Daniella Meeker

Tiffany J. Callahan, Adrianne L. Stefanski, Jordan M. Wyrwa et al.

Background: Common data models solve many challenges of standardizing electronic health record (EHR) data, but are unable to semantically integrate all the resources needed for deep phenotyping. Open Biological and Biomedical Ontology (OBO) Foundry ontologies provide computable representations of biological knowledge and enable the integration of heterogeneous data. However, mapping EHR data to OBO ontologies requires significant manual curation and domain expertise. Objective: We introduce OMOP2OBO, an algorithm for mapping Observational Medical Outcomes Partnership (OMOP) vocabularies to OBO ontologies. Results: Using OMOP2OBO, we produced mappings for 92,367 conditions, 8611 drug ingredients, and 10,673 measurement results, which covered 68-99% of concepts used in clinical practice when examined across 24 hospitals. When used to phenotype rare disease patients, the mappings helped systematically identify undiagnosed patients who might benefit from genetic testing. Conclusions: By aligning OMOP vocabularies to OBO ontologies our algorithm presents new opportunities to advance EHR-based deep phenotyping.

Erica Stutz, Giacomo Marino, Daniella Meeker et al.

Generative models are often trained with a next-token prediction objective, yet many downstream applications require the ability to estimate or control sequence-level properties. Next-token prediction can lead to overfitting of local patterns during training, underfitting of global structure, and requires significant downstream modifications or expensive sampling to guide or predict the global attributes of generated samples at inference time. Here, we introduce Conditional Attribute Transformers, a novel method for jointly estimating the next-token probability and the value of an attribute conditional on each potential next token selection. This framework enables three critical capabilities within a single forward pass, without modification of the input sequence: (1) per-token credit assignment across an entire sequence, by identifying how each token in a sequence is associated with an attribute's value; (2) counterfactual analysis, by quantifying attribute differences conditional on alternative next token choices; (3) steerable generation, by decoding sequences based on a combination of next-token and attribute likelihoods. Our approach achieves state of the art performance on sparse reward tasks, improves next-token prediction at sufficient model sizes, estimates attribute probabilities orders of magnitude faster than sampling, and can guide decoding of autoregressive sequence models on a range of language tasks.

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.

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.

Zhuohao Chen, James Gibson, Ming-Chang Chiu et al.

Empathy involves understanding other people's situation, perspective, and feelings. In clinical interactions, it helps clinicians establish rapport with a patient and support patient-centered care and decision making. Understanding physician communication through observation of audio-recorded encounters is largely carried out with manual annotation and analysis. However, manual annotation has a prohibitively high cost. In this paper, a multimodal system is proposed for the first time to automatically detect empathic interactions in recordings of real-world face-to-face oncology encounters that might accelerate manual processes. An automatic speech and language processing pipeline is employed to segment and diarize the audio as well as for transcription of speech into text. Lexical and acoustic features are derived to help detect both empathic opportunities offered by the patient, and the expressed empathy by the oncologist. We make the empathy predictions using Support Vector Machines (SVMs) and evaluate the performance on different combinations of features in terms of average precision (AP).

Jason N. Doctor, Jaideep Vaidya, Xiaoqian Jiang et al.

Secure computation of equivalence has fundamental application in many different areas, including healthcare. We study this problem in the context of matching an individual identity to link medical records across systems. We develop an efficient solution for equivalence based on existing work that can evaluate the greater than relation. We implement the approach and demonstrate its effectiveness on data, as well as demonstrate how it meets regulatory criteria for risk.