Clinical Reasoning

Clinical order generation serves as a critical bridge between clinical decision-making and real-world practice, translating medical decisions into concrete and executable orders. Existing agents mainly focus on coarse-grained decisions and overlook the fine-grained, executable information required for clinical orders. To address this gap, we propose CAREAgent, an agent for clinical order generation. To support its training, we introduce a two-stage agentic reasoning data construction method. First, we design an agent framework that constructs verifiable reasoning trajectories aligned with realistic clinical tool usage. Second, we filter reasoning trajectories by format compliance, order validity, and clinical plausibility. Building on the constructed data, the model is first trained via supervised fine-tuning to acquire fundamental reasoning formats and medical knowledge, and is subsequently optimized through reinforcement learning with multi-dimensional reward functions to enhance complex clinical reasoning capabilities. Experiments on multiple benchmarks demonstrate the effectiveness of CAREAgent. On ClinicalBench (unseen during training), CAREAgent improves the F1 score by 5.05%, 2.09%, and 0.86% over the single-agent, multi-agent, and agentic reasoning methods, respectively.

We present a protocol to evaluate ChatGPT's ability to generate disease-centric biomedical associations. It outlines how we generate the associations, validate the biological entities using biomedical ontologies, and verify associations using literature. The protocol includes a self-consistency strategy to assess generative reliability across ChatGPT models. To address ontology exact-match limitations, we provide a use case performing semantic verification through a workflow enabled by Retrieval-Augmented Generation (RAG) powered by open-source large language models (LLMs). This enables LLMs to establish truth over content generated by other LLMs and expose hallucination.

Retrieval-augmented generation combined with reinforcement learning has shown promise for grounding large language models in trustworthy medical evidence. However, existing methods rely on exact-match binary rewards, which in clinical diagnosis cause two issues: (i) semantically relevant but non-verbatim steps receive zero signal, discarding valuable learning signals; and (ii) uni-dimensional rewards cannot effectively supervise heterogeneous reasoning capabilities. To address these issues, we propose C-MIG, a Multi-view Information Gain-based retrieval-augmented generation framework for Clinical diagnosis. C-MIG estimates information gain under a frozen reference model from two complementary views, retrieved-document and document-refinement, to jointly guide what to retrieve and how to refine, alleviating the issues of valuable reward signal loss and credit assignment. We further design a multi-subquery retrieval augmentation strategy that improves knowledge recall coverage in clinical diagnostic scenarios. Comprehensive experiments on four medical benchmarks demonstrate that C-MIG achieves the best performance among all RAG-RL methods on both in-domain and out-of-domain sets, and outperforms state-of-the-art general-purpose LLMs for clinical diagnosis.

Volumetric Reasoning Segmentation (VRS) aims to segment a target region in a 3D medical scan from a free-form clinical query, where the referent is often implicit and requires both medical knowledge and volume-grounded reasoning. Existing methods typically rely on specialized segmentation tokens to connect language with mask decoding, but this coupling collapses the decision process into opaque latent representations, limiting interpretability and generalization to diverse narrative expressions. In this paper, we present MedVol-R1, a reinforcement learning-based framework for VRS that explicitly decouples evidence grounding from volumetric delineation: the LVLM grounds clinical reasoning to a verifiable 2D evidence anchor (key axial slice and 2D bounding boxes), which is then propagated into a coherent 3D mask by a frozen MedSAM2 module. We train MedVol-R1 with cold-start supervised fine-tuning followed by GRPO, guided by a multi-component reward that encourages informative evidence selection, accurate 2D spatial grounding, and cross-slice volumetric coherence, without requiring costly chain-of-thought annotations. Experiments on CT-ORG, AbdomenCT-1K, and KiTS23 from the M3D-Seg benchmark demonstrate that MedVol-R1 consistently outperforms strong baselines and achieves state-of-the-art performance, with reinforcement learning providing clear gains over pure supervised fine-tuning.

Clinical practice guidelines (CPGs) encode evidence-based decision logic that clinicians apply by evaluating patient variables, conditional criteria, and recommendation rules. However, existing methods often use CPGs as free-text training data or retrieval sources, underutilizing their procedural decision structure. To better exploit this structure, we introduce a guideline-derived training pipeline that transforms CPG recommendations into executable clinical decision logic and uses it to generate factual and counterfactual question-answering data. Theses data teach models both guideline-supported decisions and how decisions change under different patient conditions. Post-training a medical LLM on the generated data yields MedGuideX. Across four clinical reasoning benchmarks, MedGuideX achieves a 10.28% relative improvement in average accuracy. Physician evaluation further shows that MedGuideX better recovers clinician authored reasoning steps and produces physician-preferred rationales in faithfulness, validity, completeness, and clarity. Overall, our results show that executable decision logic from CPGs can be transformed into scalable supervision for building reliable medical LLMs.

Medical RAG needs evidence-grounded claims, so plugging a claim-level NLI checker into retrieval-augmented RL is intuitive. \textbf{We find that the checker's \emph{output distribution} during training, not its held-out accuracy, decides whether it provides trainable gradient.} We compare four NLI checker back-ends as process rewards inside a GRPO-trained medical RAG agent (Qwen2.5-7B, replicated on Qwen3-4B and Llama-3.1-8B) across four held-out medical QA benchmarks. Three diagnostic findings emerge. \textbf{(i)} Signal collapse is log-prob-specific: LLM log-probability scoring labels over 97% of claims neutral -- collapsing the RL gradient to zero -- while a calibrated MedNLI classifier scores the same pairs non-degenerately. \textbf{(ii)} Moderate signal beats strong signal on answer quality: a strong proprietary checker triggers a three-step reward-hacking cascade -- ultra-short answers, search avoidance, language collapse -- so a moderate-signal local classifier trains a higher-quality model (\textbf{+12% BERTScore over zero-shot, no GPT dependency}). \textbf{(iii)} Signal strength is policy-dependent: the same checker registers as moderate on one policy but strong on another without triggering the cascade end-state. We frame these as boundary conditions for verifier-as-reward systems.

Reasoning-enabled LLMs perform strongly on medical reasoning benchmarks, but it remains unclear whether these gains transfer to structured clinical documentation; we investigate this question using SOAP note generation from clinical dialogue in a source-aware benchmark spanning OMI Health, ACI-Bench, and PriMock57. We evaluate GPT-5.4, DeepSeek-V4-Flash, and Gemma-4-E4B in a controlled 2x2 design that independently toggles provider-native reasoning and same-source retrieval-augmented generation (RAG). Outputs are assessed using seven automatic metrics alongside two reference-aware LLM judges. Both evaluation approaches agree that a non-reasoning GPT-5.4 configuration achieves the highest overall quality, while DeepSeek-V4-Flash performs best among reasoning-enabled configurations. Enabling reasoning significantly degrades GPT-5.4 performance across all three datasets, whereas same-source RAG yields smaller, model-dependent improvements. Overall, the findings indicate that stronger reasoning capability should not be assumed to improve fidelity-sensitive SOAP note generation without dedicated, task-specific evaluation.

While large language models (LLMs) hold transformative potential for medicine, their reasoning robustness and safety in real-world clinical scenarios remain critically underexplored, particularly in dentistry. Here we introduce GlobalDentBench, the first multinational dental benchmark, featuring a taxonomy that encompasses 14 dental specialties across 88 countries and regions spanning six continents. The benchmark comprises 8,978 expert-validated questions across three formats (multiple-choice, short-answer, and case-based questions) and assesses three progressive reasoning levels: knowledge recall (L1), routine reasoning (L2), and individualized reasoning (L3). To ensure data quality, the automated construction framework was calibrated by six senior dentists, achieving expert agreement rates of 99.98% for multiple-choice and short-answer questions and 96.78% for the more complex case-based questions. Evaluation of 12 frontier LLMs on GlobalDentBench revealed a sharp, stepwise performance degradation with increasing reasoning complexity. Specifically, accuracy plummeted from 81.34% on multiple-choice to 64.53% on short-answer and 22.34% on case-based questions, while declining markedly from 74.01% at L1 to 55.64% at L2 and 35.71% at L3. More critically, risk analysis of real-world dental cases demonstrated an alarming overall unsafe rate of 31.01% in LLM-generated clinical recommendations, with 4.51% posing risks of irreversible patient harm and risks particularly pronounced in specialties such as orthodontics. These findings expose fundamental limitations in the medical reasoning and safety of current LLMs. Consequently, GlobalDentBench provides a scalable foundation for trustworthy clinical AI evaluation, underscoring the urgent need for rigorous validation before the safe deployment of these models in healthcare.

Vision-language models have demonstrated impressive capabilities in general medical visual question answering, yet due to limited interpretability, it remains unclear whether their predictions reflect evidence-grounded clinical reasoning or reliance on spurious priors. We introduce Med-R2 Bench, a hierarchical benchmark aligned with the clinical workflow to evaluate adversarial robustness with visual grounding. We design stepwise QA tasks to assess whether reasoning chains are strictly grounded in visual evidence across the four clinical stages, and employ adversarial perturbations to test robustness against misleading cues. Med-R2 comprises 42,432 images, 31 task categories, and 110,406 QA pairs. Evaluation across 14 VLMs reveals a sequential performance degradation along the four-stage clinical workflow. Adversarial experiments show that models rely heavily on correct prompts to guess answers. Even when provided with explicit visual cues, the models struggle to accurately align textual descriptions. Finally, we demonstrate stepwise fine-tuning using our hierarchical data significantly improves reasoning robustness, highlighting its potential to drive future improvements in evidence-based medical AI.

Biomedical knowledge graphs (KGs) treat disease associations as static facts, but temporal information is crucial for clinical reasoning, e.g., a symptom diagnostic of one disease at age 3 may imply a different disease at age 13. Existing KGs such as PrimeKG, Hetionet, and iKraph do not encode when a finding becomes clinically relevant over the course of a disease. This limits their usefulness for longitudinal clinical reasoning and retrieval augmentation. We introduce ChronoMedKG, a temporal biomedical knowledge graph that contains 460,497 evidence-linked triples (filtered from 13M raw extractions) covering 13,431 diseases. Each association is tied to temporal components like onset window or progression stage, which are backed by PMID-traceable evidence and a multi-signal credibility score. The graph is constructed through a disease-autonomous multi-agent pipeline in which multiple frontier LLMs independently extract knowledge from PubMed and PMC literature. Only those relations are kept that are supported by multi-model consensus, survive credibility filtering, as well as ontology alignment. ChronoMedKG scored 92.7% agreement against Orphadata and adds temporal grounding for 6,250 diseases absent from HPOA, Orphadata, and Phenopackets, including 1,657 Orphanet-coded rare diseases. We further introduce ChronoTQA, a benchmark of 3,341 questions across eight task types (six temporal plus two static controls), with a 12-question supplementary probe. Frontier LLMs lose roughly 30 points moving from static to temporal questions; ChronoMedKG retrieval rescues 47-65% of their long-tail failures, against 17-29% for HPOA-RAG. As such, ChronoMedKG provides a crucial temporal axis for retrieval-augmented clinical systems that was previously absent.

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.

Large Vision Language Models (LVLMs) show promise in medical applications, but their inability to faithfully ground responses in visual evidence raises serious concerns about clinical trustworthiness. While visual attribution methods are widely used to explain LVLM predictions, whether these explanations actually reflect the visual evidence underlying the model's decision is largely unverified, since ground-truth annotations for internal model reasoning are typically unavailable. We address this question for chest X-ray (CXR) reasoning by developing a causal evaluation framework that retains only CXR-VQA samples for which the expert-annotated region is verified, via counterfactual editing, to be causally responsible for the model's prediction. Using this framework across 11 attribution methods, six open-source LVLMs, and two output modes (direct answer and step-by-step reasoning), we find that existing attribution methods often fail to identify the evidence used by LVLMs. To address this failure, we propose MedFocus, a concept-based attribution method that localizes clinically meaningful anatomical regions via unbalanced optimal transport and measures their causal effect on model outputs through targeted interventions. MedFocus produces spatial, concept-level, and token-level attributions and substantially outperforms prior methods, taking a step toward more trustworthy attribution for medical LVLMs. Our data and code are available at https://github.com/gzxiong/medfocus/.

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.

Longitudinal chest X-ray (CXR) interpretation requires reasoning over disease evolution across multiple patient visits, yet most existing medical VQA benchmarks focus on single images or short-horizon image pairs. We introduce MI-CXR, a benchmark for standardized evaluation of Multi-Interval longitudinal reasoning over multi-visit CXR sequences, without requiring free-form report generation or additional clinical context. MI-CXR comprises five-way multiple-choice questions over five-visit patient timelines and instantiates three complementary task families: Temporal Event Localization, Interval-wise Change Reasoning, and Global Trajectory Summarization, which assess clinically grounded visual reasoning over time. Evaluating 14 state-of-the-art vision-language models (VLMs) shows low overall performance, with an average accuracy of 29.3%, only modestly above random guessing. Using stage-wise diagnostic probing, we find that models often produce locally plausible interval descriptions but fail to enforce temporal constraints or compose evidence into globally consistent decisions over the full timeline. These findings reveal key limitations of current VLMs and establish MI-CXR as a principled benchmark for longitudinal medical reasoning. The benchmark is available at https://github.com/AIDASLab/MI-CXR

Inpatient medication recommendation requires clinicians to repeatedly select specific medications, doses, and routes as a patient's condition evolves. Existing benchmarks formulate this task as admission-level prediction over coarse drug codes with multi-hot diagnostic and procedure code inputs, failing to capture the per-timepoint, information-rich nature of real prescribing. We propose RxEval, a prescription-level benchmark that evaluates LLM prescribing capability by multiple-choice questions: each question presents a detailed patient profile and time-ordered clinical trajectory, requiring selection of specific medication-dose-route triples from real prescriptions and patient-specific distractors generated via reasoning-chain perturbation. RxEval comprises 1,547 questions spanning 584 patients, 18 diagnostic categories, and 969 unique medications. Evaluation of 16 LLMs shows that RxEval is both challenging and discriminative: F1 ranges from 45.18 to 77.10 across models, and the best Exact Match is only 46.10%. Error analysis reveals that even frontier models may overlook stated patient information and fail to derive clinical conclusions.

Reasoning benchmarks measure clinical performance on clean inputs. We evaluate the step before reasoning: retrieval over real EHR notes, where negation, temporality, and family-versus-patient attribution can flip a correct answer to a wrong one. EpiKG carries an assertion label and a temporality tag with every fact in a patient knowledge graph, then routes retrieval by question intent. ClinicalBench is a 400-question test over 43 MIMIC-IV patients across 9 assertion-sensitive categories. A 7-condition ablation tests each piece of EpiKG across six LLMs (Claude Opus 4.6, GPT-OSS 20B, MedGemma 27B, Gemma 4 31B, MedGemma 1.5 4B, Qwen 3.5 35B). Three physicians blindly adjudicated 100 paired items. The author-blind primary endpoint, leave-author-out paired exact McNemar on 50 unanimous-strict items rated by two external physicians, yields +22.0 percentage points (95 percent Newcombe CI [+5.1, +31.5], p=0.0192). The architectural novelty, intent-aware KG-RAG over a Contriever dense-RAG baseline (C2b to C4g_kw on the change-excluded n=362 endpoint), is +8.84 percentage points (paired McNemar p=1.79e-3); +12.43 percentage points under oracle intent. Sensitivities agree directionally: three-rater physician majority +24.0 percentage points (subject to single-author circularity); deterministic keyword reproducibility proxy +39.5 percentage points. Across the six models, the gain shrinks as the LLM-alone baseline rises (beta=-1.123, r=-0.921, p=0.009). With n=6 this looks more like regression to the mean than encoding substituting for model size. Physician adjudication identified 56 percent of auto-generated reference answers as defective, a methodological finding indicating that NLP-pipeline clinical-QA benchmarks require physician adjudication to be usable. ClinicalBench, the frozen evaluator, three-rater adjudication data, and the EpiKG output stack are publicly released.

Cancer screening is a reasoning task. A radiologist observes findings, compares them to prior scans, integrates clinical context, and reaches a diagnostic conclusion confirmed by pathology. We present RadThinking, a Visual Question Answering (VQA) dataset that makes this reasoning explicit and trainable. RadThinking releases VQA pairs at three difficulty tiers. Foundation VQAs are atomic perception questions. Single-step reasoning VQAs apply one clinical rule. Compositional VQAs require multi-step chain-of-thought to reach a guideline category such as LI-RADS-5. For every compositional VQA, we release the chain of foundation VQAs that solves it. The chain follows the rules of the governing clinical reporting standard. The dataset spans 20,362 CT scans from 9,131 patients across 43 cancer groups, plus 2,077 verified healthy controls with >1-year follow-up. To our knowledge, RadThinking is the first cancer-screening VQA corpus that stratifies questions by reasoning depth and grounds compositions in clinical reporting standards. The foundation tier supplies atomic perception supervision. The compositional tier supplies chain-of-thought data and verifiable rewards for reinforcement-learning recipes such as DeepSeek-R1 and OpenAI o1. RadThinking enables systematic training and evaluation of whether AI systems can reason about cancer, not merely detect it.

Large vision-language models (VLMs) demonstrate strong performance in medical image understanding, but frequently generate clinically plausible yet incorrect statements, raising significant safety concerns. Existing medical hallucination benchmarks primarily focus on 2D imaging with one-shot diagnostic questions, offering limited insight into whether predictions are grounded in correct localization and abnormality identification, allowing critical reasoning errors to remain hidden behind seemingly correct diagnoses. We introduce Med-StepBench, the first large-scale benchmark for step-wise hallucination detection in 3D oncological PET/CT, comprising over 12,000 images and more than 1,000,000 image-statement pairs across volumetric and multi-view 2D data, which decomposes clinical reasoning into four expert-designed diagnostic stages. Using clinician-verified annotations, we perform the first step-level evaluation of general-purpose and medical VLMs, revealing systematic failure modes obscured by aggregate accuracy metrics. Furthermore, we show that current VLMs are highly susceptible to adversarial yet clinically plausible intermediate explanations, which significantly amplify hallucinations despite contradictory visual evidence. Together, our findings highlight fundamental limitations in grounding multi-step clinical reasoning and establish Med-StepBench as a rigorous benchmark for developing safer and more reliable medical VLMs.

Clinical reasoning agents based on large language models (LLMs) aim to automate tasks such as intensive care unit (ICU) monitoring and patient state tracking from electronic health records (EHRs). Existing systems typically rely on manually curated clinical tools or skills for concepts such as sepsis detection and organ failure assessment. However, maintaining these tool libraries requires substantial expert effort, while zero-shot querying or code generation often produces inefficient and unreliable reasoning chains, especially under institution-specific clinical policies. We introduce CodeClinic, a benchmark built on MIMIC-IV for evaluating whether LLM agents can synthesize and compose reusable clinical skills instead of relying on fixed toolboxes. The benchmark contains two complementary tasks: longitudinal ICU surveillance and compositional information seeking. The longitudinal setting simulates monitoring patient trajectories with structured decisions every four hours across 25 findings and eight clinical families, while the compositional setting spans 63k instances across 259 tasks in nine domains and is stratified by compositional dependency depth to evaluate increasingly complex multi-step reasoning. We further propose an offline autoformalization pipeline that converts natural-language clinical guidelines into reusable and verified Python skill libraries through iterative LLM refinement. Compared with zero-shot code generation, the resulting libraries improve consistency while reducing per-query token usage by up to 40%.

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.

Inpatient clinical reasoning is a sequential decision under partial observability: the clinician sees the admission so far and must choose the next action whose downstream consequences are not yet visible. Existing clinical-LLM evaluations and RL rewards signals collapse this into closed-form retrieval, clinical journey leakage, or unanchored LLM-as-judge scoring. We introduce CLR-voyance, a framework that reformulates inpatient reasoning as a Partially Observable Markov Decision Process (POMDP) and supervises it with rewards that are simultaneously outcome-grounded and clinician-validated. We instantiate the formulation as CLR-POMDP, which partitions successful patient journeys into a policy-visible past and an oracle-only future. Using the past information, an oracle LLM generates a case-specific query-answer pair, and the first adaptive rubric for clinical reasoning which is verifiable in the future of the patient journey. These rubrics are used for both post-training and evaluation of models for inpatient clinical reasoning. We post-train Qwen3-8B and MedGemma-4B with GRPO followed by model merging, yielding state-of-the-art inpatient clinical reasoning while retaining generalist capabilities. CLR-voyance-8B achieves 84.91% on CLR-POMDP, ahead of frontier medical reasoning models like GPT-5 (77.83%) and MedGemma-27B (66.66%) and has comparable or better performance on existing medical benchmarks. To ensure a clinically meaningful setting, we conduct a large-scale clinician alignment study, where physicians curate per-case rubrics, grade candidate responses, and provide blinded pairwise preferences of model reasoning. This study provides insights on clinical LLM-as-a-judge and clinical preference-model selection, which can inform the community at large. CLR-voyance has been deployed for 6+ months at a partner public hospital, drafting thousands of reasoning-heavy inpatient notes.

Real-world clinical diagnosis is a complex process in which the doctor is required to obtain information from both interaction with the patient and conducting medical exams. Additionally, the doctor needs to adapt to different patient personas, as well as noisy and incomplete information that can happen at any time during the process. However, existing benchmarks for medical LLMs and methods for automatic diagnosis largely simplify this process by reducing it to single-turn question answering, noise-free conversations, or sequential exam making, etc., ignoring the interactive and uncertain nature of clinical diagnosis. In this paper, we aim to address this gap by formalizing clinical diagnosis as a Partially Observable Markov Decision Process (POMDP) with three action types: questioning the patient, ordering medical exams as tool calls, and issuing a diagnosis. We also introduce a systematic noise model comprising seven patient noise types and three exam noise types. Using our proposed environment, we train an effective diagnosis agent, \textbf{MedExAgent}, through a two-stage pipeline that first performs supervised finetuning on synthetic conversations structured after the Calgary-Cambridge model for clinical interviews, and then applies DAPO to optimize a composite reward capturing diagnostic accuracy, tool call quality, and exam cost including financial cost and patient discomfort. Through extensive experiments and ablation studies, we demonstrate that MedExAgent achieves diagnostic performance comparable to larger models while maintaining cost-efficient examination strategies.

Medical multimodal large language models (MLLMs) have advanced image understanding and short-video analysis, but real clinical review often requires full-procedure video understanding. Unlike general long videos, medical procedures contain highly redundant anatomical views, while decisive evidence is temporally sparse, spatially subtle, and context dependent. Existing benchmarks often assume this evidence has already been localized through images, short clips, or pre-segmented videos, leaving the retrieval-before-reasoning problem under-tested. We introduce MedHorizon, an in-the-wild benchmark for long-context medical video understanding. MedHorizon preserves 759 hours of full-length clinical procedures and provides 1,253 evidence-grounded multiple-choice questionsthat jointly evaluate sparse evidence understanding and multi-hop clinical reasoning. Its evidence is extremely sparse, with only 0.166% evidence frames on average, requiring models to search noisy procedural streams before interpreting and aggregating findings. We evaluate representative general-domain, medical-domain, and long-video MLLMs. The best model reaches only 41.1% accuracy, showing that current systems remain far from robust full-procedure understanding. Further analysis yields four key findings: performance does not scale reliably with more frames, evidence retrieval and clinical interpretation remain primary bottlenecks; these bottlenecks are rooted in weak procedural reasoning and attention drift under redundancy, and generic sampling methods only partially balances local detail with global coverage. MedHorizon provides a rigorous testbed for MLLMs that retrieve sparse evidence and reason over complete clinical workflows.

The work in this paper evaluates zero-shot and few-shot large language models (LLMs) for safety-critical clinical action extraction using the CLIP discharge-note dataset, with particular emphasis on transitions of care and post-discharge patient safety. To manage the complexity of clinical documentation, we introduce a two-stage extraction framework that decomposes discharge notes, that are written in narrative form, into fine-grained, explicitly actionable clinical tasks through a staged prompting strategy. Our contributions include a systematic assessment of generative LLMs for clinical action extraction, a detailed comparison between general-purpose LLMs and task-specific supervised BERT-based models, and an analysis of annotation inconsistencies across different action categories. We show that contemporary LLMs achieve performance comparable to or exceeding supervised models on binary actionability detection, while supervised baselines retain a meaningful advantage on fine-grained multi-label category classification, despite the absence of task-specific fine-tuning and under strict data-privacy constraints. Qualitative error analysis reveals that many failures stem from misalignment between model reasoning and dataset annotation conventions, particularly in cases involving implicit clinical actions and rigid structural labeling rules. These results indicate that reported performance reflects model limitations due to lack of clinical reasoning, that is not captured by plain annotations. Labels without rationales make it impossible to distinguish clinical reasoning failures from annotation convention mismatches. Advancing clinical NLP requires reasoning-annotated datasets that document why specific spans are actionable, not merely which spans were labeled, enabling proper evaluation of model clinical understanding.

Evaluating large language models (LLMs) for medical applications remains challenging due to benchmark saturation, limited data accessibility, and insufficient coverage of relevant tasks. Existing suites have either saturated, heavily depend on restricted datasets, or lack comprehensive model coverage. We introduce Medmarks, a fully open-source evaluation suite with 30 benchmarks spanning question answering, information extraction, medical calculations, and open-ended clinical reasoning. We perform a systematic evaluation of 61 models across 71 configurations using verifiable metrics and LLM-as-a-Judge. Our results show that frontier reasoning models (Gemini 3 Pro Preview, GPT-5.1, & GPT-5.2) achieve the highest performance across both benchmarks, most frontier proprietary models are significantly more token efficient than open-weight alternatives, medically fine-tuned models outperform their generalist counterparts, and that models are susceptible to answer-order bias (particularly smaller models and Grok 4). A subset of our evals (Medmarks-T) can be directly used as reinforcement learning environments to post-train LLMs for medical reasoning. Code is available at https://github.com/MedARC-AI/Medmarks

Brazil's Unified Health System (SUS) relies on official clinical guidelines that define diagnostic criteria, treatments, dosages, and monitoring procedures for over 200 million citizens. Yet current LLMs perform poorly on this guideline-specific knowledge, and no benchmark evaluates clinical recall grounded in Brazilian Portuguese protocols. We address this gap by adapting Qwen2.5-14B-Instruct to the Brazilian clinical domain. From 178 official guidelines (~5.4M tokens), we generate ~70M tokens of synthetic data in three formats -- rephrases, wiki-style articles, and question-answer pairs -- using four generator LLMs. We then apply continual pre-training followed by Group Relative Policy Optimization (GRPO). We introduce HealthBench-BR, with 1,780 balanced true/false clinical assertions, and PCDT-QA, with 890 open-ended clinical questions scored by an LLM judge. Our best model achieves 83.9% on HealthBench-BR and 85.4% on PCDT-QA, outperforming GPT-5.2, Claude Sonnet 4.6, Gemini 3.1 Pro, and Google AI Overview's web-grounded RAG despite having only 14B parameters. Ablations show that generator diversity and reinforcement learning are critical to these gains. We release all datasets, benchmarks, and model weights to support reproducible clinical NLP research for Brazilian Portuguese. Code, data, and model weights are available at https://github.com/hugoabonizio/clinical-protocols-br

Clinical reasoning demands multi-step interactions -- gathering patient history, ordering tests, interpreting results, and making safe treatment decisions -- yet a unified training environment provides the breadth of clinical domains and specialized tools to train generalizable medical AI agents through reinforcement learning remains elusive. We present a comprehensive empirical study of multi-turn agentic RL for medical AI, built on \gym{}, a gymnasium-compatible environment spanning 10 clinical domains with 3.6K+ tasks, 135 domain-specific tools, and a knowledge base of 828K medical passages. Our analysis reveals that agentic multi-turn structure degrades into verbose single-turn monologues, characterized by monotonic length explosion and a simultaneous erosion of tool-use frequency. We characterize how this collapse, alongside distillation instability, stems from the misalignment of sparse terminal rewards with sequential clinical trajectories. We find that vanilla GRPO achieves strong final accuracy on some benchmarks but suffers from training instability, evidenced by significant oscillations in response length and prolonged convergence periods. To improve training efficiency and stability, we propose Turn-level Truncated On-Policy Distillation (TT-OPD), a self-distillation framework where a gradient-free EMA teacher leverages outcome-privileged information to provide dense, outcome-aware KL regularization at every conversation turn. TT-OPD achieves the best performance on 10 of 18 benchmarks with an average +3.9~pp improvement over the non-RL baseline with faster early convergence, controlled response length, and sustained multi-turn tool use.

Effective mental health counseling is a complex, theory-driven process requiring the simultaneous integration of psychological frameworks, real-time distress signals, and strategic intervention planning. This level of clinical reasoning is critical for safety and therapeutic effectiveness but is often missing in general-purpose Large Language Models (LLMs). We introduce SAGE (Strategy-Aware Graph-Enhanced), a novel framework designed to bridge the gap between structured clinical knowledge and generative AI. SAGE constructs a heterogeneous graph that unifies conversational dynamics with a psychologically grounded layer, explicitly anchoring interactions in a theory-driven lexicon. Our architecture first employs a Next Strategy Classifier to identify the optimal therapeutic intervention. Subsequently, a Graph-Aware Attention mechanism projects graph-derived structural signals into soft prompts, conditioning the LLM to generate responses that maintain clinical depth. Validated through both automated metrics and expert human evaluation, SAGE outperforms baselines in strategy prediction and recommended response quality. By providing actionable intervention recommendations, SAGE serves as a cutting-edge decision-support tool designed to augment human expertise in high-stakes crisis counseling.

Despite strong performance of deep learning models in retinal disease detection, most systems produce static predictions without clinical reasoning or interactive explanation. Recent advances in multimodal large language models (MLLMs) integrate diagnostic predictions with clinically meaningful dialogue to support clinical decision-making and patient counseling. In this study, OcularChat, an MLLM, was fine-tuned from Qwen2.5-VL using simulated patient-physician dialogues to diagnose age-related macular degeneration (AMD) through visual question answering on color fundus photographs (CFPs). A total of 705,850 simulated dialogues paired with 46,167 CFPs were generated to train OcularChat to identify key AMD features and produce reasoned predictions. OcularChat demonstrated strong classification performance in AREDS, achieving accuracies of 0.954, 0.849, and 0.678 for the three diagnostic tasks: advanced AMD, pigmentary abnormalities, and drusen size, significantly outperforming existing MLLMs. On AREDS2, OcularChat remained the top-performing method on all tasks. Across three independent ophthalmologist graders, OcularChat achieved higher mean scores than a strong baseline model for advanced AMD (3.503 vs. 2.833), pigmentary abnormalities (3.272 vs. 2.828), drusen size (3.064 vs. 2.433), and overall impression (2.978 vs. 2.464) on a 5-point clinical grading rubric. Beyond strong objective performance in AMD severity classification, OcularChat demonstrated the ability to provide diagnostic reasoning, clinically relevant explanations, and interactive dialogue, with high performance in subjective ophthalmologist evaluation. These findings suggest that MLLMs may enable accurate, interpretable, and clinically useful image-based diagnosis and classification of AMD.

We study clinical trial table reasoning, where answers are not directly stored in visible cells but must be reasoned from semantic understanding through normalization, classification, extraction, or lightweight domain reasoning. Motivated by the observation that current LLM approaches often suffer from "bad reasoning" under implicit planning assumptions, we focus on settings in which the model must recover implicit attributes such as therapy type, added agents, endpoint roles, or follow-up status from partially observed clinical-trial tables. We propose SCOPE (Structured Clinical hybrid Planning for Evidence retrieval in clinical trials), a multi-LLM planner-based framework that decomposes the task into row selection, structured planning, and execution. The planner makes the source field, reasoning rules, and output constraints explicit before answer generation, reducing ambiguity relative to direct prompting. We evaluate SCOPE on 1,500 hybrid reasoning questions over oncology clinical-trial tables against zero-shot, few-shot, chain-of-thought, TableGPT2, Blend-SQL, and EHRAgent. Results show that explicit multi-LLM planning improves accuracy for reasoning-based questions while offering a stronger accuracy-efficiency tradeoff than heavier agentic baselines. Our findings position clinical trial reasoning as a distinct table understanding problem and highlight hybrid planner-based decomposition as an effective solution

Multiple myeloma is managed through sequential lines of therapy over years to decades, with each decision depending on cumulative disease history distributed across dozens to hundreds of heterogeneous clinical documents. Whether LLM-based systems can synthesise this evidence at a level approaching expert agreement has not been established. A retrospective evaluation was conducted on longitudinal clinical records of 811 myeloma patients treated at a tertiary centre (2001-2026), covering 44,962 documents and 1,334,677 laboratory values, with external validation on MIMIC-IV. An agentic reasoning system was compared against single-pass retrieval-augmented generation (RAG), iterative RAG, and full-context input on 469 patient-question pairs from 48 templates at three complexity levels. Reference labels came from double annotation by four oncologists with senior haematologist adjudication. Iterative RAG and full-context input converged on a shared ceiling (75.4% vs 75.8%, p = 1.00). The agentic system reached 79.6% concordance (95% CI 76.4-82.8), exceeding both baselines (+3.8 and +4.2 pp; p = 0.006 and 0.007). Gains rose with question complexity, reaching +9.4 pp on criteria-based synthesis (p = 0.032), and with record length, reaching +13.5 pp in the top decile (n = 10). The system error rate (12.2%) was comparable to expert disagreement (13.6%), but severity was inverted: 57.8% of system errors were clinically significant versus 18.8% of expert disagreements. Agentic reasoning was the only approach to exceed the shared ceiling, with gains concentrated on the most complex questions and longest records. The greater clinical consequence of residual system errors indicates that prospective evaluation in routine care is required before these findings translate into patient benefit.

Diagnostic prediction and clinical reasoning are critical tasks in healthcare applications. While Large Language Models (LLMs) have shown strong capabilities in commonsense reasoning, they still struggle with diagnostic reasoning due to limited domain knowledge. Existing approaches often rely on internal model knowledge or static knowledge bases, resulting in knowledge insufficiency and limited adaptability, which hinder their capacity to perform diagnostic reasoning. Moreover, these methods focus solely on the accuracy of final predictions, overlooking alignment with standard clinical reasoning trajectories. To this end, we propose MultiDx, a two-stage diagnostic reasoning framework that performs differential diagnosis by analyzing evidence collected from multiple knowledge sources. Specifically, it first generates suspected diagnoses and reasoning paths by leveraging knowledge from web search, SOAP-formatted case, and clinical case database. Then it integrates multi-perspective evidence through matching, voting, and differential diagnosis to generate the final prediction.~Extensive experiments on two public benchmarks demonstrate the effectiveness of our approach.

Knowledge graphs (KGs) are increasingly used to support large lan guage model (LLM) reasoning, but standard triplet-based KGs treat each relation as globally valid. In many settings, whether a relation should count as evidence depends on the context. We therefore formulate triplet validity as a triplet-specific function of context and refer to this formulation as a Quantum Knowledge Graph (QKG). We instantiate QKG in medicine using a diabetes-centered PrimeKG subgraph, whose 68,651 context-sensitive relations are further annotated with patient-group-specific constraints. We evaluate it in a reasoner--validator pipeline for medical question answering on a KG-grounded subset of MedReason containing 2,788 questions. With Haiku-4.5 as both the Reasoner and the Validator, KG-backed validation significantly improves over a no-validator baseline ($+0.61$ pp), and QKG with context matching yields the largest gain, outperforming both KG validation without context matching ($+0.79$ pp) and the no-validator baseline ($+1.40$ pp; paired McNemar, all $p<0.05$). Under a stronger validator (Qwen-3.6-Plus), the raw QKG gain over the no-validator baseline grows from $+1.40$ pp to $+5.96$ pp; the context-matching gap is non-significant ($p=0.73$) on the raw set but becomes borderline significant ($p=0.05$) after adjustment for knowledge leakage and suspicious questions, consistent with a benchmark-gold ceiling rather than a QKG limitation. Taken together, the results support the view that the value of a KG in LLM-based clinical reasoning lies not merely in storing medically related facts, but in representing whether those facts are applicable to the specific patient context. For reproducibility and further research, we release the curated QKG datasets and source code.\footnote{https://github.com/HKAI-Sci/QKG}

The application of large language models (LLMs) in clinical decision support faces significant challenges of "tunnel vision" and diagnostic hallucinations present in their processing unstructured electronic health records (EHRs). To address these challenges, we propose a novel chain-based clinical reasoning framework, called DxChain, which transforms the diagnostic workflow into an iterative process by mirroring a clinician's cognitive trajectory that consists of "Memory Anchoring", "Navigation" and "Verification" phases. DxChain introduces three key methodological innovations to elicit the potential of LLM: (i) a Profile-Then-Plan paradigm to mitigate cold-start hallucinations by establishing a panoramic patient baseline, (ii) a Medical Tree-of-Thoughts (Med-ToT) algorithm for strategic look ahead planning and resource aware navigation, and (iii) a Dialectical Diagnostic Verification procedure utilizing "Angel-Devil" adversarial debates to resolve complex evidence conflicts. Evaluated on two real world benchmarks, MIMIC-IV-Ext Cardiac Disease and MIMIC-IV-Ext CDM, DxChain achieves state-of-the-art performances in both diagnostic accuracy and logical consistency, offering a modular and reliable architecture for next-generation clinical AI. The code is at https://anonymous.4open.science/r/Dx-Chain.

Large language models (LLMs) show promise in medical diagnosis, but real-world deployment remains challenging due to high-stakes clinical decisions and imperfect reasoning reliability. As a result, careful inspection of model behavior is essential for assessing whether diagnostic reasoning is reliable and clinically grounded. However, debugging medical LLMs remains difficult. First, developers often lack sufficient medical domain expertise to interpret model errors in clinically meaningful terms. Second, models can fail across a large and diverse set of instances involving different input types, tasks, and reasoning steps, making it challenging for developers to prioritize which errors deserve focused inspection. Third, developers struggle to identify recurring error patterns across cases, as existing debugging practices are largely instance-centric and rely on manual inspection of isolated failures. To address these challenges, we present VeriLLMed, a visual analytics system that integrates external biomedical knowledge to audit and debug medical LLM diagnostic reasoning. VeriLLMed transforms model outputs into comparable reasoning paths, constructs knowledge graph-grounded reference paths, and identifies three recurring classes of diagnosis errors: relation errors, branch errors, and missing errors. Case studies and expert evaluation demonstrate that VeriLLMed helps developers identify clinically implausible reasoning and generate actionable insights that can inform the improvement of medical LLMs.

Large language models (LLMs) are increasingly utilized in clinical reasoning and risk assessment. However, their interpretive reliability in critical and indeterminate domains such as psychiatry remains unclear. Prior work has identified algorithmic biases and prompt sensitivity in these systems, raising concerns about how contextual information may influence model outputs, but there remains no systematic way to assess these, especially in the psychiatric domain. We propose an approach for reliability auditing downstream LLM tasks by structuring evaluation around the impact of prompt design and the inclusion of medically insignificant inputs on predicted hospitalization risk scores, which is often the first downstream AI clinical-decision-making task. In our audit, a cohort of synthetic patient profiles (n = 50) is generated, each consisting of 15 clinically relevant features and up to 50 clinically insignificant features, across four prompt reframings (neutral, logical, human impact, clinical judgment). We audit four LLMs (Gemini 2.5 Flash, LLaMa 3.3 70b, Claude Sonnet 4.6, GPT-4o mini), and our results show that including medically insignificant variables resulted in a statistically significant increase in the absolute mean predicted hospitalization risk and output variability across all models and prompts, indicating reduced predictive stability as contextual noise increased. Clinically insignificant features had an effect on instability across many model-prompt conditions, and prompt variations independently affected the trajectory of instability in a model-dependent manner. These findings quantify how LLM-based psychiatric risk assessments are sensitive to non-clinical information, highlighting the need for systematic evaluations of attributional stability and uncertainty behavior like this before clinical deployments.

Fine-grained spatiotemporal reasoning on surgical videos is critical, yet the capabilities of Multi-modal Large Language Models (MLLMs) in this domain remain largely unexplored. To bridge this gap, we introduce SurgCoT, a unified benchmark for evaluating chain-of-thought (CoT) reasoning in MLLMs across 7 surgical specialties and 35 diverse procedures. SurgCoT assesses five core reasoning dimensions: Causal Action Ordering, Cue-Action Alignment, Affordance Mapping, Micro-Transition Localization, and Anomaly Onset Tracking, through a structured CoT framework with an intensive annotation protocol (Question-Option-Knowledge-Clue-Answer), where the Knowledge field provides essential background context and Clue provides definitive spatiotemporal evidence. Evaluation of 10 leading MLLMs shows: 1) commercial models outperform open-source and medical-specialized variants; 2) significant gaps exist in surgical CoT reasoning; 3) SurgCoT enables effective evaluation and enhances progressive spatiotemporal reasoning. SurgCoT provides a reproducible testbed to narrow the gap between MLLM capabilities and clinical reasoning demands. Code: https://github.com/CVI-SZU/SurgCoT.

Assessing chronic wound infection from photographs is challenging because visual appearance varies across wound etiologies, anatomical locations, and imaging conditions. Prior image-based deep learning methods have mainly focused on classification with limited interpretability, despite the need for evidence-grounded explanations to support point-of-care decision making. We present Infection-Reasoner, a compact 4B-parameter reasoning vision-language model for chronic wound infection classification and rationale generation. To address the scarcity of expert-labeled wound images with reasoning annotations, Infection-Reasoner is trained using a two-stage pipeline: (1) reasoning distillation, in which GPT-5.1 generates chain-of-thought rationales for unlabeled wound images to initialize wound-specific reasoning in a smaller student model (Qwen3-VL-4B-Thinking), and (2) reinforcement learning post-training with Group Relative Policy Optimization on a small labeled infection dataset to refine classification reasoning. On a held-out heterogeneous wound dataset, Infection-Reasoner achieved 86.8% accuracy, 86.4% sensitivity, and 87.1% specificity, outperforming several strong baselines, including GPT-5.1. Rationale quality was further evaluated using both multimodal large language model (MLLM) judges and wound expert review. Across four MLLM judges, visual-support agreement scores ranged from 0.722 to 0.903, while expert review rated 61.8% of rationales as Correct and 32.4% as Partially Correct.

Recent advances in deep research systems enable large language models to retrieve, synthesize, and reason over large-scale external knowledge. In medicine, developing clinical guidelines critically depends on such deep evidence integration. However, existing benchmarks fail to evaluate this capability in realistic workflows requiring multi-step evidence integration and expert-level judgment. To address this gap, we introduce MedProbeBench, the first benchmark leveraging high-quality clinical guidelines as expert-level references. Medical guidelines, with their rigorous standards in neutrality and verifiability, represent the pinnacle of medical expertise and pose substantial challenges for deep research agents. For evaluation, we propose MedProbe-Eval, a comprehensive evaluation framework featuring: (1) Holistic Rubrics with 1,200+ task-adaptive rubric criteria for comprehensive quality assessment, and (2) Fine-grained Evidence Verification for rigorous validation of evidence precision, grounded in 5,130+ atomic claims. Evaluation of 17 LLMs and deep research agents reveals critical gaps in evidence integration and guideline generation, underscoring the substantial distance between current capabilities and expert-level clinical guideline development. Project: https://github.com/uni-medical/MedProbeBench

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.

As Artificial Intelligence (AI) and Agentic AI become increasingly integrated across sectors such as education and healthcare, it is critical to ensure that Multi-Agent Education System (MAES) is explainable from the early stages of requirements engineering (RE) within the AI software development lifecycle. Explainability is essential to build trust, promote transparency, and enable effective human-AI collaboration. Although personas are well-established in human-computer interaction to represent users and capture their needs and behaviors, their role in RE for explainable MAES remains underexplored. This paper proposes a human-first, persona-driven, explainable MAES RE framework and demonstrates the framework through a MAES for clinical reasoning training. The framework integrates personas and user stories throughout the RE process to capture the needs, goals, and interactions of various stakeholders, including medical educators, medical students, AI patient agent, and clinical agents (physical exam agent, diagnostic agent, clinical intervention agent, supervisor agent, evaluation agent). The goals, underlying models, and knowledge base shape agent interactions and inform explainability requirements that guided the clinical reasoning training of medical students. A post-usage survey found that more than 78% of medical students reported that MAES improved their clinical reasoning skills. These findings demonstrate that RE based on persona effectively connects technical requirements with non-technical medical students from a human-centered approach, ensuring that explainable MAES are trustworthy, interpretable, and aligned with authentic clinical scenarios from the early stages of the AI system engineering. The partial MAES for the clinical scenario simulator is~\href{https://github.com/2sigmaEdTech/MAS/}{open sourced here}.

Evaluating medical AI systems using expert clinician panels is costly and slow, motivating the use of large language models (LLMs) as alternative adjudicators. Here, we evaluate an LLM Jury, composed of three frontier AI models, for scoring 3334 diagnoses on 300 real-world low- and middle-income country (LMIC) hospital cases. Both LLM- and clinician-generated diagnoses are scored against expert panel diagnoses across four dimensions: diagnosis, differential diagnosis, clinical reasoning, and negative treatment risk. The LLM Jury scores are compared with expert and independent re-scoring panel scores to assess error metrics, inter-rater agreement, severe-risk errors, and the effect of post hoc calibration using isotonic regression. In our data, we find that: (i) the uncalibrated LLM Jury scores preserve ordinal agreement with the expert clinician panel scores, but are systematically lower; (ii) the probability of severe-risk errors is lower for the LLM Jury than the human expert re-score panels; (iii) the LLM Jury combined with LLM diagnoses can be used to identify diagnoses at high risk of error, enabling targeted expert review and improved panel efficiency; (iv) the calibrated LLM Jury scores and rankings of diagnosing agents show excellent agreement with those of the primary expert panels; (v) LLM Jury models show no self-preference bias, they did not score diagnoses generated by their own underlying model or models from the same vendor more (or less) favourably than those generated by other models. Together, these results provide evidence that a calibrated LLM Jury is a trustworthy and reliable proxy for expert clinician evaluation in medical AI benchmarking. Confirming these findings in other clinical settings is an important direction for future work.

Evaluating large language models (LLMs) for clinical documentation tasks such as SOAP note generation remains challenging. Unlike standard summarization, these tasks require clinical abstraction, normalization of colloquial language, and medically grounded inference. However, prevailing evaluation methods including automated metrics and LLM as judge frameworks rely on lexical faithfulness, often labeling any information not explicitly present in the transcript as hallucination. We show that such approaches systematically misclassify clinically valid outputs as errors, inflating hallucination rates and distorting model assessment. Our analysis reveals that many flagged hallucinations correspond to legitimate clinical transformations, including synonym mapping, abstraction of examination findings, diagnostic inference, and guideline consistent care planning. By aligning evaluation criteria with clinical reasoning through calibrated prompting and retrieval grounded in medical ontologies we observe a significant shift in outcomes. Under a lexical evaluation regime, the mean hallucination rate is 35%, heavily penalizing valid reasoning. With inference aware evaluation, this drops to 9%, with remaining cases reflecting genuine safety concerns. These findings suggest that current evaluation practices over penalize valid clinical reasoning and may measure artifacts of evaluation design rather than true errors, underscoring the need for clinically informed evaluation in high context domains like medicine.

Large language models (LLMs) show promise in generating supportive responses for mental health and counseling applications. However, their responses often lack cultural sensitivity, contextual grounding, and clinically appropriate guidance. This work addresses the gap of how to systematically incorporate domain-specific, clinically validated knowledge into LLMs to improve counseling quality. We utilize and compare two approaches, retrieval-augmented generation (RAG) and a knowledge graph (KG)-based method, designed to support para-counselors. Our KG is constructed manually and clinically validated, capturing causal relationships between stressors, interventions, and outcomes, with contributions from multidisciplinary people. We evaluated multiple LLMs in both settings using BERTScore F1 and SBERT cosine similarity, as well as human evaluation across five metrics, which is designed to directly measure the effectiveness of counseling beyond similarity at the surface level. The results show that KG-based approaches consistently improve contextual relevance, clinical appropriateness, and practical usability compared to RAG alone, demonstrating that structured, expert-validated knowledge plays a critical role in addressing LLMs limitations in counseling tasks.

In this work, we propose Oph-Guid-RAG, a multimodal visual RAG system for ophthalmology clinical question answering and decision support. We treat each guideline page as an independent evidence unit and directly retrieve page images, preserving tables, flowcharts, and layout information. We further design a controllable retrieval framework with routing and filtering, which selectively introduces external evidence and reduces noise. The system integrates query decomposition, query rewriting, retrieval, reranking, and multimodal reasoning, and provides traceable outputs with guideline page references. We evaluate our method on HealthBench using a doctor-based scoring protocol. On the hard subset, our approach improves the overall score from 0.2969 to 0.3861 (+0.0892, +30.0%) compared to GPT-5.2, and achieves higher accuracy, improving from 0.5956 to 0.6576 (+0.0620, +10.4%). Compared to GPT-5.4, our method achieves a larger accuracy gain of +0.1289 (+24.4%). These results show that our method is more effective on challenging cases that require precise, evidence-based reasoning. Ablation studies further show that reranking, routing, and retrieval design are critical for stable performance, especially under difficult settings. Overall, we show how combining visionbased retrieval with controllable reasoning can improve evidence grounding and robustness in clinical AI applications,while pointing out that further work is needed to be more complete.

Drug recommendation requires a deep understanding of individual patient context, especially for complex conditions like Parkinson's disease. While LLMs possess broad medical knowledge, they fail to capture the subtle nuances of actual prescribing patterns. Existing RAG methods also struggle with these complexities because guideline-based retrieval remains too generic and similar-patient retrieval often replicates majority patterns without accounting for the unique clinical nuances of individual patients. To bridge this gap, we propose PACE-RAG (Patient-Aware Contextual and Evidence-Constrained RAG). Rather than directly copying frequent medications from retrieved patients, PACE-RAG personalizes recommendations by first extracting patient-specific clinical features, retrieving cases around these features, and then refining the final prescription using the patient's current symptoms, active medication history, and focus-specific prescribing tendencies. By analyzing treatment patterns tailored to specific clinical features, PACE-RAG generates patient-specific medication recommendations along with an explainable clinical summary. PACE-RAG achieved the strongest performance among the evaluated inference-only LLM-based methods, reaching F1 scores of 80.84% and 47.22% on the Parkinson's disease and MIMIC-IV cohorts, respectively. Our code is available at: https://github.com/ChaeYoungHuh/PACE-RAG.

Delineating the clinical target volume (CTV) in radiotherapy involves complex margins constrained by tumor location and anatomical barriers. While deep learning models automate this process, their rigid reliance on expert-annotated data requires costly retraining whenever clinical guidelines update. To overcome this limitation, we introduce OncoAgent, a novel guideline-aware AI agent framework that seamlessly converts textual clinical guidelines into three-dimensional target contours in a training-free manner. Evaluated on esophageal cancer cases, the agent achieves a zero-shot Dice similarity coefficient of 0.842 for the CTV and 0.880 for the planning target volume, demonstrating performance highly comparable to a fully supervised nnU-Net baseline. Notably, in a blinded clinical evaluation, physicians strongly preferred OncoAgent over the supervised baseline, rating it higher in guideline compliance, modification effort, and clinical acceptability. Furthermore, the framework generalizes zero-shot to alternative esophageal guidelines and other anatomical sites (e.g., prostate) without any retraining. Beyond mere volumetric overlap, our agent-based paradigm offers near-instantaneous adaptability to alternative guidelines, providing a scalable and transparent pathway toward interpretability in radiotherapy treatment planning.

The rise of large language models (LLMs) has shifted time series analysis from narrow analytics to general-purpose reasoning. Yet, existing benchmarks cover only a small set of health time series modalities and tasks, failing to reflect the diverse domains and extensive temporal dependencies inherent in real-world physiological modeling. To bridge these gaps, we introduce HEARTS (Health Reasoning over Time Series), a unified benchmark for evaluating hierarchical reasoning capabilities of LLMs over general health time series. HEARTS integrates 16 real-world datasets across 12 health domains and 20 signal modalities, and defines a comprehensive taxonomy of 110 tasks grouped into four core capabilities: Perception, Inference, Generation, and Deduction. Evaluating 16 state-of-the-art LLMs on more than 20K test samples reveals intriguing findings. First, LLMs substantially underperform specialized models, and their performance is only weakly related to general reasoning scores. Moreover, LLMs often rely on simple heuristics and struggle with multi-step temporal reasoning. Finally, performance declines with increasing temporal complexity, with similar failure modes within model families, indicating that scaling alone is insufficient. By making these gaps measurable, HEARTS provides a standardized testbed and living benchmark for developing next-generation LLM agents capable of reasoning over diverse health signals.

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.

In this paper, we propose a modified version of the MedQA-USMLE dataset, named MEDQA-OPEN, which contains open-ended medical questions without options to mimic clinical scenarios, along with clinician-approved reasoned answers. Additionally, we implement a prompt driven by Chain of Thought (CoT) reasoning, CLINICR, to mirror the prospective process of incremental reasoning, reaching a correct response to medical questions. We empirically demonstrate how CLINICR outperforms the state-of-the-art 5-shot CoT-based prompt (Liévin et al., 2022). We also present an approach that mirrors real-life clinical practice by first exploring multiple differential diagnoses through MCQ-CLINICR and subsequently narrowing down to a final diagnosis using MCQ-ELIMINATIVE. Finally, emphasizing the importance of response verification in medical settings, we utilize a reward model mechanism, replacing the elimination process performed by MCQ-ELIMINATIVE.

Clinical diagnosis is a gradual process of evidence integration, in which physicians move from symptoms and medical history to examinations, competing hypotheses, disease relations, and treatment decisions. Large language models have advanced medical text understanding and generation. Yet their clinical use remains limited by weak evidence grounding, opaque reasoning, and inconsistent links among differential diagnosis, final diagnosis, diagnostic basis, and treatment planning. We introduce MedCollab, a multi-agent framework for full-cycle clinical diagnosis and report generation. MedCollab coordinates specialist and examination agents according to patient records. It structures agent deliberation with an Issue-Based Information System (IBIS) protocol, so that each diagnostic position is supported by patient-specific evidence and medical knowledge. It also builds Hierarchical Disease Relation Chains (HDRC) to connect accepted hypotheses through progression, complication, and comorbidity relations. During multi-round deliberation, a verifier-guided consensus module evaluates evidence support, medical plausibility, and logical conflicts. It then adjusts agent contributions and filters unsupported reasoning. Experiments on ClinicalBench and MIMIC-IV show that MedCollab outperforms leading LLMs and medical multi-agent baselines in diagnostic accuracy, evidence consistency, and clinical reasoning quality. These results indicate that structured and auditable collaboration can produce more faithful and clinically coherent diagnostic reports.