Early stopping of randomized clinical trials for overt efficacy is problematic

Dirk Bassler, Victor M. Montori, Matthias Briel, Paul Glasziou, Gordon Guyatt

Research output: Contribution to journalReview article

84 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)241-246
Number of pages6
JournalJournal of Clinical Epidemiology
Volume61
Issue number3
DOIs
StatePublished - Mar 1 2008

Keywords

  • Data-monitoring committee
  • Interim analysis
  • Randomized controlled trial
  • STOPIT-2
  • Stopping for benefit
  • Stopping rule

ASJC Scopus subject areas

  • Epidemiology

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