Bayesian Adaptive Randomization for the I-SPY 2 SMART

Oregon Convention Center 

The I-SPY 2 sequential multiple assignment randomized trial (SMART) is designed to identify optimal treatment regimes for breast cancer. This design has three stages meant to mimic the decision-making process for sequential treatment. Subjects begin the trial with a first stage randomization to available arms. If interim information on the tumor looks promising, they can go to surgery after the first stage and their pathological complete response (pCR) status is assessed. Otherwise, they proceed to a second stage of randomization. If they do not go to surgery at the second stage, they receive a third stage of treatment then go to surgery. Due to many possible treatment regimes and the desire to improve outcomes in the trial, response-adaptive randomization provides potential statistical and ethical benefits over uniform randomization. We present a Bayesian adaptive randomization scheme known as Thompson sampling that randomizes subjects to arms based on the posterior probability that they maximize the chance of a pCR. Simulation studies show our method improves in-trial pCR rates and identifies optimal regimes at similar rates as uniform randomization.

SMART

adaptive randomization

clinical trials

precision medicine

sequential decision making

multi-armed bandits 

Biometrics Section