Role-Specialized Mixture-of-Agents with Open-Weight LLMs for Clinical Prediction

Building effective clinical decision support systems requires the synthesis of complex heterogeneous multimodal data. Such modalities include temporal electronic health records data, medical images, radiology reports, and clinical notes. Large language model (LLM)-based agents have shown impressive performance in various healthcare tasks, especially those involving textual modalities. Considering the fragmentation of healthcare data across hospital systems, collaborative agent frameworks present a promising direction to mitigate data sharing challenges. However, the effectiveness of LLM agents for multimodal clinical risk prediction remains largely unexamined. In this work, we conduct a systematic evaluation of LLM-based agents for clinical prediction tasks using large-scale real-world data. We assess performance in unimodal and multimodal settings and quantify performance gaps between single agent and multi-agent systems. Our findings highlight that single agent frameworks outperform naive multi-agent systems, are better at handling multimodal data, and are better calibrated. This underscores a critical need for improving multi-agent collaboration to better handle heterogeneous inputs. By open-sourcing our code and evaluation framework, this work offers a new benchmark to support future developments relating to agentic systems in healthcare.

Large language models applied to clinical prediction exhibit case-level heterogeneity: simple cases yield consistent outputs, while complex cases produce divergent predictions under minor prompt changes. Existing single-agent strategies sample from one role-conditioned distribution, and multi-agent frameworks use fixed roles with flat majority voting, discarding the diagnostic signal in disagreement. We propose CAMP (Case-Adaptive Multi-agent Panel), where an attending-physician agent dynamically assembles a specialist panel tailored to each case's diagnostic uncertainty. Each specialist evaluates candidates via three-valued voting (KEEP/REFUSE/NEUTRAL), enabling principled abstention outside one's expertise. A hybrid router directs each diagnosis through strong consensus, fallback to the attending physician's judgment, or evidence-based arbitration that weighs argument quality over vote counts. On diagnostic prediction and brief hospital course generation from MIMIC-IV across four LLM backbones, CAMP consistently outperforms strong baselines while consuming fewer tokens than most competing multi-agent methods, with voting records and arbitration traces offering transparent decision audits.

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.