Ministry of Health
PUBLIC HEALTH
Resolution 1480/2011
Approve the Guide for Investigations with Human Beings. Objectives.
Bs. As., 9/13/2011
HAVING SEEN File No. 1-2002-11.180 / 11-8 of the registry of the MINISTRY OF HEALTH; and
CONSIDERING:
That human health research is important for society by improving the quality of life, health protection, and care of the disease of the
individuals that compose it.
That human health research encompasses both epidemiological studies and biomedical research and clinical trials evaluating an intervention
preventive, diagnostic or therapeutic on the disease.
That all research involving human beings must be based on ethical values ​​founded on respect for the dignity of people, well-being and physical integrity and
mental of those who participate in it.
That, consequently, it is essential to systematically and methodically address both the ethical issues and the validity and scientific significance that arise from
all research in human beings, formulating the directives that accept the ethical principles to which the activity of clinical research must conform.
That there are numerous international ethical and operational guides related to human health research, including the Nüremberg Decalogue (1948), the Declaration of
Helsinki (latest version 2008), the International Ethical Guidelines for Biomedical Research in Humans (latest version 2002), the International Ethical Guidelines for
epidemiological studies (latest version 2009), the Operational Guidelines for Ethics Committees that Evaluate Biomedical Research (2000) and the Good Guidelines
Clinical Practice (1996), as well as the International Declarations on Human Genetic Data and on Bioethics and Human Rights (2003 and 2005,
respectively) to which the country has adhered.
That the research ethics committees formed in a multidisciplinary manner in the jurisdictional official field or in the institutions that carry out research to
Health constitutes the central axis of the protection surveillance of the participants in such investigations.
That the MINISTRY OF HEALTH OF THE NATION issued a GUIDE TO GOOD PRACTICES OF CLINICAL INVESTIGATION IN HUMAN BEINGS approved by Resolution
N ° 1490 of November 14, 2007, but that it is necessary to extend the ethical and operational guidelines to all research in human health.
That in compliance with the stewardship role of the MINISTRY OF HEALTH OF THE NATION, the UNDERSECRETARIAT OF SANITARY RELATIONS AND INVESTIGATION has prepared
a GUIDE FOR INVESTIGATIONS WITH HUMAN BEINGS, which contains ethical and operational guidelines to guide researchers, sponsors, members of
research ethics committees and regulatory and health authorities of the different jurisdictions in the proper development and evaluation of research in which
human beings participate.
That this GUIDE FOR INVESTIGATIONS IN HUMAN HEALTH is complemented by the Regimen of Good Clinical Practice for Clinical Pharmacology Studies approved
By Provision of the NATIONAL ADMINISTRATION OF MEDICINES, FOOD AND MEDICAL TECHNOLOGY -ANMAT N ° 6677/10.
That the promotion of health research is a function of the MINISTRY OF HEALTH OF THE NATION and that an important part of the promotion is the
systematization and dissemination of information on such research in order to socialize their results and promote their application in the formulation of policies and
health programs, as well as avoiding duplication of efforts and stimulating the transparency of the investigations that the Ministry itself finances by itself or
through its decentralized organizations or regulates through the NATIONAL ADMINISTRATION OF MEDICINES, FOOD AND MEDICAL TECHNOLOGY - ANMAT.
That the MINISTRY OF HEALTH OF THE NATION has already created a REGISTRY OF CLINICAL TRIALS IN HUMAN BEINGS through Resolution 102/09 that has not yet been
implemented but it is necessary to extend its coverage to all human health research.
That the GENERAL DIRECTORATE OF LEGAL AFFAIRS has taken the intervention of its competence.
That it acts in use of the powers granted by the Law of Ministries No. 26,338 (T.O. by Decree No. 438 of March 12, 1992 and its amendments and
complementary).
Thus,
THE MINISTER OF HEALTH
RESOLVES:
Article 1 - Approve the GUIDE FOR INVESTIGATIONS WITH HUMAN BEINGS, which as ANNEX I forms an integral part of this Resolution and whose objective
is to guide researchers, sponsors, members of research ethics committees and regulatory and health authorities from different jurisdictions in development
and proper evaluation of research involving human beings.
Art. 2 - The NATIONAL REGISTRY OF HEALTH INVESTIGATIONS is created in order to systematize, consolidate and make publicly available information regarding
human health research.
Art. 3 ° - Both the GUIDE FOR INVESTIGATIONS WITH HUMAN BEINGS and the NATIONAL REGISTRY OF INVESTIGATIONS IN HEALTH will apply
mandatory for Clinical Pharmacology Studies for registration purposes in the scope of application of the NATIONAL ADMINISTRATION OF MEDICINES, FOOD
AND MEDICAL TECHNOLOGY (ANMAT) and for all research financed with funds from the MINISTRY OF HEALTH and / or its dependent decentralized organizations.
Art. 4 - The NATIONAL HEALTH INVESTIGATION COMMISSION that works within the SUB-SECRETARY OF SANITARY RELATIONS AND INVESTIGATION is empowered
dependent on the SECRETARY OF DETERMINANTS OF HEALTH AND SANITARY RELATIONS to update or modify the GUIDE FOR INVESTIGATIONS WITH
HUMAN BEINGS when deemed necessary.
Art. 5 - Appoint the NATIONAL COMMISSION FOR INVESTIGATIONAL HEALTH of the UNDERSECRETARY OF SANITARY RELATIONS AND INVESTIGATION dependent on the
SECRETARY OF HEALTH DETERMINANTS AND HEALTH RELATIONS administrative body of the NATIONAL REGISTRY OF HEALTH INVESTIGATIONS
being empowered for its design and implementation.
Art. 6 - The Resolution of the MINISTRY OF HEALTH No. 1490 of November 14, 2007, which approved the GUIDE TO GOOD PRACTICES OF
CLINICAL INVESTIGATION IN HUMAN BEINGS, which is replaced by the GUIDE FOR INVESTIGATIONS WITH HUMAN BEINGS approved by article 1 of the
this Resolution.
Art. 7 - The Resolution of the MINISTRY OF HEALTH No. 102 of February 2, 2009, creating the REGISTRY OF CLINICAL TRIALS IN HUMAN BEINGS, is repealed, the
which is replaced by the NATIONAL REGISTRY OF HEALTH INVESTIGATIONS created by article 2 of this Resolution.
Art. 8 - This resolution will come into effect NINETY (90) days after its publication in the Official Gazette.
Art. 9 - Register, communicate, publish, give yourself to the National Directorate of the Official Registry and file. - Juan L. Manzur.
ANNEX I
GUIDE FOR HUMAN HEALTH INVESTIGATIONS
INDEX
I
NTRODUCTION
SCOPE
SECTION A: ETHICAL ASPECTS
A1. Ethical justification and scientific validity
A2. Ethical and scientific evaluation
A3. Informed consent
A4. Benefits and risks of research
TO 5. Selection of participants
A6. Confidentiality of information
A7. Conflict of interests
A8. Data and results management
A9. Special considerations for clinical trials
A10. Clinical trials of cell and gene therapies
SECTION B: OPERATIONAL ASPECTS
B1. Informed consent
B2. The research ethics committee
B3. Registration and supervision of research ethics committees
B4. Clinical trials
GLOSSARY
INTRODUCTION
This Guide is an expression of concern to ensure that human health research follows ethical guidelines and scientific and methodological techniques.
acceptable. Ethical issues are generally the result of conflicts between competing sets of values, for example the conflict between rights
individual and community development needs. The diversity of values ​​present in a society justifies the development of behavioral guidelines by consensus,
with the aim of guaranteeing the highest level of protection achievable for individuals.
The first international ethical guidelines for research were the Nuremberg Code (1947) and the Declaration of Helsinki (World Medical Association, 1964, last
2008 update), setting the ethical model still in force for conducting studies with human beings. In 1979, the Belmont Report (National Commission for the
Protection of Human Subjects of Biomedical and Behavioral Research) established ethical principles for research involving human subjects. In 1982, the Council
of International Organizations of Medical Sciences (CIOMS) formulated the International Ethical Guidelines for Biomedical Research in
Human Beings (updated in 1993 and 2002) and, in 1991, the International Guidelines for the Ethical Review of Epidemiological Studies (updated in 2009 as Guidelines
International Ethics for Epidemiological Studies).
The Good Clinical Research Practice (BPIC) is a set of ethical and scientific requirements established for the design, conduct, registration and reporting of the
Clinical trials carried out to support the registration of pharmaceutical products for human use, with the purpose of guaranteeing that the rights and protection of
integrity of the participants and that the data and results obtained are reliable and accurate. This regulation was developed in 1978 by the Food Administration
and Medicines (FDA, for its acronym in English) of the United States, and then validated in 1996 between this country, the European Union and Japan at the International Conference
of Harmonization (ICH).
In 2002, the World Health Organization issued a Handbook for Good Clinical Researc Practice (BPIC) and in 2005, the Pan American Health Organization
edited the BPIC guide known as the “Document of the Americas”, which served as the basis for the “Guide to Good Clinical Research Practices in Humans”
of the Ministry of Health of the Nation (Resolution 1490/07), intended to regulate clinical trials in its scope. Subsequently, this Guide was revised with the
The objective of expanding its scope to all human health research and this document is the result of that review.
The following documents were used as reference for the preparation of this Guide:
- Declaration of Helsinki (AMM, 2008)
- International ethical guidelines for biomedical research in human beings (CIOMS, 2002)
- International Ethics Guidelines for Epidemiological Studies (CIOMS, 2009)
- Guidelines for the Clinical Translation of Stem Cells (ISSCR, 2008)
- Operational guidelines for ethics committees that evaluate biomedical research (WHO, 2000)
- Surveying and Evaluating Ethical Review Practices (WHO, 2002)
- Guidelines for Good Clinical Practice (ICH, 1996)
- Handbook for Good Clinical Research Practice (WHO, 2002)
- Good clinical practices: Document of the Americas (PAHO, 2005)
- Ethics Committee. Standard working procedures (PAHO, 2009)
- Universal Declaration on the Human Genome and Human Rights (UNESCO, 1997)
- International Declaration on Human Genetic Data (UNESCO, 2003)
- International declaration on bioethics and human rights (UNESCO, 2005)
This Guide has been submitted for evaluation by the following entities:
- National Academy of Pharmacy and Biochemistry
- National Academy of Medicine
- National Academy of Dentistry
- National Administration of Laboratories and Health Institutes (ANLIS)
- National Administration of Medicines, Food and Medical Technology (ANMAT)
- Argentine Association of Respiratory Medicine
- Association of Medicine Faculties of the Argentine Republic (AFACIMERA)
- Association of Dentistry Faculties of the Argentine Republic (AFORA)
- Joint Commission for Health Research and Central Ethics Committee - Undersecretariat for Health Planning - Ministry of Health of the Province of Buenos Aires
- Central Committee of Research Ethics - Ministry of Health of the Government of the City of Buenos Aires (GCBA)
- Research Protocol Ethics Committee - Hospital Italiano de Buenos Aires
- Council for Ethical Evaluation of Health Research - Ministry of Health of Córdoba
- Research, Science and Technology Directorate - Undersecretariat for Planning and Control - Ministry of Health of Mendoza
- General Directorate for Teaching and Research - Ministry of Health - GCBA
- Teaching and Research Directorate - Ministry of Health of Jujuy
- Argentine Federation of Cardiology
- Argentine Federation of Nursing
- Argentine Federation of Clinical Research Societies
- Argentine Cardiology Foundation
- Foundation for Ethics and Quality of Clinical Research in Latin America
- Pan American Health Organization (PAHO)
- World Health Organization (WHO)
- Ministry of Health Programming - Ministry of Health of Córdoba
- Society of Gynecology and Obstetrics of Buenos Aires
- Argentine Society of Cardiology
- Argentine Diabetes Society
- Argentine Society of Gastroenterology
- Argentine Society of Arterial Hypertension
- Argentine Society of Infectology
- Argentine Society of Internal Medicine
- Argentine Society of Nephrology
- Argentine Nutrition Society
- Argentine Society of Clinical Oncology
- Argentine Society of Pediatrics
- Argentine Society of Rheumatology
Note: All comments and suggestions received were considered and most of them were incorporated into this Guide. In cases of dissent, the position was prioritized
presented in the international reference guides.
SCOPE
For the purposes of this Guide, “human health research” refers to any activity in the health sciences that involves the systematic collection or analysis of
data with the intention of generating new knowledge, in which humans are exposed to observation, intervention or other interaction with researchers, either
directly or through alteration of its environment or through the collection or use of biological material or personal data or other types of records.
In order to avoid the rules and procedures created in the last decades to protect children being imposed on the usual practice of medicine or epidemiology.
research participants, it is important to define that, conventionally, “research” refers to those activities designed to develop or contribute to the
generalizable knowledge. Such knowledge consists of theories, principles or relationships, or the accumulation of information on which they are based, which can be corroborated
by scientific methods of observation and inference. In the case of medical practice, a professional could modify a conventional treatment to produce a better
result for a patient; however, this individual variation does not produce generalizable knowledge; therefore, such activity is related to practice and not to
investigation. In the same way, observational studies carried out by or in compliance with health authorities, such as outbreak surveillance
epidemics or intrahospital infections, records of illnesses or adverse effects of medications or the evaluation of the impact of a health program,
they should be seen as an epidemiological or health practice and not as research.
The need to establish mechanisms of guidance, regulation and control over a given activity arises from the specific risk of causing harm to the targeted individuals.
of the activity. For the same reason, these mechanisms must correspond to the level of risk derived. First, the ethics guidelines for biomedical research
They were designed to guide researchers to plan studies in such a way that consideration for the well-being and rights of the participants is the
primary value, above the interest in science or any other interest. From these ethical guidelines arose, first, the requirement of the informed consent of the
person prior to their participation, as proof of respect for their autonomy and, second, the requirement of ethical evaluation of projects by an ethics committee in
Research (CEI), as an instance of guarantee of the adherence of researchers to such guidelines. The multi-disciplinary and multi-sectoral nature of the RECs highlights
that the interpretation and application of ethical principles can be neither rigid nor dogmatic, but must be the result of a consensus between the different actors
of the investigation with their respective approaches.
Subsequently, the drug regulatory authorities established regulations for the testing of pharmaceutical products under development, prior to registration
commercial. This set of ethical and administrative requirements, known as "Good Clinical Practice," is used as the basis for inspections that agencies
Regulators carry out to verify the protection of the rights and well-being of the participants, and the quality and veracity of the data generated to support the application.
register. To these requirements was added, later, the recommendation of the World Health Organization to implement a registration system for health research.
and accreditation and supervision of the RECs.
Considering the risk probabilities of health research, it is possible to establish, first of all, that research that is not carried out on human beings,
or that they use data already available and in the public domain, or that are made with data or biological samples stored in health services in such a way that it cannot be
determine the identity of the holders, do not represent any risk and do not require any control mechanism.
Second, observational investigations that include surveys or interviews or routine diagnostic procedures or are limited to analysis of samples
biological or data linked to people and the epidemiological or clinical experimental investigations carried out with products or procedures already registered by the
regulatory authority, require obtaining the informed consent of the participants and the initial and periodic evaluation by a CEI. Within this group,
observational studies considered low risk, that is, those that present the same risk as routine medical practice, may receive an initial evaluation
expeditious and do not require periodic review.
Third, clinical pharmacology studies for the purpose of registering or regulating a product require, in addition to the mechanisms described above, the
authorization from the National Administration of Medicines, Food and Medical Technology (ANMAT) at the national level. For their part, each health jurisdiction has
competence to establish a local regulatory and oversight body for this type of investigation.
Finally, it must be recognized that the content of this Guide will not solve all the ethical problems that may arise from health research. Some situations
will require a thorough analysis and informed opinion from researchers, members of ethics committees, health professionals, authorities and representatives
of the community.
Sanctions. Research Ethics Committees have the authority not to approve, suspend or definitively cancel an investigation that does not meet the standards
ethics, and must inform the institution or health authorities about any serious or persistent ethical breach in the development of previous investigations
approved. Failure to submit a research protocol to the evaluation of a REC is considered a serious violation of ethical standards.
Health authorities, the institution or professional associations must sanction researchers who do not adhere to ethical requirements, through fines or the
suspension of research grants.
ANMAT, in case of breach of ethical precepts and in its scope, can:
(a) object to or reject a proposed clinical pharmacology study or a proposed investigator or research center;
(b) suspend or cancel a clinical pharmacology study during its execution, and apply the corresponding administrative or financial sanctions;
(c) reject data submitted in support of a marketing registration application.
The sanctions of the health authorities of the jurisdictions and of ANMAT can apply both to the researcher and to the institution hosting the investigation and, if
corresponds also to the sponsor in the case of clinical pharmacology studies for registration purposes.
Editors of scientific journals should not publish the results of studies carried out without respect for ethical norms and subsequently disallow those articles in the
falsified data has been verified or based on unethical research.
SECTION A: ETHICAL ASPECTS
This section presents ethical guidelines for human health research aimed at guiding researchers during the planning and execution of studies.
and to members of research ethics committees for project evaluation.
A1. ETHICAL JUSTIFICATION AND SCIENTIFIC VALIDITY
P1. For human health research to be ethically justified, it must provide new and scientifically valid knowledge that
it is not feasible to obtain without their participation.
P2. All human health research must be based on current scientific knowledge and be based on a comprehensive review of the specialized literature.
Research into a new human health intervention should be based on appropriate and previous laboratory, preclinical, and clinical experimentation and justified
for its preventive, diagnostic or therapeutic value.
P3. Human health research should be conducted by researchers who have appropriate training and skills for the task.
Basic ethical principles: Health research on human beings must comply with the three basic ethical principles: respect for people, bene fi ciency and
Justice.
Respect for people. This principle implies that people who are autonomous or capable of deliberating about their decisions are respected in their capacity to
self-determination, free of undue incentive and influence and coercion, and that persons absolutely or relatively incapable of giving consent receive
additional special protections.
Autonomy is the capacity for self-determination of a person to make a decision voluntarily, based solely on their own values, interests and
preferences, and provided you have the necessary information to evaluate the options. An autonomous person, by definition, can give informed consent
with no other protection than to receive the information you need to deliberate freely. On the other hand, those individuals who have autonomy
diminished or non-existent they are in a vulnerable situation to defend their own interests and therefore require special protections. An autonomy is
considers it diminished in cases of cultural, educational, social or economic disadvantage, for example, ethnic minorities or illiterate, subordinate, refugee people,
destitute or with unmet basic needs. In clinical trials, an additional protection for them is the participation of an independent witness during the
consent process to guarantee respect for your rights and interests. The absence of autonomy occurs when an individual is legally or mentally
unable to give voluntary consent, such as in minors and those with a temporary or permanent mental disorder. In such
cases, consent must be obtained from a legally recognized representative of the potential participant, always respecting the latter's will, to the extent
that its capacity allows it.
The bene fi cence. This principle refers to the ethical requirement to achieve the maximum possible benefits and to minimize the probability of harm. This implies that
The risks of an investigation must be reasonable compared to the expected benefits, that the investigation is well designed and that the investigators are competent to
carry it out, guaranteeing the well-being of those who participate in it. Another principle follows from this principle: that of “non-maleficence”, which protects against preventable damage
participants in a study.
Justice. This principle refers to the ethical obligation to treat each person equally, unless there are relevant differences that justify different treatment.
Distributive justice requires that all the benefits and burdens of research be distributed equitably among all groups and classes in society,
especially if they are dependent or vulnerable people. Studies should be planned so that the knowledge sought benefits the group
represented by the participants. For example, the risks to vulnerable participants are more justified when they arise from interventions or procedures than
they offer a speci fi c benefit for your health. In sum, those who bear the burden of participation should receive an adequate benefit and the group that
The beneficiary must assume an equitable proportion of the risks of the study.
Respect for the communities. When a researcher plans or conducts research in communities with a culture different from his own, he must respect cultural values
and ethics of the host community. Research that seeks to stimulate a change in customs or behaviors of a community in order to achieve more
healthy or a result that is expected to be beneficial to health is considered ethical and not harmful.
In general, the investigators or sponsors of a study should not be held responsible for the unfair conditions in the place where the study is conducted,
But they must guarantee that they will not carry out practices that could increase injustice or contribute to new inequalities. Community investigations
Vulnerable people must respond to their health needs and priorities, as a way to avoid their exploitation in favor of the most favored communities.
Scientific validity. An investigation will be considered scientifically valid when the proposed methods are adequate to the objectives of the investigation and to the
field of study. Without scientific validity, research cannot generate valid knowledge, produce any benefit, or justify the exposure of the participants to the
risks of the same. Invalid studies also cause a waste of resources.
Qualified researchers. Human health research should be conducted or supervised only by researchers who demonstrate instruction, training, and experience
enough. Instruction or education refers to the possession of a tertiary professional degree, university or specialization, according to the object of research. Training
It means participation in focused training programs of relatively short duration. Experience refers to the specific work history or the
stable and prolonged performance of tasks related to professional practice and research.
In clinical trials, in particular, a qualified and properly registered physician or, if appropriate, a dentist should be responsible for the medical care of the
participants and any medical decisions made by them. The vital curriculum of researchers, including proof of degrees, specializations, qualification
Professional, training, and experience can provide information on your suitability for the sponsor, the CEI, and regulatory authorities, if applicable. The rest of
The team must certify appropriate training in the study protocol, the conduct of clinical trials and the ethical aspects of health research on
human beings.
A2. ETHICAL AND SCIENTIFIC EVALUATION
P4. Background, objectives, design, sample size and selection, participant selection mechanisms, variable measurement methods, analysis
Statistical, detail of the proposed intervention, if applicable, and the ethical, financial and administrative aspects of human health research should be detailed in detail.
Clearly and comprehensively in a study protocol.
P5. The study protocol and the information intended for potential participants must be submitted for evaluation and approval by a Research Ethics Committee (IEC)
before starting the study. The CEI must be independent of sponsors and researchers. The researcher must periodically inform the CEI about the progress of the
study and, immediately, the relevant findings or events that imply unforeseen risks for the research participants. The changes that
proposed in the study and that may affect the safety of the participants or their decision to continue participating must be evaluated and approved by the CEI before their
implementation.
Scope. The requirement that human health research projects undergo an ethical review applies independently of the project's origin:
academic-scientific, government, health care, commercial or others. Researchers must recognize the need for this evaluation.
Exceptions. The following cases do not require review by a CEI:
(a) when human beings do not participate in the investigation or when public information is used, provided that individuals are not identified in any way. By
example, the studies of Drug-economy;
(b) when the intervention is limited to the study of health systems, official public health programs or public health surveillance, provided that there is no
possibility of identifying individuals. Public health surveillance includes records that are official or made in accordance with the disease health authority
and of adverse effects of medications already registered by the competent regulatory authority.
It can sometimes be difficult to distinguish whether a specific project is for research or for the evaluation of a health program or a health service. The characteristic
What defines the research is that its purpose is to produce new and generalizable knowledge; on the other hand, an evaluation only seeks to know and describe a
characteristic or diagnosis relevant only to a person, group of them or a specific program.
The evaluation of an official health program or health service, carried out by the program operators themselves or by the staff of the institution should be considered
an action necessary to guarantee the efficacy and safety of an installation or procedure, always under the perspective of benefiting people. The same justification
applies to surveillance of epidemiological events or side effects of drugs or other products for human use. But if the examination were carried out for
research or if the scope is not clear, the project must be submitted to the CEI for evaluation and definition.
Institutional or central committees. By virtue of the responsibility of monitoring the protection of the participants, it is advisable that the RECs operate in the institutions where
Investigations are carried out or at the level of the jurisdictional authority. This does not prevent other entities such as medical colleges or associations
professionals can form a CEI in their respective fields.
In the event that an institution does not have a CEI or that it does not meet the requirements established in this Guide, its research projects should be evaluated
by a REC that belongs to another institution or to the central level of the jurisdiction.
Scientific and ethical evaluation. The main purposes of the evaluation are: to protect people against risks of harm or prejudice and to facilitate studies
bene fi cial to society. The scientific and ethical aspects are closely related: it is unethical to carry out a study that does not have scientific solidity when exposing the
participants to risks or discomforts without obtaining any benefit. RECs may require scientific advice from an expert or suitable advice, but must take their
own decision on the scientific validity of the study, based on these consultations. After establishing the scientific validity, it should be evaluated whether the expected benefits justify
the known risks to participants, whether the risks have been minimized and the benefits have been maximized, whether the selection procedures will be fair and whether the
Procedure for obtaining consent is appropriate.
Scientific evaluation also involves considering the social value of research, that is, ensuring that its results will lead to an improvement in health or well-being
of society, even when knowledge is not immediately applicable. It is unethical to subject people to the risk of an investigation if it will be of no use
nor is it fair to waste funds or resources that could be devoted to other social benefits.
Additionally, institutional RECs must consider the impact that research activities will have on the normal operation of the institution.
Assessment of risks, benefits and selection mechanisms. The RECs must pay special attention to research projects involving children, women
pregnant or breastfeeding, people with mental illness or some type of disability, members of communities unfamiliar with medical concepts
and people with restricted freedom to make decisions, such as: people deprived of their liberty, students of health sciences in research carried out
by their teachers and employees of the entities that carry out the research. They must also pay attention to selection mechanisms to avoid inequalities
based on age, socioeconomic status, degree of disability or other variables, unless they are inclusion criteria. The possible benefits or damages of the
Research should be equitably distributed among groups that differ from the point of view of age, sex, race, culture, or other variables, as well as the
inside of them.
Composition. The RECs must be composed in such a way that an adequate evaluation of the research projects is guaranteed. Among its members there must be
health professionals and experts in methodology, research ethics and participant rights, as well as legacies in science but trained to
consider a range of community, cultural and moral values. Members must be renewed periodically in order to combine the advantages of the experience with the
of the new perspectives. In order to remain independent of researchers, IRBs must prevent any member who has a direct interest in a project
participate in the evaluation and decision about it.
Functioning. An IRB should establish its standard operating procedures for, for example, the frequency of meetings, the quorum of members and the
mechanisms for analysis and decision-making, and must communicate these rules to researchers. When evaluating a project, the different sectors of the committee,
Scientists and non-scientists must be represented to ensure a comprehensive evaluation.
Member responsibilities. The members of an IRB must take special care to avoid all unethical conduct, including conflicts of interest that
may arise in evaluations. CEI members must respect the confidentiality of documents received for evaluation and committee deliberations.
A3. INFORMED CONSENT
P6. The decision of an individual or their representative to participate in an investigation must be voluntary and free from undue influence, undue incentive or coercion. To drink
a free decision, each potential participant or their legal representative must receive the information clearly and precisely about the purpose, procedures, benefits and
foreseeable risks and sources of funding for the research, and your rights to access and rectify your data and to refuse to participate in or abandon the study in
at any time, without the need to justify themselves and without being exposed to any retaliation. After verifying that the individual or his representative has understood the entire
information, the researcher must request consent.
Q7. In all experimental research, each potential participant must also be informed of the expected risks and benefits of both the experimental intervention.
as of the available alternatives; of payment for participation and remuneration for expenses, if applicable; and of the care and compensation coverage provided in the event
of damage directly related to the investigation.
Q8. During the course of the investigation, participants should be informed of any finding or event that could affect their safety or their decision to continue.
participating. At the end of the research, the results of the research must be made available to the participants.
De fi nition. Informed consent is voluntary and free when granted by an autonomous and competent person who can understand the purpose and nature of the
research, the risks you will face, and the benefits you may receive, and who knows your rights as a research participant. An autonomous person and
competent is the one capable of making a decision voluntarily, solely based on their own values, interests and preferences, and provided they have
the information necessary to evaluate your options. As a general principle, consent should be obtained for all research involving human beings or
are made with biological samples or personal data.
The informed consent process must include the following elements: competence to make decisions of the potential participant or their legal representative,
clear and complete information before and during the investigation, understanding of the information, free and voluntary decision, and documentation of the entire process. Comprehension
information depends on the maturity, intelligence and education of individuals, but also on the ability and willingness of the researcher to transmit it.
Exceptions to obtaining consent. In the following situations, applicable only to observational investigations, an IRB could exempt obtaining the
consent:
(a) when only non-binding data or samples, or publicly available information are used in the investigation. That is, it is not possible to establish the identity of the
people and therefore researchers cannot contact them to request their consent.
(b) when linkable data is used but obtaining consent is impractical or very difficult, and the proposed research represents only minimal risks.
For example, a study using only medical records. In such cases, the investigator must guarantee that it will protect the confidentiality of the data, for example,
deleting all personally identifiable information from study records after compiling health data. However, the use of medical data or
biological samples for a purpose for which it has not been consented is an ethical problem, even if it does not imply any risk for the holder; therefore, the institutions of
Those who carry out studies on medical records or sample banks must obtain advance consent from their patients for such practices, informing them
about the measures that will be taken to protect your confidentiality.
(c) when the study uses health records established or of fi cially recognized by health authorities, for example, disease or effect records
therapeutic or adverse or genetic data, provided that the recorded data is not linked to people. These records are an important source of
information for public health activities such as disease prevention and resource allocation.
Exceptions to specific requirements of the consent process. The CEI could exempt a requirement of the process of obtaining consent in the following
situations:
(a) when the advance of consent could invalidate the results of the investigation, for example, when studying the behavior of a human group. Being
When warned, subjects may modify their habitual behaviors or this may cause them unnecessary concern. Investigators must justify to the CEI the
exception and agree to obtain the consent of the participants before disseminating the results of the study;
(b) in experimental epidemiological investigations in which the intervention is directed at a group of people or a community, such as the students of a
school or all residents of a de fi ned area, for example, when studying an immunization or education strategy or fluoridation of water to prevent tooth decay, the
Consent can be obtained from a representative of the community or the corresponding authority, who must assess whether the expected benefits of the intervention in
Study for group or community outweigh your risks. Additionally, individuals should be informed about the research and have the opportunity, within
possible, to refuse your participation;
(c) in clinical trials on situations requiring immediate medical intervention, the CEI may approve the use of an abbreviated version containing information
Essential about the study for the potential participant or their representative. In such case, the information must be provided in the presence of an independent witness, who
You must sign the consent form together with the researcher and the participant or their representative.
An investigator who proposes an exception to obtaining consent or to any of the requirements of the process must justify to the IRB the basis for the
application and explain how the rights of the participants will be protected. The investigator should not proceed with the investigation without the specific approval of the
CEI for such exception.
Inability to grant consent. In the case of people who cannot grant voluntary consent for physical, mental or legal reasons, this
It must be obtained from a representative authorized by applicable laws, for example, the father or mother in the case of minors. The representative retains the
power to withdraw the research from the participant if necessary for their safety or if that were the decision that best represents their values ​​and preferences. Respect
for people who cannot give consent themselves requires that they also be given the opportunity to decide whether or not to participate in the research,
after being informed according to their ability to understand.
People who have temporary or permanent mental disorders, such as coma or Alzheimer's disease, and who do not have a representative
appointed by a judge, they pose a particular situation. From an ethical point of view, these people should not be deprived of the benefit of obtaining new knowledge.
or to develop new treatments for the condition they suffer from. In accordance with Article 7 of the National Mental Health Law No. 26,657 and Article 4 of the National Law
of Patient Rights No. 26,529, a relative up to the fourth degree of consanguinity, the patient's spouse or partner are the ones who could best answer for their
interests and for the decision that he or she would make if they were in full use of their faculties, therefore, they must represent the potential participant for the
obtaining reliable informed consent. To the extent possible, or when the participant regains the use of his faculties, he should be informed about the
research and request your consent before continuing with it.
The witness of the consent process. The figure of the investigator's independent witness is an additional guarantee to the CEI's assessment that the investigator will respect
the values ​​and interests during obtaining the consent of a potential participant vulnerable to possible undue incentive or coercion. This requirement applies
exclusively to clinical pharmacology studies for registration or regulatory purposes subject to the supervision of ANMAT, in the following cases:
(a) when the participation of vulnerable populations is foreseen for cultural, educational, social or economic reasons; and
(b) in the case of urgent situations that require the use of an abbreviated consent.
The witness must sign the consent form as proof of their participation.
Deliberate objection and assent of minors. In general, the voluntary cooperation or consent of a minor should be sought to participate in a
research, after providing you with the information appropriate to your degree of maturity. Children who are immature to nod with understanding may be able to
express a 'deliberate objection', that is, an expression of disapproval or denial of the proposed procedure, which should be respected, unless the child needs
a treatment not available outside the context of the research, the study intervention implies a probability of therapeutic benefit and there is no therapy
accepted alternative. The CEI must determine the age from which the minor's consent will be required, depending on the characteristics of each study.
Community consent. When planning research on communities or groups of people linked by ethnic, geographic, social or
common interests, the consent of a community representative should be sought, for example, by including him in the CEI evaluation. The representative must be chosen
according to the nature and traditions of the community, and CEI researchers and members should ensure that these individuals unequivocally represent the interests
of that. In communities where collective decisions are often made, researchers should consider seeking the approval of
community leaders, prior to individual decisions.
Undue incentive. Sometimes it can be difficult to clearly distinguish between legitimate motivation and the offer of excessive or inappropriate encouragement. The benefits
potential and actual research, for example, gaining knowledge, are appropriate incentives. Similarly, the promise of compensation and care
Medical damages, injuries or loss of income should not be considered as an induction to participate. On the other hand, those who lack basic goods or
appropriate health care are especially exposed to an undue incentive when they are offered goods, services or cash payments for their participation and
they therefore require a guarantee of free and voluntary consent through the presence of an independent witness in the process of obtaining it.
In research without potential benefits to the health of the participants, for example, in the case of healthy volunteers, they may receive a payment, the type or
amount must be approved by the CEI. On the other hand, when the research presents a potential benefit for the health of the participants, only a remuneration is acceptable
for expenses or lost profits.
Coercion. The intentional use of force or threats to modify the will of others, for example, a threat of physical harm or punishment such as
Loss of job or medical care for refusing to participate in an investigation is unacceptable.
Undue in fl uence. Potential participants may not feel free to refuse requests from those who have power over them, therefore they should not propose
investigations with individuals whose decision may be affected by a related authority, if they could be made with independent participants. Otherwise, the
Researchers must justify that choice to the IRB and outline how they plan to neutralize that possible influence.
Use of medical data and biological samples. Patients have the right to know if their data or samples will be used for an investigation, so researchers
they must obtain your consent in advance. A REC may approve the use for research of data or samples from healthcare, without the
prior consent of patients, only when the project is shown to be scientifically valid, a minimum risk is foreseen, obtaining consent will be
Difficult or impractical and the protection of privacy and confidentiality of individuals will be guaranteed by irreversible decoupling of data or samples
biological. A probable refusal to participate by individuals should not be considered a criterion of impracticability to approve the omission of consent.
If biological samples are obtained as part of the investigation, the informed consent must include the following information:
(a) the possible uses, direct or secondary, of biological samples obtained in the study;
(b) the fate of the biological samples at the end of the study, for example, their destruction or storage for future use. In the latter case, you must specify which
would be the possible future uses and where, how and for how long the samples will be stored, and that the participant has the right to decide on those future uses;
(c) a statement that the samples or derived data will not be marketed; and
(d) in case of considering a possible development of a commercial product from the biological samples, if it is planned to offer the participant monetary or other benefits
kind for it.
The transfer of any sample or biological material intended for scientific research between participant and researcher or between researchers or others must be free of charge,
notwithstanding that the participant may receive a financial remuneration for expenses or inconveniences suffered or that the recipient must cover the costs of sending and preserving
samples or materials.
Secondary use of biological samples. Researchers may request to use biological samples that have been obtained as part of another investigation, or
samples that at the time of collection had not been de fi ned. Secondary uses are subject to the conditions defined in the original consent, without
However, an IRB may approve a secondary use as long as the original consent specified the following:
(a) whether there will be or could be a secondary use for those samples and, if any, what type of studies could be conducted with those materials;
(b) the conditions under which researchers will have to contact participants to request additional authorization for secondary or as yet undefined use;
(c) the plan, if any, to destroy the unused samples or irreversibly dissociate them; and
(d) the right of the participants to request the destruction or dissociation of the samples.
Consent in genetic or proteomic research. Before samples are obtained for genetic or proteomic research, potential participants should be
informed about the purpose of the research, its risks and consequences, that they have the right to decide whether or not to know their genetic data and that, if they wish,
They will have access to them, unless they have been irreversibly disassociated from their identification or the information obtained has no relevant consequences for their health.
As a general rule, human genetic or proteomic data obtained for scientific research should not be kept in association with a person identi fi ed by a
longer than necessary to carry out the investigation.
Human genetic or proteomic data collected for scientific research purposes shall not be used for purposes incompatible with the original consent, a
unless a new consent is obtained from the participant or his representative. Investigators must further ensure that the use of data will not expose
individuals, families, groups or communities at risk of discrimination or stigmatization.
When genetic tests are carried out that may have relevant consequences for a person's health, counseling should be made available
suitable genetic. This advice should be non-coercive, adapt to the culture in question and serve the best interests of the person involved.
Consent by mail or by electronic means. When a survey is projected to a large number of people, researchers usually propose to carry it out by
postal mail, electronic mail or by Internet, which includes obtaining the consent of the potential respondents by the same means. The problem in this case is the
Difficulty in ensuring that participants understand the relevant aspects of their participation in the study. For this reason, it is important that the language used in the text
of consent is clear and precise, and that researchers make a telephone number or an email available to answer the questions of the
recipients of the survey. Considering, in addition, the risk of violation of correspondence by third parties, researchers should avoid the inclusion of information
potentially sensitive about individuals throughout the process.
Partial retention of information. In some studies of observation of human behavior, it is usually proposed to selectively communicate the study information to
participants to avoid influencing the behavior under investigation and obtaining responses designed to please the investigator, which seems to contradict the requirements of the
informed consent. The CEI could approve the use of this technique as long as selective retention does not induce people to do what otherwise would not
they would consent to do and the researcher agrees to communicate this information to the participants and obtain their consent before using the data that has been
generated.
Responsibilities for information for participants. Primary responsibility for information, both oral and written, for participants in the
investigation rests with the investigator. However, in cases involving health interventions with products, the veracity of the information on the effectiveness and
their safety will be the responsibility of the producer and / or sponsor of the research. In all cases, the CEI must verify that the written information is
presents properly.
A4. BENEFIT AND RISKS OF THE INVESTIGATION
Q9. All human health research projects must include a meticulous assessment of the anticipated risks and burdens compared to the bene fi ts
expected. This does not preclude the participation of healthy volunteers in medical research.
Q10. Human health research can only be carried out if the benefits to individuals or to society clearly outweigh the anticipated risks, and these have
been minimized as much as possible. The investigation must be stopped if during its course it is observed that the damages are greater than the benefits or a
Interim analysis will show that the research question has already been answered.
Q11. In all observational or experimental research, the products and procedures indicated in the protocol must be free for all participants.
Justification of risks. Participation in an investigation in which a diagnostic, therapeutic or preventive benefit is anticipated for the individual must be justified by the
expectation that the intervention will be, according to the state of knowledge, as advantageous as any other available alternative. Instead, the risks of investigations
no possibility of diagnostic, therapeutic or preventive benefit for the participant can be justified by the relevance of the new knowledge that is expected to be obtained.
Identification of risks. The term "risk" refers to the possibility of harm occurring. For their part, the expressions "low risk" and "high risk" describe the magnitude
of the probability of damage occurring in terms of frequency and severity. A risk is considered low when it is similar or equivalent to the risks of the practice
routine medical. When planning an investigation, researchers should try to identify all possible risks to the participants. The risks can be:
(a) physical: risks of adverse effects from study interventions or procedures;
(b) mental or emotional: when the sensitivity, values ​​or rights of the participants can be affected, for example, if personal information is disclosed to third parties; and
(c) economic: when the participation can cause pecuniary losses.
Minimization of risks: After identifying the risks, researchers should develop a plan to minimize their effects. The usual strategies for
minimize are:
(a) surveillance of the safety of the participants with adequate and frequent controls to quickly prevent, detect and treat the occurrence of adverse events;
(b) periodically report adverse events to the CEI and, if applicable, to the sponsor;
(c) immediately report serious and unexpected adverse events to the CEI and, if applicable, the sponsor and the regulatory authority;
(d) perform interim analyzes to detect changes in the frequency or magnitude of expected adverse events in relation to the expected benefits and / or resolution
premature research question. In clinical trials that measure the frequency of mortality or serious health events, such as cardiovascular events, or that
evaluating high-risk interventions or involving large numbers of individuals, it is advisable to have an independent data monitoring council to
evaluate the interim data; and
(e) Provisionally or definitively suspend the study intervention in a participant, or their participation in the study or, if necessary, all research to protect
the health and well-being of the participants.
Risks for groups or communities. A study can cause harm to a group or community, for example, when health personnel deviate from their routine obligations
In order to attend to the research activities, health care priorities are modified or a situation of inequity is created among users.
Investigations of preventive interventions, for example, of a vaccine, deserve special consideration, because these interventions imply that all
Participants are exposed to their potential risks while only those who would have contracted the disease would benefit if the research had not been conducted.
This is, in fact, an inherent problem in all preventive programs, and requires special attention from researchers and the ERC to assess the risks and
inconvenience for those who may not receive any direct benefit for their participation.
Another particular case is the investigations that include screening for diseases for which there is no effective treatment, since the participants will obtain a
diagnosis but with no possibility of solution. In order to justify their implementation, these projects must be of sufficient relevance to the health of third parties, for
example, in the case of a communicable infectious or genetic disease. The participant of these investigations has the right to decide whether or not to be informed of the
results of your studies, and if so, you should have appropriate professional advice, for example genetic counseling.
Maximization of benefits. The term “benefit”, in the context of human health research, refers to a positive effect related to health or the
well-being of an individual or a community. The benefits of an investigation can be maximized with the following strategies:
(a) training of health personnel: an investigation is an opportunity to train the health team in techniques and procedures that can optimize care
routine;
(b) improvement in health services: the incorporation into health services of the inputs or instruments that have been obtained or acquired for the study is a bene fi t
additional for the community where the research is carried out; and
(c) dissemination of research results: the dissemination of study results in the studied community or in the scientific field is a benefit in itself, since
that this tends to improve the health of the population.
Research funding. In any type of investigation, all the treatments and procedures defined in the protocol must be provided to all
participants at no cost to them. In the case of studies that do not have financial sponsorship or that this were only of a philanthropic or scientific nature, that is, without
industrial or commercial, it is acceptable that the treatments or procedures are covered by the participant's habitual health funder, as long as these
treatments and procedures are framed in current medical practice for the disease under study and that the cost thereof is not included in the subsidy
or funding received for research.
TO 5. SELECTION OF PARTICIPANTS
P12. Participants should be selected based on the objectives and design of the research, and the greater probability of minimizing risks and maximizing
the benefits at the individual level. All individuals and / or groups in a society should have equitable access to the possibility of benefiting from research.
scientifically valid, regardless of their cultural, educational, social or economic situation, unless there is an adequate scientific or security reason
justified.
Fair selection. Although the scientific objective of the research is the main criterion for the selection of the participants, the principles that hold that equals must
be treated in the same way and that the benefits and burdens generated by social cooperation, such as research, must be equitably distributed among
the groups involved should have similar consideration in the ethical evaluation. This does not mean that the selected individuals or groups should directly benefit
of any research project nor that marginalized, stigmatized or socioeconomically disadvantaged people should never be included.
Vulnerable population. Group of individuals with mental or legal incapacity to understand the characteristics of an investigation or to express their will or that for a
Unfavorable social, cultural, educational or economic condition is liable to be in fl uenced by the expectation of receiving a benefit for participating in research.
(undue incentive) or to be the victim of a threat by investigators or others in a position of power if they refuse to participate (coercion).
An investigation of a vulnerable population could imply an unequal distribution of its burdens and benefits, so researchers must guarantee the CEI
than:
(a) the research could not be equally well conducted with less vulnerable people;
(b) the research attempts to obtain knowledge that will lead to better care for diseases or other health problems characteristic or characteristic of the group
vulnerable;
(c) Study participants and other members of the vulnerable group will have reasonable access to the products that become available as a result of the
investigation;
(d) the risks associated with interventions or procedures without direct benefit to the health of the participants do not outweigh those associated with medical examinations or
psychological routines of such people, unless the CEI authorizes a slight increase in this level of risk;
(e) in the case of clinical trials, consent will be obtained in the presence of an independent witness to guarantee the voluntariness and freedom of the decision to
take part.
Researchers must identify those individuals or groups in situations of vulnerability in order to implement special protection for them. However, some
Vulnerabilities can be relatively easy to identify, such as the physical, legal or mental inability to grant voluntary consent, while others
they are difficult to define, such as an unfavorable economic, social, cultural or educational condition.
Individuals unable to grant consent. They are minors and people with transient, fl uctuating or permanent mental disorders. The
Research with these groups is only justified when:
(a) the knowledge expected from the investigation is sufficiently relevant in relation to the foreseeable risks;
(b) the risks of an observational study are only slightly higher than those associated with routine medical and psychological examinations of such persons in the condition
being investigated;
(c) the risks of an experimental investigation are similar to those of the interventions that individuals usually receive for the condition under investigation; and
(d) the CEI has specialists or consults experts in those particular groups.
Cultural, educational, social or economic vulnerability: the participation in clinical trials of vulnerable populations for cultural, educational, social or
economic, as in the case of ethnic minorities or illiterate, subordinate, refugee, indigent or with unsatisfied basic needs, requires
additional protections. As a guarantee that the particular values ​​and interests of the potential vulnerable participant were respected, consent must be obtained in
presence of an independent witness of the investigator and his team. As a guideline, observing one or more of the following indicators can be used to
establish the need for this additional protection:
(a) unemployment or informal or unstable work in the main breadwinner;
(b) without housing or precarious housing (hotel or pension, tenancy, house taken or construction not intended for housing) or located in unfavorable areas (village or settlement
informal);
(c) without social security coverage (social work or prepaid);
(d) illiteracy or incomplete primary study;
(e) people originating from or belonging to an ethnic group whose primary language is not Spanish;
(f) refugee or displaced status.
When proposing research in populations or communities with limited resources, researchers must ensure that the research responds to the
health needs and priorities of the population or community and that any benefit generated from the research, be it a knowledge or a product,
it will be reasonably available for the benefit of that population or community. If the knowledge obtained from the research was used primarily for the benefit of others
groups that can bear the cost of the product once marketed, the research can be characterized as exploitative and unethical.
Participation of women of reproductive age or pregnant. The possibility of becoming pregnant during the study should not, by itself, be used as a reason to exclude
o limit the participation of women of reproductive age. The requirements to minimize risks are: inform potential participants in detail about the risks
for the pregnancy and fetus and guarantee them access to pregnancy tests and effective contraceptive methods before and throughout the investigation.
In the case of pregnant women, in addition to the requirement to provide detailed information on the risks for them and for the fetus, it is recommended that the
consent of the partner of the pregnant woman, if applicable. An investigation in this population can only be carried out if it is relevant to health problems
related to pregnancy and the product of conception, and whether it is adequately supported by previous animal experiments, particularly to establish the
risks of teratogenesis and mutagenesis.
A6. CONFIDENTIALITY OF INFORMATION
P13. Investigators must take all necessary precautions to protect the privacy and confidentiality of study participants' information.
Confidentiality. Human health research frequently involves manipulating sensitive data from individuals or groups; therefore there is a risk that the
disclosure of such data to third parties may cause harm or anguish to participants. Investigators should take all possible precautions to protect the
privacy and confidentiality of the information of the participants, in accordance with the National Law 25.326 of Habeas Data, for example, omitting the data that could
identifying individuals or limiting their access only to authorized persons.
Identifiable personal data should not be used when a study can be done without it. When it is necessary to record the personal identification data, the
Investigators must justify this need to the REC, and explain how their confidentiality will be protected and what the limitations of such protection will be, for example, that
Research records will be reviewed by sponsor or regulatory authority personnel. A usual protection mechanism is the deletion of data from
Identi fi cation when results are consolidated for statistical analysis. Investigators must obtain the prior consent of potential participants to
use your data and express your commitment to preserve their confidentiality.
The CEI must approve both the information provided to potential participants and the mechanisms established to protect their privacy and confidentiality.
Unrelated information. It is the information that cannot be related to the individual to whom it refers and, since the researcher does not know the person, the
Confidentiality is not at risk and there is no need to obtain consent. The data or samples may have been originally linked and then
destroyed the link with the information that identifies the individual ("anonymization" or "irreversible dissociation"), thus making it impossible to connect a data or sample with the
person to whom it refers. In order to proceed with the anonymization of data or samples, the owner must have previously consented.
Linked information. It is the information that can be related or connected with the person to whom it refers. The linked information, for its part, can be:
(a) anonymous, when it cannot be linked to the person to whom it refers except through a code or other means known only to the owner of the information;
(b) non-nominal, when the information can be linked to the person through a code, which does not include personal identification and is known by the person and the
investigator; or
(c) nominal, when the information is linked to the person by personal identification, usually the name.
The first two cases (anonymous and non-nominal) are also known as “coded or reversibly dissociated” data and are those data not associated with a person
identified or identifiable because the information that identifies that person has been replaced or unlinked through a code that allows the reverse operation.
Confidentiality in genetic research. Whenever genetic testing of known or predictable clinical value is planned to be performed on specimens linked to an individual
identifiable, your consent must be obtained in advance. Conversely, in order to perform a genetic test of known clinical value or to provide information on a
known hereditary condition without obtaining prior consent, the investigator must ensure that the biological samples have been irreversibly dissociated from their holders
and that no information about specific individuals could be derived from the investigation.
The genetic or proteomic data of a person must not be disclosed or made available to third parties, in particular employers, insurance companies,
educational establishments or relatives of the person in question. Investigators must strive to protect the privacy of individuals and the confidentiality of
human genetic data associated with an identifiable person, family, or group. As a general rule, human genetic or proteomic data obtained with
Scientific research purposes should not be kept in association with an identifiable person any longer than is necessary to carry out the research. Although
were disassociated from the identity of a person, all necessary precautions must be taken to guarantee the security of this data.
Confidentiality when using the Internet for research. There are several ways in which researchers could use the Internet for their research:
(a) to obtain data: researchers could enroll people to answer surveys or questionnaires placed on a website or use publicly accessible sites to
observe, as a data source, what your users say or do without necessarily interacting with them.
(b) to transmit data: researchers may send electronic files with research data to other researchers for collaborative purposes, or
Sponsors install a data entry base on a website in multi-center studies.
(c) to communicate results: some researchers disseminate the results of their studies through a website.
In any case, the privacy, con fi dentiality and security of the participants must be guaranteed by the researchers during data collection, transmission to
other centers and the construction of a shared database, particularly when transmitting personally identifiable data. The researchers or sponsors
they must use passwords and the best available technology, for example encryption, to ensure that only authorized persons will be able to read the data. These requirements
They also apply when data is transmitted from implantable or portable electronic devices, for example, pacemakers or vital sign monitoring systems.
A7. CONFLICT OF INTERESTS
Q14. The primary duty of every person who plans, sponsors, conducts, or communicates human health research is to respect dignity, rights, values, and
interests, well-being, and the physical and mental integrity of the individuals who participate in it, over and above any financial, scientific, social, or other interest.
Definition: A conflict or competence of interests in the investigation is considered when the professional judgment related to an investigator's primary interest or duty,
such as the well-being of the participants or the validity of the research, may be in fl uenced by a secondary interest, for example, raising funds or
professional recognition. The interest to protect participants and obtain valid knowledge must always prevail over any other interest.
In many cases it can be really difficult to determine when there is a real conflict of interest because the competing interest is not always financial and can
be sneaky. The RECs must pay attention to the risk of conflict of interest and not approve proposals in which there is evidence that the professional judgment of the
investigators may be affected by an incompatibility of interests.
A particular case is the possible conflicts of financial, academic or political interests within the institution to which the researcher belongs. For this reason, a CEI
Institutional must incorporate impartial and external members to the institution to help the handling of a situation of these characteristics.
Declaration of conflicts of interest. Honesty, transparency and impartiality are essential to formulate, conduct, interpret and communicate the results of the
studies. Researchers should disclose to the IRB and potential research participants their sources of funding and possible conflicts of interest,
particularly in the case where a commercial or other sponsor plans to use the research results for the registration or promotion of a product or
service.
Internationally sponsored studios. Internationally sponsored studies are studies conducted in a host country but initiated, funded, and sometimes
conducted by a foreign or international entity with the collaboration or agreement of the local authority. In these cases, there could be a conflict between the interests of the
sponsoring country or entity and those of the local community, which is why the following ethical requirements must be met:
(a) projects must undergo ethical evaluation in both the sponsoring country and the host country;
(b) the host country's IRB must ensure that the project meets its ethical requirements; and
(c) researchers must adhere to the ethical rules of the sponsoring country and the host country.
The sponsoring country committee or international organization has a special responsibility to determine whether there is a justification for conducting the study in the host country
instead of taking place in the sponsoring country and if the project conforms to the ethical standards of the sponsoring country or international organization.
The host country committee has a special responsibility to determine whether the research objectives meet their own ethical requirements and the needs and
local health priorities. It should also be ensured that the proposal to conduct the research in the host country rather than the sponsoring country does not follow a
ethical impediment in the latter and, if that were the case, the proposal should not be accepted.
A8. DATA MANAGEMENT AND RESULTS
Q15. The information obtained in a human health investigation must be recorded and filed in a way that allows its adequate interpretation and verification.
P16. When publishing the result of an investigation, the accuracy of the data and its interpretation must be maintained. Publications must declare the
sources of financing, labor relations and other possible conflicts of interest. Items that do not meet ethical standards should not be accepted for
publication.
Data register. All the information obtained from the investigation must be registered, preserved, analyzed, interpreted and communicated in a way that allows
demonstrate the quality and integrity of the data. Data quality means that they must be accurate, legible, complete, contemporary (recorded at the time
that are measured or obtained) and attributable to the person who generated them. The integrity of the data is an attribution of all of them and it refers to the fact that the data is
credible, consistent and verifiable.
The data record can be handwritten or electronic. In any case, its preservation and the confidentiality of personal data must be ensured. It is called
“source” documents to those documents in which data is recorded for the first time, for example, the medical records of the participants. Meanwhile, the
“essential” documents are those that demonstrate that all ethical and scientific requirements have been met during the investigation, for example, the protocol,
the informed consent documents and the CEI approval note. Essential documents should be kept in a safe place to protect the
con fi dentiality of the information and allow its preservation and direct access for veri fi cation, if required by the CEI or the competent authority. When it comes to data
of people health, the essential documents of a study must meet the legal requirements for the preservation of medical information.
Communication of study results. Part of the benefits that communities and individuals can expect from their participation in research is that they
report the conclusions or results concerning your health. If recommendations for public health arise, they should be made available to
health authorities.
Impossibility of communicating the results of the study. In some cases, for example, when the data is not linked to people, it will not be feasible to extract from the
general results the information concerning them or their families, therefore, the participants of these studies should be warned that they will not be informed about
the conclusions concerning their health and that they should not infer therefore that they do not suffer from the disease or condition under study.
Publication of the study results. Investigators are required to disclose information that is in the public interest, by any appropriate means available and
provided that the confidentiality of the participants is respected and that the interpretations or inferences are not presented as if they were proven truths or in a way that
promote or appear to promote special interests, for example, that a product has been shown to be effective. The publication of the
results, both positive and negative, of the investigations, to facilitate their transparency and to avoid repeating studies already carried out and subjecting them to new
participants at unnecessary risk.
To ensure the integrity of scientific information and to promote the highest standards of professional conduct, researchers should present their results in
publications or at peer-reviewed scientific conferences before communicating them to the public media or patient advocacy associations.
A9. SPECIAL CONSIDERATIONS FOR CLINICAL TRIALS
Q17. The benefits and risks of a new intervention should be compared with the one that has proven to be the best so far. The use of placebo is only
acceptable when there is no proven effective alternative intervention or when this technique is necessary for valid methodological or scientific reasons and the risks
of damage or suffering are minor.
Q18. In the event of harm arising from trial participation, participants should have access to necessary medical care and appropriate compensation
by contracting insurance or another form of demonstrable guarantee.
P19. At the end of the research, all participants must share the benefits that have arisen from it, for example, continue receiving the intervention that is
I have identified as the most beneficial for them. If it is not possible to ensure that intervention, for a justified reason, access to an intervention must be guaranteed
appropriate alternative or other suitable benefit, approved by the CEI and for the period that it determines or until its access is guaranteed by another means.
Control groups. The design of control groups is justified only when there is real uncertainty in the scientific community about which of the treatments of the
This study is the best, given that it is unethical to subject participants to the risk of receiving less effective treatment. For this reason, the protocols of these trials
They should include procedures to monitor the occurrence of therapeutic failures or adverse events and the measures of the case, for example, cancel the investigation if an analysis
Acting will demonstrate that one treatment is clearly superior to the others. In this case, and as a general principle, the other participants should be offered the treatment
that it has been superior, always depending on the clinical situation and the response of each participant. In clinical trials measuring the frequency of mortality or
serious health events, evaluate high-risk interventions or include large numbers of individuals, it is advisable to have a data monitoring council and
Independent security to evaluate the interim data.
Random distribution. In the same way as for the use of control groups, trials in which the allocation of an experimental treatment is determined by means of the
Chance can only be done when there is real uncertainty about which one is best. In such a case, participants should be informed about that
uncertainty among the alternatives under study and that the purpose of the trial is to know which is the most beneficial.
People, whether chosen or excluded for the experimental treatment or procedure, may feel uneasy or concerned about the reasons why
have chosen or excluded. Investigators should communicate to potential participants the reason why randomization (prevention of bias) is used, and
reassure them that the randomization process is neither discriminatory nor based on their health status.
Considerations about the scientific need to use placebo. In cases where there is a standard therapy, the use of placebo control instead of that active control
it should be restricted to situations in which the risk of harm or suffering is less and its scientific need has been adequately justified. A beginning
Methodological indicates that the comparison between two or more active substances only shows the relative efficacy between them, while the comparison with placebo allows
establish the real efficacy and, in addition, distinguish the specific adverse effects of the active substance. This is especially relevant when the condition is characterized by
present fluctuating symptoms and / or spontaneous remission, have high response rates to placebo, and existing therapies are only partially effective or have not shown
superiority to placebo consistently in previous studies.
The placebo effect refers to the health benefits, physiological or psychological, produced by a pharmacologically inert treatment. A placebo can
modify the patient's perception of their symptoms and, therefore, cause a bias in the results of a trial, particularly when diagnostic techniques and
Measurements are based on the subjectivity of the perception of the patient or the observer. Examples of these situations are: depression (symptoms are confused with
other mental health problems or are usually in fl uenced by external factors), idiopathic hypertension (blood pressure changes spontaneously or by in fl uence of
diet, mood, etc.) and pain (pain perception varies from person to person). All this subject to the condition of minor risk. Instead, when the answer
pharmacological can be measured with objective techniques, the need to use placebo control is less likely, except in addition to standard therapy. Examples of
These cases are: infections (the evolution of pneumonia is measured with x-rays and laboratory tests) or cancer (the reduction of a tumor can be verified with
imaging or reversal of leukemia with blood cell counts).
When a project proposes the use of placebo, the CEI should assess whether the protocol includes the following mechanisms to minimize risks:
(a) consent clearly expresses the use of placebo and its risks;
(b) the treatment period is the minimum possible to reduce exposure to non-treatment;
(c) control of the participants will be frequent and strict, and it is planned to withdraw the patient from the study or transfer him to active treatment (rescue) as soon as failure is detected
therapy;
(d) there is an interim analysis plan and an independent data monitoring council, with clear rules for stopping the study for security reasons;
(e) crossover design: groups alternately receive active treatment or placebo; and
(f) addition design: when scientifically and medically possible, all participants should receive the standard treatment, adding either the experimental product
or placebo.
Particular attention should be paid to projects proposing the use of placebo in groups or communities that do not have access to standard therapy. The use of placebo does not
it must be accepted when this is its sole basis.
Accidental injury compensation. If an investigation causes harm, the sponsoring entity shall compensate the injured party appropriately according to the
damage type. Pecuniary losses must be repaired promptly. In other cases, it may be difficult to determine appropriate compensation. The violation of
Confidentiality or indiscriminate publication of a study's findings, causing loss of prestige for an individual or group, may be difficult to remedy, and the
CEI shall define what is the appropriate compensation in such cases. The approval of the study by the CEI does not exonerate the investigator, the institution or the sponsor of
no legal responsibility in case of damage suffered by the participant as a result of their participation in the study.
Access to treatment. At the end of the research, all participants should share the benefits obtained from the research, for example, by accessing the
Most beneficial intervention, alternative intervention, or other appropriate benefit.
In particular, in clinical trials sponsored by a pharmaceutical company that have shown an experimental product to be beneficial, the sponsor should
continue its provision to participants until their access is guaranteed by other means. The requirement of this requirement must be determined based on certain
relevant considerations, such as the severity of the medical condition in question and the expected effect of withdrawing or modifying treatment, for example, leaving a
sequel or cause death of the patient. Where full compliance is not possible, the provision of an alternative intervention or other benefit may be agreed.
appropriate, approved by the CEI and for the period that it determines.
A10. CLINICAL TRIALS OF CELL AND GENIC THERAPIES
P20. Clinical trials of cell and gene therapies must follow the principles that protect research participants, including: proper planning of the
trial, fair selection, informed consent, strict medical control of participants, review by an IRB and expert advice and supervision of
a competent regulatory authority.
Ethical justification for trials with cell and gene therapies. A therapeutic approach with cell and gene therapies should aim to be clinically similar or superior
to existing therapies. If effective therapy already exists, the risks associated with cell or gene therapy should be low and offer a potential advantage, for example, a
Better functional result or being a single procedure versus prolonged treatment with medications with associated adverse effects. If there is not yet
therapy, the severity of the disease could justify the risks of experimental cell or gene therapy. In any case, every effort should be made to reduce the
minimize the risks of possible adverse effects associated with the use of cells or genes and not take advantage of the hopes of patients with a poor prognosis. In
gene therapies in particular, given their complexity, the risks could go beyond the individual and affect the genetic heritage of the human being. For all this, the
The suitability and moral integrity of the investigators and the scientific validity of the investigation must be carefully evaluated.
Proper trial planning. The following guidelines should be considered when planning a clinical trial with gene or cell therapy:
(a) preclinical studies in animals and / or other models and previous clinical studies of the experimental therapeutic proposal should show convincing evidence of
safety and potential therapeutic benefits to justify its use in humans;
(b) the biological characteristics of the intervention and the production procedures must be clearly established. Whenever applicable, production should
adapt to the Good Laboratory Practice, and be carried out under the appropriate biosecurity conditions;
(c) the proposed clinical trial should provide for a short, medium and, if applicable, long-term safety assessment with a timely and effective notification plan for
adverse events;
(d) experimental therapy should be compared with the best available treatment, if any;
(e) the risks of experimental therapy should be identified and minimized, and the potential therapeutic benefits realistically defined;
(f) The evaluation and supervision of the assay requires a detailed protocol, with well defined objectives, manufacturing and laboratory standards, and information from
toxicology; and
(g) experimental therapy, if approved, should be accessible to the local population through available health services.
Participants' medical care. Participants have the right to receive any medical attention they require in case of toxicity, including the treatment of tumors
that may appear, and compensation for injuries arising from the investigation. Given the long-term persistence of implanted cell products and according to the type of
Experimental intervention, participants must undergo long-term health checks.
Informed consent. In addition to the usual requirements for the consent of potential research participants, the information must express
clearly:
(a) the foreseeable risks of the proposed experimental therapy. For example, in the case of stem cell therapies, cell proliferation and / or tumor development,
exposure to materials of animal origin and the possibility of transmission of viral vectors; and in genetics, the possible effects on gametic cells and the
offspring;
(b) the potential therapeutic benefits of the experimental intervention and the existence or not of therapeutic alternatives. Consent should emphasize the aspect
experimental intervention to avoid wrong expectations about its therapeutic potential;
(c) in the case of cell therapies, the irreversibility of cell transplantation must be clearly explained. Cells, unlike many drug products or
implantable medical devices, cannot be removed from the body and could continue to generate its adverse effects throughout the patient's life;
(d) to advance scientific knowledge, potential participants should be asked for consent so that in the event of death it is possible to carry out a
Partial or complete autopsy to assess the extent of cell implantation and its morphological and functional consequences. An autopsy request must take into account
account for family and cultural sensitivities. The subject is delicate but, without access to post-mortem material, the trial information would be affected to the detriment of
future products or product improvements.
Recognizing the potential value of new cell and gene therapies for patients with cognitive impairment and the importance that they are not excluded from such
Advances, researchers must develop a procedure so that authorized patient representatives can make a decision on their behalf. The
Representatives must be appropriately qualified and knowledgeable enough to evaluate the trial and provide adequate protection.
Expert advice. Peer review should ensure that the trial will lead to improved disease care and will generate important new ones
knowledge. This review should include a comparison of the new therapy with the available treatments. The following elements must be evaluated by experts:
preclinical in vitro and in vivo studies, previous clinical studies, scientific rationale for the trial, study objectives, statistical analysis and aspects
specific to the disease under study.
Regulatory authority oversight. The supervision of a regulatory authority should ensure that the trial with cell or gene therapies has scientific merit, was
Properly designed, it will be carried out safely and produce reliable knowledge.
SECTION B: OPERATIONAL ASPECTS
This section describes a series of operational requirements for obtaining informed consent, the ethical and scientific evaluation of research projects, the
oversight of research ethics committees and the planning and conduct of clinical trials. Compliance with these requirements will demonstrate that
respected the ethical recommendations of Section A.
B1. THE INFORMED CONSENT
1.1. Informed consent requirement and exceptions
1.1.1. Informed consent is the process that ensures that a potential participant or their legal representative takes it voluntarily, free of incentive
improper and coercive, the decision to participate in an investigation, provided that it is consistent with their values, interests and preferences. The consent process
should be conducted by the principal investigator or a member of the healthcare professional or similar, for example, a trained nurse, social worker, or psychologist
for this function. In cases where a treatment is being investigated, only a physician or dentist, where appropriate, can provide the information regarding the
patient treatment.
1.1.2. In case of legal incompetence or mental incapacity of the potential participant to give voluntary consent, this must be obtained from the legal representative. In
To the extent that their understanding allows, the consent of the potential participant should be requested, after informing them about the study. Your decision to participate or not
It must be respected.
1.1.3. In clinical trials, when the potential participant is socially, culturally, educationally or economically vulnerable, in the consent process
Informed, an independent witness of the investigator or his team must participate, who must sign and date the consent form as proof of their
participation.
1.1.4. In medical emergency situations that require immediate intervention, a summary, approved by the CEI, of the information written for the
competitor. Oral information must be provided in the presence of an independent witness, who must sign, together with the investigator, the summary of information and the
consent form. The participant or his representative must sign the consent form and then receive an original of it and a copy of the summary of
information.
1.1.5. In observational studies, it is usual to obtain the informed consent of potential participants, however, the CEI could approve the following
exceptions:
(a) when publicly available information is used. In such cases, investigators must demonstrate that there is no risk of disclosure of personal data;
(b) when obtaining consent is impracticable, as in the case of irreversibly dissociated biological data or samples, or retrospective studies of
cohort that are carried out on medical records. In the latter case, investigators must guarantee strict measures to protect the confidentiality of
information owners, for example, irreversible decoupling of health data in research records from identi fi cation data
personal; and
(c) when obtaining consent frustrates the objective of a study of the habits or behavior with respect to the health of communities or groups. Being
Informed, participants would modify the behavior they are trying to study, or this could cause unnecessary concern. In such cases, investigators
They must commit to requesting the consent of the participants when the study has concluded but before disseminating its results.
1.1.6. An investigator proposing not to obtain informed consent must justify the reason and explain to the IRB how the study will conform to ethical principles in such a case.
case. The researcher should not proceed with the research without the specific approval of the CEI for the exception of the consent of the participants.
1.1.7. In the case of surveys or interviews that are carried out remotely (by phone or email) or that will be analyzed anonymously, the
requirement to sign a document as proof of consent but the provision of the information related to the study in writing should not be omitted (personally
or by email) or verbally (survey or telephone interview). The researcher must always respect the right to confidentiality of the person surveyed or
interviewed.
1.2. Guidelines for obtaining informed consent
1.2.1. The informed consent document includes at least two sections: the participant information sheets and the signature sheet. Any document that
Plan to use in the process must be previously approved by the CEI.
1.2.2. Informed consent must be obtained before proceeding with the evaluation of the eligibility criteria or any other specific study procedure.
1.2.3. The oral and written information provided to the potential participant or their representative must be presented clearly, precisely, completely, truthfully, in language
practical and appropriate to their understanding, expressed in the primary language of the consenting person and without including any expression that may lead one to believe that the participant lacks
or waives any of its rights or that the researcher, institution or sponsor are released from their responsibilities by signing the consent. The document
writing should guide verbal explanation.
1.2.4. The researcher or his authorized delegate must ensure that the potential participant or his representative has understood all the information received, so
Which should be given an opportunity and enough time to consider all the options, ask all the questions they want and be satisfied with the answers.
1.2.5. After being informed, the potential participant or his legal representative, the investigator or his delegate and the witness, if applicable, must sign and date two originals
of the consent signature sheet, as a declaration of having received and understood the study information and of having made the free and voluntary decision to
participate in it. After the signatures, the participant or his representative must receive one of the originals of the signature sheet and a copy of the information section.
for participants.
1.2.6. In clinical trials, the process of obtaining informed consent must be documented in the participant's medical history, including their date and time of
home, that you were given time to reflect and ask questions, what were those questions, that the understanding of the information was verified, that two were signed
originals of the signature sheet and that one of them was given to the participant or his representative. In case of participation of the legal representative and / or a witness,
document the fulfillment of the corresponding requirements, including the presence or absence of the vulnerability condition.
1.2.7. All new information or changes in the protocol that could affect the participant's safety or their decision to continue the study should be communicated in
verbal and written form to the participant or their legal representative in order to obtain their consent. New participant information sheets must contain
preferably only the information that has changed and be approved by the CEI before use, unless it is necessary to immediately implement the changes to
participant safety.
1.3. Information for the potential participant or their representative
1.3.1. In observational investigations that require consent, the potential participant or his representative should be informed of the following:
(a) the title of the investigation;
(b) proof that the individual is invited to participate in the research and the reasons why it is considered appropriate to do so;
(c) proof that participation in the research is voluntary and that the potential participant may refuse to participate or abandon the research in any
moment, without having to express your reasons and without loss of the benefits to which you are entitled, for example, without affecting the relationship with your doctor or the institution
where it is served;
(d) the purpose of the research, the procedures the participant will undergo, the visits they are expected to attend and the expected duration of their participation;
(e) proof that participation in the study will have no costs for the participant;
(f) the remuneration available to the participant for the expenses derived from their participation. In the cases in which a payment to participate is acceptable, its amount and the scheme
of payment;
(g) a description of the potential benefits of the research to the participant. If no direct benefit is anticipated for the participant, this should be expressed
specifically;
(h) a description of the benefits expected from the research for the community or society in general, or its contribution to scientific knowledge;
(i) a description of the foreseeable risks or inconveniences for the participant or his environment and, in case of pregnancy or lactation, for the embryo, fetus or infant;
(j) all the commitments it assumes if it agrees to participate;
(k) the measures that will be taken to protect the confidentiality of personal data;
(l) limitations, legal or otherwise, on the ability of investigators to protect confidentiality and the possible consequences of their breach;
(m) the commitment to provide a timely response to questions, clarifications or doubts about the procedures, risks or benefits related to the investigation;
(n) the commitment to timely communication to the participant or their representative of all information related to their health status, or information about the study
that could affect your safety or your decision to continue participating in the study and the results of the research as soon as they are available;
(o) the circumstances and / or anticipated reasons why the investigation or the person's participation could be terminated prematurely, specifying that in such case
will take the necessary measures to protect your safety;
(p) a description of the person's rights as a participant in an investigation, including the right to dispose of, modify or delete their data in any
time of the investigation when required;
(q) the contact details of the CEI that has approved the investigation;
(r) what are the research sponsors or funding sources, the researcher's institutional affiliation and other potential conflicts of interest; and
(s) the contact details of the researcher and the REC that approved the study.
1.3.2. In clinical trials, the following specific information should be added:
(a) the approximate number of participants that are planned to be incorporated;
(b) a detail of the actual or potential benefits and risks of the research interventions and of the alternatives available in the event of not participating in the research.
same;
(c) an explanation about the characteristics of the design and its implications, for example, that randomness and masking are applied to avoid influences on the design.
result and that, as a result of the masking, you will not be informed of the assigned treatment until the study is completed;
(d) proof that trial interventions and procedures will be free to participants;
(e) proof that medical care will be provided at no cost to the participant in the event of damage related to the trial and the nature and duration of the trial.
Attention;
(f) if the participant or their relatives will have compensation in the event of disability or death as a result of these damages and through what mechanism will it be done
effective;
(g) if at the end of the research the participant will have access to the intervention that is most beneficial from the trial or to another appropriate intervention or benefit
appropriate, and when and how they will be available; and
(h) the contact details of the investigator and the emergency service where he will be attended in the event of an adverse event related to the investigation.
1.3.3. In the event that the study includes obtaining biological samples, the potential participant or his representative should receive the following additional information:
(a) the possible uses, direct or secondary, of biological samples obtained in the study;
(b) the fate of the biological samples at the end of the study, for example, their destruction or storage for future uses. In the latter case, you must specify
what would be the possible future uses and where, how and for how long will the samples be stored, and that the participant has the right to decide on those future uses, to
destroy the material and refuse storage;
(c) a statement that the samples or derived data will not be marketed;
(d) if commercial products could be developed from the biological samples and if it is planned to offer the participant monetary or other benefits for this
developing; and
(e) in the case of genetic research, that the participant has the right to decide whether or not to be informed of the results of their studies, as long as they have
clinical relevance and there is a course of action to modify the evolution. If you were informed of the results, where and how will you have specialized counseling.
B2. THE ETHICS COMMITTEE IN INVESTIGATION
2.1. Assessment requirement and exceptions
2.1.1. A human health research project must be submitted to the evaluation, guidance and approval of an independent Research Ethics Committee (IEC) of the
researcher and sponsor, before its start and during its development.
2.1.2. Research that is not carried out on human beings, that uses publicly available data or that is limited to
study of health systems, official health programs or public health surveillance, provided that there is no possibility of identifying individuals in the
study records. Examples of public health surveillance are records of diseases or adverse effects of medications already registered by the authority
competent regulator.
2.2. Objectives and scope of the CEI evaluation
2.2.1. The primary objective of an ERC evaluation of human health research is to protect the dignity, rights, safety, and well-being of
participants.
2.2.2. The CEI must provide an independent, competent and timely evaluation of the ethical, scientific, social and operational aspects of the proposed studies.
based on the current state of scientific knowledge and applicable ethical standards.
2.2.3. Research in human health must be evaluated by a CEI before it starts and then at least once a year until its completion. According to the degree of
risk of the same, the CEI can determine shorter intervals. Likewise, the CEI can exempt from the annual review requirement low-risk observational studies,
as defined in A4.
2.2.4. The CEI has the authority to approve, request modifications, disapprove, interrupt or cancel an investigation, before and during its development. The CEI
You must inform the investigator in writing of your opinions, including the reasons for the decision.
2.2.5. The CEI must request and make available to its members all the research documents required for a comprehensive evaluation, including:
protocol and its amendments, informed consent and its amendments, other information for participants, updated curriculum of the researcher, mechanisms for
enrollment, details of the payments and compensations expected for participants and the agreement with the sponsor, if applicable.
2.2.6. The CEI must evaluate whether the researchers are suitable for professional training and training in ethical and regulatory aspects for conducting the study; and if the
host institution is suitable for the execution of the investigation.
2.2.7. The IRB must ensure that potential participants will give their consent free of coercion and undue incentive and after receiving all the information in a timely manner.
adequate.
2.2.8. The IRB must verify that the information for participants on compensation and expected payments is accurate, understandable and does not constitute an incentive mode
improper.
2.2.9. An IRB has authority to monitor the conduct of an investigation, including the process of obtaining consent.
2.2.10. The CEI must keep all the relevant documents of the investigations, such as documents submitted for review, minutes of meetings, opinions and
communications in general, for a period of ten years after the end of the study, and make them available to the health authorities if they request it.
2.3. Composition
2.3.1. The CEI must be constituted according to the regulations and / or laws of the jurisdiction under which it was created, and in such a way as to guarantee a competent evaluation and
free from biases and influences from the ethical, scientific, social and operational aspects of the study.
2.3.2. The composition of the CEI must be multidisciplinary, multisectoral and balanced in age, sex and scientific and non-scientific training. The number of members must be
adequate to fulfill its function, preferably odd and with a minimum of five regular members and at least two alternate or alternate members in cases of absence
of the holders.
2.3.3. Members will need to renew themselves on a regular basis to combine the benefits of experience with those of new perspectives. Selection mechanisms and
Replacement members must guarantee suitability, plurality and impartiality in the election.
2.3.4. The renewal requirements must include: name or description of the person responsible for making the appointments and selection or decision procedure, for example,
by consensus, vote or direct appointment. The selection of new members should include the analysis of potential conflicts of interest and require transparency when
that risk existed.
2.3.5. The CEI must establish in its regulations the terms of the appointment, including the duration, the policy of renewal of membership and the procedures for
disqualification, resignation and replacement.
2.3.6. Members must be willing to disclose their full name, profession and institutional affiliation and sign a confidentiality agreement on the
information from research and discussions about them.
2.3.7. The CEI must establish clearly defined positions to optimize its operation, for example, president, secretary and members. A president must be elected to
to lead the meetings. The member elected as president must have experience in research evaluation and be competent and suitable to deal with and weigh
all its aspects.
2.3.8. Institutional RECs must include an external member who has no ties to the institution and who can account for the interests of the assisted community.
2.4. Functioning
2.4.1. The CEI must prepare and update standardized operating procedures (SOPs) to regulate their composition and operation, including the following:
selection of members, length of membership and renewal criteria, plan of sessions, means of convening, quorum to meet, type speci fi cations, format
and opportunity of the documents required for the evaluation of a project, evaluation procedures, notification and appeal of the opinions, of
monitoring of the studies and declaration of conflicts of interest of its members. The CEI must make its POEs public and operate in accordance with them.
2.4.2. The CEI must receive all the documentation required for the review process and make it available to all its members, notwithstanding the fact that it may
The responsibility for the preliminary review of each project should be distributed among the different members and then submitted for discussion by all the members.
2.4.3. The IRB must establish specific quorum requirements for its review meetings, including the minimum number of members to complete it and the distribution of
professions and sex. The quorum must represent both sexes, both sectors - scientific and non-scientific - and at least one independent member of the institution hosting the
study.
2.4.4. The CEI must prepare and keep updated a list of its members, indicating the name, age, sex, profession or occupation, position in the CEI and relationship with the
institution.
2.4.5. The CEI must record its meetings, deliberations and decisions, including the members who participated in them and the result of their voting.
2.4.6. The CEI may consult experts on specific topics, be they scientific, ethical or social, but without granting them the right to decide on the project. The
Participation and expert opinion should be documented.
2.4.7. A member of the ERC who is both a researcher or part of a project team should not participate in any evaluation, deliberation or decision about that project.
draft.
2.4.8. RECs must take into consideration a challenge request from one or more of its members, submitted by an investigator or other previously interested party
to the revision of a project, provided that the reasons are adequately supported.
2.4.9. In clinical trials, the REC must require the investigator to immediately communicate all relevant safety information and any changes to the protocol that increase
the risk to participants or that has been undertaken to eliminate an immediate danger to them.
2.4.10. In low-risk observational studies, as defined in A4, or in the case of proposals for administrative changes or that do not affect the safety of
Participants of an already approved investigation, the president of the CEI or a member designated for this purpose can make an expeditious evaluation of the proposal,
determine whether or not a full committee evaluation is required. Expedited evaluations must be documented and reported to the rest of the members.
2.5. Application requirements
2.5.1. The request for ethical review of a research project must be submitted by the qualified researcher responsible for the ethical and scientific conduct of the
investigation.
2.5.2. The researcher must present, at least, the following documents:
(a) application note indicating the title of the study and the financing available;
(b) study protocol identified with version number and date;
(c) informed consent;
(d) material to be used for recruiting participants, for example, notices;
(e) in clinical trials of diagnostic or therapeutic products, a summary or monograph describing the preclinical and clinical history;
(f) in clinical trials with commercial or industrial sponsorship, a copy of the financial agreement with the sponsor and the insurance or guarantee of medical coverage and the
compensation provided in case of damage caused to the participants by the research.
2.6. The review process
2.6.1. The CEI's main task is the review of research projects and supporting documents. For the review, the RECs must take into account the laws and regulations
applicable, and take into account the scientific aspects, the proposed recruitment mechanism, the informed consent process and the protection of
participants and the communities involved, during and after the research.
2.6.2. The scientific evaluation of the study must consider, at least, the following:
(a) the adequacy of the chosen design to the objectives, the statistical methodology and the potential to reach solid conclusions of the study and to provide a benefit for the
society;
(b) the adequacy of the proposed control or comparator, if any;
(c) the balance between the risks and drawbacks and the potential and actual benefits for the participants and the communities involved in the study;
(d) justification for the inclusion or exclusion of concomitant treatments;
(e) characteristics of the population to study, including sex, age, ethnicity, education and socio-economic level, among others;
(f) specific inclusion and exclusion criteria of the participants;
(g) the criteria for the premature withdrawal of research participants;
(h) the criteria for suspending or prematurely ending the investigation;
(i) the adequacy of the research center; including equipment, facilities and, in the case of clinical trials, access to emergency care;
(j) the way in which they will communicate and publish the results of the investigation.
2.6.3. Regarding the informed consent process, the CEI must consider the following:
(a) the process envisaged for obtaining informed consent;
(b) relevance, clarity and precision of the study information to be provided to potential participants or, when appropriate, to their representatives;
(c) guarantee that the participants or their representatives will receive information on the progress of the study and its results, and that they will be able to ask or make complaints
during it.
2.6.4. The CEI must review and approve the following precautions for the care and protection of research participants:
(a) the qualification, suitability and experience of the investigator to conduct the investigation;
(b) the medical care to be provided to participants;
(c) measures to minimize the risks of the investigation;
(d) the procedures for participants who decide to withdraw from the research;
(e) the guarantee of access to study treatment when the investigation is concluded;
(f) free participation in research;
(g) the expected remuneration for per diem or loss of earnings for the participants;
(h) the measures for treatment and guarantee of compensation in case of damage attributable to participation in the investigation;
(i) roles of the people who will have access to the data of the participants and the measures that will be taken to ensure the confidentiality of personal information.
2.6.5. The CEI must take into account the following aspects related to the community:
(a) the impact and relevance of the research to the community where it will be carried out;
(b) the measures to consult the community or its representatives before and during the study;
(c) the future availability of any successful research product;
(d) the availability of the research results for the communities involved;
(e) the contribution of research to health services, for example, the training of human resources and the provision of materials or equipment.
2.6.6. In clinical trials sponsored by a pharmaceutical or other commercial company, the REC must verify that the agreement or contract between the researcher, institution and
sponsor:
(a) does not include clauses that limit or appear to limit the rights of the participants;
(b) does not present inconsistencies with the information that will be provided to the participants nor does it require actions that oppose the ethical requirements of the CEI;
(c) establishes that the costs of the trial, including treatments and study procedures and full coverage in case of damage derived from them, will be covered by the
sponsor;
(d) makes explicit that the institution and the investigators will remain unscathed in any case of claim for damages caused by participation in the trial, in the
responsibilities that are the responsibility of the sponsor and that, in case of conflict between the parties, these will be settled in local courts regarding the centers of
investigation;
(e) the sponsor has an insurance or guarantee subject to Argentine law;
(f) the budget realistically contemplates all the costs of the trial, in a way that guarantees its performance and that the payments for the researcher and his team are
proportional to the task and do not constitute an undue incentive to commit ethical misconduct;
2.7. Decision making
2.7.1. To make its decisions on research projects, an IRB must consider the following procedures:
(a) the decision should be made only with a quorum present and after having sufficient time for the review and discussion of all relevant aspects of the
study;
(b) if an IRB member has a potential conflict of interest regarding a project, he / she should not participate in the discussion or decision about that project, leaving
proof of withdrawal in the corresponding minutes;
(c) only members with voting rights may be present at the time of the decision;
(d) decisions must be made following the mechanism defined in the SOPs, for example, by consensus or by vote. Whenever possible, it is preferable that the
decision is reached by consensus of the members;
(e) decisions may be accompanied by suggestions that are not binding;
(f) in cases of conditional decisions, the REC must provide clear recommendations for the required changes or clarifications and specify the procedure for its new
revision;
(g) negative decisions must be clearly supported by their reasons.
2.8. Communication of decisions
2.8.1. The decision about a research project should preferably be communicated within two weeks after it has been made, including the
following:
(a) name of the CEI;
(b) the exact title of the proposed investigation;
(c) detail of all the documents reviewed, including identification with its version number and its date;
(d) the name and title of the applicant;
(e) the name of the institution hosting the investigation;
(f) the result of the review clearly and precisely;
(g) CEI suggestions regarding the project;
(h) in the event of a positive decision, a list of the applicant's responsibilities in relation to the CEI's suggestions and the ongoing review of the study, for example, the
Confirmation of acceptance of the requirements imposed, timely submission of periodic and final reports of the investigation, of future amendments to the protocol and to the
informed consent and, where appropriate, of serious and unexpected adverse events;
(i) the CEI plan for the continuous review of the project during its development;
(j) in case of negative decision, a clear explanation of the reasons for it and what is the established procedure to appeal the decision;
(k) date and signature of the president or other authorized person of the CEI;
(l) updated list of CEI members, including name, age, sex, profession or occupation, position in the CEI and relationship with the institution that houses the committee.
2.9. Continuous review
2.9.1. The CEI must establish procedures for monitoring approved studies until their completion, including:
(a) quorum requirements and review and follow-up procedures, which may differ from that established for the initial review;
(b) interval of follow-up reviews not exceeding once per year, although the time frame may be shortened depending on the nature of the research and the risks
planned;
(c) the instances or events that require revision of the CEI and the corresponding deadlines for their communication, for example, modifications to the protocol or consent,
serious and unexpected adverse events and any other safety information that affects the risk / benefit ratio of the study;
(d) in case of suspension or premature termination of the study by the sponsor or the researcher, the requirement to notify the CEI of the reasons for such action;
(e) the requirement to present to the CEI a final report with the results of the study.
2.10. Documentation and file
2.10.1. All documentation and communications of a REC must be dated, numbered and filed in accordance with written procedures. Access to documents
It should be restricted to authorized personnel.
2.10.2. The archive of documents related to an investigation must be maintained for a period of not less than ten years after the completion or suspension of the investigation.
2.10.3. The CEI document file must include at least the following:
(a) constitution document, regulations, POE, guidelines for project presentation and, if any, management reports;
(b) CV of all the members of the CEI;
(c) registration of all income and expenses of the CEI;
(d) scheduling of meetings;
(e) minutes of the CEI meetings;
(f) copy of all documents received for initial and continuous review of the studies;
(g) communications of the results of the reviews;
(h) correspondence issued and received by the CEI.
B3. REGISTRATION AND SUPERVISION OF ETHICS COMMITTEES IN INVESTIGATION
3.1. Purposes and scope
3.1.1. The purposes of registering and auditing RECs are: a) to provide public assurance that the ethical and scientific review of research in human health is carried out
according to an established standard; and b) assist the RECs to review their procedures and practices.
3.1.2. Taking into account the country's federal organization, the responsibility for the registration and supervision of the RECs rests with the provincial health authorities, the
which should create an agency for this purpose, or assign the enforcement authority to an existing agency, for example, in areas of health research, epidemiology,
general inspection, management of health services or human resources.
3.1.3. The RECs can be formed at the central jurisdictional level or at the level of assistance and research institutions, according to the decision of the health authority of the
jurisdiction. For this decision, the local complexity of the research and healthcare network and the local presence of university science institutions can be considered.
health.
3.2. CEI registration
3.2.1. To register a CEI, the enforcement authority must request at least the following:
(a) request note from the president or coordinator of the CEI;
(b) document creating the CEI;
(c) updated list of CEI members, including name, date of birth, sex, profession or occupation, position on the committee and relationship with the institution;
(d) SOP of the CEI, which must comply with the provisions of section B2 of this Guide.
3.3. CEI supervision
3.3.1. To supervise the RECs of the jurisdiction, the enforcement authority shall prepare the POEs necessary for such activity, including the appointment of supervisors.
independent, design of the supervision plan, the documents to review, the interviews to be carried out, the supervision report model and the distribution of such report.
3.3.2. The choice of the supervisor should guarantee the following:
(a) knowledge and training in research ethics review practices;
(b) independence of the CEI. The supervisor must declare any actual or potential conflict of interest with an IRB and, if the existence of a substantial conflict is determined
of interest, the enforcement authority should assign the task to another supervisor;
(c) complete confidentiality of the groups or individuals participating in the investigations and of the design and / or data of the investigations. The supervisor shall sign a
commitment to confidentiality and no document arising from supervision should record data or information considered confidential.
3.3.3. The designated supervisor must prepare a plan for each assigned supervision, which must be communicated to the CEI prior to the supervision visit. The plan should include:
(a) supervisor identification;
(b) identification of the CEI and its representatives to be interviewed;
(c) reason (routine or for specific cause), objectives and scope of supervision;
(d) expected date / s and estimated duration of supervisory activities;
(e) schedule of interviews or meetings during supervision;
(f) base documents for supervision, for example, this Guide and the SOPs of the CEI;
(g) CEI documents to be reviewed during supervision;
(h) distribution of the supervision report.
3.4. Supervision driving
3.4.1. The supervision of the CEI begins with a meeting between the supervisor and the authorities or representatives of the CEI, with the following objectives:
(a) review of the purpose and scope of supervision;
(b) review of the supervision plan;
(c) discussion about the CEI's ethical review practices;
(d) discussion about the documents to be reviewed;
(e) discussion about the legal or regulatory requirements applicable to the ethical review;
(f) confirmation of the date and time of the supervisory closing meeting.
3.4.2. During supervision, the supervisor should review the archive facilities and at least the following documents:
(a) document creating the CEI;
(b) CEI SOP, including the reference ethical guidelines, the membership requirements and the procedures for selecting members, calling meetings, quorum,
initial, continuous and expedited review, decision-making, communication of decisions and preservation of the documentation of the investigations and the CEI;
(c) list of current members and their vital resumes;
(d) guide for the presentation of research project documents;
(e) initial, follow-up and final documents submitted by the applicants;
(f) approval and / or follow-up notes generated by the CEI;
(g) agenda and minutes of the meetings;
(h) reports generated by the CEI for the authorities.
3.4.3. After supervision, the supervisor should meet again with the authorities or representatives of the CEI to discuss the findings and clarify all their doubts.
3.4.4. The supervisory report should reflect the supervisor's findings and evaluation in a concise and clear manner and, where possible, documented
objectively. The report must contain at least the following:
(a) identification of the supervisor and the CEI and its representatives;
(b) objectives, scope and plan of supervision;
(c) identification of the establishment, people interviewed and documents reviewed;
(d) findings of supervision;
(e) evaluation of the findings by the supervisor;
(f) observations and recommendations for corrective actions;
(g) distribution list of the report, including the CEI;
(h) date and signature of the supervisor.
3.5. Final supervision report
3.5.1. The CEI is responsible for determining, initiating and completing the actions recommended by the supervisor in its initial report. The corrective action plan and its deadlines
of execution must be communicated to the official supervisory body.
3.5.2. The supervisor must prepare a monitoring plan for the actions implemented in the CEI, prior agreement with its representatives, and prepare a final report on
supervision with the initial report plus an evaluation of the actions actually implemented.
B4. CLINICAL TRIALS
4.1. objective
4.1.1. This section establishes the procedures for conducting clinical trials of products or preventive, diagnostic or therapeutic procedures performed only
with the aim of obtaining new knowledge for the best health care. In the case of clinical pharmacology studies for registration and regulatory purposes, these
have been subject to the Good Clinical Practice Regime for Clinical Pharmacology Studies - Provision 6677/10 of the National Administration of Medicines,
Food and Medical Technology.
4.2. Investigator responsibilities
4.2.1. The researcher is the person who conducts a clinical trial in a health center and who participates in its design, analysis and communication.
4.2.2. The investigator must be qualified by training and experience to conduct a clinical trial, as stated in his vital curriculum.
4.2.3. The researcher can constitute a team of qualified and trained collaborators in all the applicable requirements to carry out the research and delegate them
some of its functions but retaining the responsibility of supervising its performance. The aptitude of the collaborators must be documented in their vital resumes
updated.
4.2.4. The researcher must keep an updated list of his collaborators, indicating the name, delegated function, start date of activities and registration of signatures.
4.2.5. The researcher and his collaborators must know and respect the guidelines established in this guide, the research regulations of the health authority
jurisdictional and trial protocol.
4.2.6. The researcher must guarantee the adequacy of the center's infrastructure and of the instruments, equipment and supplies to be used for the clinical trial.
4.2.7. The planned recruitment mechanism must be approved by the CEI, including notices in any means of communication. Notices must not indicate
Implicit or explicit that the product under investigation is effective or safe or that it is equivalent to or better than other existing products.
4.2.8. It is recommended that the researcher implement a quality control process during data collection and recording in order to ensure that it is conducted
and documents according to protocol and that the data is processed correctly and is reliable.
4.3. The trial protocol
4.3.1. The protocol is the document that describes the background, justification, objectives, design, statistical analysis, measurement procedures, interventions and
ethical and administrative considerations of a study. This Guide describes the minimum structure and information that a clinical trial protocol should contain.
4.3.2. General information, background and justification.
(a) full study title and protocol version;
(b) identification of researchers and research centers;
(c) sources of financing;
(d) summary of the protocol;
(e) description of the problem to be investigated and current state of knowledge;
(f) purpose and relevance of the proposed investigation.
4.3.3. Methodological aspects
(a) description of the general and specific objectives of the trial, the hypotheses or research questions, their assumptions and their variables;
(b) study design and justification for their choice;
(c) mechanisms of random assignment and masking, including procedures for opening masking in an emergency, if applicable;
(d) expected number of participants, including calculations on the power of the test;
(e) inclusion and exclusion criteria of participants, including diagnostic criteria;
(f) withdrawal criteria of the participants;
(g) description of the statistical tests and computer tools to be used;
(h) efficacy parameters to be measured, including instruments and measurement methods;
(i) efficacy criteria;
(j) criteria for the analysis of security information;
(k) criteria for handling missing, excluded and spurious data;
(l) criteria for inclusion or exclusion of participants in the analysis;
(m) criteria for cancellation of the trial.
4.3.4. Study interventions
(a) description of research interventions;
(b) in drug trials, the dose, frequency, route of administration and duration of treatment and safety follow-up must be indicated;
(c) in the tests of biological or biotechnological products, the identification and valuation methodology that ensures the uniformity of the preparation to be studied;
(d) drugs allowed and not allowed;
(e) delivery and / or administration mechanisms of the experimental intervention. The protocol shall specify the procedures to be followed for its handling, storage and
inventory, including delivery and return of participants and their final disposal.
(f) criteria for suspension of treatment;
(g) planned rescue treatments and follow-up in the event of failure or adverse events;
4.3.5. Ethical aspects
(a) specification that the research will be reviewed by a REC;
(b) procedures for obtaining informed consent;
(c) procedures to protect the confidentiality of the participants;
(d) details of coverage and compensation for damage available to participants;
(e) justification of payments or compensation for expenses available to participants;
(f) provision for access at trial completion to the intervention identified as being beneficial in the trial, or to an appropriate alternative, or other appropriate benefit;
(g) justification for the use of placebo, if applicable;
(h) justification for conducting the research in a vulnerable group, if applicable;
(i) possible conflicts of interest.
4.3.6. Administrative aspects
(a) registration and communication of clinical data;
(b) procedure for registration and notification to the CEI of adverse events;
(c) handling of trial documents;
(d) plan and publication rights of the results.
4.3.7. Changes made in the protocol approved by the CEI must be justified based on their potential impact on the participants and the scientific validity
of the study; and require the approval of the CEI before its implementation, except when they have been carried out to preserve the safety of the participants.
4.4. Trial participant protection
4.4.1. The researcher is responsible for the process of obtaining the informed consent of all participants, even when they have delegated this function to a member
from your team. Personnel who obtain informed consent must be trained to do so.
4.4.2. Before requesting informed consent, the researcher must evaluate in each potential participant a possible condition of economic vulnerability,
educational, cultural or social, in order to determine the need or not for the presence of an independent witness in the consent process.
4.4.3. The researcher must ensure that each participant will have access to their health information and the results of the study when they are available, and that their
Right to confidentiality will be protected at all times.
4.4.4. In the case of health interventions that imply risks for the pregnancy, embryo or fetus, the following precautions should be considered:
(a) women of childbearing age should be warned of this risk before giving their consent to participate in the study and of the need to communicate immediately
to the investigator if they suspect they are pregnant at any time during the study;
(b) performing a pregnancy test on women of childbearing age prior to study entry and then at each control visit provided for in the protocol;
(c) a positive pregnancy test will imply the exclusion of the potential participant or, if already participating, the preventive suspension of the intervention, if
corresponds. In case of pregnancy, the researcher should guide the participant to receive appropriate care;
(d) the researcher should ensure the participants' access to adequate contraceptive methods, respecting their freedom of choice as much as possible and then controlling
its adherence. When non-adherence is verified, the participant should be excluded from the investigation.
4.4.5. A medical or dental professional, as appropriate, should be in charge of the participants' health care throughout the study.
4.4.6. In the event that the study jeopardizes the integrity or health of the participant, for example, due to adverse reaction or therapeutic failure, the investigator must take
all precautions to cease exposure to risk.
4.4.7. The use of placebo in a control group should be adequately justified in its methodological and ethical aspects. The strategies of addition to standard therapy, use by
Short periods and quick rescue are recommended in this type of design.
4.4.8. The investigator must ensure that participants will receive appropriate medical attention in the event of research-related adverse events, which should
be available anytime they require it. If an intercurrent disease is diagnosed using an investigation procedure, the investigator
You must guide the participant to get the care they need.
4.4.9. When a modification to the protocol is foreseen or information has been obtained that could affect the safety of the participants or their decision to remain
In the trial, consent must be requested before implementing the change or continuing the study.
4.4.10. The experimental interventions or procedures should not have any cost for the participants, regardless of the existence or not of financing
speci fi c for the test. This does not prevent the treatment or procedures required by the participant for being non-commercial scientific research.
illness are covered under your usual health coverage.
4.5. Trial supervision
4.5.1. Before starting the investigation, the investigator must have the written approval of a REC. To this end, the researcher must send you all the documentation that
it requests, including the protocol and its amendments, consent documents and their amendments, and all available information regarding interventions in
study.
4.5.2. To carry out the investigation, the investigator must obtain the authorization of the highest authority of the host institution or the authority designated by it.
4.5.3. The investigator should report to the CEI any serious and unexpected adverse reactions to the study intervention and any other event that significantly affects the
trial and / or risk to participants.
4.5.4. The investigator must inform the CEI about the progress of the trial with a minimum annual frequency. The periodic report must contain, as a minimum, the number of
enrolled, followed-up, and withdrawn participants, coded list of participants, serious adverse events, and their assumed relationship to the study intervention and
deviations to the protocol relevant to the safety of the participants observed during the period.
4.6. Study interventions
4.6.1. In tests with products not defined or governed by Good Laboratory Practice or Good Manufacturing Practice, for example, products of origin
biological, the development and control guidelines and the procedures for its use must be established in the protocol.
4.6.2. The investigator must manage, indicate and / or administer the experimental intervention in the manner established in the protocol. The researcher or his delegate must
instruct each participant on the correct use of the product / s under investigation, ensure that they have understood it and then verify at each clinical visit that has
complied with the instructions.
4.6.3. If the study uses a masking method, the protocol should specify a decoding procedure for emergency situations.
4.6.4. In the event that the researcher supplies and / or administers the experimental intervention, he must keep a record of his delivery and / or administration to the participants, with the
object to demonstrate compliance with the protocol.
4.7. Registration of clinical data
4.7.1. The protocol should describe the procedures designed to obtain and record the clinical data of the participants, as well as the method of
encryption of data to preserve its confidentiality.
4.7.2. The investigator must respect the veracity, legibility, consistency and timeliness of the clinical data records of the study, both in the medical records and in
clinical data registration forms or forms used, as well as the confidentiality of the information of the participants.
4.7.3. If automated devices are used to carry out study measurements, such as electrocardiograms and spirometries, they must be obtained and filed in the
clinical history an identifiable printed document-source of the procedure performed.
4.8. Essential essay documents
4.8.1. The investigator should keep the trial documents in a safe place, locked and with restricted access to authorized personnel.
4.8.2. Essential trial documents should be kept for ten years after completion, taking the necessary steps to prevent loss or loss.
accidental destruction of the same.
4.8.3. The documents considered essential to the trial are the following:
(a) protocol approved by the CEI;
(b) informed consent approved by the CEI;
(c) recruitment mechanism approved by the CEI, if any;
(d) note of approval of the study by the CEI, indicating the approved documents: protocol and version, informed consent and version, recruitment mechanism, etc .;
(e) authorization note from the highest authority of the institution hosting the study;
(f) dated list of members and positions of the CEI;
(g) the delegation of functions of the researcher to his team;
(h) vital resumes of the researcher and his team;
(i) amendments to the protocol approved by the CEI, if any;
(j) amendments to informed consent approved by the CEI, if any;
(k) CEI approval notes for protocol amendments and consent, if any;
(l) notifications to the CEI of serious and unexpected reactions to the study interventions or other safety information;
(m) periodic and final reports presented to the CEI;
(n) participant identification list;
(o) research product accounting forms, if applicable;
(p) signed informed consents;
(q) primary data documents, such as medical records, laboratory and pharmacy records, participant diaries, image reports, and the images themselves,
etc.;
(r) documentation of the processing of the data obtained.
GLOSSARY
AUTONOMY: a person's capacity for self-determination to make a decision freely and voluntarily, according to their own values, interests and preferences, and
as long as you have the necessary information to evaluate all the options.
GOOD PRACTICE OF CLINICAL INVESTIGATION (BPIC): set of procedural requirements for the design, conduct, registration, analysis, monitoring, audit and
clinical trial reports carried out to support the registration of pharmaceutical products for human use, in order to ensure that the
rights and integrity of the participants and that the data and results obtained are reliable and accurate.
GOOD MANUFACTURING PRACTICE (GMP): standard to guarantee a uniform production that satisfies product identity, activity and purity requirements.
GOOD LABORATORY PRACTICE (GLP): organization and laboratory tasks standard under which studies are planned, carried out, recorded, controlled and
expose.
ETHICS COMMITTEE IN INVESTIGATION (CEI): organization that acts in its field of competence, independent of the sponsor and the researcher, made up of
medical or scientific professionals and non-medical or non-scientific members whose function is to provide a public guarantee of the protection of rights, dignity,
safety and well-being of study participants, through, inter alia, review of the study protocol, the informed consent process, and the
suitability of the researcher.
CONFLICT OF INTEREST: a conflict of interest is considered whenever a primary interest, such as the well-being of a patient or the validity of an investigation,
it can be affected by a secondary interest, such as an economic gain, professional prestige or personal rivalries.
INFORMED CONSENT: process by which a person confirms his free and voluntary decision to participate in an investigation, after having been informed
about all its relevant aspects. Informed consent is documented by signing a specific form.
SOURCE DATA: information on clinical findings, observations or other activities, necessary for the reconstruction and evaluation of the clinical study and documented in
original records or copies of them certified by their responsible, called source documents. The source data must be attributable, legible, exact and contemporary.
PERSONAL DATA: information of any kind referring to determined or determinable individuals or individuals with ideal existence.
SENSITIVE DATA: personal data that reveals racial or ethnic origin, political opinions, religious, philosophical or moral convictions, union membership and information regarding
to health or sexual life. These data can only be processed when there are reasons of general interest authorized by law or statistical or scientific purposes when
their holders cannot be identified.
ESSENTIAL DOCUMENTS: documents that individually and collectively allow an evaluation of the conduct of a study and the quality of the data generated.
SOURCE DOCUMENTS: Original documents and records of the clinical data used in a study, such as medical records, laboratory or pharmacy records,
reports of images and the images themselves, participant diaries, data recorded on automated instruments, magnetic or micro fi lm media, and negatives
photographic. Includes copies certified by an authorized person or legalized by a notary public.
CLINICAL TRIAL: see EXPERIMENTAL INVESTIGATION
CLINICAL TRIAL OF CELLULAR THERAPIES: experimental research carried out in patients to establish the tolerance, safety and / or efficacy of a
product based on human cells or tissues, after having demonstrated its therapeutic potential and safety in preclinical studies. Obtaining and processing
cells and tissues must ensure, through validated procedures, the absence of conditions of transmissibility of infectious agents, prions, genetic diseases
or cancer to the host.
CLINICAL TRIAL OF MEDICAL TECHNOLOGY: the experimental research that is carried out to establish the safety and effectiveness of a medical device in human beings
humans. The investigation must establish the indications, contraindications and precautions for the use of the device. If the equipment, apparatus, device or instrument
Medical involves the use of an innovative technique, it must be validated against a comparator.
CLINICAL TRIAL OF VACCINES: experimental research that allows establishing the tolerance, safety, immunogenicity and / or efficacy of a vaccine in individuals
volunteers, healthy or sick. It may correspond to one of the following phases: (a) Phase I: first study in humans to assess tolerance, safety and effects
biological; (b) Phase II: studies that determine the antibody response (immunogenicity) elicited by the vaccine; and (c) Phase III: controlled studies, with a number
of volunteers, in order to evaluate the effectiveness of the vaccine in preventing disease and safety on a larger scale.
EPIDEMIOLOGICAL STUDY: study of the distribution and determinants of events or situations related to health in specific populations. A study
Epidemiological is based primarily on observation and does not require invasive procedures beyond routine medical questions and examinations, such as tests
laboratory or x-rays, so this type of study poses minimal risks for participants. Epidemiological studies can be observational or
experimental. The observational ones, in turn, can be of three subtypes: cross-section, case-control and cohort.
A cross-sectional study is generally performed on a random sample of a population with the objective of evaluating aspects of the health of a population, or
testing hypotheses about possible causes of disease or suspected risk factors.
A case-control study compares the history of risk exposure among patients with a specific condition (cases) with the same history of
Exposure to this risk among people who share characteristics such as age and sex with the cases, but do not present this condition (controls). The difference
Between cases and controls regarding the frequency of past risk exposure, they can be statistically analyzed to test the hypotheses about the causes or
on risk factors.
A prospective longitudinal or cohort study identifies and observes people with different levels of exposure to one or more factors during a given period.
risk, and the rates of occurrence of the condition or disease are compared in relation to the levels of exposure. It is a more robust research method than
the other two cases, but it requires the analysis of a large number of people for a long time and is also expensive.
An experimental epidemiological study is one in which the researcher selects groups of individuals or populations with eligibility criteria, intervenes in
actively on the independent or predictor variable, and observes and analyzes the changes that occur in the dependent or outcome variable as a result of the
intervention. If two interventions are compared, the research hypothesis is contrasted against a null hypothesis.
CLINICAL PHARMACOLOGY STUDY: systematic scientific study carried out with drugs or biological products on voluntary, healthy or sick individuals,
with the purpose of discovering or verifying its therapeutic effects (efficacy) and / or identifying adverse reactions (safety) and / or studying absorption, distribution, metabolism
(biotransformation) and excretion of the active ingredients. Synonym: Clinical Pharmacology Trial.
MULTICENTRIC STUDY: research conducted in more than one institution or research center but following the same protocol.
ADVERSE EVENT (AE): any unfavorable medical occurrence in a clinical trial participant, temporarily associated with the experimental intervention even
when no necessary causal relationship is established. Includes any signs, abnormal laboratory findings, symptoms, or disease.
SERIOUS ADVERSE EVENT (EAS): any unfavorable occurrence in the course and context of an investigation into a diagnostic product or procedure or
Therapeutic resulting in death, life-threatening, requires hospitalization or prolongation of existing hospitalization, resulting in persistent disability or invalidity, or
Signi fi cant, is a congenital anomaly or birth defect, or is medically signi fi cant according to medical criteria. The foregoing applies without the need for
Presumable existence of a causal link between the application of the product or treatment and the adverse event.
CONTROL GROUP: group that is used as a comparator and indicates what happens when the variable or intervention to be studied is not present.
INSTITUTION OR RESEARCH CENTER: any public or private entity, agency or medical or dental facility where clinical studies are conducted.
EXPERIMENTAL INVESTIGATION: investigation in which the investigator selects individuals with inclusion and exclusion criteria, actively intervenes on
the independent or predictor variable, and observes and analyzes the changes that occur in the dependent or outcome variable as a result of the intervention. When
two interventions are compared, the research hypothesis is contrasted against a null hypothesis. Health interventions can be: synthetic medicines,
biological or biotechnological products, medical devices, surgical techniques, etc. Synonym: Clinical trial.
OBSERVATIONAL INVESTIGATION: investigation in which the independent or predictive variable is not intervened and only the possible relationships with the
dependent or outcome variable. The selection of the participants is not made by the researcher, but by nature: healthy or ill, with or without a risk factor; user or not
user of a service or health program, etc. Two subtypes of observational research are recognized:
Descriptive or exploratory research: quantitative or qualitative description of observed facts or phenomena, without posing a hypothesis. Examples: prevalence studies,
cross-sectional, demographic, sociological, etc.
Analytical research: a hypothesis that can be association, risk or causality is proposed and this hypothesis is contrasted against a null hypothesis. The variable
predictor is the risk factor and the outcome variable is disease. The researcher only analyzes the frequency of appearance of the variables but does not intervene on
they.
INVESTIGATOR: individual responsible for conducting the investigation in the research center. If it is a team that conducts research in a center, the
investigator is responsible for the team and is called the principal investigator. The Principal Investigator may delegate tasks to his team but retains his responsibility for
supervision.
PARTICIPANT: healthy or sick individual who participates in an investigation or contributes to the investigation with his personal data or biological samples.
SPONSOR: natural or legal person responsible for the initiation, management and financing of a clinical trial.
PLACEBO: inert substance or simulated treatment or procedure that is administered to a control group in clinical trials in order to provide a baseline measurement for
the study, reducing bias due to suggestion effect.
VULNERABLE POPULATION: group of individuals with mental or legal incapacity to understand the characteristics of an investigation or to express their will or that
due to an unfavorable social, cultural, educational or economic condition, he is more susceptible to being influenced by the expectation of receiving a benefit for participating in
the investigation (undue incentive) or to be the victim of a threat by investigators or others in a position of power if they refuse to participate (coercion).
ACTIVE SUBSTANCE: chemical substance of natural, biological or synthetic origin that has a specific pharmacological effect and is used in human medicine for its potential
therapeutic.
STANDARDIZED OPERATIONAL PROCEDURES (POE): written set of instructions in order to achieve uniformity in the execution of a specific function.
PROTOCOL: document that describes the background, rationale, purpose, objectives, design, methodology, statistical plan, ethical considerations and organization of a
study.
LEGAL REPRESENTATIVE: individual authorized by Civil Code or by applicable laws who acts as representative of a potential participant who is incapable or
incompetent to grant informed consent to an investigation.
INDEPENDENT WITNESS: a person independent of the researcher and his team who participates in the process of obtaining informed consent as a guarantee of
that it respects the rights and interests of a potential vulnerable participant due to their cultural, educational, social or economic condition.