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Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII

Bayesian forecasting for dose individualization of prophylactic factor VIII replacement therapy using pharmacokinetic samples is challenged by large interindividual variability in the bleeding risk. A pharmacokinetic‐repeated time‐to‐event model‐based forecasting approach was developed to contrast t...

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Autores principales: Abrantes, João A., Solms, Alexander, Garmann, Dirk, Nielsen, Elisabet I., Jönsson, Siv, Karlsson, Mats O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930854/
https://www.ncbi.nlm.nih.gov/pubmed/31668021
http://dx.doi.org/10.1002/psp4.12464
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author Abrantes, João A.
Solms, Alexander
Garmann, Dirk
Nielsen, Elisabet I.
Jönsson, Siv
Karlsson, Mats O.
author_facet Abrantes, João A.
Solms, Alexander
Garmann, Dirk
Nielsen, Elisabet I.
Jönsson, Siv
Karlsson, Mats O.
author_sort Abrantes, João A.
collection PubMed
description Bayesian forecasting for dose individualization of prophylactic factor VIII replacement therapy using pharmacokinetic samples is challenged by large interindividual variability in the bleeding risk. A pharmacokinetic‐repeated time‐to‐event model‐based forecasting approach was developed to contrast the ability to predict the future occurrence of bleeds based on individual (i) pharmacokinetic, (ii) bleeding, and (iii) pharmacokinetic, bleeding and covariate information using observed data from the Long‐Term Efficacy Open‐Label Program in Severe Hemophilia A Disease (LEOPOLD) clinical trials (172 severe hemophilia A patients taking prophylactic treatment). The predictive performance assessed by the area under receiver operating characteristic (ROC) curves was 0.67 (95% confidence interval (CI), 0.65–0.69), 0.78 (95% CI, 0.76–0.80), and 0.79 (95% CI, 0.77–0.81) for patients ≥ 12 years when using pharmacokinetics, bleeds, and all data, respectively, suggesting that individual bleed information adds value to the optimization of prophylactic dosing regimens in severe hemophilia A. Further steps to optimize the proposed tool for factor VIII dose adaptation in the clinic are required.
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spelling pubmed-69308542019-12-27 Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII Abrantes, João A. Solms, Alexander Garmann, Dirk Nielsen, Elisabet I. Jönsson, Siv Karlsson, Mats O. CPT Pharmacometrics Syst Pharmacol Research Bayesian forecasting for dose individualization of prophylactic factor VIII replacement therapy using pharmacokinetic samples is challenged by large interindividual variability in the bleeding risk. A pharmacokinetic‐repeated time‐to‐event model‐based forecasting approach was developed to contrast the ability to predict the future occurrence of bleeds based on individual (i) pharmacokinetic, (ii) bleeding, and (iii) pharmacokinetic, bleeding and covariate information using observed data from the Long‐Term Efficacy Open‐Label Program in Severe Hemophilia A Disease (LEOPOLD) clinical trials (172 severe hemophilia A patients taking prophylactic treatment). The predictive performance assessed by the area under receiver operating characteristic (ROC) curves was 0.67 (95% confidence interval (CI), 0.65–0.69), 0.78 (95% CI, 0.76–0.80), and 0.79 (95% CI, 0.77–0.81) for patients ≥ 12 years when using pharmacokinetics, bleeds, and all data, respectively, suggesting that individual bleed information adds value to the optimization of prophylactic dosing regimens in severe hemophilia A. Further steps to optimize the proposed tool for factor VIII dose adaptation in the clinic are required. John Wiley and Sons Inc. 2019-10-30 2019-12 /pmc/articles/PMC6930854/ /pubmed/31668021 http://dx.doi.org/10.1002/psp4.12464 Text en © 2019 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://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
Abrantes, João A.
Solms, Alexander
Garmann, Dirk
Nielsen, Elisabet I.
Jönsson, Siv
Karlsson, Mats O.
Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII
title Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII
title_full Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII
title_fullStr Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII
title_full_unstemmed Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII
title_short Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII
title_sort bayesian forecasting utilizing bleeding information to support dose individualization of factor viii
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930854/
https://www.ncbi.nlm.nih.gov/pubmed/31668021
http://dx.doi.org/10.1002/psp4.12464
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