Shaoting Zhang
Publications
RareLens: Towards End-to-End Rare Disease Care via Aligning Divergent Large Language Model Reasoning
Rare diseases represent one of the most challenging settings for clinical decision-making, where heterogeneous presentations, sparse evidence and limited expertise create persistent uncertainty throughout the care pathway. Although artificial intelligence could help, existing systems largely address isolated tasks, particularly diagnosis, and usually rely on downstream investigations rather than information available at initial presentation. Here we show that clinical AI performance under uncertainty can be improved not by scaling a single model, but by exploiting the diversity of multiple imperfect reasoning systems. Across heterogeneous large language models, we identify divergent reasoning trajectories with complementary error patterns and develop RareLens, which learns to reconcile these perspectives into actionable decisions across four stages of rare disease care: risk screening, diagnosis, treatment planning and prognosis prediction. Built on RarelensBench, a real-world dataset of 157,525 cases spanning all 33 Orphanet categories and more than 7,000 conditions, RareLens outperformed every frontier model tested, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet and Gemini-2.5-Pro, across all stages. It achieved an area under the curve of 0.917 for screening and top-1 accuracies of 65.5% and 89.8% for diagnosis and treatment. In an external evaluation involving 1,287 cases and 23 physicians, autonomous RareLens and physicians assisted by RareLens both outperformed unaided physicians, while demonstrating that effective human-AI collaboration requires more than simply providing model outputs. These findings establish divergent model reasoning as an exploitable source of information and suggest a general strategy for building AI systems that operate reliably under high clinical uncertainty.
EHRWorld: A Patient-Centric Medical World Model for Long-Horizon Clinical Trajectories
World models offer a principled framework for simulating future states under interventions, but realizing such models in complex, high-stakes domains like medicine remains challenging. Recent large language models (LLMs) have achieved strong performance on static medical reasoning tasks, raising the question of whether they can function as dynamic medical world models capable of simulating disease progression and treatment outcomes over time. In this work, we show that LLMs only incorporating medical knowledge struggle to maintain consistent patient states under sequential interventions, leading to error accumulation in long-horizon clinical simulation. To address this limitation, we introduce EHRWorld, a patient-centric medical world model trained under a causal sequential paradigm, together with EHRWorld-110K, a large-scale longitudinal clinical dataset derived from real-world electronic health records. Extensive evaluations demonstrate that EHRWorld significantly outperforms naive LLM-based baselines, achieving more stable long-horizon simulation, improved modeling of clinically sensitive events, and favorable reasoning efficiency, highlighting the necessity of training on causally grounded, temporally evolving clinical data for reliable and robust medical world modeling.
MedMCP-Calc: Benchmarking LLMs for Realistic Medical Calculator Scenarios via MCP Integration
Medical calculators are fundamental to quantitative, evidence-based clinical practice. However, their real-world use is an adaptive, multi-stage process, requiring proactive EHR data acquisition, scenario-dependent calculator selection, and multi-step computation, whereas current benchmarks focus only on static single-step calculations with explicit instructions. To address these limitations, we introduce MedMCP-Calc, the first benchmark for evaluating LLMs in realistic medical calculator scenarios through Model Context Protocol (MCP) integration. MedMCP-Calc comprises 118 scenario tasks across 4 clinical domains, featuring fuzzy task descriptions mimicking natural queries, structured EHR database interaction, external reference retrieval, and process-level evaluation. Our evaluation of 23 leading models reveals critical limitations: even top performers like Claude Opus 4.5 exhibit substantial gaps, including difficulty selecting appropriate calculators for end-to-end workflows given fuzzy queries, poor performance in iterative SQL-based database interactions, and marked reluctance to leverage external tools for numerical computation. Performance also varies considerably across clinical domains. Building on these findings, we develop CalcMate, a fine-tuned model incorporating scenario planning and tool augmentation, achieving state-of-the-art performance among open-source models. Benchmark and Codes are available in https://github.com/SPIRAL-MED/MedMCP-Calc.