Risk vs. Risk Mitigation Takes on New Meaning for Researchers in a COVID-19 World
Addressing risks associated with the COVID-19 pandemic while embracing new and more accessible approaches to keep clinical trials running may have uncovered the secret to improving the pharma industry’s return on investment (ROI) in R&D.
Before COVID-19, noted Donald Deieso, executive chairman and CEO of WCG Clinical, the industry was seeing ROI on R&D below 16 percent, an unsustainable level. So adding in the pandemic just gave the industry that much more reason to try new approaches to improve that margin, he said. Deieso was one of 20 experts who discussed changes in the industry as a result of COVID-19 during a June 12 webinar sponsored by PharmaVOICE.
The notion of “normal” has been forever changed for the clinical trial industry, the experts agreed. “COVID-19 has done more than just bring a virus we have to address,” said Mark Wildgust, vice president of global medical affairs, oncology at Janssen. “We are creating a new normal and we can and should live in the new normal. We have found ways to succeed in this new virtual world and we have to retain the learnings and apply those going forward.”
Technology, Risk Tolerance and Regulatory Buy-in
“The great paradox of this industry has always been that growth in the science and understanding of biochemistry is outstanding, but management has remained the same as it was 20 years ago,” Deieso said. “But necessity is the mother of invention, and we have watched as such approaches as telemedicine, remote monitoring and in-home nurse visits have become accepted.”
Craig Lipset, former head of clinical innovation at Pfizer, said researchers generally remain risk-averse. But COVID-19 has changed the environment to the point that activities previously viewed as “risky,” such as at-home participation and reduced source data verification, are now viewed more as risk-mitigation strategies to guard against the more immediate risk of spreading the virus.
Interest had already been growing in decentralized trial designs, Lipset noted. With the pandemic forcing industry’s hand in this area, the challenges facing researchers are no longer a question of whether it can adopt decentralized approaches but how it can sustain them.
“There will definitely be a new normal in clinical development, but we all know change in our industry tends to be more incremental vs. disruptive,” John Hubbard, CEO of Signant Health, commented.
For instance, a fully virtual trial would likely be inappropriate in many instances, Lipset said. Hybrid approaches, however, have proven to be both doable and popular with patients.
Technological advancements are playing a key role in some of these novel approaches to research as well. Michelle Longmire, CEO of Medable, noted a shifting paradigm away from data capture only in clinical settings to more use of data capture directly from patients. The necessity imposed by the pandemic has shown that researchers can do this and do it well.
Wearable devices, direct-from-patient data and similar technologies are being more often employed, as are technologies like machine learning and artificial intelligence (AI). Hubbard noted that the pharma industry, including the research sector, has already been using those concepts in some areas, such as data management and biostatistics. Now machine learning and advanced AI are starting to show up in multiple areas, a trend he expects to see accelerate as they can help humans work more efficiently.
Innovation for innovation’s sake is meaningless, Percival Barretto-Ko, president of Astellas Pharma, said. It’s important that innovations be coupled with a tight focus on patient access, patient safety and data integrity.
Longmire touted the usefulness of AI, for instance, but emphasized that it should be deployed to solve particular problems, rather than just applying AI for the sake of AI. Researchers need to include the right “ingredients” to produce an AI “recipe” that meets the purpose at hand, agreed Craig Serra, global head of strategy and innovation, data operations at Novartis.
A concern with any sort of innovation is always whether regulators will accept it. Experts on the panel seemed sanguine on that topic. Regulators seem to be embracing change, emphasizing innovation alongside patient safety, Wildgust said.
Hubbard said Signant’s discussions with the FDA indicate the agency is supportive of decentralized and hybrid clinical trial models. Applying a quality-by-design approach and ensuring that well-documented processes are in place to ensure data quality and integrity, patient safety and study protocol adherence are critical to regulator buy-in, he said.
Patient Focus and Involvement
Shifts made to manage trials during the pandemic also seem to have brought to the fore new ways of recruiting, engaging and retaining patients, primarily by providing them with easier and more convenient ways of participating in clinical research.
“Our challenge is to respect the interest of potential study participants and channel this to enrollment,” said Bonnie Brescia, founding principal and corporate development officer at BBK Worldwide. “We need to further commit ourselves to eliminating or minimizing all obstacles to participation.”
Hubbard agreed that not only does the technology used during the COVID-19 outbreak aid in patient engagement, but it also can help researchers engage more closely with patients to gain insights into disease burden and the benefits of different treatment approaches. A concern has been that fewer site visits could lead to less-close relationships between patients and their study doctors and nurses, but the panel experts said that experience during the pandemic seems to indicate the opposite is true.
“One can’t get to this point and think that patients won’t find a 10-minute phone appointment with intense attention from a healthcare provider expert in their disease superior to driving to a site for a three-minute appointment that likely includes a coordinator as well as the doctor,” Deieso said.
Greater patient reach and enrollment, along with more options for convenient participating in trials could also help to address another key research concern: diversity.
“Innovative thinking is not restricted by race, religion or gender; we have to embrace a society of inclusiveness to support our goal of aiming to transform healthcare,” Wildgust said.
Black patients have historically been greatly underrepresented in every research arena, Ken Getz, deputy director and research professor at the Tufts Center for the Study of Drug Development (CSDD), said. The same is true of Hispanic patients, particularly in the area of oncology. And this has not seen improvement over the past 10 years.
In addition to diversity in patient populations, the pharma and clinical research industries need to increase diversity and inclusion among their own staff and healthcare workers involved in clinical trials, several of the experts agreed.
Collaboration as a Constant
Another hallmark of the COVID and post-COVID environment appears to be increased collaboration, both within the clinical trial industry and among researchers, drug sponsors and regulators.
This is particularly evident in research directed at the virus that causes COVID-19 itself, Wildgust noted, commenting, “Companies developing vaccines don’t see each other as competitors, we all see each other as members of the same team with one enemy and that is COVID-19. We all have the same goal and we are all cheering each other along to defeat the virus.”
And collaboration is a definite strength in the industry, Getz said. While collaboration has always been a part of clinical research, the past several months have shown a massive increase in the amount of partnerships and collaborations, according to Tufts’ tracking of trends in that area. Not only are partnerships being formed more rapidly, he added, but collaboration is occurring in more innovative and more intense ways.