Kevin Byram

Eric Wu, Kevin Wu, Jason Hom et al.

Large language models (LLMs) are increasingly central to clinician workflows, spanning clinical decision support, medical education, and patient communication. However, current evaluation methods for medical LLMs rely heavily on static, templated benchmarks that fail to capture the complexity and dynamics of real-world clinical practice, creating a dissonance between benchmark performance and clinical utility. To address these limitations, we present MedArena, an interactive evaluation platform that enables clinicians to directly test and compare leading LLMs using their own medical queries. Given a clinician-provided query, MedArena presents responses from two randomly selected models and asks the user to select the preferred response. Out of 1571 preferences collected across 12 LLMs up to November 1, 2025, Gemini 2.0 Flash Thinking, Gemini 2.5 Pro, and GPT-4o were the top three models by Bradley-Terry rating. Only one-third of clinician-submitted questions resembled factual recall tasks (e.g., MedQA), whereas the majority addressed topics such as treatment selection, clinical documentation, or patient communication, with ~20% involving multi-turn conversations. Additionally, clinicians cited depth and detail and clarity of presentation more often than raw factual accuracy when explaining their preferences, highlighting the importance of readability and clinical nuance. We also confirm that the model rankings remain stable even after controlling for style-related factors like response length and formatting. By grounding evaluation in real-world clinical questions and preferences, MedArena offers a scalable platform for measuring and improving the utility and efficacy of medical LLMs.

Cathy Shyr, Yan Hu, Rory J. Tinker et al.

Phenotyping is fundamental to rare disease diagnosis, but manual curation of structured phenotypes from clinical notes is labor-intensive and difficult to scale. Existing artificial intelligence approaches typically optimize individual components of phenotyping but do not operationalize the full clinical workflow of extracting features from clinical text, standardizing them to Human Phenotype Ontology (HPO) terms, and prioritizing diagnostically informative HPO terms. We developed RARE-PHENIX, an end-to-end AI framework for rare disease phenotyping that integrates large language model-based phenotype extraction, ontology-grounded standardization to HPO terms, and supervised ranking of diagnostically informative phenotypes. We trained RARE-PHENIX using data from 2,671 patients across 11 Undiagnosed Diseases Network clinical sites, and externally validated it on 16,357 real-world clinical notes from Vanderbilt University Medical Center. Using clinician-curated HPO terms as the gold standard, RARE-PHENIX consistently outperformed a state-of-the-art deep learning baseline (PhenoBERT) across ontology-based similarity and precision-recall-F1 metrics in end-to-end evaluation (i.e., ontology-based similarity of 0.70 vs. 0.58). Ablation analyses demonstrated performance improvements with the addition of each module in RARE-PHENIX (extraction, standardization, and prioritization), supporting the value of modeling the full clinical phenotyping workflow. By modeling phenotyping as a clinically aligned workflow rather than a single extraction task, RARE-PHENIX provides structured, ranked phenotypes that are more concordant with clinician curation and has the potential to support human-in-the-loop rare disease diagnosis in real-world settings.