Covariate-Adjusted Adaptive Designs for Continuous Responses in a Phase III Clinical Trial: Recommendation for Practice

摘要

One adaptive design is proposed and studied by Bandyopadhyay and Biswas (2001) for comparing two treatments having continuous responses with covariates at hand in a phase III clinical trial. On the other hand, a drop-the-loser urn design is recently proposed by Ivanova (2003), which is known to have the least variability among urn-based adaptive designs for binary responses. The drop-the-loser rule for continuous data was recently introduced by Ivanova et al. (2006). But neither of the works considered covariates for the allocation design. The present paper provides a version of the newly proposed adaptive design, drop-the-loser rule, but for continuous responses and by incorporating the covariate information in the allocation procedure. Several exact and limiting properties of the design, and also of a simpler version of it, are studied. We compare the design of Bandyopadhyay and Biswas (2001) with the covariate-adjusted drop-the-loser-type rule for continuous responses and conclude that, although the drop-the-loser rule is better for binary responses, the design of Bandyopadhyay and Biswas (2001) performs better than the drop-the-loser-type rule for continuous responses with covariates. We recommend the existing design of Bandyopadhyay and Biswas (2001) for practical purposes.