Long-term follow-up after authorization of gene therapy: leveraging real-world data

• Gene therapy requires long-term follow-up (LTFU) studies. • We reviewed regulatory, scientific and operational requirements and considerations. • Assessing requirements and feasibility is essential before designing LTFU studies. • Studies should integrate the patient perspective, including retention in the study. • Identified challenges require harmonized guidance and multiparty collaboration. Gene therapies are innovative treatments that could revolutionize healthcare. Given their unique mechanisms of action, methods of manufacturing and administration, and the potential for long-lasting impact, gene therapies require long-term follow-up (LTFU) of safety and effectiveness post-authorization, often using real-world data (RWD). With over 2000 gene therapies in development, there is a need for knowledge-building regarding LTFU studies. Here, we review regulatory, scientific, and operational requirements and considerations for LTFU studies using RWD from a global perspective. The insights in this review support post-authorization LTFU studies for gene therapies, thereby contributing to their safe and effective use.