STATISTICAL ASPECTS OF EARLY TERMINATION IN THE BETA-BLOCKER HEART ATTACK TRIAL

The .beta.-blocker heart attack trial was a randomized double blind controlled trial comparing propranolol with placebo in 3837 patients with a recent myocardial infarction. The trial was terminated on recommendation of the Policy and Data Monitoring Board 9 mo. before the scheduled closing date. The propranolol group, at the time of the decision, had a 26% lower mortality (z = 2.82). Many issues were considered in this decision. These included the magnitude of the overall results; consistency of results across subgroups, clinical centers, and cause of death; and completeness of follow-up. Two basic statistical methods were used in declaring the overall mortality results significant. The first method evaluated the current survival data taking into account the issue of repeated significance testing. The second method evaluated whether the observed trend was so impressive that the occlusion was unlikely to change even if the trial should continue to the scheduled end. These 2 methods, as well as other considerations, led to the recommendation to discontinue the trial.