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Complex biological processes are usually experimented along time among a collection of individuals. Longitudinal data are then available and the statistical challenge is to better understand the underlying biological mechanisms. The standard statistical approach is mixed-effects model, with regression functions that are now highly-developed to describe precisely the biological processes (solutions of multi-dimensional ordinary differential equations or of partial differential equation). When there is no analytical solution, a classical estimation approach relies on the coupling of a stochastic version of the EM algorithm (SAEM) with a MCMC algorithm. This procedure needs many evaluations of the regression function which is clearly prohibitive when a time-consuming solver is used for computing it. In this work a meta-model relying on a Gaussian process emulator is proposed to replace this regression function. The new source of uncertainty due to this approximation can be incorporated in the model which leads to what is called a mixed meta-model. A control on the distance between the maximum likelihood estimates in this mixed meta-model and the maximum likelihood estimates obtained with the exact mixed model is guaranteed. Eventually, numerical simulations are performed to illustrate the efficiency of this approach.
We consider a re-sampling scheme for estimation of the population parameters in the mixed effects nonlinear regression models of the type use for example in clinical pharmacokinetics, say. We provide an estimation procedure which {it recycles}, via r
It is well known that the minimax rates of convergence of nonparametric density and regression function estimation of a random variable measured with error is much slower than the rate in the error free case. Surprisingly, we show that if one is will
We present new results for consistency of maximum likelihood estimators with a focus on multivariate mixed models. Our theory builds on the idea of using subsets of the full data to establish consistency of estimators based on the full data. It requi
We consider a model where the failure hazard function, conditional on a covariate $Z$ is given by $R(t,theta^0|Z)=eta_{gamma^0}(t)f_{beta^0}(Z)$, with $theta^0=(beta^0,gamma^0)^topin mathbb{R}^{m+p}$. The baseline hazard function $eta_{gamma^0}$ and
The plurigaussian model is particularly suited to describe categorical regionalized variables. Starting from a simple principle, the thresh-olding of one or several Gaussian random fields (GRFs) to obtain categories, the plurigaussian model is well a