Research Ethics Committees

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RESEARCH ETHICS COMMITTEES

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The World Medical Association's Declaration of Helsinki (2000) and the Council for International Organizations of Medical Sciences' International Ethical Guidelines for Biomedical Research Involving Human Subjects (hereafter, CIOMS International Ethical Guidelines) (2002) establish as the international standard for biomedical research involving human subjects this requirement: "All proposals to conduct research involving human subjects must be submitted for review of their scientific merit and ethical acceptability to one or more scientific review and ethical review committees.… The investigator must obtain their approval or clearance before undertaking the research" (CIOMS, Guideline 2). In most of the world this committee is called the research ethics committee (REC). In the United States, federal law assigns to the committee the name institutional review board (IRB), and the authority and responsibility for approving or disapproving proposals to conduct research involving human subjects ("IRB Review of Research").

History

The Nuremberg Code (1949) and the original Declaration of Helsinki (1964) made no mention of committee review; these documents placed on the investigator all responsibility for safeguarding the rights and welfare of research subjects. The first mention of committee review in an international document was in the Tokyo revision of the Declaration of Helsinki (1975).

In the United States, the first federal document requiring committee review was issued on November 17, 1953. Titled "Group Consideration for Clinical Research Procedures Deviating from Accepted Medical Practice or Involving Unusual Hazard," its guidelines applied only to research conducted at the newly opened Clinical Center at the National Institutes of Health (Lipsett, Fletcher, and Secundy). Very little is known about peer review in other institutions in the 1950s other than that it existed in at least some medical schools. In 1961 and again in 1962, questionnaires were sent to departments of medicine at U.S. universities. Approximately one-third of those responding reported that they had committees, and one-quarter either had or were developing procedural documents (Curran).

On February 8, 1966, the surgeon general of the U.S. Public Health Service (USPHS) issued the first federal policy statement requiring research institutions to establish the committees that subsequently came to be known as RECs (Curran). This policy required recipients of USPHS grants in support of research involving human subjects to specify that

the grantee institution will provide prior review of the judgment of the principal investigator or program director by a committee of his institutional associates. This review shall assure an independent determination: (1) Of the rights and welfare of the … individuals involved, (2) Of the appropriateness of the methods used to secure informed consent, and (3) Of the risks and potential medical benefits of the investigation.

The evolution of the federal government's charges to the committee and of its recognition of the need for diversity of committee membership was reflected in several revisions of its policy between 1966 and 1969 (Veatch; Levine, 1986); these will be further discussed below.

Purpose

The purpose of the REC is to ensure that research involving human subjects is designed to conform to relevant ethical standards. Historically, the REC's primary focus was on safeguarding the rights and welfare of individual research subjects, concentrating on the plans for informed consent and the assessment of risks and anticipated benefits. In 1978 the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (hereafter, National Commission) added a requirement that the REC ensure equitableness in the selection of research subjects (Levine, 1986). The National Commission was concerned primarily with protecting vulnerable subjects from bearing a disproportionately large share of the burdens of research. Subsequently, as participation in some types of research became perceived as a benefit, RECs also assumed responsibility for ensuring disadvantaged persons equitable access to such benefits (Levine, 1994).

A source of continuing controversy is whether the REC has an obligation to approve or disapprove the scientific design of research protocols (Levine, 1986). Those who argue that they do or should have such an obligation point out that the leading ethical codes establish a requirement for good scientific design. Moreover, these observers argue, the REC's obligation to determine that risks to subjects are reasonable in relation to anticipated benefits necessarily relies on a prior determination that the scientific design is adequate, for if it is not, there will be no benefits and any risk must be considered unreasonable.

Opponents to assigning such an obligation to the REC, while conceding these two points, argue that the REC is not designed to make expert judgments about the adequacy of scientific design. RECs are generally competent to appraise the value of the science—what the Nuremberg Code calls "the humanitarian importance of the problem to be solved"—but not the validity of the methods or the results (Freedman; Veatch). In general, responsibility for assessment of scientific validity is, and ought to be, delegated to committees designed to have such competence—such as scientific review committees either within the institution or at funding agencies such as the National Institutes of Health (Levine, 1986; IOM).

Membership

The surgeon general's 1966 memo called for prior review by "a committee of [the investigator's] associates," what was commonly called "peer review." As of 1968, 73 percent of committees were limited in membership to immediate peer groups: scientists and physicians (Curran).

On May 1, 1969, USPHS guidelines were revised to indicate that a committee constituted exclusively of biomedical scientists would be inadequate to perform the functions now expected of it: "The membership should possess … competencies necessary in the judgment as to the acceptability of the research in terms of institutional regulations, relevant law, standards of professional practice and community acceptance."

Regulations of the U.S. Department of Health and Human Services (DHHS), first promulgated in 1974 and since revised several times, maintain the spirit of the 1969 policy and in addition require gender diversity; at least one nonscientist (e.g., lawyer, ethicist, member of the clergy); and at least one member who is not affiliated with the institution (commonly and incorrectly called a "community representative"). Persons having conflicting interests are to be excluded; this concern is also reflected in the CIOMS International Ethical Guidelines' requirement for "review committees independent of the research team."

According to Robert M. Veatch (1975), the REC is an intermediate case between two models of the review committee: The "interdisciplinary professional review model," made up of diverse professionals such as doctors, lawyers, scientists, and clergy, brings professional expertise to the review process, while the "jury model … reflects the common sense of the reasonable person." In the jury model "expertise relevant to the case at hand is not only not necessary, it often disqualifies one from serving on the jury" (Veatch, p. 31). Veatch conceded that in order to perform all of its functions, the REC requires both professional and jury skills. He argued, however, that the presence of professionals makes it more difficult for the REC to be responsive to the informational needs of the reasonable person or to be adept at anticipating community acceptance.

John A. Robertson (1979) recommended correcting the "structural bias" of professional domination by introducing a "subject surrogate," an expert advocate for the subjects' interests. DHHS regulations require that if an REC "regularly reviews research that involves a vulnerable category of subjects … consideration shall be given to the inclusion of … [persons who know] about and [are] experienced in working with these subjects" (IRB Membership). For research involving prisoners, the regulations require that at least one member of the REC be either a prisoner or a prisoner representative. There is unresolved controversy over whether persons with AIDS should be appointed to serve on all RECs that review research in the field of HIV infection (Levine, Dubler, and Levine).

In the United States the Institute of Medicine (IOM) endorsed the recommendation of the National Bioethics Advisory Commission (NBAC) that "at least 25 percent of [the IRB's] membership should be reserved for unaffiliated [with the institution] members and those who can provide nonscientific perspectives" (IOM, p. 96). The IOM further expressed its support for the current trends in the United States to enhance the education of REC members and to certify them as competent by independent agencies.

Locale

In the United States the first RECs were established in the institutions where research was conducted. The 1966 surgeon general's policy statement required a committee of "institutional associates." In 1971 the Food and Drug Administration (FDA) promulgated regulations that required committee review only when regulated research was conducted in institutions; hence their name, institutional review committee. Regulations proposed in 1973 by the Department of Health, Education, and Welfare, forerunner of DHHS, also reflected a local setting in their term "organizational review board." In 1974 the National research Act established a statutory requirement for review by a committee to which it assigned the name "institutional review board," a compromise between the two names then extant.

RECs are required to comply with federal regulations when reviewing activities involving FDA-regulated "test articles," such as investigational drugs and devices, and when reviewing research supported by federal funds. Moreover, all institutions that receive federal research grants and contracts are required to file "statements of assurance" of compliance with federal regulations. In these assurances virtually all institutions voluntarily promise to apply the principles of federal regulations to all research they conduct, regardless of the source of funding (Levine, 1986; IOM).

These points notwithstanding, each REC has a decidedly local character. Most have local names, such as "human investigation committee" or "committee for the protection of human subjects." Each is appointed by its own institution, and each makes its own interpretation of the requirements of federal regulations. For example, at one university, medical students are forbidden to serve as research subjects, whereas at another, involvement of medical students as research subjects is sometimes required as a condition of approval (Levine, 1986).

In its 1978 report, the National Commission recommended that RECs should be "located in institutions where research … is conducted. Compared to the possible alternatives of a regional or national review … local committees have the advantage of greater familiarity with the actual conditions" (U.S. National Commission, pp. 1–2). The National Commission envisioned the local REC as an ally of the investigator in safeguarding the rights and welfare of research subjects, as well as a contributor to the education of both the research community and the public.

The FDA's change in regulations in 1981 to require REC review of all regulated research, regardless of where it was done, created a problem for the many physicians who were conducting investigations in their private offices; many of these physicians had no ready access to RECs. In response, private corporations developed noninstitutional review boards (NRBs) (Herman). Although there are reasons to question the validity of reviews by NRBs, they appear to be performing satisfactorily (Levine and Lasagna).

In 1986 the FDA began to waive the requirement for local REC review of some protocols designed to evaluate, or to make available for therapeutic purposes, investigational new drugs, particularly those intended for the treatment of HIV infection. In such cases RECs were offered the option of accepting review by a national committee as fulfilling the regulatory requirement for REC review. Such practices have caused some commentators to question the strength of the government's commitment to the principle of local review (Levine and Lasagna).

Internationally, there is much less commitment to the importance of local review. The CIOMS International Ethical Guidelines require REC approval for all research involving human subjects and recognize the validity of review at "the institutional, local, regional or national, and in some cases, at the international level." In many European countries, RECs are regional (McNeill).

Several commentators have expressed concern that in the United States the local institution has too much power in protection of human research subjects. Robertson, for example, warned about "the danger … that research institutions will use [RECs] to protect themselves and researchers rather than subjects" (1979); others point to the close associations between RECs and risk-management offices in many institutions as evidence that RECs are being used in this manner.

Criticisms

Before 1962, "a general skepticism toward the development of ethical guidelines, codes, or sets of procedures concerning the conduct of research" prevailed in the medical research community (Curran, p. 408). In the 1970s several biomedical scientists were harshly critical of the REC system, claiming that it tended to stifle creativity and impede progress (Levine, 1986); survey research, however, showed that only 25 percent of biomedical researchers agreed with the statement that "The review … is an unwarranted intrusion on the investigator's autonomy—at least to some extent" (U.S. National Commission, p. 75). Behavioral and social scientists were considerably less accepting of review, claiming that their research activities were much less likely than those of the biomedical scientist to harm subjects. Some argued that because all they did was talk with subjects, review was an unconstitutional constraint on their freedom of speech (Levine, 1986). With the passage of time, most social and behavioral scientists have recognized the value of the REC's review of work in their fields; they have protested, however, that much of the review of social and behavioral research is unsatisfactory because RECs, in general, tend to inappropriately apply rules and procedures that were designed for the "biomedical model" (IOM).

According to Peter C. Williams (1984), RECs do an inadequate job of ensuring that risks will be reasonable in relation to anticipated benefits. This is inevitable for three reasons:

Federal regulations on this standard are written in vague language, in contrast to the clearer direction provided for protecting subjects' rights. Moreover, because the regulations permit consideration of the long-range effects of applying knowledge as benefits but not as risks, they create a bias in favor of approval.
The membership of the committee, dominated as it is by professionals, is likely to place a higher value than laypersons would on the benefit of developing new knowledge.
Groups confronted with choices involving risks may be either more or less cautious or "risk aversive" than the average of individuals within the group; this is known as the risky shift or group polarization phenomenon. Williams (1984) and Veatch (1975) have argued that in the context of RECs, the groups are likely to be more tolerant of higher levels of risk than would be the individuals who comprise the groups.

Several commentators have proposed that RECs could enhance their effectiveness by sending members to the sites of the actual conduct of research to verify compliance with protocol requirements (Robertson, 1979) or to supervise consent negotiations (Robertson, 1982). Others respond that while such activities should be done when there are reasons to suspect problems in specific protocols, routine monitoring activities might be detrimental to the successful functioning of the committee by eroding its support within the institution (Levine, 1986). The Institute of Medicine concurs with the NBAC's proposal that the REC should engage in routine monitoring of the actual conduct of research, concentrating its efforts on research projects that present to subjects relatively high levels of risks (IOM).

Evaluation

Critics of the REC system claim that there is little or no objective evidence that REC review prevents the conduct of inadequate research. For example, a national survey of RECs revealed that the rate of rejection of protocols is less than 1 in 1,000 (National Commission). Supporters of the system respond that the actual rejection rate is much higher if one includes protocols withdrawn because investigators refuse to modify them as required by RECs. Moreover, rejection rates may be a poor indicator of the REC's quality; protocols may be improved in anticipation of the REC's requirements, and investigators, fearing rejection, may decide not to submit proposals they think might be rejected.

It is very difficult to evaluate the REC's performance objectively; satisfactory subjective evaluations can be made only by experienced REC members and administrators (Levine, 1986). In his excellent theoretical analysis of RECs, published in 1981, Jerry L. Mashaw concluded:

If [the REC] is to do its core job well, we must live with its inevitable incompetence at other tasks. Moreover, we must also live with the rather vague regulatory standards and with the continuing inability of the federal funding agencies to know for sure whether [RECs] are functioning effectively. If we would have wise judges and paternalistic [skilled in protecting subjects' rights and welfare interests] professionals, we can neither specifically direct nor objectively evaluate their behavior. (Mashaw, p. 22)

robert j. levine (1995)

revised by author

BIBLIOGRAPHY

Council for International Organizations of Medical Sciences (CIOMS), in collaboration with the World Health Organization. 2002. International Ethical Guidelines for Biomedical Research Involving Human Subjects. Geneva, Switzerland: Author.

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 A. Freund. New York: George Braziller.

Freedman, Benjamin. 1987. "Scientific Value and Validity as Ethical Requirements for Research: A Proposed Explication." IRB: A Review of Human Subjects Research 9(6): 7–10.

Herman, Samuel S. 1989. "A Noninstitutional Review Board Comes of Age." IRB: A Review of Human Subjects Research 11(2): 1–6.

Institute of Medicine (IOM). Committee on Assessing the System for Protecting Human Research Participants. 2003. Responsible Research: A Systems Approach to Protecting Research Participants, ed. Daniel D. Federman, Kathi E. Hanna, and Laura L. Rodriguez. Washington, D.C.: National Academies Press.

"IRB Membership." 2002. Code of Federal Regulations Title 45, Pt. 46.107.

Levine, Carol; Dubler, Nancy N.; and Levine, Robert J. 1991. "Building a New Consensus: Ethical Principles and Policies for Clinical Research on HIV/AIDS." IRB: A Review of Human Subjects Research 13(1–2): 1–17.

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Levine, Robert J. 1994. "The Impact of HIV Infection on Society's Perception of Clinical Trials." Kennedy Institute of Ethics Journal 4(2): 93–98.

Levine, Robert J., and Lasagna, Louis. 2000. "Demystifying Central Review Boards: Current Options and Future Directions." IRB: A Review of Human Subjects Research 22(6): 1–4.

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Veatch, Robert M. 1975. "Human Experimentation Committees: Professional or Representative?" Hastings Center Report 5(5): 31–40.

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.

World Medical Association. 1964 (revised 1975, 2000). "Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects." Ferney-Voltaire, France: Author.

Encyclopedia of Bioethics