Characteristics of long-term follow-up studies for gene therapies registered on ClinicalTrials.gov.

Guidance from the U.S. Food and Drug Administration and other regulatory agencies recommends long-term follow-up (LTFU) studies of gene therapy recipients. The primary objective of LTFU studies is to understand the long-term safety of gene therapy products; evaluation of efficacy outcomes may be a secondary goal. To learn more about LTFU study design and conduct, we conducted a descriptive study of key characteristics of LTFU gene therapy study protocols registered in ClinicalTrials.gov, including data about status and duration, funding source, enrollment, number of clinical trial sites per study, eligibility criteria, geographic location, and intent to monitor and report adverse events. This analysis enabled a better understanding of how registered LTFU studies are currently designed and stimulated ideas for improvement, which are discussed. Most notably, our results suggest that there is a lack of harmonization in how safety outcomes are monitored and reported across LTFU studies. Standardization and/or harmonization of outcome reporting for LTFU studies of GTs may increase their scientific value. The development of better guidance and innovative approaches for LTFU study design and conduct would help support best practices and the fulfillment of LTFU commitments to understand the overall long-term benefit-risk profile of GT products.