Equipoise and the Ethical Justification of RCTs
It is true that not all of the feasible randomized clinical trials (RCTs) that physicians can imagine running are ethically justified, and therefore some set of principles or criteria must be formulated in order to decide which RCTs should proceed. Clinical equipoise is one such criterion, but we believe it cannot do the work of reliably differentiating between justified and unjustified RCTs for reasons different than those put forward by Rid and Miller (1).
Hey, London, and Weijer acknowledge that, like most qualitative principles, common definitions of clinical equipoise are subject to “ambiguity and limitations because it can be challenging to assess the state of uncertainty and balance of risks and benefits in a trial” (2). But this admission belies the serious logical problem with clinical equipoise: as currently conceived, it is not clear how to determine when equipoise is fulfilled. This challenge must be met in order for the principle of clinical equipoise to be applied ethically — meaning, in an unbiased and fair manner. Applications of the principle of clinical equipoise should follow relevantly similar criteria from physician to physician, context to context, and study to study. It is thus morally imperative that a standard operationalization of clinical equipoise be formulated; otherwise, we run the risk of using an ethical principle unethically (i.e. unfairly and in a biased manner).
The challenge of assessing the state of uncertainty surrounding a given research question must be met. Unfortunately, over the three decades since equipoise was first formulated, no widely accepted operationalization has been developed. We believe that this is strong inductive evidence that no such operationalization will be forthcoming. We conclude, thus, that clinical equipoise should be abandoned on the grounds that its continued use may in fact be unethical. Moreover, in work that we have published (3,4,5) and that is forthcoming (6,7), we have sought to propose an alternative standard to equipoise — one based on the same concept of uncertainty, but operationalized in terms of verifiable criteria.
(1) Rid A, Miller F. Is the concept of clinical equipoise still relevant to research? No. BMJ 2017; 359:j5787.
(2) Hey SP, London AJ, Weijer C. Is the concept of clinical equipoise still relevant to research? Yes. BMJ 2017;359:j5787.
(3) Fedyk M, Shamy M. Projectability, Disagreement and Consensus: A Challenge to Clinical Equipoise. Theoret App Ethics 2014;3:17-34.
(4) Shamy MCF, Stahnisch FW, Hill MD. Fallibility: A New Perspective on the Ethics of Clinical Trial Enrollment. Int J Stroke 2015;10:2-6.
(5) Shamy M, Fedyk M. Clinical Trials Involving Hypertension. N Engl J Med 2017;376:290.
(6) Shamy M, Fedyk M. Why the Ethical Justification of Randomized Clinical Trials is a Scientific Question. J Clin Epi 2018; forthcoming.
(7) De Meulemeester J, Jurkovic L, Fedyk M, et al. Many RCTs May Not Be Justified: A Cross-Sectional Analysis of the Ethics and Science of Randomized Clinical Trials. J Clin Epi 2018; forthcoming.
Competing interests: No competing interests