Treatment allocation methods in clinical trials: a review.

A comprehensive review of methods for allocation of treatments to patients in clinical trials is presented. Attention is restricted to controlled, prospective trials, as opposed to comparisons involving historical or other 'external' controls. We describe the features of each method and classify them according to whether their primary focus is randomization, efficiency, or balance with respect to prognostic factors. Methods which prevent bias, ensure an efficient treatment comparison and are simple to implement will contribute to the ability of clinical trials to provide precise and valid treatment comparisons. We assess critically the extent to which the methods achieve these goals, review the relationships of the allocation methods with subsequent analyses of the trial results, discuss current usage and provide guidelines for choice of method.