Modeling Patient Care Trajectories with Transformer Hawkes Processes

Accurate disease trajectory prediction is critical for early intervention, resource allocation, and improving long-term outcomes. While electronic health records (EHRs) provide a rich longitudinal view of patient health in clinical environments, models trained on curated research cohorts may not reflect routine deployment settings, and those trained on single-hospital datasets capture only fragments of each patient's trajectory. This highlights the importance of leveraging large, multi-hospital health systems for training and validation to better reflect real-world clinical complexity. In this work, we develop DT-Transformer, a foundation model trained on 57.1M structured EHR entries over 1.7M patients from Mass General Brigham (MGB), spanning 11 hospitals and a broad network of outpatient clinics. DT-Transformer achieves strong discrimination in both held-out and prospective validation settings. Next-event prediction achieves a median age- and sex-stratified AUC of 0.871 across 896 disease categories, with all categories exceeding AUC 0.5. These results support health system-scale training as a path toward foundation models suited to real-world clinical forecasting.

The digitization of healthcare has generated vast, longitudinal, and multimodal patient records over a lifetime, yet fully exploiting these data to represent and predict patient state trajectories remains a critical challenge. Current AI models often struggle to capture the complex, irregular temporal dynamics and inherent stochasticity of real-world multimodal patient data. Existing AI approaches for modeling longitudinal patient records are predominantly discriminative, limited to a few modalities, constrained by closed categorical vocabularies, treating time as a monotonic inductive bias, or they are limited in forecasting future patient states. We introduce NOAH, a time-aware, task-agnostic, generative transformer model representing and forecasting the full multimodal patient journey. NOAH features a novel bidirectional time integration and a variational latent space to capture the continuous evolution of patient states and the stochasticity of clinical trajectories. Built from over 559 million clinical events from 431,000 hospital visits of 299,000 patients across the MIMIC dataset family, NOAH natively processes medical images, time-series and numeric signals, categorical events, as well as structured and unstructured clinical records. NOAH is the first truly holistic generative model in its field, enabling autoregressive forecasting with optional time control, zero-shot classification, and counterfactual intervention simulation. It generates highly informative and predictive patient state representations that demonstrate strong performance in probing for clinical outcomes, 15 ICD chapters, and 29 comorbidities, as well as in time-to-event prediction. Seamlessly handling diverse modalities and complex temporal dynamics, NOAH provides a versatile, task-agnostic, scalable foundation for intelligent predictive systems in personalized clinical care and digital medicine.

The growing adoption of electronic health record (EHR) systems has provided unprecedented opportunities for predictive modeling to guide clinical decision making. Structured EHRs contain longitudinal observations of patients across hospital visits, where each visit is represented by a set of medical codes. While sequence-based, graph-based, and graph-enhanced sequence approaches have been developed to capture rich code interactions over time or within the same visits, they often overlook the inherent heterogeneous roles of medical codes arising from distinct clinical characteristics and contexts. To this end, in this study we propose the Disease Trajectory-aware Transformer for EHR (DT-BEHRT), a graph-enhanced sequential architecture that disentangles disease trajectories by explicitly modeling diagnosis-centric interactions within organ systems and capturing asynchronous progression patterns. To further enhance the representation robustness, we design a tailored pre-training methodology that combines trajectory-level code masking with ontology-informed ancestor prediction, promoting semantic alignment across multiple modeling modules. Extensive experiments on multiple benchmark datasets demonstrate that DT-BEHRT achieves strong predictive performance and provides interpretable patient representations that align with clinicians' disease-centered reasoning. The source code is publicly accessible at https://github.com/GatorAIM/DT-BEHRT.git.