OBJECTIVES: Nowadays, more and more drugs at an early stage of clinical development undergo HTA to provide access to patients, especially in oncology or rare diseases, often with weak or presumptive evidence. In France, the TC newly reaffirmed doctrine states that when justified, single-arm clinical trials with indirect comparison of good methodological quality may lead to valuation in the Clinical Benefit (SMR) or Clinical Added Value (ASMR). We aimed to understand how drugs with such clinical development were recently assessed and which were the drivers of the appraisals.

METHODS: We searched on HAS database with key words “single-arm” and “non-comparative” (in French) from 2020 (year of last doctrine update) to 2022. Information was collected on orphan status, clinical package submitted, solicited levels of SMR and ASMR, and final levels granted by TC.

RESULTS: 216 appraisals were screened, of which 42 assessing 47 indications were included. 55,3% of indications obtained an “important” SMR, and 19,1% obtained an “insufficient” SMR (refusal to reimbursement). Among 27 “important” SMR, there was one level 2 ASMR, nine level 3, three level 4 and thirteen level 5 (no added value). Single-arm trials were generally more accepted and appraisals were more favorable for orphan drugs (mean ASMR level: 3,9) than for non-orphan drugs (mean 4,8). Indirect comparisons were available in 21 indications (44,6%) but were not robust enough to be considered in SMR nor ASMR final granted level justification, nor seemed to influence global appraisals.

CONCLUSIONS: Drugs with clinical development based on single-arm trials were mainly assessed according to the medical need in the targeted disease, such as orphan status, to lead to a valuation in SMR or ASMR. No indirect comparisons provided by applicants with sufficient methodological quality were able to influence the final appraisal of the TC for these drugs in the last three years.