Parameter estimation in nonlinear mixed effect models based on ordinary differential equations: an optimal control approach

Quentin Clairon (), Chloé Pasin, Irene Balelli, Rodolphe Thiébaut and Mélanie Prague
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Quentin Clairon: University of Bordeaux
Chloé Pasin: University of Zurich
Irene Balelli: EPIONE Research Project
Rodolphe Thiébaut: University of Bordeaux
Mélanie Prague: University of Bordeaux

Computational Statistics, 2024, vol. 39, issue 6, No 4, 2975-3005

Abstract: Abstract We present a method for parameter estimation for nonlinear mixed-effects models based on ordinary differential equations (NLME-ODEs). It aims to regularize the estimation problem in the presence of model misspecification and practical identifiability issues, while avoiding the need to know or estimate initial conditions as nuisance parameters. To this end, we define our estimator as a minimizer of a cost function that incorporates a possible gap between the assumed population-level model and the specific individual dynamics. The computation of the cost function leads to formulate and solve optimal control problems at the subject level. Compared to the maximum likelihood method, we show through simulation examples that our method improves the estimation accuracy in possibly partially observed systems with unknown initial conditions or poorly identifiable parameters with or without model error. We conclude this work with a real-world application in which we model the antibody concentration after Ebola virus vaccination.

Keywords: Dynamic population models; Ordinary differential equations; Optimal control theory; Mechanistic models; Nonlinear mixed effects models; Clinical trial analysis (search for similar items in EconPapers)
Date: 2024
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DOI: 10.1007/s00180-023-01420-x

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