Early stopping of randomized clinical trials for overt efficacy is problematic.

OBJECTIVE To illustrate controversial issues associated with stopping randomized controlled trials (RCTs) early for apparent benefit. STUDY DESIGN AND SETTING The article presents our review of prior relevant work and our research group's reflections on early stopping. RESULTS Compelling evidence suggests that trials stopped early for benefit systematically overestimate treatment effects, sometimes by a large amount. Unresolved controversies in trials stopped early for benefit include ethical and statistical problems in the interpretation of results. CONCLUSIONS The best strategy to minimize the problems associated with early stopping of RCTs for benefit is not to stop early. As an alternative, we suggest a threefold approach: a low P-value as the threshold for stopping at the time of interim analyses, not to look before a sufficiently large number of events has accrued and continuation of enrollment and follow-up for a further period.