OBJECTIVES: The Joint Clinical Assessment (JCA) aims to harmonize the EU HTA procedure and will become mandatory for oncology drugs in 2025. As part of the JCA, member states (MS) identify PICO (Population, Intervention, Comparator, Outcome) needs, to enable manufacturers to present necessary data for the JCA. To support the JCA, the EUnetHTA21 joint consortium published the D4.4 endpoints guidelines in 2023. HTA bodies/payers do not always accept endpoints beyond overall survival (OS)/patient-reported outcomes (PROs), even though their value is frequently recognized by patients, clinicians and regulators. This study assessed the extent to which the guidelines recognize non-OS endpoints/PROs and the opportunities within the JCA to reflect their value.

METHODS: This study is informed by a literature review and 6 interviews with European HTA experts.

RESULTS: The guidelines state a preference for OS. While non-OS endpoints are accepted as surrogates where final outcomes are unavailable or unfeasible to collect, there is no recognition that they have standalone value in capturing outcomes beyond survival. E.g., progression-free survival has value as an efficacy measure independent of OS correlation, due to the direct impact of tumor progression on symptoms, HRQoL and treatment decisions. In maintenance therapies, preventing progression is a primary treatment goal where it provides patient benefit. Furthermore, experts demand greater clarity on surrogacy use cases for non-OS endpoints. The guidelines recognize the need to tailor endpoints per setting and highlight patients’ / clinicians’ roles in achieving this, but do not engage regulators or industry in defining endpoint validity.

CONCLUSIONS: The guidelines state a preference for OS and don’t explicitly recognize the standalone value of non-OS endpoints/PROs. However, MS have the opportunity to specify outcomes beyond OS via the PICO process to reflect the holistic value of novel therapies, including via HRQoL and resource use and by agreeing the relationships between surrogate endpoints and patient-centered outcomes.