Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs

The statistical procedures as outlined by the European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) guidelines for bioequivalence testing of highly variable drugs (HVDs) are complex. Additionally, the sample size is affected by clinical study designs or practical real-...

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Autores principales:	Eunjung Song, Woojoo Lee, Bo-Hyung Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	highly variable drugs reference-scaled average bioequivalence pharmacokinetic model Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/686337b3d33f4425bb72ad40e19399df
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spelling	oai:doaj.org-article:686337b3d33f4425bb72ad40e19399df2021-11-25T18:39:21ZModel-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs10.3390/ph141111011424-8247https://doaj.org/article/686337b3d33f4425bb72ad40e19399df2021-10-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1101https://doaj.org/toc/1424-8247The statistical procedures as outlined by the European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) guidelines for bioequivalence testing of highly variable drugs (HVDs) are complex. Additionally, the sample size is affected by clinical study designs or practical real-world problems, such as dropout rate or study budget. To overcome these difficulties, we propose a model-based approach for the selection of a study design with a sample size that satisfies the bioequivalence criteria using simulation studies based on a pharmacokinetic (PK) model. The designed approach was implemented using a simulation procedure considering some conventionally measured factors, such as geometric mean ratio and within-subject coefficient of variation, with various PK information important in determining bioequivalence. All simulation results were assessed according to the EMA and FDA guidelines. Furthermore, power calculations from simulation results were interpreted with regard to PK characteristics and compared among 2 × 2, 3 × 3, and 2 × 4 crossover designs to determine the efficient design considering appropriate sample size and duration of the clinical study. The proposed approach can be applied to bioequivalence studies of all drugs. However, the current study was targeted at HVDs, which are highly likely to require detailed decision making for sample size and study design.Eunjung SongWoojoo LeeBo-Hyung KimMDPI AGarticlehighly variable drugsreference-scaled average bioequivalencepharmacokinetic modelMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1101, p 1101 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	highly variable drugs reference-scaled average bioequivalence pharmacokinetic model Medicine R Pharmacy and materia medica RS1-441
spellingShingle	highly variable drugs reference-scaled average bioequivalence pharmacokinetic model Medicine R Pharmacy and materia medica RS1-441 Eunjung Song Woojoo Lee Bo-Hyung Kim Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs
description	The statistical procedures as outlined by the European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) guidelines for bioequivalence testing of highly variable drugs (HVDs) are complex. Additionally, the sample size is affected by clinical study designs or practical real-world problems, such as dropout rate or study budget. To overcome these difficulties, we propose a model-based approach for the selection of a study design with a sample size that satisfies the bioequivalence criteria using simulation studies based on a pharmacokinetic (PK) model. The designed approach was implemented using a simulation procedure considering some conventionally measured factors, such as geometric mean ratio and within-subject coefficient of variation, with various PK information important in determining bioequivalence. All simulation results were assessed according to the EMA and FDA guidelines. Furthermore, power calculations from simulation results were interpreted with regard to PK characteristics and compared among 2 × 2, 3 × 3, and 2 × 4 crossover designs to determine the efficient design considering appropriate sample size and duration of the clinical study. The proposed approach can be applied to bioequivalence studies of all drugs. However, the current study was targeted at HVDs, which are highly likely to require detailed decision making for sample size and study design.
format	article
author	Eunjung Song Woojoo Lee Bo-Hyung Kim
author_facet	Eunjung Song Woojoo Lee Bo-Hyung Kim
author_sort	Eunjung Song
title	Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs
title_short	Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs
title_full	Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs
title_fullStr	Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs
title_full_unstemmed	Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs
title_sort	model-based approach for designing an efficient bioequivalence study for highly variable drugs
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/686337b3d33f4425bb72ad40e19399df
work_keys_str_mv	AT eunjungsong modelbasedapproachfordesigninganefficientbioequivalencestudyforhighlyvariabledrugs AT woojoolee modelbasedapproachfordesigninganefficientbioequivalencestudyforhighlyvariabledrugs AT bohyungkim modelbasedapproachfordesigninganefficientbioequivalencestudyforhighlyvariabledrugs
_version_	1718410840405704704

Model-Based Approach for Designing an Efficient Bioequivalence Study for Highly Variable Drugs

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