Figure 2.

The adaptive design flow chart illustrates the various decision points and possible outcomes of the adaptive design analyses. Statistical testing using the Wilcoxon Rank sum test statistic (indicated with open circles) can lead to one of several conclusions (indicated by blue arrows). Each conclusion dictates the next step in the adaptive study design (black arrows). For example, if the results of the Wilcoxon Rank Sum test during the first interim analysis indicates ‘futility in the overall cohort’, the adaptive design dictates that the optimal subgroup is selected (white square) and that testing is repeated in this subgroup. If, on repeat testing in the optimal subgroup, neither the futility nor the benefit boundary is crossed, the trial continues but subsequent enrollment (and statistical testing) is limited to this subgroup.