Harmonizing Multi-Institutional Clinical Documentation Using Natural Language Processing in Neurofibromatosis Type 1

Machine learning (ML) and natural language processing (NLP) approaches are increasingly used to support nuanced phenotyping, surveillance, and trial readiness using electronic health records (EHRs) in neurologic disease. However, inconsistent clinical documentation limits data harmonization and model performance, particularly in complex heterogeneous disorders such as neurofibromatosis type 1 (NF1). The primary research question was whether physician-authored EHR documentation of NF1-related features demonstrates systematic lexical variation that may impede computational phenotyping. The primary objective was to characterize lexical variation and documentation completeness for core NF1 features, while a secondary objective aimed to develop a standardized, data-informed clinical lexicon aligned with contemporary clinical practice and terminology standards.

We conducted a retrospective observational study of outpatient progress notes from pediatric patients with NF1 evaluated at 2 large tertiary care programs serving similar patient populations in the Midwest. A rule-based NLP algorithm was developed to identify 10 core NF1 features and extract the range of terms used to document each feature. Lexical variants and documentation frequency were quantified across institutions, providers, and time. Based on observed usage patterns, a standardized clinical lexicon was developed and mapped to existing terminology standards.

A total of 5,393 outpatient notes representing 1,661 individual pediatric patients were analyzed. Substantial lexical variation was observed for most NF1 features, including variation within and across individual providers. Clinically significant features, such as optic pathway glioma, were documented using numerous nonstandard terms, with preferred terminology appearing in a minority of notes. Cutaneous neurofibromas demonstrated higher internal consistency but lagged behind current clinical trial nomenclature, while plexiform neurofibromas and attention-deficit/hyperactivity disorder were documented more consistently. Documentation completeness also varied across providers and over time, with many previously documented features absent from later follow-up notes.

Physician-authored EHR documentation of NF1-related features demonstrates substantial lexical variation and incomplete longitudinal capture, which limit the accuracy and generalizability of NLP-based and ML-based phenotyping. Establishing a standardized, data-informed clinical lexicon aligned with current care and research practices represents a scalable strategy to improve interoperability, phenotypic consistency, and readiness for clinical trials and real-world evidence generation in NF1 and other complex neurologic disorders.