Fragility index and fragility quotient in randomized clinical trials

García, Mario Honrubia; Ferreira, Juliana Carvalho; Caruso, Pedro

doi:10.36416/1806-3756/e20230034

Cited by 1 publication

(1 citation statement)

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“…For a study demonstrating mortality benefit with intervention, the fragility index is a mathematical tool that determines the change in number of deaths required to nullify statistical significance of benefit. It is a measure of robustness of trial results ( Walsh et al, 2014 ; Tignanelli and Napolitano, 2019 ; Andrade, 2020 ; Dettori and Norvell, 2020 ; Itaya et al, 2022 ; Garcia et al, 2023 ). The SAVE-MORE study design does not permit precise fragility assessment since calculation requires 1:1 randomization into control and experimental groups (SAVE-MORE randomized patients 2 anakinra:1 control).…”

Section: Introductionmentioning

confidence: 99%

Anakinra authorized to treat severe coronavirus disease 2019; Sepsis breakthrough or time to reflect?

Shapiro,

Scherger,

Franco-Paredes

et al. 2023

Front. Microbiol.

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IntroductionThe European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) announced conditions for using recombinant human interleukin-1 receptor antagonist (rhIL-1ra) to treat hospitalized patients with Coronavirus disease 2019 (COVID-19) and risk for progression. These decisions followed publication of the suPAR-guided Anakinra treatment for Validation of the risk and early Management OF seveRE respiratory failure by COVID-19 (SAVE- MORE) phase 3 clinical trial that yielded positive results.MethodsWe conducted a literature review and theoretical analysis of IL-1 blockade as a therapy to treat COVID-19. Using a stepwise analysis, we assessed clinical applicability of the SAVE-MORE results and evaluated conceptual support for interleukin-1 suppression as a suitable approach to COVID-19 treatment. This therapeutic approach was then examined as an example of inflammation-suppressing measures used to treat sepsis.ResultsAnakinra use as a COVID-19 therapy seems to rely on a view of pathogenesis that incorrectly reflects human disease. Since COVID-19 is an example of sepsis, COVID-19 benefit due to anti-inflammatory therapy contradicts an extensive history of unsuccessful clinical study. Repurposing rhIL-1ra to treat COVID-19 appears to exemplify a cycle followed by inflammation-suppressing sepsis treatments. A landscape of treatment failures is interrupted by a successful clinical trial. However, subsequent confirmatory study fails to replicate the positive data.DiscussionWe suggest further experimentation is not a promising pathway to discover game-changing sepsis therapies. A different kind of approach may be necessary.

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