# Managing Uncertainty in LLM-based Multi-Agent System Operation

arXiv: https://arxiv.org/abs/2602.23005 · HTML: https://mlsanity.com/paper/2602.23005/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 7 of its 38 references that are in the map.
- First posted on arXiv 26 Feb 2026.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 7 of 7)

- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [A Survey of LLM-based Agents in Medicine: How far are we from Baymax?](https://mlsanity.com/paper/2502.11211/) (2025)
- [A Survey of Uncertainty Estimation Methods on Large Language Models](https://mlsanity.com/paper/2503.00172/) (2025)
- [Large Language Models for Anomaly and Out-of-Distribution Detection: A Survey](https://mlsanity.com/paper/2409.01980/) (2024)
- [From Aleatoric to Epistemic: Exploring Uncertainty Quantification Techniques in Artificial Intelligence](https://mlsanity.com/paper/2501.03282/) (2025)
- [Prediction Surface Uncertainty Quantification in Object Detection Models for Autonomous Driving](https://mlsanity.com/paper/2107.04991/) (2021)
- [Static Sandboxes Are Inadequate: Modeling Societal Complexity Requires Open-Ended Co-Evolution in LLM-Based Multi-Agent Simulations](https://mlsanity.com/paper/2510.13982/) (2025)

## Built on by (most cited first, 1 of 1)

- [Uncertainty Quantification for LLM Agents: A Taxonomy, an Evaluation Protocol, and an Empirical Study](https://mlsanity.com/paper/2609.07395/) (2026)

## Abstract (arXiv)

Applying LLM-based multi-agent software systems in safety-critical domains such as lifespan echocardiography introduces system-level risks that cannot be addressed by improving model accuracy alone. During system operation, beyond individual LLM behavior, uncertainty propagates through agent coordination, data pipelines, human-in-the-loop interaction, and runtime control logic. Yet existing work largely treats uncertainty at the model level rather than as a first-class software engineering concern. This paper approaches uncertainty from both system-level and runtime perspectives. We first differentiate epistemological and ontological uncertainties in the context of LLM-based multi-agent software system operation. Building on this foundation, we propose a lifecycle-based uncertainty management framework comprising four mechanisms: representation, identification, evolution, and adaptation. The uncertainty lifecycle governs how uncertainties emerge, transform, and are mitigated across architectural layers and execution phases, enabling structured runtime governance and controlled adaptation. We demonstrate the feasibility of the framework using a real-world LLM-based multi-agent echocardiographic software system developed in clinical collaboration, showing improved reliability and diagnosability in diagnostic reasoning. The proposed approach generalizes to other safety-critical LLM-based multi-agent software systems, supporting principled operational control and runtime assurance beyond model-centric methods.