OBJECTIVES: From 2025, select pharmaceuticals will be mandated to undergo a joint clinical assessment (JCA) at the European level. In preparation, EUnetHTA21 (2021-2023) has developed methodological guidelines for JCAs. This research compares the methods proposed by EUnetHTA21 to methods currently used by select national agencies.

METHODS: Four EUnetHTA21 methodological guidelines (direct/indirect comparisons, endpoints, applicability of evidence; and validity of clinical studies) were reviewed alongside methodological guidelines published by national HTA agencies from Germany (G-BA), Italy (AIFA) and Denmark (DMC). Requirements on national guidelines were classified as similar, more stringent or less stringent/no comment than JCA requirements.

RESULTS: Across the published guidelines, 12 domains were identified which could potentially differ between JCA and national methods (acceptance of indirect treatment comparisons [ITCs] and ITC specifications, acceptability of surrogate outcomes, requirements for safety reporting, quality of life [QOL] inclusion, PICO mismatch, risk of bias assessment, acceptability of trial types, use of real world evidence [RWE], minimum important difference [MCD] definition, subgroup requirements, sensitivity analysis of outcomes). Overall, JCA guidelines were most aligned with the Danish guidelines; 8 of the selected domains within national guidelines were similar to the methods suggested by EunetHTA21 (3 more stringent, 1 less stringent) followed by the German (6 similar, 3 more stringent, 3 less stringent) and Italian (3 similar, 8 more stringent, 1 less stringent). Across all domains, there was broad alignment in only two domains: reporting of safety data and acceptability of trial types.

CONCLUSIONS: While the EUnetHTA21 suggested methods are most similar to those used in Denmark, there is substantial variability between all agencies assessed. For pharmaceutical companies gearing up to start JCA submissions in 2025 there is a need to fully ensure that they understand the methods they will be assessed by in order to ensure a positive outcome when it comes to the JCA.