Two-stage designs optimal under the alternative hypothesis for phase II cancer clinical trials.
Two-stage designs optimal under the alternative hypothesis for phase II cancer clinical trials.
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DOI：
10.1016/j.cct.2010.07.008
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发表时间：
2010-11
影响因子：
2.2
通讯作者：
Thompson SG
中科院分区：
文献类型：
--
作者：
Mander AP;Thompson SG
Simon两阶段优化设计常用于II期癌症临床试验。除非零假设（真实肿瘤反应率低于某一特定值）在第一阶段结束时已被接受，否则研究将继续进行第二阶段。对于给定的类型1和类型2错误率，传统的最优设计是在零假设下最小化期望样本量的设计。然而，至少有一些新的药物是有效的，应该考虑明确解决这种可能性的设计。因此，我们研究了在替代假设下最优的新设计，即肿瘤反应率高于零假设值，以及允许早期停止疗效的设计。我们提供软件来识别相应的最优和最大最小设计。如果替代假设是正确的，预期样本量的可观节省可以实现，而如果零假设是正确的，样本量也不会受到太大的影响。我们提出了一个例子，讨论在实际情况下不同设计的优点。我们的结论是，在一系列关于真实反应率的假设下考虑最佳设计是相关的，并且就预期样本量而言，允许提前停止疗效总是有利的。
The Simon two-stage optimal design is often used for phase II cancer clinical trials. A study proceeds to the second stage unless the null hypothesis, that the true tumour response rate is below some specified value, is already accepted at the end of stage one. The conventional optimal design, for given type 1 and type 2 error rates, is the one which minimises the expected sample size under the null hypothesis. However, at least some new agents are active, and designs that explicitly address this possibility should be considered. We therefore investigate novel designs which are optimal under the alternative hypothesis, that the tumour response rate is higher than the null hypothesis value, and also designs which allow early stopping for efficacy. We make available, software for identifying the corresponding optimal and minimax designs. Considerable savings in expected sample sizes can be achieved if the alternative hypothesis is in fact true, without sample sizes suffering too much if the null hypothesis is true. We present an example discussing the merits of different designs in a practical context. We conclude that it is relevant to consider optimal designs under a range of hypotheses about the true response rate, and that allowing early stopping for efficacy is always advantageous in terms of expected sample size.
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