Drug-Wide Association Study (DWAS): Challenges and Opportunities.

Cancer risk associations with commonly prescribed medications have been mainly evaluated in hypothesis-driven studies that focus on one drug at a time. Agnostic drug-wide association studies (DWAS) offer an alternative approach to simultaneously evaluate associations between a large number of drugs with one or more cancers using large-scale electronic health records. Although cancer DWAS approaches are promising, a number of challenges limit their applicability. This includes the high likelihood of false positivity; lack of biological considerations; and methodological shortcomings, such as inability to tightly control for confounders. As such, the value of DWAS is currently restricted to hypothesis generation with detected signals needing further evaluation. In this commentary, we discuss those challenges in more detail and summarize the approaches to overcome them by using published cancer DWAS studies, including the accompanied article by Støer and colleagues. Despite current concerns, DWAS future is filled with opportunities for developing innovative analytic methods and techniques that incorporate pharmacology, epidemiology, cancer biology, and genetics.See related article by Støer et al., p. 682.