The fragility index in randomised controlled trials of interventions for aneurysmal subarachnoid haemorrhage: A systematic review.

ABSTRACT

Background: Fragility analysis supplements the p-value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we determine the fragility index (FI) and fragility quotient (FQ) of randomised trials in aneurysmal subarachnoid haemorrhage. Methods: This is a systematic review registered with PROSPERO (ID CRD42020173604). Randomised controlled trials in adults with aneurysmal subarachnoid haemorrhage were analysed if they reported a statistically significant primary outcome of mortality, function (e.g. modified Rankin Scale), vasospasm or delayed neurological deterioration. Results: We identified 4825 records with 18 randomised trials selected for analysis. The median fragility index was 2.5 (inter-quartile range 0.25-5) and the median fragility quotient was 0.015 (IQR 0.02-0.039). Five of 20 trial outcomes (25%) had a fragility index of 0. In seven trials (39.0%), the number of participants lost to follow-up was greater than or equal to the fragility index. Only 16.7% of trials are at low risk of bias. Conclusion: Randomised controlled trial evidence supporting management of aneurysmal subarachnoid haemorrhage is weaker than indicated by conventional analysis using p-values alone. Increased use of fragility analysis by clinicians and researchers could improve the translation of evidence to practice.