Crouch Luis A, Dodd Lori E, Proschan Michael A
1 Department of Biostatistics, University of Washington, Seattle, WA, USA.
2 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
Clin Trials. 2017 Jun;14(3):237-245. doi: 10.1177/1740774517694130. Epub 2017 Mar 19.
Multi-arm, multi-stage trials have recently gained attention as a means to improve the efficiency of the clinical trials process. Many designs have been proposed, but few explicitly consider the inherent issue of multiplicity and the associated type I error rate inflation. It is our aim to propose a straightforward design that controls family-wise error rate while still providing improved efficiency.
In this article, we provide an analytical method for calculating the family-wise error rate for a multi-arm, multi-stage trial and highlight the potential for considerable error rate inflation in uncontrolled designs. We propose a simple method to control the error rate that also allows for computation of power and expected sample size.
Family-wise error rate can be controlled in a variety of multi-arm, mutli-stage trial designs using our method. Additionally, our design can substantially decrease the expected sample size of a study while maintaining adequate power.
Multi-arm, multi-stage designs have the potential to reduce the time and other resources spent on clinical trials. Our relatively simple design allows this to be achieved while weakly controlling family-wise error rate and without sacrificing much power.
多臂多阶段试验作为提高临床试验效率的一种手段，近来受到了关注。人们提出了许多设计方案，但很少有方案明确考虑多重性这一固有问题以及相关的 I 型错误率膨胀问题。我们的目标是提出一种直接的设计方案，在控制族系错误率的同时，仍能提高效率。
在本文中，我们提供了一种分析方法，用于计算多臂多阶段试验的族系错误率，并强调了在未控制的设计中存在相当大的错误率膨胀的可能性。我们提出了一种简单的方法来控制错误率，该方法还允许计算检验效能和预期样本量。
使用我们的方法，可以在多种多臂多阶段试验设计中控制族系错误率。此外，我们的设计可以在保持足够检验效能的同时，大幅减少研究的预期样本量。
多臂多阶段设计有可能减少临床试验所花费的时间和其他资源。我们相对简单的设计能够在适度控制族系错误率且不牺牲太多检验效能的情况下实现这一点。
