Cargando…

The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design

Mathematical modelling methods and adaptive trial design are likely to be effective for optimising vaccine dose but are not yet commonly used. This may be due to uncertainty with regard to the correct choice of parametric model for dose-efficacy or dose-toxicity. Non-parametric models have previousl...

Descripción completa

Detalles Bibliográficos
Autores principales: Benest, John, Rhodes, Sophie, Evans, Thomas G., White, Richard G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693615/
https://www.ncbi.nlm.nih.gov/pubmed/36366347
http://dx.doi.org/10.3390/vaccines10111838
_version_ 1784837588894351360
author Benest, John
Rhodes, Sophie
Evans, Thomas G.
White, Richard G.
author_facet Benest, John
Rhodes, Sophie
Evans, Thomas G.
White, Richard G.
author_sort Benest, John
collection PubMed
description Mathematical modelling methods and adaptive trial design are likely to be effective for optimising vaccine dose but are not yet commonly used. This may be due to uncertainty with regard to the correct choice of parametric model for dose-efficacy or dose-toxicity. Non-parametric models have previously been suggested to be potentially useful in this situation. We propose a novel approach for locating optimal vaccine dose based on the non-parametric Continuous Correlated Beta Process model and adaptive trial design. We call this the ‘Correlated Beta’ or ‘CoBe’ dose optimisation approach. We evaluated the CoBe dose optimisation approach compared to other vaccine dose optimisation approaches using a simulation study. Despite using simpler assumptions than other modelling-based methods, we found that the CoBe dose optimisation approach was able to effectively locate the maximum efficacy dose for both single and prime/boost administration vaccines. The CoBe dose optimisation approach was also effective in finding a dose that maximises vaccine efficacy and minimises vaccine-related toxicity. Further, we found that these modelling methods can benefit from the inclusion of expert knowledge, which has been difficult for previous parametric modelling methods. This work further shows that using mathematical modelling and adaptive trial design is likely to be beneficial to locating optimal vaccine dose, ensuring maximum vaccine benefit and disease burden reduction, ultimately saving lives
format Online
Article
Text
id pubmed-9693615
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96936152022-11-26 The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design Benest, John Rhodes, Sophie Evans, Thomas G. White, Richard G. Vaccines (Basel) Article Mathematical modelling methods and adaptive trial design are likely to be effective for optimising vaccine dose but are not yet commonly used. This may be due to uncertainty with regard to the correct choice of parametric model for dose-efficacy or dose-toxicity. Non-parametric models have previously been suggested to be potentially useful in this situation. We propose a novel approach for locating optimal vaccine dose based on the non-parametric Continuous Correlated Beta Process model and adaptive trial design. We call this the ‘Correlated Beta’ or ‘CoBe’ dose optimisation approach. We evaluated the CoBe dose optimisation approach compared to other vaccine dose optimisation approaches using a simulation study. Despite using simpler assumptions than other modelling-based methods, we found that the CoBe dose optimisation approach was able to effectively locate the maximum efficacy dose for both single and prime/boost administration vaccines. The CoBe dose optimisation approach was also effective in finding a dose that maximises vaccine efficacy and minimises vaccine-related toxicity. Further, we found that these modelling methods can benefit from the inclusion of expert knowledge, which has been difficult for previous parametric modelling methods. This work further shows that using mathematical modelling and adaptive trial design is likely to be beneficial to locating optimal vaccine dose, ensuring maximum vaccine benefit and disease burden reduction, ultimately saving lives MDPI 2022-10-30 /pmc/articles/PMC9693615/ /pubmed/36366347 http://dx.doi.org/10.3390/vaccines10111838 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Benest, John
Rhodes, Sophie
Evans, Thomas G.
White, Richard G.
The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design
title The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design
title_full The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design
title_fullStr The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design
title_full_unstemmed The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design
title_short The Correlated Beta Dose Optimisation Approach: Optimal Vaccine Dosing Using Mathematical Modelling and Adaptive Trial Design
title_sort correlated beta dose optimisation approach: optimal vaccine dosing using mathematical modelling and adaptive trial design
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693615/
https://www.ncbi.nlm.nih.gov/pubmed/36366347
http://dx.doi.org/10.3390/vaccines10111838
work_keys_str_mv AT benestjohn thecorrelatedbetadoseoptimisationapproachoptimalvaccinedosingusingmathematicalmodellingandadaptivetrialdesign
AT rhodessophie thecorrelatedbetadoseoptimisationapproachoptimalvaccinedosingusingmathematicalmodellingandadaptivetrialdesign
AT evansthomasg thecorrelatedbetadoseoptimisationapproachoptimalvaccinedosingusingmathematicalmodellingandadaptivetrialdesign
AT whiterichardg thecorrelatedbetadoseoptimisationapproachoptimalvaccinedosingusingmathematicalmodellingandadaptivetrialdesign
AT benestjohn correlatedbetadoseoptimisationapproachoptimalvaccinedosingusingmathematicalmodellingandadaptivetrialdesign
AT rhodessophie correlatedbetadoseoptimisationapproachoptimalvaccinedosingusingmathematicalmodellingandadaptivetrialdesign
AT evansthomasg correlatedbetadoseoptimisationapproachoptimalvaccinedosingusingmathematicalmodellingandadaptivetrialdesign
AT whiterichardg correlatedbetadoseoptimisationapproachoptimalvaccinedosingusingmathematicalmodellingandadaptivetrialdesign