OBJECTIVES: In rare diseases and sub-populations for specialty diseases, national and regional payer negotiations regarding funding and reimbursement of new drugs can be challenging due to the lack of available robust data to inform decision making. Clinical trials designed to ensure regulatory approval often lack the necessary information to meet the needs of a diverse range of payer and clinical stakeholders across the globe. Traditional patient registries, if available, generally do not capture the required level of detail, especially in terms of health-economic data. To ensure ongoing access, new therapies to treat rare diseases require further real world evidence to build a strong clinical and economic case for long term treatment provision.  METHOD: We employed a variety of traditional and innovative methods to collect real-world evidence on disparate populations of patients with rare diseases. Retrospective chart review studies have been conducted to understand demographics, clinical and pathological characteristics, treatment, outcomes and resource use. Patient and caregiver surveys have subsequently been used to correlate quality of life, functional status and economic burden to patient treatment pathways. RESULTS: Non-interventional studies provided a longitudinal understanding of patient care pathway from diagnosis to long-term treatment and follow-up including the natural history of a rare disease, genotypic/phenotypic variability, differences in treatment patterns across countries and the clinical drivers of therapy use. This enabled comparison of real-world treatment practice versus clinical guidelines. In addition, direct and indirect costs were calculated to understand the budget impact of treatment. Insights helped the manufacturer refine the product value proposition and provide necessary evidence to support product access and reimbursement. CONCLUSIONS: Rare disease non-interventional studies offer manufacturers the opportunity to fulfill peri and post-launch evidence needs of regulators and payers by providing bespoke and robust real world data efficiently.