The fragility index can be used for sample size calculations in clinical trials

Benjamin R Baer*, Mario Gaudino, Stephen E Fremes, Mary Charlson, Martin T Wells

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objective:The fragility index is a clinically interpretable metric increasingly used to interpret the robustness of clinical trials results that is generally not incorporated in sample size calculation and applied post-hoc. In this manuscript, we propose to base the sample size calculation on the fragility index in a way that supplements the classical prefixed alpha and power cutoffs and we provide a dedicated R software package for the design and analysis tools.

Study design and setting:This approach follows from a novel hypothesis testing framework that is based on the fragility index and builds on the classical testing approach. As case studies, we re-analyse the design of two important trials in cardiovascular medicine, the FAME and FAMOUS-NSTEMI trials.

Results:The analyses show that approach returns sample sizes which results in a higher power for the
value based test and most importantly a lower and context dependent Type I error rate for the fragility index based test compared to standard tests.

Conclusion:Our method allows clinicians to control for the fragility index during clinical trial design.
Original languageEnglish
Pages (from-to)199-209
Number of pages11
JournalJournal of Clinical Epidemiology
Early online date14 Sept 2021
Publication statusPublished - Nov 2021


  • Gragility index
  • P value
  • Statistical significance
  • Research methods
  • Sample size calculation
  • Trial design


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