Bioequivalence of ANDA Data using a Non-Informative Bayesian Procedure (BEST) Compared with the Two One‑Sided t‑Tests (TOST).

IF 5 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Jing Wang, Gregory Campbell, Jae H Lee, Meng Hu, Kairui Feng, Somesh Chattopadhyay, Liang Zhao, Carl C Peck
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引用次数: 0

Abstract

The regulatory statistical standard for evaluating average bioequivalence (BE) in generic drug testing, formulation bridging, and 505b2 drug comparisons has traditionally employed the two one-sided t-tests (TOST) procedure. A comparison of BE determinations of TOST and a t-distribution-based, non-informative Bayesian procedure (BayesT) was conducted on 2341 pharmacokinetic parameter datasets in 678 anonymized abbreviated new drug applications (ANDAs) to assess the influence of deviations from lognormality and the presence of extreme values. This research has been motivated to assess reliability of statistical inference procedures for accurate and fair regulatory assessments of BE and non-BE (NBE). The BE criterion of 90% confidence (CI) or Bayesian credible (CrI) intervals of log test/reference ratios for TOST and BayesT was 0.80-1.25. TOST. BayesT agreed on BE conclusions in 98.9% of cases. There were 20 disagreed cases in which TOST rejected BE and BayesT concluded BE, wherein all cases failed the lognormality test and 17 of which contained extreme values (4.2% of 409 cases that contained extreme values). In this circumstance, TOST can be overly conservative in the presence of extreme values. There were 7 cases in which TOST concluded BE at outer BE bounds, while BayesT marginally rejected BE, despite these cases successfully passing the lognormality test. While TOST remains a widely accepted method for BE assessment, the presence of extreme values and deviations from lognormality may lead to faulty inference of BE. The BayesT methodology offers an alternative approach to TOST that can be prespecified to assess BE in such scenarios. Pre-specified application of the BayesT procedure may ensure more reliable outcomes in regulatory assessments of BE.

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来源期刊
AAPS Journal
AAPS Journal 医学-药学
CiteScore
7.80
自引率
4.40%
发文量
109
审稿时长
1 months
期刊介绍: The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including: · Drug Design and Discovery · Pharmaceutical Biotechnology · Biopharmaceutics, Formulation, and Drug Delivery · Metabolism and Transport · Pharmacokinetics, Pharmacodynamics, and Pharmacometrics · Translational Research · Clinical Evaluations and Therapeutic Outcomes · Regulatory Science We invite submissions under the following article types: · Original Research Articles · Reviews and Mini-reviews · White Papers, Commentaries, and Editorials · Meeting Reports · Brief/Technical Reports and Rapid Communications · Regulatory Notes · Tutorials · Protocols in the Pharmaceutical Sciences In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.
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