Syneos Health

Nelly Marmy Conus

Reporting on the long-term safety of patients who receive cell and gene therapies remains vitally important to regulators. The European Union, for example, mandates continued follow-up for the remainder of the patient's life while the United States mandates a follow-up period of up to 15 years. Similarly, the need to maintain contact with patients across a range of therapy areas including oncology, rare diseases, and chronic conditions to understand long-term survival, safety, quality of life, and other parameters is essential. This, however, poses challenges for investigators, sites, patients, and sponsors. Limited budgets, a drain of site resources, and difficulties with engaging patients for extended periods make long-term follow-up (LTFU) a challenge.

Given the importance of minimizing patient attrition in long-term survival studies and the difficulties posed by traditional data collection methods, the process is ripe for an overhaul. By applying new pragmatic approaches, and making full use of the latest technologies, it is possible to better engage patients and reduce the resources required in these types of studies.

Centralize for Efficiency

Patient data lost to follow-up can impact trial findings. One solution to relieve the burden on sites is to work through a “megasite” or international coordinating center—a facility responsible for centralized medical oversight and follow-up with patients, regardless of how many sites were involved in the pivotal trial.

A centralized approach can ensure that safety signals are easily aggregated and flagged from multiple sources. In situations where the number of LTFU patients can be very high (e.g., a cardiovascular outcomes study), remote contact with patients can be maintained through a call center approach, with any clinical follow-up required being passed through to a clinical team from the megasite.

To ensure a smooth and efficient process of centralizing LTFU, key initiatives can be implemented, including early engagement with sites, patient advocacy groups, and regulatory authorities to confirm the acceptability of a megasite model and anticipate any issues or delays. Medical release approval of patients in the informed consent, appropriate system of data capture and clearly outlined data ownership will also be key for success.

Streamline Data Collection

Another challenge facing LTFU studies is the time frame in which the data is collected. Traditionally, sponsors have collected data on patients in these types of studies in an unstructured way as patients complete scheduled visits. There is, however, no requirement that data be collected in real-time.

It is far more efficient to have the megasite collect and enter data from all treating physicians (or patients) at selected points in time. For example, the megasite could ask all local treating hospitals for patient data during March. The data would then be processed all at once, which has many advantages. It streamlines data monitoring and allows better planning of interim analysis, reporting, and medical communication. Such efficiency in monitoring and analysis can also deliver significant savings in operational costs.

The challenge of enlisting investigators’ ongoing help becomes less of an issue by implementing the megasite model and compressing the data collection process to designated periods as described.

Even so, investigators may express concern over patient safety and their general loss of responsibility for patients with whom they've likely built a strong relationship. It is, therefore, important to ensure that stakeholders are given a detailed roadmap to outline how patients will be monitored in the decentralized approach and explain the safeguards in place to control patient safety, including telemedicine options.

Engaging with Patients

Patients may not automatically understand the need for LTFU after a clinical trial. Careful messaging, providing a return for their investment, and offering periodic reminders of the value of their continued participation help ensure their ongoing engagement over the life of a long-term study.

Sponsors can avoid or overcome many of the difficulties of following patients in the long term by:

• Understanding the motivations and addressing challenges of patients/caregivers to participate;

• Being proactive in developing a patient-retention strategy;

• Involving those with responsibility for the patient perspective in planning LTFU studies;

• Funding the LTFU study properly from the outset based on a plan and cost estimates from experts;

• Making full use of technology and patient-friendly digital platforms to streamline data collection and stay connected with patients;

• Being open to an innovative study structure that uses megasites to collect patient data at regular intervals.

Finally, although these considerations are all relevant for an individual LTFU study, significant cost and operational efficiencies can be generated when multiple LTFU studies are delivered within a common platform. With proper planning and resources, sponsors can adopt effective strategies for retaining patients in LTFU studies. Choosing to do so from the outset is the more cost-effective approach.

Prepare and Harness the Opportunities

Moving to a structure of centralized oversight, streamlining data collection in compressed periods, and deploying the right tools and technology to ensure patient engagement can solve many of the pain points that typically arise in LTFU studies. Doing so with proper planning and resources at the outset helps satisfy the growing regulatory requirements and can be the more cost-effective approach.