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Doctoral Dissertation Announcement
Candidate: Srinand Ponnathapura Nandakumar
Doctor of Philosophy
Title: Statistical Procedures for Bioequivalence Analysis
Dr. Joseph W. McKean, Chair
Dr. Joshua D. Naranjo
Dr. Gary L. Neidert
Date: Friday, April 24, 2009 10:00 a.m. - 12:00 p.m.
6625 Everett Tower
Applicants submitting a new drug application (NDA) or new animal drug application (NADA) under the Federal Food (section 505(b)), Drug, and Cosmetic Act (FDC Act) are required to document bioavailability (BA). If approved, an NDA drug product may subsequently become a reference listed drug (RLD). A sponsor of an abbreviated new drug application (ANDA) or abbreviated new animal drug application (ANADA) must document first pharmaceutical equivalence and then bioequivalence (BE) to be deemed therapeutically equivalent to an RLD.
BE is documented by comparing the performance of the generic (test) and listed (reference) products. The Average (ABE), Population (PBE) and Individual (IBE) bioequivalence have been used to establish the equivalence in the pharmacokinetics of the drug.
Population Bioequivalence: A small sample and a large sample PBE is analyzed with Cornish Fisher's comparison and a Bootstrap procedure. Using Delta method on small sample, we get the CF upper 95% on the point estimate and establish criteria for PBE. On Bootstraps, asymptotic theory is used on estimate the Robust parameters as a parallel to LS and compare effect of outliers on validity and power using MSE.
Average Bioequivalence: We implement and test ABE on small samples treating AUC and Cmax on a Multivariate setup with outliers. Check for a 2 one sided LS test with Generalized Robust procedures and compare effect of outliers on validity and power using MSE.