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A multi-state model for joint modelling of terminal and non-terminal events with application to Whitehall II
F Siannis1, V T Farewell, J Head
1MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge CB4 2AP, UK.
Insights
This study introduces a new statistical model to jointly analyze fatal and non-fatal coronary heart disease (CHD) events in British civil servants. The model accounts for informative censoring in non-fatal events, offering a more comprehensive understanding of CHD risk factors like civil service grade.
Area of Science:
- Epidemiology
- Biostatistics
- Cardiovascular Research
Background:
- Coronary heart disease (CHD) is a major health concern.
- The Whitehall II study tracks CHD events in British civil servants.
- Analyzing both fatal (F) and non-fatal (NF) CHD events presents statistical challenges due to informative censoring of NF events.
Purpose of the Study:
- To develop and apply a novel multi-state statistical model for the joint analysis of fatal and non-fatal CHD.
- To address the issue of potentially informative censoring in non-fatal CHD events.
- To investigate the relationship between civil service grade and CHD risk within the Whitehall II cohort.
Main Methods:
- Introduction of a multi-state model incorporating an unobserved state for joint CHD event modeling.
- Application of two model-based assumptions for ensuring model identifiability.
- Inclusion of a parameter for sensitivity analysis regarding informative censoring assumptions.
- Utilizing Weibull transition rates dependent on explanatory variables for data analysis.
Main Results:
- The study successfully implemented a joint modeling approach for fatal and non-fatal CHD events.
- The model provided insights into CHD event dynamics, accounting for censoring.
- Analysis focused on the association between civil service grade and CHD incidence.
Conclusions:
- The developed multi-state model offers a robust framework for analyzing complex event data with informative censoring.
- This approach enhances the understanding of coronary heart disease progression and risk factors.
- Findings contribute to epidemiological research on occupational health and cardiovascular disease.
Abstract:
Serious coronary heart disease (CHD) is a primary outcome in the Whitehall II study, a large epidemiological study of British civil servants. Both fatal (F) and non-fatal (NF) CHD events are of interest and while essentially complete information is available on F events, the observation of NF events is subject to potentially informative censoring. A multi-state model with an unobserved state is introduced for the joint modelling of F and NF events. Two model-based assumptions ensure identifiability of the model and a parameter is introduced to allow sensitivity analyses concerning the assumption linked to informative censoring. Weibull transition rates, which include dependence on explanatory variables, are used in the analysis of Whitehall II data with a particular focus on the relationship between civil service grade and CHD events.
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