OBJECTIVES: According to the 2009 FDA Patient Reported Outcome (PRO) guidance, one of the study design requirements for PRO labelling claims is a randomized double-blind clinical trial. However, in the context of rare diseases (RD), registration trials are frequently conducted without comparator arm. The aim of this review is to assess experience of clinical outcomes assessment (COA)/PRO with regards to label claims, using single-arm studies in the RD area.

METHODS: The US FDA labels considering single arm trials in the RD area were identified through the Prismaccess™ platform (IQVIA) from inception. For labels including COA, the outcome was further categorized as a clinician-reported outcome (ClinRO), PRO, or performance outcome (PerfO). For these labels, the 'Indications and Usage' section as well as the 'Section 14 Clinical Studies' of each label were examined. The assessment of these label sections determined whether a COA /PRO label claim was granted for these molecules.

RESULTS: As of April 6th, 2023, a total of 92 FDA labels for molecules that had FDA submissions based on single-arm studies in the RD field were found. Only four out of 92 included COA, three were ClinRO and one was PerfO. None was a PRO. The US FDA did not grant any PRO label claims, however in exceptional cases, ClinRO or PerfO label claim were awarded to products that underwent submission based on single-arm trials in RD.

CONCLUSIONS: In RD area where non-conventional study design is accepted by regulatory bodies, it would be important to increase the recognition of ClinRO, PerfO and PRO label claims in order to better inform prescribers and patients about clinical benefits expected from innovative treatment.