OBJECTIVES: Patient-centred outcomes (PCOs) focusing on patient experience beyond clinical outcomes are becoming increasingly recognised by regulators as impactful evidence. Despite 2009 FDA guidelines on the use of such outcomes, their implementation in regulatory decision-making remains unclear. A framework was developed and validated to assess PCO evidence impact (excluding EQ-5D) on regulatory approvals.

METHODS: An impact assessment framework was synthesised and tested in a study of 20 recent regulatory approvals (10 FDA [drug approval package, label]; 10 EMA [European Public Assessment Report, Summary of Product Characteristics]). All approvals included “core” PCO evidence (generic or disease-specific questionnaires) and/or additional PCO evidence (outcomes informed by patient diaries).

RESULTS: Of the 20 approvals assessed, 17 included core PCOs exclusively (all secondary or exploratory clinical endpoints) and 3 reported both core and additional PCOs (two were primary endpoints). PCO label claims were granted in 2/10 EMA and 1/10 FDA approvals. These approvals included headache diary evidence (FDA; fremanezumab [migraine treatment]), MIDAS and HIT-6 evidence (EMA; fremanezumab) and CFQ-R evidence (EMA; ivacaftor/tezacaftor/elexacaftor [cystic fibrosis treatment]). The remaining approvals denied all PCO claims, most commonly due to lack of statistical significance (5/17 approvals), trial design (3/17 approvals) and insufficient data (2/17 approvals). Although nearly half (9/20) of the approvals were for oncology indications, no PCO oncology claims were granted. Fremanezumab core PCO evidence was considered favourably by the EMA; however, these claims were rejected by the FDA due to content validity concerns.

CONCLUSIONS: This framework provides a systematic approach to analysing PCO evidence impact in regulatory approvals. Despite FDA guidelines on PCO evidence, it appears a consistent, systematic and successful approach to inclusion is yet to be established. Future research on a larger dataset may further elucidate FDA and EMA requirements.