OR WAIT 15 SECS
Hybrid studies, patient-centric tools, and collaborations create big changes for clinical trials and stakeholders during COVID-19.
This is a follow-up to a June 2020 story in Applied Clinical Trials, when the impact of the COVID-19 pandemic was in its early stages. Voices from stakeholders, including vendors and other organizations are presented, along with data from recent surveys. They provide insight into how the industry is adapting to new approaches to clinical trial conduct during the COVID-19 era, largely with the aid of virtualizing tools, strong partnerships, and regulatory guidance. Despite the upheaval in the past year, they share a sense of optimism that at least some of the systemic changes leading to the remarkably quick development of several vaccines will remain. This could involve expanded use of already popular technologies, which according to a new survey by the Society for Clinical Research Sites (SCRS) and Medidata, includes electronic clinical outcomes assessment (eCOA) (used by 72.9% of respondents), email notification (64.3%), online recruitment (63.3%), and more.1 But, for an industry that is notoriously slow-moving, not enough time has passed to determine which process changes will ultimately become standard practice post-COVID.
One key finding from the interviews was that hybrid models, as compared to fully virtual or traditional trials, are widely expected to assume a prominent role in the clinical trials landscape, as they facilitate the growing emphasis on patient centricity. There are also lessons learned, mainly involving the realization that stakeholders need a strong foundation to transition to decentralized clinical trials (DCTs), whether they are fully virtual or a hybrid of remote, in-home, and onsite visits. The foundation is rooted in strategic partnerships with contract research organizations (CROs), vendors, and associations who share collective wisdom to develop best practices or apply knowledge acquired from clinical care to the clinical trial realm. Stakeholders weigh in on the critical importance of building this foundation in order to move ahead with revamping clinical trial operations.
Finally, Applied Clinical Trials presents current thinking on how sites are becoming more comfortable with an evolving industry. Jim Kremidas, Executive Director of the Association of Clinical Research Professionals (ACRP) comments, “Sites recognize that things are changing, and they have to be looking for people with new skill sets or developing people within their organizations to leverage these new skill sets.”
So, the sector is in flux, as evidenced by the rising use of technology, greater reliance on remote visits and partnerships, and a work force that is a better fit to the new reality of conducting clinical trials during a pandemic and beyond.
When the pandemic first hit, there was a sudden awareness across the industry that if existing clinical trials were to resume, and if there was any hope of a vaccine being quickly developed, processes had to be adopted that would allow the safety of patients and site staff to remain top priority. With patients increasingly reluctant to visit sites, “safety” meant instituting at least some remote or “televisits”, a key aspect of DCTs. In the last few months, DCT uptake has grown dramatically, and is slated to continue. A recent analysis suggests that the global market for DCTs is expected to reach $10 billion by 2026, rising at a 6.5% compound annual growth rate between 2020–2026.2 As evidence of this growth, the SCRS/Medidata survey found that televisits, already used in the past two years by 45.1% of the 204 respondents, are likely to be adopted by an additional 39.2% of respondents in the next two years.1 The survey also reported that only 15.5% of respondents participated in decentralized or completely virtual trials in the past two years. But, 42.1% stated that they expect to implement them in the next two years–nearly a three-fold increase.
Research from the Tufts Center for the Study of Drug Development (CSDD) indicates that during the pandemic, telemedicine has become the most frequently used approach for supporting DCTs.3 Its use by more than 80% of companies reviewed for a recent Impact Report suggests that its growth is due mostly to the relative speed and ease of implementation. This was the finding of a CSDD analysis of the 50 largest pharmaceutical companies, based on published information, virtual conferences, and detailed interviews with 23 pharmaceutical companies conducted in August and September 2020.
Melissa Nezos, Vice President of Clinical Operations at Firma Clinical Research, a provider of in-home health services, comments on the ongoing shift toward DCTs. “What I’m hearing from big pharma is that they are setting corporate goals going forward to have a decentralized clinical trial component. Many of the large companies have innovation groups where DCT is a focus for the future. Before the pandemic, they were slowly inching toward the goal of performing more DCTs, but the pandemic has forced these innovation groups to immediately become engaged. They’re now working with partners like Firma on how to pivot their ongoing trials, and how to strategize on incorporating DCTs into their future trials,” Nezos explains.
Regarding the use of more home-based visits, Rasmus Hogreffe, Vice President of Decentralized Clinical Trial Innovation at Medable, a provider of a DCT platform, says, “We are seeing rising decentralized trial adoption in the industry on a daily basis, including home visits. Before, patients were going to the site, and now, we are seeing sites going to the patient. It’s a patient-centered approach, rather than a site-centered approach.”
To make this happen, site staff need to be trained in how to conduct a DCT. A 2019 survey of 340 site professionals conducted by SCRS in collaboration with VirTrial revealed that 60% of respondents had no experience in remote trials or any type of virtual processes, 37% claimed to have conducted a hybrid trial, and only 3% had participated in a completely virtual trial.4 With protocols embracing more virtual components, these statistics are concerning, but they were collected pre-COVID, and since then, site professionals have gained exposure to virtualizing tools and are incorporating them into ongoing studies. Kremidas of ACRP remarks, “Now that people have been forced into using virtual technologies, they’re realizing that it’s not as scary as they thought. They’ve become accustomed to using these tools, and that’s half the battle. The analogy is—when you get a new computer with unfamiliar software, you first move a little slower than you’d like, but as time passes, you get used to it, then you start to like it, and finally you can’t live without it. That’s where we are now.”
Our research shows a consensus that as the pandemic rages on, DCTs are clearly trending toward the hybrid model. While some trials may be fully virtual, and some may remain traditional, many more will be hybrid, as they are well-suited to a customizable patient-centric mix of on-site and remote visits. Ken Getz, Executive Director and Professor, at CSDD, explains, “About 55% of all trials moved to remote or a model with support from virtual technologies during the pandemic. I think once the pandemic is behind us, and there is more familiarity with these approaches, the hybrid approach is the most likely model because it’s defined by patient preferences. We are giving patients the option to come into the center or have virtual visits. Why wouldn’t we offer that for any trial?”
Similarly, Nezos of Firma comments, “Most of our current studies are hybrid. We aren’t seeing or working with companies performing fully virtual trials yet. A lot of technology would have to be in place for studies to be fully virtual and that’s something that most stakeholders don’t have. As for hybrid, sponsors are asking us to look at the protocol to see what they can do to bring in more virtual elements, so they can maximize the amount of visits that can be done in the home.” As part of this effort, she points out that many protocols include assessments and items that could be performed in the home with the help of home health practitioners, such as sample collection, blood draw, and EKG.
But there is still a vital role for site visits. For example, the first and last study visits may be more extensive, and may involve imaging, which would require visits to the site or to an imaging facility. Also, patients may want to have at least some face-to-face visits with the principal investigator and study coordinator, so to enable this, the protocol could be designed to move items originally planned for a remote second visit into an on-site first visit.
Amy (Nordo) Cramer, Global Product Development Operations Strategic Partnerships at Pfizer, sees the movement toward DCTs as operating along a spectrum, reflecting the specifics of various therapeutic areas and patient populations. “On one end is the fully virtual, completely decentralized trial, and at the other end is a study with maybe just one virtual tool, such as ePRO, with hybrid in the middle. Out of cautiousness, portions of the research community will opt to move slowly from one end of the spectrum, maybe starting with one functionality of a DCT, and as they become more comfortable, they’ll start moving across. I think other companies, like Pfizer, will be innovative and lead the industry by utilizing the full spectrum of DCT,” Cramer says.
The discussion about DCTs is also a discussion about patient centricity. DCT momentum was fueled by the COVID crisis, but their growing acceptance suggests that they are offering solutions to long standing challenges for the clinical trials sector, such as patient recruitment, enrollment, retention, and compliance. Current thinking indicates that if potential subjects could more easily enroll and participate in study visits from the convenience of home, retention and compliance might improve.
Getz from Tufts CSDD remarks, “I think the term ‘DCT’ does not go far enough in conveying what we need to do as an industry. Calling studies ‘decentralized’ is still putting the site at the center of the trial. We should be thinking about this as patient-centric. This would mean that patients who are more anxious may want to have at least some in-person visits, whereas others may want to mostly interact using a hand-held device.”
Jeremy Price, Director, Clinical Innovation & Strategic Partnerships at Pfizer, says, “We are proactively meeting with study teams and reviewing their protocols with them to see if including remote visits makes sense. If we can add some remote visits, even one or two over the duration of the study, it’s a huge win from the patients’ perspective, and they are more likely to stay in the study. It can also be a win for diversity and inclusion, as we can increase access for participants from a variety of backgrounds and locations that may be further from study centers.”
To boost patient centricity in clinical trials, Medable launched its Patient Advisory Council (PAC) in February 2020.5 It is a nationwide network of advocates who are advising the company and its biopharma customers on how to improve patient access, experience, and outcomes in clinical trials. The PAC is a network of patient advocates, advisors, and caregivers with diverse backgrounds in patient engagement and a strong understanding of patient preferences. The goal is to improve clinical trial access and efficiency by embedding patient voices and perspectives into aspects of clinical trials, and identifying and prioritizing potential hurdles that patients face. Medable is incorporating those perspectives into its DCT platform.
As greater use of DCTs unfolds, the logical next question is—which of the current changes will remain once the pandemic winds down? It is fair to say that no one knows for sure, but there are smart initiatives underway that are looking at the infrastructure and partnerships needed to make some of the changes stick.
Pfizer has been active in the DCT space for a long time, according to Price. He says the company has strong strategic partnerships with many types of clinical research community members, including those with telehealth capabilities. “Early in 2020, adoption of telehealth for clinical care increased exponentially, so we were able to jump on that and utilize those tools for visits in our trials.” Cramer adds, “We had already done a significant piece of work in trying to form a better bridge between clinical care with clinical research, so when we got into the COVID situation, and needed to find alternatives, we knew the options clinical care was using, and our strategic partnerships helped us understand how we could use existing functionality in clinical care in clinical research. Our partnerships were a large part of our ability to pivot so quickly.”
For Pfizer, the importance of partnerships is being played out in a new initiative called Vulcan. Launched in August 2020 by Health Level Seven International (HL7), Vulcan seeks to use a model for collaboration among diverse stakeholders in the translational and clinical research space to define a common set of standards that can be implemented globally, using the HL7 Fast Healthcare Interoperability (FHIR) standard for data exchange.6 The intent is to optimize the design, conduct, and reporting of clinical studies. Cramer, the group’s co-chair, mentions, “We have this opportunity as a collective group of the entire research community to work on solutions together. No longer does clinical research sit at its own table. We’ve joined a table of all of healthcare, and the benefits of this collaboration are exciting. We are actually working together in a way that I haven’t seen in my career. This is a game changer for clinical research.”
In December 2020, the formation of another alliance—Decentralized Trials & Research Alliance (DTRA)—was announced.7 The goal of DTRA is to unite a wide range of stakeholders, namely healthcare companies, regulators, patient groups and research organizations to enhance patient-focused trials and remove barriers to participation by advancing practices and technologies for decentralized studies. According to a recent DTRA press release, there hasn’t been a forum in which a diverse group of stakeholders could collaborate on this subject.7 As evidence of the strong interest in this initiative, there were 50 founding members, growing to nearly 70 members by early January 2021, just weeks after the organization’s launch.
The movement toward greater patient centricity and the adoption of decentralizing tools that enable it has been brewing for a while, but in recent months of the pandemic, there has been a dramatic uptick. So, the tide is clearly turning, and the industry’s embracing of DCTs is a silver lining. But will this momentum last?
Getz comments, “It’s hard to envision how it will play out because the pandemic forced a very abrupt change in design. Regulatory guidance has accommodated that abrupt shift. Basically, the door has been opened, and a lot of patients are going to say now that they’ve seen the light, why would they revert to only having in-person visits?”
He expects the path to a DCT world to be far from smooth, as most everything that’s been done in response to the pandemic has added more complexity and customization to clinical trials. This in turn increases cycle time, inefficiency, and cost, and the industry needs to figure out how to
Because of the unsettled landscape, CSDD is more cautious about making statements about process change being sustainable. “We aren’t convinced of that. Historical precedent would suggest that the speed and incredible collaborations and success we’ve had in developing COVID-19 vaccines may be more of a one-time occurrence unless there are a whole host of fundamental areas that are addressed,” Getz warns.
Still, this is an amazing time for the clinical trials sector, as recent success in developing several vaccines is a testament to what this industry can accomplish. But, it is shifting, so it will be critical to re-visit this subject periodically to determine which changes become permanent.
Ann Neuer, MBA, President, Medical deScriptions, LLC