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Journal of Probability and Statistics
Volume 2015, Article ID 298647, 13 pages
http://dx.doi.org/10.1155/2015/298647
Research Article

Confidence Region Approach for Assessing Bioequivalence and Biosimilarity Accounting for Heterogeneity of Variability

School of Medicine, Duke University, Durham, NC 27705, USA

Received 27 August 2015; Accepted 23 November 2015

Academic Editor: Steve Su

Copyright © 2015 Jianghao Li and Shein-Chung Chow. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

For approval of generic drugs, the FDA requires that evidence of bioequivalence in average bioequivalence in terms of drug absorption be provided through the conduct of a bioequivalence study. A test product is said to be average bioequivalent to a reference (innovative) product if the 90% confidence interval of the ratio of means (after log-transformation) is totally within (80%, 125%). This approach is considered a one-parameter approach, which does not account for possible heterogeneity of variability between drug products. In this paper, we study a two-parameter approach (i.e., confidence region approach) for assessing bioequivalence, which can also be applied to assessing biosimilarity of biosimilar products. The proposed confidence region approach is compared with the traditional one-parameter approach both theoretically and numerically (i.e., simulation study) for finite sample performance.