Introduction In 2021, non-communicable diseases caused an estimated 43.8 million deaths worldwide, accounting for approximately 75% of all non- pandemic-related deaths.2 Despite decades of evidence about effective interventions, current trajectories fall dangerously short of United Nations Sustainable Development Goal target 3.4, which commits to reducing premature NCD mortality by one-third through prevention and treatment by 2030. The UN Secretary-General’s 2025 progress report warns that without urgent action, NCDs will erode human capital, overwhelm health systems and divert resources to treating conditions that could have been prevented.3 This white paper examines countries at advanced stages of the epidemiological transition, where populations live longer with multiple chronic conditions. In these contexts, the primary challenge has shifted from preventing premature mortality to managing rising multimorbidity, coordinating fragmented care and addressing persistent inequalities. Understanding how even well-resourced systems struggle with structural barriers – and where some have succeeded – offers critical insights for health system transformation globally. This analysis is based on a synthesis of eight new country assessments conducted by PHSSR using a structured research framework developed by the LSE.4 The countries – Canada, France, Germany, Greece, Italy, Japan, Poland and Spain – represent diverse contexts: –Varied demographic stages: From relatively younger populations in Canada and Poland to super-aged societies in Japan and Italy –Different financing models: Tax-funded systems (Canada, Italy, Spain), social health insurance (France, Germany, Japan, Poland) and mixed models (Greece) –Diverse geographical challenges: From Canada’s vast distances to Greece’s island populations to urban–rural divides –Different governance structures: Centralized systems (France, Japan) vs. federal structures (Canada, Germany) vs. regional autonomy (Italy, Spain) Each country research team conducted comprehensive assessments, including desk reviews, stakeholder surveys and roundtable discussions with clinicians, policy-makers, patient advocates and private-sector representatives. This white paper examines the evolving NCD burden before analysing six health system domains, determining capacity for early action. The conclusion synthesizes key findings and presents key principles for transformation. The analysis focuses on five interrelated NCD categories accounting for over 80% of premature NCD deaths: cancer; cardiovascular disease; diabetes; chronic kidney disease; and chronic respiratory diseases.5 These conditions share common risk factors (tobacco, poor diet, physical inactivity, obesity), prevention pathways and biological mechanisms – diabetes drives kidney disease, hypertension damages both the heart and kidneys, obesity increases the incidence of multiple cancers. This interconnection means that effective action on one condition creates cascading benefits for others. The paper emphasizes cross-disease strategies that capture these synergies rather than disease-specific interventions.Early intervention in NCDs improves outcomes and can reduce costs. Transforming health systems from reactive to preventative care is one of healthcare’s most critical challenges – and opportunities. Acting Early on Non-Communicable Diseases: A Framework for Health System Transformation 5

Acting Early on Non-Communicable Diseases 2026