The fragility index in multicenter randomized controlled critical care trials

Elliott E. Ridgeon, Paul J. Young, Rinaldo Bellomo, Marta Mucchetti, Rosalba Lembo, Giovanni Landoni

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Abstract

Objectives: Recent literature has drawn attention to the potential inadequacy of frequentist analysis and threshold p values as tools for reporting outcomes in clinical trials. The fragility index, which is a measure of how many events the statistical significance of a result depends on, has been suggested as a means to aid the interpretation of trial results. This study aimed to calculate the fragility index of clinical trials in critical care medicine reporting a statistically significant effect on mortality (increasing or decreasing mortality). Data Sources: Literature search (PubMed/MEDLINE) to identify all multicenter randomized controlled trials in critical care medicine. Study Selection: We identified 862 trials; of which 56 fulfilled eligibility criteria and were included in our analysis. Data Extraction: Calculation of fragility index for trials reporting a statistically significant effect on mortality, and analysis of the relationship between trial characteristics and fragility index. Data Synthesis: The median fragility index was 2 (interquartile range, 1-3.5), and greater than 40% of trials had a fragility index of less than or equal to 1. 12.5% of trials reported loss to follow-up greater than their fragility index. Trial sample size was positively correlated, and reported p value was negatively correlated, with fragility index. Conclusions: In critical care trials reporting statistically significant effects on mortality, the findings often depend on a small number of events. Critical care clinicians should be wary of basing decisions on trials with a low fragility index. We advocate the reporting of fragility index for future trials in critical care to aid interpretation and decision making by clinicians.

Original languageEnglish
Pages (from-to)1278-1284
Number of pages7
JournalCritical Care Medicine
Volume44
Issue number7
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

  • critical care
  • intensive care
  • lost to follow-up
  • mortality
  • randomized controlled trials
  • research methodology

Cite this

Ridgeon, Elliott E. ; Young, Paul J. ; Bellomo, Rinaldo ; Mucchetti, Marta ; Lembo, Rosalba ; Landoni, Giovanni. / The fragility index in multicenter randomized controlled critical care trials. In: Critical Care Medicine. 2016 ; Vol. 44, No. 7. pp. 1278-1284.
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The fragility index in multicenter randomized controlled critical care trials. / Ridgeon, Elliott E.; Young, Paul J.; Bellomo, Rinaldo; Mucchetti, Marta; Lembo, Rosalba; Landoni, Giovanni.

In: Critical Care Medicine, Vol. 44, No. 7, 01.07.2016, p. 1278-1284.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Ridgeon, Elliott E.

AU - Young, Paul J.

AU - Bellomo, Rinaldo

AU - Mucchetti, Marta

AU - Lembo, Rosalba

AU - Landoni, Giovanni

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N2 - Objectives: Recent literature has drawn attention to the potential inadequacy of frequentist analysis and threshold p values as tools for reporting outcomes in clinical trials. The fragility index, which is a measure of how many events the statistical significance of a result depends on, has been suggested as a means to aid the interpretation of trial results. This study aimed to calculate the fragility index of clinical trials in critical care medicine reporting a statistically significant effect on mortality (increasing or decreasing mortality). Data Sources: Literature search (PubMed/MEDLINE) to identify all multicenter randomized controlled trials in critical care medicine. Study Selection: We identified 862 trials; of which 56 fulfilled eligibility criteria and were included in our analysis. Data Extraction: Calculation of fragility index for trials reporting a statistically significant effect on mortality, and analysis of the relationship between trial characteristics and fragility index. Data Synthesis: The median fragility index was 2 (interquartile range, 1-3.5), and greater than 40% of trials had a fragility index of less than or equal to 1. 12.5% of trials reported loss to follow-up greater than their fragility index. Trial sample size was positively correlated, and reported p value was negatively correlated, with fragility index. Conclusions: In critical care trials reporting statistically significant effects on mortality, the findings often depend on a small number of events. Critical care clinicians should be wary of basing decisions on trials with a low fragility index. We advocate the reporting of fragility index for future trials in critical care to aid interpretation and decision making by clinicians.

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