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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.
We present a parameter estimation method in Ordinary Differential Equation (ODE) models. Due to complex relationships between parameters and states the use of standard techniques such as nonlinear least squares can lead to the presence of poorly iden
We consider the problem of estimating parameters of stochastic differential equations (SDEs) with discrete-time observations that are either completely or partially observed. The transition density between two observations is generally unknown. We pr
We deal with the problem of parameter estimation in stochastic differential equations (SDEs) in a partially observed framework. We aim to design a method working for both elliptic and hypoelliptic SDEs, the latters being characterized by degenerate d
We consider parameter estimation of ordinary differential equation (ODE) models from noisy observations. For this problem, one conventional approach is to fit numerical solutions (e.g., Euler, Runge--Kutta) of ODEs to data. However, such a method doe
This paper introduces a general framework for survival analysis based on ordinary differential equations (ODE). Specifically, this framework unifies many existing survival models, including proportional hazards models, linear transformation models, a