Major strides have been made to improve the availability and applicability of real-world data (RWD). However, generating reliable and timely real-world evidence (RWE) is a multifaceted process facing many challenges globally. This symposium will introduce several creative approaches to generating high-value RWD, showcase patient-centric data innovations, and discuss the application of RWE to support regulatory submissions and payer negotiations. First, to augment patient-centric care, an increasing number of patient support programs (PSPs) have been implemented by pharmaceutical companies. The presenters will demonstrate how to generate high-quality RWE that leverage PSPs. Both early evidence and long-term RWE in patients’ quality-of-life and clinical benefits post product launch can be reliably developed through this approach to demonstrate the real-world value of innovative treatments. Second, two case studies will be presented to illustrate how to generate high-quality RWE in China, where RWE research has traditionally faced many challenges. In one example, researchers developed and validated algorithms to generate high-quality RWD in order to study complex patient journey in a hematologic condition based on China’s National Longitudinal Cohort of Hematological Diseases (NICHE). In another example, researchers applied a creative design of a multi-center physician survey to generate reliable RWE to support China’s National Reimbursement Drug List negotiation. Lastly, the presenters will discuss considerations in the creation of a historical control arm to support regulatory approval. We hope this symposium can introduce these recent creative solutions in generating and applying RWD to the audience and stimulate discussions to further advancing the RWE research and methodologies.