Sim, J ORCID: 0000-0002-1816-1676 (2018) Outcome-adaptive randomization in clinical trials: issues of participant welfare and autonomy. Theoretical Medicine and Bioethics. (In Press)

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Abstract

Outcome-adaptive randomization (OAR) has been proposed as a corrective to certain ethical difficulties inherent in the traditional randomized clinical trial (RCT) using fixed-ratio randomization. In particular, it has been suggested that OAR redresses the balance between individual and collective ethics in favour of the former. In this paper I examine issues of welfare and autonomy arising in relation to OAR. A central issue in discussions of welfare in OAR is equipoise, and the moral status of OAR is crucially influenced by the way in which this concept is construed. If OAR is based on a model of equipoise that demands strict indifference throughout the trial between competing interventions, such equipoise is disturbed by accruing data favouring one treatment over another; OAR seeks to redress this by weighting randomization to the seemingly superior treatment. However, this is a partial response, as patients continue to be allocated to the inferior therapy. Moreover, it rests upon considerations of aggregate harms and benefits, and does not therefore uphold individual ethics. Issues of fairness also arise, as early and late enrollees are randomized on a different basis. Fixed-ratio randomization represents a fuller and more consistent response to a loss of equipoise, as so construed. With regard to consent, the complexity of OAR poses challenges to adequate disclosure and comprehension. Additionally, OAR does not offer a remedy to the therapeutic misconception – participants’ tendency to attribute treatment allocation in an RCT to individual clinical judgments, rather than scientific consideration – and, if anything, accentuates rather than alleviates the misconception. In relation to these issues, OAR fails to offer ethical advantages over fixed-ratio randomization. More broadly, the ethical basis of OAR can be seen to lie more in collective than in individual ethics, and overall it fares worse in this territory than fixed-ratio randomization.

Item Type: Article
Additional Information: The final published version of this article will be available online at https://link.springer.com/journal/11017
Uncontrolled Keywords: outcome-adaptive randomization, clinical trials, ethics, equipoise, consent
Subjects: R Medicine > R Medicine (General)
R Medicine > RA Public aspects of medicine
Divisions: Faculty of Medicine and Health Sciences > Primary Care Health Sciences
Depositing User: Symplectic
Date Deposited: 11 Dec 2018 08:40
Last Modified: 11 Dec 2018 08:40
URI: http://eprints.keele.ac.uk/id/eprint/5572

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