Interim analyses with delayed observations in clinical trials

The interim analyses based on group sequential procedures are not convenient if the response time relative to the patient accrual rate is long. Since in most trials patients are accrued and randomized continuously, the response data from those already randomized will continue to accumulate when a trial terminates at an interim test. One should analyse all observations received after the trial terminates along with the data that led to the decision to terminate the trial. Although the most likely case is that the combined results are significant, it could happen that the combined results are not significant. We examined the likelihood of such an event. Our study indicated that the O'Brien-Fleming type of group sequential tests with conservative boundaries in the early stages protects from such an unsettling event.