Valproic acid monitoring: Serum prediction using a machine learning framework from multicenter real-world data

Abstract

BACKGROUND: Our study employs machine learning to predict serum valproic acid (VPA) concentrations, aiming to contribute to the development of non-invasive assays for therapeutic drug monitoring. METHODS: Medical records from 2002 to 2019 were obtained from the Taiwan Chang Gung Research Database. Using various machine learning algorithms, we developed predictive models to classify serum VPA concentrations into two categories (1-50 μg/ml or 51-100 μg/ml) and predicted the exact concentration value. The models were trained on 5142 samples and tested on 644 independent samples. Accuracy was the main metric used to evaluate model performance, with a tolerance of 20 μg/ml for continuous variables. Furthermore, we identified important features and developed simplified models with fewer features. RESULTS: The models achieved an average accuracy of 0.80-0.86 for binary outcomes and 0.72-0.88 for continuous outcome. Ten top features associated with higher serum VPA levels included higher VPA last and daily doses, bipolar disorder or schizophrenia spectrum disorder diagnoses, elevated levels of serum albumin, calcium, and creatinine, low platelet count, low percentage of segmented white blood cells, and low red cell distribution width-coefficient of variation. The simplified models had an average accuracy of 0.82-0.86 for binary outcome and 0.70-0.86 for continuous outcome. LIMITATIONS: The study's predictive model lacked external test data from outside the hospital for validation. CONCLUSIONS: Machine learning models have the potential to integrate real-world data and predict VPA concentrations, providing a promising tool for reducing the need for frequent monitoring of serum levels in clinical practice.

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