Figure 4

Trial sequential analysis of 8 trials comparing rivaroxaban with enoxaparin for major bleeding.

Trial sequential analysis of 8 trials (black square fill icons) illustrating that The cumulative z-curve crossed the traditional boundary but not the trial sequential monitoring boundary and did not reach the required information size, suggesting the need for more evidence to establish additional harms of rivaroxaban over enoxaparin. A diversity adjusted required information size of 22,785 patients was calculated using α = 0.05 (two sided), β = 0.20 (power 80%), a relative risk reduction of −34.59% based on trials with adequate allocation concealment and an event proportion of 1.33% in the control arm. X-axis: the number of patients randomized; Y-axis: the cumulative Z-Score; Horizontal green dotted lines: conventional boundaries (upper for benefit, Z-score = 1.96, lower for harm, Z-score = −1.96, two-sided P = 0.05); Sloping red full lines with black square fill icons: trial sequential monitoring boundaries calculated accordingly; Blue full line with black square fill icons: Z-curve; Vertical red full line: required information size calculated accordingly.