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Multiple Imputation Methods for Treatment Noncompliance and Nonresponse in Randomized Clinical Trials

机译:多种插补方法治疗随机临床试验中的不依从和无反应

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摘要

Summary: Randomized clinical trials are a powerful tool for investigating causal treatment effects, but in human trials there are oftentimes problems of noncompliance which standard analyses, such as the intention-to-treat or as-treated analysis, either ignore or incorporate in such a way that the resulting estimand is no longer a causal effect. One alternative to these analyses is the complier average causal effect (CACE) which estimates the average causal treatment effect among a subpopulation that would comply under any treatment assigned. We focus on the setting of a randomized clinical trial with crossover treatment noncompliance (e.g., control subjects could receive the intervention and intervention subjects could receive the control) and outcome nonresponse. In this article, we develop estimators for the CACE using multiple imputation methods, which have been successfully applied to a wide variety of missing data problems, but have not yet been applied to the potential outcomes setting of causal inference. Using simulated data we investigate the finite sample properties of these estimators as well as of competing procedures in a simple setting. Finally we illustrate our methods using a real randomized encouragement design study on the effectiveness of the influenza vaccine.
机译:简介:随机临床试验是研究因果关系治疗效果的有力工具,但是在人体试验中,经常会出现不合规的问题,这些标准分析(例如意向性治疗或经治疗的分析)会忽略或纳入此类分析中。这样,得出的估计值不再是因果关系。这些分析的一种替代方法是合规性平均因果效应(CACE),它估计在任何分配的治疗下都将符合的亚人群中的平均因果效应。我们着重于随机化临床试验中交叉治疗不依从性的设置(例如,对照组可以接受干预,干预组可以接受对照)和结局无反应。在本文中,我们使用多种插补方法开发了CACE的估计器,该估计器已成功应用于各种缺失数据问题,但尚未应用于因果推断的潜在结果设置。使用模拟数据,我们可以在一个简单的环境中研究这些估计量以及竞争程序的有限样本属性。最后,我们使用关于流感疫苗有效性的真正随机鼓励设计研究来说明我们的方法。

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