Generalized Optimal Design for Two-Arm, Randomized Phase II Clinical Trials with Endpoints from the Exponential Dispersion Family

• Activity Number: 353
• Type: Contributed
• Date/Time: Tuesday, August 6, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Wei Jiang*+ and Jonathan Mahnken and Jianghua He and Matthew S. Mayo
• Companies: University of Kansas Medical Center and The University of Kansas Medical Center and University of Kansas Medical Center and University of Kansas Medical Center
• Keywords: Optimized design ; Sample size ; Multiple constraints ; Standard error

Abstract

For two-arm randomized phase II clinical trials, Mayo, Mahnken, and Soong (2010) proposed an optimized design that minimizes the total sample size under multiple constraints on the precision of the estimated event rates. The original design is limited to trials with dichotomous endpoints. In this paper, we extend the method proposed by Mayo et al. to phase II clinical trials with endpoints from the exponential dispersion family distributions. The proposed optimal design minimizes the total sample size needed to provide estimators of the population means of both arms and their difference with pre-specified precisions. This method can be applied to trials with or without fixed randomization allocation ratios. Implementations of this method to different types of endpoints in the exponential dispersion family are provided. Sample sizes are calculated for multiple design considerations under each distribution.