Optimal multistage designs for randomised clinical trials with continuous outcomes
Optimal multistage designs for randomised clinical trials with continuous outcomes
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DOI：
10.1002/sim.4421
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发表时间：
2012-02-20
影响因子：
2
通讯作者：
Thompson, Simon G.
中科院分区：
文献类型：
--
作者：
Wason, James M. S.;Mander, Adrian P.;Thompson, Simon G.
多阶段设计可以大大减少试验的预期样本量。当在每个阶段允许因无效或有效而停止时，不同可能的真实治疗效应（d）下的预期样本量值得关注。d-极大极小设计是在满足I型和II型误差约束的所有设计中使最大预期样本量最小化的设计。以前的工作比较了两阶段d-极大极小设计与其他最优两阶段设计。由于计算问题，以前没有考虑将d-极大极小设计应用于具有两个以上阶段的设计。在本文中，我们通过使用模拟退火的一个新的应用程序，确定的d-极大极小设计的两个以上的阶段。并与其它最优多级设计和三角形设计进行了比较。我们发现，对于两阶段设计，d-极大极小设计在广泛的治疗效果范围内具有良好的预期样本量特性，但通常具有较高的最大样本量。为了克服这个缺点，我们使用容许设计的概念来寻找平衡最大预期样本量和最大样本量的试验。我们表明，这种设计具有良好的预期样本量特性和合理的最大样本量，因此，在临床试验中使用非常有吸引力。版权所有（C）2011约翰威利父子有限公司
Multistage designs allow considerable reductions in the expected sample size of a trial. When stopping for futility or efficacy is allowed at each stage, the expected sample size under different possible true treatment effects (d) is of interest. The d-minimax design is the one for which the maximum expected sample size is minimised amongst all designs that meet the types I and II error constraints. Previous work has compared a two-stage d-minimax design with other optimal two-stage designs. Applying the d-minimax design to designs with more than two stages was not previously considered because of computational issues. In this paper, we identify the d-minimax designs with more than two stages through use of a novel application of simulated annealing. We compare them with other optimal multistage designs and the triangular design. We show that, as for two-stage designs, the d-minimax design has good expected sample size properties across a broad range of treatment effects but generally has a higher maximum sample size. To overcome this drawback, we use the concept of admissible designs to find trials which balance the maximum expected sample size and maximum sample size. We show that such designs have good expected sample size properties and a reasonable maximum sample size and, thus, are very appealing for use in clinical trials. Copyright (C) 2011 John Wiley & Sons, Ltd.