title: Reasons for rejection of patient-reported outcome label claims: a compilation based on a review of patient-reported outcome use among new molecular entities and biologic license applications, 2006-2010.
abstract: OBJECTIVE
  Previous analyses of patient-reported outcome (PRO) label claims concentrated only on successful label claims. The goal of this research was to explore the reasons why PRO label claims were denied and to compile regulatory feedback regarding the use of PROs in clinical trials.
  
  
  METHODS
  By using the Food and Drug Administration's Drug Approval Report Web page, all new molecular entities and biologic license applications approved between January 2006 and December 2010 were identified. For identified drug products, medical review sections from publicly available drug approval packages were reviewed to identify PRO end-point status and any Study Endpoints and Label Development team comments.
  
  
  RESULTS
  Of the 116 new molecular entities and biologic license applications with accompanying drug approval packages identified and reviewed, 44.8% of the products included PROs as part of the pivotal studies; however, only 24.1% received PRO label claims. Primary reasons for denial included issues of fit for purpose, issues of study design, data quality or interpretation, statistical issues, administrative issues, and lack of demonstrated treatment benefit.
  
  
  CONCLUSIONS
  Based on drug approval packages, nearly half (45%) of new molecular entitity/biologic license application products in the years 2006 to 2010 included PROs in the clinical trials supporting their approval, yet this rate is not reflected by claims granted. Understanding the nature of PRO claims granted under the current regulatory guidance is important. In addition, a clear understanding of denied claims yields valuable insight into where sponsors may improve implementation of PROs in clinical trials and submission of PRO evidence to increase the likelihood of obtaining PRO label claims.
authors.affiliation: RTI Health Solutions, Research Triangle Park, NC 27709, USA. demuromercon@rti.org
authors.forename: Carla
authors.initials: C
authors.lastname: DeMuro
authors.forename: Marci
authors.initials: M
authors.lastname: Clark
authors.forename: Margaret
authors.initials: M
authors.lastname: Mordin
authors.forename: Sheri
authors.initials: S
authors.lastname: Fehnel
authors.forename: Catherine
authors.initials: C
authors.lastname: Copley-Merriman
authors.forename: Ari
authors.initials: A
authors.lastname: Gnanasakthy
mesh_terms: D017277:Drug Approval; D004348:Drug Labeling / Q000331:legislation & jurisprudence*; D023381:Endpoint Determination; D033161:Government Regulation; D006801:Humans; D008004:Licensure; D017063:Outcome Assessment, Health Care / Q000379:methods*; D010358:Patient Participation; D057566:Self Report; D014481:United States; D014486:United States Food and Drug Administration