Critics of clinical equipoise have long argued that it represents an overly permissive, and therefore morally unacceptable, mechanism for resolving the tensions inherent in clinical research. In particular, the equipoise requirement is often attacked on the grounds that it is not sufficiently responsive to the interests of individual patients. In this paper, we outline a view of equipoise that not only withstands a stronger version of this objection, which was recently articulated by Deborah Hellman, but also plays important roles in (...) clarifying the discussion. (shrink)

The principle of clinical equipoise has been variously characterized by ethicists and clinicians as fundamentally flawed, a myth, and even a moral balm. Yet, the principle continues to be treated as the de facto gold standard for conducting randomized control trials in an ethical manner. Why do we hold on to clinical equipoise, despite its shortcomings being widely known and well-advertised? This paper reviews the most important arguments criticizing clinical equipoise as well as what the most prominent proposed alternatives are. (...) In the process, it evaluates the justification for continuing to use clinical equipoise as the gold standard for randomized control trials. (shrink)

The physician-researcher conflict of interest, a long-standing and widely recognized ethical challenge of clinical research, has thus far eluded satisfactory solution. The conflict is fairly straightforward. Medical research and medical therapy are distinct pursuits; the former is aimed at producing generalizable knowledge for the benefit of future patients, whereas the latter is aimed at addressing the individualized medical needs of a particular patient. When the physician-researcher combines these pursuits, he or she serves two masters and cannot — no matter how (...) well-intentioned — avoid the risk of compromising the duties owed in one of the professional roles assumed. Because of the necessary rigidity of a research protocol, the more demanding of the two masters is frequently the research.The problem of the physician-researcher conflict has been evident since the first attempts to regulate human research in the United States. Otto E. Guttentag, a physician at the University of California School of Medicine in San Francisco, addressed the conflict in a 1953Sciencemagazine article. (shrink)

In his influential 1987 essay, “Equipoise and The Ethics of Randomized Clinical Research,” Benjamin Freedman argued that Charles Fried’s theoretical equipoise requirement threatened clinical research because it was overwhelmingly fragile and rendered unethical too many randomized clinical trials. Freedman, therefore, proposed an alternative requirement, the clinical equipoise requirement, which is now considered to be the fundamental or guiding principle concerning the ethics of enrolling patients in randomized clinical trials. In this essay I argue that Freedman’s clinical equipoise requirement is ambiguous (...) and can be interpreted in (at least) two different ways. I furthermore claim that, ironically, the best interpretation of the clinical equipoise requirement opens Freedman to the same objection that he leveled against Fried twenty-five years ago; namely, that it (Freedman’s clinical equipoise requirement) renders unethical too many randomized clinical trials. (shrink)

The physician-researcher conflict of interest has thus far eluded satisfactory solution. Most attempts to deal with it focus on improving informed consent. But those attempts are not successful and may even make things worse. Research subjects are already voluntarily undertaking the risks of research — we should not ask them to go it alone — to undergo medical “treatment” without medical “care.” The only effective solution is that in much clinical research, each research subject should have a doctor independent from (...) the research study. (shrink)

Data Safety and Monitoring Boards have been referred to as a “growth industry,” and this trend continues to be fueled by recent FDA guidance and the NIH's requirement that DSMBs be employed in virtually all phase III clinical trials. The widening role of DSMBs has been sporadically questioned on ethical grounds, but growth has continued, despite the fact that many of the questions endure, unanswered, save for repeated references to safeguarding the scientific integrity of trials. This may be about to (...) change. The recently appointed director of the Office for Human Research Protections , Jerry Menikoff, is on record as regarding current practices — where consent forms often promise what the DSMB has been assembled to specifically not provide — as constituting fraudulent behavior. That is, a subject may inherently rely on, to their detriment, information that has been misrepresented in the consent document. In this paper, we assemble some of the enduring questions and top them off with Menikoff's tour de force to present what we hope will be a compelling argument to require that consent forms fairly represent what the DSMB will do — and not do — with trial data as they accumulate. We argue that DSMBs should be used only in rare circumstances, and question the practice of precluding principal investigators from DSMB membership, but our main thrust is to ensure that DSMBs, when used at all, are properly described in trial consent forms. (shrink)

Randomized trials depend on clinicians feeling that they are morally justified in allowing their patients to be randomized across treatment arms. Typically such justification rides on what has been called “clinical equipoise”—when there is disagreement of opinion among the community of experts about whether one treatment is better than another, then physicians can ethically enter their patients into a clinical trial, even if individual physicians are not at equipoise. Recent debates over prominent studies, however, illustrate that controversy can be easily (...) created rather than dispelled by trials, with many clinicians choosing not to use the proven therapy until they receive more convincing evidence of its superiority. In such situations, we propose that a new standard of equipoise be used to guide decisions about the ethical justifications for research trials—a standard of behavioral equipoise. Under behavioral equipoise, a trial is potentially justifiable if it addresses behavioral resistance to prior scientific evidence. (shrink)

Data Safety and Monitoring Boards were introduced in the 1960s to monitor data in clinical trials to ensure subject safety. It was thought important that DSMB members be experts in the field of interest, but not otherwise involved in the study in order to maximize objectivity. Since then, the use of DSMBs has increased dramatically, and their scope has expanded to include scientific issues — in particular, to avoid bias that can result when trials are stopped early because of evidence (...) that one treatment has greater efficacy or causes greater harm than another; or that no treatment is likely to do better than any other. (shrink)