After a tumultuous several years for the Food and Drug Administration, the agency will soon get a new leader in President Biden’s pick, Dr. Robert Califf. In the wake of a pandemic that exposed numerous flaws in the agency’s old processes, experts expect an overhaul of clinical trial infrastructure to rank near the top of Califf’s priority list, assuming he survives the confirmation gauntlet.
“I think that Dr. Califf will remain focused on ensuring that safe and effective medicines are available for patients in need,” said Craig Lipset, managing partner at Clinical Innovation Partners. “And by ‘available,’ I mean with a certain sense of urgency. Our current system is not necessarily optimized to ensure we’re leveraging all of the resources available to us to make sure that’s possible.”
Califf, who previously served as FDA commissioner during the Obama administration, has actively advocated for change in the clinical trial process.
“It is a good time to consider a revamp and Califf has the background and expertise to do it,” said Dr. Mark McClellan, director and professor of business, medicine and policy at the Duke-Robert J. Margolis Center for Health Policy.
That’s particularly important amid a potential fourth wave of COVID-19. The broader clinical research community has united around the belief that the system in place before and during the pandemic hasn’t been as effective as it could be.
“The U.S. has had millions of COVID patients, but only a small fraction of those have been enrolled in clinical trials,” McClellan noted. “Only a small fraction of those clinical trials have actually led to definitive, actionable clinical evidence because they’ve been too small or not well-controlled. That’s why we didn’t have reliable answers as quickly as we would have liked.”
Even prior to the pandemic, the healthcare industry was grappling with significant changes in digital technology that could, at least in theory, provide better data collection capabilities. The pandemic, then, served as a catalyst for the FDA and the research community to incorporate these new technologies and methodologies to make trials run more smoothly – and, in turn, have therapies approved faster.
“We do know how to do very well-designed trials quickly, as the COVID vaccine trials showed,” McClellan said. “They did it pretty quickly by applying some of the principles Califf has developed and implemented during his career, such as ensuring more diverse patients participate and that data collection is not too burdensome.”
The efficiency of data collection has become a flashpoint. Historically, electronic records have slowed down clinical trial efficiency. Now, more progress has been made in expanding standardized data models.
“Steps that make it easier to collect data will open up more possibilities for healthcare providers to participate,” McClellan continued. “There are a lot of community hospitals that don’t have the bandwidth to hire research staff, but are willing to participate in clinical registries or trials where some of the data could be collected more simply.”
The pandemic also revealed a need for more decentralization and diversity in clinical research. To that point, the introduction of the Diverse Trials Act signified a commitment to boosting access to clinical trials among marginalized communities and people of color.
Califf’s background, Lipset said, suggests that he is committed to change on both fronts.
“That Califf made the decision to work with a company like Verily over the last few years, which has been at the forefront of remote patient-centered research, is a very positive signal,” Lipset explained. “My experiences with him have included the perspective that decentralization doesn’t mean a lack of engagement with physicians, but that its success is based on shared decision-making between the physician and patient choosing to participate in research.”
Lipset also predicts that Califf will attempt to expand the use of pragmatic trials and real-world evidence. Pragmatic trials, as opposed to traditional ones conducted in artificial settings, offer opportunities for collecting real-world data.
“Pragmatic trials make greater use of physicians in the community,” Lipset said. “So while the data we collect might not be the same as in a clinical trial, we’re not necessarily compromising on volume of data because we’re leaning more actively on real-world data sources, and looking to study people closer to real-world settings.”
Given how he’s championed them and written about them in the past, Califf will likely leverage all contemporary approaches available to make the clinical research process work better than it does today. That includes innovative study designs and novel sources of data that, when working in concert, can create radically more efficient ways for researchers to answer important questions.
The challenge for Califf, however, isn’t just from within the FDA. He will have to make sure that biotechs, pharma giants and device manufacturers take advantage of the FDA’s receptivity to change and work collaboratively with the agency.
“For that ecosystem to change, it takes the whole ecosystem,” Lipset said. “We need clear signals to researchers and industry leaders that the FDA is open for business and open for innovation. We need those in drug development today to take advantage of the pathways and opportunities that the FDA has already created.”