The Temptation of Response-Adaptive Randomization.

Response-adaptive randomization (RAR) has recently gained popularity in clinical trials. The intent is noble: minimize the number of participants randomized to inferior treatments and increase the amount of information about better treatments. Unfortunately, RAR causes many problems, including: 1) bias from temporal trends, 2) inefficiency in treatment effect estimation, 3) volatility in sample size distributions that can cause a nontrivial proportion of trials to assign more patients to an inferior arm, 4) difficulty of validly analyzing results, and 5) the potential for selection bias and other issues inherent from being unblinded to ongoing results. The problems of RAR are most acute in the very setting for which RAR has been proposed, namely long duration "platform" trials and infectious disease settings where temporal trends are ubiquitous. Response-adaptive randomization can eliminate the benefits that randomization, the most powerful tool in clinical trials, provides. Use of response adaptive randomization is discouraged.