PMID: identifiant
de la référence Pubmed : |
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 (17486667) |
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| titre : |
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Design in nonlinear mixed effects models: Optimization using the Fedorov-Wynn algorithm and power of the Wald test for binary covariates. |
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| auteur(s) : |
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Sylvie Retout ( ) 1, 2, Emmanuelle Comets1, Adeline Samson1, France Mentré1, 2 |
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| laboratoire : |
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| résumé : |
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We extend the methodology for designs evaluation and optimization in nonlinear mixed effects models with an illustration of the decrease of human immunodeficiency virus viral load after antiretroviral treatment initiation described by a bi-exponential model. We first show the relevance of the predicted standard errors (SEs) given by the computation of the population Fisher information matrix using the R function PFIM, in comparison to those computed with the stochastic approximation expectation-maximization algorithm, implemented in the Monolix software. We then highlight the usefulness of the Fedorov-Wynn (FW) algorithm for designs optimization compared to the Simplex algorithm. From the predicted SE of PFIM, we compute the predicted power of the Wald test to detect a treatment effect as well as the number of subjects needed to achieve a given power. Using the FW algorithm, we investigate the influence of the design on the power and show that, for optimized designs with the same total number of samples, the power increases when the number of subjects increases and the number of samples per subject decreases. A simulation study is also performed with the nlme function of R to confirm this result and show the relevance of the predicted powers compared to those observed by simulation. Copyright (c) 2007 John Wiley & Sons, Ltd. |
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| domaine : |
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Sciences du Vivant/Bio-Informatique, Biostatistique
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0277-6715 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1002/sim.2910 |
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| journal : |
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| Statistics in Medicine (Stat Med) |
| Publisher |
John Wiley & Sons |
| ISSN |
0277-6715 (eISSN : 1097-0258) |
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| date de publication : |
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08/05/2007 |
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date de publication
électronique : |
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08/05/2007 |
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| page, identifiant, ... : |
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2007 |
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