title: Impact of pharmacometric reviews on new drug approval and labeling decisions--a survey of 31 new drug applications submitted between 2005 and 2006.
abstract: Exploratory analyses of data pertaining to pharmacokinetic, pharmacodynamic, and disease progression are often referred to as the pharmacometrics (PM) analyses. The objective of the current report is to assess the role of PM, at the Food and Drug Administration (FDA), in drug approval and labeling decisions. We surveyed the impact of PM analyses on New Drug Applications (NDAs) reviewed over 15 months in 2005-2006. The survey focused on both the approval and labeling decisions through four perspectives: clinical pharmacology primary reviewer, their team leader, the clinical team member, and the PM reviewer. A total of 31 NDAs included a PM review component. Review of NDAs involved independent quantitative evaluation by FDA pharmacometricians. PM analyses were ranked as important in regulatory decision making in over 85% of the 31 NDAs. Case studies are presented to demonstrate the applications of PM analysis.
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Bhattaram
authors.forename: C
authors.initials: C
authors.lastname: Bonapace
authors.forename: D M
authors.initials: DM
authors.lastname: Chilukuri
authors.forename: J Z
authors.initials: JZ
authors.lastname: Duan
authors.forename: C
authors.initials: C
authors.lastname: Garnett
authors.forename: J V S
authors.initials: JV
authors.lastname: Gobburu
authors.forename: S H
authors.initials: SH
authors.lastname: Jang
authors.forename: L
authors.initials: L
authors.lastname: Kenna
authors.forename: L J
authors.initials: LJ
authors.lastname: Lesko
authors.forename: R
authors.initials: R
authors.lastname: Madabushi
authors.forename: Y
authors.initials: Y
authors.lastname: Men
authors.forename: J R
authors.initials: JR
authors.lastname: Powell
authors.forename: W
authors.initials: W
authors.lastname: Qiu
authors.forename: R P
authors.initials: RP
authors.lastname: Ramchandani
authors.forename: C W
authors.initials: CW
authors.lastname: Tornoe
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: J J
authors.initials: JJ
authors.lastname: Zheng
mesh_terms: D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D003524:Cyclosporins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003625:Data Collection; D003661:Decision Support Techniques; D018450:Disease Progression; D004334:Drug Administration Schedule; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D004341:Drug Evaluation / Q000379:methods; D004348:Drug Labeling / Q000331:legislation & jurisprudence*; D054714:Echinocandins; D000068338:Everolimus; D006801:Humans; D017387:Investigational New Drug Application / Q000331:legislation & jurisprudence / Q000706:statistics & numerical data; D055666:Lipopeptides; D008074:Lipoproteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077551:Micafungin; D010380:Peer Review; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010599:Pharmacokinetics; D010601:Pharmacology, Clinical; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018570:Risk Assessment / Q000379:methods; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence / Q000592:standards; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D003524:Cyclosporins; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D011810:Quinoxalines; D000068338:Everolimus; D000077551:Micafungin; D020123:Sirolimus; D000068580:Varenicline