论文标题
在群集随机试验中,在存在缺失效应修饰符数据的情况下评估治疗效应的异质性
Assessing treatment effect heterogeneity in the presence of missing effect modifier data in cluster-randomized trials
论文作者
论文摘要
了解以及如何在亚组中的治疗效果变化对于为临床实践和建议提供依据至关重要。因此,基于预先指定的潜在效应修饰符的异质治疗效应(HTE)的评估已成为现代随机试验中的一个共同目标。但是,当缺少一个或多个潜在效应修饰符时,完整的分析可能会导致偏见和覆盖不足。虽然已经提出了用于处理缺失数据的统计方法,并比较了具有效应修饰符数据的单个随机试验,但群集随机设置的指南很少,在效应修饰符,结果或什至缺失机制中的簇内相关性可能会引入进一步的HTE评估。在本文中,通过对群集随机试验进行的模拟研究进行了比较,并进行了连续结果和缺失的二元效应修饰符数据,并使用工作,家庭和健康研究的实际数据进一步说明。我们的结果表明,多级多重插补(MMI)和贝叶斯MMI比其他可用方法具有更好的性能,并且在存在模型规范或兼容性问题时,贝叶斯MMI的偏见较低,接近标称覆盖率。
Understanding whether and how treatment effects vary across subgroups is crucial to inform clinical practice and recommendations. Accordingly, the assessment of heterogeneous treatment effects (HTE) based on pre-specified potential effect modifiers has become a common goal in modern randomized trials. However, when one or more potential effect modifiers are missing, complete-case analysis may lead to bias and under-coverage. While statistical methods for handling missing data have been proposed and compared for individually randomized trials with missing effect modifier data, few guidelines exist for the cluster-randomized setting, where intracluster correlations in the effect modifiers, outcomes, or even missingness mechanisms may introduce further threats to accurate assessment of HTE. In this article, the performance of several missing data methods are compared through a simulation study of cluster-randomized trials with continuous outcome and missing binary effect modifier data, and further illustrated using real data from the Work, Family, and Health Study. Our results suggest that multilevel multiple imputation (MMI) and Bayesian MMI have better performance than other available methods, and that Bayesian MMI has lower bias and closer to nominal coverage than standard MMI when there are model specification or compatibility issues.