Clinical trials conducted in unique patient populations or individuals with rare diseases are typically hampered by limitations in availability of qualified patients, requiring sponsors to broaden their global outreach to achieve enrollment. Engaging clinical study centers in developing regions may offer access to a substantially larger patient pool. However, they provide a unique set of challenges based on local cultures and requirements. The DOVE study (Determining effects Of platelet inhibition on Vaso-occlusive Events) was a clinical trial of prasugrel hydrochloride (prasugrel) in pediatric patients (aged 2 to < 18 years) with sickle cell anemia. The study was conducted at centers located in both well-developed and developing regions, enrolling 341 children. Study planning and execution required careful consideration of cultural requirements in each region and im- plementation of additional trial initiation and execution processes to address those needs. Innovative strategies were employed to ensure global consistency and quality in study execution. Significant regional- and country- specific differences were observed in site activation and enrollment. Although site activation processes were more complex and slower in developing countries, enrollment rates were much higher, which helped mitigate the site activation delays and allowed significant contribution to complete study enrollment. Data quality and patient retention in developing countries were equivalent to those observed in more developed countries, further supporting the ability to successfully conduct high-quality global registration trials in those countries. This report provides an overview of the experiences in site identification, site qualification, enrollment, patient re- tention, and data quality assurance in the DOVE study.