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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Pharmaceutical Stati...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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Controlling type I error in the reference‐scaled bioequivalence evaluation of highly variable drugs

Jordi Ocaña; Joel Muñoz;

Controlling type I error in the reference‐scaled bioequivalence evaluation of highly variable drugs

Abstract

Reference-scaled average bioequivalence (RSABE) approaches for highly variable drugs are based on linearly scaling the bioequivalence limits according to the reference formulation within-subject variability. RSABE methods have type I error control problems around the value where the limits change from constant to scaled. In all these methods, the probability of type I error has only one absolute maximum at this switching variability value. This allows adjusting the significance level to obtain statistically correct procedures (that is, those in which the probability of type I error remains below the nominal significance level), at the expense of some potential power loss. In this paper, we explore adjustments to the EMA and FDA regulatory RSABE approaches, and to a possible improvement of the original EMA method, designated as HoweEMA. The resulting adjusted methods are completely correct with respect to type I error probability. The power loss is generally small and tends to become irrelevant for moderately large (affordable in real studies) sample sizes.

Subjects by Vocabulary

Microsoft Academic Graph classification: Statistics Scaling Sample size determination Value (computer science) Type I and type II errors Variable (computer science) Constant (mathematics) Bioequivalence Mathematics Statistical significance

Keywords

Pharmacology (medical), Pharmacology, Statistics and Probability, Drugs, Generic, Humans, Legislation, Drug, Pharmaceutical Preparations, Probability, Research Design, Sample Size, Therapeutic Equivalency

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Average
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
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