Some commentators have recently proposed that “clinical equipoise,” although widely accepted, is not necessary for morally acceptable research on human subjects. If this concept is rejected, however, we may find that trials not in the best medical interests of their subjects—”bad deal trials”—could be justified. To avoid exploiting participants, we must find a way to distribute the risks fairly, even if it means embracing radical changes in the way clinical research is conducted.

It is commonly believed in research ethics that some form of equipoise is a necessary condition for justifying randomized clinical trials, that without it clinicians are violating the moral duty to do what is best for the patient. Recent criticisms have shown how complex the concept of equipoise is, but often retain the commitment to some form of equipoise for randomization to be justified. This article rejects that claim. It first asks for what one should be equally poised (scientific or (...) clinical equipoise), then asks who should be equally poised (scientist, clinician, or subject), and finally asks why any of these players need be equally poised between treatment options. The article argues that only the subject's evaluation of the options is morally relevant and that even the subject need not be equally poised or indifferent between the options in order to volunteer for randomization. All that is needed is adequately informed, free, and unexploited consent. It concludes equipoise is irrelevant. (shrink)

The physician who upholds the Hippocratic oath is supposed to be loyal to his or her patients. This requires choosing only the therapy that the physician believes is best for the patient. However, knowing what is best requires randomized clinical trials. Thus, clinicians must be willing to recruit their patients to be assigned at random to one of two therapies in order to determine which is best based on the highest standards of pharmacological science.

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.

: The principle of equipoise traditionally is grounded in the special obligations of physician-investigators to provide research participants with optimal care. This grounding makes the principle hard to apply in contexts with limited health resources, to research that is not directed by physicians, or to non-therapeutic research. I propose a different version of the principle of equipoise that does not depend upon an appeal to the Hippocratic duties of physicians and that is designed to be applicable within a wider range (...) of research contexts and types—including health services research and research on social interventions. I consider three examples of ethically contentious research trials conducted in three different social settings. I argue that in each case my version of the principle of equipoise provides more plausible and helpful guidance than does the traditional version of the principle. (shrink)

: Some commentators have recently proposed that "clinical equipoise," although widely accepted, is not necessary for morally acceptable research on human subjects. If this concept is rejected, however, we may find that trials not in the best medical interests of their subjects--bad deal trials--could be justified. To avoid exploiting participants, we must find a way to distribute the risks fairly, even if it means embracing radical changes in the way clinical research is conducted.

In this article, I review and expand upon arguments showing that Freedman's so-called "clinical equipoise" criterion cannot serve as an appropriate guide and justification for the moral legitimacy of carrying out randomized clinical trials. At the same time, I try to explain why this approach has been given so much credence despite compelling arguments against it, including the fact that Freedman's original discussion framed the issues in a misleading way, making certain things invisible: Clinical equipoise is conflated with community equipoise, (...) and several versions of each are also conflated. But a misleading impression is given that, rather than distinct criteria being arbitrarily conflated, a puzzle is solved and a number of features unified. Various issues are pushed under the rug, hiding flaws of the "clinical equipoise" approach and thus deceiving us into thinking that we have a solution when we do not. Particularly significant is the ignoring of the crucial distinction between the individual patient decision and the policy decision. (shrink)

The central dilemma concerning randomized clinical trials (RCTs) arises out of some simple facts about causal methodology (RCTs are the best way to generate the reliable causal knowledge necessary for optimally-informed action) and a prima facie plausible principle concerning how physicians should treat their patients (always do what it is most reasonable to believe will be best for the patient). A number of arguments related to this in the literature are considered. Attempts to avoid the dilemma fail. Appeals to informed (...) consent and mechanisms for minimizing the resulting harm are important for policy, but informed consent is problematic and mechanisms for minimization of harm do not address the dilemma. Appeals to some sort of contract model of justification are promising and illuminating. Keywords: randomized clinical trials, ethics CiteULike Connotea Del.icio.us What's this? (shrink)

It is often claimed that a clinical investigator may ethically participate (e.g., enroll patients) in a trial only if she is in equipoise (if she has no way to ground a preference for one arm of the study). But this is a serious problem, for as data accumulate, it can be expected that there will be a discernible trend favoring one of the treatments prior to the point where we achieve the trial's objective. In this paper, I critically evaluate Benjamin (...) Freedman's 'clinical equipoise' solution to this dilemma. I argue that Freedman actually puts forth at least two distinct contrasts - one in terms of community vs. individual equipoise, and another concerning clinical vs. theoretical equipoise - and that neither of them resolves the dilemma. I then make a proposal for a more adequate account of how to think about the circumstances under which entering subjects in trials would be justified - a 'sliding-scale equipoise' that arises out of a discussion of patients' values. (shrink)

: The "difference position" holds that clinical research and therapeutic medical practice are sufficiently distinct activities to require different ethical rules and principles. The "similarity position" holds instead that clinical investigators ought to be bound by the same fundamental principles that govern therapeutic medicine—specifically, a duty to provide the optimal therapeutic benefit to each patient or subject. Some defenders of the similarity position defend it because of the overlap between the role of attending physician and the role of investigator in (...) a research trial. This overlap is maximal when the same physician occupies both roles with respect to a particular patient-subject. We address the ethical tensions inherent in that role conflict and argue that the tensions are real but manageable. The difference position provides a sound ethical framework within which to manage those tensions, while the similarity position is unsatisfactory because it seeks to deny the existence of the tensions. (shrink)

It is widely maintained that a clinical trial is ethical only if some form of equipoise between the treatments being compared obtains. To be in equipoise between two treatments A and B is to be cognitively indifferent between the statement ‘A is strictly more effective than B’ and its negation. It is natural to claim that equipoise regarding A and B is necessary for randomised assignment to treatments A and B to be beneficent and non‐maleficent and is sufficient for such (...) an assignment to be fair. Cashing this out precisely is difficult, and various forms of equipoise have been discussed which consider whose equipoise is relevant to the decision. This is to make judgement of equipoise something to be managed socially, while its prima facie significance is supposedly cognitive. Recent reconstructions of equipoise‐like concepts in epistemology give clues about how to understand equipoise cognitively. In this paper I examine some of this work and discuss how successful it has been. I suggest that while this work is promising, it still has far to go, and that while equipoise remains the best theory we have of the cognitive justification for clinical trials, it is nonetheless incoherent. (shrink)

This new edition of Charles Fried's 'Medical Experimentation' includes a general introduction by Franklin Miller and the late Alan Wertheimer, a reprint of the 1974 text, an in-depth analysis by Harvard Law School scholars I. Glenn Cohen and D. James Greiner, and a new essay by Fried reflecting on the original text and how it applies to the contemporary landscape of medicine and medical experimentation.