DeepER-Med: Advancing Deep Evidence-Based Research in Medicine Through Agentic AI
Authors: Zhizheng Wang, Chih-Hsuan Wei, Joey Chan, Robert Leaman, Chi-Ping Day, Chuan Wu, Mark A Knepper, Antolin Serrano Farias, +14 more
Organizations: Division of Intramural Research (DIR), National Library of Medicine (NLM), National Institutes of Health (NIH), Bethesda, MD 20892, USA · Hunterian Neurosurgical Laboratory, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA · Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA · Experimental Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA · Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA · Brain Tumor Genetics Lab, Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, MD 21287, USA · Division of Hematology/Oncology, University of Illinois Chicago, Chicago, IL 60612, USA · University of Illinois Cancer Center, Chicago, IL 60612, USA · Division of Epidemiology and Clinical Applications, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892, USA · University of Michigan Medical School, Ann Arbor, MI 48109, USA
Trustworthiness and transparency are essential for the clinical adoption of artificial intelligence (AI) in healthcare and biomedical research. Recent deep research systems aim to accelerate evidence-grounded scientific discovery by integrating AI agents with multi-hop information retrieval, reasoning, and synthesis. However, most existing systems lack explicit and inspectable criteria for evidence appraisal, creating a risk of compounding errors and making it difficult for researchers and clinicians to assess the reliability of their outputs. In parallel, current benchmarking approaches rarely evaluate performance on complex, real-world medical questions. Here, we introduce DeepER-Med, a Deep Evidence-based Research framework for Medicine with an agentic AI system. DeepER-Med frames deep medical research as an explicit and inspectable workflow of evidence-based generation, consisting of three modules: research planning, agentic collaboration, and evidence synthesis. To support realistic evaluation, we also present DeepER-MedQA, an evidence-grounded dataset comprising 100 expert-level research questions derived from authentic medical research scenarios and curated by a multidisciplinary panel of 11 biomedical experts. Expert manual evaluation demonstrates that DeepER-Med consistently outperforms widely used production-grade platforms across multiple criteria, including the generation of novel scientific insights. We further demonstrate the practical utility of DeepER-Med through eight real-world clinical cases. Human clinician assessment indicates that DeepER-Med's conclusions align with clinical recommendations in seven cases, highlighting its potential for medical research and decision support.
Recent advances in deep research systems enable large language models to retrieve, synthesize, and reason over large-scale external knowledge. In medicine, developing clinical guidelines critically depends on such deep evidence integration. However, existing benchmarks fail to evaluate this capability in realistic workflows requiring multi-step evidence integration and expert-level judgment. To address this gap, we introduce MedProbeBench, the first benchmark leveraging high-quality clinical guidelines as expert-level references. Medical guidelines, with their rigorous standards in neutrality and verifiability, represent the pinnacle of medical expertise and pose substantial challenges for deep research agents. For evaluation, we propose MedProbe-Eval, a comprehensive evaluation framework featuring: (1) Holistic Rubrics with 1,200+ task-adaptive rubric criteria for comprehensive quality assessment, and (2) Fine-grained Evidence Verification for rigorous validation of evidence precision, grounded in 5,130+ atomic claims. Evaluation of 17 LLMs and deep research agents reveals critical gaps in evidence integration and guideline generation, underscoring the substantial distance between current capabilities and expert-level clinical guideline development. Project: https://github.com/uni-medical/MedProbeBench
Navigating the deluge of heterogeneous medical data, from academic literature (PubMed) to clinical guidelines (Web) and private knowledge bases, remains a critical bottleneck for evidence-based medicine. While commercial black-box tools lack transparency, standard open-source RAG implementations frequently suffer from reasoning drift when handling complex, long-tail queries. We present DEEPMED Search, a fully open-source, agentic platform designed for transparent medical deep research. Built on a high-performance Next.js architecture, DEEPMED Search features a source-adaptive router that autonomously dispatches sub-queries to PubMed, web search, or local graph-based knowledge bases based on information density. Crucially, the platform integrates an introspective verification module, powered by a causal-consistent multi-agent debate framework, to validate retrieved evidence against diagnostic logic before synthesis. To demonstrate its robustness, we showcase DEEPMED Search's ability to autonomously decompose high-difficulty rare disease queries, filter out confounding noise, and generate structured, citation-backed research reports in minutes. By open-sourcing this software, we provide the community with a robust infrastructure to democratize access to trustworthy, glass-box medical reasoning in research and prototyping settings.
Reproducing and comparing deep research agents today is hard: the same backbone evaluated on the same benchmark can report different accuracies across papers because the harness and tool registry differ, and integrating a new model into a comparable evaluation surface costs weeks of model-specific engineering. These are symptoms of a broader reproducibility problem in deep research agent research. Here, we introduce BioMedArena, an open-source toolkit that addresses this reproducibility gap and provides an arena for comparing deep research agents under a shared evaluation environment. BioMedArena decouples six layers of biomedical agent evaluation -- benchmark loading, tool exposure, tool selection, harness mode, context management, and scoring -- and exposes 166 biomedical benchmarks and 75 biomedical tools across 9 functional families. Adding a new model, benchmark, or tool can be accomplished with a few-line provider adapter. Beyond evaluation infrastructure, BioMedArena ships a library of high-quality reference components: 6 agent harnesses (including our proposed Mutual-Evolve) and 6 context-management strategies, any of which can be equipped on any backbone. Equipping these components substantially improves all 12 backbones; on each of 8 representative biomedical benchmarks, the best equipped backbone surpasses prior state-of-the-art (SOTA), by 15.01 percentage points on average. The toolkit, configurations, and per-task traces are available at https://github.com/AI-in-Health/BioMedArena.