Hostname: page-component-78c5997874-4rdpn Total loading time: 0 Render date: 2024-11-02T23:52:22.477Z Has data issue: false hasContentIssue false

The Physician/Investigator's Obligation to Patients Participating in Research: The Case of Placebo Controlled Trials

Published online by Cambridge University Press:  01 January 2021

Extract

Some authors argue that the ethics of medical care and the ethics of research differ, and that it is a mistake to conflate the two. They propose “that medical research and medical treatment are two distinct forms of activities, governed by different ethical principles.” This raises the question of whether physicians who are also clinical investigators may separate their role as physician from that of researcher when they are involved in clinical trials, thereby avoiding the obligations required in the physician-patient relationship. Miller and Brody suggest that medical training is to blame for what they believe is the physicians’ tendency to confound the obligations of research and practice. “Physician-investigators, after all, went to medical school” they explain. They believe that considering research with patients outside the ethical framework of the physician-patient relationship may be “difficult and threatening” to physicians who have “psychological needs” to consider the ethical obligations flowing from their relationship with their patients.

Type
Article
Copyright
Copyright © American Society of Law, Medicine and Ethics 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Miller, F. G. Silverman, H. J., “The Ethical Relevance of the Standard of Care in the Design of Clinical Trials,” American Journal of Respiratory Critical Care Medicine 169, no. 5 (2004): 562–64; Miller, F. G. Brody, H., “The Clinician-investigator: Unavoidable but Manageable Tension,” Kennedy Institute Ethics Journal 13, no. 4 (2003): 329–46; Miller, F. G. Brody, H., “What Makes Placebo-controlled Trials Unethical?” American Journal of Bioethics 2, no. 2 (2002): 3–9.Google Scholar
Miller, F. G. Brody, H., “A Critique of Clinical Equipoise,” Hastings Center Report 33, no. 3 (2003): 1928 at 20, 24–25.CrossRefGoogle Scholar
Id. at 24.Google Scholar
Id. at 26–27.Google Scholar
Temple, R., “Government Viewpoint of Clinical Trials,” Drug Information Journal (1982): 10–17; Temple, R., “Problems in Interpreting Active Control Equivalence Trials,” Accountability 4 (1996): 267–75; Temple, R. Ellenberg, S. S., “Placebo-Controlled Trials and Active-Controlled Trials in the Evaluation of New Treatments,” Annals of Internal Medicine 133 (2001): 455–63.CrossRefGoogle Scholar
Glass, K. C. Waring, D., “Effective Trial Design Need Not Conflict with Good Patient Care,” American Journal of Bioethics 2, no. 2 (2002): 2526; Fergusson, D. Glass, K. C. Waring, D. Shapiro, S., “Turning a Blind Eye: The Success of Blinding Reported in a Random Sample of Randomized, Placebo-Controlled Trials,” British Medical Journal 328, no.7437 (2004): 432–40.Google Scholar
Id.; see also Benjamin, F., “Placebo-Controlled Trials and the Logic of Clinical Purpose,” IRB: A Review of Human Subjects Research 12 (1990): 16; Rothman, K. J. Michels, K. B., “The Continuing Unethical Use of Placebo Controls,” N. Engl. J. Med., 331 (1994): 394–98; Freedman, B. Glass, K. C. Weijer, C., “Placebo Orthodoxy in Clinical Research II: Ethical, Legal, and Regulatory Myths,” Journal of Law, Medicine & Ethics 24 (1996): 252–59, at 256; Glass, K. C. Waring, D., “Effective Trial Design Need Not Conflict With Good Patient Care,” American Journal of Bioethics 2 (2002): 25–26, at 26; Miller, F. G. Brody, H., “What Makes Placebo-Controlled Trials Unethical?” American Journal of Bioethics 2 (2002): 3–9, at 2–5; Emanuel, E. Miller, F. G., “The Ethics of Placebo-Controlled Trials: A Middle Ground,” N. Engl. J. Med., 345 (2001): 915–19; National Placebo Initiative, Health Canada & Canadian Institute of Health Research, Draft Report of the National Placebo Working Committee (October, 2004).Google Scholar
See Freedman, B. Glass, K. C. Weijer, C., supra note 7; Glass, K. C. Waring, D., supra note 6; Waring, D. Glass, K. C., “Legal Liability for Harm to Research Subjects in Placebo Controlled Trials” in New Directions in Biomedical Research: Regulation, Conflict of Interest and Liability, Lemmens, T. Waring, D. (eds) (Toronto: University of Toronto Press, in press).Google Scholar
We are aware of no such judgments. However, a Complaint and Demand for Jury Trial was filed in the Orange County, North Carolina Superior Court by a patient/plaintiff randomized to the placebo arm of a clinical trial testing a new psoriasis treatment. The plaintiff claimed damages for the development of debilitating psoriatic arthritis resulting from participation in the trial. The trial protocol required discontinuation of his current medication and withholding of the experimental drug. William Hamlet v. Genentech, Inc; Xoma, Ltd.; Western Institutional Review Board, Inc.; Parexel International, LLC; Mark. S. Fradin, M.D.; and Chapel Hill Dermatology, P.A., Superior Court of Justice, Superior Court division 03 CVS 1161, Orange County, North Carolina (July, 2003). Five of the six defendants have settled. Personal communication, Alan Milstein, attorney for the plaintiff, June 8, 2005.Google Scholar
Mello, M. M. Studdart, D. M. Brennan, T., “The Rise of Litigation in Human Subjects Research” Annals of Internal Medicine 139 (2003): 4045.Google Scholar
Bok, , Universities in the Marketplace (NJ: Princeton, 2003): At 144–50; Glass, K. C. Lemmens, T. M., “Conflict of Interest and Commercialization of Biomedical Research: What is the Role of Research Ethics Review?” in Caulfield, T. Williams-Jones, B., eds., The Commercialization of Genetic Research: Ethical, Legal and Policy Issues (New York: Plenum, 1999): 79–99 at 86–88.CrossRefGoogle Scholar
Dobbs, D. B., The Law of Torts, vol. 1 (St. Paul, MN: West Publishing Co., 2001): At 269; Robertson, G., “Negligence and Malpractice,” in Downie, J. Caufield, T. Flood, C., eds., Canadian Health Law and Policy, 2d. ed. (Markham, Ontario: Butterworths Canada Ltd., 2002): 91–109, at 91; Jones, M. A., Medical Negligence (London: Sweet and Maxwell, 1991): At 20; Giesen, D., International Medical Malpractice Law: A Comparative Law Study of Civil Liability Arising From Medical Care (Dordrecht: Nijhoff, 1988): At 25, 30–31; King, J. H. Jr., The Law of Medical Malpractice in a Nutshell, 2d. ed. (St. Paul, MN: West Publishing Co., 1986): At 9.Google Scholar
Picard, E. I. Robertson, G. B., Legal Liability of Doctors and Hospitals in Canada, 3d. ed. (Toronto: Carswell, 1996); Restatement (Second) of Torts § 282 (1965).Google Scholar
Miller, Brody, , supra note 1, at 3–5; see also Emanuel, Miller, , supra note 7, at 915–19.Google Scholar
Picard, Robertson, , supra note 13, at 1–8.Google Scholar
American Medical Association Council on Ethical and Judicial Affairs, Code of Medical Ethics, at <www.ama-assn.org/ama/pub/category/2498.html> (last visited June 22, 2005).+(last+visited+June+22,+2005).>Google Scholar
Id. at Article E-2.07, Clinical Investigation.Google Scholar
Declaration of Helsinki (Helsinki: World Medical Association, 52nd General Assembly, 2000).Google Scholar
Id. at Articles 3,5,10, and 15; see also Medical Research Council of Canada, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (Ottawa: Public Works and Government Services Canada, 1998): At i.4.Google Scholar
Hall v. Hilburn, 466 So. 2d 856, 858 (MS 1985).Google Scholar
Crits v. Sylvester, 1 D.L.R. (2d.) 502, 508, (1956), aff'd [1956] S.C.R. 991.Google Scholar
Picard, Robertson, , supra note 13, at 186.Google Scholar
Miller, Brody, , supra note 1, at 3–5; see also Emanuel, Miller, , supra note 7, at 915–19.Google Scholar
Giesen, , supra note 12, at 50.Google Scholar
Id. at 193–195.Google Scholar
Giesen, D., “Civil Liability of Physicians for New Methods of Treatment and Experimentation: A Comparative Examination,” Medical Law Review 3 (1995): 2252, at 30.CrossRefGoogle Scholar
Morreim, E. H., “Medical Malpractice Litigation and Malpractice Tort Doctrines: Courts on a Learning Curve,” Houston Journal of Health Law and Policy 4 (2003): 192, at 92. Professor Morreim published a further iteration of these arguments in “Litigation in Clinical Research: Malpractice Doctrines Versus Research Realities,” Journal of Law, Medicine & Ethics 32 no. 3 (2004): 474–484.Google Scholar
Id. at 41.Google Scholar
Id. at 52.Google Scholar
Professor Morreim does allow in her discussion of fiduciary duties that there could be a relationship in a “pure research setting, in which the patient's only relationship with an investigator is as a research subject.” Id. at 50–51. We believe that this could only be the case for “patients” who are not seeking or needing care, e.g., recruitment of persons to donate blood for a study unrelated to their own care. This situation is easily distinguishable from one in which a patient seeks advice and care from a physician who is an investigator and is recruited into a trial for a therapy addressing the patient's needs, including those with a placebo control.Google Scholar
Freedman, B., “Equipoise and the Ethics of Clinical Research,” N. Engl. J. Med. 317 (1987): 141–45.CrossRefGoogle Scholar
Rodwin, M. A., “Strains in the Fiduciary Metaphor: Divided Physician Loyalties and Obligations in a Changing Health Care System,” American Journal of Law and Medicine 21 (1995): 241–57, at 243.CrossRefGoogle Scholar
Hall, M. A. Bobinski, M. A. Orentlicher, D., Health Care Law and Ethics, 6th ed. (New York: Aspen Publishers, 2003): At 163–64; Lockett v. Goodill, 430 P.2d 589, 591 (WA, 1967); Moore v. Regents of the University of California, 793 P.2d 479 (1990); McInerney v. MacDonald (1992) 93 D.L.R. (4th) 415; Norberg v. Wynrib, (1992) 2 S.C.R. 227; Rodriguez v. British Columbia (Attorney General), (1993) 3 S.C.R. 519.Google Scholar
Hall, Bobinski, Orentlicher, , supra, at 163–64.Google Scholar
Prosser, W. L. Keeton, P., The Law of Torts, 5th ed. (St. Paul. MN: West Publishing Co, 1984).Google Scholar
Mehlman, M. J., “Fiduciary Contracting Limitations on Bargaining Between Patients and Health Care Providers,” University of Pittsburgh Law Review 51 (1989–1990): 365417, at 390.Google Scholar
Lockett v. Goodill, 430 P.2d 589, 591 (WA, 1967), as cited by Hall, Bobinski, Orenticher, , supra note 35.Google Scholar
Robertson, G., Negligence and Malpractice, in Downie, J. Caulfield, T. Flood, C., eds., Canadian Health Law and Policy, 2nd ed. (Markham, Ontario: Butterworths, 2002): 91109; Morreim, , supra note 26, at 48; Moore v. Regents of the University of California, 793 P.2d 479, 483, 488 (1990). The Supreme Court of California has determined that an interest in research can conflict with an interest in the patient-participant's health and that a physician-investigator's eagerness to promote the advancement of science may result in riskier experimental treatments. The physician-investigator must disclose to a participant “any personal interests unrelated to the patient's health, whether research or economic, that may affect the physician's professional judgment.” An action for conversion was dismissed even though the physician converted the patient-participant's blood products into a marketable commodity without consent. But the action for breach of the fiduciary duty to disclose financial interests in the research was accepted.Google Scholar
Glass, Lemmens, , supra note 11.Google Scholar
Advisory Committee on Human Radiation Experiments, The Human Radiation Experiments (New York: Oxford University Press, 1996).Google Scholar
Gomez v. Comité exécutif du Conseil des médecins, dentistes et pharmaciens de l’Hôpital universitaire de Québec, (2001) J. Q. No. 5544. This was dealt with specifically by the Quebec Court of Appeal. At issue was a complaint filed with a university hospital medical disciplinary committee by the family of a man who died after participating in a research study on prostate cancer. The complainant argued that the patient/research subject had not received the proper standard of care, and that as a result of the negligence of the physicians involved in the research project, he had not been diagnosed in a timely fashion. The researchers argued that medical research escapes the traditional disciplinary rules of the profession and is only submitted to the authority of specialized research ethics committees. The Court stated that research is part of the mission of a university hospital; that in this type of research subjects could reasonably have expected diagnostic services and exceptional care; and that the terms “medical act” and “research” cannot be strictly separated. Discussing the latter, the Court points out that clinical research is an integral part of medicine, and is undertaken by physicians whose first professional duty is the protection of the health and well-being of individuals. Biomedical research and medical acts are not in opposition to one another, the Court states. In this court's view, research subjects can rightly expect that when research activities undertaken in medical research centers involve medical procedures, such as diagnostic services, the interventions they undergo will meet the standard of care physicians owe to their patients.Google Scholar
Giesen, , supra note 12, at 595–96, § 251.Google Scholar
Gilbert, P. L. Harris, J. et al., “Neuroleptic Withdrawal in Schizophrenic Patients,” Archives of General Psychiatry 52 (1995): 173–88, at 173, 175, 182–85; Spivak, B. et al., “Neuroleptic Malignant Syndrome During Abrupt Reduction of Neuroleptic Treatment,” Acta Psychiatrica Scandinavia 81 (1990): 168–69.CrossRefGoogle Scholar
Viguera, A. C. Baldessarini, R. J. et al., “Clinical Risk Following Abrupt and Gradual Withdrawal of Maintenance Neuroleptic Treatment,” Archives of General Psychiatry 54 (1997): 4955, at 49–54.Google Scholar
Baldessarini, R. J. Viguera, A. C., “Medication Removal and Research in Psychotic Disorders,” Archives of General Psychiatry 55 (March, 1998): 281–82, at 282.CrossRefGoogle Scholar
Gilbert, Harris, et al., supra note 46, at 182.Google Scholar
Wyatt, R. J., “Neuroleptics and the Natural Course of Schizophrenia,” Schizophrenia Bulletin 17 (1991): 325–51; Greden, J. F. Tandon, R., “Long-Term Treatment for Lifetime Disorders?” Archives of General Psychiatry 52 (1995): 197–99, at 198.CrossRefGoogle Scholar
Greden, Tandon, , supra, at 198.Google Scholar
Viguera, Baldessarini, supra note 47, at 51.Google Scholar
Greden, Tandon, , supra note 51, at 198; Elliott, C. Weijer, C., “Cruel and Unusual Treatment,” Saturday Night 110, no. 10 (1995): 3134, at 32.Google Scholar
Greden, Tandon, , supra note 51, at 198. There is anecdotal evidence that details such as relapse rates have been kept out of the informed consent process because they were “overly frightening.” Put another way, such details might discourage enrollment in RCTs. The altruism that supposedly motivates some psychiatric patients to enroll in placebo-controlled trials may not endure an understanding of the potential for adverse effects. See also King, D., “Debatable Forms of Consent,” The Boston Globe, November 16, 1998, at A01. King quotes Wesley Acorn, then president of the national consumer council for the U.S. National Alliance for the Mentally Ill, as saying, “Do you think people say ‘Gee, I’ll sign up for more suffering. Many of us suffer enough on our own.’”Google Scholar
Baldessarini, Viguera, , supra note 46, at 282; Viguera, Baldessarini, et al., supra note 45, at 54; Baldessarini, R. J., “Risks and Implications of Interrupting Maintenance Psychotic Drug Therapy,” Psychotherapy and Psychosomatik 63 (1995): 137–41, at 139; Jeste, D. V. Gilbert, P. L. et al., “Considering Neuroleptic Maintenance and Taper on a Continuum,” Archives of General Psychiatry 52 (1995): 209–12, at 210; Wyatt, R., “Risks of Withdrawing Antipsychotic Medications,” Archives of General Psychiatry, 52 (1995): 205–08, at 207.CrossRefGoogle Scholar
Viguera, A. C. Baldessarini, R. J. et al., supra note 47, at 50.Google Scholar
Carpenter, W. T. Coney, R., “Sense and Nonsense: An Essay on Schizophrenia Research Ethics,” Scizophrenia Research 35 (1999): 219–25, at 222.CrossRefGoogle Scholar
Carpenter, W. T. Appelbaum, P. S. Levine, R. J., “The Declaration of Helsinki and Clinical Trials: A Focus on Placebo-Controled Trials in Schizophrenia,” American Journal of Psychiatry 160 (2003): 356–62, at 359.CrossRefGoogle Scholar
Geddes, J. R. Carey, S. M. Davis, C. Furukawa, T. A. et al., “Relapse Prevention with Antidepressant Drug Treatment in Depressive Disorders: A Systematic Review,” The Lancet 361 (2003): 653–61.CrossRefGoogle Scholar
Pincus, T. Callahan, L. F., “The ‘Side Effects’ of Rheumatoid Arthritis: Joint Destruction, Disability and Early Mortality,” British Journal of Rheumatology 32, suppl. 1 (1993): 2837; Wolfe, F. Cathey, M. A., “The Assessment and Prediction of Functional Disability in Rheumatoid Arthritis,” Journal of Rheumatology 18 (1991): 1298–1306; Reilly, P. A. Cosh, J. A. Maddison, P. J. Rasker, J. J. Silman, A., “Mortality and Survival in Rheumatoid Arthritis: A 25 Year Prospective Study of 100 Patients,” Annals of the Rheumatic Diseases 49 (1990): 363–69.Google Scholar
Emery, P., “The Roche Rheumatology Prize Lecture: The Optimal Management of Early Rheumatoid Disease: The Key to Preventing Disability,” British Journal of Rheumatology 33 (1994): 765–68; Pincus, T. Callahan, L. E., “How Many Types of Patients Meet Classification Criteria for Rheumatoid Arthritis?” Rheumatology 21 (1994): 1385–89.CrossRefGoogle Scholar
Fries, J. F. Williams, C. A. Morfeld, D. Singh, G. Sibley, J., “Reduction in Long-Term Disability in Patients with Rheumatoid Arthritis by Disease-Modifying Anti-rheumatic Drug-Based Treatment Strategies,” Arthritis & Rheumatism 39 (1996): 616–22; Van Riel, P. L. van der Heijde, D. M. Nuver-Zwart, I. H. van de Putte, L. B., “Radiographic Progression in Rheumatoid Arthritis: Results of 3 Comparative Trials,” Journal of Rheumatology 22 (1995): 1797–99; Forre, O., “Radiologic Evidence of Disease Modification in Rheumatoid Arthritis Patients Treated with Cyclosporine: Results of a 48-week Multicenter Study Comparing Low-Dose Cyclosporine with Placebo: Norwegian Arthritis Study Group,” Arthritis & Rheumatism 37 (1994): 1506–12.CrossRefGoogle Scholar
Stern, C. M. Pincus, T., “Placebo-Controlled Studies in Rheumatoid Arthritis: Ethical Issues,” The Lancet 353 (1999): 400–03, at 400.Google Scholar
Id; Temple, Ellenberg, , supra note 5.Google Scholar
Lemmens, T. Sprumont, D. Nys, H. Singh, J. Glass, K. C., “CIOMS' Placebo Rule and the Promotion of Negligent Medical Practice,” European Journal of Health Law 11 (2004): 153–74, at 163.CrossRefGoogle Scholar
Neufield v. McQuitty, 18 AR 271(1979); Halushka v. University of Saskatchewan 53 D.L.R. (2d) 436 (1965); Cryderman v. Ringrose, 3 W.W.R. 481 (Alta. CA, 1977); Coughlin v. Kuntz 17 B.C.L.R. 365 (1987); Civil Code of Quebec, S.Q., 1991, Articles 1474, 1477; Grimes v. Kennedy Kreiger Institute, 782 A.2d 807, 834 (2001); Gomez v. Comité exécutif du Conseil des médecins, dentistes et pharmaciens de l’Hôpital universitaire de Québec, supra note 43.Google Scholar
Lemmens, T. et al., supra note 65.Google Scholar
Menikov, J., Law and Bioethics: An Introduction (Washington, DC: Georgetown University Press, 2001).Google Scholar
Miller, Brody, , supra note 1.Google Scholar
Miller, , supra note 2.Google Scholar
Freedman, , supra note 34.Google Scholar
Freedman, B., “Ethics and Placebo-Controlled Thrombolytic Trials: The Future,” Coronary Artery Disease 2, no. 7 (1991): 849–52, at 850.Google Scholar
Weijer, C., “When Argument Fails,” American Journal of Bioethics 2 (2002): 1011, at 10.CrossRefGoogle Scholar
The National Placebo Working Committee Report on the Appropriate Use of Placebo in Clinical Trials (Ottawa: Health Canada and Canadian Institutes of Health Research, 2004).Google Scholar
Freedman, B. Glass, K. C. Weijer, C. supra note 7; Glass, K. C. Waring, D. supra note 7, at 26. Oberman, M., “Mothers and Doctor's Orders: Unmasking the Doctor's Fiduciary Role in Maternal-Fetal Conflicts,” Northwestern University Law Review 94 (2000): 451501, at 459.Google Scholar