Title: Calculation of the fragility index of randomized controlled trials in epilepsy published in twelve major journals

Abstract

Objective: Fragility index is the minimum number of participants in a trial whose status has to be changed from an ‘event’ to a ‘non-event’ for a dichotomous primary outcome to turn the P-value (calculated by Fischer’s exact test) statistically non-significant (P > 0.05). This study was performed to evaluate the fragility index of randomized controlled trials (RCTs) in epilepsy published in 12 major journals. Methods: We identified the relevant RCTs published in six major epilepsy-related and six Neurology journals from January 2015 to September 2019 and determined the fragility index of those RCTs which reported statistically significant results of dichotomous primary outcomes. We also calculated the Spearman correlation coefficients between the fragility index and the sample size, the event rate, and the reported P-value. Results: A total of 1395 RCTs were screened and finally ten were eligible for the analysis. The median (IQR) fragility index was only 1.5 (11). There was no significant correlation between the fragility index and the sample size (r = 0.620, P = 0.056), the event rate (r = < 0.0001, P = 1.0), and the reported P-value (r = − 0.315, P = 0.447). Conclusion: The median fragility index of the included RCTs on epilepsy was very low. The addition of only two alternate events to an arm of the average trial would have rejected the statistical significance. Fragility index should be used while reporting the results of dichotomous primary outcomes of RCTs