Diego Correa, VP and global head, CAGT Center of Excellence, IQVIA, and Jip Klerks, product strategy lead, real-world solutions at IQVIA, reflect on how engagement in CGT trials can be maintained with flexible, patient-centred studies.
Long-term follow-up (LTFU) studies are essential to understanding the curative potential of cell and gene therapies (CGT) and any associated safety risks. Today, regulators globally commonly require that patients treated with gene therapies be monitored for up to 15 years, depending on the type of therapy.
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Sustaining patient engagement over a period of several years creates long-term operational and scientific challenges. This complexity increases when sponsors must navigate changes in patients’ lives, data challenges, evolving regulatory requirements, technology shifts over that time and increasing disengagement of patients and caregivers from studies once they feel “cured”. Without a thoughtful long-term strategy, sponsors may find that their LTFU studies often fail to adapt to change and become increasingly difficult to sustain.
By designing flexible, patient-centric studies and embracing the power of real-world data, sponsors can sustain long-term patient engagement and ultimately generate more complete evidence about the long-term safety and durability of CGTs while maintaining public confidence in these therapies.
Addressing the challenges of traditional LTFU
LTFU studies are fundamentally different from traditional clinical trial follow-up. They require a long-term, forward-looking approach to address a mix of operational, scientific, financial and regulatory hurdles. Top challenges include:
Sustaining engagement for several years
Patients who experience therapeutic success are more likely to disengage, while those with poor outcomes may drop out entirely. Investigators may also lose interest after a trial’s active phase ends.
Overcoming logistical barriers
Patients often travel to a specialised centre to receive a one-time gene therapy. Regularly returning to that centre for several years can be impractical. Patients may also experience care changes, such as when they transition from paediatric to adult care, which require reconsent.
Integrating fragmented data
LTFU studies can require capturing data from disparate sources, including electronic health records (EHRs), registries and claims systems, creating challenges such as fragmented data sets. The handoff from site-based clinical trial data collection to LTFU through healthcare systems and real-world evidence sources can also be difficult to manage.
Navigating technology and standards changes
During LTFU studies that can last as long as 15 years, technologies, standards and regulations can all significantly evolve. Failure to adapt to evolving technologies, standards and regulations can result in missed opportunities or non-compliance.
Bridging separate studies
A sponsor’s LTFU obligations can span both the pre- and post-approval phases. Running separate long-term studies for clinical trial participants and commercial patients duplicates effort and increases burden on both sponsors and patients.
By rethinking how to conduct LTFU studies, sponsors can overcome these challenges and help minimise operational burdens and costs, maintain compliance and navigate the inevitable changes that occur during a study. Four priorities that should be a part of every LTFU study to help achieve these goals include:
Design studies around the patient journey
Patient-centred LTFU studies shift away from traditional site-centric models to align with patients’ real-world care pathways. This can improve retention, lower costs and increase scalability while helping sponsors maintain compliance.
A patient-centred study meets patients where they are and addresses transitions in their care. It begins with understanding how patients live, receive care and engage healthcare providers over the course of several years and how to make follow-up manageable for them over time, taking place through a patient’s local provider, telehealth visit, home nursing service or digital touchpoint.
Designing a study around the complex and dynamically changing patient journey introduces some upfront challenges but is critical to long-term sustainability. It requires considering what patients’ lives will look like over the course of a study and how to weave follow-up activities into that journey to reduce burden, such as enabling follow-up by a patient’s local provider, telehealth visit, home nursing service or digital touchpoint rather than regular trips to the original treatment centre. This decentralises data collection, so it happens closer to patients rather than primarily at a treatment centre, to help keep patients engaged and under observation even if their location, provider or health status changes.
Achieve compliance with real-world data
Sponsors can collect and unify real-world data from a variety of sources to create more complete data sets for LTFU studies while reducing operational burden.
Key data needed for LTFU studies, such as safety, efficacy and durability outcomes, is already captured during regular medical care. For example, EHR and claims data can capture details about patient hospitalisations and diagnostic tests done as part of standard care. Rather than duplicating the collection of this data through follow-up, it can be programmatically extracted from EHR systems.
Disease registries can be an important component of an LTFU data strategy by contributing baseline natural history data and capturing outcomes over time. However, registries alone rarely meet all study requirements and typically need to be integrated with other real-world data sources and supplemented with targeted primary data collection to ensure completeness and relevance. In an optimised LTFU model, direct data collection can also be used to capture critical data not available through routine care or registries, such as specialised assessments or study-specific endpoints. This targeted approach ensures that additional patient and site burden is limited to when it adds clear value while maintaining a complete and fit-for-purpose dataset. This strategy only asks for extra effort from patients when necessary, as excessive follow-up demands can undermine retention, and consequently, long-term data completeness. At the same time, this strategy requires deliberate integration planning to proactively address challenges such as data fragmentation, definition mismatches and data latency that can undermine data quality.
Ease the demands of studies with digital tools
Digital and decentralised approaches are critical enablers of scalable and sustainable LTFU, reducing burden while supporting long-term patient retention and continuous data capture. For instance, an integrated research platform can streamline data collection and support long-term patient engagement. These platforms enable direct-to-patient data collection and engagement, which allows patients to self-onboard and digitally consent to an LTFU study and then participate in the study from their own devices. At the same time, it can integrate with electronic medical records (EMRs) to streamline data collection.
Decentralising follow-up activities using telehealth technology can also sustain engagement by removing barriers like travel and time off from work. Instead of travelling for in-person visits, patients can attend virtual follow-up visits for symptom interviews, observation and functional assessments.
For activities like blood draws, biopsies or specialised exams that can’t be done virtually, mobile research nurses and phlebotomists can be deployed to patients’ homes. These services reduce burden and dropout risk and support protocol adherence across geographically dispersed populations.
Additionally, wearable devices and sensors can capture continuous, low-burden longitudinal data. These remote-monitoring technologies can create richer insights while reducing the need for episodic clinical measurements.
These digital capabilities also enable a shift in operating model, where follow-up is managed by centralised teams rather than individual sites, improving consistency, reducing site burden and supporting long-term scalability.
Future-proof studies with adaptable designs
It is impossible to predict all the changes that may occur in patients’ lives, the technology ecosystem and the regulatory environment over a 15-year period. This is why studies should be proactively designed for adaptability.
Inflexible protocols can become operational liabilities. LTFU studies that are built to evolve and minimise risk will ultimately be easier to execute over the long term, so adaptability should be a foundational design principle.
Building flexibility into protocols can help sponsors make calibrated adjustments as the study progresses. Those adjustments could include adapting visit frequency, adding new endpoints or integrating new technologies as standards evolve.
Establishing interim review points throughout the duration of an LTFU study can help sponsors reassess protocols against changing regulations, standards of care and patient needs. This structured adaptability supports continuous improvement while maintaining data integrity.
Equally important is the use of modular, interoperable data systems that allow new data sources, technologies and tools to be incorporated without disrupting study continuity. As digital health and real-world data capabilities continue to evolve, LTFU studies must be able to integrate these advancements to improve efficiency and data quality. Just as importantly, sponsors should engage with regulators early and maintain dialogue throughout a study to help clarify expectations and obligations over time. Even undesirable outcomes, such as a sponsor going bankrupt mid-study, should be planned for and discussed with regulators at the outset, so sponsors can be prepared for all contingencies.
Designing studies for long-term success
The challenge of knowing what to expect across a five- to 15-year LTFU study drives the need for these studies to be flexible, data-driven and built around the patient. Sponsors that design studies with these principles in mind will be better prepared to adapt to changes while reducing costs, lowering burden and improving the sustainability of their long-term studies.
Cell & Gene therapy coverage on Clinical Trials Arena is supported by Cytiva.
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