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Generative Modeling of Clinical Time Series via Latent Stochastic Differential Equations

arXiv 2511.16427 ↗First posted 20 Nov 2025cs.LG cs.AIcited by 0

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Abstract (arXiv)

Clinical time series data from electronic health records and medical registries offer unprecedented opportunities to understand patient trajectories and inform medical decision-making. However, leveraging such data presents significant challenges due to irregular sampling, complex latent physiology, and inherent uncertainties in both measurements and disease progression. To address these challenges, we propose a generative modeling framework based on latent neural stochastic differential equations (SDEs) that views clinical time series as discrete-time partial observations of an underlying controlled stochastic dynamical system. Our approach models latent dynamics via neural SDEs with modality-dependent emission models, while performing state estimation and parameter learning through variational inference. This formulation naturally handles irregularly sampled observations, learns complex non-linear interactions, and captures the stochasticity of disease progression and measurement noise within a unified scalable probabilistic framework. We validate the framework on two complementary tasks: (i) individual treatment effect estimation using a simulated pharmacokinetic-pharmacodynamic (PKPD) model of lung cancer, and (ii) probabilistic forecasting of physiological signals using real-world intensive care unit (ICU) data from 12,000 patients. Results show that our framework outperforms ordinary differential equation and long short-term memory baseline models in accuracy and uncertainty estimation. These results highlight its potential for enabling precise, uncertainty-aware predictions to support clinical decision-making.

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References · 20

  1. 2018Neural Ordinary Differential Equationscited by 3,779
  2. 2019Aleatoric and Epistemic Uncertainty in Machine Learning: An Introduction to Concepts and Methodscited by 913
  3. 2020Neural Controlled Differential Equations for Irregular Time Seriescited by 506
  4. 2016RETAIN: An Interpretable Predictive Model for Healthcare using Reverse Time Attention Mechanismcited by 349
  5. 2020Scalable Gradients for Stochastic Differential Equationscited by 271
  6. 2022On Neural Differential Equationscited by 268
  7. 2015Doctor AI: Predicting Clinical Events via Recurrent Neural Networkscited by 208
  8. 2019Neural Stochastic Differential Equations: Deep Latent Gaussian Models in the Diffusion Limitcited by 176
  9. 2020SDE-Net: Equipping Deep Neural Networks with Uncertainty Estimatescited by 75
  10. 2021Time Series Prediction using Deep Learning Methods in Healthcarecited by 74
  11. 2022Continuous-Time Modeling of Counterfactual Outcomes Using Neural Controlled Differential Equationscited by 59
  12. 2021Integrating Expert ODEs into Neural ODEs: Pharmacology and Disease Progressioncited by 48
8 more
  1. 2023Bayesian Neural Controlled Differential Equations for Treatment Effect Estimationcited by 26
  2. 2022Predicting the impact of treatments over time with uncertainty aware neural differential equationscited by 23
  3. 2024ODE Discovery for Longitudinal Heterogeneous Treatment Effects Inferencecited by 12
  4. 2022Generative time series models using Neural ODE in Variational Autoencoderscited by 5
  5. 2023Explainable Deep Learning for Tumor Dynamic Modeling and Overall Survival Prediction using Neural-ODEcited by 5
  6. 2024Generative Modeling of Neural Dynamics via Latent Stochastic Differential Equationscited by 4
  7. 2023Integration of Graph Neural Network and Neural-ODEs for Tumor Dynamic Predictioncited by 2
  8. 2023Time-dependent Iterative Imputation for Multivariate Longitudinal Clinical Datacited by 1

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