The statistical significance of randomized controlled trial results is frequently fragile: A case for a Fragility Index

Michael Walsh*, Sadeesh K. Srinathan, Daniel F. McAuley, Marko Mrkobrada, Oren Levine, Christine Ribic, Amber O. Molnar, Neil D. Dattani, Andrew Burke, Gordon Guyatt, Lehana Thabane, Stephen D. Walter, Janice Pogue, P. J. Devereaux

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

254 Citations (Scopus)
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Abstract

Objectives

A P-value <0.05 is one metric used to evaluate the results of a randomized controlled trial (RCT). We wondered how often statistically significant results in RCTs may be lost with small changes in the numbers of outcomes.

Study Design and Setting

A review of RCTs in high-impact medical journals that reported a statistically significant result for at least one dichotomous or time-to-event outcome in the abstract. In the group with the smallest number of events, we changed the status of patients without an event to an event until the P-value exceeded 0.05. We labeled this number the Fragility Index; smaller numbers indicated a more fragile result.

Results

The 399 eligible trials had a median sample size of 682 patients (range: 15-112,604) and a median of 112 events (range: 8-5,142); 53% reported a P-value <0.01. The median Fragility Index was 8 (range: 0-109); 25% had a Fragility Index of 3 or less. In 53% of trials, the Fragility Index was less than the number of patients lost to follow-up.

Conclusion

The statistically significant results of many RCTs hinge on small numbers of events. The Fragility Index complements the P-value and helps identify less robust results. 

Original languageEnglish
Pages (from-to)622-628
Number of pages7
JournalJournal of Clinical Epidemiology
Volume67
Issue number6
Early online date05 Feb 2014
DOIs
Publication statusPublished - 01 Jun 2014

Keywords

  • Lost to follow-up
  • Randomized controlled trials
  • Research methodology

ASJC Scopus subject areas

  • Epidemiology

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