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J Pharmacokinet Biopharm. 1997 Oct;25(5):595-614.

A parametric confidence interval for a moment-based scaled criterion for individual bioequivalence.

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  • 1Department of Biometrics and Pharmacokinetics R&D, Phoenix International Life Sciences, MontrĂ©al, Quebec, Canada.

Abstract

Confidence intervals of proposed individual bioequivalence metrics are difficult to determine in closed form because their stochastic distributions are unknown. In this article, it is shown that, with slightly modified weights, the Relative Individual Risks (RIR) moment-based scaled statistic for individual bioequivalence that was presented by Schall and Williams has an exact noncentral Fisher's F distribution with noncentrality parameter give by a scaled squared difference in formulations means. This can be approximated by a central F with adjusted degrees of freedom from which it follows that an upper (1-alpha) confidence bound for RIR is given by [formula: see text] where [formula: see text] is the least square estimate of RIR; dfER is the degrees of freedom associated with the reference intrasubject variance estimate, v is the subject-by-formulation degrees of freedom adjusted for noncentrality and alpha is the significance level. Individual bioequivalence is concluded if UL does not exceed the regulatory limit. The performance of this confidence interval was investigated by comparing its experimental bioequivalence rate to that of the unweighted metric under known parameter situations through simulations of two formulations in a fully replicated study design. Results showed that the proposed metric is slightly less biased and more precise than the unweighted metric.

PMID:
9679224
[PubMed - indexed for MEDLINE]
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