Is the concept of clinical equipoise still relevant to research?
BMJ 2017; 359 doi: https://doi.org/10.1136/bmj.j5787 (Published 28 December 2017) Cite this as: BMJ 2017;359:j5787
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
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
Dear Editor,
I read with interest the article by Hey et al (2017) describing arguments for and against the relevance of clinical equipoise in the justification of clinical trials. However, I disagree with the assertion that differing ethical premises in clinical research and clinical practice mean that clinical equipoise inappropriately aligns practice standards in these two fields. Essentially, the authors suggest that the obligation to provide competent clinical care to all patients in a trial distracts from the purpose of a trial to identify clinically useful information. However, I would suggest that enforcement of the clinical equipoise principle aligns clinical research and practice advantageously by obliging researchers to ask only questions most relevant to clinical practice.
By requiring genuine uncertainty regarding the relative efficacy of treatments in both arms of a trial, clinical equipoise provides a strong imperative to compare new treatments to the current gold standard for that disease. This is relevant where new treatments may be superior to placebo, but unless they are superior to established treatments they will offer little additional value to clinical practice. Furthermore, clinical equipoise provides a clear standard in this area compared to alternative models such as the net risks model where a variety of variables are considered to justify a trial. Thus, while I must concede that clinical equipoise constrains the conduct of clinical researchers, it does not necessarily do so to the detriment of scientific progress.
Competing interests: No competing interests
Re: Is the concept of clinical equipoise still relevant to research?
Dear Editor,
I did not find merit in Rid and Miller’s arguments that equipoise is unnecessary in clinical trials.[1] I have defined equipoise as the situation where both options offer the patient equal expected utility.[2] This means that when a patient is offered both options and cannot decide, randomisation offers equal expected utility by definition. It does not follow that proponents of equipoise ‘would not object to’ unnecessary tests. Some might not, but this is not a function of the equipoise principle. The best way to think about the issue is to ask yourself this question – “if there was no trial, then what would I tell my patient about the alternatives?” Then, in the trial, that is what the patient should be told. What if one treatment is available only in the trial? In that case, the patient should be given exactly the same information about the treatments (the usual and restricted treatment) and then offered a choice between the usual treatment and the trial. I call this ‘equipoise plus’.
Yours faithfully,
Richard Lilford
References:
1. Rid A, Miller F. Is the concept of clinical equipoise still relevant to research? No. BMJ. 2017; 359: j5787.
2. Lilford RJ. Ethics of clinical trials from a Bayesian and decision analytic perspective: whose equipoise is it anyway? BMJ. 2003; 326: 980.
Competing interests: No competing interests