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Cohort comparison studies have traditionally been hypothesis driven and conducted in carefully controlled environments (such as clinical trials). Given two groups of event sequence data, researchers test a single hypothesis (e.g., does the group taking Medication A exhibit more deaths than the group taking Medication B?). Recently, however, researchers have been moving toward more exploratory methods of retrospective analysis with existing data. In this article, we begin by showing that the task of cohort comparison is specific enough to support automatic computation against a bounded set of potential questions and objectives, a method that we refer to as High-Volume Hypothesis Testing (HVHT). From this starting point, we demonstrate that the diversity of these objectives, both across and within different domains, as well as the inherent complexities of real-world datasets, still requires human involvement to …