Large Language Models (LLMs) show great potential as clinical agents, yet existing benchmarks reduce clinical workflows to static predictions or unconstrained Markov Decision Processes (MDPs) with coarse action sets. To address this, we introduce GPAgentBench-2K, the first Constrained MDP (CMDP) LLM-agent benchmark for primary-care clinical decision-making, constructed from expert-validated records of real-world GP encounters. Our environment models a full spectrum of six foundational clinical actions, imposes a topological workflow prior over the action space, and operationalizes safety-informed abstention as a first-class outcome. Evaluating 16 state-of-the-art LLMs reveals a significant performance degradation as the action space scales. Crucially, we uncover a clinical quality-safety gap: even frontier models with the highest diagnosis accuracy violate safety constraints in over half of high-risk cases. Finally, we establish a reference point using Constrained Group Relative Policy Optimization (C-GRPO), and show that while explicitly modeling constraints improves performance over unconstrained RL methods, it remains far from clinically acceptable safety.
Clinical decision-making often involves prioritizing ethical values, such as beneficence, non-maleficence, respecting a patient's autonomy, and justice. Recent work has begun to assess how large language models (LLMs) make such subjective, value-laden clinical judgments. However, evaluations of LLM decision-making in rare disease care contexts, where ethical tensions are ubiquitous and where scarce prior information likely impacts LLM behavior, are still lacking. Here, we present a benchmark of 208 clinically grounded rare disease vignettes, each of which presents genuine, high-stakes conflicts. When prompting 11 state-of-the-art LLMs to choose between clinically defensible yet ethically conflicting next steps embedded within these vignettes, we found that all evaluated models consistently prioritized justice over other core bioethical principles. Specifically, models overwhelmingly favor equal resource allocation over need-based considerations, indicating LLMs' limited responsiveness to differences in clinical severity or situational context. We also identify a strong authority-framing effect: models favor justice in committee-based contexts and shift toward beneficence and autonomy only when final decisions are framed as being made by clinicians or patients respectively. Our work suggests that institutional pressures surrounding rare disease resource utilization may be silently reflected in LLM-based decision support systems, with finer ethical considerations disregarded.
Md Asaduzzaman Jabin, Khoa Le, Lin Zhao +1cs.LG cs.CV
Clinical decision-making is inherently experience-driven: physicians progressively refine their reasoning by synthesizing patient history, multimodal observations, and prior diagnostic experiences across interactions. In contrast, current multimodal large language model (MLLM)-based medical AI agents largely operate as stateless inference systems, generating decisions independently for each interaction without retaining or internalizing experiential knowledge. This discrepancy limits their ability to progressively improve reasoning reliability through usage and adapt to longitudinal patient contexts in real-world clinical workflows. In this study, we propose Medical Structured Multimodal Memory (MSM-Mem), an agentic memory framework that enables medical AI agents to evolve through accumulated clinical experiences. MSM-Mem organizes heterogeneous clinical experiences into semantic, episodic, and visual memory and incrementally updates them during inference, allowing the agent to retrieve prior experiences to inform current reasoning and progressively refine decision-making over time. Evaluations on MoE-LLaVA backbones demonstrate consistent performance improve- ments with further gains observed through continued usage. In general, MSM-Mem offers a viable pathway toward medical AI agents capable of evolving their reasoning competence in a manner analogous to the way clinicians learn from practice over time.
Emergency-department (ED) triage requires clinicians to rapidly identify patients who need immediate attention, determine who can safely wait, and prioritize limited clinical resources. At presentation, however, information may be limited to a chief complaint and initial vital signs. Clinically important details, including symptom onset and progression, associated symptoms, medical history, and medication use, are often obtained through focused conversation. Effective triage therefore requires clinicians to identify information gaps, ask appropriate follow-up questions, and update their assessment as new evidence becomes available. Most existing ED benchmarks evaluate acuity prediction from a fixed clinical snapshot. Although this formulation measures predictive performance after patient information has been assembled, it does not capture the interactive process through which triage-relevant evidence is elicited and interpreted. Existing medical dialogue datasets support the study of clinical communication, but dialogue statements are not always linked to temporally ordered events in the electronic health record (EHR). We introduce EHR2Dial-Triage, an agentic conversation-generation framework and benchmark grounded in MIMIC-IV-ED. The framework constructs triage conversations under explicit role-based and temporal information boundaries. Each accepted patient disclosure is linked to its supporting EHR event and the first dialogue turn at which it becomes available. EHR2Dial-Triage enables controlled evaluation of information elicitation, evidence use, five-level Emergency Severity Index prediction, and patient-facing communication across models and patient personas. It provides a structured setting for studying conversational triage as a dynamic process of clinical information acquisition, reasoning, and communication.
Sequential clinical decision-making often involves more than maximizing average efficacy. Clinicians may need to simultaneously optimize clinically relevant tails of the outcome distribution, control treatment-related risk, and choose among multiple treatment options. Existing quantile dynamic treatment regime (DTR) methods capture distributional features of treatment outcomes but remain largely restricted to efficacy-only objectives and binary treatments. To address these limitations, we propose Risk-Aware Quantile Dynamic Treatment Regimes (RQDTR), a unified framework that optimizes a prespecified quantile of the cumulative potential outcome while explicitly incorporating treatment-related risk. We also develop an angle-based formulation for jointly learning decision rules across multiple treatment categories. Our framework includes three interpretable subclasses: efficacy-only quantile learning, constraint-based learning with population-level risk control, and utility-based learning through a composite benefit-risk utility. Theoretically, we establish identification and oracle equivalence, Fisher consistency of the smoothed surrogate, consistency of the estimated regime, and finite-sample performance error rates. Extensive simulation studies and applications to All of Us major depressive disorder and MIMIC-III sepsis data demonstrate that RQDTR improves tail-oriented efficacy and achieves more favorable benefit-risk trade-offs than existing quantile DTR methods.
Background: Respiratory specialty care requires multimodal interpretation, longitudinal risk assessment, guideline-concordant intervention, and whole-course management, which are poorly represented by examination-oriented medical benchmarks. Objective: To develop RESPClinBench, a real-world scenario-based benchmark for respiratory clinical decision-making, and evaluate seven contemporary large language models across AECOPD-PIM and PNBIM. Methods: RESPClinBench cases were adapted from de-identified respiratory clinical data. Three attending-level respiratory physicians revised cases, reference answers, and atomic clinical-action points, while one senior respiratory specialist performed cross-review and final adjudication. AECOPD-PIM comprised 427 open-ended COPD cases, and PNBIM comprised 196 multimodal pulmonary nodule cases combining chest CT with structured clinical information. Seven models generated 4,361 responses through standardized API inference with temperature 0 and a maximum output length of 8192 tokens. An automated framework calculated the final score as the arithmetic mean of atomic-action recall and rubric-based LLM-as-a-Judge assessment. Results: Across 623 cases, the mean final score was 68.58. Qwen3.6-27B ranked first overall at 71.22, Qwen3.5-397B-A17B led PNBIM at 72.48, and Qwen3.6-27B led AECOPD-PIM at 71.11. Imaging hallucination and serious medical risk occurred in 31.85% and 8.16% of PNBIM responses; medication-safety risk and serious medical risk occurred in 26.93% and 1.44% of AECOPD-PIM responses. Conclusions: RESPClinBench identifies task-specific limitations in multimodal pulmonary nodule assessment and longitudinal COPD management. Combining explicit clinical-action coverage, holistic evaluation, and independent safety flags provides a clinically grounded basis for model selection and prospective validation.
Rare diseases represent one of the most challenging settings for clinical decision-making, where heterogeneous presentations, sparse evidence and limited expertise create persistent uncertainty throughout the care pathway. Although artificial intelligence could help, existing systems largely address isolated tasks, particularly diagnosis, and usually rely on downstream investigations rather than information available at initial presentation. Here we show that clinical AI performance under uncertainty can be improved not by scaling a single model, but by exploiting the diversity of multiple imperfect reasoning systems. Across heterogeneous large language models, we identify divergent reasoning trajectories with complementary error patterns and develop RareLens, which learns to reconcile these perspectives into actionable decisions across four stages of rare disease care: risk screening, diagnosis, treatment planning and prognosis prediction. Built on RarelensBench, a real-world dataset of 157,525 cases spanning all 33 Orphanet categories and more than 7,000 conditions, RareLens outperformed every frontier model tested, including GPT-5, DeepSeek-R1, Claude-3.7-Sonnet and Gemini-2.5-Pro, across all stages. It achieved an area under the curve of 0.917 for screening and top-1 accuracies of 65.5% and 89.8% for diagnosis and treatment. In an external evaluation involving 1,287 cases and 23 physicians, autonomous RareLens and physicians assisted by RareLens both outperformed unaided physicians, while demonstrating that effective human-AI collaboration requires more than simply providing model outputs. These findings establish divergent model reasoning as an exploitable source of information and suggest a general strategy for building AI systems that operate reliably under high clinical uncertainty.
In this work, we introduce LongMedBench, a real-world EHR-based benchmark for long-horizon clinical decision-making. Prior evaluations of LLM-based medical agents have largely emphasized short-context knowledge QA and tool use. However, real-world medical care is inherently longitudinal, and clinicians must aggregate evidence across repeated visits, tests, and evolving treatments. Therefore, long-horizon interaction is essential for realistic assessment. LongMedBench is constructed via a reproducible pipeline that integrates MIMIC-IV admission records and clinical notes into time-series event streams and long-context memory datasets, enabling long-horizon, multi-session interactions between agents and a clinical environment. It comprises 335 patients, with 19.72 inpatient visits per patient on average and 44.91 medical events per visit. Guided by the long-horizon decision process, we propose an evaluation taxonomy with three suites: fact-based QA, temporal reasoning, and long-horizon decision-making. This taxonomy measures how agents understand and leverage historical patient information over extended horizons. Our experiments show that while recent LLMs can make good use of explicit timestamps, they have challenges in implicit time inference; The RAG and agent memory system can improve the performance of information retrieval tasks, but the performance of decision-making tasks is highly dependent on the model's immediate context.
Offline reinforcement learning (ORL) offers the potential to improve the quality of clinical decision-making using historical electronic health record (EHR) data. Current training and evaluative practices in this field rely heavily on EHR datasets that have been temporally discretised into fixed, regular time intervals. Discretisation creates fictional representations of complex clinical scenarios and compromises the generalisability of retrospective model evaluations. In this paper, we introduce Insulin4RL, a healthcare ORL dataset featuring naturally irregular inputs and actions from real clinical trajectories. Derived from MIMIC-IV, Insulin4RL comprises over 375,000 labelled decisions across 12,209 patients requiring insulin infusion titration in the Intensive Care Unit. The dataset can thus be used for research into ORL model performance under realistic clinical sampling assumptions. We provide a description of the dataset's structure and characteristics, baseline performance metrics using model-free offline reinforcement learning, and a standardised evaluation protocol using fitted Q-evaluation. We conclude with suggested areas for future research that could be addressed using this resource.
Strabismus is a common ocular disorder that requires fine-grained subtype diagnosis for individualized treatment planning. However, existing deep learning methods mainly provide diagnostic predictions without transparent reasoning, while recent large vision-language models (LVLMs), although promising for joint image understanding and report generation, remain highly prone to hallucination in this evidence-sensitive and rule-driven medical task. To address these challenges, we propose MAGIS, an evidence-based Multi-AGent reasoning for Interpretable Strabismus diagnosis framework. MAGIS transforms black-box end-to-end generation into a structured diagnostic process consisting of candidate hypothesis generation, dual-evidence constrained context, evidence-based corrective verification, and report generation. Specifically, we introduce a Dual-Evidence Constrained Context (DECC) mechanism that jointly organizes visual evidence from the photograph of the nine cardinal positions of gaze and evidence-based clinical diagnostic rules into a constrained context for reliable diagnostic reasoning. We further develop an Evidence-Based Corrective Verification (EBCV) mechanism that verifies whether the current diagnostic hypothesis is supported by visual evidence, heatmap-based visual cues, and evidence-based clinical diagnostic rules. Hypothesis refinement is triggered when inconsistency is detected. Experiments on a fine-grained strabismus benchmark demonstrate that MAGIS not only significantly outperforms other state-of-the-art diagnostic systems, improving the weighted F1 score from 72.0% to 91.3%, but also substantially improves the clinical reliability (consistency, alignment, and completeness) of generated diagnostic reports. These results demonstrate that MAGIS provides an effective solution for building accurate, evidence-based, and clinically interpretable strabismus diagnosis systems.
Large language models (LLMs) are increasingly proposed as clinical agents, yet static, single-turn benchmarks cannot capture how a model dynamically delivers care across an encounter: gathering information, planning treatment, and adapting longitudinal management across successive patient states. Medical education has long addressed an analogous challenge through standardized patients (SPs): trained actors who consistently portray clinical cases, enabling realistic practice and objective, scripted assessment. Here we introduce MedSP1000, an SP-derived interactive benchmark for clinical-agent evaluation, including 1,638 SP cases with 24,602 trajectory-level peer-reviewed rubrics. MedSP1000 converts peer-reviewed SP teaching cases into executable scenarios with defined SP case scripts, clinical environment contexts, and human-validated structured rubric. In each simulation evaluation run, a clinical agent interacts in closed loop with a patient agent and an environment controller, and its behaviour is scored throughout the encounter against expert criteria specified in the original materials. Applying MedSP1000 to a range of general-purpose and medically specialized LLMs, we find that performance on static benchmarks does not reliably translate to such educational scenarios. The best-performing model, GPT-5.5, completes only 60.4% of expert-defined rubric items, whereas the strongest medically specialized model reaches 40.0%; increasing test-time compute produces no measurable gain. These results suggest that current LLMs, including agentic systems tuned for medicine, are not yet reliable enough to be safely integrated into actual clinical practice. More broadly, MedSP1000 shows how process-level, SP-style evaluation can reveal clinically relevant failure modes that single-turn benchmarks miss.
Large language models (LLMs) have been widely adopted in healthcare, yet they still encounter significant challenges in complex clinical decision-making scenarios. Existing benchmarks primarily assess LLM performance in single-course settings and lack systematic evaluation in multi-course scenarios, where a patient's condition evolves over time. To address this gap, we propose ClinicalMC, a benchmark for multi-course clinical decision-making. It includes 1,275 Chinese and 5,804 English samples across four stages from admission to discharge. These stages cover triage, first-course examination/diagnosis/treatment, subsequent multi-course examination/assessment/treatment, and final diagnosis. In ClinicalMC, patients in the English dataset undergo an average of 5.11 clinical courses, whereas those in the Chinese dataset undergo 3.42. To assess LLM performance, we construct a multi-agent evaluation framework that includes patient, examiner, and doctor agents. Based on the benchmark and framework, we design two experimental settings -- a single-turn static setting and a multi-turn dynamic setting -- and assess three categories of LLMs: 1) closed-source LLMs like GPT5-mini; 2) open-source LLMs like DeepSeek-V3.2; and 3) medical LLMs like HuatuoGPT-o1. Through extensive evaluation, we aim to better understand LLM performance in the medical domain and support its effective deployment in healthcare.