Evidence, illness, and causation: An epidemiological perspective on the Russo–Williamson Thesis

•We analyze the Russo-Williamson Thesis from the epidemiological perspective.•We suggest replacing “difference-making evidence” with “exposure–outcome evidence”.•We suggest distinguishing between entity-based, association-based, and activity-based mechanistic evidence in the health sciences.•We conclude that Evidence Based Medicine should include mechanistic evidence relevant to a causal claim.

According to the Russo–Williamson Thesis, causal claims in the health sciences need to be supported by both difference-making and mechanistic evidence. In this article, we attempt to determine whether Evidence-based Medicine (EBM) can be improved through the consideration of mechanistic evidence. We discuss the practical composition and function of each RWT evidence type and propose that exposure–outcome evidence (previously known as difference-making evidence) provides associations that can be explained through a hypothesis of causation, while mechanistic evidence provides finer-grained associations and knowledge of entities that ultimately explains a causal hypothesis. We suggest that mechanistic evidence holds untapped potential to add value to the assessment of evidence quality in EBM and propose initial recommendations for the integration of mechanistic and exposure–outcome evidence to improve EBM by robustly leveraging available evidence in support of good medical decisions.