Foundation Models to Unlock Real-World Evidence from Nationwide Medical Claims

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.

TrialCalibre: A Fully Automated Causal Engine for RCT Benchmarking and Observational Trial Calibration

Real-world evidence (RWE) studies that emulate target trials increasingly inform regulatory and clinical decisions, yet residual, hard-to-quantify biases still limit their credibility. The recently proposed BenchExCal framework addresses this challenge via a two-stage Benchmark, Expand, Calibrate process, which first compares an observational emulation against an existing randomized controlled trial (RCT), then uses observed divergence to calibrate a second emulation for a new indication causal effect estimation. While methodologically powerful, BenchExCal is resource intensive and difficult to scale. We introduce TrialCalibre, a conceptualized multiagent system designed to automate and scale the BenchExCal workflow. Our framework features specialized agents such as the Orchestrator, Protocol Design, Data Synthesis, Clinical Validation, and Quantitative Calibration Agents that coordi-nate the the overall process. TrialCalibre incorpo-rates agent learning (e.g., RLHF) and knowledge blackboards to support adaptive, auditable, and transparent causal effect estimation.

FastOMOP: A Foundational Architecture for Reliable Agentic Real-World Evidence Generation on OMOP CDM data

The Observational Medical Outcomes Partnership Common Data Model (OMOP CDM), maintained by the Observational Health Data Sciences and Informatics (OHDSI) collaboration, enabled the harmonisation of electronic health records data of nearly one billion patients in 83 countries. Yet generating real-world evidence (RWE) from these repositories remains a manual process requiring clinical, epidemiological and technical expertise. LLMs and multi-agent systems have shown promise for clinical tasks, but RWE automation exposes a fundamental challenge: agentic systems introduce emergent behaviours, coordination failures and safety risks that existing approaches fail to govern. No infrastructure exists to ensure agentic RWE generation is flexible, safe and auditable across the lifecycle. We introduce FastOMOP, an open-source multi-agent architecture that addresses this gap by separating three infrastructure layers, governance, observability and orchestration, from pluggable agent-teams. Governance is enforced at the process boundary through deterministic validation independent of agent reasoning, ensuring no compromised or hallucinating agent can bypass safety controls. Agent teams for phenotyping, study design and statistical analysis inherit these guarantees through controlled tool exposure. We validated FastOMOP using a natural-language-to-SQL agent team across three OMOP CDM datasets: synthetic data from Synthea, MIMIC-IV and a real-world NHS dataset from Lancashire Teaching Hospitals (IDRIL). FastOMOP achieved reliability scores of 0.84-0.94 with perfect adversarial and out-of-scope block rates, demonstrating process-boundary governance delivers safety guarantees independent of model choice. These results indicate that the reliability gap in RWE deployment is architectural rather than model capability, and establish FastOMOP as a governed architecture for progressive RWE automation.