Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease Codes in Patient Records

PURPOSE Current approaches to accurately identify immune-related adverse events (irAEs) in large retrospective studies are limited. Large language models (LLMs) offer a potential solution to this challenge, given their high performance in natural language comprehension tasks. Therefore, we investigated the use of an LLM to identify irAEs among hospitalized patients, comparing its performance with manual adjudication and International Classification of Disease (ICD) codes. METHODS Hospital admissions of patients receiving immune checkpoint inhibitor (ICI) therapy at a single institution from February 5, 2011, to September 5, 2023, were individually reviewed and adjudicated for the presence of irAEs. ICD codes and an LLM with retrieval-augmented generation were applied to detect frequent irAEs (ICI-induced colitis, hepatitis, and pneumonitis) and the most fatal irAE (ICI-myocarditis) from electronic health records. The performance between ICD codes and LLM was compared via sensitivity and specificity with an α = .05, relative to the gold standard of manual adjudication. External validation was performed using a data set of hospital admissions from June 1, 2018, to May 31, 2019, from a second institution. RESULTS Of the 7,555 admissions for patients on ICI therapy in the initial cohort, 2.0% were adjudicated to be due to ICI-colitis, 1.1% ICI-hepatitis, 0.7% ICI-pneumonitis, and 0.8% ICI-myocarditis. The LLM demonstrated higher sensitivity than ICD codes (94.7% v 68.7%), achieving significance for ICI-hepatitis ( P < .001), myocarditis ( P < .001), and pneumonitis ( P = .003) while yielding similar specificities (93.7% v 92.4%). The LLM spent an average of 9.53 seconds/chart in comparison with an estimated 15 minutes for adjudication. In the validation cohort (N = 1,270), the mean LLM sensitivity and specificity were 98.1% and 95.7%, respectively. CONCLUSION LLMs are a useful tool for the detection of irAEs, outperforming ICD codes in sensitivity and adjudication in efficiency.