Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit

M Hassan Murad, Gordon H Guyatt, Juan Pablo Domecq, Robin W M Vernooij, Patricia J Erwin, Joerg J Meerpohl, Gabriela J Prutsky, Elie A Akl, Katharina Mueller, Dirk Bassler, Stefan Schandelmaier, Stephen D Walter, Jason W Busse, Benjamin Kasenda, Gennaro Pagano, Hector Pardo-Hernandez, Victor M Montori, Zhen Wang, Matthias Briel

Research output: Contribution to journalReview articlepeer-review

Abstract

OBJECTIVE: We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question.

STUDY DESIGN AND SETTING: We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data.

RESULTS: We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1-13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision).

CONCLUSION: About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.

Original languageEnglish
Pages (from-to)12-19
Number of pages8
JournalJournal of Clinical Epidemiology
Volume82
DOIs
Publication statusPublished - 1 Feb 2017
Externally publishedYes

Keywords

  • Databases, Factual/statistics & numerical data
  • Early Termination of Clinical Trials
  • Epidemiologic Studies
  • Humans
  • Publishing/statistics & numerical data
  • Randomized Controlled Trials as Topic/statistics & numerical data
  • Methodology
  • Trial design
  • Systematic review
  • Trials stopped early for benefit
  • Early termination of trials
  • Randomized controlled trials

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