Desseaux K, Porcher R
Inserm U717, Département de Biostatistique et Informatique Médicale, Hôpital Saint-Louis, AP-HP, Université Paris 7, Paris, France.
Stat Med. 2007 Nov 30;26(27):5002-13. doi: 10.1002/sim.2966.
Flexible trials with adaptive design modification at interim analyses have been recently proposed as an answer to cope with some limitations of traditional designs for phase III trials. Actually, the sample size and duration of fixed design trials strongly depend on the determination, prior to the study, of key parameters such as the expected treatment effect and the event rates. A misspecification of these parameters may result in an underpowered or overpowered trial. In the flexible framework, the remainder of a design can be modified at an interim analysis, while preserving the initially specified global error rates. In this work, we present a flexible design with sample size re-evaluation for survival trials and study its properties in practical settings. The results show that, if parameters are initially misspecified, the proposed method allows an improved power control with a reasonable increase in sample size, if any. Practical guidelines concerning the choice of the trial parameters are also given.
近期，有人提出在期中分析时采用具有适应性设计修改的灵活试验，以应对传统III期试验设计的一些局限性。实际上，固定设计试验的样本量和持续时间在很大程度上取决于在研究之前对关键参数的确定，如预期治疗效果和事件发生率。这些参数的错误设定可能会导致试验效能不足或过高。在灵活设计框架下，设计的其余部分可在期中分析时进行修改，同时保持最初设定的整体错误率。在这项工作中，我们提出了一种用于生存试验的样本量重新评估的灵活设计，并研究其在实际环境中的特性。结果表明，如果参数最初设定错误，所提出的方法能够在合理增加样本量（如有需要）的情况下实现更好的效能控制。此外，还给出了关于试验参数选择的实用指南。
