Presentation (CTI)

OBJECTIVES: FDA and ISPOR guidance (2020-2023) emphasize the role of Patient-Reported Outcome Measures (PROMs) in clinical trials to directly capture patient perspectives and experiences. PROMs can be especially valuable in rare diseases, where consensus on meaningful endpoints for regulators and payers is evolving. This study updates the Hong et al. 2019 assessment to compare PROM labeling trends in FDA-approved orphan drugs.
METHODS: We reviewed FDA orphan drug databases to identify new molecular entities (NMEs) and biologic license applications (BLAs) receiving orphan designation between January 2018-October 2024. FDA-approved labels reporting PROM study endpoints met inclusion criteria. Trial records, package inserts, and instrument references were reviewed to abstract data on approval year, endpoint ranking, outcomes measured, and validation status. Results were analyzed descriptively; Year-over-year and overall trends were assessed (chi-square, p-value <0.05).
RESULTS: PROM-based labeling occurred in 14% (28/198) of FDA-approved orphan NMEs and BLAs (2018-2024), compared to 8% (13/156) between 2002-2017. PROMs were primary endpoints in more trials than previously reported (68%, 19/28 vs. 54%, 7/13) and secondary endpoints in fewer (36%, 10/28 vs. 54%, 7/13). PROM utilization in trials was consistent (median = 1) across 2018-2024 (range: 1-3) and 2002-2017 (range: 1-2). Use of unique tools increased twofold across study periods (27 vs. 13 tools). More PROMs in the recent versus prior study period were validated (93%, 25/27 vs. 85%, 11/13), and most captured symptom-related outcomes (78%, 21/27), an increase from 54% (7/13). No significant trends were observed for tool use, ranking, or outcome measured.
CONCLUSIONS: Orphan FDA labels referencing PROM measures, and use as the primary endpoint, increased since the prior review but remain a rarity. Given the dearth of evidence in orphan conditions, further integration of PROMs in trials may provide an opportunity to capture meaningful patient outcomes and better communicate value to payers.