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An introduction to the full random effects model

The full random‐effects model (FREM) is a method for determining covariate effects in mixed‐effects models. Covariates are modeled as random variables, described by mean and variance. The method captures the covariate effects in estimated covariances between individual parameters and covariates. Thi...

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Autores principales: Yngman, Gunnar, Bjugård Nyberg, Henrik, Nyberg, Joakim, Jonsson, E. Niclas, Karlsson, Mats O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846630/
https://www.ncbi.nlm.nih.gov/pubmed/34984855
http://dx.doi.org/10.1002/psp4.12741
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author Yngman, Gunnar
Bjugård Nyberg, Henrik
Nyberg, Joakim
Jonsson, E. Niclas
Karlsson, Mats O.
author_facet Yngman, Gunnar
Bjugård Nyberg, Henrik
Nyberg, Joakim
Jonsson, E. Niclas
Karlsson, Mats O.
author_sort Yngman, Gunnar
collection PubMed
description The full random‐effects model (FREM) is a method for determining covariate effects in mixed‐effects models. Covariates are modeled as random variables, described by mean and variance. The method captures the covariate effects in estimated covariances between individual parameters and covariates. This approach is robust against issues that may cause reduced performance in methods based on estimating fixed effects (e.g., correlated covariates where the effects cannot be simultaneously identified in fixed‐effects methods). FREM covariate parameterization and transformation of covariate data records can be used to alter the covariate‐parameter relation. Four relations (linear, log‐linear, exponential, and power) were implemented and shown to provide estimates equivalent to their fixed‐effects counterparts. Comparisons between FREM and mathematically equivalent full fixed‐effects models (FFEMs) were performed in original and simulated data, in the presence and absence of non‐normally distributed and highly correlated covariates. These comparisons show that both FREM and FFEM perform well in the examined cases, with a slightly better estimation accuracy of parameter interindividual variability (IIV) in FREM. In addition, FREM offers the unique advantage of letting a single estimation simultaneously provide covariate effect coefficient estimates and IIV estimates for any subset of the examined covariates, including the effect of each covariate in isolation. Such subsets can be used to apply the model across data sources with different sets of available covariates, or to communicate covariate effects in a way that is not conditional on other covariates.
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spelling pubmed-88466302022-02-25 An introduction to the full random effects model Yngman, Gunnar Bjugård Nyberg, Henrik Nyberg, Joakim Jonsson, E. Niclas Karlsson, Mats O. CPT Pharmacometrics Syst Pharmacol Research The full random‐effects model (FREM) is a method for determining covariate effects in mixed‐effects models. Covariates are modeled as random variables, described by mean and variance. The method captures the covariate effects in estimated covariances between individual parameters and covariates. This approach is robust against issues that may cause reduced performance in methods based on estimating fixed effects (e.g., correlated covariates where the effects cannot be simultaneously identified in fixed‐effects methods). FREM covariate parameterization and transformation of covariate data records can be used to alter the covariate‐parameter relation. Four relations (linear, log‐linear, exponential, and power) were implemented and shown to provide estimates equivalent to their fixed‐effects counterparts. Comparisons between FREM and mathematically equivalent full fixed‐effects models (FFEMs) were performed in original and simulated data, in the presence and absence of non‐normally distributed and highly correlated covariates. These comparisons show that both FREM and FFEM perform well in the examined cases, with a slightly better estimation accuracy of parameter interindividual variability (IIV) in FREM. In addition, FREM offers the unique advantage of letting a single estimation simultaneously provide covariate effect coefficient estimates and IIV estimates for any subset of the examined covariates, including the effect of each covariate in isolation. Such subsets can be used to apply the model across data sources with different sets of available covariates, or to communicate covariate effects in a way that is not conditional on other covariates. John Wiley and Sons Inc. 2022-01-04 2022-02 /pmc/articles/PMC8846630/ /pubmed/34984855 http://dx.doi.org/10.1002/psp4.12741 Text en © 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research
Yngman, Gunnar
Bjugård Nyberg, Henrik
Nyberg, Joakim
Jonsson, E. Niclas
Karlsson, Mats O.
An introduction to the full random effects model
title An introduction to the full random effects model
title_full An introduction to the full random effects model
title_fullStr An introduction to the full random effects model
title_full_unstemmed An introduction to the full random effects model
title_short An introduction to the full random effects model
title_sort introduction to the full random effects model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846630/
https://www.ncbi.nlm.nih.gov/pubmed/34984855
http://dx.doi.org/10.1002/psp4.12741
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