Background The rate of incorporation of therapeutic innovation in the Spanish National Health System (NHS) is increasing. Its budget impact and time to access are concerns for stakeholders. The aim of this study is to define a structured framework for the evaluation of therapeutic innovations that aligns the expectations of public payers and the pharmaceutical industry.Methods The development of the evaluation involved five phases: identifying the key criteria based on a review of legal, regulatory and technical evidence; positioning the innovation according to the identified criteria through a questionnaire; constructing homogeneous archetypes of product-indication; and identifying and selecting strategies that align the interests of payers and the pharmaceutical industry.Results The key criteria identified in the Spanish setting include therapeutic need, incremental clinical benefit, budget impact, incremental cost-effectiveness ratio, and economic and effectiveness uncertainties. The evaluation questionnaire consisted of 7 descriptive questions and 36 evaluative questions, grouped into 9 areas of analysis. Five archetypes were defined that share similar barriers and access facilitators access, and non-exclusive strategies were proposed to reduce the identified barriers.Conclusions This framework helps to identify clinical development needs, facilitates the decision-making process and suggests appropriate reimbursement strategies. This process is most useful when there is an explicit definition of the application of decision criteria and the needs and priorities of the NHS.