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Stochastic Differential Mixed-Effects Models
Authors:UMBERTO PICCHINI  REA DE GAETANO  SUSANNE DITLEVSEN
Institution:Department of Mathematical Sciences, University of Copenhagen;Biomathematics Laboratory, IASI–CNR;
Biomathematics Laboratory (BioMatLab) IASI–CNR;
Department of Mathematical Sciences, University of Copenhagen
Abstract:Abstract.  Stochastic differential equations have been shown useful in describing random continuous time processes. Biomedical experiments often imply repeated measurements on a series of experimental units and differences between units can be represented by incorporating random effects into the model. When both system noise and random effects are considered, stochastic differential mixed-effects models ensue. This class of models enables the simultaneous representation of randomness in the dynamics of the phenomena being considered and variability between experimental units, thus providing a powerful modelling tool with immediate applications in biomedicine and pharmacokinetic/pharmacodynamic studies. In most cases the likelihood function is not available, and thus maximum likelihood estimation of the unknown parameters is not possible. Here we propose a computationally fast approximated maximum likelihood procedure for the estimation of the non-random parameters and the random effects. The method is evaluated on simulations from some famous diffusion processes and on real data sets.
Keywords:biomedical applications  Brownian motion with drift  CIR process  closed-form transition density expansion  Gaussian quadrature  geometric Brownian motion  maximum likelihood estimation  Ornstein–Uhlenbeck process  random parameters  stochastic differential equations
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