Fig. 4

Result of TSA for allele model. Required information size was 5061 patients (α = 5 %, β = 20 %). The blue cumulative Z-curve crosses the inward sloping red trial sequential monitoring boundary for benefit during the second trial but does not reach the required information size. The horizontal green lines illustrate the conventional level of statistical significance (two-sided α = 0.05), which was intersected after the first trial. Square symbol z-score for single study, diamond symbol trial sequential monitoring boundary for benefit score for single study