ASCERTAIN (Affordability and Sustainability improvements through new pricing, Cost- Effectiveness and ReimbursemenT models to Appraise iNnovative health technologies) addresses the need of patients, physicians, payers, regulators, and manufacturers to improve the affordability and accessibility to innovative health technologies (including pharmaceuticals) in Europe. ASCERTAIN aims to enhance current methods of (value-based) pricing, cost-effectiveness modeling, threshold-setting, reimbursement, and payment, to set affordable prices, and to facilitate a cyclic assessment of broader societal benefits including costs and risks. It seeks to find a sustainable balance between access to affordable technologies, the need to stimulate innovation and entrepreneurship, and the need to consider the environmental impact of innovations. Guided by a conceptual framework integrating pricing, health technology assessment and reimbursement/payment, ASCERTAIN will develop open-access, easy to use, policy-supporting tools including (i) pricing models, (ii) value assessment models, and (iii) reimbursement models, which will be adaptable to country-specific conditions. These tools will improve transparency and accountability of decision-making, reduce uncertainty for all stakeholders, reward innovation in areas of high unmet need, accelerate access for patients, and support long-term planning in a sustainable way. Further, these tools will be developed, tested, and validated for three use cases, including precision cancer medicine, cell- and gene therapy, and medical devices (class IIb and III) or in vitro diagnostic (IVD) class D. The multinational, multidisciplinary ASCERTAIN consortium is complemented by an international advisory board consisting of key stakeholders, with whom the policy-supporting tools will be co-created. All tools will be hosted on a cloud-based, publicly accessible, user-friendly platform following open science principles.