Cargando…

External qualification of the Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) models for octocog alfa using real patient data

BACKGROUND: Existing adult patient pharmacokinetic (PK) data from the published Advate vs Kovaltry PK crossover study were used for this validation study. This data set is appropriate for qualification, given that it has not been previously submitted to Web‐Accessible Population Pharmacokinetic Serv...

Descripción completa

Detalles Bibliográficos
Autores principales: Chelle, Pierre, Hajducek, Dagmar, Mahdi, Mohammed, Young, Stuart, Iorio, Alfonso, Silvertown, Josh, Edginton, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563921/
https://www.ncbi.nlm.nih.gov/pubmed/34761154
http://dx.doi.org/10.1002/rth2.12599
_version_ 1784593505674330112
author Chelle, Pierre
Hajducek, Dagmar
Mahdi, Mohammed
Young, Stuart
Iorio, Alfonso
Silvertown, Josh
Edginton, Andrea
author_facet Chelle, Pierre
Hajducek, Dagmar
Mahdi, Mohammed
Young, Stuart
Iorio, Alfonso
Silvertown, Josh
Edginton, Andrea
author_sort Chelle, Pierre
collection PubMed
description BACKGROUND: Existing adult patient pharmacokinetic (PK) data from the published Advate vs Kovaltry PK crossover study were used for this validation study. This data set is appropriate for qualification, given that it has not been previously submitted to Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) and will not have impacted the WAPPS‐Hemo models for Kovaltry. OBJECTIVE: To compare the population PK parameters for Kovaltry (BAY 81‐8973) derived from the WAPPS‐Hemo models with PK parameters derived from noncompartmental analysis (NCA), using a validation PK dataset. METHODS: The qualification data set included Kovaltry factor activity (10 samples per infusion) and anthropometric data for 18 patients. Two analyses were performed comparison of Bayesian forecasting from the WAPPS‐Hemo models versus NCA using the full 10‐sample data set; and comparison of Bayesian forecasting using the full versus reduced 4‐ and 3‐sample data sets. Agreement between outcomes was assessed by quantifying the variability and bias of the error. RESULTS: Comparison of WAPPS‐Hemo models versus NCA led to well‐correlated outcomes despite a systematic overprediction of clearance. Population PK models demonstrated greater consistency with NCA on one‐stage data, compared with chromogenic data. WAPPS‐Hemo model results were consistent in reduced sampling compared to full sampling. Inclusion of a 48‐hour time point in the reduced sampling greatly improved the consistency with full sampling. DISCUSSION: Qualification of population PK models and their use for Bayesian forecasting in full and reduced sampling is an essential step toward their validation. The evaluations performed in this study support the confidence of PK parameter estimates provided by the models.
format Online
Article
Text
id pubmed-8563921
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-85639212021-11-09 External qualification of the Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) models for octocog alfa using real patient data Chelle, Pierre Hajducek, Dagmar Mahdi, Mohammed Young, Stuart Iorio, Alfonso Silvertown, Josh Edginton, Andrea Res Pract Thromb Haemost Original Articles BACKGROUND: Existing adult patient pharmacokinetic (PK) data from the published Advate vs Kovaltry PK crossover study were used for this validation study. This data set is appropriate for qualification, given that it has not been previously submitted to Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) and will not have impacted the WAPPS‐Hemo models for Kovaltry. OBJECTIVE: To compare the population PK parameters for Kovaltry (BAY 81‐8973) derived from the WAPPS‐Hemo models with PK parameters derived from noncompartmental analysis (NCA), using a validation PK dataset. METHODS: The qualification data set included Kovaltry factor activity (10 samples per infusion) and anthropometric data for 18 patients. Two analyses were performed comparison of Bayesian forecasting from the WAPPS‐Hemo models versus NCA using the full 10‐sample data set; and comparison of Bayesian forecasting using the full versus reduced 4‐ and 3‐sample data sets. Agreement between outcomes was assessed by quantifying the variability and bias of the error. RESULTS: Comparison of WAPPS‐Hemo models versus NCA led to well‐correlated outcomes despite a systematic overprediction of clearance. Population PK models demonstrated greater consistency with NCA on one‐stage data, compared with chromogenic data. WAPPS‐Hemo model results were consistent in reduced sampling compared to full sampling. Inclusion of a 48‐hour time point in the reduced sampling greatly improved the consistency with full sampling. DISCUSSION: Qualification of population PK models and their use for Bayesian forecasting in full and reduced sampling is an essential step toward their validation. The evaluations performed in this study support the confidence of PK parameter estimates provided by the models. John Wiley and Sons Inc. 2021-11-02 /pmc/articles/PMC8563921/ /pubmed/34761154 http://dx.doi.org/10.1002/rth2.12599 Text en © 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH). https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Chelle, Pierre
Hajducek, Dagmar
Mahdi, Mohammed
Young, Stuart
Iorio, Alfonso
Silvertown, Josh
Edginton, Andrea
External qualification of the Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) models for octocog alfa using real patient data
title External qualification of the Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) models for octocog alfa using real patient data
title_full External qualification of the Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) models for octocog alfa using real patient data
title_fullStr External qualification of the Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) models for octocog alfa using real patient data
title_full_unstemmed External qualification of the Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) models for octocog alfa using real patient data
title_short External qualification of the Web‐Accessible Population Pharmacokinetic Service–Hemophilia (WAPPS‐Hemo) models for octocog alfa using real patient data
title_sort external qualification of the web‐accessible population pharmacokinetic service–hemophilia (wapps‐hemo) models for octocog alfa using real patient data
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563921/
https://www.ncbi.nlm.nih.gov/pubmed/34761154
http://dx.doi.org/10.1002/rth2.12599
work_keys_str_mv AT chellepierre externalqualificationofthewebaccessiblepopulationpharmacokineticservicehemophiliawappshemomodelsforoctocogalfausingrealpatientdata
AT hajducekdagmar externalqualificationofthewebaccessiblepopulationpharmacokineticservicehemophiliawappshemomodelsforoctocogalfausingrealpatientdata
AT mahdimohammed externalqualificationofthewebaccessiblepopulationpharmacokineticservicehemophiliawappshemomodelsforoctocogalfausingrealpatientdata
AT youngstuart externalqualificationofthewebaccessiblepopulationpharmacokineticservicehemophiliawappshemomodelsforoctocogalfausingrealpatientdata
AT iorioalfonso externalqualificationofthewebaccessiblepopulationpharmacokineticservicehemophiliawappshemomodelsforoctocogalfausingrealpatientdata
AT silvertownjosh externalqualificationofthewebaccessiblepopulationpharmacokineticservicehemophiliawappshemomodelsforoctocogalfausingrealpatientdata
AT edgintonandrea externalqualificationofthewebaccessiblepopulationpharmacokineticservicehemophiliawappshemomodelsforoctocogalfausingrealpatientdata