A Review Of Patient-Reported Outcome Orphan Drug Labels In The United States From January 2006-September 2013: Analysis Of Evidence For Orphan Drug Pro Label Claims

Objectives: Previous reviews of patient-reported outcome (PRO) label claims did not distinguish products with orphan designation. Literature suggests that less evidence is required for orphan drug approvals compared with non-orphan drugs. This study aimed to identify orphan drug products approved by the US Food and Drug Administration (FDA) between 2006 and 2013, the prevalence of PRO label claims for these products, and levels of evidence supporting PRO claim approval. Methods: Using the Drugs@FDA website, new molecular entities and biologic licensed agents approved between January 2006 and September 2013 with orphan review classification were identified, with subsequent label review. Priority or standard review was also noted. For products with PRO claims, labels and medical and summary review sections from FDA drug approval packages were reviewed to identify indication, reviewing division, PRO endpoint status, PRO measure type, number of phase 3 trials supporting claims, and PRO-related comments from the Study Endpoints and Labeling Development (SEALD) team. Descriptive data were recorded in Microsoft Excel; frequency of measured characteristics was analyzed. Results: For the 43 products identified, a total of 7 PRO label claims were granted to 5(12%) products. Five orphan products achieved 7 PRO claims. Priority and standard review prevalence were similar (44% vs. 40%, respectively) for orphan products; most products (4 of 5) with PRO claims had priority review. A slight majority (60%; 3 of 5 orphan products) included PRO claims supported by ≤ 1 phase 3 trial. Signs/symptoms measures and secondary PRO endpoints were most common (57% each). FDA reviewing division varied. One product had documented comments from SEALD. Conclusions: For the time period evaluated, orphan products rarely included a PRO label claim. These claims may not be needed for orphan product differentiation to the degree that they are for nonorphan products. PRO claims achieved for orphan products appear to require less supporting evidence for approval than non-orphan products, consistent with orphan drug approval expectations.