A Review on the Role of Comparators in French Health Technology Assessments

OBJECTIVES: HTA ideally requires comparative clinical evidence vs. an approved treatment representing the existing standard of care. However, there is sometimes no clearly established standard of care. We reviewed HTA appraisals completed by the French HTA agency, Haute Autorité de Santé (HAS), in 2023 and examined in particular the outcomes of assessments where the comparator was deemed irrelevant by HAS.

METHODS: Structured data extracted from HAS reports published in 2023 were obtained from the NaviHTA database. First, the frequencies of different added clinical value (ASMR) ratings were compared between cases with and without relevant comparator. Then, the corresponding submitted evidence and assessment outcomes were reviewed, focusing on the justification of ASMR ratings for cases with non-relevant comparator.

RESULTS: Eighty-nine HAS reports with evidence packages including comparative trials were identified. A low or moderate ASMR (III-IV) was issued for 42 of 74 cases with relevant comparator, vs. 7 of 15 cases with non-relevant comparator. In 2 of the latter 7 cases, the ASMR III-IV was assigned for a restricted patient subgroup only. The analysis of ASMR justifications for the 7 cases with ASMR III-IV in absence of relevant comparator showed that superiority was acknowledged in all cases, high unmet needs in 3 cases and acceptable safety profile in 3 cases. An indirect treatment comparison (ITC) was submitted by the manufacturer in 2 cases, but dismissed by the agency due to limitations.

CONCLUSIONS: Comparator relevance is a major determinant of ASMR in HAS assessments. Added clinical value was acknowledged in a few cases without relevant comparator, for all patients or for a restricted subgroup, generally due to uncertainties around relevant comparators or because they were not available at the time of clinical studies for the assessed product. ITC played no role in these decisions.