title: A Bioequivalence Test by the Direct Comparison of Concentration-versus-Time Curves Using Local Polynomial Smoothers.
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.
authors.affiliation: Division of Clinical Research, First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China; Center for Clinical and Translational Science, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; School of Mathematics, Jilin University, 2699 Qianjin Street, Changchun, Jilin 130012, China.
authors.forename: Suyan
authors.identifier: 0000-0002-5942-1542
authors.initials: S
authors.lastname: Tian
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Atlanta, GA 30322, USA.
authors.forename: Howard H
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Laboratory of Molecular Neurooncology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Division of Rheumatology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Orange
authors.affiliation: Clinical Pharmacology Center, Research Institute of Translational Medicine, First Hospital of Jilin University, Dongminzhu Street, Changchun 130021, China; College of Life Science, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Jingkai
authors.identifier: 0000-0002-4731-6649
authors.initials: J
authors.lastname: Gu
authors.affiliation: Center for Clinical and Translational Science, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Center for Biostatistics, Department of Population, Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomics Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Mayte
authors.identifier: 0000-0001-8712-3553
authors.initials: M
authors.lastname: Suárez-Fariñas
mesh_terms: D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D003198:Computer Simulation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016568:Drugs, Generic / Q000494:pharmacology*; D005260:Female; D008297:Male; D015233:Models, Statistical; D004364:Pharmaceutical Preparations; D012016:Reference Values; D013810:Therapeutic Equivalency
chemical_list: D016568:Drugs, Generic; D004364:Pharmaceutical Preparations