Influence of covariance between random effects in design for nonlinear mixed-effect models with an illustration in pediatric pharmacokinetics. - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Journal of Biopharmaceutical Statistics Year : 2014

Influence of covariance between random effects in design for nonlinear mixed-effect models with an illustration in pediatric pharmacokinetics.

Abstract

Nonlinear mixed-effect models are used increasingly during drug development. For design, an alternative to simulations is based on the Fisher information matrix. Its expression was derived using a first-order approach, was then extended to include covariance and implemented into the R function PFIM. The impact of covariance on standard errors, amount of information, and optimal designs was studied. It was also shown how standard errors can be predicted analytically within the framework of rich individual data without the model. The results were illustrated by applying this extension to the design of a pharmacokinetic study of a drug in pediatric development.
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Dates and versions

inserm-00769812 , version 1 (04-06-2014)

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Cyrielle Dumont, Marylore Chenel, France Mentré. Influence of covariance between random effects in design for nonlinear mixed-effect models with an illustration in pediatric pharmacokinetics.. Journal of Biopharmaceutical Statistics, 2014, 24 (3), pp.471-92. ⟨10.1080/10543406.2014.888443⟩. ⟨inserm-00769812⟩

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