Adaptive Designs for Clinical Trials

andomized clinical trials serve as the standard for clinical research and have contributed immensely to advances in patient care. Nevertheless, several shortcomings of randomized clinical trials have been noted, including the need for a large sample size and long study duration, the lack of power to evaluate efficacy overall or in important subgroups, and cost. These and other limitations have been widely acknowledged as limiting medical innovation. 1 Adaptive trial design has been proposed as a means to increase the efficiency of randomized clinical trials, potentially benefiting trial participants and future patients while reducing costs and enhancing the likelihood of finding a true benefit, if one exists, of the therapy being studied. Adaptive designs for exploratory clinical trials deal mainly with finding safe and effective doses or with dose-response modeling. The emphasis is on strategies that will assign a larger proportion of the participants to treatment groups that are performing well, reduce the number of participants in treatment groups that are performing poorly, and investigate a dose range that is larger than ranges in corresponding trials with nonadaptive designs, in order to select effective doses for the confirmatory stage of investigation. Control of the type I error rate is less of an issue. In Table