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#natural language processing Preprint Open access

A Rubric-Guided Large Language Model Solution for Opioid Use Disorder Computable Phenotyping

Mengxian Lyu Paredes Pardo Cheng Peng Ziyi Chen Mengyuan Zhang Jieting Li Lu Gary M Reisfield William M Greene Jenny Lo-Ciganic Yonghui Wu
Sep 2026
Natural Language Processing

Abstract

Opioid use disorder (OUD) remains a public health crisis in the United States, yet it is difficult to identify from electronic health records (EHRs) because missing diagnosis codes and supporting evidence are buried in clinical narratives. Accurate OUD identification is critical to support interventions and improve health outcomes. This study developed a rubric-guided large language model (LLM) that incorporated Optimization by PROmpting (OPRO) for OUD computable phenotyping (CP). The framework used an 18-item, expert-identified rubric to instruct LLMs to automatically extract critical text with supporting evidence to determine OUD flags. Two UF Health physicians (GMR and WMG) chart-reviewed 253 patients, including 68 OUD-positive cases. Our LLM-based computable phenotype (CP) achieved the best F1 score of 0.774 and an AUROC of 0.934, outperforming the machine learning-based CP using EHR and natural language processing-extracted variables, and zero-shot LLMs by relative F1 improvements of 12.8% and 44.4%, respectively. The proposed LLM-based CP could link LLM-extracted evidence to OUD phenotyping for better explainability.

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