PROM-ising Progress? Trends in Patient- and Clinician-Reported Outcome Measures in FDA Orphan Drug Labels.

Abstract

Objectives: This study examined trends in patient-reported outcome measure (PROM) and clinician-reported outcome measure (ClinROM) use in FDA orphan drug labels from 2018 to 2024, comparing PROM utilization with findings from 2002-2017.

Methods: We reviewed FDA-approved orphan drug labels for new molecular entities (NMEs) and biologic license applications (BLAs) with orphan designation from January 1, 2018, to December 31, 2024. Eligible labels referenced a PROM and/or ClinROM. Data was abstracted on approval year, FDA expedited review pathway, study design, endpoint ranking, instrument category, outcomes measured, and published validation references. Descriptive and trend analyses (p<0.05) were conducted and PROM findings compared to 2002-2017 rates.

Results: Among 207 eligible labels from 2018-2024, 13.5% included PROMs, 10.1% included ClinROMs, and 5.3% referenced both. PROM use increased 5.2% (13.5% vs. 8.3%) from 2002-2017. PROMs were primary endpoints in >60% of 2018-2024 labels-a modest increase since 2002-2017-and ClinROMs were primary in more than three-fourths. 'Rare Disease Specific' instruments were included in <50% of PROM- and ClinROM-based labels during both review periods, one-third or fewer of which were ranked as a primary endpoint. The majority of PROM and ClinROM instruments across review periods captured symptoms and had published validation references. Significant associations (p<0.05) were observed between endpoint ranking and instrument type for labels including PROMs as well as both PROMs and ClinROMs across review periods.

Conclusions: PROM and ClinROM inclusion in FDA orphan drug labels is uncommon. Greater integration could improve care and better convey clinically meaningful treatment value.