论文标题

具有多元连续结果的梯级楔形设计的功率分析

Power analyses for stepped wedge designs with multivariate continuous outcomes

论文作者

Davis-Plourde, Kendra, Taljaard, Monica, Li, Fan

论文摘要

多元结果在务实的簇随机试验中很常见。尽管在平行分配下存在多元结果的样本量计算过程,但没有为阶梯楔设计开发。在本文中,我们介绍了具有多变量结果的梯级楔形群集随机试验(SW-CRT)的计算有效的功率和样本量程序,这些结果可区分周期内和周期间内相关系数(ICC)。在多元线性混合模型下,我们得出了干预测试统计量的联合分布,该分布可用于确定不同假设下的功率,并使用常用的相交联合测试为共同结果提供了一个示例。还提供了跨端点的常见治疗效果和常见的ICC的简化,并提供了对封闭队列设计的扩展。最后,在跨端点假设的共同ICC下,我们正式证明,与单变量线性混合模型相比,多元线性混合模型会导致更有效的治疗效应估计量,从而为使用前者使用多元结果提供了严格的理由。我们使用现有SW-CRT的数据说明了提出的方法的应用,并进行了广泛的模拟来验证方法。

Multivariate outcomes are common in pragmatic cluster randomized trials. While sample size calculation procedures for multivariate outcomes exist under parallel assignment, none have been developed for a stepped wedge design. In this article, we present computationally efficient power and sample size procedures for stepped wedge cluster randomized trials (SW-CRTs) with multivariate outcomes that differentiate the within-period and between-period intracluster correlation coefficients (ICCs). Under a multivariate linear mixed model, we derive the joint distribution of the intervention test statistics which can be used for determining power under different hypotheses and provide an example using the commonly utilized intersection-union test for co-primary outcomes. Simplifications under a common treatment effect and common ICCs across endpoints and an extension to closed cohort designs are also provided. Finally, under the common ICC across endpoints assumption, we formally prove that the multivariate linear mixed model leads to a more efficient treatment effect estimator compared to the univariate linear mixed model, providing a rigorous justification on the use of the former with multivariate outcomes. We illustrate application of the proposed methods using data from an existing SW-CRT and present extensive simulations to validate the methods.

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