Assessing the robustness of results from clinical trials and meta-analyses with the fragility index

Lifeng Lin, Aiwen Xing, Haitao Chu, M. Hassan Murad, Chang Xu, Benjamin R. Baer, Martin T. Wells, Luis Sanchez-Ramos

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations


The fragility index has been increasingly used to assess the robustness of the results of clinical trials since 2014. It aims at finding the smallest number of event changes that could alter originally statistically significant results. Despite its popularity, some researchers have expressed several concerns about the validity and usefulness of the fragility index. It offers a comprehensive review of the fragility index's rationale, calculation, software, and interpretation, with emphasis on application to studies in obstetrics and gynecology. This article presents the fragility index in the settings of individual clinical trials, standard pairwise meta-analyses, and network meta-analyses. Moreover, this article provides worked examples to demonstrate how the fragility index can be appropriately calculated and interpreted. In addition, the limitations of the traditional fragility index and some solutions proposed in the literature to address these limitations were reviewed. In summary, the fragility index is recommended to be used as a supplemental measure in the reporting of clinical trials and a tool to communicate the robustness of trial results to clinicians. Other considerations that can aid in the fragility index's interpretation include the loss to follow-up and the likelihood of data modifications that achieve the loss of statistical significance.

Original languageEnglish (US)
Pages (from-to)276-282
Number of pages7
JournalAmerican journal of obstetrics and gynecology
Issue number3
StatePublished - Mar 2023

Bibliographical note

Funding Information:
L.L. was supported, in part, by the US National Institutes of Health (NIH) National Library of Medicine (grant number R01 LM012982) and the NIH National Institute of Mental Health (grant number R03 MH128727). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
© 2022 Elsevier Inc.


  • P value
  • confidence interval
  • fragility index
  • meta-analysis
  • research replicability
  • statistical significance

PubMed: MeSH publication types

  • Journal Article
  • Review


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