Group sequential designs for stepped-wedge cluster randomised trials
Group sequential designs for stepped-wedge cluster randomised trials
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DOI：
10.1177/1740774517716937
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发表时间：
2017-10-01
期刊：
影响因子：
2.7
通讯作者：
Mander, Adrian P.
中科院分区：
文献类型：
--
作者：
Grayling, Michael J.;Wason, James M. S.;Mander, Adrian P.
背景/目的：近年来，逐步楔形分组随机试验设计受到了广泛关注。虽然已经提出了对原始设计的各种扩展，但没有关于具有中期分析的阶梯楔形集随机试验设计的指导。在个体随机试验环境中，组序贯方法可以提供显着的效率增益和伦理益处。我们解决这一问题，讨论如何建立组序贯方法可以适应于stepped-wedge designs.Methods：利用错误支出的方法，组序贯试验设计，我们详细说明了所需的假设，为确定的stepped-wedge群集随机试验与中期分析。我们考虑因有效、无效或有效和无效而提前停药。我们首先描述如何可以做到这一点，任何指定的线性混合模型的数据分析。然后，我们专注于一个特定的常用模型，并使用最近完成的阶梯楔形随机分组试验，比较了几种设计的性能与中期分析的经典阶梯楔形设计。最后，性能的分位数替代程序处理的情况下，未知的variance.Results：我们证明，纳入早期停止在步进楔形簇随机试验设计可以减少预期的样本量下的零和备择假设分别高达31%和22%，没有成本的试验的I型和II型错误率。使用限制性误差最大似然估计被认为是更重要的分位数替代控制I型errors.Conclusion：除了中期分析到步进楔形随机分组试验，可以帮助防止耗时的试验进行不良的治疗，也有助于加快实施有效的治疗。将来，试验者应根据特定试验的需要，考虑将某种形式的提前停止纳入阶梯楔形群随机试验。
Background/Aims: The stepped-wedge cluster randomised trial design has received substantial attention in recent years. Although various extensions to the original design have been proposed, no guidance is available on the design of stepped-wedge cluster randomised trials with interim analyses. In an individually randomised trial setting, group sequential methods can provide notable efficiency gains and ethical benefits. We address this by discussing how established group sequential methodology can be adapted for stepped-wedge designs.Methods: Utilising the error spending approach to group sequential trial design, we detail the assumptions required for the determination of stepped-wedge cluster randomised trials with interim analyses. We consider early stopping for efficacy, futility, or efficacy and futility. We describe first how this can be done for any specified linear mixed model for data analysis. We then focus on one particular commonly utilised model and, using a recently completed stepped-wedge cluster randomised trial, compare the performance of several designs with interim analyses to the classical stepped-wedge design. Finally, the performance of a quantile substitution procedure for dealing with the case of unknown variance is explored.Results: We demonstrate that the incorporation of early stopping in stepped-wedge cluster randomised trial designs could reduce the expected sample size under the null and alternative hypotheses by up to 31% and 22%, respectively, with no cost to the trial's type-I and type-II error rates. The use of restricted error maximum likelihood estimation was found to be more important than quantile substitution for controlling the type-I error rate.Conclusion: The addition of interim analyses into stepped-wedge cluster randomised trials could help guard against time-consuming trials conducted on poor performing treatments and also help expedite the implementation of efficacious treatments. In future, trialists should consider incorporating early stopping of some kind into stepped-wedge cluster randomised trials according to the needs of the particular trial.