1 The abbreviations HSoR will be used for “human subjects of research” (focus on the human beings who are research subjects) and HSR for “human subjects research” (focus on the activities of research involving human subjects).
2 At its May 17, 1997, meeting, the NBAC voted unanimously for this statement: “No person in the United States should be enrolled in research without the twin protections of informed consent by an authorized person and independent review of the risks and benefits of the research.”
3 McDermott, W., Opening Comments. The Changing Mores of Biomedical Research. A Colloquium on Ethical Dilemmas from Medical Advances, Ann Int Med67 (Supp.7, No. 3-Part II):39–42, 1967. “… the hard core of our moral dilemmas will not yield to the approaches of ‘Declarations’ (i.e., Helsinki) or ‘Regulations’ (i.e., the FDA’s 1967 human subjects regulations); for as things stand today such statements must completely ignore the fact that society, too, has rights in human experimentation” (p. 42).
4 Jonas, H., Philosophical Reflections on Human Experimentation, Daedalus98:245, 1969.
5 Ibid.
6 Dommel, F.W., Alexander, D., The Convention on Human Rights and Biomedicine of the Council of Europe, Kennedy Institute of Ethics Journal 7(3):259–276, 1997.
7 Robertson, J.A., The Scientist’s Right to Research: A Constitutional Analysis, Southern California Law Review51:1203–1279, 1977.
8 This term was coined by Paul Appelbaum, and the widespread power of its influence was ascertained in the Subject Interview Study of the Advisory Committee on Human Radiation Experiments, in which 1,882 patients receiving medical care in 16 outpatient facilities of private and public hospitals were surveyed.
9 “Drug manufacturers offer clinician-investigators financial inducements to enter patients into studies, typically $2000 to $5000 per patient. By contrast when a patient is entered into a NIH-sponsored study, the clinician-investigator receives capitation of approximately $1000 per patient to cover the costs of the physician-investigator’s time, the data manager’s salary, and additional expenses (secretarial, photocopying, etc.) incurred in participating in the study.” Shimm, D.S., Spece, R.G., DiGregario, M.B., Conflicts of Interest in Relationships Between Physicians and the Pharmaceutical Industry, in Spece, Shimm, and Buchanan (eds.), Conflicts of Interest in Clinical Practice and Research,New York: Oxford University Press, 1996, 323.
10 These problems are described in three recent reports: U.S. General Accounting Office, Scientific Research, Continued Vigilance Critical to Protecting Human Subjects,1996. GAO/EHS-96-72; Advisory Committee on Human Radiation Experiments, Research Ethics and the Medical Profession, JAMA276:403–409, 1996; and Moreno, J.D., Caplan, A.L., Wolpe, P.R., and the Members of the Project on Informed Consent, Human Research Ethics Group, “Updating Protections for Human Subjects Involved in Research, JAMA, 1998 280(22):1951–1958.
11 Nishimi, R.Y., Testimony for the House Committee on Government Operations, The Federal Role in Protecting Human Research Subjects,103rd Congress, 2nd Session, September 28, 1994: 158–160.
12 The occasion for the interviews was to prepare papers for presentation at the 125th anniversary of the Norwegian Academy of Sciences and for subsequent publication; i.e., Fletcher J.C., The Evolution of the Ethics of Informed Consent. In Research Ethics, Berg K., TranØy K.E. (eds.), Alan R. Liss, Inc., New York, 1983, 187–228; Boverman M., Fletcher J.C., The Evolution of the Role of an Applied Bioethicist in a Research Hospital. In Research Ethics,Berg K., TranØy K.E. (eds.), Alan R. Liss, Inc., New York, 1983, 131–158.
13 Erde, E.L., Conflicts of Interest: A Conceptual Overview, in Spece, Shimm, and Buchanan (eds.), Conflicts of Interest in Clinical Practice and Research,New York: Oxford University Press, 1996, 13.
14 Adapted from Erde, see note 13, p. 33.
15 The impact on the NIH of a case involving Dr. Chester Southam’s research at the Jewish Hospital for Chronic Diseases in Brooklyn, New York, had, in the author’s view, the most telling and persuasive influence leading to change. Dr. Southam’s license to practice medicine in New York was suspended for one year, and then he was placed on probation. For accounts of this case in historical context, see Langer E., Human Experimentations: New York Affirms Patients’ Rights. Science151:663–665, 1966; Fletcher J.C., The Evolution of the Ethics of Informed Consent. In Research Ethics,Berg K., TranØy K.E. (eds.), Alan R. Liss, Inc., New York, 1983, 187–228.
16 The term “institutional blindness” refers to the end-state of excessive loyalty to the welfare of an institution and one’s role within it. The stronger and more uncritical the loyalty to an institution and role, the more impaired are independence of observation, judgment, and action with respect to prevention or moderation of conflicts of interest. Some professions are much better prepared and trained than others to detect and prevent conflicts of interests. Physicians and biomedical researchers do not receive the same degree of education and training about such issues as attorneys and behavioral scientists. For example, “because physicians are not trained to look for conflicts of interest, they often find themselves enmeshed in them without recognizing the problem.” Spece R.G., Shimm D.S., Buchanan A.E., Conflicts of Interest in Clinical Practice and Research,New York: Oxford University Press, 1996, preface.
17 See the ACHRE report cited in note 10 for description of the norms of the wider research community, at 404–405.
18 Jones, J.H., Bad Blood,2nd ed., New York: Free Press, 1993, 191–196.
19 W hat was the involvement of the NIH, if any, in the Tuskegee study? The pre-1950s NIH was involved in analyzing spinal fluid and autopsy tissues from the subjects. Jones, see note 18, 124, 136. It is likely that no NIH physician-investigator or official was directly involved in the study itself or in its defense against Buxton’s challenges. (James Jones, personal communication, November 10, 1997). Dr. John Heller was a junior officer in the PHS Division of Venereal Diseases who was actively involved in the study.
Following his retirement as President of Sloan Kettering Hospital, he was in residence at the National Library of Medicine. In an interview with James Jones in 1977, Dr. Heller described his experience in meetings led by Dr. Raymond Vonderlehr, with the medical societies and boards of health of four Alabama counties in 1933: “...no one questioned whether the experiment was ethical;
no one even came close to doing so. ‘I don’t recall any philosophical discussions at all,’ declared Dr. Heller. W hat emerged from his comments was the image of a profession whose members had closed ranks behind a study they were told had real merit. The experiment obviously had struck their sense of scientific curiosity, and it did not occur to anyone to suggest that it should not be conducted.” Jones, see note 18, p. 144.
20 Although Peter Buxtun, a PHS employee, challenged the ethics of the Tuskegee study from within DHEW as early as November, 1966, PHS officials did little to heed his criticism. The Tuskegee story was broken by the Associated Press on July 25, 1972, in a report by Jean Heller. Cf. Jones, J.H., Bad Blood,2nd ed., New York: Free Press, 1993, 188–205. The author conducted numerous interviews and 10 focus groups with scientists and clinical investigators at the NIH from 1966 to 1968 in preparation for a Ph.D.
dissertation on the ethics of medical research. No one brought up the Tuskegee study. The author was unaware of it until the news story.
21 Beecher, H.K., Ethics and Clinical Research, N Engl J Med74:1354–60, 1966. The occasion for the interviews was to prepare papers for presentation at the 125th anniversary of the Norwegian Academy of Sciences and for subsequent publication, i.e., Fletcher, J.C., The Evolution of the Ethics of Informed Consent. In Research Ethics,Berg K., Tranfy K.E. (eds.), Alan R. Liss, Inc., New York, 1983.
22 In an earlier interview, Charles R. McCarthy, former director of the OPRR, commented: “It seems to me that… for the most part government was passive, a few farsighted individuals such as Shannon and Stewart in the Executive Branch, and Ted Kennedy in the Congress, initiated procedures that have matured into a remarkable system. These few individuals were both learners and teach-ers, but the government as a whole was at best a sleepy, distracted pupil, awakened periodically by a scandal, but otherwise content to ‘get by’ without having to recite” (personal communication, May 14, 1993).
23 Surgeon General, PHS, DHEW, Investigations Involving Human Subjects, Including Clinical Research: Requirements for Review to Ensure the Rights and Welfare of Individuals, PPO 129, Revised Policy, July 1, 1966.
24 DHEW, 45 Protection of Human Subjects 46, Federal Register,Vol. 39, No. 105, Part II, 46.1(a) (b), 1974.
25 Federal Register, Vol. 46, No. 16, January 26, 1981.
26 45 CFR 46.101(a), 56, Federal Register28003, June 18, 1991.
27 The National Institutes of Health Revitalization Act of 1993, Public Law 103-43, June 10, 1993, Section 492A.
28 This story is well told in Faden, R.R., and Beauchamp, T. L., A History and Theory of Informed Consent,New York: Oxford University Press, 1986, 206–215.
29 Ibid., 208.
30. A fuller history of HSR protection and the evolution of prior group review in the NIH intramural program is found in Boverman M., Fletcher, J.C., the Evolution of the Role of an Applied Bioethicist in a Research Hospital. In Research Ethics,Berg K., TranØy K.E.
(eds.), Alan R. Liss, Inc., New York 1983, 131–158.
31 NIH. 1958. Group Consideration of Clinical Research Procedures Deviating from Accepted Medical Practice or Involving Unusual Hazard. (Memorandum, approved by the Director, NIH, 1953); Sessions, S.M., W hat Hospitals Should Know About Investigational Drugs— Guiding Principles in Medical Research Involving Humans, Hospitals32:44–64.
32 Lipsett, M.B., Fletcher, J.C., Secundy, M., Research Review at NIH, Hastings Center Report9:18–27, 1979.
33 These programs were called “Subpanels” to overcome the difficulty of having each chartered under the Federal Advisory Committee Act, because each had one or more outside members.
34 The members of the drafting committee were Charles Lowe, Jane Fullerton, and Charles McCarthy (Charles McCarthy, personal communication, November 11, 1997).
35 See note 30.
36 McCarthy, C.R. (personal communication, November 11, 1997).
37 U.S. General Accounting Office, Scientific Research, Continued Vigilance Critical to Protecting Human Subjects,1996.
GAO/EHS-96-72, 20.
38 Project on Informed Consent of the Human Research Ethics Group. Updating Protections for Human Research Subjects, submit-ted for publication, 1997.
39 Letter, Harold Varmus to Sarah F. Jaggar, February 15, 1996 (see GAO report, 33).
40 Note 37, at 25.
41 Research Administration, OPRR Location Questioned by Rep. Shays at Hearing, The Blue Sheet40(20):2, May 14, 1997.
42 See Attachment 1 for a chart showing sign-off points within the NIH bureaucracy. Proposals for changing federal regulations that arise from NBAC’s deliberation on HSR, e.g., regarding studies involving cognitively impaired subjects, would in the near future necessarily be introduced through OPRR and be subject to the same vetting and sign-off process depicted in Attachment 1.
Many of the entities in Attachment 1 have strong vested interests in the subject matter.
43 The NIH Record,June 18, 1996, 4.
44 U.S. Office of Government Ethics, Second Biennial Report to Congress,March, 1992; Walker, J.S., A Short History of Nuclear Regulation,January 1993 (NUREG/BR-1075).
45 Letter, Gary B. Ellis to James F. Childress, April 10, 1997.
46 The preference for agencies headed by a single administrator over a commission form of agency has been generally favored for some time by scholars in the administration sciences and based on research sponsored by the Committee on Government Operations. See 95th Congress, 1st Session. Study on Federal Regulation. Vol. 1. The Regulatory appointment Process, January, 1977.
47 Ellis, Gary B. (personal communication, October 18, 1997).
48 Katz, J., Do We Need Another Advisory Commission on Human Experimentation? Hastings Center Report25(1):29–31, 1995.
49 U.S. Department of Health, Education and Welfare, Final Report of the Tuskegee Syphilis Study Ad Hoc Advisory Panel, 1973, U.S. GPO: 1973-747-022/5334, Region No. 4.
50 See Nishimi testimony, note 11.