The fragility of randomized controlled trials in intracranial hemorrhage.


Department of Intensive Care Unit, Dongyang People's Hospital, No. 60, Wuning West Road, Dongyang, Jinhua, 322100, Zhejiang, People's Republic of China. [Email]


Fragility of randomized controlled trials (RCTs) has been evaluated using a novel metric called fragility index (FI), which measures how many events the statistical significance of a dichotomous outcome depends on. This study aimed to evaluate the fragility of RCTs in intracranial hemorrhage. Literature search (PubMed/Embase) identified all RCTs of intracranial hemorrhage since 2006. The overall distribution of FI was evaluated. Subgroup and spearman correlation analyses were made to explore potential factors that may affect FI value. All the included RCTs were divided into two groups (positive and negative trials) according to the statistical significance of selected outcomes. Finally, 47 positive and 51 negative trials were included. Both the median FI ([2; IQR, 1-4] vs. [6; IQR, 4-9], p < 0.001) and the proportion of trials with FI ≤1 (2 vs. 18, p < 0.001) in positive trials were smaller than negative trials. In subgroup comparison within positive trials, sample size ([165; IQR, 87-200] vs. [83; IQR, 60-120], p = 0.015) and number of events ([35; IQR, 20-72] vs. [24; IQR, 11-32], p = 0.015) were higher in subgroup with FI >1 than the subgroup with FI ≤1. Weak positive correlations were found between FI and sample size and number of events. In the field of intracranial hemorrhage, trials reporting significant conclusions often depend on a small number of events. Compared to sample size, this phenomenon is more likely to be affected by statistical approach and trial methodology.


Fragility index,Intracranial hemorrhage,Randomized controlled trial,Review,