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Developing Parametric and Nonparametric Models for Model-Informed Precision Dosing: A Quality Improvement Effort in
Maria-Stephanie A Hughes1, Jasmine H Hughes1, Jeffrey Endicott2
1InsightRX, San Francisco, California; and.
Therapeutic Drug Monitoring
|May 17, 2024
Summary
Parametric and nonparametric models for vancomycin dosing in class 3 obesity showed similar structures. The parametric model, however, demonstrated superior performance in external validation, suggesting institution-specific models improve vancomycin pharmacokinetics management.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Computational Biology
- Drug Dosing Strategies
Background:
- Model-informed precision dosing (MIPD) utilizes statistical methods for optimizing drug therapy.
- Parametric and nonparametric approaches are proposed for MIPD, but their comparative performance is unclear.
- Vancomycin pharmacokinetics in class 3 obesity presents unique challenges for accurate dosing.
Purpose of the Study:
- To compare parametric and nonparametric statistical approaches for developing vancomycin pharmacokinetic models.
- To evaluate the precision and bias of both modeling approaches in a class 3 obesity subpopulation.
- To assess the performance of the developed parametric model using external validation data.
Main Methods:
- Retrospective analysis of vancomycin levels from 83 patients with BMI ≥ 40 kg/m².
- Development of parametric (nlmixr2/NONMEM) and nonparametric (Pmetrics) models.
- Evaluation of a priori and a posteriori predictions using normalized root mean squared error (nRMSE) and mean percentage error (MPE).
- External validation of the parametric model on a separate dataset.
Main Results:
- Both models were 2-compartmental, incorporating creatinine clearance and fat-free mass as covariates.
- A priori predictions showed minimal differences in MPE and nRMSE between models.
- A posteriori predictions indicated improved precision and reduced bias with both models, with the parametric model showing slightly better performance.
- The parametric model outperformed previous models in external validation.
Conclusions:
- Parametric and nonparametric models exhibited comparable structures and predictive errors for vancomycin in class 3 obesity.
- The parametric model's superior performance in external validation suggests its utility for institution-specific vancomycin dosing.
- Institution-specific pharmacokinetic models may enhance vancomycin management in obese populations.
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