U.S. GUIDELINES ON HUMAN EXPERIMENTATION
(Institutional Guide to DHEW PoIicy on Protection of Human Subjects)
This institutional guide, also known as the "yellow book," contains the first set of federal guidelines for human experimentation applicable to all U.S. Department of Health, Education and Welfare (DHEW) programs. Prior to 1971 here had been a series of guideline statements issued by various agencies within DHEW.
The first federal guidelines for human experimentation were established in 1953 by the Clinical Center of the National Institutes of Health (NIH). However, these guidelines were not a formal statement of NIH policy, and they applied only to research programs conducted at the Clinical Center. In 1966 the Public Health Service (PHS) issued a formal policy statement tor all PHS supported research involving human subjects. NIH revised this statement in 1969 when it set up guidelines for research projects involving human subjects funded by NIH in the document titled "Protection of the Individual as a Research Subject."
Finally, in 1971 DHEW established department-wide guidelines modeled after those of the PHS and NIH, and supplemented these general guidelines with a set of interpretive statements. The guidelines were published in a booklet titled Institutional Guide to DHEW Policy on Protection of Human Subjects. Printed below are excerpts from these guidelines, which include both official policy (in boldface type) and interpretive statements (in lightface type).
The guidelines contained in the 1971 Institutional Guide were revised slightly and officially published (30 May 1974) as part of the Code of Federal Regulations (Title 45, Subtitle A, Part 46). However, the earlier document of 1971—which is still an important and basic document—is being printed here, because the 1974 revisions included only minor changes and because the interpretive statements were not included in the 1974 regulations.
Several additional documents governing research with special populations, such as fetuses, minors, prisoners, the institutionalized, and the mentally retarded were in various stages of preparation when this Appendix was assembled (1976). Since it was anticipated that those regulations would probably be subject to development and revision for several years, they have not been reproduced here.
(For the texts of regulations published in 1973 and 1974, see United States Senate, Subcommittee on Health of the Committee on Labor and Public Welfare. Federal Regulation of Human Experimentation, 1975, 94th Congress, 1st Session. Washington, D.C.: U.S. Government Printing Office, May 1975, pp. 30-91.)
Safeguarding the rights and welfare of human subjects involved in activities supported by grants or contracts from the Department of Health, Education, and Welfare is the responsibility of the institution which receives or is accountable to the DHEW for the funds awarded for the support of the activity.
In order to provide for the adequate discharge of this institutional responsibility, it is the policy of the Department that no grant or contract for an activity involving human subjects shall be made unless the application for such support has been reviewed and approved by an appropriate institutional committee.
This review shall determine that the rights and welfare of the subjects involved are adequately protected, that the risks to an individual are outweighed by the potential benefits to him or by the importance of the knowledge to be gained, and that informed consent is to be obtained by methods that are adequate and appropriate.
In addition the committee must establish a basis for continuing review of the activity in keeping with these determinations.
The institution must submit to the DHEW, for its review, approval, and official acceptance, an assurance of its compliance with this policy. The institution must also provide with each proposal involving human subjects a certification that it has been or will be reviewed in accordance with the institution's assurance.
No grant or contract involving human subjects at risk will be made to an individual unless he is affiliated with or sponsored by an institution which can and does assume responsibility for the protection of the subjects involved.
Since the welfare of subjects is a matter of concern to the Department of Health, Education, and Welfare as well as to the institution, no grant or contract involving human subjects shall be made unless the proposal for such support has been reviewed and approved by an appropriate professional committee within the responsible component of the Department. As a result of this review, the committee may recommend to the operating agency, and the operating agency may require, the imposition of specific grant or contract terms providing for the protection of human subjects, including requirements for informed consent.
This policy applies to all grants and contracts which support activities in which subjects may be at risk.
This term describes any individual who may be at risk as a consequence of participation as a subject in research, development, demonstration, or other activities supported by DHEW funds.
This may include patients; outpatients; donors of organs, tissues, and services; informants; and normal volunteers, including students who are placed at risk during training in medical, psychological, sociological, educational, and other types of activities supported by DHEW.
Of particular concern are those subjects in groups with limited civil freedom. These include prisoners, residents or clients of institutions for the mentally ill and mentally retarded, and persons subject to military discipline.
The unborn and the dead should be considered subjects to the extent that they have rights which can be exercised by their next o£ kin or legally authorized representatives.
C. At Risk
An individual is considered to be "at risk" if he may be exposed to the possibility of harm—physical, psychological, sociological, or other—as a consequence of any activity which goes beyond the application of those established and accepted methods necessary to meet his needs. The determination of when an individual is at risk is a matter of the application of common sense and sound professional judgment to the circumstances of the activity in question. Responsibility for this determination resides at all levels of institutional and departmental review. Definitive determination will be made by the operating agency.
D. Types of Risks and Applicability of the Policy
1. Certain risks are inherent in life itself, at the time and in the places where life runs its course. This policy is not concerned with the ordinary risks of public or private living, or those risks associated with admission to a school or hospital. It is not concerned with the risks inherent in professional practice as long as these do not exceed the bounds of established and accepted procedures, including innovative practices applied in the interest of the individual patient, student or client.
Risk and the applicability of this policy are most obvious in medical and behavioral science research projects involving procedures that may induce a potentially harmful altered physical state or condition. Surgical and biopsy procedures; the removal of organs or tissues for study, reference, transplantation, or banking; the administration of drugs or radiation; the use of indwelling catheters or electrodes; the requirement of strenuous physical exertion; subjection to deceit, public embarrassment, and humiliation are all examples of procedures which require thorough scrutiny by both the Department of Health, Education, and Welfare and institutional committees. In general those projects which involve risk of physical or psychological injury require prior written consent.
2. There is a wide range of medical, social, and behavioral projects and activities in which no immediate physical risk to the subject is involved: e.g., those utilizing personality inventories, interviews, questionnaires, or the use of observation, photographs, taped records, or stored data. However, some of these procedures may involve varying degrees of discomfort, harassment, invasion of privacy, or may constitute a threat to the subject's dignity through the imposition of demeaning or dehumanizing conditions.
3. There are also medical and biomedical projects concerned solely with organs, tissues, body fluids, and other materials obtained in the course of the routine performance of medical services such as diagnosis, treatment and care, or at autopsy. The use of these materials obviously involves no element of physical risk to the subject. However, their use for many research, training, and service purposes may present psychological, sociological, or legal risks to the subject or his authorized representatives. In these instances, application of the policy requires review to determine that the circumstances under which the materials were procured were appropriate and that adequate and appropriate consent was, or can be, obtained for the use of these materials for project purposes .
4. Similarly, some studies depend upon stored data or information which was often obtained for quite different purposes. Here, the reviews should also determine whether the use of these materials is within the scope of the original consent, or whether consent can be obtained.
E. Established and Accepted Methods
Some methods become established through rigorous standardization procedures prescribed as in the case of drugs or biologicals, by law or, as in the case of many educational tests, through the aegis of professional societies or nonprofit agencies. Acceptance is a matter of professional response, and determination as to when a method passes from the experimental stage and becomes "established and accepted" is a matter of judgment.
In determining what constitutes an established and accepted method, consideration should be given to both national and local standards of practice. A management procedure may become temporarily established in the routine of a local institution but still fail to win acceptance at the national level. A psychological inventory may be accepted nationally, but still contain questions which are disturbing or offensive to a local population. Surgical procedures which are established and accepted in one part of the country may be considered experimental in another, not due to inherent deficiencies, but because of the lack of proper facilities and trained personnel. Diagnostic procedures which are routine in the United States may pose serious hazards to an undernourished, heavily infected, overseas population.
If doubt exists as to whether the procedures to be employed are established and accepted, the activity should be subject to review and approval by the institutional committee.
F. Necessity to Meet Needs
Even if considered established and accepted, the method may place the subject at risk if it is being employed for purposes other than to meet the needs of the subject. Determination by an attending professional that a particular treatment, test, regimen, or curriculum is appropriate for a particular subject to meet his needs limits the attendant risks to those inherent in the delivery of services, or in training.
On the other hand, arbitrary, random, or other assignment of subjects to differing treatment or study groups in the interests of a DHEW supported activity, rather than in the strict interests of the subject, introduces the possibility of exposing him to additional risk. Even comparisons of two or more established and accepted methods may potentially involve exposure of at least some of the subjects to additional risks. Any alteration of the choice, scope, or timing of an otherwise established and accepted method, primarily in the interests of a DHEW activity, also raises the issue of additional risk.
If doubt exists as to whether the procedures are intended solely to meet the needs of the subject, the activity should be subject to review and approval by the institutional committee.
A. Initial Review of Projects
1. Review must be carried out by an appropriate institutional committee. The committee may be an existing one, such as a board of trustees, medical staff committee, utilization committee, or research committee, or it may be specially constituted for the purpose of this review. Institutions may utilize subcommittees to represent major administrative or subordinate components in those instances where establishment of a single committee is impracticable or inadvisable. The institution may utilize staff, consultants, or both.
The committee must be composed of sufficient members with varying backgrounds to assure complete and adequate review of projects and activities commonly conducted by the institution. The committee's membership, maturity, experience, and expertise should be such as to justify respect for its advice and counsel. No member of an institutional committee shall be involved in either the initial or continuing review of an activity in which he has a professional responsibility, except to provide information requested by the committee. In addition to possessing the professional competence to review specific activities, the committee should be able to determine acceptability of the proposal in terms of institutional commitments and regulations, applicable law, standards of professional conduct and practice, and community attitudes. The committee may therefore need to include persons whose primary concerns lie in these areas rather than in the conduct of research, development, and service programs of the types supported by the DHEW.
If an institution is so small that it cannot appoint a suitable committee from its own staff, it should appoint members from outside the institution....
2. The institution should adopt a statement of principles that will assist it in the discharge of its responsibilities for protecting the rights and welfare of subjects. This may be an appropriate existing code or declaration or one formulated by the institution itself. It is to be understood that no such principles supersede DHEW policy or applicable law.
3. Review begins with the identification of those projects or activities which involve subjects who may be at risk. In institutions with large grant and contract programs, administrative staff may be delegated the responsibility of separating those projects which do not involve human subjects in any degree; i.e., animal and nonhuman materials studies. However, determinations as to whether any project or activity involves human subjects at risk is a professional responsibility to be discharged through review by the committee, or by subcommittees.
If review determines that the procedures to be applied are to be limited to those considered by the committee to be established, accepted, and necessary to the needs of the subject, review need go no further; and the application should be certified as approved by the committee. Such projects involve human subjects, but these subjects are not considered to be at risk.
If review determines that the procedures to be applied will place the subject at risk, review should be expanded to include the issues of the protection of the subject's rights and welfare, of the relative weight of risks and benefits, and of the provision of adequate and appropriate consent procedures.
Where required by workload considerations or by geographic separation of operating units, subcommittees or mail review may be utilized to provide preliminary review of applications.
Final review of projects involving subjects at risk should be carried out by a quorum of the committee. Such review should determine, through review of reports by subcommittees, or through its own examination of applications or of protocols, or through interviews with those individuals who will have professional responsibility for the proposal project or activity, or through other acceptable procedures that the requirements of the institutional assurance and of DHEW policy have been met, specifically that:
a. The rights and welfare of the subjects are adequately protected.
Institutional committees should carefully examine applications, protocols, or descriptions of work to arrive at an independent determination of possible risks. The committee must be alert to the possibility that investigators, program directors, or contractors may, quite unintentionally, introduce unnecessary or unacceptable hazards, or fail to provide adequate safeguards. This possibility is particularly true if the project crosses disciplinary lines, involves new and untried procedures, or involves established and accepted procedures which are new to the personnel applying them. Committees must also assure themselves that proper precautions will be taken to deal with emergencies that may develop even in the course of seemingly routine activities.
When appropriate, provision should be made for safeguarding information that could be traced to, or identified with, subjects. The committee may require the project or activity director to take steps to insure the confidentiality and security of data, particularly if it may not always remain under his direct control.
Safeguards include, initially, the careful design of questionnaires, inventories, interview schedules, and other data gathering instruments and procedures to limit the personal information to be acquired to that absolutely essential to the project or activity. Additional safeguards include the encoding or enciphering of names, addresses, serial numbers, and of data transferred to tapes, discs, and printouts. Secure, locked spaces and cabinets may be necessary for handling and storing documents and files. Codes and ciphers should always be kept in secure places, distinctly separate from encoded and enciphered data. The shipment, delivery, and transfer of all data, printouts, and files between offices and institutions may require careful controls. Computer to computer transmission of data may be restricted or forbidden.
Provision should also be made for the destruction of all edited, obsolete or depleted data on punched cards, tapes, discs, and other records. The committee may also determine a future date for destruction of all stored primary data pertaining to a project or activity.
Particularly relevant to the decision of the committees are those rights of the subject that are defined by law. The committee should familiarize itself through consultation with legal counsel with these statutes and common law precedents which may bear on its decisions. The provisions of this policy may not be construed in any manner or sense that would abrogate, supersede, or moderate more restrictive applicable law or precedential legal decisions.
Laws may define what constitutes consent and who may give consent, prescribe or proscribe the performance of certain medical and surgical procedures, protect confidential communications, define negligence, define invasion of privacy, require disclosure of records pursuant to legal process, and limit charitable and governmental immunity (see e.g., the University of Pittsburgh Law Manual).
b. The risks to an individual are outweighed by the potential benefits to him or by the importance of the knowledge to be gained.
The committee should carefully weigh the known or foreseeable risks to be encountered by subjects, the probable benefits that may accrue to them, and the probable benefits to humanity that may result from the subject's participation in the project or activity. If it seems probable that participation will confer substantial benefits on the subjects, the committee may be justified in permitting them to accept commensurate or lesser risks. If the potential benefits are insubstantial, or are outweighed by risks, the committee may be justified in permitting the subjects to accept these risks in the interests of humanity. The committee should consider the possibility that subjects, or those authorized to represent subjects, may be motivated to accept risks for unsuitable or inadequate reasons. In such instances the consent procedures adopted should incorporate adequate safeguards.
Compensation to volunteers should never be such as to constitute an undue inducement.
No subject can be expected to understand the issues of risks and benefits as fully as the committee. Its agreement that consent can reasonably be sought for subject participation in a project or activity is of paramount practical importance.
"The informed consent of the subject, while often a legal necessity is a goal toward which we must strive, but hardly ever achieve except in the simplest cases." (Henry K. Beecher, M.D.)
c. The informed consent of subjects will be obtained by methods that are adequate and appropriate.
Note: In the United States, adherence to the regulations of the Food and Drug Administration (21 CFR 130) governing consent in projects involving investigational new drugs (IND) is required by law.
Informed consent is the agreement obtained from a subject, or from his authorized representative, to the subject's participation in an activity. The basic elements of informed consent are:
1. A fair explanation of the procedures to be followed, including an identification of those which are experimental;
2. A description of the attendant discomforts and risks;
3. A description of the benefits to be expected;
4. A disclosure of appropriate alternative procedures that would be advantageous for the subject;
5. An offer to answer any inquiries concerning the procedures;
6. An instruction that the subject is free to withdraw his consent and to discontinue participation in the project or activity at any time. In addition, the agreement, written or oral, entered into by the subject, should include no exculpatory language through which the subject is made to waive, or to appear to waive, any of his legal rights, or to release the institution or its agents from liability for negligence.
[The foregoing definition of informed consent might be compared with the definition given in the 1974 revision of this document (Federal Register, Vol. 39, No. 105, May 30,1974, p. 18917):
“Informed consent" means the knowing consent of an individual or his legally authorized representative, so situated as to be able to exercise free power of choice without undue inducement or any element of force, fraud, deceit, duress, or other form of constraint or coercion. The basic elements of information necessary to such consent include:
1. A fair explanation of the procedures to be followed, and their purposes, including identification of any procedures which are experimental;
2. a description of any attendant discomforts and risks reasonably to be expected;
3. a description of any benefits reasonably to be expected;
4. a disclosure of any appropriate alternative procedures that might be advantageous for the subject;
5. an offer to answer any inquiries concerning the procedures; and
6. an instruction that the person is free to withdraw his consent and to discontinue participation in the project or activity at any time without prejudice to the subject.]
Informed Consent Must be Documented
Consent should be obtained, whenever practicable, from the subjects themselves. When the subject group will include individuals who are not legally or physically capable of giving informed consent, because of age, mental incapacity, or inability to communicate, the review committee should consider the validity of consent by next of kin, legal guardians, or by other qualified third parties representative of the subjects' interests. In such instances, careful consideration should be given by the committee not only to whether these third parties can be presumed to have the necessary depth of interest and concern with the subjects' rights and welfare, but also to whether these third parties will be legally authorized to expose the subjects to the risks involved. The review committee will determine if the consent required, whether to be secured before the fact, in writing or orally, or after the fact following debriefing, or whether implicit in voluntary participation in an adequately advertised activity, is appropriate in the light of the risks to the subject, and the circumstances of the project. The review committee will also determine if the information to be given to the subject, or to qualified third parties, in writing or orally, is a fair explanation of the project or activity, of its possible benefits, and of its attendant hazards.
Where an activity involves therapy, diagnosis, or management, and a professional/patient relationship exists, it is necessary "to recognize that each patient's mental and emotional condition is important. . . and that in discussing the element of risk, a certain amount of discretion must be employed consistent with full disclosure of fact necessary to any informed consent."
Where an activity does not involve therapy, diagnosis, or management, and a professional/subject rather than a professional/patient relationship exists, "the subject is entitled to a full and frank disclosure of all the facts, probabilities, and opinions which a reasonable man might be expected to consider before giving his consent."
When debriefing procedures are considered as a necessary part of the plan, the committee should ascertain that these will be complete and prompt. . . .