Sequential designs for phase III clinical trials incorporating treatment selection
Sequential designs for phase III clinical trials incorporating treatment selection
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DOI：
10.1002/sim.1362
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发表时间：
2003-03-15
影响因子：
2
通讯作者：
Todd, S
中科院分区：
文献类型：
--
作者：
Stallard, N;Todd, S
第三阶段临床试验的大多数统计方法侧重于单一试验性治疗与对照的比较。越来越多的人希望减少新药获得监管批准之前的时间，这导致了试验的两阶段或顺序设计的开发，这些设计将与第三阶段相关的最终分析与第二阶段研究的治疗选择要素相结合。在这篇文章中，我们考虑了一项试验，其中在第一次中期分析中选择了许多实验治疗中最有希望的一种。与Follman、Proschan和Geller提出的方法相比，这大大减少了与构建停止边界相关的计算量(Biometrics 1994；50：325-336)。计算要求不超过单一实验处理与对照的顺序比较。现有的方法在两个方面进行了扩展。首先，使用有效分数作为检验统计量，使得分析二进制、正常或故障时间数据以及调整协变量或分层变得简单明了。其次，还考虑了审判权力的问题，以便能够确定给予指定权力所需的样本大小。版权所有(C)2003 John Wiley Sons，Ltd.
Most statistical methodology for phase III clinical trials focuses on the comparison of a single experimental treatment with a control. An increasing desire to reduce the time before regulatory approval of a new drug is sought has led to development of two-stage or sequential designs for trials that combine the definitive analysis associated with phase III with the treatment selection element of a phase II study. In this paper we consider a trial in which the most promising of a number of experimental treatments is selected at the first interim analysis. This considerably reduces the computational load associated with the construction of stopping boundaries compared to the approach proposed by Follman, Proschan and Geller (Biometrics 1994; 50:325-336). The computational requirement does not exceed that for the sequential comparison of a single experimental treatment with a control. Existing methods are extended in two ways. First, the use of the efficient score as a test statistic makes the analysis of binary, normal or failure-time data, as well as adjustment for covariates or stratification straightforward. Second, the question of trial power is also considered, enabling the determination of sample size required to give specified power. Copyright (C) 2003 John Wiley Sons, Ltd.