Medical Reasoning

Foundation models can serve as clinical agents through tool-use harnesses. However, conventional medical benchmarks assess reasoning over preselected evidence rather than the ability to seek it across clinical records and longitudinal imaging. We propose CASE: a series of role-specific Clinical Agents for Seeking Evidence, together with a tool-use harness and an agentic post-training framework for compact vision-language policy models. We further introduce a longitudinal multimodal benchmark built on UK Biobank, comprising 50,401 clinical questions derived from real-world ICD-10-coded diagnoses of 4,739 participants. Each question links to a patient-specific environment containing clinical context and multi-sequence MRI from baseline and follow-up visits, where agents autonomously select which visits, organs, modalities, slices, and specialist tools to inspect and compare. Supervised fine-tuning transfers evidence-seeking workflows from 14,734 frontier-model interaction trajectories, followed by agentic reinforcement learning on the learner's own environment interactions. Privileged on-policy self-distillation and rubric-based LLM feedback refine evidence-to-conclusion reasoning without prescribing tool sequences. Experiments show that CASE moves beyond question-answer imitation toward transferable investigation policies, strengthening evidence-grounded longitudinal reasoning. Under matched evaluation conditions, our Qwen3-VL-8B based agent achieves over 16% and 10% relative improvements in answer accuracy over GPT-5.4 and Claude Opus 4.8. Code will be available at https://github.com/VinyehShaw/CASE.

Deploying Large Language Models (LLMs) in healthcare requires robust performance across two complementary dimensions - diagnostic reasoning: the convergent, evidence-driven task of inferring a patient's condition from clinical data to produce a diagnosis, and clinical healthcare reasoning: the broader, navigational judgment required to communicate, plan, and adapt across multi-turn clinical interactions where a single correct answer may not exist. Recent benchmarks such as HealthBench and MedXpertQA reveal persistent weaknesses in both areas, exposing failures in complex diagnostic scenarios and limitations in contextual, patient-centered dialogue. We introduce a sequential training framework that targets these facets using synthetic data and rubric-based reinforcement learning. First, we improve diagnostic reasoning using MedBullets-derived questions with rule- and rubric-guided Reinforcement Learning (RL). We then shift to clinical reasoning by generating 5.3k synthetic multi-turn scenarios, each paired with multi-dimensional rubrics to comprehensively assess the response. This approach yields over 10% improvement on MedXpertQA, and our 30B model achieves 50.1% accuracy on HealthBench-Hard, surpassing proprietary baselines including GPT-5 (thinking). Our results show that targeted synthetic datasets and rubric-based training can systematically improve both diagnostic and interactive clinical reasoning in medical LLMs.

When medical AI systems hallucinate clinical reasoning, the consequences extend beyond incorrect answers: fabricated justifications that superficially reference retrieved evidence can mislead clinicians into unsafe treatment decisions. Medical reasoning agents must therefore produce not only correct answers but also faithful justifications that clinicians can verify against cited evidence. We identify a systematic failure mode in RL-trained retrieval agents: outcome-only rewards improve accuracy while degrading faithfulness, a phenomenon we term confident hallucination. The agent learns to answer from parametric memory and backfill plausible but unsupported justifications; citation fabrication rates rise from 16.5% to 31.8% even as accuracy improves by 5 points over the supervised baseline. We address this with a faithfulness-gated reward design: accuracy credit is conditioned on evidence grounding via a hard gate, complemented by retrieval validity and conciseness signals that close exploitation paths unique to agentic retrieval. The resulting system, MedAgent-R1, reduces citation fabrication from 31.8% to 4.7% and raises evidence completeness from 58.7 to 82.6 while maintaining 75.1% accuracy, with 13.2-point gains on HealthBench Safety. Under the same agentic retrieval setup, MedAgent-R1 outscores GPT-4o on faithfulness-specific dimensions (Factual Support 4.55 vs. 4.25; Overclaiming 4.40 vs. 4.15) while remaining below GPT-4o in overall accuracy, suggesting that explicit faithfulness training yields evidence-grounding gains not achieved by scaling alone.

Applying a valid medication-safety rule when its patient-specific conditions are not met can produce an incorrect decision. Existing medical evaluations largely use isolated and fixed scenarios. A model may therefore answer correctly by recalling a drug-risk association without showing that it used patient information to decide whether the rule applies. To address this gap, we introduce MedPIC-Bench, a benchmark of source-verifiable recommendations and expert-validated questions for patient-specific medication-safety reasoning. It combines guideline-following questions with paired counterfactual questions in which a controlled change in patient information changes whether a rule applies. The benchmark contains 467 questions annotated along six clinical and reasoning dimensions. Across 28 medical-specific, general, and proprietary LLMs, every model performs worse on counterfactual questions, with mean accuracy falling from 63.6% to 45.1%. Models perform well when an explicit patient attribute directly signals a familiar contraindication, but struggle when patient information must narrow or withdraw a safety warning. Model rationales often acknowledge the changed patient information, yet the final answers retain the previous safety judgment. This vulnerability persists among medical-specific LLMs, whose average CF performance trails that of general LLMs. MedPIC-Bench therefore makes conditional rule application measurable and highlights the limitations of static medication-safety accuracy for assessing patient-specific reliability.

In medical multiple-choice question answering (MCQA), Retrieval-Augmented Generation (RAG) can supplement the domain knowledge of language models (LMs). However, since vanilla RAG indiscriminately utilizes retrieved documents, it can degrade LM performance. To address this, we propose MedJudgeRAG. Our framework represents retrieved documents as a dynamic knowledge graph (KG) composed of entities and relations. For each option, the model judges an evidence verdict from the retrieved documents and the KG. Based on the verdict combination, the model determines a knowledge utilization strategy to reason toward the final answer. These capabilities are trained via supervised fine-tuning using structured reasoning traces generated by a teacher LM. The training employs a weighted cross-entropy loss that differentially weights the KG and reasoning segments. Experiments on two medical MCQA benchmarks demonstrate that MedJudgeRAG consistently outperforms both vanilla RAG and parametric baselines. Furthermore, ablation analysis reveals that the dynamic KG is more effective as graph-conditioned supervision at training time than as an explicit output at inference time. Our code is available at https://github.com/hyu-amllab/medjudgerag, and the generated reasoning traces are released at https://huggingface.co/datasets/youarethewon/medjudgerag.

While Multimodal Large Language Models (MLLMs) have demonstrated remarkable success in 2D medical image understanding, their extension to 3D volumetric imaging remains hindered by prohibitive annotation costs and dataset opacity. Current data formats, predominantly consisting of rigid Visual Question Answering (VQA) pairs or unstructured final clinical reports, typically fail to capture explicit clinical reasoning. To address this limitation, we introduce a large-scale structured reasoning dataset constructed via a novel slice-wise data synthesis paradigm. Inspired by the genuine diagnostic workflow of radiologists, this paradigm models visual cognition by decomposing the complex 3D reading process, translating global clinical priors into fine-grained, per-slice observations that are subsequently synthesized into an interpretable Chain-of-Thought (CoT). Crucially, this synthesized reasoning framework enforces essential clinical principles: sequential spatial tracking, multi-slice spatial awareness for artifact mitigation, and differential exclusion. To validate this approach, we instruction-tune a standard 2D-pretrained MLLM baseline using the synthesized data to enhance its volumetric comprehension. Comprehensive evaluations across multiple 3D medical benchmarks demonstrate that our method yields significant performance improvements over the 2D baseline. Furthermore, the resulting model exhibits robust spatial reasoning capabilities and rivals resource-intensive native 3D architectures, effectively bridging the performance gap. Ultimately, this data-centric strategy unlocks deep volumetric understanding and highly interpretable clinical logic without requiring computationally expensive 3D-specific pre-training. The complete repository, including datasets and training workflows, is publicly available at https://github.com/2020420145009/hounsfield.

Faithful reasoning is essential in medicine, where clinical decisions require transparent justification grounded in reliable evidence. Current medical LLMs either lack active access to evidence or use retrieved evidence without supervising how it should be appraised and applied during reasoning. To address this, we formalize evidence-based medicine principles as process-level criteria and introduce FaithMed, a framework that combines clinician-designed, automatically refined rubrics with reinforcement learning using step-level process reward assignment and advantage grouping. Across seven medical benchmarks, FaithMed improves over agentic-search baselines (+9% on average) and outcome-only RL (+5.8%), while raising average evidence-based medicine rubric scores over agentic-search Qwen3 baselines (+15.5%). This work demonstrates that explicit step-level supervision can improve both task success and the faithfulness of the reasoning process. Code is available at https://github.com/cxcscmu/FaithMed.

Navigating the deluge of heterogeneous medical data, from academic literature (PubMed) to clinical guidelines (Web) and private knowledge bases, remains a critical bottleneck for evidence-based medicine. While commercial black-box tools lack transparency, standard open-source RAG implementations frequently suffer from reasoning drift when handling complex, long-tail queries. We present DEEPMED Search, a fully open-source, agentic platform designed for transparent medical deep research. Built on a high-performance Next.js architecture, DEEPMED Search features a source-adaptive router that autonomously dispatches sub-queries to PubMed, web search, or local graph-based knowledge bases based on information density. Crucially, the platform integrates an introspective verification module, powered by a causal-consistent multi-agent debate framework, to validate retrieved evidence against diagnostic logic before synthesis. To demonstrate its robustness, we showcase DEEPMED Search's ability to autonomously decompose high-difficulty rare disease queries, filter out confounding noise, and generate structured, citation-backed research reports in minutes. By open-sourcing this software, we provide the community with a robust infrastructure to democratize access to trustworthy, glass-box medical reasoning in research and prototyping settings.

Chain-of-thought (CoT) distillation trains a smaller model to imitate a teacher's reasoning trace, but it is typically evaluated by final-answer metrics including accuracy. We ask whether gains in answer quality are accompanied by improvements in the trace. In medical QA, where short answer options can leave a richer clinical justification under-specified, a Qwen3-8B student distilled from a DeepSeek-V3-family teacher improves on MedQA-USMLE answer metrics (SC@64 74.7% to 84.4%; expected calibration error (ECE) 0.096 to 0.034). Yet under a Kimi-K2.6 style-blind LLM-judge audit, its error rate over non-abstained steps rises from 30.6% to 50.3%. In this primary medical setting, answer quality and trace factuality move in opposite directions. This before--after pattern persists across evaluators, teacher strengths, student scales and families, medical benchmarks, and style, segmentation, and answer-correctness controls. A 150-step blinded audit by a clinical expert reproduces the same ordering. Boundary checks narrow the scope of the claim: the risk appears when a compact answer under-constrains the rationale and a capable student can imitate expert-like form without reliably grounding each local claim. Standard answer metrics and aggregate hedging rates do not reveal the shift. When such traces are released or reused, answer-level metrics alone are insufficient.

Medical large language models hold promise for reducing healthcare disparities, yet Hindi remains severely underrepresented. While medical LLMs excel in high-resource languages, their performance degrades sharply in Hindi, particularly on Indian systems of medicine. We argue that robust cross-lingual medical transfer requires Hindi reasoning. To this end, we introduce HiMed, a Hindi reasoning medical corpus and benchmark suite covering both Western and Indian medicine. We further propose HiMed-8B, a Hindi-form medical reasoning LLM, through the design of decaying scaffolding reward. Extensive experiments demonstrate improvement in Hindi medical reasoning performance and reduction in the English--Hindi accuracy gap. Ablation studies validate the contribution of each training stage and reward component. All data and code are available on GitHub: https://github.com/FreedomIntelligence/HiMed.

Across medical specialties, clinical practice is anchored in evidence-based guidelines that codify best studied diagnostic and treatment pathways. These pathways routinely fall short for the long tail of real-world care not covered by guidelines. Most medical large language models (LLMs), however, are trained to encode common, guideline-focused medical knowledge in their parameters. Current evaluations test models primarily on recalling and reasoning with this memorized content, often in multiple-choice settings. Given the fundamental importance of evidence-based reasoning in medicine, it is neither feasible nor reliable to depend on memorization in practice. To address this gap, we introduce OGCaReBench, a free-form retrieval-focused benchmark aimed at evaluating LLMs at answering clinical questions that require going beyond typical guidelines. Extracted from published medical case reports and validated by medical experts, OGCaReBench contains long-form clinical questions requiring free-text answers, providing a systematic framework for assessing open-ended medical reasoning in rare, case-based scenarios. Our experiments reveal that even the best-performing baseline (GPT-5.2) correctly answers only 56% of our benchmark with specialized models only reaching 42%. Augmenting models with retrieved medical articles improves this performance to up to 82% (using GPT-5.2) highlighting the importance of evidence-grounding for real-world medical reasoning tasks. This work thus establishes a foundation for benchmarking and advancing both general-purpose and medical LLMs to produce reliable answers in challenging clinical contexts.

Experienced physicians develop diagnostic expertise through clinical practice, acquiring not only disease knowledge but also the ability to differentiate confusable conditions. Current medical vision-language models (VLMs) lack this capability -- their parameters encode static knowledge that does not evolve across diagnostic encounters. We propose MedExpMem, an experience memory framework enabling VLM-based diagnostic agents to accumulate differential diagnosis expertise. Unlike retrieval-augmented generation, which retrieves encyclopedic disease descriptions, MedExpMem memorizes discriminative experience derived from the agent's own diagnostic failures and organizes them as pairwise differential notes encoding key discriminators, actionable decision rules and reasoning error patterns. The framework adopts a two-phase construction process mirroring physician learning: initial practice exposes knowledge gaps, and reflective re-diagnosis refines understanding. When encountering new cases, the agent retrieves experience memory to guide differential reasoning. We evaluate MedExpMem on a radiology benchmark spanning 11 subspecialties. Results demonstrate consistent accuracy improvements, maximum 7.0%, across diverse models and scales. Analytical experiments validate experience quality and robustness, demonstrating MedExpMem as a competitive method addresses medical adaptation needs beyond the reach of parameteric learning.

Electrocardiogram (ECG) diagnosis in clinical practice relies on structured reasoning over multiple hierarchical aspects, including cardiac rhythm, conduction properties, waveform morphology, and overall diagnostic impression. However, most existing approaches predict labels directly from ECG signals without explicit clinical reasoning, resulting in opaque decisions that lack clinical alignment. To bridge this gap, we propose CardioThink, a physician-inspired multimodal large language model (MLLM) framework that explicitly models the diagnostic reasoning process through human-interpretable intermediate stages (rhythm, conduction, morphology, and impression) to derive final classification results. Furthermore, we introduce Structured Set Policy Optimization (SSPO) to jointly optimize adherence to this structured reasoning format and the accuracy of variable-size diagnostic sets, without requiring manually annotated reasoning traces. Extensive experiments on diverse ECG benchmarks demonstrate the significant superiority of our approach in diagnostic accuracy, while simultaneously providing interpretable clinical reasoning. Notably, reasoning quality evaluations confirm that SSPO substantially enhances the clinical validity of the generated rationales. These findings reveal that moving beyond direct label prediction toward structured reasoning offers a more clinically aligned direction for future ECG modeling.

Retrieval-Augmented Generation (RAG) is widely employed to mitigate risks such as hallucinations and knowledge obsolescence in medical question answering, yet its predominantly single-round, static retrieval paradigm misaligns with the multi-stage process of clinical reasoning. This compressed workflow induces two structural deficiencies: question-to-query translation often lacks clinically grounded semantic interpretation, and retrieval lacks iterative sufficiency feedback, making it difficult to form reliable evidence chains. We argue that both issues stem from a deeper cause: overloading a single reasoning chain with heterogeneous tasks of interpretation, exploration, and adjudication. The remedy is to reconstruct the workflow via task decoupling and dynamic multi-round exploration. To this end, we propose SEMA-RAG, a Self-Evolving Multi-Agent RAG framework for medical question answering, which assigns these roles to three specialist agents: the Interpreter Agent for clinical schema interpretation, the Explorer Agent for sufficiency-driven self-evolving retrieval, and the Arbiter Agent for evidence adjudication and answer selection. Across five benchmarks and five LLM backbones, SEMA-RAG improves the strongest baseline by +6.46 accuracy points on average, measured per backbone.

Process-Level Reward Models (PRMs) are essential for guiding complex reasoning in large language models, yet existing PRM benchmarks cover only general domains such as mathematics, failing to address medical reasoning -- which is uniquely characterized by safety criticality, knowledge intensity, and diverse error patterns. Without a reliable medical PRM evaluation framework, we cannot quantify models' error detection capabilities in clinical reasoning, leaving their safety in real-world healthcare applications unverified. We propose MedPRMBench, the first process-level reward model benchmark for the medical domain. Built through a three-phase pipeline based on Clinical Reasoning Blueprints (CRBs), MedPRMBench systematically generates high-quality evaluation data from seven medical QA sources, covering 14 fine-grained error types across three categories (Simplicity, Soundness, and Sensitivity) with the first 4-level severity grading system to quantify clinical impact. The benchmark comprises 6{,}500 questions with 13{,}000 reasoning chains and 113{,}910 step-level labels, plus 6{,}879 questions for training. Our medical PRM baseline achieves an 87.1% overall PRMScore -- substantially surpassing all baselines -- and serves as a plug-and-play verifier that improves downstream medical QA accuracy by 3.2--6.7 percentage points. Systematic evaluation spanning proprietary frontier models, open-source reasoning models, and medical-specialized models reveals critical weaknesses in current models' medical reasoning error detection capabilities, providing clear directions for future PRM improvement.

Privacy and computational constraints limit the use of large language models in psychiatry, while adapting small language models (SLMs) often requires substantial data and expert annotation. We developed ClinMPO, an evidence-guided reinforcement-learning framework guided by the psychiatrist-defined Clinical Psychiatry Thinking Strategy (CPTS). ClinMPO uses ClinRM, a reward model trained on 18,569 question--answer pairs from 4,474 psychiatry articles. We evaluated four Qwen3 sizes on 1,737 model-screened questions. ClinMPO outperformed Base, supervised fine-tuning and standard group relative policy optimization across scales. From responses by 300 senior pre-licensure medical students, we established the human baseline, a medical-student reference. The 4B model approached this baseline, whereas the 8B model surpassed it and ranked first among 31 models and post-training variants. ClinMPO improved performance across two complementary schemes covering ICD-11 diagnostic categories and psychiatric practice competencies. Blinded assessment by three clinicians showed improved rationale quality across CPTS criteria. These findings highlight how existing clinical evidence and specialist knowledge can be incorporated into the development of medical AI systems through evidence-guided learning.

Chain-of-Thought (CoT) reasoning has proven effective in enhancing large language models by encouraging step-by-step intermediate reasoning, and recent advances have extended this paradigm to Multimodal Large Language Models (MLLMs). In the medical domain, where diagnostic decisions depend on nuanced visual cues and sequential reasoning, CoT aligns naturally with clinical thinking processes. However, current benchmarks for medical image understanding generally focus on the final answer while ignoring the reasoning path. Such opaque reasoning processes lack reliable bases for judgment, making it difficult to assist doctors in diagnosis. To address this gap, we introduce a new M3CoTBench benchmark specifically designed to evaluate the correctness, efficiency, impact, and consistency of CoT reasoning in medical image understanding. M3CoTBench features 1) a diverse, multi-level difficulty dataset covering 24 examination types, 2) 13 varying-difficulty tasks, 3) a suite of CoT-specific evaluation metrics (correctness, efficiency, impact, and consistency) tailored to clinical reasoning, and 4) a performance analysis of multiple MLLMs. M3CoTBench systematically evaluates CoT reasoning across diverse medical imaging tasks, revealing current limitations of MLLMs in generating reliable and clinically interpretable reasoning, and aims to foster the development of transparent, trustworthy, and diagnostically accurate AI systems for healthcare. Project page at https://juntaojianggavin.github.io/projects/M3CoTBench/.

Reliable epidemiological reasoning requires synthesizing study evidence to infer disease burden, transmission dynamics, and intervention effects at the population level. Existing medical question answering benchmarks primarily emphasize clinical knowledge or patient-level reasoning, yet few systematically evaluate evidence-grounded epidemiological inference. We present EpiQAL, to our knowledge the first diagnostic benchmark for epidemiological question answering over research literature, comprising three subsets built from open-access articles across diverse diseases. The three subsets progressively test factual recall, multi-step inference, and conclusion reconstruction under incomplete information, and are constructed through a quality-controlled pipeline combining taxonomy guidance, multi-model verification, and difficulty screening. Experiments on fifteen models spanning open-source and proprietary systems reveal that current LLMs show limited performance on epidemiological reasoning, with multi-step inference posing the greatest challenge. Model rankings shift across subsets, and scale alone does not predict success. Chain-of-Thought prompting benefits multi-step inference but yields mixed results elsewhere. EpiQAL provides fine-grained diagnostic signals for evidence-grounding, inferential reasoning, and conclusion reconstruction.

Large Language Models (LLMs) with reasoning capabilities have recently demonstrated strong potential in medical Question Answering (QA). Existing approaches are largely English-focused and primarily rely on distillation from general-purpose LLMs, raising concerns about the reliability of their medical knowledge. In this work, we present a method to generate multilingual reasoning traces based on medical knowledge extracted from Wikipedia. We produce 500k traces in English, Italian, and Spanish, using a retrieval-augmented generation approach over medical information from Wikipedia. The traces are generated to solve medical questions drawn from MedQA and MedMCQA, which we extend to Italian and Spanish. We test our pipeline in both in-domain and out-of-domain settings across Medical QA benchmarks, and demonstrate that our reasoning traces improve performance both when utilized via in-context learning (few-shot) and supervised fine-tuning, yielding state-of-the-art results among 8B-parameter LLMs. We believe that these resources can support the development of more transparent clinical decision-support tools in multilingual settings. We release the full suite of resources: reasoning traces, translated QA datasets, Medical-Wikipedia, and fine-tuned models.