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The reduction of viral load is frequently used as a primary endpoint in HIV clinical trials. Non-linear mixed-effects models are thus proposed to model this decrease of the viral load after initiation of treatment and to evaluate the intra-and inter-patient variability. However, left censoring due to quantification limits in the viral load measurement is an(More)
Consider an autoregressive model with measurement error: we observe Z i = X i + ε i , where X i is a stationary solution of the autoregressive equation X i = f θ 0 (X i−1) + ξ i. The regression function f θ 0 is known up to a finite dimensional parameter θ 0. The distributions of X 0 and ξ 1 are unknown whereas the distribution of ε 0 is completely known.(More)
Non-linear mixed models defined by stochastic differential equations (SDEs) are considered: the parameters of the diffusion process are random variables and vary among the individuals. A maximum likelihood estimation method based on the Stochastic Approximation EM algorithm, is proposed. This estimation method uses the Euler-Maruyama approximation of the(More)
Parametric incomplete data models defined by ordinary differential equations (ODEs) are widely used in biostatistics to describe biological processes accurately. Their parameters are estimated on approximate models, whose regression functions are evaluated by a numerical integration method. Accurate and efficient estimations of these parameters are critical(More)
Growth curve data consist of repeated measurements of a continuous growth process over time in a population of individuals. These data are classically analyzed by nonlinear mixed models. However, the standard growth functions used in this context prescribe monotone increasing growth and can fail to model unexpected changes in growth rates. We propose to(More)
This paper is a survey of existing estimation methods for pharmacokinetic/pharmacodynamic (PK/PD) models based on stochastic differential equations (SDEs). Most parametric estimation methods proposed for SDEs require high frequency data and are often poorly suited for PK/PD data which are usually sparse. Moreover, PK/PD experiments generally include not a(More)
This article focuses on parameter estimation of multilevel nonlinear mixed-effects models (MNLMEMs). These models are used to analyze data presenting multiple hierarchical levels of grouping (cluster data, clinical trials with several observation periods, ...). The variability of the individual parameters of the regression function is thus decomposed as a(More)
This article focuses on parameter estimation of multi-levels nonlinear mixed effects models (MNLMEMs). These models are used to analyze data presenting multiple hierarchical levels of grouping (cluster data, clinical trials with several observation periods,...). The variability of the individual parameters of the regression function is thus decomposed as a(More)
In order to provide a method for precise identification of insulin sensitivity from clinical Oral Glucose Tolerance Test (OGTT) observations, a relatively simple mathematical model (Simple Interdependent glucose/insulin MOdel SIMO) for the OGTT, which coherently incorporates commonly accepted physiological assumptions (incretin effect and saturating(More)
Parameter estimation in multidimensional diffusion models with only one coordinate observed is highly relevant in many biological applications, but a statistically difficult problem. In neuroscience, the membrane potential evolution in single neurons can be measured at high frequency, but biophysical realistic models have to include the unobserved dynamics(More)