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Abstract:Large language models have achieved strong performance on medical reasoning benchmarks, yet their deployment in clinical settings demands rigorous verification to ensure factual accuracy. While reward models offer a scalable approach for reasoning trace verification, existing methods face two limitations: they produce only scalar reward values without explicit justification, and they rely on single-pass retrieval that precludes adaptive knowledge access as verification unfolds. We introduce $\method$, an agentic framework that addresses these limitations by training medical reasoning verifiers to iteratively query external medical corpora during evaluation. Our approach combines tool-augmented verification with an iterative reinforcement learning paradigm that requires only trace-level supervision, alongside an adaptive curriculum mechanism that dynamically adjusts training data distribution. Across four medical reasoning benchmarks, $\method$ achieves substantial gains over existing methods, improving MedQA accuracy by 23.5% and MedXpertQA by 32.0% relative to the base generator in particular. Crucially, $\method$ demonstrates an $\mathbf{8\times}$ reduction in sampling budget requirement compared to prior reward model baselines. These findings establish that grounding verification in dynamically retrieved evidence offers a principled path toward more reliable medical reasoning systems.
Abstract:Biomedical retrieval-augmented generation (RAG) can ground LLM answers in medical literature, yet long-form outputs often contain isolated unsupported or contradictory claims with safety implications. We introduce MedRAGChecker, a claim-level verification and diagnostic framework for biomedical RAG. Given a question, retrieved evidence, and a generated answer, MedRAGChecker decomposes the answer into atomic claims and estimates claim support by combining evidence-grounded natural language inference (NLI) with biomedical knowledge-graph (KG) consistency signals. Aggregating claim decisions yields answer-level diagnostics that help disentangle retrieval and generation failures, including faithfulness, under-evidence, contradiction, and safety-critical error rates. To enable scalable evaluation, we distill the pipeline into compact biomedical models and use an ensemble verifier with class-specific reliability weighting. Experiments on four biomedical QA benchmarks show that MedRAGChecker reliably flags unsupported and contradicted claims and reveals distinct risk profiles across generators, particularly on safety-critical biomedical relations.
Abstract:Clinical practice guidelines (CPGs) provide evidence-based recommendations for patient care; however, integrating them into Artificial Intelligence (AI) remains challenging. Previous approaches, such as rule-based systems, face significant limitations, including poor interpretability, inconsistent adherence to guidelines, and narrow domain applicability. To address this, we develop and validate CPGPrompt, an auto-prompting system that converts narrative clinical guidelines into large language models (LLMs). Our framework translates CPGs into structured decision trees and utilizes an LLM to dynamically navigate them for patient case evaluation. Synthetic vignettes were generated across three domains (headache, lower back pain, and prostate cancer) and distributed into four categories to test different decision scenarios. System performance was assessed on both binary specialty-referral decisions and fine-grained pathway-classification tasks. The binary specialty referral classification achieved consistently strong performance across all domains (F1: 0.85-1.00), with high recall (1.00 $\pm$ 0.00). In contrast, multi-class pathway assignment showed reduced performance, with domain-specific variations: headache (F1: 0.47), lower back pain (F1: 0.72), and prostate cancer (F1: 0.77). Domain-specific performance differences reflected the structure of each guideline. The headache guideline highlighted challenges with negation handling. The lower back pain guideline required temporal reasoning. In contrast, prostate cancer pathways benefited from quantifiable laboratory tests, resulting in more reliable decision-making.




Abstract:Unstructured notes within the electronic health record (EHR) contain rich clinical information vital for cancer treatment decision making and research, yet reliably extracting structured oncology data remains challenging due to extensive variability, specialized terminology, and inconsistent document formats. Manual abstraction, although accurate, is prohibitively costly and unscalable. Existing automated approaches typically address narrow scenarios - either using synthetic datasets, restricting focus to document-level extraction, or isolating specific clinical variables (e.g., staging, biomarkers, histology) - and do not adequately handle patient-level synthesis across the large number of clinical documents containing contradictory information. In this study, we propose an agentic framework that systematically decomposes complex oncology data extraction into modular, adaptive tasks. Specifically, we use large language models (LLMs) as reasoning agents, equipped with context-sensitive retrieval and iterative synthesis capabilities, to exhaustively and comprehensively extract structured clinical variables from real-world oncology notes. Evaluated on a large-scale dataset of over 400,000 unstructured clinical notes and scanned PDF reports spanning 2,250 cancer patients, our method achieves an average F1-score of 0.93, with 100 out of 103 oncology-specific clinical variables exceeding 0.85, and critical variables (e.g., biomarkers and medications) surpassing 0.95. Moreover, integration of the agentic system into a data curation workflow resulted in 0.94 direct manual approval rate, significantly reducing annotation costs. To our knowledge, this constitutes the first exhaustive, end-to-end application of LLM-based agents for structured oncology data extraction at scale




Abstract:Objective: Fluoropyrimidines are widely prescribed for colorectal and breast cancers, but are associated with toxicities such as hand-foot syndrome and cardiotoxicity. Since toxicity documentation is often embedded in clinical notes, we aimed to develop and evaluate natural language processing (NLP) methods to extract treatment and toxicity information. Materials and Methods: We constructed a gold-standard dataset of 236 clinical notes from 204,165 adult oncology patients. Domain experts annotated categories related to treatment regimens and toxicities. We developed rule-based, machine learning-based (Random Forest, Support Vector Machine [SVM], Logistic Regression [LR]), deep learning-based (BERT, ClinicalBERT), and large language models (LLM)-based NLP approaches (zero-shot and error-analysis prompting). Models used an 80:20 train-test split. Results: Sufficient data existed to train and evaluate 5 annotated categories. Error-analysis prompting achieved optimal precision, recall, and F1 scores (F1=1.000) for treatment and toxicities extraction, whereas zero-shot prompting reached F1=1.000 for treatment and F1=0.876 for toxicities extraction.LR and SVM ranked second for toxicities (F1=0.937). Deep learning underperformed, with BERT (F1=0.873 treatment; F1= 0.839 toxicities) and ClinicalBERT (F1=0.873 treatment; F1 = 0.886 toxicities). Rule-based methods served as our baseline with F1 scores of 0.857 in treatment and 0.858 in toxicities. Discussion: LMM-based approaches outperformed all others, followed by machine learning methods. Machine and deep learning approaches were limited by small training data and showed limited generalizability, particularly for rare categories. Conclusion: LLM-based NLP most effectively extracted fluoropyrimidine treatment and toxicity information from clinical notes, and has strong potential to support oncology research and pharmacovigilance.
Abstract:Suicide remains one of the main preventable causes of death among active service members and veterans. Early detection and prediction are crucial in suicide prevention. Machine learning techniques have yielded promising results in this area recently. This study aims to assess and summarize current research and provides a comprehensive review regarding the application of machine learning techniques in assessing and predicting suicidal ideation, attempts, and mortality among members of military and veteran populations. A keyword search using PubMed, IEEE, ACM, and Google Scholar was conducted, and the PRISMA protocol was adopted for relevant study selection. Thirty-two articles met the inclusion criteria. These studies consistently identified risk factors relevant to mental health issues such as depression, post-traumatic stress disorder (PTSD), suicidal ideation, prior attempts, physical health problems, and demographic characteristics. Machine learning models applied in this area have demonstrated reasonable predictive accuracy. However, additional research gaps still exist. First, many studies have overlooked metrics that distinguish between false positives and negatives, such as positive predictive value and negative predictive value, which are crucial in the context of suicide prevention policies. Second, more dedicated approaches to handling survival and longitudinal data should be explored. Lastly, most studies focused on machine learning methods, with limited discussion of their connection to clinical rationales. In summary, machine learning analyses have identified a wide range of risk factors associated with suicide in military populations. The diversity and complexity of these factors also demonstrates that effective prevention strategies must be comprehensive and flexible.
Abstract:Cardiovascular events, such as heart attacks and strokes, remain a leading cause of mortality globally, necessitating meticulous monitoring and adjudication in clinical trials. This process, traditionally performed manually by clinical experts, is time-consuming, resource-intensive, and prone to inter-reviewer variability, potentially introducing bias and hindering trial progress. This study addresses these critical limitations by presenting a novel framework for automating the adjudication of cardiovascular events in clinical trials using Large Language Models (LLMs). We developed a two-stage approach: first, employing an LLM-based pipeline for event information extraction from unstructured clinical data and second, using an LLM-based adjudication process guided by a Tree of Thoughts approach and clinical endpoint committee (CEC) guidelines. Using cardiovascular event-specific clinical trial data, the framework achieved an F1-score of 0.82 for event extraction and an accuracy of 0.68 for adjudication. Furthermore, we introduce the CLEART score, a novel, automated metric specifically designed for evaluating the quality of AI-generated clinical reasoning in adjudicating cardiovascular events. This approach demonstrates significant potential for substantially reducing adjudication time and costs while maintaining high-quality, consistent, and auditable outcomes in clinical trials. The reduced variability and enhanced standardization also allow for faster identification and mitigation of risks associated with cardiovascular therapies.




Abstract:Medical QA systems powered by Retrieval-Augmented Generation (RAG) models support clinical decision-making but may introduce biases related to race, gender, and social determinants of health. We systematically evaluate biases in RAG-based LLM by examining demographic-sensitive queries and measuring retrieval discrepancies. Using datasets like MMLU and MedMCQA, we analyze retrieval overlap and correctness disparities. Our findings reveal substantial demographic disparities within RAG pipelines, emphasizing the critical need for retrieval methods that explicitly account for fairness to ensure equitable clinical decision-making.




Abstract:Large language models (LLMs) are increasingly utilized in healthcare applications. However, their deployment in clinical practice raises significant safety concerns, including the potential spread of harmful information. This study systematically assesses the vulnerabilities of six LLMs to three advanced black-box jailbreaking techniques within medical contexts. To quantify the effectiveness of these techniques, we propose an automated and domain-adapted agentic evaluation pipeline. Experiment results indicate that leading commercial and open-source LLMs are highly vulnerable to medical jailbreaking attacks. To bolster model safety and reliability, we further investigate the effectiveness of Continual Fine-Tuning (CFT) in defending against medical adversarial attacks. Our findings underscore the necessity for evolving attack methods evaluation, domain-specific safety alignment, and LLM safety-utility balancing. This research offers actionable insights for advancing the safety and reliability of AI clinicians, contributing to ethical and effective AI deployment in healthcare.
Abstract:Recent advancements in large language models have demonstrated their potential in numerous medical applications, particularly in automating clinical trial matching for translational research and enhancing medical question answering for clinical decision support. However, our study shows that incorporating non decisive sociodemographic factors such as race, sex, income level, LGBT+ status, homelessness, illiteracy, disability, and unemployment into the input of LLMs can lead to incorrect and harmful outputs for these populations. These discrepancies risk exacerbating existing health disparities if LLMs are widely adopted in healthcare. To address this issue, we introduce EquityGuard, a novel framework designed to detect and mitigate the risk of health inequities in LLM based medical applications. Our evaluation demonstrates its efficacy in promoting equitable outcomes across diverse populations.