Predictive Modeling of Drug-Related Adverse Events with Real-World Data: A Case Study of Linezolid Hematologic Outcomes.

Autor: Patel A; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA., Doernberg SB; Division of Infectious Diseases, Department of Medicine, University of California San Francisco, San Francisco, California, USA., Zack T; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA.; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA., Butte AJ; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA.; University of California Health, University of California, Office of the President, Oakland, California, USA., Radtke KK; Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2024 Apr; Vol. 115 (4), pp. 847-859. Date of Electronic Publication: 2024 Feb 12.
DOI: 10.1002/cpt.3201
Abstrakt: Electronic health records (EHRs) provide meaningful knowledge of drug-related adverse events (AEs) that are not captured in standard drug development and postmarketing surveillance. Using variables obtained from EHR data in the University of California San Francisco de-identified Clinical Data Warehouse, we aimed to evaluate the potential of machine learning to predict two hematological AEs, thrombocytopenia and anemia, in a cohort of patients treated with linezolid for 3 or more days. Features for model input were extracted at linezolid initiation (index), and outcomes were characterized from index to 14 days post-treatment. Random forest classification (RFC) was used for AE prediction, and reduced feature models were evaluated using cumulative importance (cImp) for feature selection. Grade 3+ thrombocytopenia and anemia occurred in 31% of 2,171 and 56% of 2,170 evaluable patients, respectively. Of the total 53 features, as few as 7 contributed at least 50% cImp, resulting in prediction accuracies of 70% or higher and area under the receiver operating characteristic curves of 0.886 for grade 3+ thrombocytopenia and 0.759 for grade 3+ anemia. Sensitivity analyses in strictly defined patient subgroups revealed similarly high predictive performance in full and reduced feature models. A logistic regression model with the same 50% cImp features showed similar predictive performance as RFC and good concordance with RFC probability predictions after isotonic calibration, adding interpretability. Collectively, this work demonstrates potential for machine learning prediction of AE risk in real-world patients using few variables regularly available in EHRs, which may aid in clinical decision making and/or monitoring.
(© 2024 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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