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

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.