OBJECTIVES: Use of non-overall survival (OS) endpoints in HTA assessments is limited by the difficulty in reliably proving long-term clinical and economic benefits. Using early breast cancer (EBC; stages 1 and 2) and multiple myeloma (MM; all stages) as examples, this research aims to identify the specific actions that must be taken to ensure that non-OS endpoints are fit-for-purpose for use in reimbursement decisions.

METHODS: This work is based on a literature review, semi-structured interviews with c.20 former representatives of reimbursement authorities (former payers) in key markets (U.S., Canada, Japan, UK, France, Germany and Italy) and 1-to-1/roundtable discussions across stakeholder types (physicians, patients, regulators and health economists).

RESULTS: Primary research indicates payers are aware of the challenges in demonstrating OS in EBC and MM and are willing to consider non-OS endpoint alternatives where there is convincing evidence. Three key approaches were identified to advance the available evidence base. Firstly, statistical validation of correlation to long-term outcomes is considered an acceptable route by many payers. Surrogacy has been demonstrated and accepted for some endpoints in some indications, such as DFS in HER2+ EBC. However, there is a need for consistent definitions and tools of measurement of non-OS endpoints across trials, and stakeholder consensus on the validation approach, to support more effective use of clinical trial data in validation studies. Secondly, generation of RWE is considered a good alternative to demonstrate long-term outcomes where correlation studies are not available. Finally, for value drivers beyond survival to be incorporated into an HTA assessments, frameworks that quantify the economic and social benefits of non-OS endpoints are required, and PRO / QoL analysis must have statistical powering.

CONCLUSIONS: Increased evidence generation is essential to facilitate the use of non-OS endpoints in reimbursement decision making and requires a cross-stakeholder approach.