The Optimization Paradox in Clinical AI Multi-Agent Systems

Abstract: Multi-agent artificial intelligence systems are increasingly deployed in clinical settings, yet the relationship between component-level optimization and system-wide performance remains poorly understood. We evaluated this relationship using 2,400 real patient cases from the MIMIC-CDM dataset across four abdominal pathologies (appendicitis, pancreatitis, cholecystitis, diverticulitis), decomposing clinical diagnosis into information gathering, interpretation, and differential diagnosis. We evaluated single agent systems (one model performing all tasks) against multi-agent systems (specialized models for each task) using comprehensive metrics spanning diagnostic outcomes, process adherence, and cost efficiency. Our results reveal a paradox: while multi-agent systems generally outperformed single agents, the component-optimized or Best of Breed system with superior components and excellent process metrics (85.5% information accuracy) significantly underperformed in diagnostic accuracy (67.7% vs. 77.4% for a top multi-agent system). This finding underscores that successful integration of AI in healthcare requires not just component level optimization but also attention to information flow and compatibility between agents. Our findings highlight the need for end to end system validation rather than relying on component metrics alone.