Stopping guidelines for clinical trials with multiple treatments.
Stopping guidelines for clinical trials with multiple treatments.
复制标题
停止多种治疗临床试验的指南。
DOI：
10.1002/sim.4780121002
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发表时间：
1993
影响因子：
2
通讯作者：
Hughes,MD
中科院分区：
文献类型：
--
作者：
Hughes,MD
停止指南广泛用于涉及两种治疗的长期临床试验。这允许对累积数据进行计划的中期分析，同时保留治疗比较的I类错误率。他们的理念被扩展到多种治疗的试验中，因此在任何中期分析中，如果治疗显著劣于将保留的所有治疗，则可以考虑从试验中退出。拟议的指南旨在保持错误率，以确定实际上最好的治疗或治疗组。使用模拟研究，为两组试验开发的停止指南被证明可直接用于多组研究，当研究的治疗都是实验性的，因此是直接竞争。当一种治疗是护理标准时，修改提供了一个更好的伦理视角，因为它还允许在被认为低于标准时放弃治疗。正态分布的反应，在试验中涉及三个或四个治疗，并使用停止边界的形式提出的奥布莱恩和弗莱明的结果。最后，我讨论了一些额外的考虑因素，在采用多种治疗的试验停止指南是重要的。
Stopping guidelines are widely used in long‐term clinical trials involving two treatments. These allow planned interim analyses of the accumulating data to be undertaken whilst preserving the type I error rate for the treatment comparison. Their philosophy is extended to the case of trials with multiple treatments so that at any interim analysis, treatments may be considered for dropping from the trial if they are significantly inferior to all treatments that will remain. The proposed guidelines are designed to preserve the error rate in determining that treatment or group of treatments which is, in reality, best. Using simulation studies, stopping guidelines developed for two‐arm trials are shown to be directly usable in multiple‐arm studies when the treatments studied are all experimental and so in direct competition. When one treatment is the standard of care, a modification gives a better ethical perspective by also permitting treatments to be dropped when they are deemed inferior to the standard. Results are presented for normally distributed responses in trials involving three or four treatments and using stopping boundaries of the form proposed by O'Brien and Fleming. In conclusion, I discuss some of the additional considerations that are important in employing stopping guidelines in trials with multiple treatments.