Since the creation of the Common Rule, government agencies, Congress, academic scholars, and the private sector have called attention to problems with the current oversight system and have recommended or taken steps to improve it.
Government Activities
In 1994, the Advisory Committee on Human Radiation Experiments (ACHRE) was created to investi-gate reports of federally sponsored human research involving radioactive materials conducted between 1944 and 1972 and to assess the current state of protections for research participants. Concerning the latter charge they found, “evidence of serious deficiencies in some parts of the current system” (ACHRE 1995, 797). Specifically, ACHRE was concerned with variability in the quality of IRBs, persistent confusion among human participants regarding whether they were involved in research or therapy, and insufficient attention to the implications of diminished decisionmaking capacity in the consent process. Several of the committee’s recommendations addressed the protection of the rights and welfare of human research participants in the future and are directly related to the present report. (Relevant recommendations are reproduced in their entirety in Exhibit C.2.)
Congressional Interest
In general, Congress has been a generous and enthu-siastic supporter of biomedical research, but at the same time some members of Congress have expressed concerns about the adequacy of oversight of human research.24 In recent years, several congressional committees have held hearings on various aspects of protection, including over-all DHHS oversight of human research, oversight of gene therapy trials,25privacy in health research,26the adminis-tration of investigational drugs to members of the armed forces,27 and the use of placebo-controls and washout periods in clinical trials.28 Legislation to strengthen the system of protection has been introduced, although none has been enacted. In addition, the Children’s Research Act of 200029 included provisions to extend protections for children participating in research.
Figure C-1: Common Rule and Agency-Specific Human Research Protection Regulations
Department of Education 34 CFR 97**
Federal Policy for the Protection of Human Subjects*
(“Common Rule”) 45 CFR 46 Subpart A Department
of Agriculture 7 CFR 1c**
Department of Commerce
15 CFR 27**
Department of Defense 32 CFR 219**
Department of Energy 10 CFR 745**
Department of Health and Human Services
45 CFR 46 Subpart A**
Department of Housing and Urban Development
24 CFR 60**
Department of Justice 28 CFR 46**
Department of Veterans Affairs
38 CFR 16** Department of
Transportation 49 CFR 11**
Consumer Product Safety Commission
16 CFR 1028**
Environmental Protection Agency
40 CFR 26**
Agency for International Development
22 CFR 225**
National Aeronautics and Space Administration
14 CFR 1230**
National Science Foundation
45 CFR 690**
Central Intelligence
Agency Executive Order 12333**
Office of Science and Technology
Policy
Social Security Administration
P.L. 103-296**
Food and Drug Administration 21 CFR 50 and 56**
38 CFR 17.85
M-3, Part 1, Chapters 9 and 15** 28 CFR 512**
45 CFR 46 Subparts B, C, D
Order 1300.3**
Order 481.1**
34 CFR 97 Subpart D**
34 CFR 98**
34 CFR 99**
34 CFR 350.4(c)**
34 CFR 356.3(c)**
10 USC 980 AR 40-38**
DoDD 3216.2 SECNAVINST 3900.39B**
DoDD 6000.8 NMRDCINST 3900.2**
AFI 40-402 BUMEDINST 6000.12**
AFI 40-403 NSHSBETHINST 6000.41A**
AR 70-25 USUHS Instruction 3201**
*= policy
**= statute, regulation, directive, executive order
= signatory to Common Rule
= signatory to Common Rule; no regulatory responsibility
❏= additional human subjects protection beyond Common Rule LEGEND
Notes
1 United States v. Karl Brandtet al. (“The Medical Case”), Trials of War Criminals Before the Nuernberg Military Tribunals Under Control Council Law 10. Nuernberg, October 1946–April 1949.
Volumes I–II. Washington, D.C.: U.S. Government Printing Office.
2 United States v. Karl Brandt,et al. (“The Medical Case”), Trials of War Criminals Before the Nuernberg Military Tribunals Under Control Council Law 10. Nuernberg, October 1946–April 1949.
Volumes I–II. Washington, D.C.: U.S. Government Printing Office.
The Nuremberg Code has been widely reproduced. See, e.g., Shuster 1997.
3 During World War II, unethical medical experiments were also performed by the Japanese, primarily against Chinese prisoners.
However, these incidents played less of a role in the development of U.S. policy, partly because the researchers were not prosecuted.
Some have alleged that the U.S. government traded immunity for investigators’ data (Harris 1994).
4 See Fletcher, J., “Location of the Office for Protection from Research Risks Within the National Institutes of Health: Problems of Status and Independent Authority.” This background paper was prepared for NBAC and is available in Volume II of this report.
5 Ibid.
Exhibit C.2: ACHRE Recommendations Relevant to This Report
■ Recommendation 9: The Advisory Committee recommends to the Human Radiation Interagency Working Group [the cabinet-level group to which ACHRE reported] that efforts be undertaken on a national scale to ensure the centrality of ethics in the conduct of scientists whose research involves human subjects.
■ Recommendation 10: The Advisory Committee recommends to the Human Radiation Interagency Working Group that the IRB component of the federal system for the protection of human subjects be changed in at least the five critical areas described below.
1. Mechanisms for ensuring that IRBs appropriately allocate their time so they can adequately review studies that pose more than minimal risk to human subjects. This may include the creation of alternative mechanisms for review and approval of minimal-risk studies.
2. Mechanisms for ensuring that the information provided to potential subjects 1) clearly distinguishes research from treatment, 2) realistically portrays the likelihood that subjects may benefit medically from their participation and the nature of the potential benefits, and 3) clearly explains the potential for discomfort and pain that may accompany participation in the research.
3. Mechanisms for ensuring that the information provided to potential subjects clearly identifies the federal agency or agencies sponsoring or supporting the research project in whole or in part and all purposes for which the research is being conducted or supported.
4. Mechanisms for ensuring that the information provided to potential subjects clearly identifies the financial implications of deciding to consent to or refuse participation in research.
5. Recognition that if IRBs are to adequately protect the interests of human subjects, they must have the respon-sibility to determine that the science is of a quality to warrant the imposition of risk or inconvenience on human subjects and, in the case of research that purports to offer a prospect of medical benefit to subjects, to deter-mine that participating in the research affords patient-subjects at least as good an opportunity of securing this medical benefit as would be available to them without participating in research.
■ Recommendation 11: The Advisory Committee recommends to the Human Radiation Interagency Working Group that a mechanism be established to provide for the continuing interpretation and application of ethics rules and principles for the conduct of human subject research in an open and public forum. This mechanism is not provided for in the Common Rule.
■ Recommendation 13: The Advisory Committee recommends that the Human Radiation Interagency Working Group take steps to improve three elements of the current federal system for the protection of the rights and interests of human subjects—oversight, sanctions, and scope: 1) oversight mechanisms to examine outcomes and performance, 2) appropriateness of sanctions for violations of human subjects protections, and 3) extension of human subjects protections to nonfederally funded research (ACHRE 1995, 816–826).
National Bioethics Advisory Commission
6 See Moreno, J., “Protectionism in Research Involving Human Subjects.” This background paper was prepared for NBAC and is available in Volume II of this report.
7 Pub. Law 781, 87th Congress.
8 See Moreno, J., “Protectionism in Research Involving Human Subjects.” This background paper was prepared for NBAC and is available in Volume II of this report.
9 See McCarthy, C.R., “Reflections on the Organizational Locus of the Office for Protection from Research Risks.” This background paper was prepared for NBAC and is available in Volume II of this report.
10 65 Fed. Reg.37136.
11 S. 934, 93rd Congress.
12 See McCarthy, C.R., “Reflections on the Organizational Locus of the Office for Protection from Research Risks.” This background paper was prepared for NBAC and is available in Volume II of this report.
13 39 Fed. Reg.18914–18920.
14 Pub. Law 348, 93rd Congress.
15 46 Fed. Reg.8366; 46 Fed. Reg.8942.
16 40 Fed. Reg.33526.
17 43 Fed. Reg.53655.
18 48 Fed. Reg.9814.
19 Porter, J., Testimony before NBAC. November 23, 1997.
Bethesda, Maryland; see McCarthy, C.R., “Reflections on the Organizational Locus of the Office for Protection from Research Risks.” This background paper was prepared for NBAC and is available in Volume II of this report.
20 56 Fed. Reg.28002–28023.
21 The 15 signatories to the Common Rule are the Department of Agriculture, the Department of Commerce, the Department of Defense, the Department of Education, the Department of Energy, the Department of Health and Human Services, the Department of Housing and Urban Development, the Department of Justice, the Department of Transportation, the Department of Veterans Affairs, the Agency for International Development, the Consumer Product Safety Commission, the Environmental Protection Agency, the National Aeronautics and Space Administration, and the National Science Foundation.
22 Pub. Law 296, 103rd Congress.
23 Executive Order. “United States Intelligence Activities, Executive Order 12333.” 46 Fed. Reg. 59941.
24 U.S. Congress. House. Committee on Government Reform.
Subcommittee on Criminal Justice, Drug Policy and Human Resources. Human Subject Research Protections.106th Congress, 2nd sess., 3 May 2000; U.S. Congress. House. Committee on
Government Reform. Subcommittee on Criminal Justice, Drug Policy and Human Resources. Protecting Human Clinical Research Patients.105th Congress, 2nd sess., 11 June 1998; U.S. Congress.
House. Committee on Government Reform. Subcommittee on Criminal Justice, Drug Policy and Human Resources. Oversight of HHS: Bioethics and the Adequacy of Informed Consent.105th Congress, 1st sess., 8 May 1997.
25 U.S. Congress. Senate. Committee on Health, Education, Labor, and Pensions. Subcommittee on Public Health. Gene Therapy: What Is the Federal Response for Patient Safety?106th Congress, 2nd sess., 25 May 2000; U.S. Congress. Senate. Committee on Health, Education, Labor, and Pensions. Subcommittee on Public Health.
Gene Therapy: Is There Oversight for Patient Safety?106th Congress, 2nd sess., 2 February 2000.
26 For example, U.S. Congress. House. Committee on Commerce.
Subcommittee on Health and Environment. Medical Records Confidentiality in the Modern Delivery of Health Care.106th Congress, 1st Session, 27 May 1999; U.S. Congress. Senate.
Committee on Health, Education, Labor, and Pensions. Privacy Under a Microscope: Balancing the Needs of Research and Confidentiality.106th Congress, 1st sess., 24 February 1999.
27 U.S. Congress. House. Committee on Government Reform.
Subcommittee on National Security, Veterans Affairs, and International Relations. Force Protection: Improving Safeguards for Administration of Investigational New Drugs to Members of the Armed Forces. 106th Congress, 1st sess., 9 November 1999.
28 U.S. Congress. House. Committee on Veterans Affairs.
Subcommittee on Oversight and Investigations and Subcommittee on Health.Suspension of Medical Research at West Los Angeles and Sepulveda VA Medical Facilities and Informed Consent and Patient Safety in VA Medical Research.106th Congress, 1st sess., 21 April 1999; U.S. Congress. House. Committee on Government Reform.
Clinical Trial Subjects: Adequate FDA Protection?105th Congress, 2nd sess., 22 April 1998.
29 Pub. Law 310, 106th Congress.
References
Advisory Committee on Human Radiation Experiments (ACHRE).
1995. Final Report. Washington, D.C.: U.S. Government Printing Office.
American Medical Association (AMA). Judicial Council. 1946.
“Supplementary Report of the Judicial Council of the American Medical Association.” Journal of the American Medical Association 132:1090.
Beecher, H.K. 1966. “Ethics and Clinical Research.” New England Journal of Medicine274(24):1354–1360.
Cohn, V. 1973. “Live-Fetus Research Debated.” Washington Post, 10 April, A-1.
Department of Health, Education, and Welfare (DHEW). 1971. The Institutional Guide to DHEW Policy on Protection of Human Subjects.
Washington, D.C.: U.S. Government Printing Office.
Faden, R.R., and T.L. Beauchamp. 1986. A History and Theory of Informed Consent. New York: Oxford University Press.
Harris, S.H. 1994. Factories of Death: Japanese Biological Warfare, 1932–1945, and the American Cover-Up. New York: Routledge.
Heller, J. 1972. “Syphilis Victims in U.S. Study Went Untreated for 40 Years.” New York Times, 26 July, A-1.
Jones, J.H. 1981. Bad Blood: The Tuskegee Syphilis Experiment.
New York: The Free Press.
Jonsen, A.R. 1998. The Birth of Bioethics. New York: Oxford University Press.
Moreno, J.D. 1999. Undue Risk: Secret State Experiments on Humans.
New York: W.H. Freeman.
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (National Commission). 1979.
Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: U.S. Government Printing Office.
National Institutes of Health (NIH). 1953. Group Consideration of Clinical Research Procedures Deviating from Accepted Medical Practice or Involving Unusual Hazard. In Final Report, Supplemental Vol. I, 321–324. Washington, D.C.: U.S.
Government Printing Office.
Pappworth, M.H. 1962. “Human Guinea Pigs: A Warning.”
Twentieth CenturyAutumn:66–75.
President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (President’s Commission). 1981. Protecting Human Subjects. First Biennial Report on the Adequacy and Uniformity of Federal Rules and Policies, and of their Implementation, for the Protection of Human Subjects.
Washington, D.C.: U.S. Government Printing Office.
———. 1983. Implementing Human Research Regulations. Second Biennial Report on the Adequacy and Uniformity of Federal Rules and Policies, and of their Implementation, for the Protection of Human Subjects. Washington, D.C.: U.S. Government Printing Office.
Public Health Service (PHS). 1966. Clinical Investigations Using Human Subjects. In Final Report, Supplemental Vol. I, 475–476.
Washington, D.C.: U.S. Government Printing Office.
Rothman, D.J. 1991. Strangers at the Bedside: A History of How Law and Bioethics Transformed Medical Decision Making. New York:
Basic Books.
Shuster, E. 1997. “Fifty Years Later: The Significance of the Nuremberg Code.” New England Journal of Medicine 337(20):1436–1440.
Stewart, W.H. 1966. Clinical Research Investigations Using Human Subjects. In Final Report, Supplemental Vol. I, 473–474.
Washington, D.C.: U.S. Government Printing Office.
Tuskegee Syphilis Study Ad Hoc Advisory Panel. 1973. Final Report. Washington, D.C.: DHEW.
Wilson, C. 1953. Memorandum for the Secretary of the Army, Secretary of the Navy, Secretary of the Air Force. In Final Report, Supplemental Vol. I, 308–310. Washington, D.C.: U.S.
Government Printing Office.