Early stopping of randomized clinical trials for overt efficacy is problematic

J Clin Epidemiol. 2008 Mar;61(3):241-6. doi: 10.1016/j.jclinepi.2007.07.016.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bias
  • Decision Making
  • Ethics, Research
  • Humans
  • Motivation
  • Randomized Controlled Trials as Topic / ethics
  • Randomized Controlled Trials as Topic / methods*
  • Treatment Outcome