Longitudinal Random Forests for Sparse and Irregular Response Trajectories
Authors: Yangsheng Wang, Xiaotian Dai, Haoda Fu, Guifang Fu
Organizations: Department of Mathematics and Statistics, Binghamton University, Binghamton, New York 13902, USA · Department of Mathematics, Illinois State University, Normal, Illinois 61790, USA · Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Longitudinal studies often collect data at sparse, irregular, and unequally spaced time points. Such heterogeneity is often driven by subject-specific covariates, yet existing methods have been restricted to a scalar endpoint value, completely neglecting the underlying response trajectories. We propose a novel Longitudinal Random Forest (LRF) framework that leverages tree-based ensemble machine learning with adaptive node-wise longitudinal trajectory estimation. The LRF framework makes five methodological contributions. it captures each subject's individual response trajectory while simultaneously accommodating within-node correlation, between-node heterogeneity, and nonlinear and interactive covariate effects. It introduces a novel trajectory-based splitting criterion that maximizes trajectory separation while incorporating a size-weighted penalty; it provides two variants, Principal Analysis by Conditional Expectation (LRF-PACE) and adaptive linear mixed-effects models (LRF-adaptiveLMM), which employ nonparametric and semiparametric node-wise smoothers, respectively, while learning covariate effects in a data-driven manner. It provides a comprehensive interpretation of covariates using both the classical trajectory-based permutation variable importance measure (PVIM) and a newly proposed finite-way interaction frequency count, and it not only predicts entire trajectories for new subjects but also forecasts future trajectories for existing subjects. Extensive simulation studies demonstrate that LRF achieves superior performance over several competing methods, even under severe sparsity. The practical significance of the LRF framework lies in its ability to address five important clinical questions.
Clinical data sources such as electronic health records and wearable sensors record patient status repeatedly over follow-up, often at irregular times and on different schedules for different measurements. These data create opportunities for continuously updated, individualized risk prediction. Existing approaches, however, often simplify the temporal structure for model fitting. We introduce Random Hazard Forests (RHF), a survival tree ensemble that estimates how a patient's hazard changes in continuous time as new measurements become available. The method formulates the estimation problem directly through a nonparametric hazard likelihood for predictable covariate processes. An efficient working model guides tree construction, after which flexible time-varying hazards are estimated for each terminal node. Given any predictable covariate path, each tree follows the path through its terminal nodes over time and assembles the corresponding node-level hazards into a trajectory. Averaging these trajectories across trees yields the pathwise hazard estimate. Because routing at each time uses only the covariate state available immediately beforehand, the construction accommodates internal longitudinal covariates without lookahead. Simulations and an intensive care application show that the forest accurately estimates changing risk under irregular and asynchronous covariate updates.
Hemant Ishwaran, Eileen M. Hsich, Udaya B. Kogalur +1
Longitudinal cohort studies produce repeated data that enable the assessment of time-varying association patterns between exposures and health outcomes. Classical linear mixed-effects models (LMMs) can accommodate a large variety of association patterns while accounting for the irregularly spaced, partially observed measurement. But they require the analyst to pre-specify the functional form linking the exposure history to the outcome. We propose the Neural ODE-LMM, which embeds a Neural Ordinary Differential Equation (Neural ODE) within the linear mixed-effects framework: a learned vector field encodes covariate trajectories into a continuous-time latent state that drives both the fixed- and random-effect design, while preserving the standard LMM observation model. This retains classical likelihood-based inference while learning complex, potentially cumulative, covariate effects flexibly. All parameters are estimated by maximising a penalised marginal likelihood. To quantify covariate effects, we introduce contrasts of counterfactual predictions that compare the expected outcome under alternative covariate trajectories with variance estimated via the delta method. In simulations, the model recovers both instantaneous and cumulative-burden effects without prior specification of the functional form. Applied to the Trois-Cités (3C) cohort, a population-based study of 7{,}324 participants, the method reveals trajectory-dependent associations of BMI and fasting glucose with cognitive decline.
We present a regression-adjustment framework designed for the estimation of longitudinal treatment effects in randomized experiments under static regimes. While regression-adjustment methods are useful for variance reduction in randomized experiments by using pre-treatment covariates, they usually focus only on average effects, from which we cannot obtain valuable insights into when the effects appear and how long they continue. To address this issue, we consider intermediate outcomes and evolving post-treatment covariates over time, and we represent such dynamic trajectories using transition kernels. Furthermore, we establish the asymptotic normality and the semiparametric efficiency bound for our estimator, enabling more powerful statistical inference. Simulation studies and empirical analysis using A/B test data from a streaming platform in Japan show the practical advantages of our method.