethical Guidelines
p.000109: for Biomedical Research Involving Human Subjects. From 2006 to 2013 Dr Toure was a member of the UNESCO International
p.000109: Committee on Bioethics and as such participated to reports on various bioethics topics. Dr Aissatou Toure was also a
p.000109: member of the Working Group established in 2014 by WHO during the Ebola outbreak to advise and make recommendations on
p.000109: specific ethical issues raised by the Ebola crisis. She participated in the elaboration of WHO ethical guidance
p.000109: for managing infectious disease outbreaks. Aissatou Toure participates regularly in different activities of
p.000109: capacity building in ethics at the national level as well at the international level.
p.000109:
p.000109: Advisors
p.000109: Abha Saxena, WHO
p.000109: An anaesthesiologist and a specialist in pain and palliative care by training, in 2001, she relocated from New Delhi,
p.000109: India, to join the Research Policy Department of World Health Organization, in which department she re-established
p.000109: the Research Ethics Review Committee of the Organization (WHO ERC), and led efforts to develop norms and
p.000109: standards for research ethics committees, and training tools in the area of research ethics. Currently as
p.000109: coordinator, she leads the Global Health Ethics team providing expertise on ethical issues to Member States and
p.000109: the three levels of the Organization. The function ensures ethical considerations are included in the elaboration and
...
p.000110: Previously, she was Ethics Advisor at the Institut Pasteur, worked for the French National Agency for Research on Aids
p.000110: and Viral Hepatitis, and practised law at Hogan & Hartson LLP, a law firm now called Hogan Lovells. Co-editor of the
p.000110: Ethics of Research Section in the Elsevier International Encyclopedia of the Social and Behavioural
p.000110: Sciences, Ingrid Callies has also participated in major research projects, including LeukoTreat (a
p.000110: collaborative European project on leukodystrophy) and Satori (Stakeholders Acting Together On the ethical impact
p.000110: assessment of Research and Innovation).
p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
p.000110:
p.000110: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000111: 111
p.000111:
p.000111:
p.000111:
p.000111:
p.000111:
p.000111: APPENDIX 4
p.000111: COMMENTATORS
p.000111:
p.000111:
p.000111:
p.000111: Institution/Organization Country Surname First name
p.000111: 1 Brazil Neto
p.000111: Sodre
p.000111: 2 Areteva, Nottingham United Kingdom Corfield Julie
p.000111:
p.000111: 3 Association of Clinical Research Professionals, Alexandria, VA
p.000111: 4 Caribbean Public Health Agency Research Ethics Committee
p.000111: 5 Centro de Bioética, Persona y Familia
p.000111: 6 CIOMS, Former President, Geneva
p.000111: 7 CIOMS, Senior Adviser, Geneva
p.000111: 8 Comite Etico-Cientifico, Universidad de Ciencias Médicas de Costa Rica
p.000111: United States Kremidas Jim
p.000111:
p.000111:
p.000111: Roopchand-Martin Sharmella
p.000111:
p.000111:
p.000111: Argentina Pucheta Leonardo
p.000111:
p.000111: Switzerland Vallotton Michel
p.000111:
p.000111: Switzerland Fluss Sev
p.000111:
p.000111: Costa Rica Vargas Jorge Quesada
p.000111: 9 Dalhousie University, Halifax Canada Baylis
p.000111: Francoise
p.000111: MacQuarrie Robyn
p.000111:
p.000111: 10 Novel Tech Ethics, Dalhousie University, Halifax
p.000111: 11 Department of Bioethics, National Institutes of Health, Bethesda, Maryland
p.000111: 12 Disaster Bioethics COST Action, Research Ethics Working Group, Dublin
p.000111: 13 Division of Medical Ethics, NYU Medical School,
p.000111: New York
p.000111: 14 Eli Lilly and Company, Indianapolis, Indiana
p.000111: Canada Petropanagos Angel
p.000111:
p.000111: United States Millum Joseph
p.000111: Wendler David
p.000111: Grady Christine
p.000111: Ireland O’Mathúna Dónal
p.000111:
p.000111:
p.000111: United States Curry David
p.000111:
p.000111:
p.000111: United States Van Campen Luann
...
p.000120:
p.000120:
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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p.000121: 121
p.000121:
p.000121: Risks 2, 5, 7 - 13, 15 - 19, 23, 26, 34 - 39, 41, 44, 47, 49, 50, 53, 54, 58, 59, 61 - 63, 65 - 67,
p.000121: 69 - 73, 75 - 77, 80, 81, 83 - 85, 88, 91, 92, 96, 100, 102, 104 - 106
p.000121: S
p.000121: Scientific value 2, 9 - 13, 51, 91
p.000121: Secondary use 49
p.000121: Social value 1 - 4, 8 - 11, 19, 25, 26, 30, 37, 38, 41, 44, 47, 50, 62, 65, 71, 73, 75, 77, 88, 91
p.000121: Specific informed consent 41 - 44, 47, 48, 49
p.000121: Storage 36, 41, 43, 45, 47 - 50, 52, 105
p.000121: U
p.000121: (Un)solicited findings xi, 44, 45, 51
p.000121: Undue inducement 53, 54, 73
p.000121: Use of biological material 44, 105
p.000121: V
p.000121: Voluntary, voluntariness 10, 35, 36, 39, 58, 59, 78, 96, 103
p.000121: Vulnerable viii, ix, xi, 3, 8, 54, 57 - 59, 69, 77, 84, 88, 89, 100, 106
p.000121: W
p.000121: Waivers of informed consent 33, 35 - 37, 43, 49, 63, 68, 76, 78, 79
p.000121: Withdrawal 44, 49, 50, 54, 63
p.000121: Women 7, 8, 25, 58, 69, 70 - 73, 88, 101, 105, 106
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000122: 122
p.000122: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000122:
p.000122: CIOMS, in association with the World Health Organization, started its work on ethics in health-related
p.000122: research in the late 1970s. Accordingly, CIOMS set out, in cooperation with WHO, to prepare guidelines
p.000122: to indicate how the ethical principles set forth in the Declaration of Helsinki of the World Medical
p.000122: Association, could be effectively applied, particularly in low-resource settings, given their socio-economic
...
p.000122: CIOMS to again revise their ethical guidelines. The result is now available in this new publication.
p.000122:
p.000122: In the new 2016 version of the ethical guidelines, CIOMS provides answers to a number of pressing issues in research
p.000122: ethics. The Council does so by stressing the need for research having scientific and social value, by providing special
p.000122: guidelines for health-related research in low-resource settings, by detailing the provisions for involving
p.000122: vulnerable groups in research and for describing under what conditions biological samples and health-related data
p.000122: can be used for research.
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122: International Ethical Guidelines for Health-related Research Involving Humans. Geneva: Council for International
p.000122: Organizations of Medical Sciences (CIOMS); 2016.
p.000122: CIOMS publications may be obtained directly from CIOMS by e-mail to info@cioms.ch.
p.000122: CIOMS, P.O. Box 2100, CH1211 Geneva 2, Switzerland, www.cioms.ch
p.000122: CIOMS publications are also distributed by the World Health Organization, 20 Avenue Appia, CH-1211 Geneva 27,
p.000122: Switzerland.
p.000122:
p.000122:
p.000122:
p.000122:
p.000122: ISBN 978-929036088-9
p.000122:
p.000122:
p.000122:
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...
General/Other / cultural difference
Searching for indicator culturally:
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p.000034: researchers or participants until the study has been concluded. In long-term studies, the willingness of each
p.000034: participant to continue in the study must be ensured.
p.000034:
p.000034: Individual informed consent and access to research populations. In some circumstances, a researcher may
p.000034: enter a community or institution to conduct research or approach potential participants for their individual
p.000034: consent only after obtaining permission from an institution such as a school or a prison, or from a community leader, a
p.000034: council of elders, or another designated authority. Such institutional procedures or cultural customs should be
p.000034: respected. In no case, however, may the permission of a community leader or other authority substitute for individual
p.000034: informed consent. In some populations, the use of local languages may facilitate the communication of information to
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
p.000034: factors can be internal to participants, such as mental illness, whereas other influences can be external, such as a
p.000034: dependent relationship between participants and clinician-researchers. Circumstances such as severe illness or poverty
p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
...
p.000076: randomised-controlled trial design is often considered the “gold standard” for collecting robust data. However,
p.000076: researchers, sponsors, research ethics committees and others must explore alternative trial designs that may increase
p.000076: trial efficiency and access to promising experimental interventions while still maintaining scientific validity. The
p.000076: methodological and ethical merits of alternative trial designs must be carefully assessed before these designs are
p.000076: used. For example, when testing experimental treatments or vaccines during an epidemic, the appropriate trial
p.000076: design will depend on the promise of the investigational agent,
p.000076:
p.000076:
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p.000077:
p.000077:
p.000077:
p.000077:
p.000077:
p.000077: a variation in critical background factors (for example mortality and infection rates), and measurement of outcomes,
p.000077: among others. Researchers and sponsors must carefully evaluate the relative merits of different designs (for example
p.000077: observational or placebo-controlled) based on these factors.
p.000077:
p.000077: Community engagement. Because disasters often lead to vulnerability and fragile political and social situations,
p.000077: engaging local communities about the research at an early stage is essential for maintaining public trust and ensuring
p.000077: that studies are conducted in a culturally sensitive manner (see Guideline 7 – Community engagement). Researchers and
p.000077: sponsors can use creative mechanisms to expedite and facilitate community engagement in a disaster situation (for
p.000077: example, by using social media). Fostering community leadership will often be important to address distrust and
p.000077: communicate effectively in order to gain support for the study design. In engaging with communities, researchers,
p.000077: sponsors and research ethics committees should be aware of potential conflicts of interest vis-à-vis the proposed
p.000077: research. For example, community leaders might seek to reassert their own authority by providing services to their
p.000077: communities through research.
p.000077:
p.000077: Ethical review and oversight. The standard mechanism for ethical review will often be too time-consuming
p.000077: to enable full research protocols to be prepared and reviewed at the outset of a disaster. Procedures
p.000077: should be developed to facilitate and accelerate ethical review in a situation of crisis. For example, research ethics
p.000077: committees or a specialist ethics committee (perhaps on a national or regional level) may conduct an initial
p.000077: accelerated review of study protocols and continue oversight if studies raise significant ethical concerns. Research in
p.000077: disaster situations should ideally be planned in advance. This can involve, among other things, submitting partial
p.000077: study protocols for ethical “pre-screening” and drafting arrangements for data and sample sharing among collaborators.
...
p.000088: – Collaborative partnership and capacity building for research and review). Researchers and sponsors who plan to
p.000088: perform research in settings where research ethics committees are absent or lack adequate training should
p.000088: help to establish such committees according to their ability before the research is initiated, and make provisions
p.000088: for their education in research ethics (see Guideline 8 – Collaborative partnership and capacity building for research
p.000088: and review).
p.000088:
p.000088: Externally sponsored research must be reviewed at the site of the sponsor as well as locally. The ethical standards
p.000088: should be no less stringent than they would be for research carried out in the country of the sponsoring organization
p.000088: (see also Guideline 2 – Research conducted in low-resource settings). Local committees must be fully empowered to
p.000088: disapprove a study that they believe to be unethical.
p.000088:
p.000088: Multi-centre research. Some research projects are designed to be conducted in a number of centres in
p.000088: different communities or countries. To ensure that the results are valid, the study must be conducted in a
p.000088: methodologically identical way at each centre. However, committees at individual centres must be authorized to adapt
p.000088: the informed consent document provided by the sponsor or the lead institution in the multi-centre trial in order to
p.000088: make it culturally appropriate.
p.000088:
p.000088: To avoid lengthy procedures, multi-centre research in a single jurisdiction (state or country) should be reviewed by
p.000088: only one research ethics committee. In cases of multi-centre research, if a local
p.000088:
p.000088:
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p.000089:
p.000089:
p.000089:
p.000089:
p.000089:
p.000089: review committee proposes changes to the original protocol that it believes are necessary to protect the research
p.000089: participants, these changes must be reported to the research institution or sponsor responsible for the whole research
p.000089: programme for consideration and possible action. This should ensure that all persons are protected and that the
p.000089: research will be valid across sites.
p.000089:
p.000089: Ideally, review procedures should be harmonized, which may decrease the time needed for review and accordingly, speed
p.000089: up the research process. In order to harmonize review processes and to maintain sufficient quality of these processes,
p.000089: ethics committees must develop quality indicators for ethical review. Appropriate review must be sensitive to increases
p.000089: in risk of harm or wrongs to local participants and populations.
p.000089:
p.000089: Exemptions from review. Some studies may be exempt from review. For example, when publicly available data are analysed
...
General/Other / declaration of helsinki
Searching for indicator helsinki:
(return to top)
p.000119: Accordingly, CIOMS set out, in cooperation with WHO, to prepare guidelines. The aim of the guidelines was (and still
p.000119: is) to provide internationally vetted ethical principles and detailed commentary on how universal ethical principles
p.000119: should be applied, with particular attention to conducting research in low-resource settings. The outcome of the
p.000119: CIOMS/WHO collaboration was entitled Proposed International Ethical Guidelines for Biomedical Research Involving
p.000119: Human Subjects.
p.000119:
p.000119: The second version of the CIOMS Guidelines (1993)
p.000119: The period that followed saw the outbreak of the HIV/AIDS pandemic and proposals for large-scale trials of prevention
p.000119: and treatment for the disease. These developments raised new ethical issues that had not been considered in the
p.000119: preparation of the Proposed Guidelines. There were other factors also – rapid advances in medicine and
p.000119: biotechnology, changing research practices such as multinational field trials, experimentation involving
p.000119: vulnerable population groups, and also a new perspective in both high- and low-resource settings, that research
p.000119: involving humans could be beneficial to participants rather than threatening. The World Medical Association’s
p.000119: Declaration of Helsinki was revised twice in the 1980s – in 1983 and 1989. It was timely to revise and update the 1982
p.000119: Guidelines, and CIOMS, with the collaboration of WHO and its Global Programme on AIDS, undertook the
p.000119: task. The outcome was the issue of two sets of guidelines: International Guidelines for Ethical Review of
p.000119: Epidemiological Studies in 1991, and International Ethical Guidelines for Biomedical Research Involving Human Subjects
p.000119: in 1993.
p.000119:
p.000119: The third version of the CIOMS Guidelines (2002)
p.000119: After 1993, ethical issues arose for which the 1993 CIOMS Guidelines had no specific provisions. They related mainly
p.000119: to externally sponsored clinical trials carried out in low-resource settings. In particular, the use of
p.000119: comparators other than an established effective intervention used in low- resource settings became a concern.
p.000119: Commentators took opposing sides on this issue. This debate necessitated the revision and updating of the 1993
p.000119: Guidelines. CIOMS organized a consultation meeting with eight commissioned papers. After this meeting, a WG was set
p.000119: up that laboured over a period of two years during which there was a public posting of a draft with a request for
p.000119: comments. The revision process was finished in 2002.
p.000119:
p.000119: Epidemiological Guidelines (2009)
p.000119: The process of revising the 1993 version of the biomedical research Guidelines made clear that
p.000119: developments in the ethical analysis of all types of research using human subjects had potential
...
p.000119: types of research, the core group decided to prepare a Supplement to the 2002 document that would address the special
p.000119: features of epidemiological studies. In February 2006, a draft of the supplement was posted on the CIOMS website and
p.000119: opened to comment from interested parties. The response from groups and individuals involved in biomedical research was
p.000119: largely positive, but many objected that epidemiologists were not necessarily conversant with the 2002 Guidelines and
p.000119: would therefore find it burdensome to have to switch back and forth between the epidemiology supplement and the
p.000119: biomedical research document. Eventually, therefore, the final version of the Guidelines (2009) combined both
p.000119: documents.
p.000119:
p.000119: The fourth version of the CIOMS Guidelines (2016)
p.000119: During its annual meeting in 2009 the Executive Committee of CIOMS considered the desirability of a revision of the
p.000119: CIOMS Ethical Guidelines for Biomedical Research. Since 2002 several developments had taken place including: a
p.000119: heightened emphasis on the importance of translational research, a felt need to clarify what counts as fair research in
p.000119: low-resource settings, more emphasis on community engagement in research, the awareness that exclusion of
p.000119: potentially vulnerable groups in many cases has resulted in a poor evidence base, and the increase of big data
p.000119: research. Moreover the Declaration of Helsinki of 2008 was revised again at that moment. The Executive Committee
p.000119: therefore decided to first explore the desirability of such a revision.
p.000119:
p.000119: The revision process of the 2002 version
p.000119: In 2011, the CIOMS Executive Committee decided to set up a Working Group to revise the CIOMS Guidelines
p.000119: and fund the work from internal means. This Group met three times each year from September 2012 until September
p.000119: 2015. Virtually all Guidelines underwent major revisions. Some Guidelines were merged (for example, 2002
p.000119: Guidelines 4 and 6 both dealt with informed consent), and others were newly created (for example,
p.000119: Guideline 20 on research in disaster and disease outbreaks). Furthermore, the Working Group decided to merge the
p.000119: CIOMS Guidelines for Biomedical Research with the CIOMS Guidelines for Epidemiological Research. At the same time, in
p.000119: order to ensure the epidemiological dimension, an epidemiologist, who was also a member of the Working Group, closely
p.000119: read the revisions from an epidemiological perspective.
p.000119:
p.000119: Scope of the 2016 version
p.000119: The Working Group decided to broaden the scope of the 2002 Guidelines from “biomedical research” to “health-related
p.000119: research”. The Working Group considered biomedical research too narrow since that term would not cover research with
p.000119: health-related data, for example. At the same time, the Working Group acknowledged that this new scope also had
...
p.000119: Asian & Western Pacific Region (FERCAP) in Manila in a plenary session with more than 800 attendees. The revision was
p.000119: also discussed at the Advancing Research Ethics Training in Southern Africa (ARESA) Seminar on 17—18 September 2015 in
p.000119: Cape Town and at CENTRES (Clinical Ethics Network & Research Ethics Support), in Singapore in November 2015.
p.000119:
p.000119: Specific feedback was sought from the member organizations of CIOMS and from members of National Ethics
p.000119: Committees participating in the Global Summit of National Ethics Committees (2014).
p.000119:
p.000119: At the end of September 2015 the Working Group opened its draft guidelines for public comments until 1 March 2016.
p.000119: The Working Group received comments from 57 different institutions and organizations. In many cases these
p.000119: comments were prepared by several persons from one institution. The commentators represented all parts of the world
p.000119: (see Appendix 4). The Working Group received over 250 pages of comments, ranging from minor editorial issues to
p.000119: in-depth, detailed comments. In June 2016 the Working Group met a final time.
p.000119:
p.000119: The close cooperation with the World Medical Association during the revision process ensured that the final draft was
p.000119: in line with the Declaration of Helsinki.
p.000119:
p.000119: At the beginning of October 2016 the final draft was submitted to the CIOMS Executive Committee, which approved the
p.000119: text at its General Assembly meeting in Geneva in November 2016.
p.000119:
p.000119: The final draft replaces all previous versions of the CIOMS ethical guidelines, both in the domain of
p.000119: biomedical and epidemiological research. At the same time, research projects that have been ethically
p.000119: assessed on the basis of previous versions of the guidelines may be continued on the terms and conditions as set out in
p.000119: those previous versions.
p.000119:
p.000119: Reactions to the Guidelines are welcome and should be addressed to the Secretary-General, Council for International
p.000119: Organizations of Medical Sciences, P.O. Box 2100, CH-1211 Geneva 2, Switzerland; or by email to info@cioms.ch.
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119: x
p.000119:
p.000119: EVIDENCE RETRIEVAL AND SYNTHESIS
p.000119: In the revision process, literature reviews were used as sources for further ethical deliberation.
p.000119: Authoritative declarations, reports and guidance documents have had a prominent role in these discussions,
p.000119: such as the Nuremberg Code (1947), the Universal Declaration of Human Rights of the United Nations (1948), the
p.000119: International Covenant on Civil and Political Rights of the United Nations (1966), the Belmont Report (1979), the
p.000119: Guideline on Good Clinical Practice (GCP) of the International Conference on Harmonisation of Technical Requirements
p.000119: for Registration of Pharmaceuticals for Human Use (ICH) (1996), the Oviedo Convention of the Council of Europe (1997),
p.000119: the Universal Declaration on Bioethics and Human Rights of UNESCO (2005), the UNAIDS/WHO Ethical
p.000119: Considerations in Biomedical HIV Prevention Trials (2007/2012), Standards and operational guidance for
p.000119: ethics review of health-related research with human participants of the WHO (2011), and the Declaration of Helsinki of
p.000119: the World Medical Association (2013). Some of these guidelines have been extensively used, in particular the UNAIDS/WHO
p.000119: document (2012) for Guideline 7 on community engagement.
p.000119:
p.000119: Textbooks, existing ethical frameworks for human subjects research and reports on research involving human beings
p.000119: were also valuable sources of information. The Working Group reviewed papers in major ethics journals (in
p.000119: alphabetical order) such as the American Journal of Bioethics, Bioethics, BMC Medical Ethics, the Cambridge
p.000119: Quarterly of Healthcare Ethics, Developing World Bioethics, the Hastings Center Report, the Journal of Bioethical
p.000119: Inquiry, the Journal of Empirical Research on Human Research Ethics, the Journal of Law, Medicine and Ethics,
p.000119: the Journal of Medical Ethics, the Journal of Medicine and Philosophy, Medicine, Health Care and Philosophy, as
p.000119: well as articles in leading medical or scientific journals, such as BMJ, The Lancet, the New England
p.000119: Journal of Medicine and Science.
p.000119:
p.000119: Literature reviews were used in three ways. First, we searched main ethical guidelines on research with humans and
...
p.000055: absolve a researcher from responsibility in the case of harm, or that would imply that participants waive their right
p.000055: to seek compensation (see Guideline 9 – Individuals capable of giving informed consent). They must also be
p.000055: told what medical service, organization or individual will provide the treatment and what organization will be
p.000055: responsible for providing compensation.
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055:
p.000055: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000056: 56
p.000056:
p.000056:
p.000056:
p.000056:
p.000056:
p.000056: GUIDELINE 15:
p.000056: RESEARCH INVOLVING VULNERABLE PERSONS AND GROUPS
p.000056:
p.000056: When vulnerable individuals and groups are considered for recruitment in research, researchers and research
p.000056: ethics committees must ensure that specific protections are in place to safeguard the rights and welfare of these
p.000056: individuals and groups in the conduct of the research.
p.000056:
p.000056:
p.000056: Commentary on Guideline 15
p.000056: General considerations. According to the Declaration of Helsinki, vulnerable groups and individuals “may have an
p.000056: increased likelihood of being wronged or of incurring additional harm.” This implies that vulnerability involves
p.000056: judgments about both the probability and degree of physical, psychological, or social harm, as well as a greater
p.000056: susceptibility to deception or having confidentiality breached. It is important to recognize that vulnerability
p.000056: involves not only the ability to provide initial consent to participate in research, but also aspects of the ongoing
p.000056: participation in research studies. In some cases, persons are vulnerable because they are relatively (or
p.000056: absolutely) incapable of protecting their own interests. This may occur when persons have relative or absolute
p.000056: impairments in decisional capacity, education, resources, strength, or other attributes needed to protect their own
p.000056: interests. In other cases, persons can also be vulnerable because some feature of the circumstances (temporary or
p.000056: permanent) in which they live makes it less likely that others will be vigilant about, or sensitive to, their
...
p.000121: Specific informed consent 41 - 44, 47, 48, 49
p.000121: Storage 36, 41, 43, 45, 47 - 50, 52, 105
p.000121: U
p.000121: (Un)solicited findings xi, 44, 45, 51
p.000121: Undue inducement 53, 54, 73
p.000121: Use of biological material 44, 105
p.000121: V
p.000121: Voluntary, voluntariness 10, 35, 36, 39, 58, 59, 78, 96, 103
p.000121: Vulnerable viii, ix, xi, 3, 8, 54, 57 - 59, 69, 77, 84, 88, 89, 100, 106
p.000121: W
p.000121: Waivers of informed consent 33, 35 - 37, 43, 49, 63, 68, 76, 78, 79
p.000121: Withdrawal 44, 49, 50, 54, 63
p.000121: Women 7, 8, 25, 58, 69, 70 - 73, 88, 101, 105, 106
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000121:
p.000122: 122
p.000122: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000122:
p.000122: CIOMS, in association with the World Health Organization, started its work on ethics in health-related
p.000122: research in the late 1970s. Accordingly, CIOMS set out, in cooperation with WHO, to prepare guidelines
p.000122: to indicate how the ethical principles set forth in the Declaration of Helsinki of the World Medical
p.000122: Association, could be effectively applied, particularly in low-resource settings, given their socio-economic
p.000122: circumstances, laws and regulations, and executive and administrative arrangements. Since then revised editions of
p.000122: the CIOMS ethical guidelines were published in 1993 and 2002. New developments in research have prompted
p.000122: CIOMS to again revise their ethical guidelines. The result is now available in this new publication.
p.000122:
p.000122: In the new 2016 version of the ethical guidelines, CIOMS provides answers to a number of pressing issues in research
p.000122: ethics. The Council does so by stressing the need for research having scientific and social value, by providing special
p.000122: guidelines for health-related research in low-resource settings, by detailing the provisions for involving
p.000122: vulnerable groups in research and for describing under what conditions biological samples and health-related data
p.000122: can be used for research.
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122:
p.000122: International Ethical Guidelines for Health-related Research Involving Humans. Geneva: Council for International
p.000122: Organizations of Medical Sciences (CIOMS); 2016.
...
General/Other / oviedo
Searching for indicator oviedo:
(return to top)
p.000119: text at its General Assembly meeting in Geneva in November 2016.
p.000119:
p.000119: The final draft replaces all previous versions of the CIOMS ethical guidelines, both in the domain of
p.000119: biomedical and epidemiological research. At the same time, research projects that have been ethically
p.000119: assessed on the basis of previous versions of the guidelines may be continued on the terms and conditions as set out in
p.000119: those previous versions.
p.000119:
p.000119: Reactions to the Guidelines are welcome and should be addressed to the Secretary-General, Council for International
p.000119: Organizations of Medical Sciences, P.O. Box 2100, CH-1211 Geneva 2, Switzerland; or by email to info@cioms.ch.
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000119: x
p.000119:
p.000119: EVIDENCE RETRIEVAL AND SYNTHESIS
p.000119: In the revision process, literature reviews were used as sources for further ethical deliberation.
p.000119: Authoritative declarations, reports and guidance documents have had a prominent role in these discussions,
p.000119: such as the Nuremberg Code (1947), the Universal Declaration of Human Rights of the United Nations (1948), the
p.000119: International Covenant on Civil and Political Rights of the United Nations (1966), the Belmont Report (1979), the
p.000119: Guideline on Good Clinical Practice (GCP) of the International Conference on Harmonisation of Technical Requirements
p.000119: for Registration of Pharmaceuticals for Human Use (ICH) (1996), the Oviedo Convention of the Council of Europe (1997),
p.000119: the Universal Declaration on Bioethics and Human Rights of UNESCO (2005), the UNAIDS/WHO Ethical
p.000119: Considerations in Biomedical HIV Prevention Trials (2007/2012), Standards and operational guidance for
p.000119: ethics review of health-related research with human participants of the WHO (2011), and the Declaration of Helsinki of
p.000119: the World Medical Association (2013). Some of these guidelines have been extensively used, in particular the UNAIDS/WHO
p.000119: document (2012) for Guideline 7 on community engagement.
p.000119:
p.000119: Textbooks, existing ethical frameworks for human subjects research and reports on research involving human beings
p.000119: were also valuable sources of information. The Working Group reviewed papers in major ethics journals (in
p.000119: alphabetical order) such as the American Journal of Bioethics, Bioethics, BMC Medical Ethics, the Cambridge
p.000119: Quarterly of Healthcare Ethics, Developing World Bioethics, the Hastings Center Report, the Journal of Bioethical
p.000119: Inquiry, the Journal of Empirical Research on Human Research Ethics, the Journal of Law, Medicine and Ethics,
...
General/Other / participants in a control group
Searching for indicator control group:
(return to top)
p.000007: products developed as a result of the research.
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007:
p.000007: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000008: 8
p.000008:
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: GUIDELINE 4:
p.000008: POTENTIAL INDIVIDUAL BENEFITS AND RISKS OF RESEARCH
p.000008:
p.000008: To justify imposing any research risks on participants in health research, the research must have social
p.000008: and scientific value. Before inviting potential participants to join a study, the researcher, sponsor and the
p.000008: research ethics committee must ensure that risks to participants are minimized and appropriately balanced in
p.000008: relation to the prospect of potential individual benefit and the social and scientific value of the research.
p.000008:
p.000008: The potential individual benefits and risks of research must be evaluated in a two-step process. First,
p.000008: the potential individual benefits and risks of each individual research intervention or procedure in the study
p.000008: must be evaluated.
p.000008: f For research interventions or procedures that have the potential to benefit participants, risks are acceptable if
p.000008: they are minimized and outweighed by the prospect of potential individual benefit and the available evidence suggests
p.000008: that the intervention will be at least as advantageous, in the light of foreseeable risks and benefits, as any
p.000008: established effective alternative. Therefore, as a general rule, participants in the control group of a trial must
p.000008: receive an established effective intervention. The conditions under which a placebo may be used are spelled out in
p.000008: Guideline 5 – Choice of control in clinical trials.
p.000008: f For research interventions or procedures that offer no potential individual benefits to participants, the risks
p.000008: must be minimized and appropriate in relation to the social and scientific value of the knowledge to be gained
p.000008: (expected benefits to society from the generalizable knowledge).
p.000008: f In general, when it is not possible or feasible to obtain the informed consent of participants,
p.000008: research interventions or procedures that offer no potential individual benefits must pose no more than minimal
p.000008: risks. However, a research ethics committee may permit a minor increase above minimal risk when it is not possible to
p.000008: gather the necessary data in another population or in a less risky or burdensome manner, and the social and scientific
p.000008: value of the research is compelling (see Guideline 16 – Research involving adults incapable of giving informed
p.000008: consent, and Guideline 17 – Research involving children and adolescents).
p.000008:
p.000008: In a second step, the aggregate risks and potential individual benefits of the entire study must be assessed and must
p.000008: be considered appropriate.
...
p.000010: f avoiding unnecessary procedures (for example, by performing laboratory tests on existing blood samples instead of
p.000010: drawing new blood, where scientifically appropriate); and
p.000010: f excluding participants who are at a significantly increased risk of being harmed from an intervention
p.000010: or procedure.
p.000010:
p.000010: Measures to minimize risks need to be carefully balanced with competing considerations regarding the scientific and
p.000010: value of research and fair subject selection. For example, decisions to stop a trial due to early,
p.000010: significant findings have to be balanced with the need to collect robust data on investigational interventions that are
p.000010: adequate to guide clinical practice.
p.000010:
p.000010: Researchers, sponsors and research ethics committees must then ensure that the risks of each intervention
p.000010: and procedure, once minimized, are appropriately balanced in relation to the intervention’s prospect of benefit for the
p.000010: individual participant and the social and scientific value of the research. For interventions that have a prospect of
p.000010: potential individual benefit, risks are acceptable if they are outweighed by the potential individual benefits for the
p.000010: individual participant and the intervention’s risk- benefit profile is at least as advantageous as any established
p.000010: effective alternative. Participants in the
p.000010:
p.000010: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000011: 11
p.000011:
p.000011:
p.000011:
p.000011:
p.000011:
p.000011: control group of a clinical trial must be provided with an established effective intervention; exceptions to this
p.000011: general rule are set out and discussed in Guideline 5 – Choice of control in clinical trials.
p.000011:
p.000011: Judgments about the risk-benefit profile of study interventions, and how they compare with the risk- benefit profile of
p.000011: any established alternatives, must be based on the available evidence. Therefore, researchers and sponsors have an
p.000011: obligation to provide, in the research protocol and other documents submitted to the research ethics committee, a
p.000011: comprehensive and balanced overview of the available evidence that is relevant for evaluating the risks and potential
p.000011: individual benefits of the research. In research protocols for clinical trials, researchers and sponsors must clearly
p.000011: describe results from preclinical studies and, where applicable, early phase or exploratory trials of the study
p.000011: intervention involving humans. They must also note in the documents sent to the committee any limitations of the
p.000011: available data as well as any disagreement about the foreseeable risks and potential individual benefits, including
p.000011: potential conflicts of interests that might influence conflicting opinions. Researchers should provide a credible
p.000011: interpretation of the available evidence to support their judgment that an investigational agent has a favourable
...
p.000012: a way that compensates for any disruption caused by the research.
p.000012:
p.000012: In assessing the risks and potential individual benefits that a study presents to a population, research ethics
p.000012: committees should consider the potential harm that could result from forgoing the research or from failing to publish
p.000012: the results.
p.000012:
p.000012: Risks to researchers. In addition to participants, investigators themselves can be exposed to risks that result from
p.000012: research activities. For example, research involving radiation can expose researchers to risks and studies on
p.000012: infectious disease can pose risks to laboratory staff who are handling samples. Sponsors should carefully
p.000012: assess and minimize risks to researchers; specify and explain the risks of undertaking the research to investigators
p.000012: and other research staff; and provide adequate compensation in case any members of the research team incur harm as a
p.000012: result of the research.
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012:
p.000012: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000013: 13
p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: GUIDELINE 5:
p.000013: CHOICE OF CONTROL IN CLINICAL TRIALS
p.000013:
p.000013: As a general rule, the research ethics committee must ensure that research participants in the control group of a trial
p.000013: of a diagnostic, therapeutic, or preventive intervention receive an established effective intervention.
p.000013:
p.000013: Placebo may be used as a comparator when there is no established effective intervention for the condition under
p.000013: study, or when placebo is added on to an established effective intervention.
p.000013:
p.000013: When there is an established effective intervention, placebo may be used as a comparator without providing the
p.000013: established effective intervention to participants only if:
p.000013: f there are compelling scientific reasons for using placebo; and
p.000013: f delaying or withholding the established effective intervention will result in no more than a minor
p.000013: increase above minimal risk to the participant and risks are minimized, including through the use of effective
p.000013: mitigation procedures.
p.000013:
p.000013: Risks and benefits of other study interventions and procedures should be evaluated according to the criteria set out in
p.000013: Guideline 4 – Potential individual benefits and risks of research.
p.000013:
p.000013:
p.000013: Commentary on Guideline 5
p.000013: General considerations for controlled clinical trials. The conduct of controlled clinical trials is
...
p.000015: withheld or substituted with an inferior intervention only if there are compelling scientific reasons for doing so; the
p.000015: risks of withholding the established intervention or substituting it with an inferior one will result in no
p.000015: more than a minor increase above minimal risk to participants; and the risks to participants are minimized.
p.000015:
p.000015: Placebo. An inert substance or sham procedure is provided to research participants with the aim of making it impossible
p.000015: for them, and usually the researchers themselves, to know who is receiving an active or inactive intervention. Placebo
p.000015: interventions are methodological tools used with the goal of isolating the clinical effects of the investigational drug
p.000015: or intervention. This enables researchers to treat participants in the study arm and the control arm in exactly the
p.000015: same way, except that the
p.000015:
p.000015:
p.000015:
p.000015: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000016: 16
p.000016:
p.000016:
p.000016:
p.000016:
p.000016:
p.000016: study group receives an active substance and the control group does not. The risks of the placebo intervention itself
p.000016: are typically very low or non-existent (for example, ingestion of an inert substance).
p.000016:
p.000016: In some fields, such as surgery and anaesthesia, testing the effectiveness of interventions may require the use of sham
p.000016: interventions. For example, the participants in the active arm of a surgery trial may receive arthroscopic surgery
p.000016: on their knees, while participants in the control group may receive only a minor skin incision. In other
p.000016: cases, both groups may receive an invasive procedure, such as inserting a catheter into a person’s artery. The catheter
p.000016: is threaded into the heart of participants in the active arm, but stopped short of the heart in participants in the
p.000016: control arm. The risks of sham procedures can be considerable (for example, surgical incision under general
p.000016: anaesthesia) and must be carefully considered by a research ethics committee.
p.000016:
p.000016: Placebo controls. The use of placebo is usually uncontroversial in the absence of an established effective
p.000016: intervention. As a general rule, when an established effective intervention exists for the condition under
p.000016: investigation, study participants must receive that intervention within the trial. This does not preclude
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p.000078: study unless a waiver or modification of consent is granted by a research ethics committee (see Guideline 10 –
p.000078: Modifications and waivers of informed consent). Waivers or modifications of informed consent may be necessary in some
p.000078: CRTs in which it is virtually impossible to obtain individual informed consent. This occurs when the
p.000078: intervention is directed at an entire community, making it impossible to avoid the intervention. Examples
p.000078: include a study comparing methods of incinerating waste or fluoridating the drinking-water supply to
p.000078: prevent dental carries. Members of the intervention community cannot avoid being affected by the intervention, so
p.000078: obtaining individual informed consent is impossible. Similarly, if the units in a cluster are hospitals or health
p.000078: centres, it could be difficult for patients to find another hospital or general practice to avoid a new method of
p.000078: delivery of preventive services. Another reason for the use of waivers or modifications
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p.000079:
p.000079: of consent in CRTs is that researchers may want to avoid participants in the control group learning about the
p.000079: intervention in the intervention group and accordingly, change their behaviour or try to get the intervention at
p.000079: another location, thereby compromising the results of the study.
p.000079:
p.000079: When a study is conducted at a cluster level (different hospitals, clinics, or communities), the requirement to obtain
p.000079: consent from health care workers can compromise the results or make it difficult to analyse the results.
p.000079: When health care workers are the subjects, the refusal of some workers to be observed or to apply a new diagnostic or
p.000079: therapeutic tool could confound the results of the research. Researchers would not be able to tell whether a new
p.000079: intervention is sufficiently effective if some health care workers refuse to participate and employ their usual
p.000079: procedures. A waiver of consent would then be an option (see Guideline 4 – Potential individual benefits and risks of
p.000079: research), but health care workers must nevertheless be notified that a study is taking place. If the
p.000079: interventions are directly carried out on patients, they would normally also be considered research subjects and their
p.000079: consent to receive the intervention would be required.
p.000079:
p.000079: Although in many CRTs participants cannot consent to being randomized, depending on the type of study design they may
p.000079: be able to give informed consent to receive the intervention. The intervention may be delivered at the individual level
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p.000008: GUIDELINE 4:
p.000008: POTENTIAL INDIVIDUAL BENEFITS AND RISKS OF RESEARCH
p.000008:
p.000008: To justify imposing any research risks on participants in health research, the research must have social
p.000008: and scientific value. Before inviting potential participants to join a study, the researcher, sponsor and the
p.000008: research ethics committee must ensure that risks to participants are minimized and appropriately balanced in
p.000008: relation to the prospect of potential individual benefit and the social and scientific value of the research.
p.000008:
p.000008: The potential individual benefits and risks of research must be evaluated in a two-step process. First,
p.000008: the potential individual benefits and risks of each individual research intervention or procedure in the study
p.000008: must be evaluated.
p.000008: f For research interventions or procedures that have the potential to benefit participants, risks are acceptable if
p.000008: they are minimized and outweighed by the prospect of potential individual benefit and the available evidence suggests
p.000008: that the intervention will be at least as advantageous, in the light of foreseeable risks and benefits, as any
p.000008: established effective alternative. Therefore, as a general rule, participants in the control group of a trial must
p.000008: receive an established effective intervention. The conditions under which a placebo may be used are spelled out in
p.000008: Guideline 5 – Choice of control in clinical trials.
p.000008: f For research interventions or procedures that offer no potential individual benefits to participants, the risks
p.000008: must be minimized and appropriate in relation to the social and scientific value of the knowledge to be gained
p.000008: (expected benefits to society from the generalizable knowledge).
p.000008: f In general, when it is not possible or feasible to obtain the informed consent of participants,
p.000008: research interventions or procedures that offer no potential individual benefits must pose no more than minimal
p.000008: risks. However, a research ethics committee may permit a minor increase above minimal risk when it is not possible to
p.000008: gather the necessary data in another population or in a less risky or burdensome manner, and the social and scientific
p.000008: value of the research is compelling (see Guideline 16 – Research involving adults incapable of giving informed
p.000008: consent, and Guideline 17 – Research involving children and adolescents).
p.000008:
p.000008: In a second step, the aggregate risks and potential individual benefits of the entire study must be assessed and must
p.000008: be considered appropriate.
p.000008: f The aggregate risks of all research interventions or procedures in a study must be considered
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p.000012: committees should consider the potential harm that could result from forgoing the research or from failing to publish
p.000012: the results.
p.000012:
p.000012: Risks to researchers. In addition to participants, investigators themselves can be exposed to risks that result from
p.000012: research activities. For example, research involving radiation can expose researchers to risks and studies on
p.000012: infectious disease can pose risks to laboratory staff who are handling samples. Sponsors should carefully
p.000012: assess and minimize risks to researchers; specify and explain the risks of undertaking the research to investigators
p.000012: and other research staff; and provide adequate compensation in case any members of the research team incur harm as a
p.000012: result of the research.
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p.000013:
p.000013:
p.000013:
p.000013:
p.000013:
p.000013: GUIDELINE 5:
p.000013: CHOICE OF CONTROL IN CLINICAL TRIALS
p.000013:
p.000013: As a general rule, the research ethics committee must ensure that research participants in the control group of a trial
p.000013: of a diagnostic, therapeutic, or preventive intervention receive an established effective intervention.
p.000013:
p.000013: Placebo may be used as a comparator when there is no established effective intervention for the condition under
p.000013: study, or when placebo is added on to an established effective intervention.
p.000013:
p.000013: When there is an established effective intervention, placebo may be used as a comparator without providing the
p.000013: established effective intervention to participants only if:
p.000013: f there are compelling scientific reasons for using placebo; and
p.000013: f delaying or withholding the established effective intervention will result in no more than a minor
p.000013: increase above minimal risk to the participant and risks are minimized, including through the use of effective
p.000013: mitigation procedures.
p.000013:
p.000013: Risks and benefits of other study interventions and procedures should be evaluated according to the criteria set out in
p.000013: Guideline 4 – Potential individual benefits and risks of research.
p.000013:
p.000013:
p.000013: Commentary on Guideline 5
p.000013: General considerations for controlled clinical trials. The conduct of controlled clinical trials is
p.000013: methodologically essential in order to test the relative merits of investigational interventions. To obtain
p.000013: valid results in a controlled trial, researchers must compare the effects of an experimental intervention on
p.000013: participants assigned to the investigational arm (or arms) of a trial with the effects that a control intervention
p.000013: produces in persons drawn from the same population. Randomization is the preferred method for assigning
p.000013: participants to the arms of controlled trials. Assignment to treatment arms by randomization tends to produce study
p.000013: groups comparable with respect to factors that might influence study outcomes, removes researcher bias in the
p.000013: allocation of participants, and helps to ensure that the study results reflect the effects of administered
p.000013: interventions and not the influence of extraneous factors.
p.000013:
p.000013: The use of placebo controls in clinical trials creates the potential for conflict between the demands of sound
p.000013: science and the obligation to safeguard the health and welfare of study participants. In general, studies
p.000013: must be designed to generate accurate scientific information without delaying or withholding established effective
p.000013: interventions from participants. Researchers and sponsors may deviate from this rule when withholding such
p.000013: interventions is methodologically necessary and exposes participants to no more than a minor increase above minimal
p.000013: risk.
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p.000015:
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p.000015:
p.000015:
p.000015: Although conventional randomized controlled clinical trials are often considered the gold standard, other study
p.000015: designs such as response-adaptive trial designs, observational studies, or historical comparisons can also
p.000015: yield valid research results. Researchers and sponsors must carefully consider whether the research question
p.000015: can be answered with an alternative design, and whether the risk-benefit profile of alternative designs is more
p.000015: favourable when compared to a conventional randomized controlled trial.
p.000015:
p.000015: Established effective intervention. An established effective intervention for the condition under study exists when it
p.000015: is part of the medical professional standard. The professional standard includes, but is not limited to, the best
p.000015: proven intervention for treating, diagnosing or preventing the given condition. In addition, the professional
p.000015: standard includes interventions that may not be the very best when compared to available alternatives, but are
p.000015: nonetheless professionally recognized as a reasonable option (for example, as evidenced in treatment guidelines).
p.000015:
p.000015: Yet established effective interventions may need further testing, especially when their merits are subject
p.000015: to reasonable disagreement among medical professionals and other knowledgeable persons. Clinical trials may be
p.000015: warranted in this case, in particular if the efficacy of an intervention or procedure has not been determined in
p.000015: rigorous clinical trials. Trials may also be useful when the risk-benefit profile of a treatment is not clearly
p.000015: favourable, such that patients might reasonably forgo the usual intervention for the condition (for example, antibiotic
p.000015: treatment for otitis media in children, or arthroscopic knee surgery). When there are several treatment
p.000015: options but it remains unknown which treatment works best for whom, comparative effectiveness research may help to
p.000015: further determine the effectiveness of an intervention or procedure for specific groups. This may include testing an
p.000015: established effective intervention against a placebo, provided the conditions of this Guideline are met.
p.000015:
p.000015: Some people contend that it is never acceptable for researchers to withhold or withdraw established effective
p.000015: interventions. Others argue that it may be acceptable, provided that the risks of withholding an established
p.000015: intervention are acceptable, and withholding the established effective intervention is necessary to ensure that
p.000015: the results are interpretable and valid. In such cases, an intervention known to be inferior, a placebo (see below) or
p.000015: no intervention may be substituted for the established intervention. This Guideline takes a middle stance on
p.000015: this issue. The preferred option is to test potential new interventions against an established effective
p.000015: intervention. When researchers propose to deviate from this option, they must provide a compelling methodological
p.000015: justification and evidence that the risks from withholding or delaying the established intervention are no greater than
p.000015: a minor increase above minimal risk.
p.000015:
p.000015: These principles on the use of placebo also apply to the use of control groups who receive no treatment or who
p.000015: receive a treatment that is known to be inferior to an established treatment. Sponsors, researchers, and
p.000015: research ethics committees should evaluate the risks of providing no treatment (and no placebo) or an inferior
p.000015: treatment, compared to the risks and potential individual benefits of providing an established treatment, and apply the
p.000015: criteria for placebo use in this Guideline. In sum, when an established effective intervention exists, it may be
p.000015: withheld or substituted with an inferior intervention only if there are compelling scientific reasons for doing so; the
p.000015: risks of withholding the established intervention or substituting it with an inferior one will result in no
p.000015: more than a minor increase above minimal risk to participants; and the risks to participants are minimized.
p.000015:
p.000015: Placebo. An inert substance or sham procedure is provided to research participants with the aim of making it impossible
p.000015: for them, and usually the researchers themselves, to know who is receiving an active or inactive intervention. Placebo
p.000015: interventions are methodological tools used with the goal of isolating the clinical effects of the investigational drug
p.000015: or intervention. This enables researchers to treat participants in the study arm and the control arm in exactly the
p.000015: same way, except that the
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p.000016: study group receives an active substance and the control group does not. The risks of the placebo intervention itself
p.000016: are typically very low or non-existent (for example, ingestion of an inert substance).
p.000016:
p.000016: In some fields, such as surgery and anaesthesia, testing the effectiveness of interventions may require the use of sham
p.000016: interventions. For example, the participants in the active arm of a surgery trial may receive arthroscopic surgery
p.000016: on their knees, while participants in the control group may receive only a minor skin incision. In other
p.000016: cases, both groups may receive an invasive procedure, such as inserting a catheter into a person’s artery. The catheter
p.000016: is threaded into the heart of participants in the active arm, but stopped short of the heart in participants in the
p.000016: control arm. The risks of sham procedures can be considerable (for example, surgical incision under general
p.000016: anaesthesia) and must be carefully considered by a research ethics committee.
p.000016:
p.000016: Placebo controls. The use of placebo is usually uncontroversial in the absence of an established effective
p.000016: intervention. As a general rule, when an established effective intervention exists for the condition under
p.000016: investigation, study participants must receive that intervention within the trial. This does not preclude
p.000016: comparing the effects of potential new interventions against a placebo control in cases where all participants receive
p.000016: the established effective intervention and are then randomized to the investigational intervention or placebo. Such
p.000016: add-on designs are common in oncology where all participants receive an established effective treatment, and are then
p.000016: randomized to placebo or the investigational intervention.
p.000016:
p.000016: Alternatively, when there is credible uncertainty about the superiority of an established effective
p.000016: intervention over an investigational agent (“this is known as clinical equipoise”), it is permissible to compare its
p.000016: effects directly against an established effective intervention. In these cases, the study design safeguards the
p.000016: welfare of participants by ensuring that they are not deprived of care or prevention that is believed to be
p.000016: an effective response to their health needs.
p.000016:
p.000016: Finally, the use of placebo is usually uncontroversial when an established effective intervention is not known to be
p.000016: safe and effective in a particular local context. For example, viruses often have different strains
p.000016: whose occurrence varies geographically. An established vaccine may have been shown to be safe and
p.000016: effective against a particular strain, but there may be credible uncertainty about its effects against a
p.000016: different strain in a different geographical context. In this situation, it can be acceptable to use a placebo control
p.000016: because it is uncertain whether the established vaccine is effective in the local context.
p.000016:
p.000016: Compelling scientific reasons. Compelling scientific reasons for placebo controls exist when a trial cannot distinguish
p.000016: effective from ineffective interventions without a placebo control (sometimes referred to as “assay sensitivity”).
p.000016: Examples of “compelling scientific reasons” include the following: the clinical response to the established effective
p.000016: intervention is highly variable; the symptoms of the condition fluctuate and there is a high rate of spontaneous
p.000016: remission; or the condition under study is known to have a high response to placebos. In these situations, it can be
p.000016: difficult to determine without a placebo control whether the experimental intervention is effective, as the condition
p.000016: may be improving on its own (spontaneous remission) or the observed clinical response may be due to a placebo effect.
p.000016:
p.000016: In some cases an established effective intervention is available but the existing data may have been
p.000016: obtained under conditions that are substantially different from local health care practices (for example, a different
p.000016: route of administration for drugs). In this situation, a placebo-controlled trial can be the best way of evaluating the
p.000016: intervention as long as this trial is responsive to local health needs, as set out in Guideline 2 – Research conducted
p.000016: in low-resource settings, and all other requirements in these Guidelines are met.
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p.000017:
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p.000017:
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p.000017: When a researcher invokes compelling scientific reasons to justify the use of placebo, the research ethics committee
p.000017: should seek expert advice, if such expertise is not already present among members of the committee, as to whether use
p.000017: of an established effective intervention in the control arm would invalidate the results of the research.
p.000017:
p.000017: Minimizing risks to participants. Even when placebo is justified by one of the conditions in this Guideline, the
p.000017: possibly harmful effects of receiving this comparator must be minimized consistent with the general requirements to
p.000017: minimize the risks of research interventions (Guideline 4 – Potential individual benefits and risks of research). The
p.000017: following conditions apply to placebo-controlled trials.
p.000017:
p.000017: First, researchers must decrease the period of placebo use to the shortest possible time consistent with achieving
p.000017: the scientific aims of the study. Risks in the placebo arm may be further reduced by permitting a change
p.000017: to active treatment (“escape treatment”). The protocol should establish a threshold beyond which the participant should
p.000017: be offered the active treatment.
p.000017:
p.000017: Second, as discussed in Guideline 4 – Commentary, the researcher must minimize harmful effects of placebo-controlled
p.000017: studies by providing safety monitoring of research data during the trial.
p.000017:
p.000017: Minimal risks of receiving placebo. Risks of receiving placebo count as minimal when the risk of serious harm is
p.000017: very unlikely and the potential harms associated with more common adverse events are small, as described in
p.000017: Guideline 4 – Potential individual benefits and risks of research. For example, when the investigational intervention
p.000017: is aimed at a relatively trivial condition, such as the common cold in an otherwise healthy person, or hair loss, and
p.000017: using a placebo for the duration of a trial would deprive control groups of only minor benefits, the risks of using a
p.000017: placebo-control design are minimal. The risks of receiving placebo in the presence of an established effective
p.000017: intervention must be compared with the risks that an average, normal, healthy individual experiences in
p.000017: daily life or during routine examinations.
p.000017:
p.000017: Minor increase above minimal risk. Consistent with Guideline 4 – Potential individual benefits and risks of
p.000017: research, the minor increase above minimal risk standard also applies to placebo- controlled trials.
p.000017:
p.000017: Placebo control in a low-resource setting when an established effective intervention cannot be made available
p.000017: for economic or logistic reasons. In some cases, an established effective intervention for the condition under study
p.000017: exists, but for economic or logistic reasons this intervention may not be possible to implement or made available in
p.000017: the country where the study is conducted. In this situation, a trial may seek to develop an intervention that could be
p.000017: made available, given the finances and infrastructure of the country (for example, a shorter or less complex course of
p.000017: treatment for a disease). This can involve testing an intervention that is expected or even known to be inferior to the
p.000017: established effective intervention, but may nonetheless be the only feasible or cost-effective and beneficial option
p.000017: in the circumstances. Considerable controversy exists in this situation regarding which trial design is
p.000017: both ethically acceptable and necessary to address the research question. Some argue that such studies should be
p.000017: conducted with a non-inferiority design that compares the study intervention with an established effective
p.000017: method. Others argue that a superiority design using a placebo can be acceptable.
p.000017:
p.000017: The use of placebo controls in these situations is ethically controversial for several reasons:
p.000017: 1. Researchers and sponsors knowingly withhold an established effective intervention from participants in the control
p.000017: arm. However, when researchers and sponsors are in a position to provide an intervention that would
p.000017: prevent or treat a serious disease, it is difficult to see why they are under no obligation to provide it. They could
p.000017: design the trial as an equivalency trial to determine whether the experimental intervention is as good or almost as
p.000017: good as the established effective intervention.
p.000017:
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p.000018:
p.000018: 2. Some argue that it is not necessary to conduct clinical trials in populations in low-resource settings in order to
p.000018: develop affordable interventions that are substandard compared to the available interventions in other
p.000018: countries. Instead, they argue that drug prices for established treatments should be negotiated and increased funding
p.000018: from international agencies should be sought.
p.000018:
p.000018: When controversial, placebo-controlled trials are planned, research ethics committees in the host country must:
p.000018: 1. seek expert opinion, if not available within the committee, as to whether use of placebo may lead to
p.000018: results that are responsive to the needs or priorities of the host country (see Guideline 2
p.000018: – Research conducted in low-resource settings); and
p.000018:
p.000018: 2. ascertain whether arrangements have been made for the transition to care after research for study
p.000018: participants (see Guideline 6 – Caring for participants’ health needs), including post-trial arrangements
p.000018: for implementing any positive trial results, taking into consideration the regulatory and health care policy framework
p.000018: in the country.
p.000018:
p.000018: Comparative effectiveness and standard of care trials. For many conditions and diseases, one or more
p.000018: established effective treatments exist. Physicians and hospitals may then use different treatments for the same
p.000018: condition. Yet often the relative merits of these treatments are unknown. Comparative effectiveness research, as well
p.000018: as systematic reviews, have received growing attention over the past few years. In comparative effectiveness research,
p.000018: two or more interventions regarded as standards of care are directly compared. Comparative effectiveness
p.000018: research may help to determine which standard of care has better outcomes or more acceptable risks. Research ethics
p.000018: committees should carefully distinguish between marketing studies that aim to position a product (sometimes called
p.000018: seeding trials) and comparative effectiveness studies in which scientific and public health perspectives are the
p.000018: primary objectives. Research ethics committees should not approve the first type of studies.
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p.000034: Participants must be given such information promptly. In most clinical trials, interim results are not disclosed to
p.000034: researchers or participants until the study has been concluded. In long-term studies, the willingness of each
p.000034: participant to continue in the study must be ensured.
p.000034:
p.000034: Individual informed consent and access to research populations. In some circumstances, a researcher may
p.000034: enter a community or institution to conduct research or approach potential participants for their individual
p.000034: consent only after obtaining permission from an institution such as a school or a prison, or from a community leader, a
p.000034: council of elders, or another designated authority. Such institutional procedures or cultural customs should be
p.000034: respected. In no case, however, may the permission of a community leader or other authority substitute for individual
p.000034: informed consent. In some populations, the use of local languages may facilitate the communication of information to
p.000034: potential participants and the ability of a researcher to ensure that individuals truly understand the material facts.
p.000034: Many people in all cultures are unfamiliar with, or do not readily understand, scientific concepts such as placebo or
p.000034: randomization. Sponsors and researchers must use culturally appropriate ways to communicate information necessary for
p.000034: adherence to the requirements of the informed consent process. They must also describe and justify in the research
p.000034: protocol the procedure they plan to use in communicating information to participants. The project must include any
p.000034: resources needed to ensure that informed consent can be properly obtained in different linguistic and cultural
p.000034: settings.
p.000034:
p.000034: Voluntariness and undue influence. Informed consent is voluntary if an individual’s decision to participate is free
p.000034: from undue influence. A variety of factors may affect the voluntariness with which consent is provided. Some of these
p.000034: factors can be internal to participants, such as mental illness, whereas other influences can be external, such as a
p.000034: dependent relationship between participants and clinician-researchers. Circumstances such as severe illness or poverty
p.000034: may threaten voluntariness, but do not necessarily imply that participants cannot give voluntary informed
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p.000076: chosen so that studies will yield meaningful data in a rapidly evolving situation. Study designs must be feasible in a
p.000076: disaster situation but still appropriate to ensure the study’s scientific validity. Without scientific validity, the
p.000076: research lacks social value and must not be conducted (see Guideline 1 – Scientific and social value and respect for
p.000076: rights). Research may even divert personnel or resources from the disaster response. In clinical trials, the
p.000076: randomised-controlled trial design is often considered the “gold standard” for collecting robust data. However,
p.000076: researchers, sponsors, research ethics committees and others must explore alternative trial designs that may increase
p.000076: trial efficiency and access to promising experimental interventions while still maintaining scientific validity. The
p.000076: methodological and ethical merits of alternative trial designs must be carefully assessed before these designs are
p.000076: used. For example, when testing experimental treatments or vaccines during an epidemic, the appropriate trial
p.000076: design will depend on the promise of the investigational agent,
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p.000077:
p.000077:
p.000077:
p.000077:
p.000077: a variation in critical background factors (for example mortality and infection rates), and measurement of outcomes,
p.000077: among others. Researchers and sponsors must carefully evaluate the relative merits of different designs (for example
p.000077: observational or placebo-controlled) based on these factors.
p.000077:
p.000077: Community engagement. Because disasters often lead to vulnerability and fragile political and social situations,
p.000077: engaging local communities about the research at an early stage is essential for maintaining public trust and ensuring
p.000077: that studies are conducted in a culturally sensitive manner (see Guideline 7 – Community engagement). Researchers and
p.000077: sponsors can use creative mechanisms to expedite and facilitate community engagement in a disaster situation (for
p.000077: example, by using social media). Fostering community leadership will often be important to address distrust and
p.000077: communicate effectively in order to gain support for the study design. In engaging with communities, researchers,
p.000077: sponsors and research ethics committees should be aware of potential conflicts of interest vis-à-vis the proposed
p.000077: research. For example, community leaders might seek to reassert their own authority by providing services to their
p.000077: communities through research.
p.000077:
p.000077: Ethical review and oversight. The standard mechanism for ethical review will often be too time-consuming
p.000077: to enable full research protocols to be prepared and reviewed at the outset of a disaster. Procedures
p.000077: should be developed to facilitate and accelerate ethical review in a situation of crisis. For example, research ethics
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p.000079: in that cluster. For example, parents will not be able to consent to their children’s school being randomized to a
p.000079: vaccination programme or to being allocated to that cluster, but they could consent or refuse to consent to their
p.000079: child’s vaccination at school. In other CRTs, both the intervention and the community are randomized at the cluster
p.000079: level. These trials are called cluster-cluster randomized trials (for example, all the students in a school or
p.000079: all residents of a community). In cluster-cluster randomized trials, individual informed consent for receiving the
p.000079: intervention is typically difficult to obtain since it is almost impossible to avoid the intervention. At the same
p.000079: time, individual consent for data collection procedures is usually possible in both types of cluster randomized trials.
p.000079:
p.000079: Ethical acceptability of a no-intervention group. Some CRTs investigate interventions that have been proven
p.000079: to be effective elsewhere; this is termed implementation research. This type of research is often conducted in
p.000079: low-resource settings. An ethical question pertaining to this type of study is whether it is acceptable
p.000079: to withhold the proven intervention from a control group in a CRT. This situation is analogous to that of
p.000079: placebo controls in a randomized, controlled trial when an established, effective prevention or treatment exists. If
p.000079: withholding the proven intervention from the control cluster would expose participants to more than a minor
p.000079: increase above minimal risk, it would be unethical to use that study design. An example would be the introduction of
p.000079: sterilizing equipment or disposable needles in a resource-poor health centre with a high infection rate among the
p.000079: patients. In the implementation CRT, health care workers would have to be educated in the use of the new equipment
p.000079: and instructed to throw away the disposable needles. Since the reuse of needles without sterilization would
p.000079: expose patients to more than a minor increase above minimal risk, it would be unethical for the control cluster to
p.000079: continue the usual practice. In such cases, it is necessary for researchers to explore an alternative design, such as
p.000079: using historical controls from the same facility. Research ethics committees have the responsibility to
p.000079: determine whether the proposed research is ethically acceptable when the methodology calls for withholding an
p.000079: established effective treatment from the control cluster.
p.000079:
p.000079: Gatekeeping in cluster randomized trials. When a CRT substantially affects cluster or organizational
p.000079: interests, and a gatekeeper (for example, a community leader, headmaster, or local health council) possesses the
...
p.000119: Informed opt-out /opt-in 41, 44, 47, 49, 83
p.000119: In-kind 54
p.000119: Interventions 1 - 4, 9 - 12, 15 - 19, 21 - 23, 26, 30, 53, 55, 56, 61 - 63, 65, 66, 71 - 73, 75 - 81, 84,
p.000119: 88, 91, 100, 101, 104
p.000119:
p.000119:
p.000119:
p.000119:
p.000119:
p.000120: 120
p.000120: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000120:
p.000120: L
p.000120: Lactating. See Breastfeeding
p.000120: Legally authorized representative 37, 54, 61 - 63, 65, 67
p.000120: Local 3 - 5, 13, 17, 21 - 23, 26, 30, 35, 41, 45, 47, 52 - 54, 73, 78, 80, 87, 89, 90
p.000120: Long-term studies 33, 35
p.000120: Low-resource settings viii, ix, 3 - 5, 7, 17, 19, 22, 23, 26, 45, 47, 52, 75 - 77, 80, 89, 92
p.000120: M
p.000120: Management (of risks) 8, 42, 45, 48, 51, 85, 95 - 97
p.000120: Material Transfer Agreement 41, 45
p.000120: Minimal risk 9, 13, 15, 16, 18, 38, 62, 65, 66, 71, 72, 80, 88, 100
p.000120: Minor increase above minimal risk 13, 18
p.000120: Mitigation 11, 15, 76, 85, 95, 97
p.000120: Modification of informed consent 33, 37
p.000120: Money 54, 103
p.000120: Multi-centre research 87, 89
p.000120: O
p.000120: Observational ix, xii, 16, 53, 72, 78
p.000120: Online 27, 83 - 85, 106
p.000120: Opt-out/opt-in. See Informed opt-out/opt-in
p.000120: P
p.000120: Parent 65, 67, 68, 101
p.000120: Payment 54, 88, 101
p.000120: Permission 35, 38, 54, 58, 59, 61 - 63, 65, 67 - 71, 79, 80, 81, 83, 101
p.000120: Placebo 9, 15 - 19, 35, 78, 80
p.000120: Post-trial access. See Continued access
p.000120: Pregnant women 7, 8, 58, 70 - 73, 101
p.000120: Privacy 68, 83 - 85, 92, 93, 100, 101, 104, 106
p.000120: Procedures xi, 9 - 12, 15, 17, 19, 23, 26, 33 - 35, 37, 38, 42, 53 - 55, 59, 61, 62, 65 - 67, 71,
p.000120: 76 - 80, 87 - 90, 95, 97, 100 - 103
p.000120: Protocol 2, 12, 18, 23, 25, 35, 36, 43, 49, 55, 56, 58, 76, 83, 87 - 90, 92, 96, 99, 101, 102, 105
p.000120: Public accountability 11, 13, 29, 31, 51, 91
p.000120: Publication ii, 29, 31, 84, 91, 92, 95, 102
p.000120: R
p.000120: Registries 36, 38, 39, 47, 49, 51, 72, 91
p.000120: Rehabilitation 55, 104
p.000120: Reimbursement 53, 54
p.000120: Research ethics committee 2, 9, 10, 12, 15, 17, 18, 23, 25, 27, 33, 34 - 39, 41, 43 - 45, 47,
p.000120: 49 - 51, 53, 54, 56, 58, 61 - 63, 65, 68, 71, 73, 79, 85, 87 - 91, 95, 96, 98, 102, 103, 105
p.000120: Residual tissue 41, 43, 44
p.000120: Responsiveness 3, 4, 17, 19, 63, 75, 76
p.000120: Return of results 44, 45, 51
p.000120:
p.000120:
p.000120:
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p.000121: 121
p.000121:
p.000121: Risks 2, 5, 7 - 13, 15 - 19, 23, 26, 34 - 39, 41, 44, 47, 49, 50, 53, 54, 58, 59, 61 - 63, 65 - 67,
p.000121: 69 - 73, 75 - 77, 80, 81, 83 - 85, 88, 91, 92, 96, 100, 102, 104 - 106
p.000121: S
p.000121: Scientific value 2, 9 - 13, 51, 91
p.000121: Secondary use 49
p.000121: Social value 1 - 4, 8 - 11, 19, 25, 26, 30, 37, 38, 41, 44, 47, 50, 62, 65, 71, 73, 75, 77, 88, 91
...
Orphaned Trigger Words
p.000119: importance of such information can vary depending on the significance of the health need, the novelty and expected
p.000119: merits of the approach, the merits of alternative means of addressing the problem, and other considerations. For
p.000119: example, a well-designed, late phase clinical trial could lack social value if its endpoints are
p.000119: unrelated to clinical decision-making so that clinicians and policy-makers are unlikely to alter their practices
p.000119: based on the study’s findings.
p.000119:
p.000119:
p.000119:
p.000119: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000001: 1
p.000001:
p.000001:
p.000001:
p.000001:
p.000001:
p.000001: Similarly, although replication serves an important role in scientific research, well-designed studies that lack
p.000001: sufficient novelty may also lack social value.
p.000001:
p.000001: Researchers, sponsors, research ethics committees and relevant health authorities, such as regulators and
p.000001: policy-makers, must ensure that a study has sufficient social value to justify its associated risks, costs and burdens.
p.000001: In particular, there must be sufficient social value to justify risks to participants in studies that lack the prospect
p.000001: of potential individual benefit to them (see Guideline 4 – Potential individual benefits and risks of research).
p.000001:
p.000001: Scientific value. Scientific value refers to the ability of a study to produce reliable, valid information capable of
p.000001: realizing the stated objectives of the research. The requirement of scientific value applies to all
p.000001: health-related research with humans, regardless of funding source or degree of risk to participants. In part, this is
p.000001: because a diverse range of stakeholders (including patients, clinicians, researchers, policy-makers, industrial
p.000001: sponsors and others) rely on the information that research generates to make decisions that have
p.000001: important consequences for individual and public health. For example, evidence produced in early phase research
p.000001: provides the foundation for subsequent studies, and methodological shortcomings can derail promising avenues of
p.000001: research and squander valuable resources. Many other forms of research, such as clinical trials, health systems
p.000001: research, epidemiological studies or post-marketing studies, generate data that are relevant for clinical
p.000001: decision-making, health and social policy, or resource allocation. Ensuring that studies uphold high scientific
p.000001: standards is essential for maintaining the integrity of the research enterprise and its ability to fulfil its social
p.000001: function.
p.000001:
p.000001: Although the quality of the information produced by research depends critically on the scientific value of
p.000001: a study, scientific value alone does not make a study socially valuable. For example, a study can be rigorously
p.000001: designed but lack social value when the research question has been successfully addressed in prior research. However, a
p.000001: study cannot be socially valuable without appropriate and rigorous research methods to address the question at
p.000001: hand. In other words, scientific value is a necessary but not a sufficient condition for the social value of
p.000001: health research.
p.000001:
p.000001: Qualification of research personnel. Sponsors, researchers, and research ethics committees must ensure that all
...
p.000002: high- income countries. Moreover, a setting can change over time and no longer be considered low-resource.
p.000002:
p.000002: Responsiveness of research to health needs or priorities. The responsiveness requirement can be met by demonstrating
p.000002: that research is needed to provide new knowledge about the best means of addressing a health condition present in that
p.000002: community or region. Where communities or policy- makers have determined that research on particular health needs
p.000002: constitutes a public health priority, studies that address such needs seek to provide social value to the community or
p.000002: population and are therefore responsive to their health needs. Concerns about responsiveness might hinge on the
p.000002: relevance to the community of the information a study is designed to produce. For example, a question about
p.000002: responsiveness might arise if a study of a new intervention is planned for a community in which
p.000002: established effective interventions for a health condition are not locally available and the new
p.000002:
p.000002:
p.000002: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000003: 3
p.000003:
p.000003:
p.000003:
p.000003:
p.000003:
p.000003: intervention has features that would make it difficult to implement in that community. In such cases, researchers and
p.000003: sponsors must consider whether the study could be made more relevant to local health needs. If the knowledge to be
p.000003: gained from the research is intended for use primarily for the benefit of populations other than those involved
p.000003: in the research, the responsiveness requirement is violated. In such cases, the research raises serious
p.000003: concerns about justice, which requires a fair distribution of the benefits and burdens of research (see Guideline
p.000003: 3 – Equitable distribution of benefits and burdens in the selection of individuals and groups of participants in
p.000003: research).
p.000003:
p.000003: Some research is intended to generate information relevant to the health needs of people in low- resource settings
p.000003: but is not carried out in populations that are the intended beneficiaries of the research. As an exception
p.000003: to the general rule specified in this Guideline, such studies can be justified because the effort to generate
p.000003: information relevant to significant health needs of people in low- resource settings represents an important
p.000003: demonstration of solidarity with burdened populations. For example, during the Ebola outbreak of 2014, phase one
p.000003: studies on investigational Ebola vaccines were carried out in low-resource communities not experiencing an Ebola
p.000003: outbreak.
p.000003:
p.000003: Responsibilities and plans. When the research has important potential individual benefits to the population or
p.000003: community, the responsibility to make any intervention or product developed available to this population is shared
p.000003: among researchers, sponsors, governments, and civil society. For this reason, the negotiation among stakeholders must
p.000003: include representatives in the community or country, including, where appropriate, the national government, the health
p.000003: ministry, local health authorities, relevant scientific and ethics groups, as well as members of the communities from
p.000003: which persons are drawn, patent-holders if they are other than the sponsor, and nongovernmental organizations such as
...
p.000008: appropriate in light of the potential individual benefits to participants and the scientific social value of the
p.000008: research.
p.000008: f The researcher, sponsor and research ethics committee must also consider risks to groups and
p.000008: populations, including strategies to minimize these risks.
p.000008:
p.000008:
p.000008:
p.000008:
p.000008: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000009: 9
p.000009:
p.000009:
p.000009:
p.000009:
p.000009:
p.000009: f The potential individual benefits and risks of research studies must be evaluated in consultation with
p.000009: the communities to be involved in the research (see Guideline 7 – Community engagement).
p.000009:
p.000009:
p.000009: Commentary on Guideline 4
p.000009: General considerations. Participants in health research are often exposed to a variety of interventions or procedures,
p.000009: many of which pose some risk. In this Guideline, the term “intervention” refers to the objects of study, such as new or
p.000009: established therapies, diagnostic tests, preventive measures and various techniques (for example, financial
p.000009: incentives) that might be used to modify health-related behaviours. The term “procedure” refers to research
p.000009: activities that provide information about the object of study, for example the safety and efficacy of a new therapy.
p.000009: Procedures include surveys and interviews, clinical exams, monitoring (for example, an electrocardiogram), blood draws,
p.000009: biopsies, imaging, as well as methods used in the conduct of the research, such as randomization.
p.000009:
p.000009: Many research interventions and procedures pose risks to participants. Risk is generally understood as an estimate
p.000009: of two factors: first, how likely it is that a participant will experience a physical, psychological,
p.000009: social or other harm; and second, the magnitude or significance of the harm. This understanding of risk
p.000009: implies that discomfort, inconvenience or burdens are harms of a very small magnitude that are almost certain to occur.
p.000009: The ethical justification for exposing participants to risks is the social and scientific value of research, namely the
p.000009: prospect of generating the knowledge and means necessary to protect and promote people’s health (see Guideline 1 –
p.000009: Scientific and social value and respect for rights). However, some risks cannot be justified, even when the research
p.000009: has great social and scientific value and adults who are capable of giving informed consent would give their
p.000009: voluntary, informed consent to participate in the study. For example, a study that involves deliberately
p.000009: infecting healthy individuals with anthrax or Ebola - both of which pose a very high mortality risk due
p.000009: to the absence of effective treatments - would not be acceptable even if it could result in developing an effective
p.000009: vaccine against these diseases. Therefore, researchers, sponsors, and research ethics committees must ensure that
p.000009: the risks are reasonable in light of the social and scientific value of the research, and that the study does
p.000009: not exceed an upper limit of risks to study participants.
p.000009:
p.000009: What constitutes an appropriate risk-benefit ratio cannot be expressed in a mathematical formula or algorithm. Rather,
p.000009: it is a judgment that results from a careful assessment and reasonable balancing of a study’s risks and potential
p.000009: individual benefits. The steps outlined in this Guideline are intended to ensure protection of the rights and welfare
p.000009: of study participants.
p.000009:
p.000009: It is important to evaluate the potential individual benefits and risks of proposed research in
p.000009: consultation with the communities to be involved in the research (see Guideline 7 – Community
p.000009: engagement). This is because a community’s values and preferences are relevant in determining what
p.000009: constitute benefits and acceptable risks. Evaluating risks and potential individual benefits also requires a good
p.000009: understanding of the context in which a study is to be conducted. This is best obtained in consultation
p.000009: with communities. Moreover, the risk-benefit ratio of a study can change as it progresses. Researchers, sponsors and
p.000009: research ethics committee should therefore re-evaluate the risks and potential individual benefits of studies on a
p.000009: regular basis.
p.000009:
p.000009: Evaluation of individual research interventions and procedures. To evaluate the risks and potential
p.000009: individual benefits of a research study, researchers, sponsors, and research ethics committees must first
p.000009: assess the risks and potential individual benefits of each individual research intervention and procedure, and then
p.000009: judge the aggregate risks and potential individual benefits of the study as a whole. Taking these successive steps is
p.000009: important because overall judgments of the risk-benefit profile of a study as a whole are more likely to be inaccurate
p.000009: because they may miss
p.000009:
p.000009: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000010: 10
p.000010:
p.000010:
p.000010:
p.000010:
p.000010:
p.000010: concerns raised by individual interventions. For example, a study may involve research procedures that do not pose
p.000010: significant risks, yet the procedures fail to yield important information. Global risk- benefit judgments would likely
p.000010: miss this concern. In contrast, scrutiny of each individual research intervention and procedure in the study would
p.000010: result in removing duplicative procedures and thereby minimize risks to participants.
p.000010:
p.000010: Potential individual benefits. Research has a range of potential individual benefits. It generates the knowledge
p.000010: necessary to protect and promote the health of future patients (the social and scientific value of research; see
p.000010: Guideline 1 – Scientific and social value and respect for rights). A study intervention offers a prospect
p.000010: of clinical benefit when previous studies provide credible evidence that the intervention’s potential clinical benefits
p.000010: will outweigh its risks. For example, many investigational drugs in Phase III trials offer a prospect of potential
p.000010: individual benefit. Researchers, sponsors and research ethics committees must maximize the potential individual
p.000010: benefits of studies for both future patients and study participants. For instance, the social and scientific value
p.000010: of studies can be maximized by making data or specimens available for future research (see Guideline 24 – Public
p.000010: accountability for health-related research). Potential clinical benefits to participants can be maximized by targeting
p.000010: populations who stand to benefit most from the intervention under study. Measures to maximize potential individual
p.000010: benefits need to be carefully balanced with competing considerations. For example, sharing data or specimens for future
p.000010: research can pose risks to participants, especially when adequate safeguards to protect confidentiality are not in
p.000010: place.
p.000010:
p.000010: Risks to research participants. To evaluate the acceptability of risks in a given study, researchers, sponsors and
p.000010: research ethics committees must begin by ensuring that the study poses a socially valuable research question and
p.000010: employs sound scientific methods for addressing this question. They must then determine for each
p.000010: intervention and procedure in the study that the associated risks to participants are minimized and that
p.000010: mitigation procedures are in place. This can involve ensuring that plans and procedures exist to adequately
p.000010: manage and reduce risks, for example by:
p.000010: f monitoring the study and providing mechanisms for responding to adverse events;
p.000010: f establishing a Data Safety and Monitoring Committee (DSMC) to review and decide on data on harms and benefits as a
p.000010: study progresses;
p.000010: f instituting clear criteria for stopping a study;
...
p.000026: 26
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026: trust, and ensure relevance. The value of beginning community involvement at the earliest opportunity is that any such
p.000026: disagreements can be aired, and if unable to be resolved, the research may have to be forgone (see Guideline 8 –
p.000026: Collaborative partnership and capacity-building for research and research review). If a research ethics committee is
p.000026: confronted with a severe split in the community about the design or conduct of a proposed study, the committee should
p.000026: urge the researchers to conduct the study in another community.
p.000026:
p.000026: Engagement by communities or groups. In some cases, communities or groups themselves initiate or conduct
p.000026: research projects. For example, patients with rare diseases may connect on online platforms and decide to collectively
p.000026: alter their treatment regimen while documenting the resulting clinical effects. Researchers should engage with these
p.000026: initiatives, which can offer valuable insights into their own work.
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026:
p.000026: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000027: 27
p.000027:
p.000027:
p.000027:
p.000027:
p.000027:
p.000027: GUIDELINE 8:
p.000027: COLLABORATIVE PARTNERSHIP AND CAPACITY-BUILDING FOR RESEARCH AND RESEARCH REVIEW
p.000027:
p.000027: It is the responsibility of governmental authorities in charge of health-related research involving human
p.000027: participants to ensure that such research is reviewed ethically and scientifically by competent and
p.000027: independent research ethics committees and is conducted by competent research teams. Independent scientific and
p.000027: ethical review is critical to engender community trust for research (see Guideline 23 – Requirements for
p.000027: establishing research ethics committees and for their review of protocols). Health-related research often requires
p.000027: international collaboration and some communities lack the capacity to assess or ensure the scientific quality or
p.000027: ethical acceptability of health-related research proposed or carried out in their jurisdictions. Researchers and
p.000027: sponsors who plan to conduct research in these communities should contribute to capacity-building for research and
p.000027: review.
p.000027:
p.000027: Capacity-building may include, but is not limited to, the following activities:
p.000027: f research infrastructure building and strengthening research capacity;
p.000027: f strengthening research ethics review and oversight capacity in host communities (see Guideline 23 – Requirements
p.000027: for establishing research ethics committees and for their review of protocols);
p.000027: f developing technologies appropriate to health care and health-related research;
p.000027: f educating research and health-care personnel and making arrangements to avoid undue displacement of health
p.000027: care personnel;
p.000027: f engaging with the community from which research participants will be drawn (see Guideline 7 – Community
p.000027: engagement);
p.000027: f arranging for joint publication consistent with recognized authorship requirements and data sharing (see Guideline
p.000027: 24 – Public accountability for health-related research); and
p.000027: f preparing a benefit-sharing agreement to distribute eventual economic gains from the research.
p.000027:
p.000027:
p.000027: Commentary on Guideline 8
p.000027: General considerations. Governmental authorities in charge of health-related research involving human participants
p.000027: have to ensure that such research is reviewed ethically and scientifically by competent and independent
p.000027: research ethics committees and is conducted by competent research teams (see Guideline 23 – Requirements for
...
p.000035: included in a health registry to obtain additional information from them for new research, such studies require
p.000035: informed consent.
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035:
p.000035: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000036: 36
p.000036:
p.000036:
p.000036:
p.000036:
p.000036:
p.000036: GUIDELINE 10:
p.000036: MODIFICATIONS AND WAIVERS OF INFORMED CONSENT
p.000036:
p.000036: Researchers must not initiate research involving humans without obtaining each participant’s individual informed
p.000036: consent or that of a legally authorized representative, unless researchers have received explicit approval to do so
p.000036: from a research ethics committee. Before a waiver of informed consent is granted, researchers and research
p.000036: ethics committees should first seek to establish whether informed consent could be modified in a way
p.000036: that would preserve the participant’s ability to understand the general nature of the investigation and to
p.000036: decide whether to participate.
p.000036:
p.000036: A research ethics committee may approve a modification or waiver of informed consent to research if:
p.000036: f the research would not be feasible or practicable to carry out without the waiver or modification;
p.000036: f the research has important social value; and
p.000036: f the research poses no more than minimal risks to participants.
p.000036:
p.000036: Additional provisions may apply when waivers or modifications of informed consent are approved in specific
p.000036: research contexts.
p.000036:
p.000036:
p.000036: Commentary on Guideline 10
p.000036: General considerations. A modification of informed consent involves making changes to the informed consent
p.000036: process, most frequently in relation to providing information and documenting the participant’s informed consent. A
p.000036: waiver of consent allows researchers to conduct studies without obtaining fully informed consent.
p.000036:
p.000036: As stated in Guideline 9 – Individuals capable of giving informed consent, individuals or their legally authorized
p.000036: representatives must give their informed consent for all health-related research involving humans. Modifications or
p.000036: waivers of informed consent require justification and approval. In general, researchers and research ethics
p.000036: committees must seek to preserve as much of the informed consent process as possible. They must carefully
p.000036: consider whether a modification of the informed consent process would still enable participants to understand
p.000036: the general nature of a study and make a meaningfully informed decision whether or not to participate. For
p.000036: instance, in some cases it may be possible to describe the purpose of a study without informing potential participants
p.000036: of the detailed procedures in the trial arms.
p.000036:
p.000036: Modifying the informed consent process by withholding information in order to maintain the scientific validity of the
p.000036: research. It is sometimes necessary to withhold information in the consent process to ensure the validity of the
p.000036: research. In health-related research, this typically
p.000036:
p.000036: INTERNATIONAL ETHICAL GUIDELINES FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
p.000037: 37
p.000037:
p.000037:
p.000037:
p.000037:
p.000037:
p.000037: involves withholding information about the purpose of specific procedures. For example, participants in clinical trials
p.000037: are often not told the purpose of tests performed to monitor their compliance with the regimen, since if they knew
p.000037: their compliance was being monitored they might modify their behaviour and hence invalidate results. In most such
p.000037: cases, potential participants must be asked to consent to remain uninformed of the purpose of some procedures
p.000037: until the research is completed. After their participation in the study ends, they must be given the
p.000037: omitted information. In other cases, because a request for permission to withhold some information would jeopardize
p.000037: the validity of the research, participants cannot be told that some information has been withheld until the data have
p.000037: been collected. Any such procedure may be implemented only if it receives explicit approval from a research ethics
p.000037: committee. Moreover, before study results are analysed, participants must be provided with the information
p.000037: withheld and given the possibility to withdraw their data collected under the study. The potential impact on
p.000037: the validity of the study when participants withdraw their data must be considered before a study starts.
p.000037:
p.000037: Modifying the informed consent process by actively deceiving participants. Active deception of participants is
p.000037: considerably more controversial than simply withholding certain information. However, social and behavioural
p.000037: scientists sometimes deliberately misinform participants in order to study their attitudes and behaviour. For example,
p.000037: researchers use “pseudo-patients” or “mystery clients” to study the behaviour of health-care professionals in their
p.000037: natural settings.
p.000037:
p.000037: Some people maintain that active deception is never permissible. Others would permit it in certain circumstances.
p.000037: Deception is not permissible in cases in which the study exposes participants to more than minimal risk.
p.000037: When deception is deemed indispensable for obtaining valid results in a study, researchers must convince the research
p.000037: ethics committee that no other method could obtain valid and reliable data; that the research has significant social
p.000037: value; and that no information has been withheld that, if divulged, would cause a reasonable person to refuse to
p.000037: participate. Researchers and research ethics committees must be aware that deceiving research participants
p.000037: may wrong them as well as harm them; participants may resent not having been informed when they learn that they have
p.000037: participated in a study under false pretences. Whenever this is necessary to maintain the scientific
p.000037: validity of the research, potential participants must be asked to agree to receiving incomplete information
p.000037: during the informed consent process (meaning that researchers obtain consent in advance for the deception). The
p.000037: research ethics committee must determine how participants must be informed of the deception upon completion of the
p.000037: research. Such informing, commonly called “debriefing”, ordinarily entails explaining the reasons for the deception.
p.000037: Debriefing is an essential part of trying to rectify the wrong of deception. Participants who disapprove of having been
p.000037: deceived for research purposes must be offered an opportunity to refuse to allow the researcher to use their data
p.000037: obtained through deception. In exceptional cases, a research ethics committee may approve the retention of
p.000037: non-identifiable information. For example, an option to withdraw data may not be offered in cases where research is
p.000037: evaluating quality of services or competence of providers (for example, studies involving “mystery” clients or
p.000037: patients).
p.000037:
p.000037: Waiving informed consent. A research ethics committee may waive informed consent if it is convinced that
p.000037: the research would not be feasible or practicable to carry out without the waiver, the research has
p.000037: important social value, and the research poses no more than minimal risks to participants. These three
p.000037: conditions must also be met even when a study involves identifiable data or biological specimens, meaning that the data
p.000037: or specimens carry a person’s name or are linked to a person by a code. The conditions must also be met when studies
...
p.000038: constitutes) a public health activity, the researcher must seek individual consent for the use of the data or
p.000038: demonstrate that the research meets the conditions for waiving informed consent, as set out in this Guideline. Research
p.000038: projects using data from one or more mandatory population-based registries should be submitted to a research ethics
p.000038: committee, except for data analyses involving internal institutional activity of a registry.
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p.000039:
p.000039:
p.000039:
p.000039:
p.000039:
p.000039: GUIDELINE 11:
p.000039: COLLECTION, STORAGE AND USE OF BIOLOGICAL MATERIALS AND RELATED DATA
p.000039:
p.000039: When biological materials and related data, such as health or employment records, are collected and stored,
p.000039: institutions must have a governance system to obtain authorization for future use of these materials in research.
p.000039: Researchers must not adversely affect the rights and welfare of individuals from whom the materials were collected.
p.000039:
p.000039: When specimens are collected for research purposes, either specific informed consent for a particular use or broad
p.000039: informed consent for unspecified future use must be obtained from the person from whom the material originally is
p.000039: obtained. The ethical acceptability of broad informed consent relies on proper governance. This type of
p.000039: consent must be obtained in the same way as described in Guideline 9 – Individuals capable of giving
p.000039: informed consent.
p.000039:
p.000039: When human biological materials are left over after clinical diagnosis or treatment (so-called “residual tissue”) and
p.000039: are stored for future research, a specific or broad informed consent may be used or may be substituted by an
p.000039: informed opt-out procedure. This means that the material is stored and used for research unless the
p.000039: person from whom it originates explicitly objects. The informed opt-out procedure must fulfil the
p.000039: following conditions:
p.000039: 1) patients need to be aware of its existence; 2) sufficient information needs to be provided;
p.000039: 3) patients need to be told that they can withdraw their data; and 4) a genuine possibility to object has to be
p.000039: offered.
p.000039:
p.000039: When researchers seek to use stored materials collected for past research, clinical or other purposes
p.000039: without having obtained informed consent for their future use for research, the research ethics committee may waive the
p.000039: requirement of individual informed consent if:
p.000039: 1) the research would not be feasible or practicable to carry out without the waiver; 2) the research has important
p.000039: social value; and 3) the research poses no more than minimal risks to participants or to the group to which
p.000039: the participant belongs.
p.000039:
p.000039: Custodians of biological materials must arrange to protect the confidentiality of the information linked
...
p.000044: disposal of the biological material and data should be developed in collaboration with local health authorities.
p.000044:
p.000044: Storing and using material from low-resource settings in biobanks. Biobanks have become a global phenomenon.
p.000044: Nevertheless, some low-resource settings may be inexperienced in storing and using biological materials. In
p.000044: addition to what is stated in this Guideline, requirements for community engagement, capacity-building and
p.000044: equitable distribution of burdens and benefits of research as described in other guidelines also apply to biobank
p.000044: research in low-resource settings (see Guideline 3 – Equitable distribution of benefits and burdens in the selection of
p.000044: individuals and groups of participants in research, Guideline 7 – Community engagement, and Guideline 8 – Collaborative
p.000044: partnership and capacity building for research and review).
p.000044:
p.000044:
p.000044:
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p.000045:
p.000045:
p.000045:
p.000045:
p.000045:
p.000045: GUIDELINE 12:
p.000045: COLLECTION, STORAGE AND USE OF DATA IN HEALTH-RELATED RESEARCH
p.000045:
p.000045: When data are stored, institutions must have a governance system to obtain authorization for future use of these data
p.000045: in research. Researchers must not adversely affect the rights and welfare of individuals from whom the data were
p.000045: collected.
p.000045:
p.000045: When data are collected and stored for research purposes, either specific informed consent for a particular use or
p.000045: broad informed consent for unspecified future use must be obtained from the person from whom the data were originally
p.000045: obtained. The ethical acceptability of broad informed consent relies on proper governance. This type of
p.000045: informed consent must be obtained in the same way as described in Guideline 9 – Individuals capable of
p.000045: giving informed consent.
p.000045:
p.000045: When data are used that were collected in the context of routine clinical care, an informed opt-out procedure must
p.000045: be used. This means that the data may be stored and used for research unless a person explicitly objects.
p.000045: However, a person’s objection is not applicable when it is mandatory to include data in population-based registries.
p.000045: The informed opt-out procedure must fulfil the following conditions: 1) patients need to be aware of its existence;
p.000045: 2) sufficient information needs to be provided; 3) patients need to be informed that they can withdraw their data; and
p.000045: 4) a genuine possibility to object has to be offered.
p.000045:
p.000045: When researchers seek to use stored data collected for past research, clinical or other purposes without having
p.000045: obtained informed consent for their future use for research, the research ethics committee may consider to
p.000045: waive the requirement of individual informed consent if: 1) the research would not be feasible or practicable to carry
p.000045: out without the waiver; and 2) the research has important social value; and 3) the research poses no more
p.000045: than minimal risks to participants or to the group to which the participant belongs.
p.000045:
p.000045: Custodians of the data must arrange to protect the confidentiality of the information linked to the data, by
...
p.000048: research ethics committee must determine whether explicit informed consent is required.
p.000048:
p.000048: Secondary use of stored data. Sometimes data are collected in databanks, during research or during other activities
p.000048: (for example, clinical practice, health insurance), that can be used in future research. Typically the precise research
p.000048: questions will be unknown at the time of data collection. In those cases, it is acceptable to use the data for
p.000048: secondary analysis when the intended use falls within the scope of the original (broad) informed consent.
p.000048:
p.000048: Withdrawal of consent. Donors or their legal representatives at any time and without any charges or losses, should
p.000048: have the possibility to withdraw their consent for use of data in a databank. The withdrawal of consent
p.000048: should be formalized by written documentation signed by the donor or
p.000048:
p.000048:
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p.000049:
p.000049:
p.000049:
p.000049:
p.000049:
p.000049: the legal representative of the donor, and the data should be either destroyed or returned to the donor. Future use of
p.000049: the data is not permitted after the withdrawal of consent.
p.000049:
p.000049: Authorization for research with archived data. When existing data, collected and stored without a specific
p.000049: or broad informed consent process, offer important and otherwise unobtainable information, a research ethics committee
p.000049: needs to decide whether the use of such data is justified. The most common justification for using data collected in
p.000049: the past without consent is that it would be impracticable or prohibitively expensive to locate the persons whose data
p.000049: are to be examined. This may happen when, for instance, the study involves reviewing hospital records from a time when
p.000049: consent to future research uses of such data was not usually sought. In addition, the research must have important
p.000049: social value, and the research must pose no more than minimal risks to participants or to the group from which the
p.000049: participant originates.
p.000049:
p.000049: Re-contacting participants. Long-term projects often include plans to search for and re-contact participants who have
p.000049: been lost to follow-up. Such outreach might also occur when researchers wish to obtain consent for a new use of stored
p.000049: biological material or data that still has personal identifiers. Participants or service users must be made aware of
p.000049: this possibility at the time of initial consent and given the choice to opt-out of being re-contacted. Researchers must
p.000049: also establish acceptable modalities for establishing contact with those participants or service users who
p.000049: are willing to be reached out to for the above-mentioned purposes.
p.000049:
p.000049: In cases where a researcher does plan to contact persons based on their inclusion in a health-related registry, the
p.000049: researcher must bear in mind that these persons may be unaware that their data were submitted to the registry or
...
p.000073: research and uphold ethical principles in its conduct.
p.000073:
p.000073: Researchers, sponsors, international organizations, research ethics committees and other relevant stakeholders should
p.000073: ensure that:
p.000073: f studies are designed so as to yield scientifically valid results under the challenging and often rapidly evolving
p.000073: conditions of disasters and disease outbreaks (see Guideline 1
p.000073: – Scientific and social value and respect for rights);
p.000073: f the research is responsive to the health needs or priorities of the disaster victims and affected
p.000073: communities and cannot be conducted outside a disaster situation (see Guideline 2 – Research conducted in low-resource
p.000073: settings);
p.000073: f participants are selected fairly and adequate justification is given when particular populations are
p.000073: targeted or excluded, for example health workers (see Guideline 3 – Equitable distribution of benefits and burdens in
p.000073: the selection of individuals and groups of participants in research);
p.000073: f the potential burdens and benefits of research participation and the possible benefits of the research are
p.000073: equitably distributed (see Guideline 3 – Equitable distribution of benefits and burdens in the selection of individuals
p.000073: and groups of participants in research);
p.000073: f the risks and potential individual benefits of experimental interventions are assessed realistically, especially
p.000073: when they are in the early phases of development (see Guideline 4
p.000073: – Potential individual benefits and risks of research);
p.000073: f communities are actively engaged in study planning in order to ensure cultural sensitivity, while
p.000073: recognizing and addressing the associated practical challenges (see Guideline 7 – Community engagement);
p.000073: f the individual informed consent of participants is obtained even in a situation of duress, unless the conditions
p.000073: for a waiver of informed consent are met (see Guideline 9 –
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p.000075:
p.000075:
p.000075:
p.000075:
p.000075:
p.000075: Individuals capable of giving informed consent, and Guideline 10 – Modifications and waivers of informed consent); and
p.000075: f research results are disseminated, data are shared, and any effective interventions developed or
p.000075: knowledge generated are made available to the affected communities (see Guideline 2 – Research conducted in
p.000075: low-resource settings, and Guideline 23
p.000075: – Requirements for establishing research ethics committees and for their review of protocols).
p.000075:
p.000075: Research in disasters and disease outbreaks should ideally be planned ahead. Health officials and research
p.000075: ethics committees should develop procedures to ensure appropriate, expedient and flexible mechanisms and
p.000075: procedures for ethical review and oversight. For example, research ethics committees could pre-screen study
p.000075: protocols in order to facilitate and expedite ethical review in a situation of crisis. Similarly,
p.000075: researchers and sponsors could make pre-arrangements on data- and sample-sharing that research ethics committees
p.000075: review in advance.
p.000075:
p.000075: Sponsors and research ethics committees should evaluate and seek to minimize the risks to researchers and
p.000075: health professionals conducting research in a disaster context. Sponsors should include in the protocol a plan for
p.000075: mitigating adverse events. Furthermore, appropriate resources for mitigation measures should be included in the
p.000075: protocol budget.
p.000075:
p.000075:
p.000075: Commentary on Guideline 20
...
p.000080: before taking the decision to permit the study.
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p.000081:
p.000081:
p.000081:
p.000081:
p.000081:
p.000081: GUIDELINE 22:
p.000081: USE OF DATA OBTAINED FROM THE ONLINE ENVIRONMENT AND
p.000081: DIGITAL TOOLS IN HEALTH-RELATED RESEARCH
p.000081:
p.000081: When researchers use the online environment and digital tools to obtain data for health- related research they should
p.000081: use privacy-protective measures to protect individuals from the possibility that their personal information is
p.000081: directly revealed or otherwise inferred when datasets are published, shared, combined or linked. Researchers should
p.000081: assess the privacy risks of their research, mitigate these risks as much as possible and describe the remaining risks
p.000081: in the research protocol. They should anticipate, control, monitor and review interactions with their data
p.000081: across all stages of the research.
p.000081:
p.000081: Researchers should inform persons whose data may be used in the context of research in the online environment of:
p.000081: f the purpose and context of intended uses of data and information;
p.000081: f the privacy and security measures used to protect their data, and any related privacy risks; and
p.000081: f the limitations of the measures used and the privacy risks that may remain despite the safeguards put
p.000081: in place.
p.000081:
p.000081: In case of a refusal by the person approached, researchers should refrain from using the data of this individual. This
p.000081: informed opt-out procedure must fulfil the following conditions:
p.000081: 1) persons need to be aware of its existence; 2) sufficient information needs to be provided;
p.000081: 3) persons need to be told that they can withdraw their data; and 4) a genuine possibility to object has to be offered.
p.000081:
p.000081: Researchers collecting data on individuals and groups through publicly accessible websites without direct interaction
p.000081: with persons should, at a minimum, obtain permission from website owners, post a notice of research intent,
p.000081: and ensure compliance with published terms of website use.
p.000081:
p.000081: Researchers must describe in the protocol how data obtained from online environments and digital tools will be treated,
p.000081: along with the potential risks of the research and how the potential risks are mitigated.
p.000081:
p.000081:
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p.000083:
p.000083:
p.000083:
p.000083:
p.000083:
p.000083: Commentary on Guideline 22
p.000083: General considerations. The vast range of data sources and technologies for collecting, analysing and sharing large
p.000083: quantities of data about individuals in the online environment has significantly expanded research opportunities,
p.000083: particularly with respect to studying personal and group characteristics, behaviours and interactions. The
...
p.000083: as data are accumulated, combined and used in a wide variety of contexts. For example, research on clinical or public
p.000083: health interventions using mobile devices is increasingly common. The convenience and reach of mobile
p.000083: devices, whether in the hands of persons or researchers, enables the convenient collection and rapid transmission of
p.000083: data in a variety of settings. Researchers using mobile phones and apps to collect data must be aware that these
p.000083: devices and applications each may have vastly different privacy-related characteristics and limitations.
p.000083:
p.000083: Privacy risks are not a simple function of the presence or absence of specific fields, attributes or keywords in a set
p.000083: of data. Much of the potential for privacy risks stems from what can be inferred about individuals from the data as a
p.000083: whole or when the data are linked with other available information. Approaches to privacy protection in common
p.000083: use often provide limited protection. Traditional de- identification techniques have notable limitations,
p.000083: and definitions based on a simple concept of “identifiability” lack sufficient precision to be used as a
p.000083: standard. Very few data points can be used
p.000083:
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p.000084:
p.000084:
p.000084:
p.000084:
p.000084:
p.000084: to uniquely identify an individual in a set of data. Researchers who use only redaction of names or other clearly
p.000084: identifying information may reveal information that exposes individuals to privacy risks.
p.000084:
p.000084: Mitigation of privacy risk. Selection and implementation of appropriate measures to mitigate privacy risks
p.000084: by investigators is essential and entails adopting privacy and security controls suited to the intended uses and
p.000084: privacy risks associated with the data. These measures in turn require a systematic analysis of the primary and
p.000084: secondary uses of the data, considering not just re-identification risks but also inference risks. This analysis should
p.000084: take into account not only whether a person can be directly associated with a particular attribute, but also the extent
p.000084: to which attributes that may be revealed or inferred depend on an individual’s data and the potential harm that may
p.000084: result. It also takes into account the potential uses of the data, which in turn affects data management, output, and
p.000084: the privacy controls that may ultimately be suitable. The types of uses or analytic purposes intended
p.000084: impact the choice of privacy controls at each stage, as some techniques may enable or restrict certain types of uses.
p.000084:
p.000084: Researchers should identify and manage risks during data collection, processing and dissemination. Privacy
p.000084: considerations require a conservative approach to data dissemination on the Internet. Academic publications and some
p.000084: institutions often require researchers to make their datasets publicly available, sometimes in an open data format.
p.000084: Public disclosure in such formats is problematic for datasets that contain identifiers, key-attributes and secondary
p.000084: attributes, as these enable re-identification of subjects by linking the records with auxiliary datasets. Once a
p.000084: dataset is released online, the researcher has lost control over how the data will be used, and the context of uses may
p.000084: change.
p.000084:
p.000084: Guidance to research ethics committees. Research ethics committees may wish to consult a regularly updated list of
p.000084: specific privacy and security measures such as the one envisaged by WHO, that would be deemed to satisfy the
p.000084: requirement for reasonable and appropriate safeguards. There should be a requirement for implementing these safeguards
p.000084: broadly, covering some categories of research activities that may fall within an exemption to research ethics committee
p.000084: review. Research ethics committees should understand the application of controls that are calibrated to
p.000084: different categories of data sharing (meaning in some cases, data shared publicly would be subject to more stringent
p.000084: requirements than data shared among researchers). In efforts to harmonize approaches across regulations and
p.000084: institutional policies, research ethics committees should emphasize the need to provide similar levels of protection to
p.000084: research activities that pose similar privacy risks.
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p.000085:
p.000085:
p.000085:
p.000085:
p.000085:
p.000085: GUIDELINE 23:
p.000085: REQUIREMENTS FOR ESTABLISHING RESEARCH ETHICS COMMITTEES
p.000085: AND FOR THEIR REVIEW OF PROTOCOLS
p.000085:
p.000085: All proposals to conduct health-related research involving humans must be submitted to a research ethics committee
p.000085: to determine whether they qualify for ethical review and to assess their ethical acceptability, unless
p.000085: they qualify for an exemption from ethical review (which may depend upon the nature of the research and
p.000085: upon applicable law or regulations). The researcher must obtain approval or clearance by such a
p.000085: committee before beginning the research. The research ethics committee should conduct further reviews as
p.000085: necessary, for example, when there are significant changes in the protocol.
p.000085:
p.000085: Research ethics committees must review research protocols according to the principles set out in these Guidelines.
p.000085:
p.000085: Research ethics committees must be formally established and given adequate mandate and support to ensure timely and
p.000085: competent review according to clear and transparent procedures. Committees must include multidisciplinary membership in
p.000085: order to competently review the proposed research. Committee members must be duly qualified and regularly update their
p.000085: knowledge of ethical aspects of health-related research. Research ethics committees must have mechanisms to
p.000085: ensure independence of their operations.
p.000085:
p.000085: Research ethics committees from different institutions or countries should establish efficient communication
p.000085: in cases of externally sponsored and multi-centre research. In externally sponsored research, ethical review
p.000085: must take place in both the host and the sponsoring institution.
p.000085:
p.000085: Research ethics committees should have a clear procedure for researchers or sponsors to make legitimate appeals against
p.000085: the decisions of research ethics committees.
p.000085:
p.000085:
p.000085: Commentary on Guideline 23
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p.000085: ethical review process. Contributions of study sponsors to institutions or governments to support ethics
p.000085: review must be transparent.
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p.000087:
p.000087:
p.000087:
p.000087:
p.000087:
p.000087: Under no circumstances may payment be offered or accepted to procure a committee’s approval or clearance of a protocol.
p.000087:
p.000087: Scientific and ethical review. Although in some instances scientific review precedes ethical review,
p.000087: research ethics committees must always have the opportunity to combine scientific and ethical review in
p.000087: order to ensure the social value of the research (see Guideline 1 – Scientific and social value and respect for
p.000087: rights). The ethical review must consider, among other aspects: the study design; provisions for minimizing
p.000087: risk; an appropriate balance of risks in relation to potential individual benefits for participants and the
p.000087: social value of the research; safety of the study site, medical interventions, and monitoring safety during
p.000087: the study; and the feasibility of the research. Scientifically unsound research involving humans is unethical in that
p.000087: it may expose them to risk or inconvenience for no purpose. Even if there is no risk of injury, involving persons’ and
p.000087: researchers’ time in unproductive activities wastes valuable resources. Research ethics committees must therefore
p.000087: recognize that the scientific validity of the proposed research is essential for its ethical acceptability. Committees
p.000087: must either carry out a proper scientific review, verify that a competent expert body has determined the research to be
p.000087: scientifically sound, or consult with competent experts to ensure that the research design and methods are appropriate.
p.000087: If research ethics committees do not have expertise to judge science or feasibility, they must draw on relevant
p.000087: expertise.
p.000087:
p.000087: Accelerated review. Accelerated review (sometimes called expedited review) is a process by which studies that involve
p.000087: no more than minimal risk may be reviewed and approved in a timely manner by an individual research ethics committee
p.000087: member or a designated subset of the full committee. Relevant authorities or research ethics committees may establish
p.000087: procedures for the accelerated review of research proposals. These procedures should specify the following:
p.000087: f the nature of the applications, amendments, and other considerations that will be eligible for
p.000087: accelerated review;
p.000087: f the minimum number of committee members required for accelerated review; and
p.000087: f the status of decisions (for example, subject to confirmation by a full research ethics committee or not).
p.000087:
p.000087: Relevant authorities or research ethics committees must establish a list of criteria for protocols that qualify for an
p.000087: accelerated review process.
p.000087:
p.000087: Further review. The research ethics committee must conduct further reviews of approved studies as necessary, in
p.000087: particular if there are significant changes in the protocol that require re-consent by participants,
p.000087: affect the safety of participants, or other ethical matters that emerge during the course of the study.
p.000087: These further reviews include progress reports submitted by researchers and possible monitoring of researchers’
p.000087: compliance with approved protocols.
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p.000087: Committee membership. The research ethics committee must be constituted according to a document that
p.000087: specifies the manner in which members and the chair will be appointed, reappointed, and replaced. Research ethics
p.000087: committees must have members capable of providing competent and thorough review of research proposals. Membership
p.000087: normally must include physicians, scientists and other professionals such as research coordinators, nurses,
p.000087: lawyers, and ethicists, as well as community members or representatives of patients’ groups who can represent
p.000087: the cultural and moral values of study participants. Ideally, one or more members should have experience as study
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p.000089: review committee proposes changes to the original protocol that it believes are necessary to protect the research
p.000089: participants, these changes must be reported to the research institution or sponsor responsible for the whole research
p.000089: programme for consideration and possible action. This should ensure that all persons are protected and that the
p.000089: research will be valid across sites.
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p.000089: Ideally, review procedures should be harmonized, which may decrease the time needed for review and accordingly, speed
p.000089: up the research process. In order to harmonize review processes and to maintain sufficient quality of these processes,
p.000089: ethics committees must develop quality indicators for ethical review. Appropriate review must be sensitive to increases
p.000089: in risk of harm or wrongs to local participants and populations.
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p.000089: Exemptions from review. Some studies may be exempt from review. For example, when publicly available data are analysed
p.000089: or the data for the study are generated by observation of public behaviour, and data that could identify individual
p.000089: persons or groups are anonymized or coded, the study may be exempt. Health systems research may be exempted from review
p.000089: if public officials are interviewed in their official capacity on issues that are in the public domain.
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p.000089: Monitoring. Research ethics committees must be authorized to monitor ongoing studies. The researcher must
p.000089: provide relevant information to the committee to permit monitoring of research records, especially information about
p.000089: any serious adverse events. Following the analysis of the study data, researchers must submit a final report to the
p.000089: committee containing a summary of the study’s findings and conclusions.
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p.000089: Protocol amendments, deviations, violations and sanctions. During the study, deviations from the original
p.000089: study might occur, such as changes in the sample size or analysis of the data as described in the protocol. Deviations
p.000089: must be reported to research ethics committees. In the case of permanent deviations, researchers may write an
p.000089: amendment. The research ethics committee must decide whether a deviation is legitimate or illegitimate. Protocol
p.000089: violations are deviations from the original protocol that significantly affect the rights or interests of
p.000089: research participants and significantly impact the scientific validity of the data. In the case of
p.000089: protocol violations, research ethics committees should ensure that study participants will be informed and provision
p.000089: will be made for the protection of their safety and welfare.
p.000089:
p.000089: A researcher may fail to submit a protocol to a research ethics committee for prospective review. This omission is a
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p.000096: situation to research ethics committees reviewing their protocols. Disclosure forms should provide a definition of
p.000096: conflicts of interest, along with some examples, and help researchers understand that a conflict of interest is not
p.000096: necessarily disqualifying, but may be managed. When research ethics committees have credible evidence about serious
p.000096: conflicts of interest related to a study that are not disclosed in the materials submitted to the committee, the member
p.000096: of the research team with the apparent conflict should be contacted for further information. Research
p.000096: ethics committees may also consult with the Conflict of Interest Coordinator in their institution.
p.000096:
p.000096: 3. Disclosure of interests to participants. Research ethics committees may require that conflicts of interest be
p.000096: disclosed to potential study participants in the informed consent discussion and documents (for example, stock
p.000096: ownership). The disclosure must allow potential participants to judge the seriousness of the conflict of interest. This
p.000096: goes beyond describing “the nature and sources of funding for the research,” which is an element of informed consent
p.000096: (see Appendix 2). In the case of serious conflicts of interest, studies suggest that disclosure works best when it is
p.000096: provided by a health professional independent of the study team and potential participants are given time to reflect.
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p.000096: 4. Mitigation of conflicts. Research ethics committees may consider a range of other measures to mitigate or manage
p.000096: conflicts of interest beyond disclosing these conflicts to potential participants. For example, where appropriate,
p.000096: research ethics committees may require a member of the study team who has no leading role in its
p.000096: design to obtain the informed consent of potential participants. Research ethics committees may also require
p.000096: limiting the involvement of researchers in a study when they have a serious conflict of interest. For instance, a
p.000096: researcher with a serious conflict may be involved only as a collaborator or consultant for specific tasks that require
p.000096: such
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p.000097: expertise, but not as a principal investigator or co-researcher. Alternatively, research ethics committees
p.000097: may require independent monitoring and review of studies where, for reasons of expertise, the full
p.000097: involvement of researchers with a serious conflict of interest is necessary. In cases where a serious
p.000097: conflict of interest cannot be adequately mitigated, research ethics committees may decide not to approve a
p.000097: study. Research ethics committees themselves must employ similar measures to identify, mitigate and manage the
p.000097: conflicts of interests of their own members. When necessary, research ethics committees may require members with a
p.000097: serious conflict to withdraw from deliberations of the research ethics committee and its decisions (see Guideline 23 –
p.000097: Requirements for establishing research ethics committees and for their review of protocols).
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p.000098: APPENDIX 1
p.000098: ITEMS TO BE INCLUDED IN A PROTOCOL (OR ASSOCIATED
p.000098: DOCUMENTS) FOR HEALTH-RELATED RESEARCH INVOLVING HUMANS
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Appendix
Indicator List
| Indicator | Vulnerability |
|---|
| HIV | HIV/AIDS |
| abuse | Victim of Abuse |
| access | Access to Social Goods |
| age | Age |
| alcoholism | alcoholism |
| another country | Other Country |
| armed forces | Soldier |
| arrest | person under arrest |
| asylum | Refugee Status |
| authority | Relationship to Authority |
| autonomy | Impaired Autonomy |
| belief | Religion |
| belmont | belmont |
| blind | visual impairment |
| blinded | visual impairment |
| breastfeeding | breastfeeding |
| child | Child |
| children | Child |
| cioms | cioms guidelines |
| cognitive | Cognitive Impairment |
| control group | participants in a control group |
| culturally | cultural difference |
| dependency | Drug Dependence |
| dependent | Dependent |
| diminished | Diminished Autonomy |
| disability | Mentally Disabled |
| disabled | Mentally Disabled |
| displaced | displaced |
| drug | Drug Usage |
| education | education |
| educational | education |
| elderly | Elderly |
| 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 |
| helsinki | declaration of helsinki |
| hiv/aids | HIV/AIDS |
| home | Property Ownership |
| homeless | Homeless Persons |
| illegal | Illegal Activity |
| illiterate | Literacy |
| illness | Physically Disabled |
| impairment | Cognitive Impairment |
| incapable | Mentally Incapacitated |
| incapacitated | Incapacitated |
| incapacity | Incapacitated |
| infant | Infant |
| influence | Drug Usage |
| institutionalized | Institutionalized |
| language | Linguistic Proficiency |
| linguistic | Linguistic Proficiency |
| literacy | Literacy |
| literate | Literacy |
| manipulate | Manipulable |
| married | Marital Status |
| military | Soldier |
| minor | Youth/Minors |
| mothers | Mothers |
| nomads | nomad |
| officer | Police Officer |
| opinion | philosophical differences/differences of opinion |
| oviedo | oviedo |
| 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 |
| poverty | Economic/Poverty |
| pregnant | Pregnant |
| prison | Incarcerated |
| prisoners | Criminal Convictions |
| property | Property Ownership |
| prostitution | sex worker |
| race | Racial Minority |
| racial | Racial Minority |
| research staff | Laboratory Staff |
| sex work | sex worker |
| sex workers | sex worker |
| sexually transmitted | sexually transmitted disases |
| single | Marital Status |
| social status | Economic/Poverty |
| std | sexually transmitted disases |
| stigma | Threat of Stigma |
| stigmatized | Threat of Stigma |
| student | Student |
| substance | Drug Usage |
| trauma | Victim of Abuse |
| underdeveloped | Developing Country |
| undue influence | Undue Influence |
| unemployed | Unemployment |
| usage | Drug Usage |
| violence | Threat of Violence |
| volunteers | Healthy People |
| vulnerability | vulnerable |
| vulnerable | vulnerable |
| women | Women |
Indicator Peers (Indicators in Same Vulnerability)
| Indicator | Peers |
|---|
| HIV | ['hiv/aids'] |
| abuse | ['trauma'] |
| armed forces | ['military'] |
| blind | ['blinded'] |
| blinded | ['blind'] |
| child | ['children'] |
| children | ['child'] |
| cognitive | ['impairment'] |
| control group | ['placebo'] |
| disability | ['disabled'] |
| disabled | ['disability'] |
| drug | ['influence', 'substance', 'usage'] |
| education | ['educational'] |
| educational | ['education'] |
| ethnic | ['ethnicity'] |
| ethnicity | ['ethnic'] |
| fetus | ['fetuses'] |
| fetuses | ['fetus'] |
| hiv/aids | ['HIV'] |
| home | ['property'] |
| illiterate | ['literacy', 'literate'] |
| illness | ['physically'] |
| impairment | ['cognitive'] |
| incapacitated | ['incapacity'] |
| incapacity | ['incapacitated'] |
| influence | ['drug', 'substance', 'usage'] |
| language | ['linguistic'] |
| linguistic | ['language'] |
| literacy | ['illiterate', 'literate'] |
| literate | ['illiterate', 'literacy'] |
| married | ['single'] |
| military | ['armedXforces'] |
| officer | ['police'] |
| opinion | ['philosophy'] |
| parent | ['parents'] |
| parents | ['parent'] |
| party | ['political'] |
| philosophy | ['opinion'] |
| physically | ['illness'] |
| placebo | ['controlXgroup'] |
| police | ['officer'] |
| political | ['party'] |
| poor | ['poverty', 'socialXstatus'] |
| poverty | ['poor', 'socialXstatus'] |
| property | ['home'] |
| prostitution | ['sexXwork', 'sexXworkers'] |
| race | ['racial'] |
| racial | ['race'] |
| sex work | ['prostitution', 'sexXworkers'] |
| sex workers | ['prostitution', 'sexXwork'] |
| sexually transmitted | ['std'] |
| single | ['married'] |
| social status | ['poor', 'poverty'] |
| std | ['sexuallyXtransmitted'] |
| stigma | ['stigmatized'] |
| stigmatized | ['stigma'] |
| substance | ['drug', 'influence', 'usage'] |
| trauma | ['abuse'] |
| usage | ['drug', 'influence', 'substance'] |
| vulnerability | ['vulnerable'] |
| vulnerable | ['vulnerability'] |
Trigger Words
capacity
coercion
consent
cultural
developing
easy availability
ethics
harm
justice
protect
protection
risk
sensitive
volunteer
welfare
Applicable Type / Vulnerability / Indicator Overlay for this Input