Potential of patient-reported outcomes as nonprimary endpoints in clinical trials

Abstract

BackgroundThe purpose of this research was to fully explore the impact of endpoint type (primary vs. nonprimary) on decisions related to patient-reported outcome (PRO) labeling claims supported by PRO measures and to determine if nonprimary PRO endpoints are being fully optimized.This review examines the use of PROs as both primary and nonprimary endpoints in support of demonstration of treatment benefit of new molecular entities (NMEs) and biologic license applications (BLAs) in the United States in the years 2000 to 2012.MethodsAll NMEs and BLAs approved by the Food and Drug Administration (FDA) between January 2000 and June 2012 were identified using the FDA Drug Approval Reports Web page. Generic products granted tentative approvals were excluded. For all identified products, medical review sections from publicly available drug approval packages were reviewed to identify PRO endpoint status. Product labels (indication, clinical trials sections) were reviewed to determine the number and type of PRO claim.ResultsA total of 308 NMEs/BLAs were identified. Of these, 70 NMEs/BLAs (23%) were granted PRO claims. The majority of product claims were for disease- or condition-specific signs and symptoms. Of the 70 products with PRO claims, a PRO was a primary endpoint for the vast majority (57 [81%]). A total of 19 of the 70 products were granted a PRO claim based on a nonprimary endpoint. While nonprimary endpoints were used most often to support claims of improved signs or symptoms, nonprimary endpoints were much more likely to support claims of higher order impacts.ConclusionsSuccessful PRO labeling claims are typically based on primary endpoints assessing signs and symptoms. Based on this research, studies with PROs as primary endpoints are far more likely to facilitate positive regulatory review and acceptance of PROs in support of labeling claims. Although inclusion of PROs as nonprimary endpoints in clinical trials has its challenges, recent PRO labels granted by the FDA show that they can indeed be candidates for PRO labeling claims as long as they are supported by evidence.

Streamlining the Validation of Patient Reported Outcome (PRO) Measures in Drug Regulatory Processes

“…Patient reported outcome labels were approved in 23 % (n = 70 products) of all new molecular entities/biologic license approvals at the FDA over the period 2000-2012 (n = 308) [33], more frequently when used as a primary than as a secondary endpoint [33]. Differences have been observed with approvals across therapeutic areas.…”

An introduction to patient-reported outcome measures in ophthalmic research

“…Of 308 drugs approved during this period, 70 were specifically approved for 'PRO labelling', and for 57 of these, this was based on studies in which the PRO was the primary outcome. 12 There are some areas of medicine where the measurement of a PRO is self-evidently essential and therefore should be a primary trial outcome (eg, pain in a trial of analgesic efficacy). Arguably, however, the assessment of PROs should be a required part of all comparative effectiveness trials.…”

Lebensqualität bei pulmonal arterieller und chronisch thromboembolischer pulmonaler Hypertonie

“…wurden diese von den Gesundheitsbehörden verlangt [85,86]. PRO wird als Oberbegriff für viele verschiedene Konzepte zur Messung subjektiv empfundener Gesundheitszustände und Therapieeffekte gebraucht [87].…”