Drug Evaluation Committee Causal Inference for Interpretation - Causal Mediated Analysis
June 2024
The deliverables related to causal inference—created with the hope of deepening understanding of the “estimand” previously published by the Data Science Subcommittee of the Drug Evaluation Committee of the Japan Pharmaceutical Manufacturers Association—outlined the conceptual framework of causal inference aimed at evaluating causal relationships between treatments of interest and outcomes.While these are the primary focus of many clinical studies, there may also be interest in the mechanisms and pathways of these causal relationships, as well as the influence of variables (mediators) between the treatment and the outcome, in order to gain a deeper understanding of the data obtained from clinical studies.In the context of drug development, pharmacodynamic markers and surrogate endpoints can be considered mediating variables. To examine the influence of such mediating variables, a causal inference approach known as mediation analysis is required.
Therefore, we—the Task Force 3-1 for the 2023 fiscal year of the Data Science Subcommittee of the Drug Evaluation Committee of the Japan Pharmaceutical Manufacturers Association—have produced a document on causal mediation analysis as one of the methods useful for interpreting results.Chapter 1 explains the rationale for mediation analysis along with specific examples of its application, and outlines the roles and considerations for both clinical and statistical personnel when conducting mediation analysis.Furthermore, starting in Chapter 2, with statisticians as the intended audience, we organize the fundamental aspects of causal mediation analysis, present estimation methods tailored to different types of outcomes, describe sensitivity analysis techniques, and provide numerical examples and analysis code.
We hope this document will assist clinicians and statisticians in planning, analyzing, and interpreting the results when implementing causal mediation analysis.
Japan Pharmaceutical Manufacturers Association (JPMA) Drug Evaluation Committee
Data Science Subcommittee FY2023 Task Force 3-1
Causal Inference for Interpretation - Causal Mediated Analysis