标题： 将新的试验组添加到随机临床试验中：对误差率的影响 显示英文标题

标题： Adding new experimental arms to randomised clinical trials: impact on error rates

摘要： 背景：实验性治疗要经过多个发展阶段。 如果一种治疗通过了早期阶段的实验，研究者可能希望在晚期随机对照试验中评估它。 一种有效的方法是将它作为新的研究组添加到正在进行的试验中。 这允许在现有组继续进行的同时添加新治疗。 家庭误差率（FWER）通常是在多组试验中一个关键感兴趣的数量。 我们旨在阐明当在试验开始一段时间后添加新组时，应该如何计算它。 方法：我们展示了当一个新的组被添加到平台试验中时，如何计算FWER、任意对和所有对的统计功效。 我们扩展了Dunnett概率，并推导出现有成对比较和新添加组的检验统计量之间的相关性的解析公式。 我们还通过模拟验证了我们的解析推导。 结果：我们的结果表明，FWER依赖于共享对照组的信息（即连续和二元结果中的个体以及时间至事件结果中的主要结果事件）来自共同对照组患者和分配比例。 FWER更多地由成对比较的数量和相应的（成对）I型错误率驱动，而不是由新组添加的时间驱动。 如果成对比较的检验统计量之间的相关性小于0.30，可以使用Šidák校正来估计FWER。 结论：我们在本文中提出的发现可用于设计具有预先计划的延迟组的试验，或在正在进行的平台试验中设计新的成对比较，其中需要控制成对误差率（PWER）或FWER（成对比较子集）。 显示英文摘要

摘要： Background: Experimental treatments pass through various stages of development. If a treatment passes through early phase experiments, the investigators may want to assess it in a late phase randomised controlled trial. An efficient way to do this is adding it as a new research arm to an ongoing trial. This allows to add the new treatment while the existing arms continue. The familywise type I error rate (FWER) is often a key quantity of interest in any multi-arm trial. We set out to clarify how it should be calculated when new arms are added to a trial some time after it has started. Methods: We show how the FWER, any-pair and all-pairs powers can be calculated when a new arm is added to a platform trial. We extend the Dunnett probability and derive analytical formulae for the correlation between the test statistics of the existing pairwise comparison and that of the newly added arm. We also verify our analytical derivation via simulations. Results: Our results indicate that the FWER depends on the shared control arm information (i.e. individuals in continuous and binary outcomes and primary outcome events in time-to-event outcomes) from the common control arm patients and the allocation ratio. The FWER is driven more by the number of pairwise comparisons and the corresponding (pairwise) Type I error rates than by the timing of the addition of the new arms. The FWER can be estimated using \v{S}id\'{a}k's correction if the correlation between the test statistics of pairwise comparisons is less than 0:30. Conclusions: The findings we present in this article can be used to design trials with pre-planned deferred arms or to design new pairwise comparisons within an ongoing platform trial where control of the pairwise error rate (PWER) or FWER (for a subset of pairwise comparisons) is required.