Equipoise in Research: Integrating Ethics and Science in Human Research

INTRODUCTION

This JAMA Guide to Statistics and Methods reviews the concept of equipoise, which allows for randomization of interventions while also respecting the rights of human subjects in clinical research.

The principle of equipoise states that, when there is uncertainty or conflicting expert opinion about the relative merits of diagnostic, prevention, or treatment options, allocating interventions to individuals in a manner that allows the generation of new knowledge (eg, randomization) is ethically permissible.^1,2 The principle of equipoise reconciles 2 potentially conflicting ethical imperatives: to ensure that research involving human participants generates scientifically sound and clinically relevant information while demonstrating proper respect and concern for the rights and interests of study participants.¹

Lascarrou et al³ reported the results of a randomized trial designed to investigate whether the “routine use of the video laryngoscope for orotracheal intubation of patients in the ICU increased the frequency of successful first-pass intubation compared with use of the Macintosh direct laryngoscope.” Intubation in the intensive care unit (ICU) is associated with the potential for serious adverse events, and video laryngoscopy in the ICU has gained support from some clinicians who believe it to be superior to direct laryngoscopy. Such practitioners may therefore regard it as unethical to randomize study participants to direct laryngoscopy because they consider it to be an inferior intervention. But requiring uncertainty of individual clinicians to conduct a clinical trial gives too much ethical weight to personal judgment, hindering valuable research without providing benefit to patients. Therefore, it is important to understand the role of conflicting expert medical judgment in establishing equipoise and how this principle applies to the trial conducted by Lascarrou et al.³

WHAT IS EQUIPOISE?

Two features of medical research pose special challenges for the goal of ensuring respect and concern for the rights and interests of participants. First, to generate reliable information, research often involves design features that alter the way participants are treated. For example, randomization and blinding are commonly used to reduce selection bias and treatment bias.⁴ Controlling how interventions are allocated and what researchers and participants know about who is receiving which interventions helps to more clearly distinguish the effects of the intervention from confounding effects. But randomization severs the link between what a participant receives and the recommendation of a treating clinician with an ethical duty to provide the best possible care for the individual person. In the study by Lascarrou et al,³ patients were randomized to undergo intubation with the video laryngoscope or the direct laryngoscope, independent of the preference of the treating physician.

Second, medical research involves exposing people to interventions whose risks and potential therapeutic, prophylactic, or diagnostic merits may be unknown, unclear, or the subject of disagreement within the medical community. In the present case, some clinicians may maintain that video laryngoscopy is the superior strategy for orotracheal intubation in ...