MedAgent-R1: Faithfulness-Aware Reinforcement Learning for Evidence-Grounded Medical Reasoning

Faithful reasoning is essential in medicine, where clinical decisions require transparent justification grounded in reliable evidence. Current medical LLMs either lack active access to evidence or use retrieved evidence without supervising how it should be appraised and applied during reasoning. To address this, we formalize evidence-based medicine principles as process-level criteria and introduce FaithMed, a framework that combines clinician-designed, automatically refined rubrics with reinforcement learning using step-level process reward assignment and advantage grouping. Across seven medical benchmarks, FaithMed improves over agentic-search baselines (+9% on average) and outcome-only RL (+5.8%), while raising average evidence-based medicine rubric scores over agentic-search Qwen3 baselines (+15.5%). This work demonstrates that explicit step-level supervision can improve both task success and the faithfulness of the reasoning process. Code is available at https://github.com/cxcscmu/FaithMed.

Retrieval-augmented generation evaluation checks whether model claims are factually grounded in retrieved documents. It does not check whether retrieved evidence is attributed to the correct entity. A clinical RAG response can pass every automated check (zero hallucinations, near-perfect faithfulness, real citations) while presenting drug Y's clinical evidence as evidence about queried drug X. We term this deceptive grounding (DG): a failure invisible to faithfulness, hallucination, and citation checks because every claim is sourced from a real document, about the wrong entity. Using a controlled factorial benchmark across 13 models, we find DG rates spanning 8-87% at peak adversarial conditions. Medical and biomedical fine-tuned models reach up to 86.7%; domain specialization amplifies the failure rather than mitigating it. A controlled ablation identifies the mechanism: removing entity-specific clinical evidence from retrieved documents eliminates entity-attribution failure entirely, shifting all failures to confabulation. The two failure modes respond to the same trigger, taking different paths. Production measurement across 740 drug-disease pairs finds 7.8% overall DG in a deployed RAG system, rising to 13.6% for recently approved drugs. Entity-attribution verification (checking that cited evidence applies to the queried entity) detects DG at 97.0% precision and 98.7% DG recall (IPW-adjusted human gold standard); no existing framework implements it.

Treatment reasoning underpins every therapeutic decision, integrating disease context, comorbidities, medications, contraindications, and evolving biomedical knowledge to select an appropriate therapy. It is inherently iterative: candidates are weighed against many constraints, revised as evidence emerges, and grounded in verifiable sources. Here we introduce ATHENA-R1, an AI agent for treatment reasoning across all FDA approved drugs since 1939, trained by reinforcement learning over a universe of 212 biomedical tools. At each step it identifies missing information, selects and runs relevant tools, and incorporates the evidence. To train it without human-annotated traces, we build a two-level self-learning framework: multi-agent systems construct the tools, tasks, and reasoning trajectories for supervised fine-tuning, then reinforcement learning with scientific feedback rewards reasoning quality (evidence gathering, grounded tool use, logical non-redundancy). Across five benchmarks of 3,168 drug reasoning tasks and 456 patient treatment cases, ATHENA-R1 outperforms language models and tool-use systems, reaching 94.7% accuracy on open-ended drug reasoning and 82.9% on treatment reasoning, 17.8 and 10.7 points above GPT-5. In blinded evaluations by experts from 28 rare disease organizations, it is preferred over reference models on all criteria, and physicians rated it favorably on complex hospitalized cardiovascular and infectious-disease cases. Adverse-event hypotheses it generated, tested in electronic health records from 5.4 million patients, reached adjusted odds ratios of 1.48-1.84, with no elevation among negative controls. Because it requires knowing what evidence to seek before concluding, treatment reasoning has long been hard for AI; we show it can be reframed as a learnable process of iterative evidence gathering that reinforcement learning can train AI to perform.