Early stopping of randomized clinical trials for overt efficacy is problematic

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

*Corresponding author for this work

Research output: Contribution to journalReview articleResearchpeer-review

84 Citations (Scopus)

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. (C) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)241-246
Number of pages6
JournalJournal of Clinical Epidemiology
Volume61
Issue number3
DOIs
Publication statusPublished - Mar 2008
Externally publishedYes

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