Seamless Phase II/III Combination Study Through Response Adaptive Randomization

Abstract

In clinical trials, multiple doses of a new drug are often tested in a Phase II dose finding study. A promising dose then is chosen for further testing and confirmation of its effectiveness in a Phase III study. Although this approach is pragmatically sound, it is known to be inefficient and unreliable because of the time and resource spent on and the very limited information generated from the Phase II study. In this research, a seamless design based on adaptive patient allocation is proposed to combine the traditional Phase II and Phase III steps to achieve the objectives of dose identification and confirmation at the same time within one study. The control of type I error rate is discussed and simulations show that with the proposed method the type I error rate of the study is controlled, and its efficiency and reliability are greatly improved as compared to the traditional approach.