OBJECTIVES: The EU Regulation on HTA applies in 2025 which involves joint clinical assessments (JCA) across Member States (MS). The JCA scoping process aims to ensure that all PICOs relevant to MS will be included. Concerns were raised that a significant number of PICOs must be incorporated which may potentially lengthen the JCA process and delays may spillover to MS HTA processes, but the extent remains unclear. By example, this study aims to compare the extent of difference of PICOs of current ATMP HTAs in FR, DE, UK, and the potential impact on the upcoming regulation.

METHODS: Comparative analysis of PICOs in HTA reports of ATMPS assessed in FR, DE, UK.

RESULTS: Out of the 24 ATMPS with marketing approval (2023), 7 ATMPS covering 9 rare indications, thus 9 HTA reports, were included in the analysis. The population(P) and intervention(I) are similar across countries. There were differences in the comparators(C) in 7 out of 9 reports. The rarity of the indications contributed to differences as they are mostly managed by non-standardized best supportive care (BSC) or salvage chemotherapies which differ per system. For the outcomes(O), endpoints have been similarly based on the clinical data and indirect comparisons from the manufacturers.

CONCLUSIONS: The extent of difference in the comparators(C) are relevant. ATMPs, the first to be assessed by JCA, may be subject to a complex, long process. Aside from the inherent complexity of the technology, a significant number of comparative therapies may need to be considered relative to the number of MS included. To avoid challenges in the scoping process and delays in the assessment, an early coordination between the manufacturers and the HTA coordination group (HTACG) through the joint scientific consultations may provide an opportunity to validate PICO scope at an EU-level at an early clinical development stage.