Equipoise and the Dilemma of Randomized Clinical Trials

Abstract

This chapter argues that clinical equipoise does not offer sound ethical guidance regarding the appropriateness of randomized clinical trials as tools to generate the knowledge needed for drug approval or coverage decisions. It discusses five considerations that militate against appeal to equipoise as the arbiter of the ethical legitimacy of randomized trials to evaluate new treatments, even for life-threatening or highly debilitating conditions: the imprecision in defining the concept of equipoise; the reliance on expert opinion; the limitations of determining efficacy on the basis of surrogate outcomes; the high costs of new treatments; and the tendency toward premature termination of randomized clinical trials. The chapter also examines equipoise-driven consequences that bias the evidence base relevant to risk-benefit assessment. Finally, it illustrates the problem with using equipoise to determine whether a randomized clinical trial is ethically appropriate by focusing on the recent controversy surrounding the development of a new drug for patients with metastatic melanoma.