Can LLM Agents Generate Real-World Evidence? Evaluating Observational Studies in Medical Databases

We introduce PhysicianBench, a benchmark for evaluating LLM agents on physician tasks grounded in real clinical setting within electronic health record (EHR) environments. Existing medical agent benchmarks primarily focus on static knowledge recall, single-step atomic actions, or action intent without verifiable execution against the environment. As a result, they fail to capture the long-horizon, composite workflows that characterize real clinical systems. PhysicianBench comprises 100 long-horizon tasks adapted from real consultation cases between primary care and subspecialty physicians, with each task independently reviewed by a separate panel of physicians. Tasks are instantiated in an EHR environment with real patient records and accessed through the same standard APIs used by commercial EHR vendors. Tasks span 21 specialties (e.g., cardiology, endocrinology, oncology, psychiatry) and diverse workflow types (e.g., diagnosis interpretation, medication prescribing, treatment planning), requiring an average of 27 tool calls per task. Solving each task requires retrieving data across encounters, reasoning over heterogeneous clinical information, executing consequential clinical actions, and producing clinical documentation. Each task is decomposed into structured checkpoints (670 in total across the benchmark) capturing distinct stages of completion graded by task-specific scripts with execution-grounded verification. Across 13 proprietary and open-source LLM agents, the best-performing model achieves only 46% success rate (pass@1), while open-source models reach at most 19%, revealing a substantial gap between current agent capabilities and the demands of real-world clinical workflows. PhysicianBench provides a realistic and execution-grounded benchmark for measuring progress toward autonomous clinical agents.

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.

Large language models (LLMs) have saturated standard medical benchmarks that test factual recall, yet their ability to perform higher-order reasoning, such as synthesizing evidence from multiple sources, remains critically under-explored. To address this gap, we introduce MedMeta, the first benchmark designed to evaluate an LLM's ability to generate conclusions from medical meta-analyses using only the abstracts of cited studies. MedMeta comprises 81 meta-analyses from PubMed (2018--2025) and evaluates models using two distinct workflows: a Retrieval-Augmented Generation (Golden-RAG) setting with ground-truth abstracts, and a Parametric-only approach relying on internal knowledge. Our evaluation framework is validated by a well-structured analysis showing our LLM-as-a-judge protocol strongly aligns with human expert ratings, as evidenced by high Pearson's r correlation (0.81) and Bland-Altman analysis revealing negligible systematic bias, establishing it as a reliable proxy for scalable evaluation. Our findings underscore the critical importance of information grounding: the Golden-RAG workflow consistently and significantly outperforms the Parametric-only approach across models. In contrast, the benefits of domain-specific fine-tuning are marginal and largely neutralized when external material is provided. Furthermore, stress tests show that all models, regardless of architecture, fail to identify and reject negated evidence, highlighting a critical vulnerability in current RAG systems. Notably, even under ideal RAG conditions, current LLMs achieve only slightly above-average performance (~2.7/5.0). MedMeta provides a challenging new benchmark for evidence synthesis and demonstrates that for clinical applications, developing robust RAG systems is a more promising direction than model specialization alone.