Fractional Two-Step Adaptive Randomization Procedure for Delayed Response in Clinical Trials

• Activity Number: 36
• Type: Contributed
• Date/Time: Sunday, July 29, 2012 : 2:00 PM to 3:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Jiajing Xu*+
• Companies: The University of Hong Kong
• Keywords: Response-adaptive Randomization ; Delayed Response ; Likelihood Ratio Test ; Kaplan-Meier estimator

Abstract

In clinical trials, despite the widespread use of equal randomization in practice,response-adaptive randomization has attracted considerable interest. There is typically a prerun of equal randomization before the implementation of response-adaptive randomization, while it is not clear how many subjects are needed in this equal randomization prephase. We propose a two-step procedure to achieve a balance between power and response. The new design is equipped with a likelihood ratio test before skewing the allocation probability. In addition, real-time response-adaptive randomization often requires patient response to be immediately available after the treatment, while clinical response, such as tumor shrinkage, may take a period of time to exhibit. We develop both a parametric optimal allocation scheme and a nonparametric fractional model to tackle the common problem caused by delayed response in response-adaptive randomization. We evaluate the operating characteristics of the two-stage design through extensive simulation studies. The numerical results show that the proposed method satisfactorily resolves the issues involved in response-adaptive randomization and delayed response.