The challenge of uncertainty quantification of large language models in medicine
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Abstract (arXiv)
This study investigates uncertainty quantification in large language models (LLMs) for medical applications, emphasizing both technical innovations and philosophical implications. As LLMs become integral to clinical decision-making, accurately communicating uncertainty is crucial for ensuring reliable, safe, and ethical AI-assisted healthcare. Our research frames uncertainty not as a barrier but as an essential part of knowledge that invites a dynamic and reflective approach to AI design. By integrating advanced probabilistic methods such as Bayesian inference, deep ensembles, and Monte Carlo dropout with linguistic analysis that computes predictive and semantic entropy, we propose a comprehensive framework that manages both epistemic and aleatoric uncertainties. The framework incorporates surrogate modeling to address limitations of proprietary APIs, multi-source data integration for better context, and dynamic calibration via continual and meta-learning. Explainability is embedded through uncertainty maps and confidence metrics to support user trust and clinical interpretability. Our approach supports transparent and ethical decision-making aligned with Responsible and Reflective AI principles. Philosophically, we advocate accepting controlled ambiguity instead of striving for absolute predictability, recognizing the inherent provisionality of medical knowledge.
Key facts. Cited by 14 papers in the map (data through 14 Oct 2026). Builds on 34 of its 117 references that are in the map. First posted on arXiv 7 Apr 2025.
Builds on
34 of 117 references.
References · 34
- 2016Simple and Scalable Predictive Uncertainty Estimation using Deep Ensemblescited by 3,926
- 2019Advances and Open Problems in Federated Learningcited by 3,046
- 2017What Uncertainties Do We Need in Bayesian Deep Learning for Computer Vision?cited by 2,352
- 2019A Survey on Bias and Fairness in Machine Learningcited by 1,917
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- 2023Can LLMs Express Their Uncertainty? An Empirical Evaluation of Confidence Elicitation in LLMscited by 974
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- 2019Aleatoric and Epistemic Uncertainty in Machine Learning: An Introduction to Concepts and Methodscited by 913
- 2020A Review of Uncertainty Quantification in Deep Learning: Techniques, Applications and Challengescited by 819
- 2021A Survey of Uncertainty in Deep Neural Networkscited by 680
- 2020Selective Question Answering under Domain Shiftcited by 238
22 more
- 2021Expanding Explainability: Towards Social Transparency in AI systemscited by 124
- 2023Evaluating Language Models for Mathematics through Interactionscited by 70
- 2019Unremarkable AI: Fitting Intelligent Decision Support into Critical, Clinical Decision-Making Processescited by 53
- 2023Llamas Know What GPTs Don't Show: Surrogate Models for Confidence Estimationcited by 39
- 2020Selective Classification Can Magnify Disparities Across Groupscited by 36
- 2023Quantifying Uncertainty in Natural Language Explanations of Large Language Modelscited by 32
- 2020Deep Generative Model-based Quality Control for Cardiac MRI Segmentationcited by 22
- 2020Uncertainty-Aware Deep Ensembles for Reliable and Explainable Predictions of Clinical Time Seriescited by 13
- 2020Uncertainty Estimation and Sample Selection for Crowd Countingcited by 11
- 2024Uncertainty-Aware Explainable Recommendation with Large Language Modelscited by 10
- 2020The Four Dimensions of Social Network Analysis: An Overview of Research Methods, Applications, and Software Toolscited by 9
- 2024Explainable Natural Language Processing for Corporate Sustainability Analysiscited by 9
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- 2023Structural-Based Uncertainty in Deep Learning Across Anatomical Scales: Analysis in White Matter Lesion Segmentationcited by 7
- 2019Selective prediction-set models with coverage guaranteescited by 6
- 2022Segmentation of Bruch's Membrane in retinal OCT with AMD using anatomical priors and uncertainty quantificationcited by 5
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- 2023Reflective Artificial Intelligencecited by 4
- 2024NPB-REC: A Non-parametric Bayesian Deep-learning Approach for Undersampled MRI Reconstruction with Uncertainty Estimationcited by 4
- 2024Reimagining Self-Adaptation in the Age of Large Language Modelscited by 4
- 2025Self-Reported Confidence of Large Language Models in Gastroenterology: Analysis of Commercial, Open-Source, and Quantized Modelscited by 3
- 2023Uncertainty Estimation and Out-of-Distribution Detection for Deep Learning-Based Image Reconstruction using the Local Lipschitzcited by 2
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Citing papers per year: 2025: 8; 2026: 6.
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- 2025LEC: Linear Expectation Constraints for Selection-Conditioned Risk Control in Selective Prediction and Routing Systemscited by 7
- 2025Rethinking Testing for LLM Applications: Characteristics, Challenges, and a Lightweight Interaction Protocolcited by 6
- 2026Mind the Ambiguity: Aleatoric Uncertainty Quantification in LLMs for Safe Medical Question Answeringcited by 2
- 2025Mind the Gap: Benchmarking LLM Uncertainty and Calibration with Specialty-Aware Clinical QA and Reasoning-Based Behavioural Featurescited by 1
- 2025Rule-Based Moral Principles for Explaining Uncertainty in Natural Language Generationcited by 1
- 2026Uncertainty and Fairness Awareness in LLM-Based Recommendation Systemscited by 1
- 2026Aligning Clinical Needs and AI Capabilities: A Survey on LLMs for Medical Reasoningcited by 1
- 2025Evaluating Prompt Engineering Techniques for Accuracy and Confidence Elicitation in Medical LLMscited by 0
- 2025ScenarioBench: Trace-Grounded Compliance Evaluation for Text-to-SQL and RAGcited by 0
- 2025Kantian-Utilitarian XAI: Meta-Explainedcited by 0
- 2025Generative Artificial Intelligence in Bioinformatics: A Systematic Review of Models, Applications, and Methodological Advancescited by 0
- 2026Towards Reliable Medical LLMs: Benchmarking and Enhancing Confidence Estimation of Large Language Models in Medical Consultationcited by 0
- 2026GUT: Quantifying and Optimizing the Reasoning Uncertainty of LLMs via Graph Complexity4 Sep 2026
- 2026Aligning Clinical Needs and AI Capabilities: A Survey on LLMs for Medical Reasoning8 Jul 2026
- 2026MedGuards: Multi-Agent System for Reliable Medical Error Detection and Correction24 Jun 2026
- 2026Uncertainty and Fairness Awareness in LLM-Based Recommendation Systems31 Jan 2026
- 2026Mind the Ambiguity: Aleatoric Uncertainty Quantification in LLMs for Safe Medical Question Answering24 Jan 2026
- 2026Towards Reliable Medical LLMs: Benchmarking and Enhancing Confidence Estimation of Large Language Models in Medical Consultation22 Jan 2026
- 2025LEC: Linear Expectation Constraints for Selection-Conditioned Risk Control in Selective Prediction and Routing Systems1 Dec 2025
- 2025Generative Artificial Intelligence in Bioinformatics: A Systematic Review of Models, Applications, and Methodological Advances5 Nov 2025
- 2025Kantian-Utilitarian XAI: Meta-Explained4 Oct 2025
- 2025ScenarioBench: Trace-Grounded Compliance Evaluation for Text-to-SQL and RAG29 Sep 2025
- 2025Rule-Based Moral Principles for Explaining Uncertainty in Natural Language Generation8 Sep 2025
- 2025Rethinking Testing for LLM Applications: Characteristics, Challenges, and a Lightweight Interaction Protocol28 Aug 2025
- 2025Rethinking Testing for LLM Applications: Characteristics, Challenges, and a Lightweight Interaction Protocolcited by 6
- 2025Mind the Gap: Benchmarking LLM Uncertainty and Calibration with Specialty-Aware Clinical QA and Reasoning-Based Behavioural Featurescited by 1
- 2026Aligning Clinical Needs and AI Capabilities: A Survey on LLMs for Medical Reasoningcited by 1
- 2026GUT: Quantifying and Optimizing the Reasoning Uncertainty of LLMs via Graph Complexitycited by 0
- 2026GUT: Quantifying and Optimizing the Reasoning Uncertainty of LLMs via Graph Complexity4 Sep 2026
- 2026Aligning Clinical Needs and AI Capabilities: A Survey on LLMs for Medical Reasoning8 Jul 2026
- 2025Rethinking Testing for LLM Applications: Characteristics, Challenges, and a Lightweight Interaction Protocol28 Aug 2025
- 2025Mind the Gap: Benchmarking LLM Uncertainty and Calibration with Specialty-Aware Clinical QA and Reasoning-Based Behavioural Features12 Jun 2025
- 2025LEC: Linear Expectation Constraints for Selection-Conditioned Risk Control in Selective Prediction and Routing Systemscited by 7
- 2026Mind the Ambiguity: Aleatoric Uncertainty Quantification in LLMs for Safe Medical Question Answeringcited by 2
- 2025Rule-Based Moral Principles for Explaining Uncertainty in Natural Language Generationcited by 1
- 2026Uncertainty and Fairness Awareness in LLM-Based Recommendation Systemscited by 1
- 2025Evaluating Prompt Engineering Techniques for Accuracy and Confidence Elicitation in Medical LLMscited by 0
- 2025Kantian-Utilitarian XAI: Meta-Explainedcited by 0
- 2025Generative Artificial Intelligence in Bioinformatics: A Systematic Review of Models, Applications, and Methodological Advancescited by 0
- 2026Towards Reliable Medical LLMs: Benchmarking and Enhancing Confidence Estimation of Large Language Models in Medical Consultationcited by 0
- 2026Uncertainty and Fairness Awareness in LLM-Based Recommendation Systems31 Jan 2026
- 2026Mind the Ambiguity: Aleatoric Uncertainty Quantification in LLMs for Safe Medical Question Answering24 Jan 2026
- 2026Towards Reliable Medical LLMs: Benchmarking and Enhancing Confidence Estimation of Large Language Models in Medical Consultation22 Jan 2026
- 2025LEC: Linear Expectation Constraints for Selection-Conditioned Risk Control in Selective Prediction and Routing Systems1 Dec 2025
- 2025Generative Artificial Intelligence in Bioinformatics: A Systematic Review of Models, Applications, and Methodological Advances5 Nov 2025
- 2025Kantian-Utilitarian XAI: Meta-Explained4 Oct 2025
- 2025Rule-Based Moral Principles for Explaining Uncertainty in Natural Language Generation8 Sep 2025
- 2025Evaluating Prompt Engineering Techniques for Accuracy and Confidence Elicitation in Medical LLMs29 May 2025