Subgroup-adaptive randomization for subgroup confirmation in clinical trials.

Abstract

A well-known issue when testing for treatment-by-subgroup interaction is its low power, as clinical trials are generally powered for establishing efficacy claims for the overall population, and they are usually not adequately powered for detecting interaction (Alosh, Huque, & Koch [2015] Journal of Biopharmaceutical Statistics, 25, 1161-1178). Hence, it is necessary to develop an adaptive design to improve the efficiency of detecting heterogeneous treatment effects within subgroups. Considering Neyman allocation can maximize the power of usual Z-test (see p. 194 of the book edited by Rosenberger and Lachin), we propose a subgroup-adaptive randomization procedure aiming to achieve Neyman allocation in both predefined subgroups and overall study population in this paper. To verify whether the proposed randomization procedure works as intended, relevant theoretical results are derived and displayed . Numerical studies show that the proposed randomization procedure has obvious advantages in power of tests compared with complete randomization and Pocock and Simon's minimizationmethod.