Presentation (CTI)

OBJECTIVES: Patient-reported outcomes (PROs) are increasingly recognised in HTA as critical evidence of patient-relevant benefit, particularly for orphan medicines where trial populations are small and PROs may represent the primary means of capturing meaningful treatment effects. In Italy, AIFA monitoring registries govern real-world prescribing by defining criteria for treatment initiation and continuation, determining what evidence justifies continued access. Whether PROs that demonstrate benefit at HTA are subsequently used to inform these decisions remains unclear. This study assesses whether PROs are retained from pivotal trials through to AIFA monitoring registries, or whether their role is confined to the HTA stage.
METHODS: We conducted a cross-sectional analysis of AIFA schede for orphan-designated products with an active monitoring registry opened from 1 January 2024. Products were included only where a PRO was a primary, key secondary, or secondary trial endpoint; those with no PRO or exploratory-only PROs were excluded. For each product we recorded the PRO's endpoint tier, domain (symptoms/functioning/HRQoL), and instrument, then assessed whether it appeared in the scheda (PRO retention vs drop-out). Where present, the PRO was classified as a decision criterion (gating initiation or continuation) or observational.
RESULTS: Of 144 schede screened, 42 (29%) were orphan-designated and 27 (19%) met inclusion criteria; the PRO was a primary or key secondary endpoint in 5 (19%). A PRO was retained in only 8 of 27 products (30%), giving a drop-out rate of 70%. Where retained, it appeared at both baseline and re-evaluation for prescribing in all cases but it functioned as a decision criterion in only 3 (11%); in the remaining 5 it was observational only.
CONCLUSIONS: Even where PROs served as trial endpoints, they rarely informed AIFA's real-world prescribing criteria. This disconnect between evidence prioritised at HTA and that governing post-approval access represents a missed opportunity to embed PROs into access decisions for orphan medicines.