Up-front versus sequential randomizations for inference on adaptive treatment strategies

Abstract

Adaptive treatment strategies are useful in the treatment of chronic diseases such as AIDS and cancer because they allow tailoring the treatment to a patient's need and disease status. We consider two randomization schemes for clinical trials that are commonly used to design studies comparing adaptive treatment strategies, namely, up-front randomization and sequential randomization. Up-front randomization is the classical method of randomization where patients are randomized at the beginning of the study to pre-specified treatment strategies. In sequentially randomized trials, patients are randomized sequentially to available treatment options over the duration of the therapy as they become eligible to receive subsequent treatments. We compare the efficiency and the power of the traditional up-front randomized trials with that of sequentially randomized trials designed for comparing adaptive treatment strategies based on a continuous outcome. The analytical and simulation results indicate that, when properly analyzed, sequentially randomized trials are more efficient and powerful than up-front randomized trials.