OBJECTIVES: Previous analyses of PRO label claims concentrated only on successful label claims. The goal of this research was to explore the reasons why PRO label claims were either denied or not sought.
METHODS: Using the FDA Drug Approval Report Webpage, all approved new molecular entities (NMEs) and biologic license applications (BLAs) between February 2006 and December 2010 were identified. For identified drug products, medical review sections from publicly available summary basis of approvals (SBAs) were reviewed to identify PRO endpoint status and any FDA Study Endpoints and Label Development comments.
RESULTS: Out of the 116 NMEs/BLAs identified and accompanying SBAs reviewed, 44.8% of products included PROs as part of the pivotal studies; however, only 24.1% received PRO claims. Primary reasons for denial (where data available) included a lack of demonstration of content validity (inclusive of general measures such as the EQ5D and SF-36) as well as use of PROs to assess symptoms in an open-label setting, lack of consensus on clinically meaningful change, interpretation of or missing PRO data, lack of measurement of full constellation of symptoms, issues of multiplicity and concerns of “bias” in certain PRO measures.
CONCLUSIONS: Nearly half (45%) of submissions included PROs yet this rate is not reflected by claims granted. Understanding the nature of PRO claims granted under the current regulatory guidance is important. Additionally, a clear understanding of claims denied yields valuable insight into where sponsors may improve implementation of PROs in clinical trials and the PRO evidence submitted in order to increase the likelihood of obtaining PRO label claims.
