MACD: Multi-Agent Clinical Diagnosis with Self-Learned Knowledge for LLM

Wenliang Li, Rui Yan, Xu Zhang, Li Chen, Hongji Zhu, Jing Zhao, Junjun Li, Mengru Li, Wei Cao, Zihang Jiang, Wei Wei, Kun Zhang, Shaohua Kevin Zhou

Published: 2025/9/24

Abstract

Large language models (LLMs) have demonstrated notable potential in medical applications, yet they face substantial challenges in handling complex real-world clinical diagnoses using conventional prompting methods. Current prompt engineering and multi-agent approaches typically optimize isolated inferences, neglecting the accumulation of reusable clinical experience. To address this, this study proposes a novel Multi-Agent Clinical Diagnosis (MACD) framework, which allows LLMs to self-learn clinical knowledge via a multi-agent pipeline that summarizes, refines, and applies diagnostic insights. It mirrors how physicians develop expertise through experience, enabling more focused and accurate diagnosis on key disease-specific cues. We further extend it to a MACD-human collaborative workflow, where multiple LLM-based diagnostician agents engage in iterative consultations, supported by an evaluator agent and human oversight for cases where agreement is not reached. Evaluated on 4,390 real-world patient cases across seven diseases using diverse open-source LLMs (Llama-3.1 8B/70B, DeepSeek-R1-Distill-Llama 70B), MACD significantly improves primary diagnostic accuracy, outperforming established clinical guidelines with gains up to 22.3% (MACD). On the subset of the data, it achieves performance on par with or exceeding that of human physicians (up to 16% improvement over physicians-only diagnosis). Additionally, on the MACD-human workflow, it achieves an 18.6% improvement compared to physicians-only diagnosis. Moreover, self-learned knowledge exhibits strong cross-model stability, transferability, and model-specific personalization, while the system can generate traceable rationales, enhancing explainability. Consequently, this work presents a scalable self-learning paradigm for LLM-assisted diagnosis, bridging the gap between the intrinsic knowledge of LLMs and real-world clinical practice.

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