A Family-based Graphical Approach for Testing Hierarchically Ordered Families of Hypotheses

In applications of clinical trials, tested hypotheses are often grouped as multiple hierarchically ordered families. To test such structured hypotheses, various gatekeeping strategies have been developed in the literature, such as series gatekeeping, parallel gatekeeping, tree-structured gatekeeping strategies, etc. However, these gatekeeping strategies are often either non-intuitive or less flexible when addressing increasingly complex logical relationships among families of hypotheses. In order to overcome the issue, in this paper, we develop a new family-based graphical approach, which can easily derive and visualize different gatekeeping strategies. In the proposed approach, a directed and weighted graph is used to represent the generated gatekeeping strategy where each node corresponds to a family of hypotheses and two simple updating rules are used for updating the critical value of each family and the transition coefficient between any two families. Theoretically, we show that the proposed graphical approach strongly controls the overall familywise error rate at a pre-specified level. Through some case studies and a real clinical example, we demonstrate simplicity and flexibility of the proposed approach.