Protection of Human Subjects
Vulnerable Populations, Institutional Review Boards, Informed Consent
In 1974, after a long history of harmful research studies conducted on unwilling human subjects (such as the Tuskegee Syphilis Study initiated in the 1930s and a series of studies conducted in the 1960s at the Willowbrook State School, a New York institution for "mentally defective" children), the U.S. Congress established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Four years later, this commission issued the Belmont Report, which is the cornerstone of the ethical principals guiding federal regulations for the protection of human subjects.
There are three fundamental ethical principles, as outlined in the Belmont Report, that guide research involving human subjects: (1) respect for persons, (2) beneficence, and (3) justice. By 1991, seventeen federal departments and agencies had adopted the federal regulations known as the Common Rule (Title 45 Code of Federal Regulations Part 46 [43CFR46]).
Research is defined as a systematic investigation (including development, testing, and evaluation of programs and methods) designed to discover or contribute to a body of generalizable knowledge. Not all scientific or scholarly activities qualify as research, nor does all research involve human participants. A human subject is a living individual about whom an investigator obtains either (1) data through interaction or intervention with the person, or (2) identifiable private information. Each investigator must decide if their study is to include human participants. If human participants are to be involved, the researcher is ethically obligated to become familiar with and adhere to the regulations governing the rights and safety of the human research participants.
Certain groups of human research participants–such as children, prisoners, individuals with questionable capacity to consent, students, or employees of the institution conducting the research–are considered to be either relatively or absolutely incapable of protecting their own interests. Because children have not legally attained an age where they can consent on their own to research or treatment, a parent or legal guardian may provide consent for a child to participate in a study. Above the age of seven, the child must also show willingness to participate by assenting to the study. Although many college students are below the age of twenty-one, they are generally treated as "emancipated adults" for the purpose of consenting to participate in research studies.
Institutional Review Boards
The National Research Act passed by Congress in 1974 that resulted in the Belmont Report also required the establishment of Institutional Review Boards (IRBs) to review all research involving human subjects funded by the Department of Health and Human Services. The regulations governing IRBs were revised in 1981.
Every institution in the United States receiving federal support for research with human subjects has to have its own IRB or access to an IRB. An IRB protects the rights, safety, and welfare of human research participants by: (1) reviewing research plans to ensure that, in its judgement, the research meets the criteria found in 45CFR46.111; (2) confirming that the research plans do not expose participants to unreasonable risks; (3) conducting continuing review of approved research at intervals commensurate with the degree of risk of the trial–but not less than once a year–to assure that human participant protections remain in force; and (4) assessing suspected or alleged protocol violations, complaints raised by research participants, or violations of institutional policies.
The IRB has the authority to approve, disapprove, or terminate all research activities that fall within its jurisdiction; require modifications in protocols, including previously approved research; require that information, in addition to that specifically mentioned in 45CFR46.116, be given to participants when the IRB deems that this information would add to the protection of their rights and welfare; and require documentation of informed consent or allow waiver of documentation, in accordance with 45CFR46.117.
IRBs must have at least five members with varied backgrounds who have no vested interest in the conduct or outcomes of the proposed research. At least one member of the IRB must not be affiliated with the institution, and the membership should be as diverse as possible. Most IRBs have many more than five members, and most are divided into subcommittees for the purpose of handling different types of studies, such as biomedical or behavioral studies.
In order to approve a research study, the IRB must assure that risks to participants are reasonable and minimized; that the selection of participants is equitable; that informed consent from each participant is sought and documented; and, when appropriate, that there are adequate provisions to protect the safety and privacy of the participants and the confidentiality of the data. Depending on the level of risk and the type of subject population, review may be done by the full IRB, or it may be expedited. Certain types of studies are exempted from IRB review and approval. Even in these exempt cases (many of which involve educational practices or tests), however, it is not the researcher but the IRB that makes this determination.
Informed consent, as a legal, regulatory, and ethical concept, has become widely accepted as an integral part of research involving human subjects. A written consent document is a key part of the proposal submitted to an IRB. This is a document written to the proposed subject in a language understandable by the subject. All of the elements required by 45CFR46.116 must be included, plus any other information necessary for the prospective participant to make an informed decision. The required elements include a statement that the study involves research; an explanation of the purpose of the research, including why the individual was selected and the expected duration of the individual's participation; a description of all procedures to be followed; a description of any foreseeable risks, discomforts, and inconveniences (and what will be done to minimize or deal with them); a description of any anticipated benefits, both to the individual subject and to society; information about who to contact if there are additional questions; a statement that participation in the research is voluntary, that withdrawal may occur at any time, and that there is no penalty for withdrawal or refusal to participate; and, finally, an invitation for the participant to ask any questions about the proposed study before agreeing to participate.
In 2001 the National Cancer Institute of the National Institutes of Health introduced an online training program to educate research teams about human participant protections. This free access program available via the Internet elaborates greatly on all of the information contained in this article.
DEPARTMENT OF HEALTH AND HUMAN SERVICES. 1991. Code of Federal Regulations: Title 45, Public Welfare; Part 46, Protection of Human Subjects. Washington, DC: Department of Health and Human Services.
NATIONAL COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS OF BIOMEDICAL AND BEHAVIORAL RESEARCH. 1978. Belmont Report: Ethical Principals and Guidelines for Research Involving Human Subjects. Washington, DC: U.S. Government Printing Office.
ROTHMAN, D. J. 1982. "Were Tuskeegee and Willowbrook Studies in Nature?" Hastings Center Report 12 (2):5–7.
NATIONAL INSTITUTES OF HEALTH. 2001. "Human Protection for Research Teams." <http://cme.nci.nih.gov>.
KENNETH A. WALLSTON