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Christophe Tzourio

Publications and source records attributed to Christophe Tzourio.

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A Two-Stage Bayesian Approach for Variable Selection in Joint Modeling of Multiple Longitudinal Markers with Competing Risks

In many clinical and epidemiological studies, collecting longitudinal measurements together with time-to-event outcomes is essential. Accurately estimating the association between longitudinal markers and event risks, as well as identifying key markers for prediction, is especially important in the presence of competing risks. However, as the number of markers increases, fitting full joint models becomes computationally difficult and may lead to convergence issues. We propose a two-stage Bayesian approach for variable selection in joint models with multiple longitudinal markers and competing risks. The method efficiently identifies important longitudinal markers and covariates. In the first stage, a one-marker joint model is fitted for each marker with the competing risks outcome, and individual marker trajectories are predicted, reducing bias from informative dropout. In the second stage, a cause-specific hazards model is fitted, incorporating the predicted current values of all markers as time-dependent covariates. We consider both continuous and Dirac spike-and-slab priors for Bayesian variable selection, implemented through MCMC algorithms. Our approach enables risk prediction using a large number of longitudinal markers, which is often infeasible for standard joint models. We evaluate performance through simulation studies, examining both variable selection and predictive accuracy. Finally, we apply the method to predict dementia risk in the Three-City (3C) study, a French cohort with competing risks of death. To facilitate use, we provide an R package, VSJM, available at: https:/github.com/tbaghfalaki/VSJM.

stat.ME

A location-scale joint model for studying the link between the time-dependent subject-specific variability of blood pressure and competing events

Given the high incidence of cardio and cerebrovascular diseases (CVD), and its association with morbidity and mortality, its prevention is a major public health issue. A high level of blood pressure is a well-known risk factor for these events and an increasing number of studies suggest that blood pressure variability may also be an independent risk factor. However, these studies suffer from significant methodological weaknesses. In this work we propose a new location-scale joint model for the repeated measures of a marker and competing events. This joint model combines a mixed model including a subject-specific and time-dependent residual variance modeled through random effects, and cause-specific proportional intensity models for the competing events. The risk of events may depend simultaneously on the current value of the variance, as well as, the current value and the current slope of the marker trajectory. The model is estimated by maximizing the likelihood function using the Marquardt-Levenberg algorithm. The estimation procedure is implemented in a R-package and is validated through a simulation study. This model is applied to study the association between blood pressure variability and the risk of CVD and death from other causes. Using data from a large clinical trial on the secondary prevention of stroke, we find that the current individual variability of blood pressure is associated with the risk of CVD and death. Moreover, the comparison with a model without heterogeneous variance shows the importance of taking into account this variability in the goodness-of-fit and for dynamic predictions.

stat.ME