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Definition of individual bioequivalence: occasion‐to‐occasion versus mean switchability
Author(s) -
Kimanani Ebi K.
Publication year - 2000
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/1097-0258(20001030)19:20<2797::aid-sim546>3.0.co;2-5
Subject(s) - bioequivalence , mathematics , interpretability , resampling , metric (unit) , statistics , parametric statistics , variance (accounting) , econometrics , computer science , medicine , artificial intelligence , operations management , business , accounting , economics , pharmacology , bioavailability
Two moment‐based scaled definitions of individual bioequivalence are discussed. Based on a mixed effects linear model, their evaluations respectively lead to an unweighted (θ 11 ) and a parametric (θ 15 ) metric. The two metrics are estimated with respect to study design and two estimation methods. Results show that the two IBE metrics perform equivalently in the fully replicated design. In the semi‐replicated design, the definition of θ 11 may not be valid while the evaluation of θ 15 results in a reduction of the weights in the mean difference and switchability components of the metric. Percentage rejection rates in the latter design indicate that θ 11 is more conservative than θ 15 . This is because there is an increase of about 15 per cent in the producer risk in θ 11 relative to θ 15 compared to a 7 per cent increase in the consumer risk in θ 15 relative to θ 11 . A further disadvantage of the design is that there is a 33 per cent loss in the subject‐by‐treatment variance efficiency which is reflected in a similar amount of decreased sensitivity to departures from perfect bioequivalence even when more subjects are used to equalize the number of exposure occasions in the two designs. It is concluded that a mean switchability criterion may be more appropriate from an interpretability perspective, the bootstrap resampling method used to evaluate individual bioequivalence based on θ 11 may need to be bias‐corrected and that the semi‐replicated design should be used cautiously. Copyright © 2000 John Wiley & Sons, Ltd.