Brannath Werner, König Franz, Bauer Peter
Section of Medical Statistics, Core Unit for Medical Statistics and Informatics, Medical University of Vienna, Spitalgasse 23, A-1090 Wien, Austria.
Stat Med. 2006 Oct 15;25(19):3366-81. doi: 10.1002/sim.2258.
Adaptive test designs for clinical trials allow for a wide range of data driven design adaptations using all information gathered until an interim analysis. The basic principle is to use a test statistics which is invariant with respect to the design adaptations under the null hypothesis. This allows for a control of the type I error rate for the primary hypothesis even for adaptations not specified a priori in the study protocol. Estimation is usually another important part of a clinical trial, however, is more difficult in adaptive designs. In this research paper we give an overview of point and interval estimates for flexible designs and compare methods for typical sample size rules. We also make some proposals for confidence intervals which have nominal coverage probability also after an unforeseen design adaptation and which contain the maximum likelihood estimate and the usual unadjusted confidence interval.
临床试验的适应性试验设计允许使用在中期分析之前收集的所有信息进行广泛的数据驱动设计调整。基本原则是使用在原假设下相对于设计调整不变的检验统计量。这使得即使对于研究方案中未预先指定的调整，也能控制原假设的I型错误率。估计通常是临床试验的另一个重要部分，然而，在适应性设计中更具挑战性。在本研究论文中，我们概述了灵活设计的点估计和区间估计，并比较了典型样本量规则的方法。我们还对置信区间提出了一些建议，这些置信区间在意外的设计调整后也具有名义覆盖概率，并且包含最大似然估计和通常的未调整置信区间。
