Inference on tree-structured subgroups with subgroup size and subgroup effect relationship in clinical trials

Abstract

When multiple candidate subgroups are considered in clinical trials, we often need to make statistical inference on the subgroups simultaneously. Classical multiple testing procedures might not lead to an interpretable and efficient inference on the subgroups as they often fail to take subgroup size and subgroup effect relationship into account. In this paper, built on the selective traversed accumulation rules (STAR), we propose a data-adaptive and interactive multiple testing procedure for subgroups which can take subgroup size and subgroup effect relationship into account under prespecified tree structure. The proposed method is easy-to-implement and can lead to a more interpretable and efficient inference on prespecified tree-structured subgroups. Possible accommodations to post hoc identified tree-structure subgroups are also discussed in the paper. We demonstrate the merit of our proposed method by re-analyzing the panitumumab trial with the proposed method.

Keywords: efficiency; interpretability; multiple testing; subgroup analysis.