Digital solutions hold the key to managing long-term follow-up for gene and cell therapies

As approvals accelerate, technology is critical to easing patient burden, improving data, and lowering costs in long-term cell and gene therapy trials.

Cell and gene therapies (CGTs) are on the frontiers in medicine, offering the ability to treat both common and rare conditions by altering the body at the cellular or genetic level. Yet the extraordinary potential of CGTs has been hampered by regulatory approval, due to a fundamental mismatch between traditional regulatory paradigms and the distinctive nature of CGTs (especially for rare diseases). Specifically, these challenges are due to complex manufacturing processes and the need to maintain stringent quality control, adding layers of regulatory considerations; unique issues handling living diseases; the personalized nature of CGTs, which creates variability; the potential for long-lived effects necessitates stringent and lengthy post-marketing surveillance; and evolving regulatory landscape that has adopted some breakthrough designations to expedite approval, but challenges remain. As of 2023, just 18 CGTs were authorized in the United States. Recently, however, the U.S. Food and Drug Administration (FDA) has begun to move on CGTs, authorizing new treatments for recessive dystrophic epidermolysis bullosa and macular telangiectasia type 2. The FDA is still on track to approve at least 10-20 CGTs annually in the coming years.

CGTs are already considered a mainstream treatment option for lymphomas and all multiple myelomas, but there are still true barriers because it is logistically complex, expensive, and only administered at limited locations, explained Kaitlin Morrison, MD, Assistant Professor of Medicine and Executive Director of Clinical Research at University of North Carolina's Lineberger Cancer Center.Pamela Tenaerts, MD, Chief Medical Officer, Medable

Because CGTs are designed to deliver long-lasting or permanent effects, regulators mandate extended long-term follow-up (LTFU), often spanning many years. This monitoring helps identify any delayed adverse events and assess the durability of treatment benefits over time, ultimately enhancing patient safety and informing clinical decision-making for future patients.

Complexity creates challenges

CGTs present steep hurdles to both development and delivery. Research and development (R&D) costs remain extraordinarily high, averaging between $1.4 billion and $2.5 billion. These costs are driven by frequent trial failures, complex manufacturing processes, and narrow patient enrollment.

The demands on patients can be daunting. Many must travel long distances to reach specialized treatment centers, only to face years of follow-up visits. During the first five years post-treatment, patients typically undergo multiple annual visits involving physical exams, lab work, and imaging. Even after this intensive phase, yearly checkups are still required for up to 15 years for most therapies.

Manufacturing costs remain high as well, up to $475,000 for individual doses.

Because of the complex manufacturing involved in many CGTs, there are fewer locations that offer the treatment so patients must often travel really far, explained Morrison.

According to a 2024 survey, approximately 20% of CAR-T patients discontinue participation, with 80% of these withdrawals occurring at or after the five-year mark. Much of this dropout is tied to logistical challenges, given that nearly a third of participants live six or more hours from their treatment site.

In addition, costs for transportation, lodging, lost wages, childcare, elder care, and the cumulative physical and emotional toll all create significant barriers that risk compromising study data quality. With attrition rates often 20% or higher for CGT s, trial results can often be invalidated.

Research sites also carry a burden. Many institutions juggle competing demands, such as enrolling new patients in trials while managing years of LTFU obligations for past participants. Eventually, these operational strains become untenable, pulling valuable resources away from new research efforts.

Digital tools can be transformative

Digital technologies offer a way to mitigate the enormous burdens that threaten to slow the progress of CGT development. By integrating decentralized trial models, telehealth, and remote monitoring, digital tools can significantly reduce costs and burdens for sponsors, sites, and patients alike.

Virtual visits and telemedicine allow patients to consult with their care teams from home, minimizing travel and scheduling disruptions. Remote data capture through electronic patient-reported outcomes (ePRO) and electronic clinical outcomes (eCOA) allow participants to log symptoms and report emerging issues. Routine lab work can often be completed at local facilities, eliminating frequent long-distance travel to central study sites.

Digital platforms also foster stronger patient engagement. Mobile apps and patient portals give participants easy access to study materials, appointment reminders, medication schedules, and educational resources. Automated notifications via text, email, or app can help keep patients on track, while gamification elements like badges or progress trackers provide extra motivation.

These digital tools not only ease the burden but also create more efficient and cost-effective models for long-term trial management. Sites can devote more time to active studies while better maintaining LTFU commitments. Sponsors benefit from higher data quality and lower attrition rates. Ultimately, this creates a more sustainable ecosystem for advancing CGTs without compromising safety or data integrity.

Patients prefer digital trials

Patients have shown a preference for digitally enabled trials. A 2019 CTTI survey found that most participants would choose mobile-enabled studies over traditional in-person models, citing greater convenience and improved data accuracy. The pandemic accelerated this digital shift across age groups, including older adults who were once assumed to be less comfortable with technology. Today, many patients are comfortable with telehealth platforms and remote data submission.

The promise of CGTs remains enormous, but the operational realities of LTFU, including high costs, patient attrition, and site burdens, pose serious threats to continued progress. Digital solutions offer a powerful way forward. Through telemedicine, remote data capture, and patient engagement technologies, digital innovations are redefining how long-term follow-up can be conducted, ensuring that CGT advances remain both scientifically rigorous and economically viable for years to come.

Header image: Depositphotos@OlenaPavlovich