Sponsors Looking to Life Study Burdens Off Patients And Sites
By Deborah Borfitz
June 15, 2021 | Changes required of study sites during the COVID-19 pandemic, and their evolving role in the clinical trial ecosystem, was the subject of a panel discussion at the recent DIA 2021 Global Annual Meeting. The need to give sites greater flexibility and respect—and for industry to collaborate to reduce the burden of studies on patients and sites and deal with Europe’s new data protection law—were among the main points of consensus.
The pandemic hit in an asynchronous manner, but Merck had business continuity plans ready to deploy for each country and geography detailing how to respond during a crisis, says Andy Lee, senior vice president and head of global clinical trial operations at Merck. “We remained open for business globally… we locked 300 databases; not one was missed. Some studies accelerated recruitment.”
Overall, 97% of corporate milestones were delivered on time during the pandemic, Lee says.
Likewise, at Pfizer, country-specific business continuity plans were executed and it “happened seamlessly,” says Liz Rogers, the company’s vice president and head of global site and study operations. “Pfizer took a slightly different approach and paused recruitment into some clinical studies... based on feedback from sites. They were being pulled into the community to serve.”
No studies were closed, says Rogers, and those that were paused resumed recruitment after six or seven weeks. But all protocols were assessed for ways to make them as “flexible as possible,” which required protocol amendments allowing for telehealth, home health, and use of local lab collection to be options for sites.
Collaboration occurred across the clinical trials industry to keep patients on studies where appropriate, says Sandy Smith, senior vice president of clinical solutions and strategic partnerships at WCG. “It was business as usual at some sites.”
The ability to obtain tissue samples from enrolled patients in the operating room was limited, Smith says, and some sites completely shifted their focus to COVID-19 to help with vaccine development. There was also a widespread pivot to telehealth and “a major need to adapt and be flexible.” Study visits were often by phone, and sites exerted a lot of effort to allow monitoring to occur.
Janssen has been focused on enhancing “clinical trial patient-centricity” for years, including how to bring studies to patients to improve diversity and access, says Greg Tuyteleers, global lead for the company’s decentralized trials program. With sites in some cases closing during the pandemic, adoption and acceptance of decentralized processes and technologies suddenly accelerated—including use of home health services and drug shipment to patients.
To reduce the burden on sites, Pfizer is increasingly using direct access to electronic health records (EHRs) for study monitoring, especially in the U.S., in addition to WebEx, FaceTime, and Microsoft Teams, says Rogers. The company has also given investigators the option of using a cloud-based system for downloading records that monitoring staff can then access, although this creates additional work for sites.
In Europe, Pfizer is still “working through” the GDPR regulatory terrain. The data protection law has clear criteria, but adoption is on a country-by-country basis, which has been challenging, she says. It may take collaboration as an industry to wield any influence in that arena, Rogers adds.
Merck is taking a “no patient left behind” approach to ongoing and future trials, but it is impossible to pivot overnight to decentralized clinical trials, says Lee. The company’s focus currently is on maintaining the “planes in the sky.” Around 70% of studies run by Merck are in critical care oncology where patients are too sick to even be at home.
Adoption of decentralized approaches varies “country by country and site to site,” Lee continues. Uptake of at-home therapy infusion has been nonexistent because investigators are unwilling to subject patients to the associated risks and cancer patients reject home health nurses they do not know. Many of them even have a “favorite” imaging machine, he adds.
Currently, between 10,000 and 11,000 study monitoring visits are happening monthly and half of them are being done remotely via access to EHRs, says Lee. While no remote monitoring is happening in China, it is now the norm in the U.S. where EHR access has risen from 20% to 80%. GDPR has hampered EHR access in Europe. Standardization will be the key to innovation, he adds.
Lee credits adoption of an “integrated monitoring” approach to enabling study continuation and database locks during the pandemic. Where telehealth is being used, he notes, it easily doubles the burden and cost for sites.
Janssen both enabled sites to adopt certain technologies and offered them tools to use at their discretion, says Tuyteleers. Adoption was driven by what would integrate with platforms already being used. Sites often had a system available for telemedicine consults and larger centers started offering home health services on their own.
Simply being adaptable has been the biggest challenge for an industry that likes standards, he says.
To be adopted, decentralized solutions need to strike a balance between what is easy for patients and what is comfortable for physicians, says Smith. Home health nurses are not always embraced for oncology studies because investigators are concerned about their ability to provide appropriate oversight.
At oncology-focused Merck, “recruitment is ahead of schedule against all speculation” and that extends to the HIV and infectious disease arena, says Lee. Retention is also good, he adds. “Where we struggle is with pediatric neonatal type [studies], especially [for] respiratory diseases… parents are unwilling to let their kids participate.” Trials involving elective surgery have also slowed down due to patients withdrawing from the studies.
Competition for study staff has created a “talent war,” the result of sponsors over-allocating sites to compensate for the slowdown and uncertainty, Lee says. At Merck, the motto is “stick to your plans” and people on the ground have been empowered to make adaptations. Protocol deviations linked to COVID have been “minimal,” he notes.
A Look Forward
Post-pandemic, which new capabilities make sense to add to trials in an integrated way will be considered at the study design stage, based in part on the trial phase and therapeutic area as well as the need for diversity and reducing the burden on sites, says Tuyteleers. Janssen has a “decision framework” for this with defined criteria.
Pfizer had already piloted a lot of technologies on a smaller scale, so it was able to quickly scale their use during the pandemic, Rogers says. “Our intention is to use existing technologies when we can… and not [unnecessarily] introduce new ones,” telehealth tools being a prime example. Sponsor companies also needs to collaborate more to reduce the burden on sites, she adds, citing the Shared Investigator Platform of the nonprofit industry collaborative TransCelerate of which Pfizer—as well as Merck and Janssen’s parent Johnson & Johnson—are members.
One of the lessons learned during the pandemic is that technology can be an enabler in terms of enrolling patients into studies with eConsent, telehealth for virtual study visits, and EHR access for remote monitoring, says Smith. She adds that there is “fear that things will go back to the way they were done before, like in China,” and it is her hope that sponsors, CROs, and sites can work together on an alternative long-term solution.
Lee believes the way forward is through innovations that support a study’s primary endpoint, “bespoke verticals as needed for a protocol” and therefore of practical value. That would include technologies that bump up monitoring efficiency.
Telemedicine, Lee stresses, is an “added complexity that introduces privacy issues.” Home nursing is “great in principle,” but required a means to get that data into the study database. The technology exists but needs to be scaled—but not to the point where trials are “overengineered.”
In Africa, where Merck conducts studies for an Ebola vaccine and HIV therapies, technologies can be an “inhibitory component” of trials because they are unavailable in that geography. They can also potentially exclude diverse populations unskilled in their use.
Rogers, in her closing remarks, says it will be important for the industry and governing agencies to work together to ensure both the flexibility needs of sites and the regulation-based needs of sponsors are being met. “Put the patient at the forefront and work backwards.”
From the perspective of sites, “the number one issue is people,” says Smith. A shortage of research-certified professionals was an issue even before the pandemic, and the number of investigators in the U.S. has been declining year over year. In addition to addressing the human capital problem, greater collaboration is needed with patients to reduce trial complexity.
Lee says he wants to “valorize” the positions of principal investigators, study nurses, site staff, and monitors, who are all playing pivotal roles in getting companies through the pandemic. “We need to spend more time listening to them.”