AB - The doctrine of clinical equipoise is appealing because it appears to permit physicians to maintain their therapeutic obligation to offer optimal medical care to patients while conducting randomized controlled trials (RCTs). The appearance, however, is deceptive. In this article we argue that clinical equipoise is defective and incoherent in multiple ways. First, it conflates the sound methodological principle that RCTs should begin with an honest null hypothesis with the questionable ethical norm that participants in these trials should never be randomized to an intervention known to be inferior to standard treatment. Second, the claim that RCTs preserve the therapeutic obligation of physicians misrepresents the patient-centered orientation of medical care. Third, the appeal to clinical equipoise as a basic principle of risk-benefit assessment for RCTs is incoherent. Finally, the difficulties with clinical equipoise cannot be resolved by viewing it as a presumptive principle subject to exceptions. In the final sections of the article, we elaborate on the non-exploitation framework for the ethics clinical research and indicate issues that warrant further inquiry.
AB - This chapter examines the doctrine of clinical equipoise within the context of research ethics. It first considers the two components of clinical equipoise that are often erroneously conflated: the "honest null hypothesis" principle and the "no inferior treatment" principle. It then turns to instances of theoretical and practical incoherence in research ethics attributable to endorsing clinical equipoise as a fundamental principle, with particular emphasis on the incoherence of the therapeutic orientation to clinical trials and incoherence in risk-benefit assessment. It argues that clinical equipoise's basic appeal to the ethics of therapeutic medicine is misguided, since no ethical physician would treat patients in the way that clinical equipoise would allow research participants to be treated, and that clinical equipoise cannot be rendered coherent merely by carving out exceptions. Finally, the chapter discusses the non-exploitation framework by addressing the views of Jansen (2005).
The concept of equipoise is considered by many to be part of the ethical justification for using human subjects in clinical research. In general, equipoise indicates some uncertainty about the relative merits of the experimental intervention compared to existing treatments. Relieving this uncertainty gives scientific value to an experiment, thereby making the risks to human subjects in the trial acceptable, other considerations notwithstanding. But characterizing equipoise remains controversial since Freedman’s groundbreaking publication on the subject. We offer a new account of equipoise that draws on and extends an option Freedman discarded. After establishing the importance of some account of equipoise as part of ethically justified clinical trials, we revisit Freedman’s distinction between clinical and theoretical equipoise. We raise concerns about Freedman’s preferred clinical equipoise and then rehabilitate theoretical equipoise. In particular, we use a variety of arguments from epistemology to show how Freedman was too hasty in rejecting theoretical equipoise. In addition, we argue that theoretical equipoise is a subspecies of epistemic equipoise, which we characterize as a form of uncertainty that is the result of the possibility of error. This type of uncertainty can best be alleviated by research, which produces beliefs supported by strong statistical evidence, which is a key aim of clinical trials. Further, this type of uncertainty can explain why even clinicians with more firsthand experience with an intervention than their peers, and who may not be in theoretical equipoise, could still justifiably support a trial designed to ameliorate the possibility of error due to cognitive bias.