LAUSR

For decades, the sufficient cause model and the counterfactual model have shaped our understanding of causation in biomedical science, and the link between these two models has enabled us to obtain a deeper understanding of causality. Recently, a new causal model-the marginal sufficient component cause model-was proposed and applied in the context of interaction or mediation. The proponents of this model have emphasized its utility in visualizing the presence of "agonism" (a subtype of mechanistic interaction) in the counterfactual framework, claiming that the concept of agonism has not been clearly defined in causal inference and that agonistic interaction cannot be visualized by the conventional sufficient cause model. In this article, we illustrate that careful scrutiny based on the conventional sufficient cause model yields further insights into the concept of agonism in a more biologic sense. We primarily focus on the following three points: (1) "agonism" defined in the counterfactual model can be visualized as sets of sufficient causes in the conventional sufficient cause model; (2) although the so-called independent competing assumption or no redundancy assumption may seem irrelevant in the marginal sufficient component cause model, researchers do need to assume that potential completion times of relevant marginal sufficient causes differ; and (3) possibly differing potential completion times of marginal sufficient causes cannot be discerned until their hidden mechanistic paths are considered in the conventional sufficient cause model. In this rapidly progressing field of research, decades after its introduction, the sufficient cause model retains its worth.