析因试验的估算指标。

Estimands for factorial trials.

机构信息

MRC Clinical Trials Unit at UCL, London, UK.

Health Services Research Unit, University of Aberdeen, Aberdeen, UK.

出版信息

Stat Med. 2022 Sep 30;41(22):4299-4310. doi: 10.1002/sim.9510. Epub 2022 Jun 25.

Abstract

Factorial trials offer an efficient method to evaluate multiple interventions in a single trial, however the use of additional treatments can obscure research objectives, leading to inappropriate analytical methods and interpretation of results. We define a set of estimands for factorial trials, and describe a framework for applying these estimands, with the aim of clarifying trial objectives and ensuring appropriate primary and sensitivity analyses are chosen. This framework is intended for use in factorial trials where the intent is to conduct "two-trials-in-one" (ie, to separately evaluate the effects of treatments A and B), and is comprised of four steps: (i) specifying how additional treatment(s) (eg, treatment B) will be handled in the estimand, and how intercurrent events affecting the additional treatment(s) will be handled; (ii) designating the appropriate factorial estimator as the primary analysis strategy; (iii) evaluating the interaction to assess the plausibility of the assumptions underpinning the factorial estimator; and (iv) performing a sensitivity analysis using an appropriate multiarm estimator to evaluate to what extent departures from the underlying assumption of no interaction may affect results. We show that adjustment for other factors is necessary for noncollapsible effect measures (such as odds ratio), and through a trial re-analysis we find that failure to consider the estimand could lead to inappropriate interpretation of results. We conclude that careful use of the estimands framework clarifies research objectives and reduces the risk of misinterpretation of trial results, and should become a standard part of both the protocol and reporting of factorial trials.

摘要

析因试验提供了一种在单次试验中评估多种干预措施的有效方法,然而,使用额外的治疗方法可能会使研究目标变得模糊,导致分析方法不当和结果解释不合理。我们定义了一组析因试验的评估指标,并描述了应用这些评估指标的框架,旨在阐明试验目标,并确保选择适当的主要和敏感性分析。该框架旨在用于旨在进行“一次试验中包含两个试验”(即,分别评估治疗 A 和 B 的效果)的析因试验中,由四个步骤组成:(i)指定在评估指标中如何处理额外的治疗方法(例如治疗 B),以及如何处理影响额外治疗方法的并发事件;(ii)指定适当的析因估计量作为主要分析策略;(iii)评估交互作用,以评估支撑析因估计量的假设的合理性;(iv)使用适当的多臂估计量进行敏感性分析,以评估偏离无交互作用的基本假设对结果的影响程度。我们表明,对于不可折叠的效应量(如比值比),需要进行其他因素的调整,并且通过试验重新分析,我们发现如果不考虑评估指标,可能会导致对结果的不当解释。我们得出结论,仔细使用评估指标框架可以阐明研究目标,并降低对试验结果的误解风险,应该成为析因试验的方案和报告的标准组成部分。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索