From Study End to Long-Term Insight: Choosing the Right Vaccine Follow-up Strategy

Long-term follow-up is a necessity for vaccine development, and is critical for establishing safety data, determining how long a vaccine’s efficacy lasts, and identifying when boosters may be required. With shifting regulatory requirements and public concerns leading to an increased demand for longitudinal vaccine safety and efficacy data, vaccine developers must carefully plan for lengthy follow-up periods.

For vaccines, long-term follow-up typically takes the form of extension studies, which allow Phase III participants to be monitored following the completion of the initial clinical trial. Traditionally, extension studies collect participant data through continued, if less frequent, site visits.

New methods for gathering long-term data are emerging through the use of real-world data (RWD), which is composed of health information collected from sources outside of clinical trials, such as electronic medical records, pharmacy records, medical claims, and other such data. One approach, clinical trial tokenization, passively links participants to de-identified RWD, aiding in the collection of long-term outcomes without compromising patient identifiable information. This enables sponsors to follow consented patients after clinical studies end with greater visibility into the clinical activity of participants. It also enables researchers to benchmark study patients to the real-world population.

Deciding on the best follow-up approach can be challenging, as vaccine developers must weigh the benefits of traditional onsite extension studies and newer methods, such as tokenization. Each has their own unique benefits, and, in some cases, a combination of both may be the most effective. Here, we explore key questions vaccine developers should ask to guide this decision.

How long will your follow-up last?

While vaccine follow-up typically spans 6 to 12 months, the duration can vary widely depending on several factors. Regulatory bodies may determine the need for a longer period based on the modality of a vaccine or the goal of follow-up. Additionally, developers can use long-term follow-up to guide booster schedule recommendations, taking the vaccine’s expected duration of effectiveness into account.

Although traditional sites may be practical for the shorter end of the spectrum, conducting regular site visits to collect patient data can become quite costly for longer periods of time. Also, as follow-up times extend past the typical timeframe into longer studies, it becomes increasingly challenging to track participants for the full length of the follow-up. This is in large part due to participant attrition, which can become more pronounced as time progresses.

For these reasons, tokenization becomes a more practical choice for lengthy follow-up timelines. Because researchers can passively collect data without requiring patients to attend onsite check-ins, it becomes easier to retain participants and gather long-term information.

What kind of data will you need to collect?

Collecting data on appropriate markers and endpoints is a pivotal element of any study, and can influence the type of follow-up chosen. Some information cannot be obtained from RWD alone. For example, vaccines against pulmonary infectious agents may require chest x-rays, and the assessment of vaccine-induced antibodies typically requires blood samples. In these cases, traditional follow-up with active surveillance and site visits remains the preferable choice, since tokenization and passive data collection cannot capture these measurements.

Conversely, if follow-up can be conducted observationally without clinical assessments, it may be preferable to rely on tokenization instead of continuing onsite visits. Through diagnosis codes within medical, hospital and prescription claims data, RWD can indicate whether participants experience the disease the vaccine is designed to protect against, along with other related health outcomes.

In some situations, combining tokenization with active follow-up can be advantageous. With a strategic protocol, site visits can be infrequent and limited to only what is strictly necessary, while other monitoring needs can be conducted through RWD. This approach is useful when active follow-up is required, but patient burden must be minimized.

What patient population are you studying?

While healthy adults are generally the initial participants for vaccine clinical trials, other patient populations may be studied once safety is established. Many of these unique patient groups may necessitate lengthier follow-up to account for immunologic differences, such as for geriatric, pediatric, or immunocompromised populations. Additionally, patient burden may be more acutely felt in these groups, as frequent travel for site visits can be challenging.

For these reasons, developers should consider employing tokenization for follow-up in specialized patient populations. However, it is important to balance these considerations against the need for active monitoring, particularly in immunocompromised patients or those with comorbidities who may have unexpected reactions to vaccines.

It is also critical to include pregnant participants in clinical trials and long-term follow-up. Tokenization can be an invaluable tool for pregnant patients, as it enables retrospective outcome tracking, while protecting privacy.

The impact of asking questions early

Asking these three questions in the initial planning of vaccine clinical trials is critical, since implementing tokenization in earlier phases provides greater efficiencies than adding it later. Early planning allows access to a wider range of patient data, including historical and post-study data, and streamlines follow-up processes for smoother implementation. Although long-term follow-up may seem distant during early planning, determining the best approach as soon as possible ensures the greatest benefit from follow-up efforts.

About the authors

Dinah Knotts-Keeterle, vice president, project management, vaccines and infectious diseases, ICON

Dinah is currently leading the Vaccines and Infectious Diseases group at ICON, and has 25 years of experience working in the clinical trial industry. She has been with ICON for over 12 years and has held many leadership roles across multiple therapeutic areas including vaccines, oncology, cardiovascular, rare disease, dermatology, CNS, and gastrointestinal.

Mandy Armitage, project manager, eClinical development and delivery, clinical trial tokenization, ICON

Mandy is an expert in clinical trial tokenization currently working as a project manager within the eClinical Development and Delivery team with ICON. She has over 12 years of experience supporting clinical research, including in innovative programs for clinical trials including Clinical Trial Tokenization, data, and analytics programs.