Outcome-Adaptive Randomization: Is It Useful?

Abstract

Outcome-adaptive randomization is one of the possible elements of an adaptive trial design in which the ratio of patients randomly assigned to the experimental treatment arm versus the control treatment arm changes from 1:1 over time to randomly assigning a higher proportion of patients to the arm that is doing better. Outcome-adaptive randomization has intuitive appeal in that, on average, a higher proportion of patients will be treated on the better treatment arm (if there is one). In both the randomized phase II and phase III settings with a short-term binary outcome, we compare outcome-adaptive randomization with designs that use 1:1 and 2:1 fixed-ratio randomizations (in the latter, twice as many patients are randomly assigned to the experimental treatment arm). The comparisons are done in terms of required sample sizes, the numbers and proportions of patients having an inferior outcome, and we restrict attention to the situation in which one treatment arm is a control treatment (rather than the less common situation of two experimental treatments without a control treatment). With no differential patient accrual rates because of the trial design, we find no benefits to outcome-adaptive randomization over 1:1 randomization, and we recommend the latter. If it is thought that the patient accrual rates will be substantially higher because of the possibility of a higher proportion of patients being randomly assigned to the experimental treatment (because the trial will be more attractive to patients and clinicians), we recommend using a fixed 2:1 randomization instead of an outcome-adaptive randomization.