Blinded Sample Size Re-Estimation in Comparative Clinical Trials With Overdispersed Count Data: Incorporation of Misspecification of the Variance Function

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.