Parameter estimation in nonlinear mixed effect models based on ordinary differential equations: An optimal control approach
CLAIRON, Quentin
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
See more >
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
CLAIRON, Quentin
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
THIEBAUT, Rodolphe
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
PRAGUE, Melanie
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
< Reduce
Statistics In System biology and Translational Medicine [SISTM]
Bordeaux population health [BPH]
Language
EN
Article de revue
This item was published in
Computational Statistics. 2023-10-14
English Abstract
We present a parameter estimation method for nonlinear mixed effect models based on ordinary differential equations (NLME-ODEs). The method presented here aims at regularizing the estimation problem in presence of model ...Read more >
We present a parameter estimation method for nonlinear mixed effect models based on ordinary differential equations (NLME-ODEs). The method presented here aims at regularizing the estimation problem in presence of model misspecifications, practical identifiability issues and unknown initial conditions. For doing so, we define our estimator as the minimizer of a cost function which incorporates a possible gap between the assumed model at the population level and the specific individual dynamic. The cost function computation leads to formulate and solve optimal control problems at the subject level. This control theory approach allows to bypass the need to know or estimate initial conditions for each subject and it regularizes the estimation problem in presence of poorly identifiable parameters. Comparing to maximum likelihood, we show on simulation examples that our method improves 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 application on antibody concentration data after vaccination against Ebola virus coming from phase 1 trials. We use the estimated model discrepancy at the subject level to analyze the presence of model misspecification.Read less <
English Keywords
Dynamic population models
Ordinary differential equations
Optimal control theory
Clinical trial analysis
European Project
European Union’s Horizon 2020 research and innovation programme