Robustness of Significant Dichotomous Outcomes in Randomized Controlled Trials in the Treatment of Patients with COVID-19: A Systematic Analysis.

Purpose: Significant results of randomized controlled trials (RCTs) should be properly weighed. This study adopted fragility index (FI) to evaluate the robustness of significant dichotomous outcomes from RCTs on coronavirus disease 2019 (COVID-19) treatment.

Materials and methods: ClinicalTrials.gov and PubMed were searched from inception to July 31, 2021. FIs were calculated and their distribution was depicted. FI's categorical influential factors were analyzed. Spearman correlation coefficient (r _s) was reported for the relationship between FI and the continuous characteristics of RCTs.

Results: Fifty RCTs with 120 outcomes in 7869 patients were included. The FI distribution was abnormal with median 3 (interquartile range 1-7, P = 0.0001). The FIs and robustness were affected by the outcomes of interest, various patient populations, and interventions (T = 18.215,16.667, 23.107; P = 0.02,0.0001, 0.001, respectively). A cubic relationship between the FIs and absolute difference of events between groups with R square of 0.848 (T = 215.828, P = 0.0001, R square = 0.865) was observed. A strong negative logarithmic relationship existed between FI and the P value with R square = - 0.834.

Conclusion: The robustness of significant dichotomous outcomes of COVID-19 treatments was fragile and affected by the outcomes of interest, patients, interventions, P value, and absolute difference of events between the groups. FI was an useful quantitative metric for the binary significant outcomes on COVID-19 treatments.

Registration: PROSPERO (CRD42021272455).

Supplementary information: The online version contains supplementary material available at 10.1007/s44231-022-00027-y.