OBJECTIVES: SIMPATHY (Stimulating Innovation Management of Polypharmacy and Adherence in The Elderly) is a consortium of 10 organizations, aiming to stimulate innovation around polypharmacy and adherence. The aim of this study is to present the change management process and policies for improved outcomes from multi-disciplinary healthcare delivery for elderly patients with comorbidities through the provision of useful managerial tools against polypharmacy and non adherence. METHODS: A PESTEL (Political, Economic, Social, Technological, Environmental and Legal) tool has been developed, in order to prompt stakeholders and health professionals to address influential factors and understand the degree of their impact in the different health systems currently and in 2025. The tool has been built in several steps: 1) creation of a common framework in order to help the partners to conduct the analysis. 2) a pilot testing for assessing the specificity, objectivity and robustness of the multidimensional content has been performed. 3) focus on the conduction of the analysis through interviews and workshops among various focus groups across all the countries. 4) identification of the potential drivers and barriers related to polypharmacy landscape. RESULTS: Factors that countries scored as high influential are: (Political) health services delivery, primary health care - chronic disease management, governance structure/ decision making and resulting impact, corruption level, (Economic) overall economic success, health system’s structure and financing, number of pharmacies per inhabitants, (Social) access to health care, attitudes and beliefs, cross-cultural diversities, education, (Technological) existence of ICT integrated systems, innovative drugs policies, (Legal) legal authorities and regulatory bodies, roles and responsibilities, patients' rights empowerment, code of ethics, EU guidelines. CONCLUSIONS: PESTEL seems to be a tool that can successfully capture the beliefs of stakeholders and health professionals and build a common EU professional culture against inappropriate polypharmacy and non adherence.