HTA Assessment of Single-Arm Trials: Comparison between the HAS and SMC

OBJECTIVES: While the French Health Technology Assessment (HTA) agency adopts a clinically driven approach, the Scottish Medicines Consortium (SMC) in Scotland follows an economically driven model. This study seeks to analyse discrepancies in HTA decisions issued by the Haute Autorité de Santé (HAS) in France and the SMC, for products submitting single-arm trials as pivotal evidence.

METHODS: HAS reports for drugs with single-arm trials published between 2018 and 2022 were identified. The following exclusion criteria were applied: vaccines, blood-derived medicines, reassessment reports, pharmacokinetic trials. Subsequently, the corresponding SMC reports were identified for comparative analysis.

RESULTS: Twenty-two drugs, evaluated by both agencies across 28 indications, were identified. All assessed indications pertained to severe diseases, with 24 in oncology and 5 gene therapies. In 43% of cases, the HTA decisions demonstrated concordance (12 recommendations without restrictions, including 3 conditional approvals). The HAS acknowledged 19 indications as rare conditions, while the SMC reported 26 indications for drugs meeting orphan (N=19) or ultra-orphan (N=7) criteria. Sixteen indications were subject to divergent decisions between the agencies (HAS recommended/SMC not recommended (N=2); HAS not recommended/SMC recommended (N=5); HAS recommended/SMC restricted (N=2); HAS restricted/SMC recommended (N=6)); HAS restricted/SMC not recommended (N=1)).

CONCLUSIONS: The HAS requires direct head-to-head comparisons, while SMC accepts indirect comparisons. HAS considers factors such as disease severity, incidence, and the availability of alternative therapies in its decision-making process. On the other hand, SMC takes into account end-of-life criteria or decision facilitators for all orphan or ultra-orphan drugs, allowing for greater acceptance of uncertainty in the economic case. Despite different decision drivers, close to 50% of decisions were identified as similar.