Andrew Loza

Fan Ma, Yuntian Liu, Xiang Lan et al.

Evidence derived from large-scale real-world data (RWD) is increasingly informing regulatory evaluation and healthcare decision-making. Administrative claims provide population-scale, longitudinal records of healthcare utilization, expenditure, and detailed coding of diagnoses, procedures, and medications, yet their potential as a substrate for healthcare foundation models remains largely unexplored. Here we present ReClaim, a generative transformer trained from scratch on 43.8 billion medical events from more than 200 million enrollees in the MarketScan claims data spanning 2008-2022. ReClaim models longitudinal trajectories across diagnoses, procedures, medications, and expenditure, and was scaled to 140 million, 700 million, and 1.7 billion parameters. Across over 1,000 disease-onset prediction tasks, ReClaim achieved a mean AUC of 75.6%, substantially outperforming disease-specific LightGBM (66.3%) and the transformer-based Delphi model (69.4%), with the largest gains for rare diseases. These advantages held across retrospective and prospective evaluations and in external validation on two independent datasets. Performance improved monotonically with scale, and post-training added 13.8 percentage points over pre-training alone. Beyond disease prediction, ReClaim captured financial outcomes and improved real-world evidence (RWE) analyses: for healthcare expenditure forecasting it increased explained variance from 0.28 to 0.37 relative to LightGBM, and in a target trial emulation it reduced systematic bias by 72% on average relative to Delphi. Together, these results establish administrative claims as a scalable substrate for healthcare foundation models and show that learned representations generalize across time periods and data sources, supporting disease surveillance, expenditure forecasting, and RWE generation.

Xi Zhang, Yuan Pu, Yuki Kawamura et al.

Modeling stochastic and irregularly sampled time series is a challenging problem found in a wide range of applications, especially in medicine. Neural stochastic differential equations (Neural SDEs) are an attractive modeling technique for this problem, which parameterize the drift and diffusion terms of an SDE with neural networks. However, current algorithms for training Neural SDEs require backpropagation through the SDE dynamics, greatly limiting their scalability and stability. To address this, we propose Trajectory Flow Matching (TFM), which trains a Neural SDE in a simulation-free manner, bypassing backpropagation through the dynamics. TFM leverages the flow matching technique from generative modeling to model time series. In this work we first establish necessary conditions for TFM to learn time series data. Next, we present a reparameterization trick which improves training stability. Finally, we adapt TFM to the clinical time series setting, demonstrating improved performance on three clinical time series datasets both in terms of absolute performance and uncertainty prediction.

Shane Waxler, Paul Blazek, Davis White et al.

Realizing personalized medicine at scale calls for methods that distill insights from longitudinal patient journeys, which can be viewed as a sequence of medical events. Foundation models pretrained on large-scale medical event data represent a promising direction for scaling real-world evidence generation and generalizing to diverse downstream tasks. Using Epic Cosmos, a dataset with medical events from de-identified longitudinal health records for 16.3 billion encounters over 300 million unique patient records from 310 health systems, we introduce the Curiosity models, a family of decoder-only transformer models pretrained on 118 million patients representing 115 billion discrete medical events (151 billion tokens). We present the largest scaling-law study of medical event data, establishing a methodology for pretraining and revealing power-law scaling relationships for compute, tokens, and model size. Consequently, we pretrained a series of compute-optimal models with up to 1 billion parameters. Conditioned on a patient's real-world history, Curiosity autoregressively predicts the next medical event to simulate patient health timelines. We studied 78 real-world tasks, including diagnosis prediction, disease prognosis, and healthcare operations. Remarkably for a foundation model with generic pretraining and simulation-based inference, Curiosity generally outperformed or matched task-specific supervised models on these tasks, without requiring task-specific fine-tuning or few-shot examples. Curiosity's predictive power consistently improves as the model and pretraining scale. Our results show that Curiosity, a generative medical event foundation model, can effectively capture complex clinical dynamics, providing an extensible and generalizable framework to support clinical decision-making, streamline healthcare operations, and improve patient outcomes.

Kriti Bhattarai, Vipina K. Keloth, Donald Wright et al.

Objective: Large language models (LLMs) are increasingly applied in biomedical settings, and existing benchmark datasets have played an important role in supporting model development and evaluation. However, these benchmarks often have limitations. Many rely on static or outdated datasets that fail to capture the dynamic, context-rich, and high-stakes nature of biomedical knowledge. They also carry increasing risk of data leakage due to overlap with model pretraining corpora and often overlook critical dimensions such as robustness to linguistic variation and potential demographic biases. Materials and Methods: To address these gaps, we introduce BioPulse-QA, a benchmark that evaluates LLMs on answering questions from newly published biomedical documents including drug labels, trial protocols, and clinical guidelines. BioPulse-QA includes 2,280 expert-verified question answering (QA) pairs and perturbed variants, covering both extractive and abstractive formats. We evaluate four LLMs - GPT-4o, GPT-o1, Gemini-2.0-Flash, and LLaMA-3.1 8B Instruct - released prior to the publication dates of the benchmark documents. Results: GPT-o1 achieves the highest relaxed F1 score (0.92), followed by Gemini-2.0-Flash (0.90) on drug labels. Clinical trials are the most challenging source, with extractive F1 scores as low as 0.36. Discussion and Conclusion: Performance differences are larger for paraphrasing than for typographical errors, while bias testing shows negligible differences. BioPulse-QA provides a scalable and clinically relevant framework for evaluating biomedical LLMs.