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Group sequential crossover trial designs with strong control of the familywise error rate

机译:分组顺序交叉试验设计,具有对家庭错误率的强大控制

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Crossover designs are an extremely useful tool to investigators, and group sequential methods have proven highly proficient at improving the efficiency of parallel group trials. Yet, group sequential methods and crossover designs have rarely been paired together. One possible explanation for this could be the absence of a formal proof of how to strongly control the familywise error rate in the case when multiple comparisons will be made. Here, we provide this proof, valid for any number of initial experimental treatments and any number of stages, when results are analyzed using a linear mixed model. We then establish formulae for the expected sample size and expected number of observations of such a trial, given any choice of stopping boundaries. Finally, utilizing the four-treatment, four-period TOMADO trial as an example, we demonstrate that group sequential methods in this setting could have reduced the trials expected number of observations under the global null hypothesis by over 33%.
机译:交叉设计对研究人员而言是极为有用的工具,事实证明,组序方法在提高并行组试验效率方面非常熟练。但是,组顺序方法和交叉设计很少配对在一起。对此的一种可能的解释可能是,在进行多次比较的情况下,没有正式证据证明如何严格控制家庭错误率。在此,当使用线性混合模型分析结果时,我们提供此证明对任何数量的初始实验处理和任何阶段均有效。然后,在选择任何终止边界的情况下,我们将为此类试验的预期样本量和预期观察次数建立公式。最后,以四次治疗,四次TOMADO试验为例,我们证明了在这种情况下采用组序贯方法可以使试验在整体无效假设下的预期观察数减少33%以上。

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