4.

Trial Sequential Analysis of randomised clinical trials evaluating flumazenil versus placebo for people with cirrhosis and hepatic encephalopathy. The outcome is hepatic encephalopathy. The original meta‐analysis included 11 randomised clinical trials with 824 participants. The Trial Sequential Analysis is made with alpha 3%, power 90%, relative risk reduction 20%, assumed control risk 60%, and diversity 10%. The blue line (Z‐curve) corresponds to the cumulative meta‐analysis, the black horizontal line is the conventional boundary (3% level of significance), and the inward sloping green line is the Trial Sequential Monitoring Boundary. The analysis found that the Z‐curve crossed the monitoring boundary before reaching the diversity‐adjusted required information size of 914 participants.