Development and Internal Validation of a Large Language Model Pipeline for Multi-Label Classification of Patient Portal Messages

Objectives: Characterizing patient portal message content at scale can help target efforts to manage administrative work. We developed and validated a large language model (LLM) pipeline for multi-label classification of messages using an expert-derived topic taxonomy, then characterized topic distribution across a two-year corpus. Materials and Methods: We studied all medical advice request messages sent to ambulatory clinicians at an academic medical center from 2024-2025. We convened an expert panel that derived an 11-category taxonomy through a modified Delphi process. Two annotators labeled 750 randomly selected messages (Cohen kappa 0.80), holding out 500 for evaluation. The pipeline used GPT-4o-mini in a zero-shot prompt. On the held-out set, we measured micro- and macro-averaged precision, recall, and F1, and label stability across runs. We then characterized topic distribution and co-occurrence across the corpus. Results: The pipeline achieved micro- and macro-averaged F1 of 0.89 and 0.86. Labels were identical across runs for 93.6% of messages. Across 2.4 million messages, content concentrated on a few topics. The two most common topics, Problems & Management and Medications & Prescriptions, were present in 67.9% of messages, and the four most common in 93.9%. 51.7% of messages addressed multiple topics. Discussion and Conclusion: The pipeline classified patient message topics accurately and stably across millions of messages. Message content was concentrated within a small number of topics, highlighting opportunities for targeted interventions and enabling more efficient triage, routing, and patient-facing support.