OBJECTIVES: Health Technology Assessment (HTA) bodies are increasingly facing Surrogates Endpoints (SE) when assessing drugs as part of the reimbursement process, when data on a final clinical outcome are not available yet or not measurable at the regulatory approval stage. The objectives of our study were to assess SEs’ acceptability by the transparency committee (TC), France’s HTA body, and how they impact opinions’ main outcomes (clinical benefit [SMR] and clinical added value [ASMR]).

METHODS: A database comprising the contents of all TC transcripts published between November 2019 and October 2022 was searched to identify cases where SE’s acceptability and their impact on reimbursement decisions were discussed. Debates and key information from the transcripts and associated opinions (study design and methodology, patients’ characteristics, results, SMR/ASMR) were extracted and analyzed.

RESULTS: Fifty-five transcripts corresponding to 50 opinions (9.0% of opinions published over the period) were identified. SMR was high/moderate/low/insufficient in 71%/15%/6%/8% and ASMR levels I/II/III/IV/V were reported in 2%/4%/13%/48%/25%, respectively. Insufficient SMR and ASMR V were mainly driven by methodological limitations, effect size, and rarely only by SE. Discussions focused on the role of SEs in clinical practice and guidelines rather than their statistical validation. However, ASMR≥IV were often granted based on additional evidence (i.e., final clinical outcomes).

CONCLUSIONS: SEs do not prevent reimbursement or ASMR>V: identified opinions were associated with similar proportions of insufficient SMR and more ASMR IV compared to all opinions published over the period. This is consistent with the TC's doctrine, where ASMR IV indicate a suboptimal demonstration, whereas ASMR I-III levels require significant superiority on mortality or morbidity. The use of SEs should not be discarded for access in France. However, there is no fixed rule: the relevance of SEs is assessed for each situation, emphasizing the importance of consulting experts and previous opinions to anticipate their acceptability.