EGIP: An Evidence-Grounded Interaction Protocol for Clinical Agents

Interactive clinical agents operate under partial observability, so reliable care depends on reaching the correct diagnosis through evidence-grounded, safe interactions. Yet existing agents struggle to convert experience into reusable process knowledge with explicit provenance and authority. To address this gap, we introduce MediSkill-Evo, which self-evolves governed process knowledge without fine-tuning the backbone. It realizes this self-evolution by updating clinical, process, symbolic, and visual knowledge in four typed banks under type-specific validation and scope rules. The Process-Constrained Preference Harness then turns validated knowledge into action by grounding candidates in evidence and prioritizing safer decisions. We evaluate on 300 MIMIC-IV-derived FullChain encounters, 180 hard-isolation conditions covering six process obligations, and 100 multimodal NEJM image-diagnosis cases. On Qwen FullChain, MediSkill-Evo improves diagnosis accuracy by 7.81% and treatment-intent coverage by 70.67% over the best-performing prior agent, while reducing critical failures by 43.04%. Under stress, it improves the stress-process composite by 7.77% and required-action completion by 12.41% over the best-performing agent for each metric, with stronger patient-fact, temporal-evidence, and triage-red-flag recovery and no controller-scored errors in unavailable-evidence, treatment, and triage safety checks. On multimodal NEJM diagnosis, MediSkill-Evo with optional MedSAM localization improves diagnosis accuracy by 2.56% and core score by 18.96% over the best-performing memory agent. Code is available at https://anonymous.4open.science/r/mediskill-evo_anonymous-68E7.

Clinical diagnosis is an active evidence-seeking process in which clinicians acquire evidence, update competing hypotheses, and decide when the available evidence is sufficient for diagnosis. Yet many medical diagnosis systems built around large language models (LLMs) still formulate diagnosis as static case-to-answer prediction, with limited support for evidence acquisition. Agentic LLMs offer a dynamic alternative through tool use and intermediate diagnostic trajectories, but existing systems often under-specify how patient evidence should be exposed, scaffolded, and controlled at runtime. We introduce EviDx, an evidence-aware active diagnosis framework that pairs patient-specific diagnostic environments with a clinical diagnostic scaffold and an observer-guided runtime harness. In EviDx, $\mathcal{E}$-Synthesis constructs interactive environments from raw clinical cases; the scaffold organizes role-specialized agents, evidence tools, and evolving evidence states; and the harness regulates diagnostic termination by tracking uncertainty and evidence coverage. A 3-level evaluation pyramid assesses execution robustness, reasoning dynamics, and diagnostic outcomes. Experiments show that EviDx improves diagnostic performance and process stability while revealing model-dependent capability boundaries.

Large language models (LLMs) are increasingly used for health-related decision support. Yet most evaluations treat diagnosis as a single-shot task with complete information provided upfront, often as a multiple-choice selection. This diverges from clinical practice, where diagnosis is interactive and open-ended, involving sequential hypothesis refinement through targeted questioning. We address this gap. We build MeDxBench, a large-scale benchmark of 4,421 clinical cases across 20 specialties. We further propose MeDxAgent, a multi-agent consultation system for interactive diagnosis, and systematically study its prompt-, flow- and agent-level design choices. MeDxAgent achieves a 10.3% accuracy gain over the baseline on MeDxBench, closing 52.3% of the gap to a full-information oracle. We find that specific design choices: collecting demographics first, passing summarized dialogue for diagnosis, and feeding candidate diagnoses for targeted questioning, improve accuracy, mirroring how physicians reason, though their effect emerges fully only in combination. Code and dataset will be released upon publication.