Interim analyses and early termination of clinical trials.

The group sequential tests (GST) are appropriate for performing interim analyses in clinical trials. Various GST are reviewed and compared in this paper in terms of the expected sample size, the maximum sample size, and other practical aspects. Also discussed are the p-values of the significant differences for GST. Common problems and difficulties of using GST in practice are examined. One problem is difficulties associated with the delayed data accumulated after a trial is terminated at an interim test. The GST with O'Brien-Fleming type of boundaries are found to be safe in dealing with delayed observations. Possible approaches for performing futility analyses are illustrated with examples. It is recommended that futility analysis with GST be built into the design of large clinical trials.