title: Impact of pharmacometric analyses on new drug approval and labelling decisions: a review of 198 submissions between 2000 and 2008.
abstract: Pharmacometric analyses have become an increasingly important component of New Drug Application (NDA) and Biological License Application (BLA) submissions to the US FDA to support drug approval, labelling and trial design decisions. Pharmacometrics is defined as a science that quantifies drug, disease and trial information to aid drug development, therapeutic decisions and/or regulatory decisions. In this report, we present the results of a survey evaluating the impact of pharmacometric analyses on regulatory decisions for 198 submissions during the period from 2000 to 2008. Pharmacometric review of NDAs included independent, quantitative analyses by FDA pharmacometricians, even when such analysis was not conducted by the sponsor, as well as evaluation of the sponsor's report. During 2000-2008, the number of reviews with pharmacometric analyses increased dramatically and the number of reviews with an impact on approval and labelling also increased in a similar fashion. We also present the impact of pharmacometric analyses on selection of paediatric dosing regimens, approval of regimens that had not been directly studied in clinical trials and provision of evidence of effectiveness to support a single pivotal trial. Case studies are presented to better illustrate the role of pharmacometric analyses in regulatory decision making.
authors: Division of Pharmacometrics, Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, MD, USA. jooyeon2.lee@fda.hhs.gov
authors: Joo Yeon
authors: JY
authors: Lee
authors: Christine E
authors: CE
authors: Garnett
authors: Jogarao V S
authors: JV
authors: Gobburu
authors: Venkatesh A
authors: VA
authors: Bhattaram
authors: Satjit
authors: S
authors: Brar
authors: Justin C
authors: JC
authors: Earp
authors: Pravin R
authors: PR
authors: Jadhav
authors: Kevin
authors: K
authors: Krudys
authors: Lawrence J
authors: LJ
authors: Lesko
authors: Fang
authors: F
authors: Li
authors: Jiang
authors: J
authors: Liu
authors: Rajnikanth
authors: R
authors: Madabushi
authors: Anshu
authors: A
authors: Marathe
authors: Nitin
authors: N
authors: Mehrotra
authors: Christoffer
authors: C
authors: Tornoe
authors: Yaning
authors: Y
authors: Wang
authors: Hao
authors: H
authors: Zhu
mesh_terms: D002986:Clinical Trials as Topic; D003661:Decision Support Techniques; D004305:Dose-Response Relationship, Drug; D004348:Drug Labeling / Q000331:legislation & jurisprudence / Q000379:methods / Q000592:standards* / Q000706:statistics & numerical data*; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D017387:Investigational New Drug Application / Q000331:legislation & jurisprudence / Q000379:methods / Q000706:statistics & numerical data*; D008954:Models, Biological; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015507:Drugs, Investigational