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Simultaneous confidence regions for multivariate bioequivalence

Pallmann, Philip ORCID: and Jaki, Thomas 2017. Simultaneous confidence regions for multivariate bioequivalence. Statistics in Medicine 36 (29) , pp. 4585-4603. 10.1002/sim.7446

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Demonstrating bioequivalence of several pharmacokinetic (PK) parameters, such as AUC and Cmax, that are calculated from the same biological sample measurements is in fact a multivariate problem, even though this is neglected by most practitioners and regulatory bodies, who typically settle for separate univariate analyses. We believe, however, that a truly multivariate evaluation of all PK measures simultaneously is clearly more adequate. In this paper, we review methods to construct joint confidence regions around multivariate normal means and investigate their usefulness in simultaneous bioequivalence problems via simulation. Some of them work well for idealised scenarios but break down when faced with real-data challenges such as unknown variance and correlation among the PK parameters. We study the shapes of the confidence regions resulting from different methods, discuss how marginal simultaneous confidence intervals for the individual PK measures can be derived, and illustrate the application to data from a trial on ticlopidine hydrochloride. An R package is available.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Wiley
ISSN: 0277-6715
Related URLs:
Date of First Compliant Deposit: 16 March 2018
Date of Acceptance: 2 August 2017
Last Modified: 07 Nov 2023 10:57

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