OBJECTIVES: To outline the experience and challenges encountered by our program over two years of collaboration with Spanish health system organizations, focusing on the production and utilization of Living Evidence Synthesis (LES) to inform real-world clinical and policy decisions.

METHODS: Using a "learning-by-doing" approach, we assisted groups in developing LES from initial planning to final report, encompassing evidence surveillance and monitoring processes. Employing strategies and tools like the web-based Living Evidence to Inform Health Decisions (LE-IHD) framework and its handbook, we guided groups applying appropriate criteria at all stages, including identifying relevant questions for "living mode," protocol development, conducting baseline synthesis, monitoring emerging evidence, and incorporating findings into health decisions. We also offered training via online modules and provided free access to technological tools supporting evidence surveillance.

RESULTS: Since September 2022, we've supported eight organizations, primarily Health Technology Assessment (HTA) agencies, in developing 14 LE-Synthesis as part of their commissioned projects. The identification, screening and surveillance of evidence have been facilitated through the Epistemonikos Foundation's Living Overview of Evidence (L.OVE) platform. By September 2024 we will have 18 months' worth of results from evidence surveillance and will provide updated results of key challenges related to these LES. Currently, the likelihood of an eligible study emerging within 12 months of evidence monitoring is very low (<0.05), with an even lower probability of new studies addressing outcomes crucial for decision-making.

CONCLUSIONS: Our ongoing studies indicate that while the LE approach proves highly effective in fields with abundant scientific output, it may not be suitable for the majority of urgent questions identified as priorities for health systems.

Declaration of funding: The program received funding from the Spanish Government: Instituto de Salud Carlos III (ISC-III), Madrid, Spain. Grant PI21/01564; project “Strengthening decision-making capacity in the Spanish Health System through living evidence: An innovative framework”.