How digital can ease the burden of cell and gene therapy long-term follow-up

Cell and gene therapies (CGTs) have the potential to offer curative possibilities for many conditions, some more common and some with few, or even no, effective treatments.

The clinical potential of these groundbreaking therapies is immense,¹ however, their pace of release has not been nearly as groundbreaking. By the end of 2023, only a handful had received authorization in major pharmaceutical markets: 18 in the U.S., 17 in the EU, and fewer in other countries. Thankfully, less than two years later, CGTs are starting to gain momentum. So far this year, the U.S. Food and Drug Administration (FDA) has already approved several CGTs, including those for recessive dystrophic epidermolysis bullosa and for macular telangiectasia type 2. These approvals herald a trend of increasing approvals,² with the anticipation of 20 or more CGTs getting approved annually.

“CGTs are already considered a mainstream treatment option for lymphomas and all multiple myeloma, but there are still true barriers because it is logistically complex, expensive, and only administered at limited locations,” explains Dr. Kaitlin Morrison, assistant professor of medicine and executive director of clinical research at University of North Carolina’s Lineberger Cancer Center. “Unfortunately, it is still a predominantly first-world treatment. Even as other countries are evolving, there are barriers to third-world countries having access.”

Because CGTs are designed to have lasting and lifelong effects, regulatory bodies including the FDA and the European Medicines Agency (EMA), often mandate 15-year, long-term follow-up (LTFU).³ LTFU allows the industry to uncover potential delayed or rare side effects while measuring the durability of treatment, ultimately making the treatment better understood and safer for future patients. Further, this empowers patients, their caregivers, and physicians with more data to make more informed decisions about pursuing CGT options in the future.

Without this long-term perspective, medicine is navigating uncharted waters; Fully understanding this landscape is paramount for the responsible and successful integration of CGTs into clinical care. Fortunately, collaborative groups such as the LTFU working group at the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard (MRCT Center) are creating resources and recommendations for these emerging studies.⁴

“We launched the Cell and Gene Therapies project at the MRCT Center in the fall of 2023, and quickly realized that long-term follow-up was an unresolved challenge for this class of therapeutics,” explains Barbara Bierer, faculty director of the MRCT Center, a research and policy center that functions as an independent convener to bring together collaborative multidisciplinary teams to address critical issues in the conduct and oversight of clinical trials.

The Center’s LTFU working group currently has 26 members, including representatives from pharma companies, clinical research organizations, academic researchers, ethicists, and patients. The group, led by Dr. Carolyn Chapman, plans to release its initial set of practical deliverables in October 2025.

The inherent challenges of CGT trials

CGTs can be extremely difficult to deliver for broad market access. The high price tag of R&D, due to high failure rates, lengthy timelines, trials with limited participation, and manufacturing complexity, requires an enormous financial outlay from sponsors. The average R&D cost of CGTs ranges between $1.4 and $2.5 billion.⁵ This staggering expense plays a major role in limiting both their development and accessibility — the additional burden of long-term follow-up only adds to the challenge.

Equally as difficult is the impact on patients and sites. Consider a patient who travels to a specialized research center for CGT treatment only to discover that their treatment requires more than a decade of follow-up appointments, often located hundreds or even thousands of miles from home. The first five years of follow-up are particularly intensive for patients, too, with two or more visits annually, before settling into annual check-ups involving physical exams, blood draws, and imaging or other lab work. In addition, CGTs’ complex manufacturing, especially with viral vector production, make treatments expensive — autologous cell therapies like CAR-Ts can run as high as $475,000 per dosage.⁶

“Because of the complex manufacturing involved in many CGTs, there are fewer locations that off er treatments so patients must often travel really far. We have patients coming from Australia, Canada, Hawaii, and more,” says Dr. Morrison. “In addition, for both commercially available and in-trial products, patients must be followed by the trial site for at least 15 years. Also, for pediatric patients on Medicaid, it is very difficult for them to cross state borders to get treatment. These are all real barriers to their participation.”

Challenges and the burden on participants in LTFU studies have serious consequences, with 20% of CAR T-cell therapy patients ending their participation altogether, and 80% of that group ceasing participation at or after five years post-treatment, according to a 2024 survey.⁷ A significant portion of this attrition can be attributed to logistical burden. For instance, 31% of patients in these studies live six or more hours away from their original study sites, making regular, in-person visits incredibly difficult.

The key barriers are multifaceted: direct travel costs for flights, accommodation, and ground transportation; lost wages from time off work; challenges of arranging child or elder care; and simply the sheer mental and physical exhaustion of constant travel. These aren’t trivial inconveniences but rather significant obstacles that can impact a patient’s ability to remain engaged in LTFU studies. And while losing 5% of patients to follow-up may not adversely impact overall trial results, losses of 20% or more are likely to introduce issues with the reliability of the findings.⁸

LTFU burdens extend beyond the patient, into the research centers and medical sites that administer these therapies. Facilities find themselves in a delicate balancing act as they are constantly striving to enroll new patients in cutting-edge clinical trials, which often come with pioneering new treatments. On the other hand, they bear the responsibility of managing 15-year LTFU studies for their existing and expanding patient cohorts. Over time, sites are left managing follow-ups for different sets of patients over decades — a significant drain on resources and pulling staff away from other patients in active trials.

Digital eases LTFU for all stakeholders

The extended duration of LTFU trials can make traditional trial approaches cost-prohibitive and burdensome on all parties over time — effectively threatening CGT advancement. Digital technology can help ease the burdens on patients and sites, while also reducing costs for sponsors.

Digital increases convenience and accessibility, particularly through decentralized trial models which allow flexibility in where and how participants interact with study requirements. Telemedicine reduces the burden of travel and scheduling by allowing patients to consult with health care providers remotely, with options to be seen by local providers. Remote data collection tools, including electronic patient-reported outcomes (ePRO) and electronic clinical outcome assessments (eCOA) enable participants to capture signs and symptoms with appropriate follow-up in case of emerging issues, while blood and lab work can be done locally, reducing the need for frequent research site visits.

Digital can also help keep patients more engaged in the trial. Patient portals and mobile apps serve as centralized platforms where patients can easily access study information, receive personalized reminders for medications and appointments, and track progress. These platforms often include educational materials to help patients better understand the trial and reinforce their commitment. At the same time, automated reminders delivered through text, email, or app notifications help patients stay on track with visits and data submissions. Gamification, such as badges and progress tracking, can further motivate patients by making the experience more engaging — even over the long haul.

The convergence of these digital technologies with local support creates a comprehensive ecosystem that fundamentally transforms the economics of LTFU study management, offering substantial cost reduction opportunities while simultaneously improving data quality, patient engagement, and operational efficiency over extended study periods. As the biotech industry continues to embrace these technological innovations for LTFU studies, the economic advantages of digital clinical trial methodologies will likely become increasingly pronounced, establishing new standards for cost-effective long-term drug safety and efficacy monitoring processes.

A global digital world

Thankfully, participants around the globe are already engaged in a digital world. In a 2019 CTTI survey, most respondents reported that they would prefer participating in a clinical trial that used mobile technology than a traditional trial that relied on standard in-clinic assessments.⁹ They remarked that mobile clinical trials off ered greater convenience, a reduction of in-person clinic visits, and greater data collection accuracy.

Additionally, the COVID-19 pandemic significantly accelerated the adoption of technology and telehealth services across all demographics — including older adults historically misperceived as less tech savvy. Older populations have demonstrated their ability and willingness to use telehealth when needed, with usage levels remaining higher than what the industry observed pre-pandemic.¹⁰

The future of CGT depends on digital

CGTs hold science-fiction-level promise but the challenges in LTFU trials, from patient inconvenience to high operational costs, threaten to hinder its pace. The integration of digital solutions including telemedicine and remote monitoring, along with local support offers a transformative approach.

References

1. de Haart, K., et. al. (2025, April). Long-term follow-up after authorization of gene therapy: leveraging real-world data. Drug Discovery Today, 30(5), 104337.

2. FDA-approved cell and gene therapies. (2025, May). RegMedNet.

3. U.S. FDA. (2020, Jan). Long Term Follow-Up After Administration of Human Gene Therapy Products. [Guidance for Industry]

4. Cell and Gene Therapies. MRCT Center of Brigham and Women’s Hospital and Harvard. [project resources]

5. Sabatini, M., & Chalmers, M. (2023). The Cost of Biotech Innovation: Exploring Research and Development Costs of Cell and Gene Therapies. Pharmaceutical medicine, 37(5), 365–375.

6. The Economics of CAR T-Cell Therapy. (2024). Association of Cancer Care Centers.

7. Eastwood, G., et. al. (2025). Amplifying the Voice of CAR T-Cell Therapy Patients and Caregivers. The Emily Whitehead Foundation. [whitepaper/survey results]

8. Lost to follow-up: Where did the lost patients go? Power. [accessed June 2025]

9. Perry, B., et. al. (2019, Jun). Patient preferences for using mobile technologies in clinical trials. Contemporary clinical trials communications, 15, 100399.

10. Mace, R., et. al. (2022, Sept). Older adults can use technology: why healthcare professionals must overcome ageism in digital health. Translational behavioral medicine, 12(12), 1102–1105.