Time-dependent mediators in survival analysis: Modeling direct and indirect effects with the additive hazards model.
Pubmed ID: 30779372
Journal: Biometrical journal. Biometrische Zeitschrift
Publication Date: May 1, 2020
MeSH Terms: Humans, Survival Analysis, Clinical Trials as Topic, Blood Pressure, Models, Statistical, Biometry
Grants: 239956/F20, 107617/Z/15/Z, 795292
Authors: Stensrud MJ, Strohmaier S, Aalen OO, Didelez V, Daniel R, Røysland K
Cite As: Aalen OO, Stensrud MJ, Didelez V, Daniel R, Røysland K, Strohmaier S. Time-dependent mediators in survival analysis: Modeling direct and indirect effects with the additive hazards model. Biom J 2020 May;62(3):532-549. Epub 2019 Feb 19.
Studies:
- Systolic Blood Pressure Intervention Trial (SPRINT)
- Systolic Blood Pressure Intervention Trial Primary Outcome Paper (SPRINT-POP) Data
Abstract
We discuss causal mediation analyses for survival data and propose a new approach based on the additive hazards model. The emphasis is on a dynamic point of view, that is, understanding how the direct and indirect effects develop over time. Hence, importantly, we allow for a time varying mediator. To define direct and indirect effects in such a longitudinal survival setting we take an interventional approach (Didelez, 2018) where treatment is separated into one aspect affecting the mediator and a different aspect affecting survival. In general, this leads to a version of the nonparametric g-formula (Robins, 1986). In the present paper, we demonstrate that combining the g-formula with the additive hazards model and a sequential linear model for the mediator process results in simple and interpretable expressions for direct and indirect effects in terms of relative survival as well as cumulative hazards. Our results generalize and formalize the method of dynamic path analysis (Fosen, Ferkingstad, Borgan, & Aalen, 2006; Strohmaier et al., 2015). An application to data from a clinical trial on blood pressure medication is given.