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Two-Stage Adaptive Designs In Nonlinear Mixed Effects Models: Application To Pharmacokinetics In Children

By Cyrielle Dumont, Marylore Chenel and France Mentré


International audienceNonlinear mixed effects models (NLMEM) are used in pharmacokinetics to analyse concentrations of patients during drug development, particularly for pediatric studies. Approaches based on the Fisher information matrix can be used to optimize their design. Local design needs some a priori parameter values which might be difficult to guess. Therefore two-stage adaptive designs are useful to provide some flexibility. We implemented in the R function PFIM the Fisher matrix for two-stage designs in NLMEM. We evaluated, with simulations, the impact of one-stage and two-stage designs on the precision of parameter estimation when the true and a priori parameters are different

Topics: design optimization, nonlinear mixed effects models, Adaptive design, Population pharmacokinetics, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM]
Publisher: Taylor & Francis
Year: 2014
DOI identifier: 10.1080/03610918.2014.930901
OAI identifier: oai:HAL:inserm-01076940v1
Provided by: Hal-Diderot

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