A nonparametric approach to practical identifiability of nonlinear mixed effects models

Fuente: arXiv
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Main Authors: Cassidy, Tyler, Johnston, Stuart T., Plank, Michael, Botha, Imke, Flegg, Jennifer A., Murphy, Ryan J., Hamis, Sara
Format: Preprint
Published: 2025
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author Cassidy, Tyler
Johnston, Stuart T.
Plank, Michael
Botha, Imke
Flegg, Jennifer A.
Murphy, Ryan J.
Hamis, Sara
author_facet Cassidy, Tyler
Johnston, Stuart T.
Plank, Michael
Botha, Imke
Flegg, Jennifer A.
Murphy, Ryan J.
Hamis, Sara
contents Mathematical modelling is a widely used approach to understand and interpret clinical trial data. This modelling typically involves fitting mechanistic mathematical models to data from individual trial participants. Despite the widespread adoption of this individual-based fitting, it is becoming increasingly common to take a hierarchical approach to parameter estimation, where modellers characterize the population parameter distributions, rather than considering each individual independently. This hierarchical parameter estimation is standard in pharmacometric modelling. However, many of the existing techniques for parameter identifiability do not immediately translate from the individual-based fitting to the hierarchical setting. Here, we propose a nonparametric approach to study practical identifiability within a hierarchical parameter estimation framework. We focus on the commonly used nonlinear mixed effects framework and investigate two well-studied examples from the pharmacometrics and viral dynamics literature to illustrate the potential utility of our approach.
format Preprint
id arxiv_https___arxiv_org_abs_2507_20288
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle A nonparametric approach to practical identifiability of nonlinear mixed effects models
Cassidy, Tyler
Johnston, Stuart T.
Plank, Michael
Botha, Imke
Flegg, Jennifer A.
Murphy, Ryan J.
Hamis, Sara
Methodology
Quantitative Methods
Mathematical modelling is a widely used approach to understand and interpret clinical trial data. This modelling typically involves fitting mechanistic mathematical models to data from individual trial participants. Despite the widespread adoption of this individual-based fitting, it is becoming increasingly common to take a hierarchical approach to parameter estimation, where modellers characterize the population parameter distributions, rather than considering each individual independently. This hierarchical parameter estimation is standard in pharmacometric modelling. However, many of the existing techniques for parameter identifiability do not immediately translate from the individual-based fitting to the hierarchical setting. Here, we propose a nonparametric approach to study practical identifiability within a hierarchical parameter estimation framework. We focus on the commonly used nonlinear mixed effects framework and investigate two well-studied examples from the pharmacometrics and viral dynamics literature to illustrate the potential utility of our approach.
title A nonparametric approach to practical identifiability of nonlinear mixed effects models
topic Methodology
Quantitative Methods
url https://arxiv.org/abs/2507.20288