Office for Human Research Protections (OHRP)|
Policy Guidance documents
December 26, 1984
This document is intended to provide guidance concerning studies involving acquired immune deficiency syndrome (AIDS) which are subject to the Department of Health and Human Services (HHS) Regulations for the Protection of Human Subjects, 45 CFR 46. Subpart A of these regulations contains general provisions which apply to all research covered by the regulations. Subparts B, C and D, require additional protections for fetuses, pregnant women, prisoners and children. These additional protections must be observed whenever applicable.
Additionally, the Food and Drug Administration (FDA) regulations, 21 CFR 50 and 56, pertaining to informed consent and Institutional Review Boards (IRBs) and 21 CFR 312 regulations pertaining to new drugs for investigational use, must be observed whenever AIDS studies are subject to FDA jurisdiction. Insofar as the FDA regulations pertain to the membership requirements and functions of IRBs, FDA and HHS regulations are essentially congruent.
Because of the special sensitivity of AIDS research, IRBs are cautioned to exercise particular care in observing all applicable regulatory provisions. IRBs have a responsibility to see that risks to subjects are minimized consistent with sound research design. Whenever appropriate, procedures already being performed on subjects for diagnostic or treatment purposes should be used. IRBs should determine that risks to subjects are reasonable in relation to benefits and the importance of the knowledge that may reasonably be expected to result. The IRBs have primary responsibility for making certain that the informed consent process is properly designed for each research project and that accurate and complete information is provided to subjects.
For regulatory purposes [HHS at 45 CFR 46.102(f)] a human subject means a living individual, about whom an investigator conducting research obtains (1) data through intervention or interaction with the investigator, or (2) identifiable private information. Some research designs may involve only the study of existing data, documents, records, pathological specimens or diagnostic specimens, and in these types or designs, if information is recorded by investigators in such a manner that subjects cannot be identified directly or through identifiers, HHS regulations are not applicable. When reviewing studies based on such existing data, documents or specimens, it is sufficient for the IRB to determine that there is not link between the item under study and any living human being.
IRBs should exercise meticulous care in ensuring accurate and complete informed consent procedures and documentation essential to providing protection for the rights and welfare of human subjects. Special attention must be given to implementing the informed consent requirements of 45 CFR 46.116 and 46.117 and 21 CFR 50.25 and interpreting these requirements in a manner that is appropriate for AIDS research.
To ensure adequate review of AIDS studies IRBs may wish to consult with persons who have special expertise and with persons who are qualified to represent the interests of the subject population.
The Assistant Secretary for Health has provided information to Public Health Service (PHS) officials reminding them of the important of informed consent in AIDS research. This information is attached.
No investigator may engage in human subjects research until legally effective informed consent of the subjects (or the subjects' legally authorized representative) is obtained. Informed consent procedures are to be designed to provide subjects with ample opportunity to consider whether or not to participate. Subjects must be free from coercion and undue influence. The information given to subjects is to be in language understandable to them, and must not include exculpatory language that appears to make the subjects waive any legal rights or that appears to release the investigator, institution or sponsor conducting the research from liability.
IRBs should give careful consideration to the circumstances under which participants may be recontacted for follow-up studies. New informed consent procedures will be employed if additional studies not addressed by the first informed consent process are to be performed involving materials or data collected in the original study.
IRBs are expected to see that each of the basic elements of informed consent, 45 CFR 46.116(a) and 21 CFR 50.25(a), is included in the informed consent process and that additional elements described in 45 CFR 46.116(b) and 21 CFR 50.25 (b) are included whenever appropriate. Also an IRB may require that information, in addition to that required in these sections, be given to the subject as part of the informed consent process, when in the IRB's judgment the information would meaningfully add to the protection of the rights and welfare of subjects.
Ordinarily, informed consent is recorded by the use of a written informed consent document that is approved by the IRB and signed by the subject. The subject signing the document is to be given a copy. The informed consent document must contain all the basic elements of informed consent and the additional elements when appropriate. It may be read to the subject of the research, but thee must always be a chance for the subject to read it before signing.
The informed consent document must identify persons to contact for answers to questions about the research and the research subjects' rights and whom to contact in the event of a research-related injury.
Informed consent information must include a statement that participation is voluntary and that refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled. Investigators and the IRB must be certain that these conditions can actually be met before asking individuals to participate.
Subjects are to be informed if tests confirm the presence of HTLV-III antibodies in their blood. Careful attention is to be given to the methods employed to inform subjects of positive findings. Persons providing this information should be qualified to impart sensitive information, alert to privacy and confidentiality issues, and prepared to provide subjects with references for additional counseling.
IRBs must make sure that significant new findings developed during the course of the research which may relate to subjects' willingness to continue to participate are provided to subjects in a timely fashion.
Perhaps the most sensitive aspect of AIDS research from the perspective of the rights and welfare of the subjects is the matter of confidentiality. 45 CFR 46.116(a)(5) and 21 CFR 50.25(a)(5) require a statement of the extent to which confidentiality of records identifying the subject will be maintained.
Improper disclosure could have the most serious consequences for research participants, by threatening family relationships, job security, employability, or ability to obtain credit or insurance. In light of these risks, special precautions should be taken to preserve confidentiality, and potential subjects should be advised with care of the limits of that confidentiality, so they can make thoughtful, informed decisions, in light of their own circumstances, as to whether to participate.
Each study is to be designed with administrative, management and technical safeguards to control authorized use and disclosure of information and to protect against unauthorized disclosure of information and to protect against unauthorized disclosure. Where identifiers are not required by the design of the study, they are not to be recorded. If identifiers are recorded, they should be separated, if possible, from data and stored securely, with linkage restored only when necessary to conduct the research. No lists should be retained identifying those who elected not to participate. Participants must be given a fair, clear explanation of how information about them will be handled.
As a general principle, information is not to be disclosed without the subject's consent. The protocol must clearly state who is entitled to see records with identifiers, both within and outside the project. This statement must take account of the possibility of review of records by the funding agency, and by FDA officials if the research is subject to FDA regulations (21 CFR 50).
IRBs should consider what information will be recorded in the subjects medical records, and may wish to minimize the recording of data from AIDS related studies in the medical records. Some states or other jurisdictions may require AIDS to be reported and may require followup. Participation in research does not exempt compliance with those laws, but potential study participants must be fully informed of laws requiring disclosure of information before they volunteer for the studies.
IRBs should take account of the possibility of attempts under compulsory legal process to force disclosure of records, how such attempts will be responded to and whether individuals will be notified of such attempts. The IRB should consider and establish procedures for information disclosure in emergency situations involving the health either of research subjects or others. Whether and how to notify subjects; physicians of findings about a subject should be addressed.
The protocol should contain information setting forth how to respond to requests by third parties who have authorizations for disclosure of information signed by subjects. (Particular attention should be given to handling blanket authorizations that purport to authorize disclosure of all the data relating to a given person.)
The informed consent requirements set forth in the regulations are based on legal decisions, recommendations of national advisory bodies and years of experience and careful application by researchers and research institutional officials. The procedures have been designed to afford full opportunity for potential subjects to make informed decisions and for protection of the rights, welfare and dignity of those who agree to assist in obtaining important knowledge that will benefit society.
The Office for Protection from Research Risks will be pleased to assist investigators and IRBs in the development of informed consent documents. If you would like assistance pertaining to HHS regulations, please contact:
Office for Protection for Research Risks
Office of the Director
National Institutes of Health
9000 Rockville Pike
Bethesda, Maryland 20892
Because of the wide publicity and special sensitivity associated with AIDS, the following information is provided for research investigators, contractor institutions, Institutional Review Boards (IRBs) and others who share the responsibility for conducting this research in a fashion that is both scientifically rigorous and fully consistent with the rights and the welfare of the subjects involved in the research.
There are three ethical considerations that must be observed in the conduct of this AIDS related research.
1. There must be fairness in the distribution of both risks and benefits of research
Caution is needed to make sure that age, competence, experience, education, position, life style, etc., are not used to determine eligibility for entrance into a study unless these factors are necessary for the research design.
2. Possible benefits of the research must be maximized and possible harms minimized
As the research develops these matters will have to be reviewed from time to time to clarify what benefits may accrue to society as a whole, what benefits may accrue to subjects, and what possible harms may come to subjects. Special care must be taken to establish safeguards to prevent accidental or careless disclosure of confidential information. Improper disclosure could threaten family relationships, job security, employability or ability to obtain credit or insurance.
Therefore, staff persons must be trained to handle information and data with due regard for the rights of subjects.
3. the rights of research subjects to make choices based on informed judgments must be respected
These rights must be protected through a consent procedure which:
(1) is legally effective;
(2) is obtained in non-coercive circumstances with sufficient time and opportunity for subjects to make an informed decision;
(3) does not attempt to waive the rights of subjects, or contain exculpatory language which is intended to limit the legal liability of the institution; and
(4) is presented to subjects in language that is understandable to them--if necessary in language other than English.