The question "When are research risks reasonable in relation to anticipated benefits?" is at the heart of disputes in the ethics of clinical research. Institutional review boards are often criticized for inconsistent decision-making, a problem that is compounded by a number of contemporary controversies, including the ethics of research involving placebo controls, developing countries, incapable adults and emergency rooms. If this pressing ethical question is to be addressed in a principled way, then a systematic approach to the ethics of risk (...) in research is required. Component analysis provides such a systematic approach. (shrink)

The principle of clinical equipoise requires that, aside from certain exceptional cases, second generation treatments ought to be tested against standard therapy. In violation of this principle, placebo-controlled trials (PCTs) continue to be used extensively in the development and licensure of second-generation treatments. This practice is typically justified by appeal to methodological arguments that purport to demonstrate that active-controlled trials (ACTs) are methodologically flawed. Foremost among these arguments is the so called assay sensitivity argument. In this paper, I take a (...) closer look at this argument. Following Duhem, I argue that all trials, placebo-controlled or not, rely on external information for their meaningful interpretation. Pending non-circular empirical evidence that we can trust the findings of PCTs to a greater degree than the findings of ACTs, I conclude that the assay sensitivity argument fails to demonstrate that placebo-controlled trials are preferable, methodologically or otherwise, to active-controlled trials. Contrary to the intentions of its authors, the fundamental lesson taught by the assay sensitivity argument is Duhemian: the validity of all clinical trials depends on external information. (shrink)

Any view of equipoise faces perhaps the most radical and far-reaching objections from moral foundations. These objections hold that the equipoise requirement conflates the ethics of medical research and the ethics of clinical medicine. Once this conflation is recognized, this position holds, research can be given a new foundation on the imperative to avoid exploiting research participants. This article argues that what is novel in this critique is not as successful as its proponents claim and that the ultimate success of (...) this approach actually hinges on a version of the objection from utility. Nevertheless, this criticism highlights the limited scope of applicability of the equipoise requirement. The article concludes, therefore, by describing the outlines of what the article calls an ‘integrative approach’ to clinical trials. This approach represents one way in which the normative requirements of equipoise and the non-exploitation approach might be unified under a single, broad framework. (shrink)

A predominant ethical view holds that physician‐investigators should conduct their research with therapeutic intent. And since a physician offering a therapy wouldn't prescribe second‐rate treatments, the experimental intervention and the best proven therapy should appear equally effective. "Clinical equipoise" is necessary. But this perspective is flawed. The ethics of research and of therapy are fundamentally different, and clinical equipoise should be abandoned.

In February 2010, the World Medical Association hosted an international symposium on the ethics of placebo controls in clinical trials (WMA 2010). Despite years of debate, ethicists, clinical trialists, and policy makers remain divided over the ethical acceptability of using placebos in research when a proven, effective treatment is available. The protracted nature of this problem is due, at least in part, to a perceived conflict between the opposing demands placed on clinical research by science and ethics. A good, scientifically (...) valid trial, it is argued, must be “assay sensitive,” and without using a placebo control, there can be no guarantee that it is. In this article, we revisit some of the claims made about .. (shrink)

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)