Fig. 4

Showing trial sequential monitoring boundaries for benefit and futility in cumulative meta-analysis. The Z-value is the test statistic and |Z| = 1.96 corresponds to P = 0.05; the higher Z-values, the lower P-values. a Shows how trial sequential monitoring of a cumulative meta-analysis, before the requiered information size (IS) is achieved, makes it likely that the assumed effect is in fact absent when the Z-curve surpasses the futility-boundary (etched curve). b Shows how trial sequential monitoring of a cumulative meta-analysis, before the required information size (RIS) is achieved, makes it likely that the assumed effect is in fact true when the Z-curve surpasses the trial sequential monitoring boundary for benefit (etched curve). Lan-DeMets’ α-spending-function has been applied for the construction of the trial sequential monitoring boundaries, the critical Z-values [10]