Figure 1.

Trial Sequential Analysis of randomised clinical trials evaluating flumazenil versus placebo for people with hepatic encephalopathy. The outcome is all‐cause mortality. The original meta‐analysis included 11 randomised clinical trials with 842 participants. The Trial Sequential Analysis ignored three randomised clinical trials due to insufficient information size (Cadranel 1995; Gyr 1996; Zhu 1998). The analysis was made with alpha 3%, power 90%, relative risk reduction 20%, assumed control risk 10%, 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. Futility boundaries are ignored because the information is insufficient. The analysis found no evidence to support or refute a beneficial or harmful effect of flumazenil on mortality.