I am very grateful for the kind and generous help accorded to me by many people during the course of this process. Ada Sue Selwitz (University of Kentucky), Joan Rachlin (PRIM& R), Paula Knudson (University of Texas Health Science Center at Houston), Eric Meslin (NBAC), Gary Ellis (OPRR), and Michael Walker (University of Illinois) reviewed drafts of this paper in progress and provided many helpful comments; any errors that remain are my own.
A number of people gave graciously of their time and expertise in response to requests, including Stuart Gilman of the Office of Government Ethics, Victor Baird of the Senate Ethics Committee, Michelle Russell-Einhorn and Tom Puglisi of the Office for Protection from Research Risks, Allan Shipp of the American Association of Medical Colleges, Sal Giorgiani of Pfizer Pharmaceuticals, Mark Frankel and Al Teich of the American Association for the Advancement of Science, Erica Heath of Independent Review Consulting, Inc., and Robert Levine of Yale University.
Melanie Marino provided research support and editorial assistance throughout the development of this paper. Debra Kincaid was her usual cheerful self in helping to make room for this project amongst many others.
Attachments
A: Kolata, G. “Doctors Debate Use of Drug to Help Women’s Sex Lives.” New York Times National.
April 25, 1998.
B: Robberson, T. “Plan for Student Database Stirs Opposition in Fairfax.” Washington Post.January 9, 1997.
C1: OPRR Compliance Oversight Log. Letter to Dr. Melody Lin, Compliance Oversight, NIH, received June 18, 1993. Obtained from the OPRR under the Freedom of Information Act.
C2: OPRR Compliance Oversight Log. Regarding the Newark Beth Israel Medical Center, received September 28, 1994. Obtained from the OPRR under the Freedom of Information Act.
C3: OPRR Compliance Oversight Log. Regarding the St. Vincent Hospital Medical Center, Portland, Oregon, received April 13, 1995. Obtained from the OPRR under the Freedom of Information Act.
C4: Ivy, E.J., Lorenc, Z., and Aston, S.J. “Is there a Difference? A Prospective Study Comparing Lateral and Standard SMAS Face Lifts with Extended SMAS and Composite Rhytidectomies.” Plastic and Reconstructive Surgery.December 1996.
C5: “Adolf Coors Foundation Grants $240,000 to UCCS to Study Effects of Mercury Fillings.” University of Colorado at Colorado Springs, Office of Public Relations. November 9, 1995. Obtained from the OPRR under the Freedom of Information Act request by C.K. Gunsalus, 1998.
C6: OPRR Compliance Oversight Log. Received January 29, 1993. Obtained from the OPRR under the Freedom of Information Act request by C.K. Gunsalus, 1998.
C7: Romano, L. “A Night at the Office Became a Nightmare.” Washington Post.January 29, 1997.
C8: Letter from Dr. Gary Ellis to Dr. Curt Tompkins with attachments, April 28, 1997. Letter from Dr. Gary Ellis to Sung M. Lee, July 21, 1997. Obtained from the OPRR under the Freedom of Information Act request by C.K. Gunsalus, 1998.
C9: Kolata, G. “Selling Growth Drug for Children: The Legal and Ethical Questions.” New York Times National.
August 15, 1997.
D: U.S. Office of Government Ethics. www.usoge.gov. Accessed June 11, 1998.
E: U.S. Office of Special Counsel. www.access.gpo.gov/osc. Accessed June 11, 1998.
F: U.S. Nuclear Regulatory Commission. www.nrc.gov. Accessed June 11, 1998.
Notes
1 NBAC, Full Commission Meeting, Arlington, Virginia, May 17, 1997.
2 William Jefferson Clinton, Morgan State University Commencement Address, May 18, 1997.
3 To be fair, research involving human subjects encompasses a much broader range of activities than does research involving ani-mals. Few of the difficult issues raised by behavioral research, violations of confidentiality, or invasion of privacy arise when work-ing with animals, for example, which makes the prospect of more broadly regulatwork-ing research on humans more complex in some ways than devising regulations for the appropriate treatment of animal subjects of research.
4 OIG, DHHS, Institutional Review Boards: A Time for Reform(OEI-01-97-00193), U.S. Government Printing Office, Washington, D.C., June 1998. U.S. Government, Human Radiation Interagency Working Group, Building Public Trust: Actions to Respond to the Report of the Advisory Committee on Human Radiation Experiments,March 1997. Final Report: Advisory Committee on Human Radiation Experiments,U.S. Government Printing Office, Washington, D.C., October 1995.
5 Statement of Robyn Y. Nishimi, Ph.D., Senior Associate, OTA, Hearing Before the Legislation and National Security Subcommittee of the Committee on Government Operations, House of Representatives, September 28, 1994, U.S. Government Printing Office, Washington, D.C., p. 164, referencing statements of Dr. Charles R. McCarthy, retired Director of OPRR. The DHHS OIG and GAO studies reinforce this conclusion.
6 Estimates of the number of IRBs operating in the United States range from around 3,000 to more than 5,000. OPRR oversees 700 IRBs associated with MPAs; about 1,250 associated with Cooperative Project Assurances; and around another 3,000 associated with SPAs. Personal communication from Tom Puglisi, OPRR, to C. K. Gunsalus, September 1998.
7 Report of GAO to the Ranking Minority Member, Committee on Governmental Affairs, U.S. Senate, Scientific Research: Continued Vigilance Critical to Protecting Human Subjects,U. S. Government Printing Office, Washington, D.C., March 1996, p. 17.
8 Rothman, D. J., Strangers at the Bedside: A History of How Law and Bioethics Transformed Medical Decision Making,Basic Books, 1991, pp. 168–189.
9 Beecher, H.K., 1966, “Ethics and Clinical Research,” New England Journal of Medicine274:1354–1360.
10 Report and Recommendations of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research,U.S. Government Printing Office, Washington, D.C., 1978.
11 The Model Federal Policy for the Protection of Human Subjects, 56 Federal Register28002, June 19, 1991.
12 Nishimi testimony, pp. 149–150.
13 45 CFR 46, Revised June 18, 1991 (Effective August 19, 1991) Subpart A— Federal Policy for the Protection of Human Subjects (Basic DHHS Policy for Protection of Human Research Subjects):
“Unless otherwise required by department or agency heads, research activities, in which the only involvement of human subjects will be in one or more of the following categories, are exempt from this policy:
1. Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special education instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods.
2. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) any disclosure of the human subjects’
responses outside the research could reasonably place the subjects at risk of criminal or civil liability, or be damaging to the subjects’ financial standing, employability, or reputation.
3. Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if: (i) the human subjects are elected or appointed public officials or candidates for public office; or (ii) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter.
4. Research, involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available, or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.
5. Research and demonstration projects, which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine: (i) public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures;
or (iv) possible changes in methods or levels of payment for benefits or services under those programs.
6. Taste and food quality evaluation and consumer acceptance studies, (i) if wholesome foods without additives are consumed, or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricul-tural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration, or approved by the Environmental Protection Agency, or the Food Safety and Inspection Service of the U.S. Department of Agriculture.”
14 45 CFR 46.110. Expedited review procedures for certain kinds of research involving no more than minimal risk, and for minor changes in approved research.
15 Report of the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, Protecting Human Subjects,U. S. Government Printing Office, Washington, D.C., 1981.
16 Nishimi testimony, pp. 162–163.
17 21 CFR. 56 155 (b) states: “The records required by this regulation shall be retained for at least 3 years after completion of the research, and the records shall be accessible for inspection and copying by authorized representatives of the Food and Drug Administration at reasonable times and in a reasonable manner.” OPRR’s authority to investigate derives from the Public Health Service Act, as amended by the Health Research Extension Act of 1985, Public Law 99-158, November 20, 1985, Section 491(2) which states: “The Secretary shall establish a process for the prompt and appropriate response to information provided to the director of NIH respecting incidences of violations of the rights of human subjects of research for which funds have been made available under this Act. The process shall include procedures for the receiving of reports of such information from recipients of funds under this Act and taking appropriate action with respect to such violations.”
18 Nishimi testimony, p. 162.
19 Final Report: Advisory Committee on Human Radiation Experiments,Chapter 18, Recommendation 13, Commentary.
20 45 CFR Part 46.103(a).
21 Scientific Research: Continued Vigilance Critical to Protecting Human Subjects,p. 6.
22 There is one MPA institution in Canada (McGill). Statistics on OPRR assurances and oversight in personal communication from OPRR to C.K. Gunsalus, August 10, 1998.
23 Statistics on OPRR caseload from personal communication, Gary R. Ellis to C.K. Gunsalus, April 1998.
24 Scientific Research: Continued Vigilance Critical to Protecting Human Subjects,pp. 19–20. Institutional Review Boards: Their Role in Reviewing Approved Research,p. 13.
25 Scientific Research: Continued Vigilance Critical to Protecting Human Subjects,pp. 8, 19. McCarthy, C.R., Report for NBAC, Reflections on the Organizational Focus of the Office for Protection from Research Risks,1996, p. 10. Institutional Review Boards: Their Role in Reviewing Approved Research,p. 12.
26 Final Report: Advisory Committee on Human Radiation Experiments,Chapter 18, Recommendation 9.
27 Testimony of Dr. Gary B. Ellis, Director, OPRR, Office of Extramural Research, NIH, DHHS, before the Subcommittee on Human Resources, of the Committee on Government Reform and Oversight of the U.S. House of Representatives, June 11, 1998.
28 Scientific Research: Continued Vigilance Critical to Protecting Human Subjects,p. 12.
29 Scientific Research: Continued Vigilance Critical to Protecting Human Subjects,p. 21.
30 Ellis testimony.
31 Final Report: Advisory Committee on Human Radiation Experiments.
32 President Clinton’s Order directs that all departments and agencies of the government “cease immediately sponsoring or con-ducting any experiments involving humans that do not fully comply with the Federal Policy.” Memorandum for the Vice President, the Heads of Executive Departments and Agencies, Subject: Review of Federal Policy for the Protection of Human Subjects, February 17, 1994.
33 OIG, DHHS, Institutional Review Boards: Their Role in Reviewing Approved Research(OEI-01-97-00190);Institutional Review Boards:
Promising Approaches(OEI-01-98-0091); Institutional Review Boards: The Emergence of Independent Boards(OEI-01-97-00192);
Institutional Review Boards: A Time for Reform(OEI-01-97-00193), U.S. Government Printing Office, Washington, D.C., June 1998.
Scientific Research: Continued Vigilance Critical to Protecting Human Subjects.
34 Nishimi testimony, p. 157, footnote 3.
35 Final Report: Advisory Committee on Human Radiation Experiments,Chapter 17, Finding 22.
36 Testimony of Sarah F. Jagger, Director, Health Financing and Public Health Issues, Health Education and Human Services Division, U.S. GAO, before the Committee on Governmental Affairs, U.S. Senate, March 12, 1996.
37 Ibid.
38 Scientific Research: Continued Vigilance Critical to Protecting Human Subjects,p. 20.
39 Institutional Review Boards: A Time for Reform, p. ii.
40 Ibid.
41 Ellis testimony.
42 45 CFR Part 46.103(b) requires that each institution provide certain specific information to OPRR.
43 Supplemental Submission by Sarah F. Jagger, Director, Health Financing and Public Health Issues, U.S. GAO, contained in letter to the Honorable Ted Stevens, Chairman, Committee on Governmental Affairs, U.S. Senate, March 20, 1996, in the Proceedings of the Hearing Before the Committee on Governmental Affairs, U.S. Senate, U.S. Government Printing Office, Washington, D.C., March 12, 1996, p. 399.
44 Nishimi testimony, 1994.
45 Letter from Dr. Gary B. Ellis, Director, OPRR to James F. Childress, Ph.D., Chairman, Human Subjects Subcommittee, NBAC, April 10, 1997.
46 Kolata, G., “Doctors Debate Use of Drugs to Help Women’s Sex Lives,” New York Times,Sec. A, April 25, 1998.
47 Robberson, T., “Plan for Student Database Stirs Opposition in Fairfax,” Washington Post,Sec. A, January 9, 1997.
48 OPRR Compliance Oversight Log, Letter to Dr. Melody Lin, Compliance Oversight, NIH, received June 18, 1993. Obtained from the OPRR under the Freedom of Information Act request by C.K. Gunsalus, 1998.
49 OPRR Compliance Oversight Log, Regarding the Newark Beth Israel Medical Center, received September 28, 1994. Obtained from the OPRR under the Freedom of Information Act request by C.K. Gunsalus, 1998.
50 OPRR Compliance Oversight Log, Regarding the St. Vincent Hospital Medical Center, Portland, Oregon, received April 13, 1995. Obtained from the OPRR under the Freedom of Information Act request by C.K. Gunsalus, 1998.
51 Ivy, E.J., Lorenc, Z., and Aston, S.J., “Is There a Difference? A Prospective Study Comparing Lateral and Standard SMAS Face Lifts with Extended SMAS and Composite Rhytidectomies,” Plastic and Reconstructive Surgery,December 1996.
52 “Adolf Coors Foundation Grants $240,000 to UCCS to Study Effects of Mercury Fillings,” University of Colorado at Colorado Springs, Office of Public Relations, November 9, 1995. Obtained from the OPRR under the Freedom of Information Act request by C.K. Gunsalus, 1998.
53 OPRR Compliance Oversight Log, received January 29, 1993. Obtained from the OPRR under the Freedom of Information Act request by C.K. Gunsalus, 1998.
54 Romano, L., “A Night at the Office Became a Nightmare,” Washington Post,January 29, 1997.
55 The National Human Genome Research Institute, Final Report of the Task Force on Genetic Testing: Promoting Safe and Effective Genetic Testing in the United States,September 1997.
56 Letter from Dr. Gary Ellis to Dr. Curt Tompkins with attachments, April 28, 1997. Letter from Dr. Gary Ellis to Sung M. Lee, July 21, 1997. Obtained from the OPRR under the Freedom of Information Act request by C.K. Gunsalus, 1998.
57 Kolata, G., “Selling Growth Drug for Children: The Legal and Ethical Questions,” New York Times National,August 15, 1997.
58 45 CFR 46.102: “Human subject” means a living individual about whom an investigator, (whether professional or student) conducting research obtains (a) data through intervention or interaction with the individual, or (b) identifiable private information.
“Intervention” includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject’s environment that are performed for research purposes.
“Interaction” includes communication or interpersonal contact between investigator and subject.
“Private information” includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information), in order for obtaining the information to constitute research involving human subjects.”
59 Levine, R.J., ”The Boundaries Between Biomedical or Behavioral Research and the Accepted and Routine Practice of Medicine,”
July 14, 1975; London, P. and Klerman, G., “Boundaries Between Research and Therapy, Especially in Mental Health;” papers by David Sabiston, M.D. and John Robertson, J.D., 1975. Commissioned Papers for the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research,U.S. Government Printing Office, Washington, D.C., 1978.
60 Federal Register,Vol. 46, No. 18, January 26, 1981, pp. 8372–8373.
61 Ibid. At the same time, other changes were made in the Belmont Report’sproposed definition. In response to other concerns about the breadth of the proposed definition of research, DHHS inserted the term “living” into the definition of human subject to clarify that historical and biographical research were not covered. The final regulation also used “private” to modify “information” to make it clear that the “regulations are applicable only to research which involves intervention or interaction with an individual or identifiable private information.” Private information was clearly defined, with the following concluding comment: “It is expected that this definition exempts from the regulations nearly all library-based political, literary and historical research, as well as purely observational research in most public contexts, such as behavior on the street and in crowds.”
62 Expedited reviews cost $200 each. Independent Review Consulting, Inc., Institutional Review Board, Fee Schedule, 1997.
63 Final Report: Advisory Committee on Human Radiation Experiments,Commentary following Finding 22, Chapter 17, 1995.
64 Public Health Service Act, as amended by the Health Research Extension Act of 1985, Public Law 99-158, November 20, 1995.