Acceptability of RWE by HTA Bodies Across Europe to Support Clinical Benefit Assessments of Rare Disease Therapies

OBJECTIVES: Despite published guidance across Europe, there is a lack of stakeholder knowledge surrounding the acceptance of real-world evidence (RWE) for non-oncology orphan medicinal products (non-onco OMP). This research aimed at capturing the extent to which RWE was accepted as part of the clinical assessments of non-onco OMP by HTA bodies across Europe.

METHODS: EMA database was queried to identify non-onco OMP approvals (2018-2023) that included RWE. Corresponding HTA reports across four European HTA bodies (NICE, England; HAS, France; IQWIG, Germany; TLV, Sweden) were analyzed to assess: 1/ Whether RWE was considered in recommendations; 2/ Type of real-world data (RWD) used; 3/ Type of evidence (clinical/ safety/ quality-of-life [QoL]/ economic).

RESULTS: Of the 105 non-onco OMPs identified in the EMA database, the number of corresponding HAS, IQWIG, NICE, TLV HTA reports was 78, 68, 37, and 23, respectively. 30% (7 for TLVL and 20 for IQWIG), 53% (41 for HAS) and 73% (27 for NICE) of these HTA reports included RWE, of which, registry (47%) and retrospective observational studies (24%) were the most frequent RWD sources. The proportion of positive HTA recommendations where RWE was used ranged from 71% (TLVL) to 100% (IQWIG). Among the 95 applications with positive recommendations (range 5, Sweden to 40, France), RWE most commonly consisted of clinical (65%), followed by safety (27%), economic (17%), and QoL (10%) evidence packages.

CONCLUSIONS: RWE was found to be considered and accepted as supportive evidence for clinical assessments of non-onco OMPs across the four European HTA bodies. However, the level of acceptance varied across these geographies. Whilst extracting data directly from HTA dossiers brings a valuable viewpoint on how RWE is perceived by HTA bodies, it was not possible to establish whether RWE was a determinant factor for final HTA recommendations. Further qualitative research is required to investigate this topic in more depth.