Abstract

In randomized clinical trials to compare overdispersed count data between treatment groups, blinded sample size re-estimation (BSSR) is an effective approach to ensure power control even under possible misspecifications of the variance function on overdispersion specified at the design stage. Based on interim clinical trial data, the existing BSSR methods try to find a more appropriate value of the dispersion parameter for a “fixed” variance function specified at the design stage. In this article, we develop a new BSSR method that allows for modification of the variance function itself. Simulation studies demonstrated a stable power control of the proposed method. An application to a phase III clinical trial in chronic obstructive pulmonary disease also demonstrated effectiveness of the proposed method.

摘要

在比较治疗组之间过度分散的计数数据的随机临床试验中，盲样重新估计（BSSR）是一种有效的方法，即使在设计阶段指定的过度分散方差函数可能存在错误指定的情况下，也能确保功率控制。基于临时临床试验数据，现有的BSSR方法试图为设计阶段指定的“固定”方差函数找到​​更合适的色散参数值。在本文中，我们开发了一种新的BSSR方法，该方法允许修改方差函数本身。仿真研究证明了所提出方法的稳定功率控制。在慢性阻塞性肺疾病的III期临床试验中的应用也证明了该方法的有效性。