Randomized play-the-winner clinical trials: review and recommendations.

The randomized play-the-winner rule is an adaptive randomized design, based on an urn model, that is used occasionally in clinical trials. This paper discusses practical and theoretical issues arising from its use, including stratification, delayed response, operating characteristics, selection of urn parameters, and inference. The paper also discusses recent experience with adaptive clinical trials within the pharmaceutical industry. The author concludes that the randomized play-the-winner rule is appropriate for some clinical trials, but intense and thoughtful planning must take place in the design phase. Such planning should incorporate considerations of variability, power, and appropriate techniques.