Sim Julius
Institute for Primary Care and Health Sciences, Keele University, Staffordshire, ST5 5BG, UK.
Theor Med Bioeth. 2019 Apr;40(2):83-101. doi: 10.1007/s11017-019-09481-0.
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 between competing interventions throughout the trial, 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 to scientific considerations-and, if anything, accentuates rather than alleviates this 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.
结果适应性随机分组（OAR）已被提出，作为对传统固定比例随机分组的随机临床试验（RCT）中某些内在伦理困境的一种纠正措施。特别是，有人认为OAR纠正了个体伦理与集体伦理之间的平衡，更倾向于前者。在本文中，我探讨了与OAR相关的福利和自主性问题。OAR中福利讨论的一个核心问题是 equipoise，OAR的道德地位受到对这一概念解释方式的关键影响。如果OAR基于一种equipoise模型，该模型要求在整个试验过程中对相互竞争的干预措施保持严格的无差异，那么随着有利于一种治疗方法的数据积累，这种equipoise就会被打破；OAR试图通过对看似更优的治疗方法进行加权随机分组来纠正这一点。然而，这只是部分回应，因为患者仍会被分配到较差的治疗方法。此外，它基于总体危害和益处的考虑，因此并不维护个体伦理。公平问题也会出现，因为早期和晚期入组者的随机分组依据不同。按照这种理解，固定比例随机分组对equipoise丧失的回应更全面、更一致。关于同意，OAR的复杂性对充分披露和理解构成了挑战。此外，OAR并不能解决治疗性误解——参与者倾向于将RCT中的治疗分配归因于个体临床判断，而非科学考量——而且，如果有什么不同的话，它加剧而非减轻了这种误解。就这些问题而言，OAR相较于固定比例随机分组并没有伦理优势。更广泛地说，OAR的伦理基础更多地在于集体伦理而非个体伦理，总体而言，在这方面它比固定比例随机分组表现更差。
