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dc.rights.licenseopenen_US
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCLAIRON, Quentin
dc.contributor.authorPASIN, Chloe
dc.contributor.authorBALELLI, Irene
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTHIEBAUT, Rodolphe
hal.structure.identifierStatistics In System biology and Translational Medicine [SISTM]
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorPRAGUE, Melanie
dc.date.accessioned2023-03-06T09:58:41Z
dc.date.available2023-03-06T09:58:41Z
dc.date.issued2023-10-14
dc.identifier.issn0943-4062
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/172167
dc.description.abstractEnWe present a parameter estimation method for nonlinear mixed effect models based on ordinary differential equations (NLME-ODEs). The method presented here aims at regularizing the estimation problem in presence of model misspecifications, practical identifiability issues and unknown initial conditions. For doing so, we define our estimator as the minimizer of a cost function which incorporates a possible gap between the assumed model at the population level and the specific individual dynamic. The cost function computation leads to formulate and solve optimal control problems at the subject level. This control theory approach allows to bypass the need to know or estimate initial conditions for each subject and it regularizes the estimation problem in presence of poorly identifiable parameters. Comparing to maximum likelihood, we show on simulation examples that our method improves estimation accuracy in possibly partially observed systems with unknown initial conditions or poorly identifiable parameters with or without model error. We conclude this work with a real application on antibody concentration data after vaccination against Ebola virus coming from phase 1 trials. We use the estimated model discrepancy at the subject level to analyze the presence of model misspecification.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enDynamic population models
dc.subject.enOrdinary differential equations
dc.subject.enOptimal control theory
dc.subject.enClinical trial analysis
dc.title.enParameter estimation in nonlinear mixed effect models based on ordinary differential equations: An optimal control approach
dc.title.alternativeComputation Stat
dc.typeArticle de revueen_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.description.sponsorshipEuropeEuropean Union’s Horizon 2020 research and innovation programmeen_US
bordeaux.journalComputational Statistics
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamSISTM_BPHen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Computational%20Statistics&rft.date=2023-10-14&rft.eissn=0943-4062&rft.issn=0943-4062&rft.au=CLAIRON,%20Quentin&PASIN,%20Chloe&BALELLI,%20Irene&THIEBAUT,%20Rodolphe&PRAGUE,%20Melanie&rft.genre=article


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