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

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

arXiv.org Artificial Intelligence

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). In direct comparison with physician-only diagnosis under the same evaluation protocol, MACD achieves comparable or superior performance, with improvements up to 16%. Furthermore, the MACD-human workflow yields an 18.6% improvement over physician-only diagnosis, demonstrating the synergistic potential of human-AI collaboration. Notably, the self-learned clinical knowledge exhibits strong cross-model stability, transferability across LLMs, and capacity for model-specific personalization.This work thus presents a scalable self-learning paradigm that bridges the gap between the intrinsic knowledge of LLMs.