A Strategic Roadmap to Support Communication on and Acceptance of Surrogate Endpoints: The REnal Surrogacy accEpTance in Chronic Kidney Disease (RESET CKD) Collaboration.

Introduction: Developing effective treatments in chronic, progressive diseases like chronic kidney disease (CKD) is challenging because patients may only experience relevant outcomes such as kidney failure after long periods of disease progression. Surrogate endpoints provide a valuable alternative to definitive final patient-relevant outcomes, which may accelerate clinical development processes. However, optimal utilization of surrogate endpoints for reimbursement decisions requires alignment across multiple stakeholders, including health technology assessment (HTA) bodies and reimbursement agencies, who are generally more cautious than regulatory bodies in their acceptance of surrogate endpoint evidence. The aim of this paper is to propose a strategic roadmap to facilitate cross-stakeholder collaboration and support the consideration of surrogate endpoints in regulatory and reimbursement decisions.

Methods: An international group of experts in surrogate endpoints, reimbursement decisions, and kidney disease formed The REnal Surrogacy accEpTance in Chronic Kidney Disease (RESET CKD) Collaboration. This scientific steering committee held several meetings to develop a roadmap of activities with the aim of enabling the appropriate consideration of surrogate endpoints through structured multi-stakeholder engagement involving regulators, clinicians, HTA bodies, payers, industry, and patients.

Results: The strategic roadmap focuses on four areas: identifying the need for evidence; engaging stakeholders; collaborating in regulatory and reimbursement processes; and disseminating evidence. The RESET CKD collaboration is currently implementing the roadmap in the field of CKD through collating relevant evidence for a CKD-relevant surrogate endpoint in a scientific playbook, conducting economic evaluations, developing a position paper, and engaging patient groups.

Conclusions: Disparities between regulatory and reimbursement processes and decisions underscore the need for a structured approach to enhancing transparency, consistency, and timeliness in the use of surrogate endpoint evidence in healthcare decision-making. The roadmap developed through the RESET CKD Collaboration addresses this need and is already demonstrating practical value in its implementation. Although initially focused on CKD, the framework is designed to be transferable to other therapeutic areas. Key challenges remain, including the integration of surrogate endpoints into adaptive pricing models and performance-based agreements.