Federated generative event models for tokenized electronic health records

Synthetic Electronic Health Record (EHR) generation provides a promising avenue for data augmentation and cross-hospital modeling in privacy-constrained healthcare settings. However, most existing EHR generative models are centralized and require pooling data across hospitals, which is often infeasible when real-world data sharing is restricted. While federated EHR generation offers a natural solution, direct federated modeling often collapses or diverges due to the high dimensionality, sparsity, and cross-hospital heterogeneity of EHR data. In this work, we propose FedEHR-Gen, the first federated framework for synthetic time-series EHR generation across distributed hospitals. FedEHR-Gen uses a two-stage learning paradigm. First, we introduce a federated autoencoder that projects high-dimensional and sparse EHR features onto a compact latent space. To ensure semantic consistency across hospitals, we develop a layer-wise matching aggregation mechanism that aligns local encoders into a unified global latent space. Second, operating on this aligned latent space, we train a federated temporal conditional variational autoencoder (TCVAE) with distribution-aware aggregation, enabling stable temporal generative modeling under severe cross-hospital heterogeneity. Extensive experiments on the eICU and MIMIC-III datasets demonstrate that FedEHR-Gen achieves generation fidelity, downstream utility, and privacy risk comparable to centralized training, while consistently outperforming the standard federated baseline.

Generative medical event models use tokenized sequences of patient timelines as input, but practical guidance on the many decisions around tokenization is limited. We benchmark quantization granularity, reference-range anchoring, code--value fusion, numeric and temporal encodings, and native versus harmonized event representations from an expert-mapped common data model. Using both Llama and Qwen architectures, 156 models were trained from three initialization seeds, with each configuration following a shared training recipe for up to five epochs. We evaluated learned representations from the first 24 hours of hospitalization with linear probes to predict binary and continuous outcomes during hours 24-48. Fused tokens pairing codes with value deciles increased performance across all eight outcome families relative to the equivalent unfused tokenized input with area under the receiver operating characteristic curve (AUROC) gains of $+0.002$ to $+0.033$ and Spearman correlation gains of $+0.025$ to $+0.114$. Neither anchoring value bins to reference ranges nor increasing quantization granularity consistently improved performance, while xVal variants underperformed both discrete and soft encodings. Alternatives to explicit time tokens, such as event-order and admission-relative rotary position embeddings (RoPE), yielded higher family-mean point estimates across all eight families while reducing input length. When evaluating native input against input mapped to the Common Longitudinal Intensive Care Unit Data Format (CLIF), the CLIF pipeline used 30.8% as many training tokens while improving performance in six of eight outcome families. These findings show tokenization and event encoding are consequential design choices when learning patient representations for downstream classification and regression.

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.