Daily Papers

Real-world clinical text-to-SQL requires reasoning over heterogeneous EHR tables, temporal windows, and patient-similarity cohorts to produce executable queries. We introduce CLINSQL, a benchmark of 633 expert-annotated tasks on MIMIC-IV v3.1 that demands multi-table joins, clinically meaningful filters, and executable SQL. Solving CLINSQL entails navigating schema metadata and clinical coding systems, handling long contexts, and composing multi-step queries beyond traditional text-to-SQL. We evaluate 22 proprietary and open-source models under Chain-of-Thought self-refinement and use rubric-based SQL analysis with execution checks that prioritize critical clinical requirements. Despite recent advances, performance remains far from clinical reliability: on the test set, GPT-5-mini attains 74.7% execution score, DeepSeek-R1 leads open-source at 69.2% and Gemini-2.5-Pro drops from 85.5% on Easy to 67.2% on Hard. Progress on CLINSQL marks tangible advances toward clinically reliable text-to-SQL for real-world EHR analytics.

Cancer patients are increasingly turning to large language models (LLMs) as a new form of internet search for medical information, making it critical to assess how well these models handle complex, personalized questions. However, current medical benchmarks focus on medical exams or consumer-searched questions and do not evaluate LLMs on real patient questions with detailed clinical contexts. In this paper, we first evaluate LLMs on cancer-related questions drawn from real patients, reviewed by three hematology oncology physicians. While responses are generally accurate, with GPT-4-Turbo scoring 4.13 out of 5, the models frequently fail to recognize or address false presuppositions in the questions-posing risks to safe medical decision-making. To study this limitation systematically, we introduce Cancer-Myth, an expert-verified adversarial dataset of 585 cancer-related questions with false presuppositions. On this benchmark, no frontier LLM -- including GPT-4o, Gemini-1.Pro, and Claude-3.5-Sonnet -- corrects these false presuppositions more than 30% of the time. Even advanced medical agentic methods do not prevent LLMs from ignoring false presuppositions. These findings expose a critical gap in the clinical reliability of LLMs and underscore the need for more robust safeguards in medical AI systems.

Medical Vision-Language Models (VLMs) are prone to hallucinations, compromising clinical reliability. While reinforcement learning methods like Group Relative Policy Optimization (GRPO) offer a low-cost alignment solution, their reliance on sparse, outcome-based rewards inadvertently encourages models to "overthink" -- generating verbose, convoluted, and unverifiable Chain-of-Thought reasoning to justify answers. This focus on outcomes obscures factual errors and poses significant safety risks. To address this, we propose CheXPO-v2, a novel alignment framework that shifts from outcome to process supervision. Our core innovation is a Knowledge Graph Consistency Reward mechanism driven by Entity-Relation Matching. By explicitly parsing reasoning steps into structured "Disease, Relation, Anatomy" triplets, we provide fine-grained supervision that penalizes incoherent logic and hallucinations at the atomic level. Integrating this with a hard-example mining strategy, our approach significantly outperforms GRPO and state-of-the-art models on benchmarks like MIMIC-CXR-VQA. Crucially, CheXPO-v2 achieves new state-of-the-art accuracy using only 5k samples, demonstrating exceptional data efficiency while producing clinically sound and verifiable reasoning. The project source code is publicly available at: https://github.com/ecoxial2007/CheX-Phi4MM.

Traditional Chinese Medicine (TCM) has seen increasing adoption in healthcare, with specialized Large Language Models (LLMs) emerging to support clinical applications. A fundamental requirement for these models is accurate identification of TCM drug ingredients. In this paper, we evaluate how general and TCM-specialized LLMs perform when identifying ingredients of Chinese drugs. Our systematic analysis reveals consistent failure patterns: models often interpret drug names literally, overuse common herbs regardless of relevance, and exhibit erratic behaviors when faced with unfamiliar formulations. LLMs also fail to understand the verification task. These findings demonstrate that current LLMs rely primarily on drug names rather than possessing systematic pharmacological knowledge. To address these limitations, we propose a Retrieval Augmented Generation (RAG) approach focused on ingredient names. Experiments across 220 TCM formulations show our method significantly improves accuracy from approximately 50% to 82% in ingredient verification tasks. Our work highlights critical weaknesses in current TCM-specific LLMs and offers a practical solution for enhancing their clinical reliability.

Automated pain assessment from facial expressions is crucial for non-communicative patients, such as those with dementia. Progress has been limited by two challenges: (i) existing datasets exhibit severe demographic and label imbalance due to ethical constraints, and (ii) current generative models cannot precisely control facial action units (AUs), facial structure, or clinically validated pain levels. We present 3DPain, a large-scale synthetic dataset specifically designed for automated pain assessment, featuring unprecedented annotation richness and demographic diversity. Our three-stage framework generates diverse 3D meshes, textures them with diffusion models, and applies AU-driven face rigging to synthesize multi-view faces with paired neutral and pain images, AU configurations, PSPI scores, and the first dataset-level annotations of pain-region heatmaps. The dataset comprises 82,500 samples across 25,000 pain expression heatmaps and 2,500 synthetic identities balanced by age, gender, and ethnicity. We further introduce ViTPain, a Vision Transformer based cross-modal distillation framework in which a heatmap-trained teacher guides a student trained on RGB images, enhancing accuracy, interpretability, and clinical reliability. Together, 3DPain and ViTPain establish a controllable, diverse, and clinically grounded foundation for generalizable automated pain assessment.

Integration of Vision-Language Models (VLMs) in surgical intelligence is hindered by hallucinations, domain knowledge gaps, and limited understanding of task interdependencies within surgical scenes, undermining clinical reliability. While recent VLMs demonstrate strong general reasoning and thinking capabilities, they still lack the domain expertise and task-awareness required for precise surgical scene interpretation. Although Chain-of-Thought (CoT) can structure reasoning more effectively, current approaches rely on self-generated CoT steps, which often exacerbate inherent domain gaps and hallucinations. To overcome this, we present SurgRAW, a CoT-driven multi-agent framework that delivers transparent, interpretable insights for most tasks in robotic-assisted surgery. By employing specialized CoT prompts across five tasks: instrument recognition, action recognition, action prediction, patient data extraction, and outcome assessment, SurgRAW mitigates hallucinations through structured, domain-aware reasoning. Retrieval-Augmented Generation (RAG) is also integrated to external medical knowledge to bridge domain gaps and improve response reliability. Most importantly, a hierarchical agentic system ensures that CoT-embedded VLM agents collaborate effectively while understanding task interdependencies, with a panel discussion mechanism promotes logical consistency. To evaluate our method, we introduce SurgCoTBench, the first reasoning-based dataset with structured frame-level annotations. With comprehensive experiments, we demonstrate the effectiveness of proposed SurgRAW with 29.32% accuracy improvement over baseline VLMs on 12 robotic procedures, achieving the state-of-the-art performance and advancing explainable, trustworthy, and autonomous surgical assistance.

Medical vision-language models often struggle with generating accurate quantitative measurements in radiology reports, leading to hallucinations that undermine clinical reliability. We introduce FactCheXcker, a modular framework that de-hallucinates radiology report measurements by leveraging an improved query-code-update paradigm. Specifically, FactCheXcker employs specialized modules and the code generation capabilities of large language models to solve measurement queries generated based on the original report. After extracting measurable findings, the results are incorporated into an updated report. We evaluate FactCheXcker on endotracheal tube placement, which accounts for an average of 78% of report measurements, using the MIMIC-CXR dataset and 11 medical report-generation models. Our results show that FactCheXcker significantly reduces hallucinations, improves measurement precision, and maintains the quality of the original reports. Specifically, FactCheXcker improves the performance of 10/11 models and achieves an average improvement of 135.0% in reducing measurement hallucinations measured by mean absolute error. Code is available at https://github.com/rajpurkarlab/FactCheXcker.

Checklists are simple decision aids that are often used to promote safety and reliability in clinical applications. In this paper, we present a method to learn checklists for clinical decision support. We represent predictive checklists as discrete linear classifiers with binary features and unit weights. We then learn globally optimal predictive checklists from data by solving an integer programming problem. Our method allows users to customize checklists to obey complex constraints, including constraints to enforce group fairness and to binarize real-valued features at training time. In addition, it pairs models with an optimality gap that can inform model development and determine the feasibility of learning sufficiently accurate checklists on a given dataset. We pair our method with specialized techniques that speed up its ability to train a predictive checklist that performs well and has a small optimality gap. We benchmark the performance of our method on seven clinical classification problems, and demonstrate its practical benefits by training a short-form checklist for PTSD screening. Our results show that our method can fit simple predictive checklists that perform well and that can easily be customized to obey a rich class of custom constraints.

Purpose: In radiology, large language models (LLMs), including ChatGPT, have recently gained attention, and their utility is being rapidly evaluated. However, concerns have emerged regarding their reliability in clinical applications due to limitations such as hallucinations and insufficient referencing. To address these issues, we focus on the latest technology, retrieval-augmented generation (RAG), which enables LLMs to reference reliable external knowledge (REK). Specifically, this study examines the utility and reliability of a recently released RAG-equipped LLM (RAG-LLM), NotebookLM, for staging lung cancer. Materials and methods: We summarized the current lung cancer staging guideline in Japan and provided this as REK to NotebookLM. We then tasked NotebookLM with staging 100 fictional lung cancer cases based on CT findings and evaluated its accuracy. For comparison, we performed the same task using a gold-standard LLM, GPT-4 Omni (GPT-4o), both with and without the REK. Results: NotebookLM achieved 86% diagnostic accuracy in the lung cancer staging experiment, outperforming GPT-4o, which recorded 39% accuracy with the REK and 25% without it. Moreover, NotebookLM demonstrated 95% accuracy in searching reference locations within the REK. Conclusion: NotebookLM successfully performed lung cancer staging by utilizing the REK, demonstrating superior performance compared to GPT-4o. Additionally, it provided highly accurate reference locations within the REK, allowing radiologists to efficiently evaluate the reliability of NotebookLM's responses and detect possible hallucinations. Overall, this study highlights the potential of NotebookLM, a RAG-LLM, in image diagnosis.

Deep learning (DL) has become the dominant approach for medical image segmentation, yet ensuring the reliability and clinical applicability of these models requires addressing key challenges such as annotation variability, calibration, and uncertainty estimation. This is why we created the Calibration and Uncertainty for multiRater Volume Assessment in multiorgan Segmentation (CURVAS), which highlights the critical role of multiple annotators in establishing a more comprehensive ground truth, emphasizing that segmentation is inherently subjective and that leveraging inter-annotator variability is essential for robust model evaluation. Seven teams participated in the challenge, submitting a variety of DL models evaluated using metrics such as Dice Similarity Coefficient (DSC), Expected Calibration Error (ECE), and Continuous Ranked Probability Score (CRPS). By incorporating consensus and dissensus ground truth, we assess how DL models handle uncertainty and whether their confidence estimates align with true segmentation performance. Our findings reinforce the importance of well-calibrated models, as better calibration is strongly correlated with the quality of the results. Furthermore, we demonstrate that segmentation models trained on diverse datasets and enriched with pre-trained knowledge exhibit greater robustness, particularly in cases deviating from standard anatomical structures. Notably, the best-performing models achieved high DSC and well-calibrated uncertainty estimates. This work underscores the need for multi-annotator ground truth, thorough calibration assessments, and uncertainty-aware evaluations to develop trustworthy and clinically reliable DL-based medical image segmentation models.

Medical Visual Language Models have shown great potential in various healthcare applications, including medical image captioning and diagnostic assistance. However, most existing models rely on text-based instructions, limiting their usability in real-world clinical environments especially in scenarios such as surgery, text-based interaction is often impractical for physicians. In addition, current medical image analysis models typically lack comprehensive reasoning behind their predictions, which reduces their reliability for clinical decision-making. Given that medical diagnosis errors can have life-changing consequences, there is a critical need for interpretable and rational medical assistance. To address these challenges, we introduce an end-to-end speech-driven medical VLM, SilVar-Med, a multimodal medical image assistant that integrates speech interaction with VLMs, pioneering the task of voice-based communication for medical image analysis. In addition, we focus on the interpretation of the reasoning behind each prediction of medical abnormalities with a proposed reasoning dataset. Through extensive experiments, we demonstrate a proof-of-concept study for reasoning-driven medical image interpretation with end-to-end speech interaction. We believe this work will advance the field of medical AI by fostering more transparent, interactive, and clinically viable diagnostic support systems. Our code and dataset are publicly available at SiVar-Med.

Medical Visual Question Answering (MedVQA) is a promising field for developing clinical decision support systems, yet progress is often limited by the available datasets, which can lack clinical complexity and visual diversity. To address these gaps, we introduce Kvasir-VQA-x1, a new, large-scale dataset for gastrointestinal (GI) endoscopy. Our work significantly expands upon the original Kvasir-VQA by incorporating 159,549 new question-answer pairs that are designed to test deeper clinical reasoning. We developed a systematic method using large language models to generate these questions, which are stratified by complexity to better assess a model's inference capabilities. To ensure our dataset prepares models for real-world clinical scenarios, we have also introduced a variety of visual augmentations that mimic common imaging artifacts. The dataset is structured to support two main evaluation tracks: one for standard VQA performance and another to test model robustness against these visual perturbations. By providing a more challenging and clinically relevant benchmark, Kvasir-VQA-x1 aims to accelerate the development of more reliable and effective multimodal AI systems for use in clinical settings. The dataset is fully accessible and adheres to FAIR data principles, making it a valuable resource for the wider research community. Code and data: https://github.com/Simula/Kvasir-VQA-x1 and https://huggingface.co/datasets/SimulaMet/Kvasir-VQA-x1

Machine learning models are routinely used to support decisions that affect individuals -- be it to screen a patient for a serious illness or to gauge their response to treatment. In these tasks, we are limited to learning models from datasets with noisy labels. In this paper, we study the instance-level impact of learning under label noise. We introduce a notion of regret for this regime, which measures the number of unforeseen mistakes due to noisy labels. We show that standard approaches to learning under label noise can return models that perform well at a population-level while subjecting individuals to a lottery of mistakes. We present a versatile approach to estimate the likelihood of mistakes at the individual-level from a noisy dataset by training models over plausible realizations of datasets without label noise. This is supported by a comprehensive empirical study of label noise in clinical prediction tasks. Our results reveal how failure to anticipate mistakes can compromise model reliability and adoption -- we demonstrate how we can address these challenges by anticipating and avoiding regretful decisions.

With the proliferation of Large Language Models (LLMs) in diverse domains, there is a particular need for unified evaluation standards in clinical medical scenarios, where models need to be examined very thoroughly. We present CliMedBench, a comprehensive benchmark with 14 expert-guided core clinical scenarios specifically designed to assess the medical ability of LLMs across 7 pivot dimensions. It comprises 33,735 questions derived from real-world medical reports of top-tier tertiary hospitals and authentic examination exercises. The reliability of this benchmark has been confirmed in several ways. Subsequent experiments with existing LLMs have led to the following findings: (i) Chinese medical LLMs underperform on this benchmark, especially where medical reasoning and factual consistency are vital, underscoring the need for advances in clinical knowledge and diagnostic accuracy. (ii) Several general-domain LLMs demonstrate substantial potential in medical clinics, while the limited input capacity of many medical LLMs hinders their practical use. These findings reveal both the strengths and limitations of LLMs in clinical scenarios and offer critical insights for medical research.

Clinical dialogue represents a complex duality requiring both the empathetic fluency of natural conversation and the rigorous precision of evidence-based medicine. While Large Language Models possess unprecedented linguistic capabilities, their architectural reliance on reactive and stateless processing often favors probabilistic plausibility over factual veracity. This structural limitation has catalyzed a paradigm shift in medical AI from generative text prediction to agentic autonomy, where the model functions as a central reasoning engine capable of deliberate planning and persistent memory. Moving beyond existing reviews that primarily catalog downstream applications, this survey provides a first-principles analysis of the cognitive architecture underpinning this shift. We introduce a novel taxonomy structured along the orthogonal axes of knowledge source and agency objective to delineate the provenance of clinical knowledge against the system's operational scope. This framework facilitates a systematic analysis of the intrinsic trade-offs between creativity and reliability by categorizing methods into four archetypes: Latent Space Clinicians, Emergent Planners, Grounded Synthesizers, and Verifiable Workflow Automators. For each paradigm, we deconstruct the technical realization across the entire cognitive pipeline, encompassing strategic planning, memory management, action execution, collaboration, and evolution to reveal how distinct architectural choices balance the tension between autonomy and safety.

Users typically engage with LLMs interactively, yet most existing benchmarks evaluate them in a static, single-turn format, posing reliability concerns in interactive scenarios. We identify a key obstacle towards reliability: LLMs are trained to answer any question, even with incomplete context or insufficient knowledge. In this paper, we propose to change the static paradigm to an interactive one, develop systems that proactively ask questions to gather more information and respond reliably, and introduce an benchmark - MediQ - to evaluate question-asking ability in LLMs. MediQ simulates clinical interactions consisting of a Patient System and an adaptive Expert System; with potentially incomplete initial information, the Expert refrains from making diagnostic decisions when unconfident, and instead elicits missing details via follow-up questions. We provide a pipeline to convert single-turn medical benchmarks into an interactive format. Our results show that directly prompting state-of-the-art LLMs to ask questions degrades performance, indicating that adapting LLMs to proactive information-seeking settings is nontrivial. We experiment with abstention strategies to better estimate model confidence and decide when to ask questions, improving diagnostic accuracy by 22.3%; however, performance still lags compared to an (unrealistic in practice) upper bound with complete information upfront. Further analyses show improved interactive performance with filtering irrelevant contexts and reformatting conversations. Overall, we introduce a novel problem towards LLM reliability, an interactive MediQ benchmark and a novel question-asking system, and highlight directions to extend LLMs' information-seeking abilities in critical domains.

Case Report Forms (CRFs) are largely used in medical research as they ensure accuracy, reliability, and validity of results in clinical studies. However, publicly available, wellannotated CRF datasets are scarce, limiting the development of CRF slot filling systems able to fill in a CRF from clinical notes. To mitigate the scarcity of CRF datasets, we propose to take advantage of available datasets annotated for information extraction tasks and to convert them into structured CRFs. We present a semi-automatic conversion methodology, which has been applied to the E3C dataset in two languages (English and Italian), resulting in a new, high-quality dataset for CRF slot filling. Through several experiments on the created dataset, we report that slot filling achieves 59.7% for Italian and 67.3% for English on a closed Large Language Models (zero-shot) and worse performances on three families of open-source models, showing that filling CRFs is challenging even for recent state-of-the-art LLMs. We release the datest at https://huggingface.co/collections/NLP-FBK/e3c-to-crf-67b9844065460cbe42f80166

Once deployed, medical image analysis methods are often faced with unexpected image corruptions and noise perturbations. These unknown covariate shifts present significant challenges to deep learning based methods trained on "clean" images. This often results in unreliable predictions and poorly calibrated confidence, hence hindering clinical applicability. While recent methods have been developed to address specific issues such as confidence calibration or adversarial robustness, no single framework effectively tackles all these challenges simultaneously. To bridge this gap, we propose LaDiNE, a novel ensemble learning method combining the robustness of Vision Transformers with diffusion-based generative models for improved reliability in medical image classification. Specifically, transformer encoder blocks are used as hierarchical feature extractors that learn invariant features from images for each ensemble member, resulting in features that are robust to input perturbations. In addition, diffusion models are used as flexible density estimators to estimate member densities conditioned on the invariant features, leading to improved modeling of complex data distributions while retaining properly calibrated confidence. Extensive experiments on tuberculosis chest X-rays and melanoma skin cancer datasets demonstrate that LaDiNE achieves superior performance compared to a wide range of state-of-the-art methods by simultaneously improving prediction accuracy and confidence calibration under unseen noise, adversarial perturbations, and resolution degradation.

We introduce Baichuan-M3, a medical-enhanced large language model engineered to shift the paradigm from passive question-answering to active, clinical-grade decision support. Addressing the limitations of existing systems in open-ended consultations, Baichuan-M3 utilizes a specialized training pipeline to model the systematic workflow of a physician. Key capabilities include: (i) proactive information acquisition to resolve ambiguity; (ii) long-horizon reasoning that unifies scattered evidence into coherent diagnoses; and (iii) adaptive hallucination suppression to ensure factual reliability. Empirical evaluations demonstrate that Baichuan-M3 achieves state-of-the-art results on HealthBench, the newly introduced HealthBench-Hallu and ScanBench, significantly outperforming GPT-5.2 in clinical inquiry, advisory and safety. The models are publicly available at https://huggingface.co/collections/baichuan-inc/baichuan-m3.

Evaluating large language models (LLMs) in medicine is crucial because medical applications require high accuracy with little room for error. Current medical benchmarks have three main types: medical exam-based, comprehensive medical, and specialized assessments. However, these benchmarks have limitations in question design (mostly multiple-choice), data sources (often not derived from real clinical scenarios), and evaluation methods (poor assessment of complex reasoning). To address these issues, we present LLMEval-Med, a new benchmark covering five core medical areas, including 2,996 questions created from real-world electronic health records and expert-designed clinical scenarios. We also design an automated evaluation pipeline, incorporating expert-developed checklists into our LLM-as-Judge framework. Furthermore, our methodology validates machine scoring through human-machine agreement analysis, dynamically refining checklists and prompts based on expert feedback to ensure reliability. We evaluate 13 LLMs across three categories (specialized medical models, open-source models, and closed-source models) on LLMEval-Med, providing valuable insights for the safe and effective deployment of LLMs in medical domains. The dataset is released in https://github.com/llmeval/LLMEval-Med.

The increasing use of tools and solutions based on Large Language Models (LLMs) for various tasks in the medical domain has become a prominent trend. Their use in this highly critical and sensitive domain has thus raised important questions about their robustness, especially in response to variations in input, and the reliability of the generated outputs. This study addresses these questions by constructing a textual dataset based on the ICD-10-CM code descriptions, widely used in US hospitals and containing many clinical terms, and their easily reproducible rephrasing. We then benchmarked existing embedding models, either generalist or specialized in the clinical domain, in a semantic search task where the goal was to correctly match the rephrased text to the original description. Our results showed that generalist models performed better than clinical models, suggesting that existing clinical specialized models are more sensitive to small changes in input that confuse them. The highlighted problem of specialized models may be due to the fact that they have not been trained on sufficient data, and in particular on datasets that are not diverse enough to have a reliable global language understanding, which is still necessary for accurate handling of medical documents.

In this study, we present Colon-X, an open initiative aimed at advancing multimodal intelligence in colonoscopy. We begin by constructing ColonVQA, the most comprehensive multimodal dataset ever built for colonoscopy, featuring over 1.1M+ visual question answering entries across 76 clinical findings and 18 multimodal tasks. Beyond serving as a community-wide data foundation, we further investigate a critical yet underexplored transition in colonoscopy - evolving from multimodal understanding to clinical reasoning: (a) To capture the current landscape of multimodal understanding behaviors, we systematically assess the generalizability of 22 multimodal large language models and examine their reliability under human-induced perturbations. The results reveal that clinical outputs from leading MLLMs remain far from robust and trustworthy. (b) To narrow this gap, we further explore reasoning-centric intelligence tailored for colonoscopy. Specifically, we curate ColonReason, a clinically grounded reasoning dataset annotated through a multi-expert debating pipeline, and develop ColonR1, the first R1-styled model incorporating task-adaptive rewarding and gradient-stable optimization techniques. Under data-scarce conditions, our ColonR1 achieves 56.61% overall accuracy, outperforming supervised fine-tuning by 25.22%, and sets a new reasoning-enabled baseline for multimodal colonoscopy analysis. All data and model resources are publicly available at https://github.com/ai4colonoscopy/Colon-X.

Recent progress in multimodal large language models (MLLMs) has demonstrated promising performance on medical benchmarks and in preliminary trials as clinical assistants. Yet, our pilot audit of diagnostic cases uncovers a critical failure mode: instability in early evidence interpretation precedes hallucination, creating branching reasoning trajectories that cascade into globally inconsistent conclusions. This highlights the need for clinical reasoning agents that constrain stochasticity and hallucination while producing auditable decision flows. We introduce MedMMV, a controllable multimodal multi-agent framework for reliable and verifiable clinical reasoning. MedMMV stabilizes reasoning through diversified short rollouts, grounds intermediate steps in a structured evidence graph under the supervision of a Hallucination Detector, and aggregates candidate paths with a Combined Uncertainty scorer. On six medical benchmarks, MedMMV improves accuracy by up to 12.7% and, more critically, demonstrates superior reliability. Blind physician evaluations confirm that MedMMV substantially increases reasoning truthfulness without sacrificing informational content. By controlling instability through a verifiable, multi-agent process, our framework provides a robust path toward deploying trustworthy AI systems in high-stakes domains like clinical decision support.

Large language models (LLMs) have significantly advanced natural language processing tasks, yet they are susceptible to generating inaccurate or unreliable responses, a phenomenon known as hallucination. In critical domains such as health and medicine, these hallucinations can pose serious risks. This paper introduces HALO, a novel framework designed to enhance the accuracy and reliability of medical question-answering (QA) systems by focusing on the detection and mitigation of hallucinations. Our approach generates multiple variations of a given query using LLMs and retrieves relevant information from external open knowledge bases to enrich the context. We utilize maximum marginal relevance scoring to prioritize the retrieved context, which is then provided to LLMs for answer generation, thereby reducing the risk of hallucinations. The integration of LangChain further streamlines this process, resulting in a notable and robust increase in the accuracy of both open-source and commercial LLMs, such as Llama-3.1 (from 44% to 65%) and ChatGPT (from 56% to 70%). This framework underscores the critical importance of addressing hallucinations in medical QA systems, ultimately improving clinical decision-making and patient care. The open-source HALO is available at: https://github.com/ResponsibleAILab/HALO.

Ensuring the safety and reliability of large language models (LLMs) in clinical practice is critical to prevent patient harm and promote trustworthy healthcare applications of AI. However, LLMs are advancing so rapidly that static safety benchmarks often become obsolete upon publication, yielding only an incomplete and sometimes misleading picture of model trustworthiness. We demonstrate that a Dynamic, Automatic, and Systematic (DAS) red-teaming framework that continuously stress-tests LLMs can reveal significant weaknesses of current LLMs across four safety-critical domains: robustness, privacy, bias/fairness, and hallucination. A suite of adversarial agents is applied to autonomously mutate test cases, identify/evolve unsafe-triggering strategies, and evaluate responses, uncovering vulnerabilities in real time without human intervention. Applying DAS to 15 proprietary and open-source LLMs revealed a stark contrast between static benchmark performance and vulnerability under adversarial pressure. Despite a median MedQA accuracy exceeding 80\%, 94\% of previously correct answers failed our dynamic robustness tests. We observed similarly high failure rates across other domains: privacy leaks were elicited in 86\% of scenarios, cognitive-bias priming altered clinical recommendations in 81\% of fairness tests, and we identified hallucination rates exceeding 66\% in widely used models. Such profound residual risks are incompatible with routine clinical practice. By converting red-teaming from a static checklist into a dynamic stress-test audit, DAS red-teaming offers the surveillance that hospitals/regulators/technology vendors require as LLMs become embedded in patient chatbots, decision-support dashboards, and broader healthcare workflows. Our framework delivers an evolvable, scalable, and reliable safeguard for the next generation of medical AI.

We introduce a novel uncertainty-aware multimodal segmentation framework that leverages both radiological images and associated clinical text for precise medical diagnosis. We propose a Modality Decoding Attention Block (MoDAB) with a lightweight State Space Mixer (SSMix) to enable efficient cross-modal fusion and long-range dependency modelling. To guide learning under ambiguity, we propose the Spectral-Entropic Uncertainty (SEU) Loss, which jointly captures spatial overlap, spectral consistency, and predictive uncertainty in a unified objective. In complex clinical circumstances with poor image quality, this formulation improves model reliability. Extensive experiments on various publicly available medical datasets, QATA-COVID19, MosMed++, and Kvasir-SEG, demonstrate that our method achieves superior segmentation performance while being significantly more computationally efficient than existing State-of-the-Art (SoTA) approaches. Our results highlight the importance of incorporating uncertainty modelling and structured modality alignment in vision-language medical segmentation tasks. Code: https://github.com/arya-domain/UA-VLS

Automatic medical report generation supports clinical diagnosis, reduces the workload of radiologists, and holds the promise of improving diagnosis consistency. However, existing evaluation metrics primarily assess the accuracy of key medical information coverage in generated reports compared to human-written reports, while overlooking crucial details such as the location and certainty of reported abnormalities. These limitations hinder the comprehensive assessment of the reliability of generated reports and pose risks in their selection for clinical use. Therefore, we propose a Granular Explainable Multi-Agent Score (GEMA-Score) in this paper, which conducts both objective quantification and subjective evaluation through a large language model-based multi-agent workflow. Our GEMA-Score parses structured reports and employs NER-F1 calculations through interactive exchanges of information among agents to assess disease diagnosis, location, severity, and uncertainty. Additionally, an LLM-based scoring agent evaluates completeness, readability, and clinical terminology while providing explanatory feedback. Extensive experiments validate that GEMA-Score achieves the highest correlation with human expert evaluations on a public dataset, demonstrating its effectiveness in clinical scoring (Kendall coefficient = 0.70 for Rexval dataset and Kendall coefficient = 0.54 for RadEvalX dataset). The anonymous project demo is available at: https://github.com/Zhenxuan-Zhang/GEMA_score.

Large language models (LLMs) are rapidly transitioning into medical clinical use, yet their reliability under realistic, multi-turn interactions remains poorly understood. Existing evaluation frameworks typically assess single-turn question answering under idealized conditions, overlooking the complexities of medical consultations where conflicting input, misleading context, and authority influence are common. We introduce MedQA-Followup, a framework for systematically evaluating multi-turn robustness in medical question answering. Our approach distinguishes between shallow robustness (resisting misleading initial context) and deep robustness (maintaining accuracy when answers are challenged across turns), while also introducing an indirect-direct axis that separates contextual framing (indirect) from explicit suggestion (direct). Using controlled interventions on the MedQA dataset, we evaluate five state-of-the-art LLMs and find that while models perform reasonably well under shallow perturbations, they exhibit severe vulnerabilities in multi-turn settings, with accuracy dropping from 91.2% to as low as 13.5% for Claude Sonnet 4. Counterintuitively, indirect, context-based interventions are often more harmful than direct suggestions, yielding larger accuracy drops across models and exposing a significant vulnerability for clinical deployment. Further compounding analyses reveal model differences, with some showing additional performance drops under repeated interventions while others partially recovering or even improving. These findings highlight multi-turn robustness as a critical but underexplored dimension for safe and reliable deployment of medical LLMs.

Focused Ultrasound Ablation Surgery (FUAS) has emerged as a promising non-invasive therapeutic modality, valued for its safety and precision. Nevertheless, its clinical implementation entails intricate tasks such as multimodal image interpretation, personalized dose planning, and real-time intraoperative decision-making processes that demand intelligent assistance to improve efficiency and reliability. We introduce FUAS-Agents, an autonomous agent system that leverages the multimodal understanding and tool-using capabilities of large language models (LLMs). By integrating patient profiles and MRI data, FUAS-Agents orchestrates a suite of specialized medical AI tools, including segmentation, treatment dose prediction, and clinical guideline retrieval, to generate personalized treatment plans comprising MRI image, dose parameters, and therapeutic strategies. We evaluate the system in a uterine fibroid treatment scenario. Human assessment by four senior FUAS experts indicates that 82.5%, 82.5%, 87.5%, and 97.5% of the generated plans were rated 4 or above (on a 5-point scale) in terms of completeness, accuracy, fluency, and clinical compliance, respectively. These results demonstrate the potential of LLM-driven agents in enhancing decision-making across complex clinical workflows, and exemplify a translational paradigm that combines general-purpose models with specialized expert systems to solve practical challenges in vertical healthcare domains.

Uncertainty estimation is essential for the safe clinical deployment of medical image segmentation systems, enabling the identification of unreliable predictions and supporting human oversight. While prior work has largely focused on pixel-level uncertainty, landmark-based segmentation offers inherent topological guarantees yet remains underexplored from an uncertainty perspective. In this work, we study uncertainty estimation for anatomical landmark-based segmentation on chest X-rays. Inspired by hybrid neural network architectures that combine standard image convolutional encoders with graph-based generative decoders, and leveraging their variational latent space, we derive two complementary measures: (i) latent uncertainty, captured directly from the learned distribution parameters, and (ii) predictive uncertainty, obtained by generating multiple stochastic output predictions from latent samples. Through controlled corruption experiments we show that both uncertainty measures increase with perturbation severity, reflecting both global and local degradation. We demonstrate that these uncertainty signals can identify unreliable predictions by comparing with manual ground-truth, and support out-of-distribution detection on the CheXmask dataset. More importantly, we release CheXmask-U (huggingface.co/datasets/mcosarinsky/CheXmask-U), a large scale dataset of 657,566 chest X-ray landmark segmentations with per-node uncertainty estimates, enabling researchers to account for spatial variations in segmentation quality when using these anatomical masks. Our findings establish uncertainty estimation as a promising direction to enhance robustness and safe deployment of landmark-based anatomical segmentation methods in chest X-ray. A fully working interactive demo of the method is available at huggingface.co/spaces/matiasky/CheXmask-U and the source code at github.com/mcosarinsky/CheXmask-U.

Agentic systems offer a potential path to solve complex clinical tasks through collaboration among specialized agents, augmented by tool use and external knowledge bases. Nevertheless, for chest X-ray (CXR) interpretation, prevailing methods remain limited: (i) reasoning is frequently neither clinically interpretable nor aligned with guidelines, reflecting mere aggregation of tool outputs; (ii) multimodal evidence is insufficiently fused, yielding text-only rationales that are not visually grounded; and (iii) systems rarely detect or resolve cross-tool inconsistencies and provide no principled verification mechanisms. To bridge the above gaps, we present RadAgents, a multi-agent framework for CXR interpretation that couples clinical priors with task-aware multimodal reasoning. In addition, we integrate grounding and multimodal retrieval-augmentation to verify and resolve context conflicts, resulting in outputs that are more reliable, transparent, and consistent with clinical practice.

Large language models (LLMs) have demonstrated strong performance and rapid progress in a wide range of medical reasoning tasks. However, their sequential autoregressive decoding forces inherently parallel clinical reasoning, such as differential diagnosis, into a single linear reasoning path, limiting both efficiency and reliability for complex medical problems. To address this, we propose MedVerse, a reasoning framework for complex medical inference that reformulates medical reasoning as a parallelizable directed acyclic graph (DAG) process based on Petri net theory. The framework adopts a full-stack design across data, model architecture, and system execution. For data creation, we introduce the MedVerse Curator, an automated pipeline that synthesizes knowledge-grounded medical reasoning paths and transforms them into Petri net-structured representations. At the architectural level, we propose a topology-aware attention mechanism with adaptive position indices that supports parallel reasoning while preserving logical consistency. Systematically, we develop a customized inference engine that supports parallel execution without additional overhead. Empirical evaluations show that MedVerse improves strong general-purpose LLMs by up to 8.9%. Compared to specialized medical LLMs, MedVerse achieves comparable performance while delivering a 1.3x reduction in inference latency and a 1.7x increase in generation throughput, enabled by its parallel decoding capability.

Foundation Models that are capable of processing and generating multi-modal data have transformed AI's role in medicine. However, a key limitation of their reliability is hallucination, where inaccurate or fabricated information can impact clinical decisions and patient safety. We define medical hallucination as any instance in which a model generates misleading medical content. This paper examines the unique characteristics, causes, and implications of medical hallucinations, with a particular focus on how these errors manifest themselves in real-world clinical scenarios. Our contributions include (1) a taxonomy for understanding and addressing medical hallucinations, (2) benchmarking models using medical hallucination dataset and physician-annotated LLM responses to real medical cases, providing direct insight into the clinical impact of hallucinations, and (3) a multi-national clinician survey on their experiences with medical hallucinations. Our results reveal that inference techniques such as Chain-of-Thought (CoT) and Search Augmented Generation can effectively reduce hallucination rates. However, despite these improvements, non-trivial levels of hallucination persist. These findings underscore the ethical and practical imperative for robust detection and mitigation strategies, establishing a foundation for regulatory policies that prioritize patient safety and maintain clinical integrity as AI becomes more integrated into healthcare. The feedback from clinicians highlights the urgent need for not only technical advances but also for clearer ethical and regulatory guidelines to ensure patient safety. A repository organizing the paper resources, summaries, and additional information is available at https://github.com/mitmedialab/medical hallucination.

Immunohistochemistry (IHC) provides information on protein expression in tissue sections and is commonly used to support pathology diagnosis and disease triage. While AI models for H\&E-stained slides show promise, their applicability to IHC is limited due to domain-specific variations. Here we introduce HPA10M, a dataset that contains 10,495,672 IHC images from the Human Protein Atlas with comprehensive metadata included, and encompasses 45 normal tissue types and 20 major cancer types. Based on HPA10M, we trained iSight, a multi-task learning framework for automated IHC staining assessment. iSight combines visual features from whole-slide images with tissue metadata through a token-level attention mechanism, simultaneously predicting staining intensity, location, quantity, tissue type, and malignancy status. On held-out data, iSight achieved 85.5\% accuracy for location, 76.6\% for intensity, and 75.7\% for quantity, outperforming fine-tuned foundation models (PLIP, CONCH) by 2.5--10.2\%. In addition, iSight demonstrates well-calibrated predictions with expected calibration errors of 0.0150-0.0408. Furthermore, in a user study with eight pathologists evaluating 200 images from two datasets, iSight outperformed initial pathologist assessments on the held-out HPA dataset (79\% vs 68\% for location, 70\% vs 57\% for intensity, 68\% vs 52\% for quantity). Inter-pathologist agreement also improved after AI assistance in both held-out HPA (Cohen's κ increased from 0.63 to 0.70) and Stanford TMAD datasets (from 0.74 to 0.76), suggesting expert--AI co-assessment can improve IHC interpretation. This work establishes a foundation for AI systems that can improve IHC diagnostic accuracy and highlights the potential for integrating iSight into clinical workflows to enhance the consistency and reliability of IHC assessment.

Large Language Models (LLMs) show potential in medicine, yet clinical adoption is hindered by concerns over factual accuracy, language-specific limitations (e.g., Japanese), and critically, their reliability when required to generate reasoning explanations -- a prerequisite for trust. This paper introduces Preferred-MedLLM-Qwen-72B, a 72B-parameter model optimized for the Japanese medical domain to achieve both high accuracy and stable reasoning. We employ a two-stage fine-tuning process on the Qwen2.5-72B base model: first, Continued Pretraining (CPT) on a comprehensive Japanese medical corpus instills deep domain knowledge. Second, Reasoning Preference Optimization (RPO), a preference-based method, enhances the generation of reliable reasoning pathways while preserving high answer accuracy. Evaluations on the Japanese Medical Licensing Exam benchmark (IgakuQA) show Preferred-MedLLM-Qwen-72B achieves state-of-the-art performance (0.868 accuracy), surpassing strong proprietary models like GPT-4o (0.866). Crucially, unlike baseline or CPT-only models which exhibit significant accuracy degradation (up to 11.5\% and 3.8\% respectively on IgakuQA) when prompted for explanations, our model maintains its high accuracy (0.868) under such conditions. This highlights RPO's effectiveness in stabilizing reasoning generation. This work underscores the importance of optimizing for reliable explanations alongside accuracy. We release the Preferred-MedLLM-Qwen-72B model weights to foster research into trustworthy LLMs for specialized, high-stakes applications.

Large language models (LLMs) are increasingly used in healthcare, but their reliability is heavily influenced by user-driven factors such as question phrasing and the completeness of clinical information. In this study, we examined how misinformation framing, source authority, model persona, and omission of key clinical details affect the diagnostic accuracy and reliability of LLM outputs. We conducted two experiments: one introducing misleading external opinions with varying assertiveness (perturbation test), and another removing specific categories of patient information (ablation test). Using public datasets (MedQA and Medbullets), we evaluated proprietary models (GPT-4o, Claude 3.5 Sonnet, Claude 3.5 Haiku, Gemini 1.5 Pro, Gemini 1.5 Flash) and open-source models (LLaMA 3 8B, LLaMA 3 Med42 8B, DeepSeek R1 8B). All models were vulnerable to user-driven misinformation, with proprietary models especially affected by definitive and authoritative language. Assertive tone had the greatest negative impact on accuracy. In the ablation test, omitting physical exam findings and lab results caused the most significant performance drop. Although proprietary models had higher baseline accuracy, their performance declined sharply under misinformation. These results highlight the need for well-structured prompts and complete clinical context. Users should avoid authoritative framing of misinformation and provide full clinical details, especially for complex cases.

In medical imaging, vision-language models face a critical duality: pretrained networks offer broad robustness but lack subtle, modality-specific characteristics, while fine-tuned expert models achieve high in-distribution accuracy yet falter under modality shift. Existing model-merging techniques, designed for natural-image benchmarks, are simple and efficient but fail to deliver consistent gains across diverse medical modalities; their static interpolation limits reliability in varied clinical tasks. To address this, we introduce Test-Time Task adaptive merging (T^3), a backpropagation-free framework that computes per-sample interpolation coefficients via the Jensen-Shannon divergence between the two models' output distributions. T^3 dynamically preserves local precision when models agree and defers to generalist robustness under drift. To overcome the inference costs of sample-wise merging, we further propose a batch-wise extension, T^3_B, that computes a merging coefficient across a batch of samples, dramatically reducing computational bottleneck. Recognizing the lack of a standardized medical-merging benchmark, we present a rigorous cross-evaluation protocol spanning in-domain, base-to-novel, and corruptions across four modalities. Empirically, T^3 sets new state-of-the-art in Top-1 accuracy and error reduction, outperforming strong baselines while maintaining efficiency, paving the way for adaptive MVLM deployment in clinical settings. Our code is available at https://github.com/Razaimam45/TCube.

Optical Coherence Tomography Angiography (OCTA) and its derived en-face projections provide high-resolution visualization of the retinal and choroidal vasculature, which is critical for the rapid and accurate diagnosis of retinal diseases. However, acquiring high-quality OCTA images is challenging due to motion sensitivity and the high costs associated with software modifications for conventional OCT devices. Moreover, current deep learning methods for OCT-to-OCTA translation often overlook the vascular differences across retinal layers and struggle to reconstruct the intricate, dense vascular details necessary for reliable diagnosis. To overcome these limitations, we propose XOCT, a novel deep learning framework that integrates Cross-Dimensional Supervision (CDS) with a Multi-Scale Feature Fusion (MSFF) network for layer-aware vascular reconstruction. Our CDS module leverages 2D layer-wise en-face projections, generated via segmentation-weighted z-axis averaging, as supervisory signals to compel the network to learn distinct representations for each retinal layer through fine-grained, targeted guidance. Meanwhile, the MSFF module enhances vessel delineation through multi-scale feature extraction combined with a channel reweighting strategy, effectively capturing vascular details at multiple spatial scales. Our experiments on the OCTA-500 dataset demonstrate XOCT's improvements, especially for the en-face projections which are significant for clinical evaluation of retinal pathologies, underscoring its potential to enhance OCTA accessibility, reliability, and diagnostic value for ophthalmic disease detection and monitoring. The code is available at https://github.com/uci-cbcl/XOCT.

Objective: Question answering (QA) systems have the potential to improve the quality of clinical care by providing health professionals with the latest and most relevant evidence. However, QA systems have not been widely adopted. This systematic review aims to characterize current medical QA systems, assess their suitability for healthcare, and identify areas of improvement. Materials and methods: We searched PubMed, IEEE Xplore, ACM Digital Library, ACL Anthology and forward and backward citations on 7th February 2023. We included peer-reviewed journal and conference papers describing the design and evaluation of biomedical QA systems. Two reviewers screened titles, abstracts, and full-text articles. We conducted a narrative synthesis and risk of bias assessment for each study. We assessed the utility of biomedical QA systems. Results: We included 79 studies and identified themes, including question realism, answer reliability, answer utility, clinical specialism, systems, usability, and evaluation methods. Clinicians' questions used to train and evaluate QA systems were restricted to certain sources, types and complexity levels. No system communicated confidence levels in the answers or sources. Many studies suffered from high risks of bias and applicability concerns. Only 8 studies completely satisfied any criterion for clinical utility, and only 7 reported user evaluations. Most systems were built with limited input from clinicians. Discussion: While machine learning methods have led to increased accuracy, most studies imperfectly reflected real-world healthcare information needs. Key research priorities include developing more realistic healthcare QA datasets and considering the reliability of answer sources, rather than merely focusing on accuracy.

Clinical evidence, derived from rigorous research and data analysis, provides healthcare professionals with reliable scientific foundations for informed decision-making. Integrating clinical evidence into real-time practice is challenging due to the enormous workload, complex professional processes, and time constraints. This highlights the need for tools that automate evidence synthesis to support more efficient and accurate decision making in clinical settings. This study introduces Quicker, an evidence-based clinical decision support system powered by large language models (LLMs), designed to automate evidence synthesis and generate clinical recommendations modeled after standard clinical guideline development processes. Quicker implements a fully automated chain that covers all phases, from questions to clinical recommendations, and further enables customized decision-making through integrated tools and interactive user interfaces. To evaluate Quicker's capabilities, we developed the Q2CRBench-3 benchmark dataset, based on clinical guideline development records for three different diseases. Experimental results highlighted Quicker's strong performance, with fine-grained question decomposition tailored to user preferences, retrieval sensitivities comparable to human experts, and literature screening performance approaching comprehensive inclusion of relevant studies. In addition, Quicker-assisted evidence assessment effectively supported human reviewers, while Quicker's recommendations were more comprehensive and logically coherent than those of clinicians. In system-level testing, collaboration between a single reviewer and Quicker reduced the time required for recommendation development to 20-40 minutes. In general, our findings affirm the potential of Quicker to help physicians make quicker and more reliable evidence-based clinical decisions.

In response to the pressing need for advanced clinical problem-solving tools in healthcare, we introduce BooksMed, a novel framework based on a Large Language Model (LLM). BooksMed uniquely emulates human cognitive processes to deliver evidence-based and reliable responses, utilizing the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework to effectively quantify evidence strength. For clinical decision-making to be appropriately assessed, an evaluation metric that is clinically aligned and validated is required. As a solution, we present ExpertMedQA, a multispecialty clinical benchmark comprised of open-ended, expert-level clinical questions, and validated by a diverse group of medical professionals. By demanding an in-depth understanding and critical appraisal of up-to-date clinical literature, ExpertMedQA rigorously evaluates LLM performance. BooksMed outperforms existing state-of-the-art models Med-PaLM 2, Almanac, and ChatGPT in a variety of medical scenarios. Therefore, a framework that mimics human cognitive stages could be a useful tool for providing reliable and evidence-based responses to clinical inquiries.

Large-language models have recently demonstrated impressive zero-shot capabilities in a variety of natural language tasks such as summarization, dialogue generation, and question-answering. Despite many promising applications in clinical medicine, adoption of these models in real-world settings has been largely limited by their tendency to generate incorrect and sometimes even toxic statements. In this study, we develop Almanac, a large language model framework augmented with retrieval capabilities for medical guideline and treatment recommendations. Performance on a novel dataset of clinical scenarios (n = 130) evaluated by a panel of 5 board-certified and resident physicians demonstrates significant increases in factuality (mean of 18% at p-value < 0.05) across all specialties, with improvements in completeness and safety. Our results demonstrate the potential for large language models to be effective tools in the clinical decision-making process, while also emphasizing the importance of careful testing and deployment to mitigate their shortcomings.

Integrating language models (LMs) in healthcare systems holds great promise for improving medical workflows and decision-making. However, a critical barrier to their real-world adoption is the lack of reliable evaluation of their trustworthiness, especially in multilingual healthcare settings. Existing LMs are predominantly trained in high-resource languages, making them ill-equipped to handle the complexity and diversity of healthcare queries in mid- and low-resource languages, posing significant challenges for deploying them in global healthcare contexts where linguistic diversity is key. In this work, we present CLINIC, a Comprehensive Multilingual Benchmark to evaluate the trustworthiness of language models in healthcare. CLINIC systematically benchmarks LMs across five key dimensions of trustworthiness: truthfulness, fairness, safety, robustness, and privacy, operationalized through 18 diverse tasks, spanning 15 languages (covering all the major continents), and encompassing a wide array of critical healthcare topics like disease conditions, preventive actions, diagnostic tests, treatments, surgeries, and medications. Our extensive evaluation reveals that LMs struggle with factual correctness, demonstrate bias across demographic and linguistic groups, and are susceptible to privacy breaches and adversarial attacks. By highlighting these shortcomings, CLINIC lays the foundation for enhancing the global reach and safety of LMs in healthcare across diverse languages.

Several studies showed that Large Language Models (LLMs) can answer medical questions correctly, even outperforming the average human score in some medical exams. However, to our knowledge, no study has been conducted to assess the ability of language models to validate existing or generated medical text for correctness and consistency. In this paper, we introduce MEDEC (https://github.com/abachaa/MEDEC), the first publicly available benchmark for medical error detection and correction in clinical notes, covering five types of errors (Diagnosis, Management, Treatment, Pharmacotherapy, and Causal Organism). MEDEC consists of 3,848 clinical texts, including 488 clinical notes from three US hospital systems that were not previously seen by any LLM. The dataset has been used for the MEDIQA-CORR shared task to evaluate seventeen participating systems [Ben Abacha et al., 2024]. In this paper, we describe the data creation methods and we evaluate recent LLMs (e.g., o1-preview, GPT-4, Claude 3.5 Sonnet, and Gemini 2.0 Flash) for the tasks of detecting and correcting medical errors requiring both medical knowledge and reasoning capabilities. We also conducted a comparative study where two medical doctors performed the same task on the MEDEC test set. The results showed that MEDEC is a sufficiently challenging benchmark to assess the ability of models to validate existing or generated notes and to correct medical errors. We also found that although recent LLMs have a good performance in error detection and correction, they are still outperformed by medical doctors in these tasks. We discuss the potential factors behind this gap, the insights from our experiments, the limitations of current evaluation metrics, and share potential pointers for future research.

Specialized clinical AI assistants are rapidly entering medical practice, often framed as safer or more reliable than general-purpose large language models (LLMs). Yet, unlike frontier models, these clinical tools are rarely subjected to independent, quantitative evaluation, creating a critical evidence gap despite their growing influence on diagnosis, triage, and guideline interpretation. We assessed two widely deployed clinical AI systems (OpenEvidence and UpToDate Expert AI) against three state-of-the-art generalist LLMs (GPT-5, Gemini 3 Pro, and Claude Sonnet 4.5) using a 1,000-item mini-benchmark combining MedQA (medical knowledge) and HealthBench (clinician-alignment) tasks. Generalist models consistently outperformed clinical tools, with GPT-5 achieving the highest scores, while OpenEvidence and UpToDate demonstrated deficits in completeness, communication quality, context awareness, and systems-based safety reasoning. These findings reveal that tools marketed for clinical decision support may often lag behind frontier LLMs, underscoring the urgent need for transparent, independent evaluation before deployment in patient-facing workflows.

Finding relevant literature underpins the practice of evidence-based medicine. From 2014 to 2016, TREC conducted a clinical decision support track, wherein participants were tasked with finding articles relevant to clinical questions posed by physicians. In total, 87 teams have participated over the past three years, generating 395 runs. During this period, each team has trialled a variety of methods. While there was significant overlap in the methods employed by different teams, the results were varied. Due to the diversity of the platforms used, the results arising from the different techniques are not directly comparable, reducing the ability to build on previous work. By using a stable platform, we have been able to compare different document and query processing techniques, allowing us to experiment with different search parameters. We have used our system to reproduce leading teams runs, and compare the results obtained. By benchmarking our indexing and search techniques, we can statistically test a variety of hypotheses, paving the way for further research.

Discharge summaries in Electronic Health Records (EHRs) are crucial for clinical decision-making, but their length and complexity make information extraction challenging, especially when dealing with accumulated summaries across multiple patient admissions. Large Language Models (LLMs) show promise in addressing this challenge by efficiently analyzing vast and complex data. Existing benchmarks, however, fall short in properly evaluating LLMs' capabilities in this context, as they typically focus on single-note information or limited topics, failing to reflect the real-world inquiries required by clinicians. To bridge this gap, we introduce EHRNoteQA, a novel benchmark built on the MIMIC-IV EHR, comprising 962 different QA pairs each linked to distinct patients' discharge summaries. Every QA pair is initially generated using GPT-4 and then manually reviewed and refined by three clinicians to ensure clinical relevance. EHRNoteQA includes questions that require information across multiple discharge summaries and covers eight diverse topics, mirroring the complexity and diversity of real clinical inquiries. We offer EHRNoteQA in two formats: open-ended and multi-choice question answering, and propose a reliable evaluation method for each. We evaluate 27 LLMs using EHRNoteQA and examine various factors affecting the model performance (e.g., the length and number of discharge summaries). Furthermore, to validate EHRNoteQA as a reliable proxy for expert evaluations in clinical practice, we measure the correlation between the LLM performance on EHRNoteQA, and the LLM performance manually evaluated by clinicians. Results show that LLM performance on EHRNoteQA have higher correlation with clinician-evaluated performance (Spearman: 0.78, Kendall: 0.62) compared to other benchmarks, demonstrating its practical relevance in evaluating LLMs in clinical settings.

Qualitative research faces a critical reliability challenge: traditional inter-rater agreement methods require multiple human coders, are time-intensive, and often yield moderate consistency. We present a multi-perspective validation framework for LLM-based thematic analysis that combines ensemble validation with dual reliability metrics: Cohen's Kappa (κ) for inter-rater agreement and cosine similarity for semantic consistency. Our framework enables configurable analysis parameters (1-6 seeds, temperature 0.0-2.0), supports custom prompt structures with variable substitution, and provides consensus theme extraction across any JSON format. As proof-of-concept, we evaluate three leading LLMs (Gemini 2.5 Pro, GPT-4o, Claude 3.5 Sonnet) on a psychedelic art therapy interview transcript, conducting six independent runs per model. Results demonstrate Gemini achieves highest reliability (κ= 0.907, cosine=95.3%), followed by GPT-4o (κ= 0.853, cosine=92.6%) and Claude (κ= 0.842, cosine=92.1%). All three models achieve a high agreement (κ> 0.80), validating the multi-run ensemble approach. The framework successfully extracts consensus themes across runs, with Gemini identifying 6 consensus themes (50-83% consistency), GPT-4o identifying 5 themes, and Claude 4 themes. Our open-source implementation provides researchers with transparent reliability metrics, flexible configuration, and structure-agnostic consensus extraction, establishing methodological foundations for reliable AI-assisted qualitative research.

This study investigates GPT-4's assessment of its performance in healthcare applications. A simple prompting technique was used to prompt the LLM with questions taken from the United States Medical Licensing Examination (USMLE) questionnaire and it was tasked to evaluate its confidence score before posing the question and after asking the question. The questionnaire was categorized into two groups-questions with feedback (WF) and questions with no feedback(NF) post-question. The model was asked to provide absolute and relative confidence scores before and after each question. The experimental findings were analyzed using statistical tools to study the variability of confidence in WF and NF groups. Additionally, a sequential analysis was conducted to observe the performance variation for the WF and NF groups. Results indicate that feedback influences relative confidence but doesn't consistently increase or decrease it. Understanding the performance of LLM is paramount in exploring its utility in sensitive areas like healthcare. This study contributes to the ongoing discourse on the reliability of AI, particularly of LLMs like GPT-4, within healthcare, offering insights into how feedback mechanisms might be optimized to enhance AI-assisted medical education and decision support.

Doctors and patients alike increasingly use Large Language Models (LLMs) to diagnose clinical cases. However, unlike domains such as math or coding, where correctness can be objectively defined by the final answer, medical diagnosis requires both the outcome and the reasoning process to be accurate. Currently, widely used medical benchmarks like MedQA and MMLU assess only accuracy in the final answer, overlooking the quality and faithfulness of the clinical reasoning process. To address this limitation, we introduce MedCaseReasoning, the first open-access dataset for evaluating LLMs on their ability to align with clinician-authored diagnostic reasoning. The dataset includes 14,489 diagnostic question-and-answer cases, each paired with detailed reasoning statements derived from open-access medical case reports. We evaluate state-of-the-art reasoning LLMs on MedCaseReasoning and find significant shortcomings in their diagnoses and reasoning: for instance, the top-performing open-source model, DeepSeek-R1, achieves only 48% 10-shot diagnostic accuracy and mentions only 64% of the clinician reasoning statements (recall). However, we demonstrate that fine-tuning LLMs on the reasoning traces derived from MedCaseReasoning significantly improves diagnostic accuracy and clinical reasoning recall by an average relative gain of 29% and 41%, respectively. The open-source dataset, code, and models are available at https://github.com/kevinwu23/Stanford-MedCaseReasoning.

Access to the right evidence does not guarantee that large language models (LLMs) will reason with it correctly. This gap between retrieval and reasoning is especially concerning in clinical settings, where outputs must align with structured protocols. We study this gap using Written Exposure Therapy (WET) guidelines as a testbed. In evaluating model responses to curated clinician-vetted questions, we find that errors persist even when authoritative passages are provided. To address this, we propose an evaluation framework that measures accuracy, consistency, and fidelity of reasoning. Our results highlight both the potential and the risks: retrieval-augmented generation (RAG) can constrain outputs, but safe deployment requires assessing reasoning as rigorously as retrieval.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate clinical quality, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

We present MedXIAOHE, a medical vision-language foundation model designed to advance general-purpose medical understanding and reasoning in real-world clinical applications. MedXIAOHE achieves state-of-the-art performance across diverse medical benchmarks and surpasses leading closed-source multimodal systems on multiple capabilities. To achieve this, we propose an entity-aware continual pretraining framework that organizes heterogeneous medical corpora to broaden knowledge coverage and reduce long-tail gaps (e.g., rare diseases). For medical expert-level reasoning and interaction, MedXIAOHE incorporates diverse medical reasoning patterns via reinforcement learning and tool-augmented agentic training, enabling multi-step diagnostic reasoning with verifiable decision traces. To improve reliability in real-world use, MedXIAOHE integrates user-preference rubrics, evidence-grounded reasoning, and low-hallucination long-form report generation, with improved adherence to medical instructions. We release this report to document our practical design choices, scaling insights, and evaluation framework, hoping to inspire further research.

With the rapid development of large language models (LLMs), assessing their performance on health-related inquiries has become increasingly essential. It is critical that these models provide accurate and trustworthy health information, as their application in real-world contexts--where misinformation can have serious consequences for individuals seeking medical advice and support--depends on their reliability. In this work, we present CHBench, the first comprehensive Chinese Health-related Benchmark designed to evaluate LLMs' capabilities in understanding physical and mental health across diverse scenarios. CHBench includes 6,493 entries related to mental health and 2,999 entries focused on physical health, covering a broad spectrum of topics. This dataset serves as a foundation for evaluating Chinese LLMs' capacity to comprehend and generate accurate health-related information. Our extensive evaluations of four popular Chinese LLMs demonstrate that there remains considerable room for improvement in their understanding of health-related information. The code is available at https://github.com/TracyGuo2001/CHBench.

With the growing use of language models (LMs) in clinical environments, there is an immediate need to evaluate the accuracy and safety of LM-generated medical text. Currently, such evaluation relies solely on manual physician review. However, detecting errors in LM-generated text is challenging because 1) manual review is costly and 2) expert-composed reference outputs are often unavailable in real-world settings. While the "LM-as-judge" paradigm (a LM evaluating another LM) offers scalable evaluation, even frontier LMs can miss subtle but clinically significant errors. To address these challenges, we propose MedVAL, a self-supervised framework that leverages synthetic data to train evaluator LMs to assess whether LM-generated medical outputs are factually consistent with inputs, without requiring physician labels or reference outputs. To evaluate LM performance, we introduce MedVAL-Bench, a dataset containing 840 outputs annotated by physicians, following a physician-defined taxonomy of risk levels and error categories. Across 6 diverse medical tasks and 10 state-of-the-art LMs spanning open-source, proprietary, and medically adapted models, MedVAL fine-tuning significantly improves (p < 0.001) alignment with physicians on both seen and unseen tasks, increasing average F1 scores from 66% to 83%, with per-sample safety classification scores up to 86%. MedVAL improves the performance of even the best-performing proprietary LM (GPT-4o) by 8%. To support a scalable, risk-aware pathway towards clinical integration, we open-source the 1) codebase ( https://github.com/StanfordMIMI/MedVAL ), 2) MedVAL-Bench ( https://huggingface.co/datasets/stanfordmimi/MedVAL-Bench ), and 3) MedVAL-4B ( https://huggingface.co/stanfordmimi/MedVAL-4B ), the best-performing open-source LM. Our research provides the first evidence of LMs approaching expert-level validation ability for medical text.

We develop an algorithm which exceeds the performance of board certified cardiologists in detecting a wide range of heart arrhythmias from electrocardiograms recorded with a single-lead wearable monitor. We build a dataset with more than 500 times the number of unique patients than previously studied corpora. On this dataset, we train a 34-layer convolutional neural network which maps a sequence of ECG samples to a sequence of rhythm classes. Committees of board-certified cardiologists annotate a gold standard test set on which we compare the performance of our model to that of 6 other individual cardiologists. We exceed the average cardiologist performance in both recall (sensitivity) and precision (positive predictive value).

Seeking health-related advice on the internet has become a common practice in the digital era. Determining the trustworthiness of medical claims found online and finding appropriate evidence for this information is increasingly challenging. Fact-checking has emerged as an approach to assess the veracity of factual claims using evidence from credible knowledge sources. To help advance the automation of this task, in this paper, we introduce a novel dataset of 750 health-related claims, labeled for veracity by medical experts and backed with evidence from appropriate clinical studies. We provide an analysis of the dataset, highlighting its characteristics and challenges. The dataset can be used for Machine Learning tasks related to automated fact-checking such as evidence retrieval, veracity prediction, and explanation generation. For this purpose, we provide baseline models based on different approaches, examine their performance, and discuss the findings.

Current benchmarks for AI clinician systems, often based on multiple-choice exams or manual rubrics, fail to capture the depth, robustness, and safety required for real-world clinical practice. To address this, we introduce the GAPS framework, a multidimensional paradigm for evaluating Grounding (cognitive depth), Adequacy (answer completeness), Perturbation (robustness), and Safety. Critically, we developed a fully automated, guideline-anchored pipeline to construct a GAPS-aligned benchmark end-to-end, overcoming the scalability and subjectivity limitations of prior work. Our pipeline assembles an evidence neighborhood, creates dual graph and tree representations, and automatically generates questions across G-levels. Rubrics are synthesized by a DeepResearch agent that mimics GRADE-consistent, PICO-driven evidence review in a ReAct loop. Scoring is performed by an ensemble of large language model (LLM) judges. Validation confirmed our automated questions are high-quality and align with clinician judgment. Evaluating state-of-the-art models on the benchmark revealed key failure modes: performance degrades sharply with increased reasoning depth (G-axis), models struggle with answer completeness (A-axis), and they are highly vulnerable to adversarial perturbations (P-axis) as well as certain safety issues (S-axis). This automated, clinically-grounded approach provides a reproducible and scalable method for rigorously evaluating AI clinician systems and guiding their development toward safer, more reliable clinical practice.

Medical imaging is essential in modern radiotherapy, supporting diagnosis, treatment planning, and monitoring. Synthetic imaging, particularly synthetic computed tomography (sCT), is gaining traction in radiotherapy. The SynthRAD2025 dataset and Grand Challenge promote advancements in sCT generation by providing a benchmarking platform for algorithms using cone-beam CT (CBCT) and magnetic resonance imaging (MRI). The dataset includes 2362 cases: 890 MRI-CT and 1472 CBCT-CT pairs from head-and-neck, thoracic, and abdominal cancer patients treated at five European university medical centers (UMC Groningen, UMC Utrecht, Radboud UMC, LMU University Hospital Munich, and University Hospital of Cologne). Data were acquired with diverse scanners and protocols. Pre-processing, including rigid and deformable image registration, ensures high-quality, modality-aligned images. Extensive quality assurance validates image consistency and usability. All imaging data is provided in MetaImage (.mha) format, ensuring compatibility with medical image processing tools. Metadata, including acquisition parameters and registration details, is available in structured CSV files. To maintain dataset integrity, SynthRAD2025 is divided into training (65%), validation (10%), and test (25%) sets. The dataset is accessible at https://doi.org/10.5281/zenodo.14918089 under the SynthRAD2025 collection. This dataset supports benchmarking and the development of synthetic imaging techniques for radiotherapy applications. Use cases include sCT generation for MRI-only and MR-guided photon/proton therapy, CBCT-based dose calculations, and adaptive radiotherapy workflows. By integrating diverse acquisition settings, SynthRAD2025 fosters robust, generalizable image synthesis algorithms, advancing personalized cancer care and adaptive radiotherapy.

Clinical trials are fundamental in developing new drugs, medical devices, and treatments. However, they are often time-consuming and have low success rates. Although there have been initial attempts to create large language models (LLMs) for clinical trial design and patient-trial matching, these models remain task-specific and not adaptable to diverse clinical trial tasks. To address this challenge, we propose a clinical trial foundation model named Panacea, designed to handle multiple tasks, including trial search, trial summarization, trial design, and patient-trial matching. We also assemble a large-scale dataset, named TrialAlign, of 793,279 trial documents and 1,113,207 trial-related scientific papers, to infuse clinical knowledge into the model by pre-training. We further curate TrialInstruct, which has 200,866 of instruction data for fine-tuning. These resources enable Panacea to be widely applicable for a range of clinical trial tasks based on user requirements. We evaluated Panacea on a new benchmark, named TrialPanorama, which covers eight clinical trial tasks. Our method performed the best on seven of the eight tasks compared to six cutting-edge generic or medicine-specific LLMs. Specifically, Panacea showed great potential to collaborate with human experts in crafting the design of eligibility criteria, study arms, and outcome measures, in multi-round conversations. In addition, Panacea achieved 14.42% improvement in patient-trial matching, 41.78% to 52.02% improvement in trial search, and consistently ranked at the top for five aspects of trial summarization. Our approach demonstrates the effectiveness of Panacea in clinical trials and establishes a comprehensive resource, including training data, model, and benchmark, for developing clinical trial foundation models, paving the path for AI-based clinical trial development.

Predictive artificial intelligence (AI) offers an opportunity to improve clinical practice and patient outcomes, but risks perpetuating biases if fairness is inadequately addressed. However, the definition of "fairness" remains unclear. We conducted a scoping review to identify and critically appraise fairness metrics for clinical predictive AI. We defined a "fairness metric" as a measure quantifying whether a model discriminates (societally) against individuals or groups defined by sensitive attributes. We searched five databases (2014-2024), screening 820 records, to include 41 studies, and extracted 62 fairness metrics. Metrics were classified by performance-dependency, model output level, and base performance metric, revealing a fragmented landscape with limited clinical validation and overreliance on threshold-dependent measures. Eighteen metrics were explicitly developed for healthcare, including only one clinical utility metric. Our findings highlight conceptual challenges in defining and quantifying fairness and identify gaps in uncertainty quantification, intersectionality, and real-world applicability. Future work should prioritise clinically meaningful metrics.

Medical benchmarks are indispensable for evaluating the capabilities of language models in healthcare for non-English-speaking communities,therefore help ensuring the quality of real-life applications. However, not every community has sufficient resources and standardized methods to effectively build and design such benchmark, and available non-English medical data is normally fragmented and difficult to verify. We developed an approach to tackle this problem and applied it to create the first Vietnamese medical question benchmark, featuring 14,000 multiple-choice questions across 34 medical specialties. Our benchmark was constructed using various verifiable sources, including carefully curated medical exams and clinical records, and eventually annotated by medical experts. The benchmark includes four difficulty levels, ranging from foundational biological knowledge commonly found in textbooks to typical clinical case studies that require advanced reasoning. This design enables assessment of both the breadth and depth of language models' medical understanding in the target language thanks to its extensive coverage and in-depth subject-specific expertise. We release the benchmark in three parts: a sample public set (4k questions), a full public set (10k questions), and a private set (2k questions) used for leaderboard evaluation. Each set contains all medical subfields and difficulty levels. Our approach is scalable to other languages, and we open-source our data construction pipeline to support the development of future multilingual benchmarks in the medical domain.

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise.

Large Multimodal Models (LMMs) have shown remarkable progress in the field of medical Visual Question Answering (Med-VQA), achieving high accuracy on existing benchmarks. However, their reliability under robust evaluation is questionable. This study reveals that state-of-the-art models, when subjected to simple probing evaluation, perform worse than random guessing on medical diagnosis questions. To address this critical evaluation problem, we introduce the Probing Evaluation for Medical Diagnosis (ProbMed) dataset to rigorously assess LMM performance in medical imaging through probing evaluation and procedural diagnosis. Particularly, probing evaluation features pairing original questions with negation questions with hallucinated attributes, while procedural diagnosis requires reasoning across various diagnostic dimensions for each image, including modality recognition, organ identification, clinical findings, abnormalities, and positional grounding. Our evaluation reveals that top-performing models like GPT-4V and Gemini Pro perform worse than random guessing on specialized diagnostic questions, indicating significant limitations in handling fine-grained medical inquiries. Besides, models like LLaVA-Med struggle even with more general questions, and results from CheXagent demonstrate the transferability of expertise across different modalities of the same organ, showing that specialized domain knowledge is still crucial for improving performance. This study underscores the urgent need for more robust evaluation to ensure the reliability of LMMs in critical fields like medical diagnosis, and current LMMs are still far from applicable to those fields.

Objective: Using natural language processing (NLP) to find sentences that state treatment plans in a clinical note, would automate plan extraction and would further enable their use in tools that help providers and care managers. However, as in the most NLP tasks on clinical text, creating gold standard to train and test NLP models is tedious and expensive. Fortuitously, sometimes but not always clinical notes contain sections with a heading that identifies the section as a plan. Leveraging contents of such labeled sections as a noisy training data, we assessed accuracy of NLP models trained with the data. Methods: We used common variations of plan headings and rule-based heuristics to find plan sections with headings in clinical notes, and we extracted sentences from them and formed a noisy training data of plan sentences. We trained Support Vector Machine (SVM) and Convolutional Neural Network (CNN) models with the data. We measured accuracy of the trained models on the noisy dataset using ten-fold cross validation and separately on a set-aside manually annotated dataset. Results: About 13% of 117,730 clinical notes contained treatment plans sections with recognizable headings in the 1001 longitudinal patient records that were obtained from Cleveland Clinic under an IRB approval. We were able to extract and create a noisy training data of 13,492 plan sentences from the clinical notes. CNN achieved best F measures, 0.91 and 0.97 in the cross-validation and set-aside evaluation experiments respectively. SVM slightly underperformed with F measures of 0.89 and 0.96 in the same experiments. Conclusion: Our study showed that the training supervised learning models using noisy plan sentences was effective in identifying them in all clinical notes. More broadly, sections with informal headings in clinical notes can be a good source for generating effective training data.

For safety, medical AI systems undergo thorough evaluations before deployment, validating their predictions against a ground truth which is assumed to be fixed and certain. However, this ground truth is often curated in the form of differential diagnoses. While a single differential diagnosis reflects the uncertainty in one expert assessment, multiple experts introduce another layer of uncertainty through disagreement. Both forms of uncertainty are ignored in standard evaluation which aggregates these differential diagnoses to a single label. In this paper, we show that ignoring uncertainty leads to overly optimistic estimates of model performance, therefore underestimating risk associated with particular diagnostic decisions. To this end, we propose a statistical aggregation approach, where we infer a distribution on probabilities of underlying medical condition candidates themselves, based on observed annotations. This formulation naturally accounts for the potential disagreements between different experts, as well as uncertainty stemming from individual differential diagnoses, capturing the entire ground truth uncertainty. Our approach boils down to generating multiple samples of medical condition probabilities, then evaluating and averaging performance metrics based on these sampled probabilities. In skin condition classification, we find that a large portion of the dataset exhibits significant ground truth uncertainty and standard evaluation severely over-estimates performance without providing uncertainty estimates. In contrast, our framework provides uncertainty estimates on common metrics of interest such as top-k accuracy and average overlap, showing that performance can change multiple percentage points. We conclude that, while assuming a crisp ground truth can be acceptable for many AI applications, a more nuanced evaluation protocol should be utilized in medical diagnosis.

In natural language processing applied to the clinical domain, utilizing large language models has emerged as a promising avenue for error detection and correction on clinical notes, a knowledge-intensive task for which annotated data is scarce. This paper presents MedReAct'N'MedReFlex, which leverages a suite of four LLM-based medical agents. The MedReAct agent initiates the process by observing, analyzing, and taking action, generating trajectories to guide the search to target a potential error in the clinical notes. Subsequently, the MedEval agent employs five evaluators to assess the targeted error and the proposed correction. In cases where MedReAct's actions prove insufficient, the MedReFlex agent intervenes, engaging in reflective analysis and proposing alternative strategies. Finally, the MedFinalParser agent formats the final output, preserving the original style while ensuring the integrity of the error correction process. One core component of our method is our RAG pipeline based on our ClinicalCorp corpora. Among other well-known sources containing clinical guidelines and information, we preprocess and release the open-source MedWiki dataset for clinical RAG application. Our results demonstrate the central role of our RAG approach with ClinicalCorp leveraged through the MedReAct'N'MedReFlex framework. It achieved the ninth rank on the MEDIQA-CORR 2024 final leaderboard.

The meaningful use of electronic health records (EHR) continues to progress in the digital era with clinical decision support systems augmented by artificial intelligence. A priority in improving provider experience is to overcome information overload and reduce the cognitive burden so fewer medical errors and cognitive biases are introduced during patient care. One major type of medical error is diagnostic error due to systematic or predictable errors in judgment that rely on heuristics. The potential for clinical natural language processing (cNLP) to model diagnostic reasoning in humans with forward reasoning from data to diagnosis and potentially reduce the cognitive burden and medical error has not been investigated. Existing tasks to advance the science in cNLP have largely focused on information extraction and named entity recognition through classification tasks. We introduce a novel suite of tasks coined as Diagnostic Reasoning Benchmarks, DR.BENCH, as a new benchmark for developing and evaluating cNLP models with clinical diagnostic reasoning ability. The suite includes six tasks from ten publicly available datasets addressing clinical text understanding, medical knowledge reasoning, and diagnosis generation. DR.BENCH is the first clinical suite of tasks designed to be a natural language generation framework to evaluate pre-trained language models. Experiments with state-of-the-art pre-trained generative language models using large general domain models and models that were continually trained on a medical corpus demonstrate opportunities for improvement when evaluated in DR. BENCH. We share DR. BENCH as a publicly available GitLab repository with a systematic approach to load and evaluate models for the cNLP community.

Brief hospital course (BHC) summaries are common clinical documents generated by summarizing clinical notes. While large language models (LLMs) depict remarkable capabilities in automating real-world tasks, their capabilities for healthcare applications such as BHC synthesis have not been shown. To enable the adaptation of LLMs for BHC synthesis, we introduce a novel benchmark consisting of a pre-processed dataset extracted from MIMIC-IV notes, encapsulating clinical note, and brief hospital course (BHC) pairs. We assess the performance of two general-purpose LLMs and three healthcare-adapted LLMs to improve BHC synthesis from clinical notes. Using clinical notes as input for generating BHCs, we apply prompting-based (using in-context learning) and fine-tuning-based adaptation strategies to three open-source LLMs (Clinical-T5-Large, Llama2-13B, FLAN-UL2) and two proprietary LLMs (GPT-3.5, GPT-4). We quantitatively evaluate the performance of these LLMs across varying context-length inputs using conventional natural language similarity metrics. We further perform a qualitative study where five diverse clinicians blindly compare clinician-written BHCs and two LLM-generated BHCs for 30 samples across metrics of comprehensiveness, conciseness, factual correctness, and fluency. Overall, we present a new benchmark and pre-processed dataset for using LLMs in BHC synthesis from clinical notes. We observe high-quality summarization performance for both in-context proprietary and fine-tuned open-source LLMs using both quantitative metrics and a qualitative clinical reader study. We propose our work as a benchmark to motivate future works to adapt and assess the performance of LLMs in BHC synthesis.

Large language models (LLMs) have demonstrated remarkable capabilities in natural language understanding and generation across various domains, including medicine. We present a comprehensive evaluation of GPT-4, a state-of-the-art LLM, on medical competency examinations and benchmark datasets. GPT-4 is a general-purpose model that is not specialized for medical problems through training or engineered to solve clinical tasks. Our analysis covers two sets of official practice materials for the USMLE, a three-step examination program used to assess clinical competency and grant licensure in the United States. We also evaluate performance on the MultiMedQA suite of benchmark datasets. Beyond measuring model performance, experiments were conducted to investigate the influence of test questions containing both text and images on model performance, probe for memorization of content during training, and study probability calibration, which is of critical importance in high-stakes applications like medicine. Our results show that GPT-4, without any specialized prompt crafting, exceeds the passing score on USMLE by over 20 points and outperforms earlier general-purpose models (GPT-3.5) as well as models specifically fine-tuned on medical knowledge (Med-PaLM, a prompt-tuned version of Flan-PaLM 540B). In addition, GPT-4 is significantly better calibrated than GPT-3.5, demonstrating a much-improved ability to predict the likelihood that its answers are correct. We also explore the behavior of the model qualitatively through a case study that shows the ability of GPT-4 to explain medical reasoning, personalize explanations to students, and interactively craft new counterfactual scenarios around a medical case. Implications of the findings are discussed for potential uses of GPT-4 in medical education, assessment, and clinical practice, with appropriate attention to challenges of accuracy and safety.

Clinical diagnosis is critical in medical practice, typically requiring a continuous and evolving process that includes primary diagnosis, differential diagnosis, and final diagnosis. However, most existing clinical diagnostic tasks are single-step processes, which does not align with the complex multi-step diagnostic procedures found in real-world clinical settings. In this paper, we propose a multi-step diagnostic task and annotate a clinical diagnostic dataset (MSDiagnosis). This dataset includes primary diagnosis, differential diagnosis, and final diagnosis questions. Additionally, we propose a novel and effective framework. This framework combines forward inference, backward inference, reflection, and refinement, enabling the LLM to self-evaluate and adjust its diagnostic results. To assess the effectiveness of our proposed method, we design and conduct extensive experiments. The experimental results demonstrate the effectiveness of the proposed method. We also provide a comprehensive experimental analysis and suggest future research directions for this task.

Global healthcare providers are exploring use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested if LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in less than 34.5% of cases and disposition in less than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities prior to public deployments in healthcare.

We introduce RJUA-QA, a novel medical dataset for question answering (QA) and reasoning with clinical evidence, contributing to bridge the gap between general large language models (LLMs) and medical-specific LLM applications. RJUA-QA is derived from realistic clinical scenarios and aims to facilitate LLMs in generating reliable diagnostic and advice. The dataset contains 2,132 curated Question-Context-Answer pairs, corresponding about 25,000 diagnostic records and clinical cases. The dataset covers 67 common urological disease categories, where the disease coverage exceeds 97.6\% of the population seeking medical services in urology. Each data instance in RJUA-QA comprises: (1) a question mirroring real patient to inquiry about clinical symptoms and medical conditions, (2) a context including comprehensive expert knowledge, serving as a reference for medical examination and diagnosis, (3) a doctor response offering the diagnostic conclusion and suggested examination guidance, (4) a diagnosed clinical disease as the recommended diagnostic outcome, and (5) clinical advice providing recommendations for medical examination. RJUA-QA is the first medical QA dataset for clinical reasoning over the patient inquiries, where expert-level knowledge and experience are required for yielding diagnostic conclusions and medical examination advice. A comprehensive evaluation is conducted to evaluate the performance of both medical-specific and general LLMs on the RJUA-QA dataset.

This research tests the role of Large Language Models (LLMs) as formal second opinion tools in professional decision-making, particularly focusing on complex medical cases where even experienced physicians seek peer consultation. The work analyzed 183 challenging medical cases from Medscape over a 20-month period, testing multiple LLMs' performance against crowd-sourced physician responses. A key finding was the high overall score possible in the latest foundational models (>80% accuracy compared to consensus opinion), which exceeds most human metrics reported on the same clinical cases (450 pages of patient profiles, test results). The study rates the LLMs' performance disparity between straightforward cases (>81% accuracy) and complex scenarios (43% accuracy), particularly in these cases generating substantial debate among human physicians. The research demonstrates that LLMs may be valuable as generators of comprehensive differential diagnoses rather than as primary diagnostic tools, potentially helping to counter cognitive biases in clinical decision-making, reduce cognitive loads, and thus remove some sources of medical error. The inclusion of a second comparative legal dataset (Supreme Court cases, N=21) provides added empirical context to the AI use to foster second opinions, though these legal challenges proved considerably easier for LLMs to analyze. In addition to the original contributions of empirical evidence for LLM accuracy, the research aggregated a novel benchmark for others to score highly contested question and answer reliability between both LLMs and disagreeing human practitioners. These results suggest that the optimal deployment of LLMs in professional settings may differ substantially from current approaches that emphasize automation of routine tasks.

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

Although large language models (LLMs) have been assessed for general medical knowledge using medical licensing exams, their ability to effectively support clinical decision-making tasks, such as selecting and using medical calculators, remains uncertain. Here, we evaluate the capability of both medical trainees and LLMs to recommend medical calculators in response to various multiple-choice clinical scenarios such as risk stratification, prognosis, and disease diagnosis. We assessed eight LLMs, including open-source, proprietary, and domain-specific models, with 1,009 question-answer pairs across 35 clinical calculators and measured human performance on a subset of 100 questions. While the highest-performing LLM, GPT-4o, provided an answer accuracy of 74.3% (CI: 71.5-76.9%), human annotators, on average, outperformed LLMs with an accuracy of 79.5% (CI: 73.5-85.0%). With error analysis showing that the highest-performing LLMs continue to make mistakes in comprehension (56.6%) and calculator knowledge (8.1%), our findings emphasize that humans continue to surpass LLMs on complex clinical tasks such as calculator recommendation.

Skin carcinoma is the most prevalent form of cancer globally, accounting for over $8 billion in annual healthcare expenditures. Early diagnosis, accurate and timely treatment are critical to improving patient survival rates. In clinical settings, physicians document patient visits using detailed SOAP (Subjective, Objective, Assessment, and Plan) notes. However, manually generating these notes is labor-intensive and contributes to clinician burnout. In this work, we propose skin-SOAP, a weakly supervised multimodal framework to generate clinically structured SOAP notes from limited inputs, including lesion images and sparse clinical text. Our approach reduces reliance on manual annotations, enabling scalable, clinically grounded documentation while alleviating clinician burden and reducing the need for large annotated data. Our method achieves performance comparable to GPT-4o, Claude, and DeepSeek Janus Pro across key clinical relevance metrics. To evaluate this clinical relevance, we introduce two novel metrics MedConceptEval and Clinical Coherence Score (CCS) which assess semantic alignment with expert medical concepts and input features, respectively.

Background: Clinical documentation represents a significant burden for healthcare providers, with physicians spending up to 2 hours daily on administrative tasks. Recent advances in large language models (LLMs) offer promising solutions, but privacy concerns and computational requirements limit their adoption in healthcare settings. Objective: To develop and evaluate a privacy-preserving, on-device medical transcription system using a fine-tuned Llama 3.2 1B model capable of generating structured medical notes from medical transcriptions while maintaining complete data sovereignty entirely in the browser. Methods: We fine-tuned a Llama 3.2 1B model using Parameter-Efficient Fine-Tuning (PEFT) with LoRA on 1,500 synthetic medical transcription-to-structured note pairs. The model was evaluated against the base Llama 3.2 1B on two datasets: 100 endocrinology transcripts and 140 modified ACI benchmark cases. Evaluation employed both statistical metrics (ROUGE, BERTScore, BLEURT) and LLM-as-judge assessments across multiple clinical quality dimensions. Results: The fine-tuned OnDevice model demonstrated substantial improvements over the base model. On the ACI benchmark, ROUGE-1 scores increased from 0.346 to 0.496, while BERTScore F1 improved from 0.832 to 0.866. Clinical quality assessments showed marked reduction in major hallucinations (from 85 to 35 cases) and enhanced factual correctness (2.81 to 3.54 on 5-point scale). Similar improvements were observed on the internal evaluation dataset, with composite scores increasing from 3.13 to 4.43 (+41.5%). Conclusions: Fine-tuning compact LLMs for medical transcription yields clinically meaningful improvements while enabling complete on-device browser deployment. This approach addresses key barriers to AI adoption in healthcare: privacy preservation, cost reduction, and accessibility for resource-constrained environments.

Unstructured clinical notes contain essential patient information but are challenging for physicians to search and interpret efficiently. Although large language models (LLMs) have shown promise in question answering (QA), most existing systems lack transparency, usability, and alignment with clinical workflows. This work introduces an interactive QA system that enables physicians to query clinical notes via text or voice and receive extractive answers highlighted directly in the note for traceability. The system was built using OpenAI models with zero-shot prompting and evaluated across multiple metrics, including exact string match, word overlap, SentenceTransformer similarity, and BERTScore. Results show that while exact match scores ranged from 47 to 62 percent, semantic similarity scores exceeded 87 percent, indicating strong contextual alignment even when wording varied. To assess usability, the system was also evaluated using simulated clinical personas. Seven diverse physician and nurse personas interacted with the system across scenario-based tasks and provided structured feedback. The evaluations highlighted strengths in intuitive design and answer accessibility, alongside opportunities for enhancing explanation clarity.

Multimodal large language models (MLLMs) hold considerable promise for applications in healthcare. However, their deployment in safety-critical settings is hindered by two key limitations: (i) sensitivity to prompt design, and (ii) a tendency to generate incorrect responses with high confidence. As clinicians may rely on a model's stated confidence to gauge the reliability of its predictions, it is especially important that when a model expresses high confidence, it is also highly accurate. We introduce Prompt4Trust, the first reinforcement learning (RL) framework for prompt augmentation targeting confidence calibration in MLLMs. A lightweight LLM is trained to produce context-aware auxiliary prompts that guide a downstream task MLLM to generate responses in which the expressed confidence more accurately reflects predictive accuracy. Unlike conventional calibration techniques, Prompt4Trust specifically prioritizes aspects of calibration most critical for safe and trustworthy clinical decision-making. Beyond improvements driven by this clinically motivated calibration objective, our proposed method also improves task accuracy, achieving state-of-the-art medical visual question answering (VQA) performance on the PMC-VQA benchmark, which is composed of multiple-choice questions spanning diverse medical imaging modalities. Moreover, our framework trained with a small downstream task MLLM showed promising zero-shot generalization to larger MLLMs in our experiments, suggesting the potential for scalable calibration without the associated computational costs. This work demonstrates the potential of automated yet human-aligned prompt engineering for improving the the trustworthiness of MLLMs in safety critical settings. Our codebase can be found at https://github.com/xingbpshen/prompt4trust.

Numerous medical systems powered by Large Language Models (LLMs) have achieved remarkable progress in diverse healthcare tasks. However, research on their medication safety remains limited due to the lack of real world datasets, constrained by privacy and accessibility issues. Moreover, evaluation of LLMs in realistic clinical consultation settings, particularly regarding medication safety, is still underexplored. To address these gaps, we propose a framework that simulates and evaluates clinical consultations to systematically assess the medication safety capabilities of LLMs. Within this framework, we generate inquiry diagnosis dialogues with embedded medication risks and construct a dedicated medication safety database, RxRisk DB, containing 6,725 contraindications, 28,781 drug interactions, and 14,906 indication-drug pairs. A two-stage filtering strategy ensures clinical realism and professional quality, resulting in the benchmark RxSafeBench with 2,443 high-quality consultation scenarios. We evaluate leading open-source and proprietary LLMs using structured multiple choice questions that test their ability to recommend safe medications under simulated patient contexts. Results show that current LLMs struggle to integrate contraindication and interaction knowledge, especially when risks are implied rather than explicit. Our findings highlight key challenges in ensuring medication safety in LLM-based systems and provide insights into improving reliability through better prompting and task-specific tuning. RxSafeBench offers the first comprehensive benchmark for evaluating medication safety in LLMs, advancing safer and more trustworthy AI-driven clinical decision support.

Objectives: While Large Language Models (LLMs) have been widely used to assist clinicians and support patients, no existing work has explored dialogue systems for standard diagnostic interviews and assessments. This study aims to bridge the gap in mental healthcare accessibility by developing an LLM-powered dialogue system that replicates clinician behavior. Materials and Methods: We introduce TRUST, a framework of cooperative LLM modules capable of conducting formal diagnostic interviews and assessments for Post-Traumatic Stress Disorder (PTSD). To guide the generation of appropriate clinical responses, we propose a Dialogue Acts schema specifically designed for clinical interviews. Additionally, we develop a patient simulation approach based on real-life interview transcripts to replace time-consuming and costly manual testing by clinicians. Results: A comprehensive set of evaluation metrics is designed to assess the dialogue system from both the agent and patient simulation perspectives. Expert evaluations by conversation and clinical specialists show that TRUST performs comparably to real-life clinical interviews. Discussion: Our system performs at the level of average clinicians, with room for future enhancements in communication styles and response appropriateness. Conclusions: Our TRUST framework shows its potential to facilitate mental healthcare availability.

Clinical notes contain information about patients that goes beyond structured data like lab values and medications. However, clinical notes have been underused relative to structured data, because notes are high-dimensional and sparse. This work develops and evaluates representations of clinical notes using bidirectional transformers (ClinicalBERT). ClinicalBERT uncovers high-quality relationships between medical concepts as judged by humans. ClinicalBert outperforms baselines on 30-day hospital readmission prediction using both discharge summaries and the first few days of notes in the intensive care unit. Code and model parameters are available.

Clinical trial matching is the task of identifying trials for which patients may be potentially eligible. Typically, this task is labor-intensive and requires detailed verification of patient electronic health records (EHRs) against the stringent inclusion and exclusion criteria of clinical trials. This process is manual, time-intensive, and challenging to scale up, resulting in many patients missing out on potential therapeutic options. Recent advancements in Large Language Models (LLMs) have made automating patient-trial matching possible, as shown in multiple concurrent research studies. However, the current approaches are confined to constrained, often synthetic datasets that do not adequately mirror the complexities encountered in real-world medical data. In this study, we present the first, end-to-end large-scale empirical evaluation of clinical trial matching using real-world EHRs. Our study showcases the capability of LLMs to accurately match patients with appropriate clinical trials. We perform experiments with proprietary LLMs, including GPT-4 and GPT-3.5, as well as our custom fine-tuned model called OncoLLM and show that OncoLLM, despite its significantly smaller size, not only outperforms GPT-3.5 but also matches the performance of qualified medical doctors. All experiments were carried out on real-world EHRs that include clinical notes and available clinical trials from a single cancer center in the United States.

This paper describes the results of SemEval 2023 task 7 -- Multi-Evidence Natural Language Inference for Clinical Trial Data (NLI4CT) -- consisting of 2 tasks, a Natural Language Inference (NLI) task, and an evidence selection task on clinical trial data. The proposed challenges require multi-hop biomedical and numerical reasoning, which are of significant importance to the development of systems capable of large-scale interpretation and retrieval of medical evidence, to provide personalized evidence-based care. Task 1, the entailment task, received 643 submissions from 40 participants, and Task 2, the evidence selection task, received 364 submissions from 23 participants. The tasks are challenging, with the majority of submitted systems failing to significantly outperform the majority class baseline on the entailment task, and we observe significantly better performance on the evidence selection task than on the entailment task. Increasing the number of model parameters leads to a direct increase in performance, far more significant than the effect of biomedical pre-training. Future works could explore the limitations of large models for generalization and numerical inference, and investigate methods to augment clinical datasets to allow for more rigorous testing and to facilitate fine-tuning. We envisage that the dataset, models, and results of this task will be useful to the biomedical NLI and evidence retrieval communities. The dataset, competition leaderboard, and website are publicly available.

Radiological imaging is central to diagnosis, treatment planning, and clinical decision-making. Vision-language foundation models have spurred interest in automated radiology report generation (RRG), but safe deployment requires reliable clinical evaluation of generated reports. Existing metrics often rely on surface-level similarity or behave as black boxes, lacking interpretability. We introduce ICARE (Interpretable and Clinically-grounded Agent-based Report Evaluation), an interpretable evaluation framework leveraging large language model agents and dynamic multiple-choice question answering (MCQA). Two agents, each with either the ground-truth or generated report, generate clinically meaningful questions and quiz each other. Agreement on answers captures preservation and consistency of findings, serving as interpretable proxies for clinical precision and recall. By linking scores to question-answer pairs, ICARE enables transparent, and interpretable assessment. Clinician studies show ICARE aligns significantly more with expert judgment than prior metrics. Perturbation analyses confirm sensitivity to clinical content and reproducibility, while model comparisons reveal interpretable error patterns.

Large language models have demonstrated remarkable performance in a wide range of medical benchmarks. Yet underneath the seemingly promising results lie salient growth areas, especially in cutting-edge frontiers such as multimodal reasoning. In this paper, we introduce a series of adversarial stress tests to systematically assess the robustness of flagship models and medical benchmarks. Our study reveals prevalent brittleness in the presence of simple adversarial transformations: leading systems can guess the right answer even with key inputs removed, yet may get confused by the slightest prompt alterations, while fabricating convincing yet flawed reasoning traces. Using clinician-guided rubrics, we demonstrate that popular medical benchmarks vary widely in what they truly measure. Our study reveals significant competency gaps of frontier AI in attaining real-world readiness for health applications. If we want AI to earn trust in healthcare, we must demand more than leaderboard wins and must hold AI systems accountable to ensure robustness, sound reasoning, and alignment with real medical demands.

Large Language Models (LLMs) have attained human-level accuracy on medical question-answer (QA) benchmarks. However, their limitations in navigating open-ended clinical scenarios have recently been shown, raising concerns about the robustness and generalizability of LLM reasoning across diverse, real-world medical tasks. To probe potential LLM failure modes in clinical problem-solving, we present the medical abstraction and reasoning corpus (M-ARC). M-ARC assesses clinical reasoning through scenarios designed to exploit the Einstellung effect -- the fixation of thought arising from prior experience, targeting LLM inductive biases toward inflexible pattern matching from their training data rather than engaging in flexible reasoning. We find that LLMs, including current state-of-the-art o1 and Gemini models, perform poorly compared to physicians on M-ARC, often demonstrating lack of commonsense medical reasoning and a propensity to hallucinate. In addition, uncertainty estimation analyses indicate that LLMs exhibit overconfidence in their answers, despite their limited accuracy. The failure modes revealed by M-ARC in LLM medical reasoning underscore the need to exercise caution when deploying these models in clinical settings.

Current medical language models, adapted from large language models (LLMs), typically predict ICD code-based diagnosis from electronic health records (EHRs) because these labels are readily available. However, ICD codes do not capture the nuanced, context-rich reasoning clinicians use for diagnosis. Clinicians synthesize diverse patient data and reference clinical practice guidelines (CPGs) to make evidence-based decisions. This misalignment limits the clinical utility of existing models. We introduce GARMLE-G, a Generation-Augmented Retrieval framework that grounds medical language model outputs in authoritative CPGs. Unlike conventional Retrieval-Augmented Generation based approaches, GARMLE-G enables hallucination-free outputs by directly retrieving authoritative guideline content without relying on model-generated text. It (1) integrates LLM predictions with EHR data to create semantically rich queries, (2) retrieves relevant CPG knowledge snippets via embedding similarity, and (3) fuses guideline content with model output to generate clinically aligned recommendations. A prototype system for hypertension diagnosis was developed and evaluated on multiple metrics, demonstrating superior retrieval precision, semantic relevance, and clinical guideline adherence compared to RAG-based baselines, while maintaining a lightweight architecture suitable for localized healthcare deployment. This work provides a scalable, low-cost, and hallucination-free method for grounding medical language models in evidence-based clinical practice, with strong potential for broader clinical deployment.

We present VinDr-CXR-VQA, a large-scale chest X-ray dataset for explainable Medical Visual Question Answering (Med-VQA) with spatial grounding. The dataset contains 17,597 question-answer pairs across 4,394 images, each annotated with radiologist-verified bounding boxes and clinical reasoning explanations. Our question taxonomy spans six diagnostic types-Where, What, Is there, How many, Which, and Yes/No-capturing diverse clinical intents. To improve reliability, we construct a balanced distribution of 41.7% positive and 58.3% negative samples, mitigating hallucinations in normal cases. Benchmarking with MedGemma-4B-it demonstrates improved performance (F1 = 0.624, +11.8% over baseline) while enabling lesion localization. VinDr-CXR-VQA aims to advance reproducible and clinically grounded Med-VQA research. The dataset and evaluation tools are publicly available at huggingface.co/datasets/Dangindev/VinDR-CXR-VQA.

Accurate estimation of brain infarction (i.e., irreversibly damaged tissue) is critical for guiding treatment decisions in acute ischemic stroke. Reliable infarct prediction informs key clinical interventions, including the need for patient transfer to comprehensive stroke centers, the potential benefit of additional reperfusion attempts during mechanical thrombectomy, decisions regarding secondary neuroprotective treatments, and ultimately, prognosis of clinical outcomes. This work introduces the Ischemic Stroke Lesion Segmentation (ISLES) 2024 challenge, which focuses on the prediction of final infarct volumes from pre-interventional acute stroke imaging and clinical data. ISLES24 provides a comprehensive, multimodal setting where participants can leverage all clinically and practically available data, including full acute CT imaging, sub-acute follow-up MRI, and structured clinical information, across a train set of 150 cases. On the hidden test set of 98 cases, the top-performing model, a multimodal nnU-Net-based architecture, achieved a Dice score of 0.285 (+/- 0.213) and an absolute volume difference of 21.2 (+/- 37.2) mL, underlining the significant challenges posed by this task and the need for further advances in multimodal learning. This work makes two primary contributions: first, we establish a standardized, clinically realistic benchmark for post-treatment infarct prediction, enabling systematic evaluation of multimodal algorithmic strategies on a longitudinal stroke dataset; second, we analyze current methodological limitations and outline key research directions to guide the development of next-generation infarct prediction models.

Recruiting patients to participate in clinical trials can be challenging and time-consuming. Usually, participation in a clinical trial is initiated by a healthcare professional and proposed to the patient. Promoting clinical trials directly to patients via online recruitment might help to reach them more efficiently. In this study, we address the case where a patient is initiating their own recruitment process and wants to determine whether they are eligible for a given clinical trial, using their own language to describe their medical profile. To study whether this creates difficulties in the patient trial matching process, we design a new dataset and task, Natural Language Inference for Patient Recruitment (NLI4PR), in which patient language profiles must be matched to clinical trials. We create it by adapting the TREC 2022 Clinical Trial Track dataset, which provides patients' medical profiles, and rephrasing them manually using patient language. We also use the associated clinical trial reports where the patients are either eligible or excluded. We prompt several open-source Large Language Models on our task and achieve from 56.5 to 71.8 of F1 score using patient language, against 64.7 to 73.1 for the same task using medical language. When using patient language, we observe only a small loss in performance for the best model, suggesting that having the patient as a starting point could be adopted to help recruit patients for clinical trials. The corpus and code bases are all freely available on our Github and HuggingFace repositories.

We present Eir Thai Medical LLM, a large language model with 8 billion parameters, specifically designed to enhance the accuracy of handling medical tasks in the Thai language. This model focuses on providing clear and easy-to-understand answers for both healthcare professionals and patients, thereby improving the efficiency of diagnosis and treatment processes. Human evaluation was conducted to ensure that the model adheres to care standards and provides unbiased answers. To prioritize data security, the model is deployed within the hospital's internal network, ensuring both high security and faster processing speeds. The internal API connection is secured with encryption and strict authentication measures to prevent data leaks and unauthorized access. We evaluated several open-source large language models with 8 billion parameters on four medical benchmarks: MedQA, MedMCQA, PubMedQA, and the medical subset of MMLU. The best-performing baselines were used to develop Eir Thai Medical LLM. Our evaluation employed multiple questioning strategies, including zero-shot, few-shot, chain-of-thought reasoning, and ensemble/self-consistency voting methods. Our model outperformed commercially available Thai-language large language models by more than 10%. In addition, we developed enhanced model testing tailored for clinical use in Thai across 18 clinical tasks, where our model exceeded GPT-4o performance by more than 11%

Background: Recent advancements in large language models (LLMs) offer potential benefits in healthcare, particularly in processing extensive patient records. However, existing benchmarks do not fully assess LLMs' capability in handling real-world, lengthy clinical data. Methods: We present the LongHealth benchmark, comprising 20 detailed fictional patient cases across various diseases, with each case containing 5,090 to 6,754 words. The benchmark challenges LLMs with 400 multiple-choice questions in three categories: information extraction, negation, and sorting, challenging LLMs to extract and interpret information from large clinical documents. Results: We evaluated nine open-source LLMs with a minimum of 16,000 tokens and also included OpenAI's proprietary and cost-efficient GPT-3.5 Turbo for comparison. The highest accuracy was observed for Mixtral-8x7B-Instruct-v0.1, particularly in tasks focused on information retrieval from single and multiple patient documents. However, all models struggled significantly in tasks requiring the identification of missing information, highlighting a critical area for improvement in clinical data interpretation. Conclusion: While LLMs show considerable potential for processing long clinical documents, their current accuracy levels are insufficient for reliable clinical use, especially in scenarios requiring the identification of missing information. The LongHealth benchmark provides a more realistic assessment of LLMs in a healthcare setting and highlights the need for further model refinement for safe and effective clinical application. We make the benchmark and evaluation code publicly available.

Clinical diagnosis prediction models, when provided with a patient's medical history, aim to detect potential diseases early, facilitating timely intervention and improving prognostic outcomes. However, the inherent scarcity of patient data and large disease candidate space often pose challenges in developing satisfactory models for this intricate task. The exploration of leveraging Large Language Models (LLMs) for encapsulating clinical decision processes has been limited. We introduce MERA, a clinical diagnosis prediction model that bridges pertaining natural language knowledge with medical practice. We apply hierarchical contrastive learning on a disease candidate ranking list to alleviate the large decision space issue. With concept memorization through fine-tuning, we bridge the natural language clinical knowledge with medical codes. Experimental results on MIMIC-III and IV datasets show that MERA achieves the state-of-the-art diagnosis prediction performance and dramatically elevates the diagnosis prediction capabilities of generative LMs.

With the rapid development of artificial intelligence, large language models (LLMs) have shown promising capabilities in mimicking human-level language comprehension and reasoning. This has sparked significant interest in applying LLMs to enhance various aspects of healthcare, ranging from medical education to clinical decision support. However, medicine involves multifaceted data modalities and nuanced reasoning skills, presenting challenges for integrating LLMs. This paper provides a comprehensive review on the applications and implications of LLMs in medicine. It begins by examining the fundamental applications of general-purpose and specialized LLMs, demonstrating their utilities in knowledge retrieval, research support, clinical workflow automation, and diagnostic assistance. Recognizing the inherent multimodality of medicine, the review then focuses on multimodal LLMs, investigating their ability to process diverse data types like medical imaging and EHRs to augment diagnostic accuracy. To address LLMs' limitations regarding personalization and complex clinical reasoning, the paper explores the emerging development of LLM-powered autonomous agents for healthcare. Furthermore, it summarizes the evaluation methodologies for assessing LLMs' reliability and safety in medical contexts. Overall, this review offers an extensive analysis on the transformative potential of LLMs in modern medicine. It also highlights the pivotal need for continuous optimizations and ethical oversight before these models can be effectively integrated into clinical practice. Visit https://github.com/mingze-yuan/Awesome-LLM-Healthcare for an accompanying GitHub repository containing latest papers.

Clinical calculators play a vital role in healthcare by offering accurate evidence-based predictions for various purposes such as prognosis. Nevertheless, their widespread utilization is frequently hindered by usability challenges, poor dissemination, and restricted functionality. Augmenting large language models with extensive collections of clinical calculators presents an opportunity to overcome these obstacles and improve workflow efficiency, but the scalability of the manual curation process poses a significant challenge. In response, we introduce AgentMD, a novel language agent capable of curating and applying clinical calculators across various clinical contexts. Using the published literature, AgentMD has automatically curated a collection of 2,164 diverse clinical calculators with executable functions and structured documentation, collectively named RiskCalcs. Manual evaluations show that RiskCalcs tools achieve an accuracy of over 80% on three quality metrics. At inference time, AgentMD can automatically select and apply the relevant RiskCalcs tools given any patient description. On the newly established RiskQA benchmark, AgentMD significantly outperforms chain-of-thought prompting with GPT-4 (87.7% vs. 40.9% in accuracy). Additionally, we also applied AgentMD to real-world clinical notes for analyzing both population-level and risk-level patient characteristics. In summary, our study illustrates the utility of language agents augmented with clinical calculators for healthcare analytics and patient care.

The deployment of Large Language Models (LLMs) in high-stakes clinical settings demands rigorous and reliable evaluation. However, existing medical benchmarks remain static, suffering from two critical limitations: (1) data contamination, where test sets inadvertently leak into training corpora, leading to inflated performance estimates; and (2) temporal misalignment, failing to capture the rapid evolution of medical knowledge. Furthermore, current evaluation metrics for open-ended clinical reasoning often rely on either shallow lexical overlap (e.g., ROUGE) or subjective LLM-as-a-Judge scoring, both inadequate for verifying clinical correctness. To bridge these gaps, we introduce LiveMedBench, a continuously updated, contamination-free, and rubric-based benchmark that weekly harvests real-world clinical cases from online medical communities, ensuring strict temporal separation from model training data. We propose a Multi-Agent Clinical Curation Framework that filters raw data noise and validates clinical integrity against evidence-based medical principles. For evaluation, we develop an Automated Rubric-based Evaluation Framework that decomposes physician responses into granular, case-specific criteria, achieving substantially stronger alignment with expert physicians than LLM-as-a-Judge. To date, LiveMedBench comprises 2,756 real-world cases spanning 38 medical specialties and multiple languages, paired with 16,702 unique evaluation criteria. Extensive evaluation of 38 LLMs reveals that even the best-performing model achieves only 39.2%, and 84% of models exhibit performance degradation on post-cutoff cases, confirming pervasive data contamination risks. Error analysis further identifies contextual application-not factual knowledge-as the dominant bottleneck, with 35-48% of failures stemming from the inability to tailor medical knowledge to patient-specific constraints.

The ability of large language models (LLMs) to follow natural language instructions with human-level fluency suggests many opportunities in healthcare to reduce administrative burden and improve quality of care. However, evaluating LLMs on realistic text generation tasks for healthcare remains challenging. Existing question answering datasets for electronic health record (EHR) data fail to capture the complexity of information needs and documentation burdens experienced by clinicians. To address these challenges, we introduce MedAlign, a benchmark dataset of 983 natural language instructions for EHR data. MedAlign is curated by 15 clinicians (7 specialities), includes clinician-written reference responses for 303 instructions, and provides 276 longitudinal EHRs for grounding instruction-response pairs. We used MedAlign to evaluate 6 general domain LLMs, having clinicians rank the accuracy and quality of each LLM response. We found high error rates, ranging from 35% (GPT-4) to 68% (MPT-7B-Instruct), and an 8.3% drop in accuracy moving from 32k to 2k context lengths for GPT-4. Finally, we report correlations between clinician rankings and automated natural language generation metrics as a way to rank LLMs without human review. We make MedAlign available under a research data use agreement to enable LLM evaluations on tasks aligned with clinician needs and preferences.

LLMs have demonstrated impressive performance in answering medical questions, such as passing scores on medical licensing examinations. However, medical board exam questions or general clinical questions do not capture the complexity of realistic clinical cases. Moreover, the lack of reference explanations means we cannot easily evaluate the reasoning of model decisions, a crucial component of supporting doctors in making complex medical decisions. To address these challenges, we construct two new datasets: JAMA Clinical Challenge and Medbullets. JAMA Clinical Challenge consists of questions based on challenging clinical cases, while Medbullets comprises USMLE Step 2&3 style clinical questions. Both datasets are structured as multiple-choice question-answering tasks, where each question is accompanied by an expert-written explanation. We evaluate four LLMs on the two datasets using various prompts. Experiments demonstrate that our datasets are harder than previous benchmarks. The inconsistency between automatic and human evaluations of model-generated explanations highlights the need to develop new metrics to support future research on explainable medical QA.

Although large language models (LLMs) demonstrate expert-level medical knowledge, aligning their open-ended outputs with fine-grained clinician preferences remains challenging. Existing methods often rely on coarse objectives or unreliable automated judges that are weakly grounded in professional guidelines. We propose a two-stage framework to address this gap. First, we introduce HealthRubrics, a dataset of 7,034 physician-verified preference examples in which clinicians refine LLM-drafted rubrics to meet rigorous medical standards. Second, we distill these rubrics into HealthPrinciples: 119 broadly reusable, clinically grounded principles organized by clinical dimensions, enabling scalable supervision beyond manual annotation. We use HealthPrinciples for (1) offline alignment by synthesizing rubrics for unlabeled queries and (2) an inference-time tool for guided self-revision. A 30B parameter model that activates only 3B parameters at inference trained with our framework achieves 33.4% on HealthBench-Hard, outperforming much larger models including Deepseek-R1 and o3, establishing a resource-efficient baseline for clinical alignment.

With the emergence of large-scale vision language models (VLM), it is now possible to produce realistic-looking radiology reports for chest X-ray images. However, their clinical translation has been hampered by the factual errors and hallucinations in the produced descriptions during inference. In this paper, we present a novel phrase-grounded fact-checking model (FC model) that detects errors in findings and their indicated locations in automatically generated chest radiology reports. Specifically, we simulate the errors in reports through a large synthetic dataset derived by perturbing findings and their locations in ground truth reports to form real and fake findings-location pairs with images. A new multi-label cross-modal contrastive regression network is then trained on this dataset. We present results demonstrating the robustness of our method in terms of accuracy of finding veracity prediction and localization on multiple X-ray datasets. We also show its effectiveness for error detection in reports of SOTA report generators on multiple datasets achieving a concordance correlation coefficient of 0.997 with ground truth-based verification, thus pointing to its utility during clinical inference in radiology workflows.

Ensuring the accuracy of responses provided by large language models (LLMs) is crucial, particularly in clinical settings where incorrect information may directly impact patient health. To address this challenge, we construct K-QA, a dataset containing 1,212 patient questions originating from real-world conversations held on K Health (an AI-driven clinical platform). We employ a panel of in-house physicians to answer and manually decompose a subset of K-QA into self-contained statements. Additionally, we formulate two NLI-based evaluation metrics approximating recall and precision: (1) comprehensiveness, measuring the percentage of essential clinical information in the generated answer and (2) hallucination rate, measuring the number of statements from the physician-curated response contradicted by the LLM answer. Finally, we use K-QA along with these metrics to evaluate several state-of-the-art models, as well as the effect of in-context learning and medically-oriented augmented retrieval schemes developed by the authors. Our findings indicate that in-context learning improves the comprehensiveness of the models, and augmented retrieval is effective in reducing hallucinations. We make K-QA available to to the community to spur research into medically accurate NLP applications.

Recent advancements in reasoning-enhanced large language models (LLMs), such as DeepSeek-R1 and OpenAI-o3, have demonstrated significant progress. However, their application in professional medical contexts remains underexplored, particularly in evaluating the quality of their reasoning processes alongside final outputs. Here, we introduce MedR-Bench, a benchmarking dataset of 1,453 structured patient cases, annotated with reasoning references derived from clinical case reports. Spanning 13 body systems and 10 specialties, it includes both common and rare diseases. To comprehensively evaluate LLM performance, we propose a framework encompassing three critical examination recommendation, diagnostic decision-making, and treatment planning, simulating the entire patient care journey. To assess reasoning quality, we present the Reasoning Evaluator, a novel automated system that objectively scores free-text reasoning responses based on efficiency, actuality, and completeness using dynamic cross-referencing and evidence checks. Using this benchmark, we evaluate five state-of-the-art reasoning LLMs, including DeepSeek-R1, OpenAI-o3-mini, and Gemini-2.0-Flash Thinking, etc. Our results show that current LLMs achieve over 85% accuracy in relatively simple diagnostic tasks when provided with sufficient examination results. However, performance declines in more complex tasks, such as examination recommendation and treatment planning. While reasoning outputs are generally reliable, with factuality scores exceeding 90%, critical reasoning steps are frequently missed. These findings underscore both the progress and limitations of clinical LLMs. Notably, open-source models like DeepSeek-R1 are narrowing the gap with proprietary systems, highlighting their potential to drive accessible and equitable advancements in healthcare.

Large language models (LLMs) are transforming the landscape of medicine, yet two fundamental challenges persist: keeping up with rapidly evolving medical knowledge and providing verifiable, evidence-grounded reasoning. Retrieval-augmented generation (RAG) has been widely adopted to address these limitations by supplementing model outputs with retrieved evidence. However, whether RAG reliably achieves these goals remains unclear. Here, we present the most comprehensive expert evaluation of RAG in medicine to date. Eighteen medical experts contributed a total of 80,502 annotations, assessing 800 model outputs generated by GPT-4o and Llama-3.1-8B across 200 real-world patient and USMLE-style queries. We systematically decomposed the RAG pipeline into three components: (i) evidence retrieval (relevance of retrieved passages), (ii) evidence selection (accuracy of evidence usage), and (iii) response generation (factuality and completeness of outputs). Contrary to expectation, standard RAG often degraded performance: only 22% of top-16 passages were relevant, evidence selection remained weak (precision 41-43%, recall 27-49%), and factuality and completeness dropped by up to 6% and 5%, respectively, compared with non-RAG variants. Retrieval and evidence selection remain key failure points for the model, contributing to the overall performance drop. We further show that simple yet effective strategies, including evidence filtering and query reformulation, substantially mitigate these issues, improving performance on MedMCQA and MedXpertQA by up to 12% and 8.2%, respectively. These findings call for re-examining RAG's role in medicine and highlight the importance of stage-aware evaluation and deliberate system design for reliable medical LLM applications.

Large language models (LLMs) have shown great potential for healthcare applications. However, existing evaluation benchmarks provide minimal coverage of Alzheimer's Disease and Related Dementias (ADRD). To address this gap, we introduce ADRD-Bench, the first ADRD-specific benchmark dataset designed for rigorous evaluation of LLMs. ADRD-Bench has two components: 1) ADRD Unified QA, a synthesis of 1,352 questions consolidated from seven established medical benchmarks, providing a unified assessment of clinical knowledge; and 2) ADRD Caregiving QA, a novel set of 149 questions derived from the Aging Brain Care (ABC) program, a widely used, evidence-based brain health management program. Guided by a program with national expertise in comprehensive ADRD care, this new set was designed to mitigate the lack of practical caregiving context in existing benchmarks. We evaluated 33 state-of-the-art LLMs on the proposed ADRD-Bench. Results showed that the accuracy of open-weight general models ranged from 0.63 to 0.93 (mean: 0.78; std: 0.09). The accuracy of open-weight medical models ranged from 0.48 to 0.93 (mean: 0.82; std: 0.13). The accuracy of closed-source general models ranged from 0.83 to 0.91 (mean: 0.89; std: 0.03). While top-tier models achieved high accuracies (>0.9), case studies revealed that inconsistent reasoning quality and stability limit their reliability, highlighting a critical need for domain-specific improvement to enhance LLMs' knowledge and reasoning grounded in daily caregiving data. The entire dataset is available at https://github.com/IIRL-ND/ADRD-Bench.

Despite growing interest in using large language models (LLMs) in healthcare, current explorations do not assess the real-world utility and safety of LLMs in clinical settings. Our objective was to determine whether two LLMs can serve information needs submitted by physicians as questions to an informatics consultation service in a safe and concordant manner. Sixty six questions from an informatics consult service were submitted to GPT-3.5 and GPT-4 via simple prompts. 12 physicians assessed the LLM responses' possibility of patient harm and concordance with existing reports from an informatics consultation service. Physician assessments were summarized based on majority vote. For no questions did a majority of physicians deem either LLM response as harmful. For GPT-3.5, responses to 8 questions were concordant with the informatics consult report, 20 discordant, and 9 were unable to be assessed. There were 29 responses with no majority on "Agree", "Disagree", and "Unable to assess". For GPT-4, responses to 13 questions were concordant, 15 discordant, and 3 were unable to be assessed. There were 35 responses with no majority. Responses from both LLMs were largely devoid of overt harm, but less than 20% of the responses agreed with an answer from an informatics consultation service, responses contained hallucinated references, and physicians were divided on what constitutes harm. These results suggest that while general purpose LLMs are able to provide safe and credible responses, they often do not meet the specific information need of a given question. A definitive evaluation of the usefulness of LLMs in healthcare settings will likely require additional research on prompt engineering, calibration, and custom-tailoring of general purpose models.

The emergence of large language models (LLMs) has significantly influenced numerous fields, including healthcare, by enhancing the capabilities of automated systems to process and generate human-like text. However, despite their advancements, the reliability and accuracy of LLMs in medical contexts remain critical concerns. Current evaluation methods often lack robustness and fail to provide a comprehensive assessment of LLM performance, leading to potential risks in clinical settings. In this work, we propose Med-CoDE, a specifically designed evaluation framework for medical LLMs to address these challenges. The framework leverages a critique-based approach to quantitatively measure the degree of disagreement between model-generated responses and established medical ground truths. This framework captures both accuracy and reliability in medical settings. The proposed evaluation framework aims to fill the existing gap in LLM assessment by offering a systematic method to evaluate the quality and trustworthiness of medical LLMs. Through extensive experiments and case studies, we illustrate the practicality of our framework in providing a comprehensive and reliable evaluation of medical LLMs.

Electronic Health Records (EHRs) are integral for storing comprehensive patient medical records, combining structured data (e.g., medications) with detailed clinical notes (e.g., physician notes). These elements are essential for straightforward data retrieval and provide deep, contextual insights into patient care. However, they often suffer from discrepancies due to unintuitive EHR system designs and human errors, posing serious risks to patient safety. To address this, we developed EHRCon, a new dataset and task specifically designed to ensure data consistency between structured tables and unstructured notes in EHRs. EHRCon was crafted in collaboration with healthcare professionals using the MIMIC-III EHR dataset, and includes manual annotations of 3,943 entities across 105 clinical notes checked against database entries for consistency. EHRCon has two versions, one using the original MIMIC-III schema, and another using the OMOP CDM schema, in order to increase its applicability and generalizability. Furthermore, leveraging the capabilities of large language models, we introduce CheckEHR, a novel framework for verifying the consistency between clinical notes and database tables. CheckEHR utilizes an eight-stage process and shows promising results in both few-shot and zero-shot settings. The code is available at https://github.com/dustn1259/EHRCon.

This technical report introduces a Named Clinical Entity Recognition Benchmark for evaluating language models in healthcare, addressing the crucial natural language processing (NLP) task of extracting structured information from clinical narratives to support applications like automated coding, clinical trial cohort identification, and clinical decision support. The leaderboard provides a standardized platform for assessing diverse language models, including encoder and decoder architectures, on their ability to identify and classify clinical entities across multiple medical domains. A curated collection of openly available clinical datasets is utilized, encompassing entities such as diseases, symptoms, medications, procedures, and laboratory measurements. Importantly, these entities are standardized according to the Observational Medical Outcomes Partnership (OMOP) Common Data Model, ensuring consistency and interoperability across different healthcare systems and datasets, and a comprehensive evaluation of model performance. Performance of models is primarily assessed using the F1-score, and it is complemented by various assessment modes to provide comprehensive insights into model performance. The report also includes a brief analysis of models evaluated to date, highlighting observed trends and limitations. By establishing this benchmarking framework, the leaderboard aims to promote transparency, facilitate comparative analyses, and drive innovation in clinical entity recognition tasks, addressing the need for robust evaluation methods in healthcare NLP.

We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of biomarkers. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.

Large Language Models (LLMs) have great potential in the field of health care, yet they face great challenges in adapting to rapidly evolving medical knowledge. This can lead to outdated or contradictory treatment suggestions. This study investigated how LLMs respond to evolving clinical guidelines, focusing on concept drift and internal inconsistencies. We developed the DriftMedQA benchmark to simulate guideline evolution and assessed the temporal reliability of various LLMs. Our evaluation of seven state-of-the-art models across 4,290 scenarios demonstrated difficulties in rejecting outdated recommendations and frequently endorsing conflicting guidance. Additionally, we explored two mitigation strategies: Retrieval-Augmented Generation and preference fine-tuning via Direct Preference Optimization. While each method improved model performance, their combination led to the most consistent and reliable results. These findings underscore the need to improve LLM robustness to temporal shifts to ensure more dependable applications in clinical practice.

Large language models (LLMs) have exhibited remarkable capabilities across various domains and tasks, pushing the boundaries of our knowledge in learning and cognition. The latest model, OpenAI's o1, stands out as the first LLM with an internalized chain-of-thought technique using reinforcement learning strategies. While it has demonstrated surprisingly strong capabilities on various general language tasks, its performance in specialized fields such as medicine remains unknown. To this end, this report provides a comprehensive exploration of o1 on different medical scenarios, examining 3 key aspects: understanding, reasoning, and multilinguality. Specifically, our evaluation encompasses 6 tasks using data from 37 medical datasets, including two newly constructed and more challenging question-answering (QA) tasks based on professional medical quizzes from the New England Journal of Medicine (NEJM) and The Lancet. These datasets offer greater clinical relevance compared to standard medical QA benchmarks such as MedQA, translating more effectively into real-world clinical utility. Our analysis of o1 suggests that the enhanced reasoning ability of LLMs may (significantly) benefit their capability to understand various medical instructions and reason through complex clinical scenarios. Notably, o1 surpasses the previous GPT-4 in accuracy by an average of 6.2% and 6.6% across 19 datasets and two newly created complex QA scenarios. But meanwhile, we identify several weaknesses in both the model capability and the existing evaluation protocols, including hallucination, inconsistent multilingual ability, and discrepant metrics for evaluation. We release our raw data and model outputs at https://ucsc-vlaa.github.io/o1_medicine/ for future research.

Integrating large language models (LLMs) like DeepSeek R1 into healthcare requires rigorous evaluation of their reasoning alignment with clinical expertise. This study assesses DeepSeek R1's medical reasoning against expert patterns using 100 MedQA clinical cases. The model achieved 93% diagnostic accuracy, demonstrating systematic clinical judgment through differential diagnosis, guideline-based treatment selection, and integration of patient-specific factors. However, error analysis of seven incorrect cases revealed persistent limitations: anchoring bias, challenges reconciling conflicting data, insufficient exploration of alternatives, overthinking, knowledge gaps, and premature prioritization of definitive treatment over intermediate care. Crucially, reasoning length correlated with accuracy - shorter responses (<5,000 characters) were more reliable, suggesting extended explanations may signal uncertainty or rationalization of errors. While DeepSeek R1 exhibits foundational clinical reasoning capabilities, recurring flaws highlight critical areas for refinement, including bias mitigation, knowledge updates, and structured reasoning frameworks. These findings underscore LLMs' potential to augment medical decision-making through artificial reasoning but emphasize the need for domain-specific validation, interpretability safeguards, and confidence metrics (e.g., response length thresholds) to ensure reliability in real-world applications.

Large language models have exhibited exceptional performance on various Natural Language Processing (NLP) tasks, leveraging techniques such as the pre-training, and instruction fine-tuning. Despite these advances, their effectiveness in medical applications is limited, due to challenges such as factual inaccuracies, reasoning abilities, and lack grounding in real-world experience. In this study, we present ClinicalGPT, a language model explicitly designed and optimized for clinical scenarios. By incorporating extensive and diverse real-world data, such as medical records, domain-specific knowledge, and multi-round dialogue consultations in the training process, ClinicalGPT is better prepared to handle multiple clinical task. Furthermore, we introduce a comprehensive evaluation framework that includes medical knowledge question-answering, medical exams, patient consultations, and diagnostic analysis of medical records. Our results demonstrate that ClinicalGPT significantly outperforms other models in these tasks, highlighting the effectiveness of our approach in adapting large language models to the critical domain of healthcare.

The integration of Artificial Intelligence (AI), especially Large Language Models (LLMs), into the clinical diagnosis process offers significant potential to improve the efficiency and accessibility of medical care. While LLMs have shown some promise in the medical domain, their application in clinical diagnosis remains underexplored, especially in real-world clinical practice, where highly sophisticated, patient-specific decisions need to be made. Current evaluations of LLMs in this field are often narrow in scope, focusing on specific diseases or specialties and employing simplified diagnostic tasks. To bridge this gap, we introduce CliBench, a novel benchmark developed from the MIMIC IV dataset, offering a comprehensive and realistic assessment of LLMs' capabilities in clinical diagnosis. This benchmark not only covers diagnoses from a diverse range of medical cases across various specialties but also incorporates tasks of clinical significance: treatment procedure identification, lab test ordering and medication prescriptions. Supported by structured output ontologies, CliBench enables a precise and multi-granular evaluation, offering an in-depth understanding of LLM's capability on diverse clinical tasks of desired granularity. We conduct a zero-shot evaluation of leading LLMs to assess their proficiency in clinical decision-making. Our preliminary results shed light on the potential and limitations of current LLMs in clinical settings, providing valuable insights for future advancements in LLM-powered healthcare.

Medical tasks such as diagnosis and treatment planning require precise and complex reasoning, particularly in life-critical domains. Unlike mathematical reasoning, medical reasoning demands meticulous, verifiable thought processes to ensure reliability and accuracy. However, there is a notable lack of datasets that provide transparent, step-by-step reasoning to validate and enhance the medical reasoning ability of AI models. To bridge this gap, we introduce MedReason, a large-scale high-quality medical reasoning dataset designed to enable faithful and explainable medical problem-solving in large language models (LLMs). We utilize a structured medical knowledge graph (KG) to convert clinical QA pairs into logical chains of reasoning, or ``thinking paths'', which trace connections from question elements to answers via relevant KG entities. Each path is validated for consistency with clinical logic and evidence-based medicine. Our pipeline generates detailed reasoning for various medical questions from 7 medical datasets, resulting in a dataset of 32,682 question-answer pairs, each with detailed, step-by-step explanations. Experiments demonstrate that fine-tuning with our dataset consistently boosts medical problem-solving capabilities, achieving significant gains of up to 7.7% for DeepSeek-Ditill-8B. Our top-performing model, MedReason-8B, outperforms the Huatuo-o1-8B, a state-of-the-art medical reasoning model, by up to 4.2% on the clinical benchmark MedBullets. We also engage medical professionals from diverse specialties to assess our dataset's quality, ensuring MedReason offers accurate and coherent medical reasoning. Our data, models, and code will be publicly available.

Recent advances in generative models, including large language models (LLMs), vision language models (VLMs), and diffusion models, have accelerated the field of natural language and image processing in medicine and marked a significant paradigm shift in how biomedical models can be developed and deployed. While these models are highly adaptable to new tasks, scaling and evaluating their usage presents new challenges not addressed in previous frameworks. In particular, the ability of these models to produce useful outputs with little to no specialized training data ("zero-" or "few-shot" approaches), as well as the open-ended nature of their outputs, necessitate the development of new guidelines for robust reporting of clinical generative model research. In response to gaps in standards and best practices for the development of clinical AI tools identified by US Executive Order 141103 and several emerging national networks for clinical AI evaluation, we begin to formalize some of these guidelines by building on the original MI-CLAIM checklist. The new checklist, MI-CLAIM-GEN (Table 1), aims to address differences in training, evaluation, interpretability, and reproducibility of new generative models compared to non-generative ("predictive") AI models. This MI-CLAIM-GEN checklist also seeks to clarify cohort selection reporting with unstructured clinical data and adds additional items on alignment with ethical standards for clinical AI research.

Clinical trials disruption has always represented a non negligible part of the ending of interventional studies. While the SARS-CoV-2 (COVID-19) pandemic has led to an impressive and unprecedented initiation of clinical research, it has also led to considerable disruption of clinical trials in other disease areas, with around 80% of non-COVID-19 trials stopped or interrupted during the pandemic. In many cases the disrupted trials will not have the planned statistical power necessary to yield interpretable results. This paper describes methods to compensate for the information loss arising from trial disruptions by incorporating additional information available from auxiliary data sources. The methods described include the use of auxiliary data on baseline and early outcome data available from the trial itself and frequentist and Bayesian approaches for the incorporation of information from external data sources. The methods are illustrated by application to the analysis of artificial data based on the Primary care pediatrics Learning Activity Nutrition (PLAN) study, a clinical trial assessing a diet and exercise intervention for overweight children, that was affected by the COVID-19 pandemic. We show how all of the methods proposed lead to an increase in precision relative to use of complete case data only.

Current medical retrieval benchmarks primarily emphasize lexical or shallow semantic similarity, overlooking the reasoning-intensive demands that are central to clinical decision-making. In practice, physicians often retrieve authoritative medical evidence to support diagnostic hypotheses. Such evidence typically aligns with an inferred diagnosis rather than the surface form of a patient's symptoms, leading to low lexical or semantic overlap between queries and relevant documents. To address this gap, we introduce R2MED, the first benchmark explicitly designed for reasoning-driven medical retrieval. It comprises 876 queries spanning three tasks: Q&A reference retrieval, clinical evidence retrieval, and clinical case retrieval. These tasks are drawn from five representative medical scenarios and twelve body systems, capturing the complexity and diversity of real-world medical information needs. We evaluate 15 widely-used retrieval systems on R2MED and find that even the best model achieves only 31.4 nDCG@10, demonstrating the benchmark's difficulty. Classical re-ranking and generation-augmented retrieval methods offer only modest improvements. Although large reasoning models improve performance via intermediate inference generation, the best results still peak at 41.4 nDCG@10. These findings underscore a substantial gap between current retrieval techniques and the reasoning demands of real clinical tasks. We release R2MED as a challenging benchmark to foster the development of next-generation medical retrieval systems with enhanced reasoning capabilities. Data and code are available at https://github.com/R2MED/R2MED