ABSTRACT
This chapter is devoted to the study of a so-called group-sequential CARA randomized controlled trial (RCT), with a particular focus on incorporating more flexible (i.e., data-adaptive) techniques to model the response. A CARA RCT is covariate-adjusted: the treatment randomization schemes are allowed to be a function of the patients’ pre-treatment covariates. In addition, a CARA RCT is response-adaptive: the investigators have the opportunity to adjust these schemes during the course of the trial based on accruing information, including previous responses, in order to meet some pre-specified objectives. In a group-sequential CARA RCT, the latter adjustments are made at interim time points given by sequential inclusion of blocks of c patients, where c ≥ 1 is a pre-specified integer. We consider the case of c = 1 for simplicity of exposition, though the discussions generalize to any c > 1.
