Recent reasoning-centric Large Language Models (LLMs) have made significant strides, yet they predominantly operate on a passive-inference pattern that assumes complete information. In contrast, real-world clinical intelligence is inherently an iterative investigative process requiring strategic evidence acquisition. To bridge this gap, we formalize medical diagnosis as an Iterative Evidence-Seeking Task. We leverage Reinforcement Learning with Verifiable Rewards (RLVR) to elicit intrinsic reasoning within a closed-loop environment, guided by a novel suite of rewards that enforce diagnostic precision and examination consistency. To facilitate this, we introduce the Retrieval-Augmented Generation-based Examination Simulator (RAGES), a high-fidelity clinical oracle that provides realistic, knowledge-grounded follow-up evidence. Empirical results across diverse datasets demonstrate that our framework enables LLMs to transition from passive responders to autonomous assistants. Notably, our model demonstrates comparable performance to larger and reasoning-enhanced baselines, while RAGES proves superior to vanilla LLMs in generating biologically plausible clinical feedback.
Shengyi Hua, Kangzhe Hu, Conghui He et al.· 1 citation
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.
Xi Chen, Hongru Zhou, Shiyu Feng et al.· 0 citations