To present the methodology for developing and lesson learned from implementing a long-term follow-up (LTFU) rollover protocol at Kite.
Method
A working group was formed in 2020 to evaluate the feasibility of consolidating LTFU activities into a single, standalone protocol. Requirements were defined and the protocol finalized in 2021. An abstract was developed in 2022 to document lessons learned following implementation.
Results
There were six key lessons learned. (1) Feedback obtained from regulatory agencies thus far has been positive and resulted in minimal changes to the protocol. (2) The Kite team encountered resistance from regulatory authorities due to the inclusion of an interventional retreatment arm in the otherwise non-interventional LTFU study. The retreatment arm was subsequently removed from the protocol following regulatory feedback and an examination of other internal and external barriers. (3) Site activation projections were developed based on pre-pandemic IRB/EC and budget/contract cycle times. Activation timelines during 2021 - 2022 were delayed as sites continued to work through pandemic-related staffing challenges and prioritized new interventional studies. As a result, Kite's ability to transition subjects and close parent studies was delayed. (4) In addition to site activation delays, the subject rollover process was further delayed by subjects who were unable or unwilling to return to the investigational sites for unscheduled rollover visits. In some cases investigators were unable or unwilling to bring subjects in for unscheduled visits or implement other solutions, like remote consent, to facilitate the rollover process. (5) Subjects are currently offered the opportunity to consent to the LTFU study after the site has been activated by Kite and the subject has completed the parent study. This presented unexpected challenges to obtaining timely consent from subjects to rollover, resulted in unplanned extensions of certain parent studies. (6) The Kite LTFU study was designed to collect minimal data without the expectation of generating publication-worthy datasets. Based on evolving data generation expectations from global payers and the broader medical community Kite is now reevaluating study plans in order to generate publication-worthy datasets from the LTFU study.
Conclusion
Kite has implemented a new protocol to consolidate LTFU activities for subjects treated in ongoing parent studies. The expected benefits of this approach include cost savings achieved through earlier closure of completed parent studies, increased bandwidth of Kite team members to manage new projects, and a reduced burden of continued participation in Kite-sponsored studies for subjects, investigators, and investigational site staff. The Kite team plans to open the LTFU study at more sites in additional countries in the future to realize these operational efficiencies at a larger scale. Despite several barriers encountered during the early phase of implementation the Kite team is actively applying lessons learned to accelerate future site activation and subject rollover timelines.
