Fig. 3

Showing trial sequential monitoring boundaries for benefit and harm in a 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 the P-values. a Shows how an early statistical significance no longer is present in a cumulative meta-analysis when the required information size has been reached. b Shows how an early lack of statistical significance emerges later when the requiered information size is achieved. c Shows how an early statistical significance can be avoided by adjusting the level of statistical significance. The etched upper curve is the group sequential boundary adjusting the level of statistical significance for multiple testing and sparse data. Z-value is shown on the y-axis and on the x-axis IS is the required information size [10]