Impact of Real-World Evidence in the HTA Process in France: Analysis of Transparency Commission Appraisals in Rare Diseases

OBJECTIVES: Given the importance of the French HTA in enabling patient access to new treatment for Rare Diseases (RD), in France and in other EU countries, this study aimed to describe the use and impact of real-world evidence (RWE) in the French National Authority for Health (HAS) Transparency Committee (TC) opinions for value demonstration.

METHODS: A retrospective study on French HTA TC appraisals in the RD domain (RD or orphan drugs) from February 2023 (latest HAS recommendation) to April 2024 was performed, focusing on initial opinions (including extensions of indication) and reevaluations. A review based on screening of appraisals mentioning RWE (including early access data) and a detailed analysis were conducted. RWE impact was qualified as direct (RWE referred to in the SMR/ASMR (medical benefit/ improvement in medical benefit) justification, whatever levels obtained), indirect (detailed results, no significant criticism, not highlighted in the SMR/ASMR justification), or absent (significant methodological criticism or minimally detailed RWE).

RESULTS: Among the 67 eligible TC appraisals identified in the study period, 52 (78%) featured RWE, 8 supporting target population section only and 44 supporting value demonstration. 24/52 (46%) featured early access data, 13/24 detailed. Among the 44 appraisals where RWE supported value demonstration, 28 were initial opinions and 16 were reevaluations. RWE directly impacted 18% of opinions (8/44) (3 indirect comparisons with an external arm and 5 non-comparative studies confirming clinical results), indirectly impacted 20% (9/44), and had no impact on 61% (27/44), mainly due to methodological limitations.

CONCLUSIONS: This study provides preliminary evidence that RWE can potentially have a direct impact on TC opinions in the RD domain in France. Encouraging close collaboration between pharmaceutical companies and authorities would be helpful to leverage RWE in final HTA TC appraisals, especially given the specificities of the RD, where establishing a continuum of evidence generation is crucial.