In this issue of the Journal of Law, Medicine & Ethics Peter Clark provides a comprehensive and sound ethical analysis of clinical trials examining the treatment of advanced Parkinson's disease with fetal tissue transplantation. These studies raise profound questions about how clinical trials of surgical interventions ought to be conducted. At stake is not only the ethical basis of such trials, but differing views as to the proper role of science in medicine and its limitations.Experience with the broader debate on (...) the ethical permissibility of placebo controls has taught us that the choice of control treatment is an aspect of trial design in which ethical and scientific issues overlap. Accordingly, I will highlight, and perhaps expand upon, three issues raised by Clark: What scientific questions ought clinical trials of surgical interventions ask? How should the ethical analysis of risk for such trials be conceived? And, are surgical patients a vulnerable population? (shrink)

The most recent (Fifth) revision of the Declaration of Helsinki, adopted in October 2000 by the World Medical Association (WMA), reinforces the longstanding prohibition against offering placebo instead of effective therapy. The WMA left no doubt that if a beneficial treatment for a condition has already been recognised, it is unethical to offer placebo in place of such treatment to anyone in a study of the same condition. We have previously drawn attention to the discrepancy between the spirit of the (...) Declaration and the common practice of using placebo controls in randomised trials even if effective treatment exists. Despite the mandates of the Declaration of Helsinki and concern from ethicists and scientists, the US Food and Drug Administration (FDA) continues to demand and defend placebo‐controlled evidence of efficacy and safety for the development of many new pharmaceuticals, even if effective therapy exists. We suggest that the FDA's arguments defending their practice are insufficient to justify medical research that violates the Declaration of Helsinki. (shrink)

Recently a number of AIDS/AZT research studies, carried out by U.S. universities, have come under intense ethical scrutiny. In these studies, control groups of HIV-positive pregnant women were being given a placebo rather than AZT. Such research protocols would be illegal if practiced in the U.S. I examine a number of lamentable ethical lapses in the studies, and conclude that at least some of these ethical problems are traceable to a troubling contradiction between differing international codes of ethics. In a (...) word, some international codes mandate that all research subjects (including control groups) receive the best standard of care available in the country sponsoring the research, while others suggest that providing only a “Iocal” standard of care is ethically appropriate. I argue that these two ethical mandates cannot both be satisfied, and that host country populations will remain subject to exploitation unless this contradiction is resolved. (shrink)

Beginning with a review of the role of placebos in the history of medicine, this book investigates the current surge of interest in placebos, and probes the methodological difficulties of saying scientifically just what placebos can and cannot do.

Recent debates over the use of sham surgery as a control for studies of fetal tissue transplantation for Parkinson’s disease have focused primarily on rival interpretations of the US federal regulations governing human-subjects research. Using the core ethical and methodological considerations that underwrite the equipoise requirement, we nd strong prima facie reasons against using sham surgery as a control in studies of cellular-based therapies for Parkinson’s disease and more broadly in clinical research. Additionally, we believe that these reasons can be (...) generalized to apply to the use of other placebo controls that carry signi cant risks of positive harms in and of themselves. As a result, our arguments are centrally relevant to the emerging drive to subject therapies with a surgical component to the same rigorous standards of evaluation as those governing the approval of new pharmaceuticals. (shrink)