INSTITUTIONAL REVIEW BOARDS

Established by Congress in the 1974 National Research Act, institutional review boards (IRBs) are decentralized committees that review and monitor nearly all federally funded research projects involving human subjects in the United States. In most other nations these groups are called research ethics committees (RECs). The purpose of IRBs is to ensure that research conforms to ethical standards and protects the rights and welfare of the people who participate as research subjects. This is accomplished through the IRB Review of Research process, which involves the review of protocols, informed consent documents, and related materials for proposed research. Although flawed and contentious, the IRB regulatory framework is improving in its ability to assure the upholding of ethical standards in a rapidly evolving research context.

Background

The unethical practices of Nazi doctors at concentration camps spurred several attempts to formulate ethical principles for the conduct of research involving human subjects and institutionalize political mechanisms capable of upholding those principles. The most notable international efforts include the 1948 Nuremberg Code and the 1964 Declaration of Helsinki made by the World Medical Association. In 1975 the Helsinki Declaration was revised to include a statement recommending that independent committees review research proposals. The declaration has been revised five more times (1983, 1989, 1996, 2000, and 2002), but the role of ethical review committees has remained central.

In the United States the first federal document requiring committee review was issued in 1953, but it applied only to research conducted at one National Institutes of Health (NIH) facility. In 1966 the U.S. Public Health Service required recipients of its grants to establish committees to review the ethical merits of proposed research involving human subjects. In the early 1970s the U.S. Food and Drug Administration (FDA) and the U.S. Department of Health, Education, and Welfare (DHEW) (forerunner to the Department of Health and Human Services [DHHS]) both promulgated regulations that required committee review of research conducted in institutions.

In 1974, one year after the unethical Tuskegee syphilis study was discontinued, the National Research Act established a statutory requirement for review of FDA- and DHEW-funded research by a committee to which it called an institutional review board (IRB National Research Act 1976). That act also created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (hereafter the Commission) to identify the basic ethical principles that should underlie the conduct of research involving human subjects and to develop guidelines to assure that that research is conducted in accordance with those principles. In 1978 the Commission added a requirement to ensure the equitable selection of research subjects.

In the next year the Commission issued its basic ethical principles and guidelines in the Belmont Report, which resulted from a four-day period of discussions held in February 1976 at the Smithsonian Institution's Belmont Conference Center. The three basic ethical principles identified in the report are justice, beneficence, and respect for persons. The Belmont Report did not make specific recommendations for administrative action by the Secretary of DHEW. Instead, the Commission recommended that the report be adopted in its entirety as a statement of the department's policy. The subsequent adoption of the Belmont Report represents a rare instance of the federal government formally accepting a moral theory as the foundation for legislation (Callahan 2003).

Each of the three principles outlined in the Belmont Report has engendered specific regulations for the practice of research involving human subjects. The principle of justice focuses on the question of who should receive the benefits and bear the burdens of research. It has given rise to both federal and NIH regulations that ensure that the selection of research subjects is equitable (that is, no discrimination against such groups as women, children, and minorities) and that research subjects not be coerced or manipulated in any way. The principle of beneficence entails producing the greatest good while minimizing harm. This principle is reflected in federal regulations that require risk-benefit assessments. The principle of respect for persons highlights researchers' responsibility to treat autonomous persons as such and to protect those with diminished autonomy. The first aspect of that principle is reflected in the regulation requiring informed consent from potential participants. The second is embodied in special regulations designed to protect vulnerable populations, including children, fetuses, and prisoners.

Institutionalization and Criticism

In 1981 the FDA and the U.S. Department of Health and Human Services issued regulations in reaction to the Belmont Report. In that year the FDA created non-institutional review boards (NRBs) to accommodate the increased scope of the review process. In 1991 more than a dozen federal departments and agencies adopted the IRB process as the official Federal Policy for the Protection of Human Subjects, or "Common Rule." The Common Rule includes requirements for (1) assessing compliance; (2) informed consent; (3) IRB membership, function, operations, review of research, and record keeping; and (4) protection for vulnerable research subjects.

The IRB system has improved research practices by making researchers aware of ethical norms and exercising the power to withhold approval for substandard proposals. It is essential for the protection of human subjects and "is an important structural innovation in the social control of science" (Robertson 1979, p. 29). Nonetheless, the IRB system is "under strain" and "in need of reform," and "significant doubt exists regarding [its] capacity to meet its core objectives" (Federman et al. 2003, p. 5).

Central to this debate is whether the regulations unduly inhibit scientific output and progress. Before this question can be answered, however, more data about the impacts of IRBs must be collected. Frustrating this task is the absence of a national registry of all subjects participating in biomedical or social science research. Also, many people claim that the system is too strict in regard to less invasive social science projects and too lenient in regard to more risky research. A failure to balance risk-benefit ratios often hurts the credibility of the IRB system, and this weakens its capacities to achieve its goals (Levine 1986).

A third contentious issue is the decentralized structure of the system and the difficulty of applying general guidelines to specific research projects. Although the decentralized system allows IRBs to remain close to ongoing research, there may be too much local discretion and inadequate oversight of both researchers and individual IRBs. Without adequate assurance of compliance, research institutions may utilize IRBs to protect themselves and researchers rather than to protect subjects.

A fourth area of debate concerns the proper scope of IRB authority. An example from this set of issues is the question of whether IRBs should have the authority to approve or disapprove the scientific design of research protocols.

Assessment

IRBs have been the subject of intense scrutiny, and in 1979 the Hastings Center established a journal, IRB: A Review of Human Subject Research, devoted exclusively to issues raised by and within the system. As with any regulatory framework, the IRB system has had a host of administrative and structural challenges, yet it has proved to be resilient and adaptable. One example is the membership structure of IRBs. Early review committees were limited to immediate peer groups within the research community, but subsequent reforms have led to the requirements of gender diversity, the presence of at least one nonscientist, and the inclusion of at least one member not affiliated with the institution. Further reform efforts are improving the ethics education and certification requirements for IRB members.

The charge that the IRB system may impede scientific output is dubious in light of the rapid development of new drugs and other products and the fact that very few research proposals are rejected by IRBs. Daniel Callahan states that current scientific practice is motivated more and more by the imperative to do research and less and less by the quest for meaningful, life-enhancing knowledge and products (Callahan 2003).

RECs in other countries may offer lessons for reform of the U.S. IRB system. One example is the use of regional, national, and even international committees in other parts of the world. For example, in contrast to the U.S. commitment to local IRBs, many European RECs are regional (McNeill 1989). One issue that will always plague RECs and IRBs, however, is the difficulty of establishing objective criteria by which to evaluate their effectiveness. Most likely, assessment will remain a contested topic that is as much philosophical as it is empirical in nature.

ADAM BRIGGLE

SEE ALSO Bioethics;Bioethics Commissions and Committees;Institutional Biosafety Committees.

BIBLIOGRAPHY

Callahan, Daniel. (2003). What Price Better Health? Hazards of the Research Imperative. Berkeley, CA: University of California Press. Examines the "research imperative" in the United States and the ways in which it can be distorted into harmful practices.

Curran, William J. (1970). "Governmental Regulation of the Use of Human Subjects in Medical Research: The Approach of Two Federal Agencies." In Experimentation with Human Subjects, ed. Paul Freund. New York: George Braziller. Compares the FDA and the NIH review protocols and argues that their differences stem from the fact that they are different types of agencies: One is regulatory, and the other funds exogenous research.

Federman, Daniel D.; Kathi E. Hanna; and Laura L. Rodriguez, eds. (2003). Responsible Research: A Systems Approach to Protecting Research Participants. Washington DC: National Academies Press. An Institute of Medicine study commissioned by the DHHS to assess the national system for providing protection for research subjects. An excellent overview with insightful recommendations.

IRB National Research Act. (1976). Code of Federal Regulations, Title 45, Pt. 46.

Levine, Robert J. (1986). Ethics and Regulation of Clinical Research, 2nd edition. New Haven, CT: Yale University Press.

MacKay, Charles R. (1995). "The Evolution of the Institutional Review Board: A Brief Overview." Clinical Research and Regulatory Affairs 12(2): 65–94.

McNeill, Paul M. (1989). "Research Ethics Committees in Australia, Europe, and North America." IRB: A Review of Human Subjects Research 11(3): 4–7. A look at RECs worldwide.

Robertson, John A. (1979). "Ten Ways to Improve IRBs." Hastings Center Report 9(1): 29–33. A brief summary of the performance of IRBs followed by ten recommendations for improvement. Categorizes defects into two types: administrative and structural.

Sherman, Max, and John D. Van Vleet. (1991). "The History of Institutional Review Boards." Regulatory Affairs Journal 3: 615–27.

U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. (1978). Report and Recommendations: Institutional Review Boards. Washington, DC: U.S. Government Printing Office.

Williams, Peter C. (1984). "Success in Spite of Failure: Why IRBs Falter in Reviewing Risks and Benefits." IRB: A Review of Human Subjects Research 6(3): 1–4. An assessment of inherent defects in the IRB system.