Adaptive Design and the Estimand Framework

Abstract

the observed difference in proportions cured between the treatment and control groups without considering the difference in patient characteristics in the population at these two (interim and final) stages, the resulting estimate may not reflect the estimand. This is because the estimate of the unobserved population quantity is obtained from a population that does not reflect the patients randomized. Similarly, if study adaptation Abstract Adaptive designs allow prospectively planned modifications of a study without undermining the integrity and validity of the study. The draft ICH E9 addendum recommends the estimand framework in design, conduct, analysis, and interpretation of clinical trials for assessment of effectiveness of therapies. Herein, we discuss the possible impact and scientific implications when incorporating the estimand framework to adaptively designed clinical trials. It is hoped that this will elucidate how this framework provides a language for discussing relevant questions, related to the attributes of the estimand, that may arise from study adaptations.