Organizations: School of Computing and Communications, Lancaster University · Lancaster Medical School, Lancaster University · PUC-Rio, Puc-Behring Institute for AI
Abstract
While interpretable prototype networks offer compelling case-based reasoning for clinical diagnostics, their raw continuous outputs lack the semantic structure required for medical documentation. Bridging this gap via standard Retrieval-Augmented Generation (RAG) routinely triggers ``retrieval sycophancy,'' where Large Language Models (LLMs) hallucinate post-hoc rationalizations to align with visual predictions. We introduce ProtoMedAgent, a framework that formalizes multimodal clinical reporting as an iterative, zero-gradient test-time optimization problem over a strict neuro-symbolic bottleneck. Operating on a frozen prototype backbone, we distill latent visual and tabular features into a discrete semantic memory. Online generation is strictly constrained by exact set-theoretic differentials and a reflective Scribe-Critic loop, mathematically precluding unsupported narrative claims. To safely bound data disclosure, we introduce a semantic privacy gate governed by k-anonymity and ℓ-diversity. Evaluated on a 4,160-patient clinical cohort, ProtoMedAgent achieves 91.2% Comparison Set Faithfulness where it fundamentally outperforms standard RAG (46.2%). ProtoMedAgent additionally leverages a binding ℓ-diversity phase transition to systematically reduce artifact-level membership inference risks by an absolute 9.8%.
Retrieval-Augmented Generation (RAG) is widely employed to mitigate risks such as hallucinations and knowledge obsolescence in medical question answering, yet its predominantly single-round, static retrieval paradigm misaligns with the multi-stage process of clinical reasoning. This compressed workflow induces two structural deficiencies: question-to-query translation often lacks clinically grounded semantic interpretation, and retrieval lacks iterative sufficiency feedback, making it difficult to form reliable evidence chains. We argue that both issues stem from a deeper cause: overloading a single reasoning chain with heterogeneous tasks of interpretation, exploration, and adjudication. The remedy is to reconstruct the workflow via task decoupling and dynamic multi-round exploration. To this end, we propose SEMA-RAG, a Self-Evolving Multi-Agent RAG framework for medical question answering, which assigns these roles to three specialist agents: the Interpreter Agent for clinical schema interpretation, the Explorer Agent for sufficiency-driven self-evolving retrieval, and the Arbiter Agent for evidence adjudication and answer selection. Across five benchmarks and five LLM backbones, SEMA-RAG improves the strongest baseline by +6.46 accuracy points on average, measured per backbone.
Most reported gains on agentic-LLM clinical benchmarks are often attributed to prompt engineering, yet our results suggest that larger improvements can come from architectural and engine-level design. We present MDIA, a Multi-agent Diagnostic Intelligence Agent implemented as a 7-node specialty-routed clinical reasoning graph, on the full HealthBench Professional benchmark (n = 525), on a non-fine-tuned LLM. MDIA achieves 0.6272 under OpenAI's GPT-5.4-2026-03-05, which is +3.72 pp above the performance of OpenAI's ChatGPT for Clinicians. The experimental work shows that performance lift is attributable to system architecture: specialty routing, multi-turn context preservation, drug-state safety gating, site-filtered search, length-aware synthesis, and engine-level reliability. These findings support the view that agentic clinical benchmark performance is shaped both by the underlying foundation model and the orchestration architecture. Nevertheless, we also noticed notable differences when using other models as a grader; in particular, when using Gemini 2.5 Pro, MDIA scored 0.6585, which suggests that the choice of grader is a source of variability. Robust evaluation of LLMs would therefore require assessment across several independent grader models.
We present Multi-Agent Reasoning and Coordination (MARC), an open-source framework that replaces monolithic LLM prompting with deterministic multi-agent orchestration for clinical reasoning. MARC coordinates role-specialized agents for extraction, reasoning, answer generation, and evaluation, with explicit context passing and traceable intermediate outputs, enabling stage-wise failure attribution. We additionally introduce a Decomposer module that generates task-specific agent prompts from a plain-language description, eliminating manual prompt engineering. The framework supports both API-based and local CPU-compatible deployments and is entirely configurable via YAML, without code modifications. MARC is designed to be model-agnostic, interpretable, and accessible to clinical domain experts without programming expertise. The full framework is available at https://github.com/Penn-RAIL/MARC-v1.