A Bioequivalence Test by the Direct Comparison of Concentration-versus-Time Curves Using Local Polynomial Smoothers

• Type of Material: Article
• Authors: Suyan Tian, Jilin University; Howard Chang, Emory University; Dana Orange, Rockefeller University; Jingkai Gu, Jilin University; Mayte Suárez-Fariñas, Rockefeller University
• Language: English
• Date: 2016-01-01
• Publisher: Hindawi Publishing Corporation
• Publication Version: Final Published Version
• Copyright Statement: © 2016 Suyan Tian et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1155/2016/4680642
• Title of Journal or Parent Work: Computational and Mathematical Methods in Medicine
• ISSN: 1748-670X
• Volume: 2016
• Start Page: 4680642
• End Page: 4680642
• Grant/Funding Information: This research was supported by a Clinical and Translational Science Award Grant UL1RR024143; Suyan Tian was also supported by the National Natural Science Foundation of China (no. 31401123); Mayte Suárez-Fariñas was also partially supported by the Irma T Hirschl Career Scientist Award; Jingkai Gu was supported by the National Natural Science Foundation of China (no. 81102383), the Science and Technology Major Specialized Projects for “Significant New Drugs Creation” of the 12th five-year plan (2012ZX09303-015), and the National Key Technology R&D Program of the Ministry of Science and Technology (2012BAI30B00).
• Keywords: EQUIVALENCE; Mathematical & Computational Biology; Science & Technology; LONGITUDINAL DATA-ANALYSIS; Life Sciences & Biomedicine; BANDWIDTH
• Research Categories: Health Sciences, Pharmacology; Biology, Biostatistics

Abstract

In order to test if two chemically or pharmaceutically equivalent products have the same efficacy and/or toxicity, a bioequivalence (BE) study is conducted. The 80%/125% rule is the most commonly used criteria for BE and states that BE cannot be claimed unless the 90% CIs for the ratio of selected pharmacokinetics (PK) parameters of the tested to the reference drug are within 0.8 to 1.25. Considering that estimates of these PK parameters are derived from the concentration-versus-time curves, a direct comparison between these curves motivates an alternative and more flexible approach to test BE. Here, we propose to frame the BE test in terms of an equivalence of concentration-versus-time curves which are constructed using local polynomial smoother (LPS). A metric is presented to quantify the distance between the curves and its 90% CIs are calculated via bootstrapping. Then, we applied the proposed procedures to data from an animal study and found that BE between a generic drug and its brand name cannot be concluded, which was consistent with the results by applying the 80%/125% rule. However, the proposed procedure has the advantage of testing only on a single metric, instead of all PK parameters.