An introduction to the use of interim data analyses in clinical trials.

During a controlled clinical trial, data accumulate that contain information on the relative efficacy of the two treatments, yet these data often are not inspected or analyzed until the planned sample size has been reached and the trial has been terminated. This type of fixed-sample-size trial design, with a single terminal data analysis, has the ethical disadvantage that more patients than are necessary to obtain a reliable result may be randomized to the less efficacious treatment, whichever one that turns out to be. Thus, it often is desirable to schedule one or more analyses of the data, to be conducted before planned termination, to see if a reliable conclusion may be drawn from the data and the trial terminated early. Such analyses are called interim analyses. When interim analyses occur after each of severe relatively large groups of patients, the trial is called a group-sequential trial. Interim data analyses must be planned in advance to avoid increasing the risk of committing a Type I error and to achieve adequate power. This article introduces the statistical issues involved in the planning of interim data analyses and the design of group-sequential clinical trials.