Related Experiment Video
Updated: Sep 19, 2025

Problem-Solving Before Instruction PS-I: A Protocol for Assessment and Intervention in Students with Different Abilities
Published on: September 11, 2021
Definition and Interpretation of Separable Path-specific Effects With Multiple Ordered Mediators
Yan-Lin Chen1, Sheng-Hsuan Lin1,2,3,4
1From the Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
None:
Causal mediation analysis examines the mechanism by which exposure affects outcome via mediators. In contrast to single-mediator scenarios, the presence of multiple ordered mediators introduces complex pathways and corresponding path-specific effects, which are difficult to interpret due to the cross-world counterfactual definition. Path-specific effects also require convoluted and unverifiable assumptions for identification. This article proposes a framework of separable path-specific effects as an extension of the separable effect method to the case of multiple ordered mediators. Compared to the traditional approach, separable path-specific effects can be interpreted as the causal effects of several separated components on the outcome, facilitating a more intuitive understanding of underlying mechanisms. We elucidate the relationship between separable and traditional path-specific effects by demonstrating their equivalence under the individual-level isolation assumptions and identifying both effects under the finest fully randomized causally interpretable structured tree graph (FFRCISTG) model, which inherently makes individual-level isolation assumptions. Moreover, weakening the individual-level isolation assumptions to their population-level counterparts, separable path-specific effects remain identifiable under the FFRCISTG model. Under this causal model, the assumptions for identifying separable path-specific effects can be verified in future experiments, thereby addressing the problem of relying on unverifiable cross-world assumptions in the traditional method. We also discuss how this framework can detect violations of assumptions such as the presence of intermediate confounders and the misspecification of causal order among mediators. In summary, compared with the traditional path-specific effects method, the proposed separable method provides a more verifiable and interpretable approach for causal multiple mediation analysis.
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Epistasis Analysis
Mechanistic Models: Overview of Compartment Models
Parameters Affecting Nonlinear Elimination: Zero-Order Input, First-Order Absorption and Two-Compartment Model
When a drug is administered through a constant intravenous infusion and eliminated via nonlinear pharmacokinetics, it follows zero-order input. For example, oral drugs undergo first-order absorption upon administration and are eliminated through nonlinear pharmacokinetics.
In the case of subcutaneously administered drugs,...
Diversity in Cell Signaling Responses
Graded and Abrupt Responses
Some signaling systems generate...
Multicompartment Models: Overview
These models offer a more comprehensive representation of drug behavior in the body than one-compartment models. They accommodate the complexity of drug distribution,...

