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Abstract

Predicting the individual risk of clinical events using the complete patient history is a major challenge in personalized medicine. Analytical methods have to account for a possibly large number of time-dependent predictors, which are often characterized by irregular and error-prone measurements, and are truncated early by the event. In this work, we extended the competing-risk random survival forests to handle such endogenous longitudinal predictors when predicting event probabilities. The method, implemented in the R package DynForest, internally transforms the time-dependent predictors at each node of each tree into time-fixed features (using mixed models) that can then be used as splitting candidates. The final individual event probability is computed as the average of leaf-specific Aalen–Johansen estimators over the trees. Using simulations, we compared the performances of DynForest to accurately predict an event with (i) a joint modeling alternative when considering two longitudinal predictors only, and with (ii) a regression calibration method that ignores the informative truncation by the event when dealing with a large number of longitudinal predictors. Through an application in dementia research, we also illustrated how DynForest can be used to develop a dynamic prediction tool for dementia from multimodal repeated markers, and quantify the importance of each marker.

Keywords

Individual dynamic prediction multivariate predictors random survival forest longitudinal data survival data competing risks

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Random survival forests with multivariate longitudinal endogenous covariates

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