A critique of the fragility index

Desnoyers, Alexandra; Nadler, Michelle; Wilson, Brooke E; Amir, Eitan

doi:10.1016/s1470-2045(19)30583-2

Cited by 12 publications

(7 citation statements)

References 4 publications

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“…They do not account for the time at which events occurred which is a very important consideration, especially in oncological research. 31 FI alone does not convey a measure of precision so it has to be read in conjunction with the p value, sample size, CI, and number lost to follow-up. Because of these limitations, the present study could not analyze less than half of the RCTs included in SSG.…”

Section: Discussionmentioning

confidence: 99%

How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines

Choupoo

Das

Saikia

et al. 2021

Indian Journal of Critical Care Medicine

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A bstract Objectives “Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016” provides guidelines in regard to prompt management and resuscitation of sepsis or septic shock. The study is aimed to assess the robustness of randomized controlled trials (RCTs) that formulate these guidelines in terms of fragility index and reverse fragility index. Method RCTs that contributed to these guidelines having parallel two-group design, 1:1 allocation ratio, and at least one dichotomous outcome were included in the study. The median fragility index was calculated for RCTs with significant statistical outcomes, whereas the median reverse fragility index was calculated for RCTs with nonsignificant statistical results. Results Hundred RCTs that met the inclusion criteria were analyzed. The median fragility index was 5.5 [95% confidence interval (CI) 1–30] and median reverse fragility index was 13 (95% CI 12.07–16.8) at a p value of 0.05. The median reverse fragility index was 16 (95% CI 10–26) at a p value of 0.01. Most of the RCTs included in this analysis were of good quality, having a median Jadad score of 6. Conclusion This analysis found that the surviving sepsis guidelines were based on highly robust RCTs with statistically insignificant results and on some moderately robust RCTs with statistically significant results. RCTs with statistically insignificant results were more robust than RCTs with statistically significant results in regard to these guidelines. Highlights The study assessed the robustness of randomized controlled trials (RCTs) that were used to formulate surviving sepsis guidelines. Most RCTs showed statistically nonsignificant results. RCTs with statistically significant results were moderately fragile whereas RCTs with nonsignificant results were more robust. How to cite this article Choupoo NS, Das SK, Saikia P, Dey S, Ray S. How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines. Indian J Crit Care Med 2021;25(7):773–779.

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Section: Discussionmentioning

confidence: 99%

How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines

Choupoo

Das

Saikia

et al. 2021

Indian Journal of Critical Care Medicine

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“…In some cases, the FI may be highly correlated with P-value and sample size [61][62][63]; it may not provide much more information than these well-reported metrics. The concept of FI considered in this article is restricted to studies with binary outcomes, and it might not be suitable for time-to-event data [64].…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Fragility index of network meta-analysis with application to smoking cessation data

Xing

Chu

Lin

2020

Journal of Clinical Epidemiology

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“…However, in oncology, FI was previously calculated by dichotomizing the final event data without accounting for the time‐to‐event 12 . In cancer, where the benefit of a drug is often measured by its ability to prolong life and/or delay disease progression or relapse, ignoring the time‐to‐event occurrence can over‐estimate the fragility of trials, as demonstrated previously 13‐15 . We have previously developed alternative methods for calculating the FI 3 .…”

Section: Introductionmentioning

confidence: 99%

“… 12 In cancer, where the benefit of a drug is often measured by its ability to prolong life and/or delay disease progression or relapse, ignoring the time‐to‐event occurrence can over‐estimate the fragility of trials, as demonstrated previously. 13 , 14 , 15 We have previously developed alternative methods for calculating the FI. 3 Among a subset of tumor types, estimated median FI was 28.…”

Section: Introductionmentioning

confidence: 99%

Fragility of randomized trials supporting cancer drug approvals stratified by approval pathway and review designations

et al. 2021

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Background It has been suggested that the results from fragile trials are less likely to translate into benefit in routine clinical practice. Methods We searched the Food and Drug Administration (FDA) archives to identify drug approvals for solid organ malignancies between 2010 and 2019. We calculated the Fragility Index (FI) supporting each approval, using methods to account for time‐to‐event. We compared FI and trial and approval characteristics using Mann‐Whitney U and Kruskal‐Wallis test. Using logistic regression, we examined study characteristics associated with withdrawal of consent or lost to follow‐up (WCLFU) exceeding the calculated FI. Results The median FI among 125 included studies was 23 (range 1–322). The FI was ≤10 in 35 studies (28%), 11–20 in 21 (17%), and >20 in 69 (55%). The median FI/Nexp was 7.7% (range 0.1–51.7%). The median FI was significantly lower among approvals processed through the accelerated vs regular pathway (5.5 vs 25, p = 0.001), but there was no difference in median FI/Nexp. The WCLFU exceeded FI in 42% of studies. Overall survival endpoints were more likely to have a WCLFU exceeding FI (OR 3.16, p = 0.003). WCLFU exceeding FI was also associated with a lesser magnitude of effect (median HR 0.69 vs 0.55, p < 0.001). In a sensitivity analysis including only studies with 1:1 randomization, 51% of studies had WCLFU >FI. Conclusion The median FI among all trials was 23, and WCLFU exceeded FI in 42%. Comparative trials in solid tumors supporting approval through the accelerated pathway are more fragile compared to trials approved through the regular pathway, an observation likely explained by a lower sample size in the experimental arm.

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A critique of the fragility index

Cited by 12 publications

References 4 publications

How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines

How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines

Fragility index of network meta-analysis with application to smoking cessation data

Fragility of randomized trials supporting cancer drug approvals stratified by approval pathway and review designations

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