Ethical Practices And Enforcement Research Paper

The Declaration of Helsinki establishes as the international standard for biomedical research involving human subjects the requirement that each research ‘… protocol should be submitted for consideration, comment, guidance, and where appropriate, approval to a specially appointed ethical review committee …’ (World Medical Assoication 2000, Article 13). 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 (Robertson 1979b). In Canada, the Research Ethics Board (REB) has similar authority to approve or disapprove research proposals, not merely to offer ‘consideration, comment and guidance’ (Medical Research Council of Canada 1987, p. 48).

1. History

The Nuremberg Code (Superintendent of Documents 1950) and the original Declaration of Helsinki (World Medical Association 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 (World Medical Association 1975).

In the United States, the first federal document requiring committee review was issued on November 17, 1953. Entitled ‘Group Consideration for Clinical Research Procedures Deviating from Accepted Medical Practice or Involving Unusual Hazard,’ its guide-lines applied only to research conducted at the newly opened Clinical Center at the National Institutes of Health (NIH) (Lipsett et al. 1979). We know very little about committee review in other institutions in the 1950s other than that it existed at least in some medical schools. In 1961 and again in 1962, questionnaires were sent to American university departments of medicine. Approximately one-third of those responding reported that they had committees and one-quarter either had or were developing procedural documents (Curran 1970).

On February 8, 1966, the Surgeon General of the United States Public Health Service (USPHS) issued the first federal policy statement requiring research institutions to establish the committees which subsequently became known as RECs (Curran 1970). 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: (a) of the rights and welfare of the … individuals involved, (b) of the appropriateness of the methods used to secure informed consent, and (c) 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 its membership was reflected in several revisions of its policy between 1966 and 1969 (Veatch 1975, Levine 1988); these will be discussed further shortly.

2. Purpose

The purpose of the REC is to assure that research involving human subjects is designed to conform to relevant ethical and legal 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 US National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission) added a requirement that the REC assure equitableness in the selection of research subjects (Levine 1988, pp. 67ff). 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 assuring disadvantaged persons equitable access to such benefits (C. Levine 1988).

A source of continuing controversy is whether the REC has an obligation to approve or disapprove the scientific design of research protocols (Levine 1988, pp. 20–5). Those who argue that they do or should have such an obligation point out that the leading ethical codes establish an ethical requirement for good scientific design. Moreover, they 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 1987, Veatch 1975). In general, responsibility for assessment of scientific validity is and ought to be delegated to committees designed to have such competence—e.g., scientific review committees either within the institution or at funding agencies such as the NIH (Levine 1988, pp. 21–3).

3. 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; viz., scientists and physicians (Curran 1970, p. 443).

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 such a committee: ‘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 US 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 otherwise 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 Declaration of Helsinki’s requirement of a ‘committee independent of the investigator and sponsor.’

According to Robert Veatch, the REC is an intermediate case between two models of the review committee (1975): 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 concedes that in order to perform all of its functions the REC requires both professional and jury skills. However, he argues 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 Robertson (1979a) would correct the ‘structural bias’ of professional domination by introducing a ‘subject surrogate,’ an expert advocate for the subjects’ interests. DHHS regulations require that a REC which ‘regularly reviews research that involves a vulnerable category of subjects, … shall include one or more individuals who are primarily concerned with the welfare of these subjects.’ For research involving prisoners, for example, 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 membership on all RECs which review research in the field of HIV infection (C Levine et al. 1991).

4. Locale

In the United States the first RECs were established in the institutions in which research was conducted. The 1966 Surgeon General’s policy statement required a committee of ‘institutional associates.’ In 1971 the FDA promulgated regulations which required committee review only when regulated research was conducted in institutions; hence their name, Institutional Review Committee (IRC). 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 (ORB). In 1974 the National Research Act established a statutory requirement for review by a committee to which it assigned the name, Institutional Review Board (IRB), 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 (Robertson 1979b). 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.

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 lends its own interpretation to the requirements of federal regulations. For example, at one university medical students are forbidden to serve as research subjects while at another, involvement of medical students as research subjects is sometimes required as a condition of approval (Levine 1988, pp. 80–2).

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’ (1978, 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.

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 whom had no ready access to RECs. In response, private corporations developed ‘noninstitutional review boards’ (NRBs) (Herman 1989). Although there are theoretical reasons to question the validity of NRB review, they appear to be performing satisfactorily (Levine and Lasagna 2000).

In 1986, FDA began to waive the requirement for local REC review for 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.

Internationally, there is much less commitment to the importance of local review. The International Ethical Guidelines for Biomedical Research Involving Human Subjects, promulgated by the Council for International Organizations of Medical Sciences, require REC approval for all research involving human subjects and recognize the validity of review at a regional or, ‘in a highly centralized administration,’ a national level (1992). In many European countries, RECs are regional (McNeill 1989).

Several commentators have expressed concern that in the United States the local institution has too much power in the field of protection of human research subjects. Robertson, for example, alerts us to ‘the danger … that research institutions will use [RECs] to protect themselves and researchers rather than subjects’ (1979a); 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.

5. 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 1970). In the 1970s several biomedical scientists were harshly critical of the REC system claiming that it tended to stifle creativity and impede progress (Levine 1988, pp. 345–8); 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’ (National Commission 1978, 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 since all they did is talk with subjects, review was an unconstitutional constraint on their freedom of speech (Levine 1988, p. 359).

According to Peter Williams, RECs do an inadequate job of assuring that risks will be reasonable in relation to anticipated benefits (1984). This is in-evitable for three reasons: (a) Federal regulations on this standard are written in vague language in contrast to the more clear direction provided for protecting subjects’ rights. Moreover, since 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. (b) 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. (c) 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) believe that in the context of RECs, the groups are likely to be more tolerant of higher levels of risk than they would be as individuals.

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 1979a) or to supervise consent discussions (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 1988, pp. 341ff).

6. 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 one in one thousand (National Commission 1978, pp. 1–216). 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 by the committee.

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 1988, pp. 358–9). Jerry Mashaw concludes in his excellent theoretical analysis of RECs that: ‘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’ (1982, p. 22).

Bibliography:

1. Annas G 1991 Ethics committees: From ethical comfort to ethical cover. Hastings Center Report 21(3): 18–21
2. Council for International Organizations of Medical Sciences 1992 International Ethical Guidelines for Biomedical Research Involving Human Subjects. Council for International Organizations of Medical Sciences, Geneva
3. Curran W J 1970 Government regulation of the use of human subjects in medical research: The approaches of two federal agencies. In: Freund P A (ed.) Experimentation with Human Subjects. George Braziller, New York. pp. 402–54
4. Freedman B 1987 Scientific value and validity as ethical requirements for research: A proposed explication. IRB: A Review of Human Subjects Research 9(6): 7–10
5. Herman S S 1989 A noninstitutional review board comes of age. IRB: A Review of Human Subjects Research 11(2): 1–6
6. Levine C 1988 Has AIDS changed the ethics of human subjects research? Law, Medicine & Health Care 16: 167–73
7. Levine C, Dubler N N, Levine R 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 and 2): 1–17
8. Levine R J 1988 Ethics and Regulation of Clinical Research. 2nd edn. Yale University Press, New Haven, CT
9. Levine R J, Lasagna L 2000 Demystifying central review boards: Current options and future directions. IRB: A Review of Human Subjects Research 22(6): 1–4
10. Lipsett M B, Fletcher J C, Secundy M 1979 Research review at NIH. Hastings Center Report 9(1): 18–21
11. Mashaw J L 1982 Thinking about institutional review boards. Whistleblowing in Biomedical Research: Policies and Procedures for Responding to Reports of Misconduct. The President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, Washington, DC, pp. 3–22
12. McNeill P M 1989 Research ethics committees in Australia, Europe, and North America IRB: A Review of Human Subjects Research 11(3): 4–7
13. Medical Research Council of Canada 1987 Guidelines on Research Involving Human Subjects. Medical Research Council of Canada, Ottawa, Canada
14. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research 1978 Institutional Review Boards: Report and Recommendations. DHEW, Washington, DC, Publication No (OS) 78–0008
15. Robertson J A 1979a Ten ways to improve IRBs. Hastings Center Report 9(1): 29–33
16. Robertson J A 1979b The law of Institutional Review Boards UCLA Law Review 26: 484–549
17. Robertson J A 1982 Taking consent seriously: IRB intervention in the consent process IRB: A Review of Human Subjects Research 4(5): 1–5
18. Superintendent of Documents, US Government Printing Office 1950 Trials of war criminals before the Nuremberg military tribunals under Control Council Law 10. Military Tribunal 1, Case 1, United States . Karl Brandt et al., October 1946–April 1949 1: 1–1004; 2: 1–352, US Government Printing Office, Washington, DC
19. Veatch R M 1975 Human experimentation committees: Professional or representative? Hastings Center Report 5(5): 31–40
20. Williams P 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
21. World Medical Association 1964 Declaration of Helsinki: Ethical principles for medical research involving human subjects. 18th WMA General Assembly, Helsinki, Finland, June 1964
22. World Medical Association 1975 Declaration of Helsinki: Ethical principles for medical research involving human subjects (amended). 29th WMA General Assembly, Tokyo, Japan, October 1975
23. World Medical Association 1983 Declaration of Helsinki: Ethical principles for medical research involving human subjects (amended). 35th WMA General Assembly, Venice, Italy, October 1983
24. World Medical Association 1989 Declaration of Helsinki: Ethical principles for medical research involving human subjects (amended). 41st WMA General Assembly, Hong Kong, September 1989
25. World Medical Association 1996 Declaration of Helsinki: Ethical principles for medical research involving human subjects (amended). 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996
26. World Medical Association 2000 Declaration of Helsinki: Ethical principles for medical research involving human subjects (amended). 52nd WMA General Assembly, Edinburgh, Scotland, October 2000 http://www.wma.net/e/policy/17c.pdf