OBJECTIVES: The joint clinical assessment (JCA) according to Regulation (EU) 2021/2282 (EU HTA) will initially be implemented for oncology drugs and ATMPs from January 2025. All JCA procedures are commenced by the scoping process: The formulation of a member state-specific research question, represented as individual PICO schemes. Patient population, intervention, comparator, and study endpoints to measure the outcome are determined by the authorities as basis for clinical evaluation. Given the diversity of standards of care in Europe, multiple PICOs can be demanded. By simulating an EU HTA-like scoping process as of today, this analysis aims to assess the risk of receiving numerous PICOs. How complex will it be?

METHODS: To determine heterogeneity of expected PICO schemes, completed national HTA assessments from the “EU big 6” member states were compared regarding several oncology drugs of specific indications. Procedures from the voluntary earlier joint clinical evaluation Joint Action 3 were used as supplement.

RESULTS: Complexity of the number and design of PICO schemes for oncologics was identified: chosen patient groups and interventions were largely consistent between HTA assessments, whereas selection of comparators differed and resulted in indication-dependent heterogeneity with up to 5 PICOs for 6 member states. The acceptance of outcomes was consistent, albeit relevance of progression-free survival varied significantly.

CONCLUSIONS: EU HTA is supposed to reduce redundancies and bureaucracy by harmonization. However, the diverse standard of care across member states needs to be reflected in the EU HTA dossier through numerous PICO schemes, especially in dynamic indications. This analysis supports the anticipation of strategic and operational effort for future EU HTA dossiers. Compared to national HTA procedures, this will create complexity and uncertainty in predictability of the statistical analyses required for assessment. It is therefore questionable whether EU HTA can comply with its objective.