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Placebo Orthodoxy in Clinical Research II: Ethical, Legal, and Regulatory Myths

Published online by Cambridge University Press:  01 January 2021

Benjamin Freedman ,
Kathleen Cranley Glass  and
Charles Weijer
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Extract

Placebo-controlled trials are held by many, including regulators at agencies like the United States Food and Drug Administration (FDA), to be the gold standard in the assessment of new medical interventions. Yet the use of placebo controls in clinical trials has been the focus of considerable controversy. In this two-part article, we challenge a number of common beliefs concerning the value of placebo controls. Part I critiques statistical and other scientific justifications for the use of placebo controls in clinical research. The continued use of placebo controls in clinical trials on diseases for which accepted treatment exists raises equally important ethical, legal, and regulatory issues for which various justifications have been given. Defense of this practice relies on normative as well as empirical myths.

In their attack on the prevailing use of placebo controls, Kenneth Rothman and Karin Michels emphasize that this practice stands in violation of the World Medical Association's guidelines on the ethics of human experimentation, most commonly known as the Helsinki Declaration.

Type
Article
Information
Journal of Law, Medicine & Ethics , Volume 24 , Issue 3 , Fall 1996 , pp. 252 - 259
Copyright
Copyright © American Society of Law, Medicine and Ethics 1996

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References

Rothman, K.J. Michels, K.B., “The Continuing Unethical Use of Placebo Controls,” N. Engl. J. Med., 331 (1994): 394–98.CrossRefGoogle Scholar
Id.Google Scholar
Declaration of Helsinki (Helsinki: 18th World Medical Assembly, 1964; rev., Tokyo: 29th World Medical Assembly, 1975; rev., Venice, 35th World Medical Assembly, 1983; rev., Hong Kong: 41st World Medical Assembly, 1989; rev., Somerset West, South Africa, 48th General Assembly, 1996): At II.3. The 1996 revision added the following sentence to II.3. “This does not exclude the use of inert placebo in studies where no proven diagnostic or therapeutic method exists.”Google Scholar
Lasagna, L., “The Helsinki Declaration: Timeless Guide or Irrelevant Anachronism?,” Journal of Clinical Psychopharmacology, 2(1995): 96–98.CrossRefGoogle Scholar
Council for International Organizations of Medical Sciences, International Ethical Guidelines for Biomedical Research Involving Human Subjects (Geneva: World Health Organization, 1993): At 52.Google Scholar
Freedman, B., “Placebo Controlled Trials and the Logic of Clinical Purpose,” IRB: A Review of Human Subjects Research, 1, no. 6 (1990): 1–6.Google Scholar
Medical Research Council of Canada, Guidelines on Research Involving Human Subjects (Ottawa: Minister of Supply & Services, 1987).Google Scholar
American Medical Association, “Ethical Guidelines for Clinical Investigation, 1966,” in Reich, W.T., ed., Encyclopedia of Bioethics (New York: Free Press, vols. 3, 4, 1978): 1773-74.Google Scholar
Rickels, K., “Use of Placebo in Clinical Trials?,” Psychopharmacology Bulletin, 22, no. 1 (1986): 19–24; and Klerman, G.L., “Scientific and Ethical Considerations in the Use of Placebo Controls in Clinical Trials in Psychopharmacology,” Psychopharmacology Bulletin, 22, no. 1 (1986): 25–29.Google Scholar
Pohl, R. Baron, R., letter; comment; discussion, “The Use of Placebo Controls,” N. Engl. J. Med., 332 (1995): 61–62.Google Scholar
Levine, R., oral comment, Public Responsibility in Medicine & Research Conference, Nov. 1, 1994.Google Scholar
Lasagna, , supra note 4.Google Scholar
Temple, R., “Government Viewpoint of Clinical Trials,” Drug Information Journal, Jan./Feb. (1982): 10–17.CrossRefGoogle Scholar
Levine, R.J., “The Use of Placebos in Randomized Clinical Trials,” IRB: A Review of Human Subjects Research, 7, no. 2 (1985): 1–4.CrossRefGoogle Scholar
Clery, D., “Use of Placebo Controls in Clinical Trials Disputed,” Science, 267 (1995): 2–26.Google Scholar
Freedman, B., “Ethics and Placebo-Controlled Thrombolytic Trials: The Future,” Coronary Artery Disease, 2 (1991): 849–52; Geraci, E., “Enrolment in Trials of Thrombolysis,” Lancet, 336 (1990): 1069–70; and Brody, B.A., Ethical Issues in Drug Testing, Approval, and Pricing (New York: Oxford University Press, 1995>): Ch. 2.Google Scholar
Curson, D.A.et al., “Does Short Term Placebo Treatment of Chronic Schizophrenia Produce Long Term Harm?,” British Medical Journal (Clinical Research Edition), 293 (1986): 726–28.CrossRefGoogle Scholar
Id.Google Scholar
Id.Google Scholar
National Institutes of Health, Office for Protection from Research Risks, Protecting Human Subjects: Institutional Review Board Handbook (Washington, D.C.: U.S. Government Printing Office, 1993): At 4–23.Google Scholar
Picard, E., Legal Liability of Doctors and Hospitals in Canada (Toronto: Carswell, 2nd ed., 1994); and Prosser, W. Keaton, W., The Law of Torts (St. Paul: West, 5th ed., 1984).Google Scholar
Halushka v. University of Saskatchewan, (1965) 93 D.L.R. 2d 436; and Kus v. Sherman Hospital, 644 N.E.2d 1214 (Ill. App. 1995).Google Scholar
Mason, J.K. McCall-Smith, R.A., Law & Medical Ethics (London: Butterworth, 2nd ed., 1987); Giesen, D., International Medical Malpractice Law (Dordrecht: Nijhoff, 1988): At § 48, para. 1200; and Baudouin, J.-L., “L'Experimentation sur les Humains: Un Conflit de Valeurs,” McGill Law Journal, 26 (1986): 809–46.Google Scholar
Simmons, L., “Problems in Deceptive Medical Procedures: An Ethical and Legal Analysis of the Administration of Placebos,” Journal of Medical Ethics, 4 (1978): 172–81; Kapp, M.B., “Placebo Therapy & the Law: Prescribe with Care,” American Journal of Law & Medicine, 8 (1983): 371–405; Mason, McCall-Smith, , supra note 23; Giesen, , supra note 23; and Baudouin, , supra note 23.CrossRefGoogle Scholar
Mason, Smith, McCall, supra note 23; and Giesen, , supra note 23,Google Scholar
Halushka, 93 D.L.R. 2d at 436; and Sherman Hospital, 644 N.E.2d at 1214.Google Scholar
Prosser, Keaton, , supra note 21, at § 68.Google Scholar
Kennedy, I. Grubb, I., Medical Law: Text and Materials (London: Butterworth, 1989): At 452; and Perry, C.B., “Conflicts of Interest and the Physician's Duty to Inform,” American Journal of Medicine, 96 (1994): 375–80.Google Scholar
Giesen, , supra note 23, § 46, para. 1200.Google Scholar
Prosser, Keaton, , supra note 21, at §§ 106–07; and Perry, , supra note 28.Google Scholar
Mason, McCall-Smith, , supra note 23.Google Scholar
Giesen, , supra note 23.Google Scholar
Clery, , supra note 15.Google Scholar
45 C.F.R. § 46.111(a)(2) (1991).Google Scholar
Appelbaum, P.S. Litz, C.W. Meisel, A., Informed Consent: Legal Theory and Clinical Practice (New York: Oxford University Press, 1987): At 60–62.Google Scholar
Faden, R. Beauchamp, T., A History and Theory of Informed Consent (New York: Oxford University Press, 1986): At 274, 287–94.Google Scholar
Lidz, C.W.et al., Informed Consent: A Study of Decisionmaking in Psychiatry (New York: Guilford Press, 1984): At 235.Google Scholar
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,” OPRR Reports, Apr. 18 (1979): 1–8; and Ratzan, R., “Being Old Makes You Different: The Ethics of Research with Elderly Subjects,” Hastings Center Report, 10, no. 5 (1980): 32–46.Google Scholar
Picard, , supra note 21, at 61, 119.Google Scholar
Baker, C.D., Tort (London: Sweet & Maxwell, 2nd ed., 1976): At 52; and Kennedy, Grubb, , supra note 28, at 279.Google Scholar
Prosser, Keaton, , supra note 21, at § 68.Google Scholar
Kapp, , supra note 24.Google Scholar
Food, Drug, and Cosmetic Act of 1938, 52 Stat. 1040, 21 U.S.C. §§ 301 et seq. at § 505(d) (as amended 1962).Google Scholar
21 C.F.R. § 314.26(b)(2) (1991).Google Scholar
“Investigation of Drugs in Humans; Availability of Guidelines,” 44 Fed. Reg. 20,796 (1979).Google Scholar
“Guidelines for the Conduct of Clinical Trials: FDA Guidelines for Psychotropic Drugs,” Psychopharmacology Bulletin, 1, no. 4 (1974): 70–91; and “FDA Guidelines for the Clinical Evaluation of Psychotropic Drugs—Antidepressant and Antianxiety Drugs,” Psychopharmacology Bulletin, 14, no. 2 (1978): 45–63.Google Scholar
“FDA Guidelines,” supra note 46.Google Scholar
“Guidelines for the Conduct of Clinical Trials,” supra note 46.Google Scholar
“Investigation of Drugs in Humans,” supra note 45.Google Scholar
“Guidelines for the Conduct of Clinical Trials,” supra note 46.Google Scholar
21 C.F.R. § 314.26(b)(2)(iv) (1991).Google Scholar
Ballin, J.C., “Who Makes the Therapeutic Decisions?,” JAMA, 242 (1979): 2875.Google Scholar
Hutt, P.B. Merrill, R.A., Food and Drug Law (Westbury: Foundation Press: 1991): At 528n.Google Scholar
44 Fed. Reg. 51,512 (Aug. 31, 1979).Google Scholar