Statistical Inference of Adaptive Designs with Binary Responses

Abstract

Adaptive designs of clinical trials are ethical alternatives when the traditional randomization becomes ethically infeasible in desperate medical situations. However, such a design creates a dependency among trial data and its statistical analysis becomes more complex than the analysis for traditional randomized clinical trials. In this article, we examine adaptive designs with dichotomous responses from two treatments and extend some commonly used statistical methods for independent data. Under a regularity condition, the estimated odds ratio and its logarithm are shown to follow asymptotically normal distributions. Moreover, the ordinary goodness-of-fit test statistic for two-by-two contingency tables with dependent data is shown to be asymptotically chi-square distributed. We also discuss the consistency of maximum likelihood estimators of the unknown parameters for a wide class of adaptive designs.