Mediation analysis for a survival outcome with time‐varying exposures, mediators, and confounders

We propose an approach to conduct mediation analysis for survival data with time‐varying exposures, mediators, and confounders. We identify certain interventional direct and indirect effects through a survival mediational g‐formula and describe the required assumptions. We also provide a feasible pa...

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Bibliographic Details
Published in:Statistics in medicine 2017-11, Vol.36 (26), p.4153-4166
Main Authors: Lin, Sheng‐Hsuan, Young, Jessica G., Logan, Roger, VanderWeele, Tyler J.
Format: Article
Language:English
Subjects:
Algorithms
Cardiovascular disease
Cohort Studies
Confounding Factors, Epidemiologic
Coronary Artery Disease - epidemiology
Coronary Artery Disease - mortality
Coronary vessels
Environmental Exposure - adverse effects
Health risk assessment
Humans
Longitudinal Studies
mechanism investigation
mediation analysis
Models, Statistical
Mortality
path analysis
Risk Factors
Smoking
survival
Survival Analysis
time varying
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Summary:We propose an approach to conduct mediation analysis for survival data with time‐varying exposures, mediators, and confounders. We identify certain interventional direct and indirect effects through a survival mediational g‐formula and describe the required assumptions. We also provide a feasible parametric approach along with an algorithm and software to estimate these effects. We apply this method to analyze the Framingham Heart Study data to investigate the causal mechanism of smoking on mortality through coronary artery disease. The estimated overall 10‐year all‐cause mortality risk difference comparing “always smoke 30 cigarettes per day” versus “never smoke” was 4.3 (95% CI = (1.37, 6.30)). Of the overall effect, we estimated 7.91% (95% CI: = 1.36%, 19.32%) was mediated by the incidence and timing of coronary artery disease. The survival mediational g‐formula constitutes a powerful tool for conducting mediation analysis with longitudinal data.
ISSN:0277-6715
1097-0258
DOI:10.1002/sim.7426