Vaccine Clinical Trials

There are three key factors that are essential to the successful completion of a vaccine clinical trial:

1. Safety: The immediate detection of adverse events  

2. Study Power: Patient populations that are large and diverse enough to reduce the probability of false null hypotheses

3. Time: Data must be measured longitudinally to track changes in efficacy, safety, or patient health status  

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Site-based studies have been challenged on all three fronts. They are subject to limited recruitment pools, greater inconvenience for participants, and fewer regular check-ins.  

In the words of a patient who took part in one of Moderna’s COVID-19 vaccine trials, the experience of participating in the study was “exhausting” and required “seven visits to a hospital, 24 phone calls, dozens of diary entries, repeated batteries of questions about [his] private life, five blood draws, and numerous nasopharyngeal swabs.” While some of these requirements may be unavoidable, others can be minimized or made less arduous through the decentralization of certain steps in the trial process, improving the overall experience for the participant as well as the quality of the outcomes.  

Safety: Capturing adverse events with real-time data reporting and monitoring

Some sponsors are hesitant to adopt models that don’t feature continued, direct interactions between provider and participant, fearing that adverse events may go undetected and that participants’ well-being might be at risk. These concerns can be addressed through smart hybrid study designs, which ensure the careful oversight of patients while reducing—or even eliminating—the number of site visits.  

Contrary to certain assumptions, the integrated devices and intuitive apps now commonly used in hybrid trials enable real-time monitoring, which decreases the likelihood of an undetected adverse event. Virtual research organizations like ObvioHealth have evolved vaccine protocols, enabling trial coordinators to quickly identify any changes in health status, often more quickly than would be the case in a traditional trial. This is a game-changer for detecting adverse events. Virtual communication tools also increase the frequency of communication between the patient and researcher: Questions and concerns can be addressed, and AEs can be quickly processed through to resolution. Imagine a scenario in which a study participant does an initial visit with an HCP at a trial site, receives a vaccine, and returns home. Once the participant leaves the site, technology—such as ObvioHealth’s app—provides them with continuous access to a study team to report any reactions or side effects at the click of a button.

At Roche, the company’s global regulatory lead shared, "COVID-19 has been a catalyst and shows us what’s possible in the use of innovative technologies, combined with local health services, to meet the needs of patients at home.”  This trend is further supported by a recent study published by Oracle, which indicates that 76% of researchers currently run decentralized clinical trials, and 38% of respondents report more than half of their trials are decentralized.  

The ideal design to ensure the rapid and sensitive capture of AEs includes three unique components:

1. Apps that facilitate ePRO: Electronic diaries make daily reporting easier and traceable. A series of simple tasks nudge participants to signal anything that has changed in their health status. Pre-programmed questions and scales then probe the nature and intensity of the change. Failure of participants to provide the regular assurance of “unchanged health status” alerts study staff to potential concerns in a timely manner.

2. Devices and features that augment ePRO: Patients can provide additional data and richer information to study teams to help Principal Investigators (PIs) evaluate any potential issues by using image, audio, and video capture features. For example, if patients mention a skin irritation or rash, ObvioHealth has an image capture function on its app that collects images of the injection site, alleviating the usual need for patients to travel to the clinic. A range of easy-to-use diagnostic devices can also be shipped to participants to capture vitals where relevant. In some cases, information can be shared with central raters or experts for evaluation.  

3. Virtual site teams: Patients' submissions are viewed in near real-time by trained clinicians. In the case of ObvioHealth, the COACH (Clinical Oversight And Coordination Hub) team monitors all significant data and can initiate a text or video chat with patients when further information is required. When necessary, the team is then able to rapidly refer patients to the PIs for further review.

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A range of communication tools allow participants to interact with the study team without leaving their homes and using whatever means are most convenient for them. These communication tools (text, video chats, phone calls, etc.) ensure patient safety while improving vaccine trial efficiency.

Study Power: Ensuring sufficient size and diversity of patient populations in vaccine clinical trials

Fortunately, adverse events for most vaccines are infrequent. But, this means vaccine clinical trials must have large patient populations to detect them and ensure the accuracy of study results on a large scale. Finding and recruiting sufficient numbers of participants can be challenging. Drop-outs are also an issue and are especially common for longer and more burdensome studies. As a result, it is essential to have a robust participant pool to compensate for those who opt-out. Site-based recruitments can be very costly and inefficient; in fact, many sites can fail to recruit even a single patient. Virtualization can help to overcome these obstacles, enabling researchers to reach and recruit patients more cost-effectively using targeted digital media. The expansion of geographic reach makes it easier to recruit more patients more quickly.

Increasingly, researchers are complementing digital recruitment with minute clinic or pharmacy partnerships to expand study populations even further. These partnerships provide options for participants who may not be comfortable with digital enrollment or who seek the convenience of local access to staff. Participants can also be recruited online for local visits. According to the CDC, more than 90% of the U.S. population live within 5 miles of a community pharmacy, and patients visit these locations 12 times more frequently than their primary care provider. Therefore, pharmacists play an important role in providing care for patients, especially those in economically and geographically underserved populations.

In addition to recruitment and enrollment, these neighborhood clinics can serve as sites where participants go for follow-up blood draws or nasopharyngeal swabs. This allows participants to visit more convenient and familiar locations for follow-up visits.  

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Time: Supporting the success of long-term follow-up for vaccine studies

Most vaccine trials require some in-person interaction with HCPs, especially at the beginning of a study when baseline evaluations and vaccine administration is needed. The start of trials is generally when patients feel the most motivated, making these appointments the least likely to be missed. As trials lag, and site visits compound, participants are more likely to want to drop out. This makes vaccine trials particularly challenging, because many require significant follow-up to determine efficacy and any ensuing AEs or SAEs.  

Virtual components can help keep patients engaged to make long-term follow-ups more convenient, thus increasing retention. Protocols can be designed so face-to-face visits occur at the beginning of studies. As the trial progresses, an increasing proportion of communication can occur digitally.  

Conclusion of vaccine clinical trials

Virtual clinical trials have benefits across therapeutic areas, but the unique nature of vaccine trials make virtual solutions particularly effective at ensuring safety, speeding vaccine approval and enabling longer-term follow-up. Virtual tools are helping vaccine trials demonstrate protection from viruses like COVID-19 while giving researchers the rich data they need to evaluate the long-term effects on patient immunity and overall health.

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