Overcoming the Challenges of Long-Term Follow-Up Studies for Cell and Gene Therapy

Cell and gene therapy (CAGT) is delivering a wide group of promising new treatments that offer hope for addressing or even curing many conditions and improving life for patients and their families. Providing these therapies comes with unique operational challenges when conducting regulator mandated long-term follow-up surveillance post exposure. Commitments of 5 to 15 years of follow-up data collection are not unusual and these studies are expensive and of limited interest to principal investigators and even patients. Here we will explore some of the key challenges that companies face when designing and implementing these long-term follow-up studies and ideas for overcoming these challenges.

Matching the long-term follow-up to the mechanism of action

For now, all cell and gene therapies are subject to regulations from the FDA, EMA and other regulators around long-term data collection. For each study, the sponsor must educate regulators on the mechanisms of action for their specific treatment, and work with the regulators to determine both the duration of follow-up and the data to be collected. For example, some therapies may require frequent blood tests or biopsies to measure biomarkers or gene expression, while others may rely on imaging techniques or clinical assessments to evaluate outcomes. Eventually the market may mature enough that the regulations become more differentiated, but for now, it is a case-by-case discussion.

Sourcing data from the expected patient journey

One of the main challenges to securing long-term follow-up data after cell or gene therapy is that many patients will have traveled to participate in the clinical trial or to receive these specialized treatments. In many cases, it is unrealistic to expect them to continue to return to treatment centers for long-term follow-up data collection. If that is true, then we must think about how to meet the patients where they are, and this requires a realistic understanding of the patient journey, not only within the healthcare system but through life:

• Where did these patients come from before they were in the trial or exposed commercially?
• Which doctors cared for them before the treatment?
• Who will see them after the treatment?
• If a pediatric population, will they cross lines of consent during the follow-up window, meaning re-consent of adult patients are needed?  Will they need re-treatment?
• Are they aligned with an advocacy group, or a specialist treatment center?
• Will they move within or between countries as their lives unfold?

The answers to these questions can give clues to where in the healthcare system these patients will be found and give ideas on how and where to engage with them.

One place in the patient journey where data may be collected for rare disease patients is in existing or modified disease registries. Registries are a natural fit for long-term follow-up studies, as they typically rely on standard of care data and minimize the burden on patients and providers. However, registries may not have all the data needed for long-term follow-up studies, such as specialty tests, imaging, or treatment persistence, so you may need to add additional data sources or modify existing registries to suit the study’s needs. For example, the study may add an arm to the registry to capture additional data on the subset of treated patients under the operational umbrella of the registry or use digital tools or remote visits to collect data from patients who return to their home territories after receiving the therapy.  

For data not available via standard of care information, and requiring intervention to collect, it is important to understand when and where the patient is receiving their care, and work with the patient to determine the best ways to collect that additional data. Virtual physician visits, visiting nurses or digital wearable technologies are all ways to help generate additional data in a patient-centered way. By understanding the way the patient will be interacting with the healthcare system, we can plan the required data collection.

Evolving technology and patient expectations

A final challenge is coping with changes in technology and patient expectations. Technology is constantly evolving, offering new opportunities in how we collect and communicate medical information. While new devices or platforms may enable more efficient data collection or analysis, they may also introduce new sources of error or bias. Similarly, new therapies or standards of care may appear, affecting the comparability or relevance of study results. Patient expectations about how they interact with a study or a healthcare system may also change over time. Companies need to keep abreast of the latest developments in technology and patient advocacy and be ready to adjust their study plans accordingly.

One way to cope with the changes in technology and patient expectations is to partner with experts who have specific experience in delivering long-term follow-up studies for cell and gene therapy. Knowledge of the latest technology platforms, data sources, analytical methods, and operational strategies can help companies design and implement their studies efficiently and effectively.

Conclusion

Long-term follow-up studies for cell and gene therapy are required by regulators to ensure the safety and efficacy of these therapies, but successful delivery requires companies to think differently about these programs. By understanding the patient journey and data requirements, ensuring patient centricity and study flexibility, and anticipating changes in technology and patient expectations, companies can overcome these challenges, efficiently deliver high-quality long-term follow-up studies, and bring new, innovative drugs to patients in need.