Skip to Main content Skip to Navigation
Journal articles

Design evaluation and optimisation in multiple response nonlinear mixed effect models: PFIM 3.0

Abstract : Nonlinear mixed effect models (NLMEM) with multiple responses are increasingly used in pharmacometrics, one of the main examples being the joint analysis of the pharmacokinetics (PK) and pharmacodynamics (PD) of a drug. Efficient tools for design evaluation and optimisation in NLMEM are necessary. The R functions PFIM 1.2 and PFIMOPT 1.0 were proposed for these purposes, but accommodate only single response models. The methodology used is based on the Fisher information matrix, developed using a linearisation of the model. In this paper, we present an extended version, PFIM 3.0, dedicated to both design evaluation and optimisation for multiple response models, using a similar method as for single response models. In addition to handling multiple response models, several features have been integrated into PFIM 3.0 for model specification and optimisation. The extension includes a library of classical analytical pharmacokinetics models and allows the user to describe more complex models using differential equations. Regarding the optimisation algorithm, an alternative to the Simplex algorithm has been implemented, the Fedorov-Wynn algorithm to optimise more practical D-optimal design. Indeed, this algorithm optimises design among a set of sampling times specified by the user. This R function is freely available at http://www.pfim.biostat.fr. The efficiency of this approach and the simplicity of use of PFIM 3.0 are illustrated with a real example of the joint PKPD analysis of warfarin, an oral anticoagulant, with a model defined by ordinary differential equations.
Complete list of metadatas

Cited literature [30 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-00431457
Contributor : Emmanuelle Comets <>
Submitted on : Thursday, November 12, 2009 - 12:25:58 PM
Last modification on : Thursday, November 19, 2020 - 1:00:54 PM
Long-term archiving on: : Thursday, June 17, 2010 - 8:09:39 PM

File

CMPB-D-09-00097-2_HAL.pdf.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Caroline Bazzoli, Sylvie Retout, France Mentré. Design evaluation and optimisation in multiple response nonlinear mixed effect models: PFIM 3.0. Computer Methods and Programs in Biomedicine, Elsevier, 2010, 98 (1), pp.55-65. ⟨10.1016/j.cmpb.2009.09.012⟩. ⟨inserm-00431457⟩

Share

Metrics

Record views

868

Files downloads

896