Presentation (CTI)

OBJECTIVES: The EU HTA Regulation introduced Joint Clinical Assessment (JCA) to reduce duplication in clinical evidence review while preserving national appraisal and reimbursement autonomy. However, JCA’s value depends on both the extent of convergence in national HTA clinical evidence requirements and the evidentiary expectations around which they converge. This study assessed both dimensions to identify where country-specific evidence adaptation may persist.
METHODS: We reviewed HTA guidance from 11 EU Member States selected for geographic and economic diversity and established HTA systems. Two reviewers independently coded 9 clinical evidence domains using an ordered framework (A=most flexibility, B=conditional flexibility, C=most restrictive, D=unspecified). Domain-level convergence was measured using modal-category agreement (high≥75%, moderate=50-74%, low<50%) and interpreted alongside category direction and an HTA Flexibility Index (FI: A=1.0, B=0.5, C=0.0, D=excluded). Herfindahl-Hirschman Index and entropy-based convergence were applied as robustness checks of concentration and dispersion.
RESULTS: Three domains showed high convergence, but with different evidentiary implications. Comparator requirements converged on the most restrictive category (C=100%), reflecting local standard-of-care expectations, whereas endpoint expectations and uncertainty management converged on conditional flexibility (B=100% and 91%, respectively). Several non-traditional evidence domains showed moderate convergence on conditional flexibility: real-world evidence (B=64%), external control arms (B=64%), indirect treatment comparisons (B=55%), and biomarker-defined subgroups (B=55%); however, indirect comparisons were relatively flexible overall (domain-level FI=0.73). Residual adaptation needs were suggested by low convergence for subgroup analyses (B=45%), fragmented and often unspecified approaches to extrapolation of immature evidence (D=45%), and national-level FI scores ranging from 0.17 (low) to 0.56 (moderate).
CONCLUSIONS: Convergence may mask meaningful differences in evidentiary positions. JCA can reduce duplication where national requirements are concentrated but is unlikely to eliminate variation in evidentiary tolerance. For high-uncertainty and precision therapies, the residual burden may lie less in producing a single EU dossier than in anticipating how national systems interpret uncertainty, subgroup evidence, and non-traditional evidence designs.