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

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