title: Early stopping of randomized clinical trials for overt efficacy is problematic.
abstract: OBJECTIVE
  To illustrate controversial issues associated with stopping randomized controlled trials (RCTs) early for apparent benefit.
  
  
  METHODS
  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.
authors.affiliation: Department of Neonatology, University Children's Hospital, Tübingen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bassler
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
authors.forename: Paul
authors.initials: P
authors.lastname: Glasziou
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
mesh_terms: D015982:Bias; D003657:Decision Making; D032984:Ethics, Research; D006801:Humans; D009042:Motivation; D016032:Randomized Controlled Trials as Topic / Q000941:ethics / Q000379:methods*; D016896:Treatment Outcome