Stepwise Fine and Gray: Subject-Specific Variable Selection Shows When Hemodynamic Data Improves Prognostication of Comatose Post-Cardiac Arrest Patients

Xiaobin Shen, Jonathan Elmer, George H. Chen

Abstract: Prognostication for comatose post‐cardiac arrest patients is a critical challenge that directly impacts clinical decision-making in the ICU. Clinical information that informs prognostication is collected serially over time. Shortly after cardiac arrest, various time-invariant baseline features are collected (e.g., demographics, cardiac arrest characteristics). After ICU admission, additional features are gathered, including time-varying hemodynamic data (e.g., blood pressure, doses of vasopressor medications). We view these as two phases in which we collect new features. In this study, we propose a novel stepwise dynamic competing risks model that improves the prediction of neurological outcomes by automatically determining when to take advantage of time-invariant features (first phase) and time-varying features (second phase). A key finding is that it is not always beneficial to use all features (first and second phase) for prediction. Notably, our model finds patients for whom this second phase (time-varying hemodynamic) information is beneficial for prognostication and also when this information is beneficial (as we collect more hemodynamic data for a patient over time, how important these data are for prognostication varies). Our approach extends the standard Fine and Gray model to explicitly model the two phases and to incorporate neural networks to flexibly capture complex nonlinear feature relationships. Evaluated on a retrospective cohort of 2,278 comatose post-arrest patients, our model demonstrates robust discriminative performance for the competing outcomes of awakening, withdrawal of life-sustaining therapy, and death despite maximal support. Subgroup analyses based on the motor component of the FOUR score reveal that patients with severe neurological dysfunction receive minimal additional prognostic benefit from hemodynamic data, whereas those with moderate-to-mild impairment derive significant incremental risk information. These findings underscore the potential of dynamic risk modeling for enhancing prognostication. Our approach generalizes to more than two phases in which new features are collected and could be used in other dynamic prediction tasks, where it may be helpful to know when and for whom newly collected features significantly improve prediction.