Clinical Researcher—August 2021 (Volume 35, Issue 6)

TRIALS & TECHNOLOGY

Jonathan Andrus

The immediate need to control SARS-CoV-2 and the ongoing need to treat diseases such as malaria, tuberculosis, and pneumonia highlight the critical nature of research and development of new anti-infectives and vaccines. Speed is an advantage here, as ready availability of effective vaccines and therapies has a direct impact on the magnitude of epidemics and pandemics.

We can learn from the experiences of COVID-19 vaccine developers and clinical trial sponsors who continued or completed studies during the pandemic as we devise practical solutions for future development. Most of these lessons involve the use of eSource technology that allows clinical trial sponsors to develop therapies more efficiently, at a lower cost, with less burden on patients and sites.

Implementing technologies such as videoconferencing, mobile technology, and remote patient monitoring (pulse oximeters, blood glucose monitors) allows patients to participate from anywhere. Real-time access to direct data capture (DDC), electronic patient-reported outcomes (ePRO), and electronic clinical outcomes assessments (eCOA) provides study teams with immediate insights and interim analysis reporting.

Not all commonly used technology improves clinical trial efficiency. Many sponsors utilize electronic data capture (EDC) systems to collect clinical data. With EDC, clinicians typically record vitals, outcome assessments, and other patient data on paper. As an additional step in the process, data are later transcribed into the EDC system and saved in an electronic case report form (eCRF). After this step, data in the eCRF are verified against the paper form—a process called source data verification (SDV). With SDV complete, clinicians can access data and manage queries.

During the pandemic, many sponsors moved to a decentralized approach out of necessity, recognizing that a paper-based process does not integrate with advanced digital technology. A more immediate approach using DDC, ePRO, eCOA, and similar electronic forms, which we collectively call eSource DDC, eliminates the paper-form step and nearly all SDV.

Using eSource DDC, timelines shorten by months—in some cases, time to database lock is reduced from months to 48 hours. When time, budget, and patient access are high priorities, advanced digital technology that integrates seamlessly with remote technology and eliminates paper-based processes is an asset for clinical trial deployment.

Be Ready to Switch Gears

eSource DDC platforms are designed to handle the complex workflows that are part of decentralized trials. They’re also designed to scale as needed when protocols change or an outbreak occurs.

If a public health emergency strikes mid-program, for example, that program must pivot quickly. A recent neurology study enrolled nearly 2,000 patients across more than 250 sites for Phase II and Phase III clinical trials. By the time the studies started, the SARS-CoV-2 virus had spread around the world. Participants did not want to visit research sites for fear of contracting COVID-19.

To keep patients enrolled, the sponsor rapidly transitioned from paper-based assessments to eCOA and ePRO and adopted a bring your own device (BYOD) strategy. It built and deployed 10 different collection forms for home use as quickly as possible. By reducing the amount of user acceptability testing and proactively reaching out to questionnaire license holders, the sponsor completed the build and was in production within 10 days.

All participants completed assessments from home and attended virtual clinic visits. If they didn’t have access to a mobile device, the sponsor provided one.

As a result of its ability to shift to a new approach quickly, the sponsor retained participants who would have otherwise dropped out of the study, and because of the 10-day build, the study stayed on track. This positive outcome happened because of the flexibility gained by using eCOA, BYOD, and eSource DDC.

Design the Study for the Patients

Remote technology not only allows sponsors to recruit more patients—an advantage for large, late-phase studies—it allows them to use both structured and unstructured data in a meaningful way.

For example, a leading pharmaceutical company moved from EDC to eSource DDC for a SARS-CoV-2 prophylactic Phase III trial. The study aimed to evaluate post-exposure prophylaxis and preemptive treatment in 1,000 participants, all of whom were age 60 or more and lived in long-term care facilities. These high-risk patients could no longer travel to sites, nor could they risk contracting or transmitting the virus.

To keep the study running, the sponsor hired traveling coordinators and nurses to remotely collect data. Clinicians captured vitals, handwritten notes, and photos of drug dispensation records directly into the electronic record using eSource DDC. Unlike EDC systems, most eSource DDC platforms accept both structured and unstructured data.

Because of the rapidly evolving COVID-19 situation, clinicians needed to respond quickly if a patient’s health status changed or if health departments updated mandates. Real-time data made this happen. Edit checks allowed for on- or offline, in-form, and cross-form/cross-visit alerts and calculations (derivations, scoring, etc.). All edit checks were performed during the patient visit and all were critical to patients’ health.

By shifting to a decentralized model, participants could fully participate in the trial without leaving their communities. As a result, the sponsor not only kept its clinical trial on track, but it also completed study startup in 10 weeks—significantly quicker than would have been possible using traditional methods.

Integrating digital technology such as eSource into anti-infective clinical trials enables faster study startup and access to a wider range of data. By capturing and validating data directly into the electronic record at the point of care, sponsors can address abnormally high and low values with the participant present. Addressing anomalies early helps prevent data queries later, leading to a more efficient clinical trial overall.

Advancing Antiviral Drug Development

To continue to advance clinical research, we must learn from our victories as well as our mistakes. We can model new victories from the success of COVID-19 vaccine developers, which used all available resources and the latest technology to develop vaccines in a tenth of the standard time.

We’re moving in the right direction. The recently formed Decentralized Trials & Research Alliance (DTRA) is dedicated to accelerating adoption of patient-focused decentralized trials and research. One of the priorities for the organization and its more than 100 members is to identify and remove barriers to decentralized research implementation.

In March 2020, a group of more than 20 life sciences companies formed the COVID R&D Alliance to further coronavirus drug development. The Rapidly Emerging Antiviral Drug Development Initiative (READDI) brings together worldwide industry leaders to develop antivirals.

Remote monitoring, eSource DDC, and related solutions such as telemedicine and remote patient monitoring are pivotal in enabling these organizations and other pharma and biopharma companies to develop vaccines and therapies with efficiency and speed unheard of in the pre-pandemic era. These tools also encourage research participation by putting the patient at the center of the clinical trial experience, a crucial consideration in the race to control infectious diseases.