Uncertainty Quantification for Large Language Models: MUSE, a Multi-LLM Subset Ensemble Approach

Mon, 04 May 2026 00:00:00 +0000

Uncertainty quantification (UQ) and calibration for large language models — a simple, information-theoretic method that aggregates multiple LLMs for reliable confidence estimates in high-stakes decision-making.

Lead: This project was led by Maya Kruse, a former NLP Data Scientist at the LARK Lab.

Project Motivation

Large language models often behave inconsistently across inputs—a signal of underlying uncertainty that matters enormously in high-stakes settings like clinical decision support. Uncertainty quantification (UQ)—estimating how much to trust a model’s prediction—is therefore a prerequisite for safe LLM deployment. Yet most existing uncertainty quantification and calibration methods focus on individual models, ignoring a valuable resource: model diversity. Because LLMs differ in training data, architecture, and scale—and because language itself follows a Zipfian distribution—different models make complementary predictions.

This project asks a fundamental question:

Can we get more reliable uncertainty estimates by intelligently combining multiple LLMs, rather than trusting any single one?

What We Did

We propose MUSE (Multi-LLM Uncertainty via Subset Ensembles), a simple information-theoretic framework for multi-LLM uncertainty quantification that:

Uses Jensen-Shannon Divergence to measure agreement among candidate LLMs
Identifies well-calibrated subsets of models rather than naively averaging all of them
Aggregates subset outputs into a single, more reliable uncertainty estimate

Beyond post-hoc estimation, we also explored using MUSE-derived uncertainty as guided signals for chain-of-thought distillation, fine-tuning LLMs to be better calibrated by construction.

Key Findings

Subset selection beats naive ensembling. Aggregating only well-calibrated model subsets improves both calibration and predictive performance over single models and full ensembles on binary prediction tasks.
Model diversity is a feature, not a bug. Complementary errors across LLMs can be exploited systematically with a principled information-theoretic criterion.
Uncertainty signals can teach models. Using MUSE as supervision in chain-of-thought distillation offers a path toward LLMs that are calibrated at inference time without ensemble overhead.
Simplicity matters. MUSE requires no architectural changes or access to model internals, making it portable across model families and application domains.

Why This Matters

Deploying LLMs in high-stakes domains requires knowing not just what a model predicts, but how much to trust that prediction. MUSE provides a lightweight, generalizable uncertainty quantification method that works with off-the-shelf models—no access to model internals required—making it an essential building block for safe AI-assisted decision-making in medicine and beyond.

Broader Impact

This work anchors LARK Lab’s broader research agenda on uncertainty quantification for trustworthy AI—spanning calibration of clinical LLMs, communicating model confidence to clinicians, and calibration-aware fine-tuning and distillation.

Publication

This project was published at EMNLP 2025 (main conference).

Maya Kruse, Majid Afshar, Saksham Khatwani, Anoop Mayampurath, Guanhua Chen, and Yanjun Gao. 2025. Simple Yet Effective: An Information-Theoretic Approach to Multi-LLM Uncertainty Quantification. In Proceedings of the 2025 Conference on Empirical Methods in Natural Language Processing, pages 30493–30504.

Code: https://github.com/LARK-NLP-Lab/MUSE

This research is a R00 project funded by National Instiute of Health, National Library of Medicine (LM014308).

LLM Calibration | LARK: NLP & AI Research Lab @ CU