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Complex Bayesian Modeling Workflows Encoding and Execution Made Easy With a Novel WinBUGS Plugin of the Drug Disease Model Resources Interoperability Framework

The Drug Disease Model Resources (DDMoRe) Interoperability Framework (IOF) enables pharmacometric model encoding and execution via Model Description Language (MDL) and R language, through the ddmore package. Through its components and converter plugins, the IOF can execute pharmacometric tasks using...

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Detalles Bibliográficos
Autores principales: Larizza, Cristiana, Borella, Elisa, Pasotti, Lorenzo, Tartaglione, Palma, Smith, Mike, Moodie, Stuart, Magni, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561612/
https://www.ncbi.nlm.nih.gov/pubmed/29575824
http://dx.doi.org/10.1002/psp4.12285
Descripción
Sumario:The Drug Disease Model Resources (DDMoRe) Interoperability Framework (IOF) enables pharmacometric model encoding and execution via Model Description Language (MDL) and R language, through the ddmore package. Through its components and converter plugins, the IOF can execute pharmacometric tasks using different target tools, starting from a single MDL‐encoded model. In this article, we present the WinBUGS plugin and show how its integration in the IOF enables an easy implementation of complex Bayesian workflows. We selected a published diabetes‐linked study as a real‐world example, in which two inter‐related models are used to estimate insulin secretion rate in response to a glucose stimulus from intravenous glucose tolerance test (IVGTT) data. This model was implemented following different approaches to propagate uncertainty, via diverse IOF target tools (NONMEM, WinBUGS, PsN, and Xpose). The developed software supports a plethora of pharmacokinetic/pharmacodynamic (PK/PD) modeling features. It provides solutions to reproducibility and interoperability issues in Bayesian modeling, and facilitates the difficult encoding of complex PK/PD models in WinBUGS.