OBJECTIVES:

Patient-reported outcomes (PROs) focus on the patient experience. Despite 2009 FDA guidelines on PRO use, it is unclear how they inform regulatory and reimbursement processes. This review assessed research related to PRO impact on regulatory, health technology assessment (HTA) and market access (MA) milestones. From this, a framework was developed and validated to assess PRO evidence impact on regulatory approvals.

METHODS:

A literature review was undertaken to identify research on the impact of PROs (excluding EQ-5D) on the three milestones (01/01/2009-18/08/2020). An impact assessment framework was then synthesised and tested in a study of 20 regulatory approvals spanning 28/08/2018-6/11/2020 (10 EMA; 10 FDA).

RESULTS:

The literature review included 77 studies (Regulatory 37; HTA 19; MA 47). The most common regulatory impact category was “support drug labelling and approval” (30/37). Nine studies reported that the EMA is more accepting of PRO claims than the FDA. For HTA, 12/19 studies reported the impact of PROs in “supporting reimbursement decisions”. Several PRO impact categories were identified for MA; however, overall study quality was low. Across all milestones, the most common barriers to PRO impact were inadequate clinical trial design, insufficient data analysis and a lack of evidence of PRO validity.

In the study, the regulatory impact assessment framework found that PRO label claims were granted in 2/10 EMA and 1/10 FDA approvals. The remaining approvals denied all PRO claims, most commonly due to lack of statistical significance (5/17) and trial design (3/17).

CONCLUSIONS:

This review shows that most quantitative research on PRO impact has focused on regulatory approval; HTA impact is underexplored and MA impact has been analysed more qualitatively. The regulatory framework provides a systematic approach to analysing the impact of PRO evidence. However, despite FDA guidelines, a consistent and successful approach to PRO inclusion is yet to be established.