Virtually overnight, the most basic business model of one of the Triangle’s largest industries collapsed.
In the course of just weeks, the contract research organizations (CROs) that create thousands of Triangle jobs, and billions in revenue, by running clinical trials across the globe saw nearly all of their sites shutter.
Clinical trials are a critical step in developing drugs, and the Triangle has been at the epicenter of the industry. Companies such as Quintiles (now Iqvia) and Duke Clinical Research Institute exploded in recent decades. The Triangle now has more than 151 CROs employing more than 24,000 employees, making it one of the driving forces of the local economy.
In the trials, patients try new drugs, the outcomes are checked by site monitors, and the results reported to the U.S. Food and Drug Administration. FDA approval can mean enormous revenue for the drug companies, and, of course, better outcomes for patients.
For an industry whose fundamental commodities are control, process, and access, the chaos of the Covid-19 pandemic posed an unimaginable challenge to its operations.
“Right now people aren’t even turning up in emergency rooms,” said Kent Thoelke, the chief scientific officer of Raleigh’s PRA Health Sciences. “Getting patients to sites for trials is especially difficult.”
Just a decade ago, it would be hard to imagine how many of these CROs and their shimmering towers across the Triangle would manage to survive. the current conditions.But for years these companies have been slowly developing new, virtual, trial models that were just beginning to see the light of day as Covid-19 struck.
Prior to the pandemic, progress on virtual trials had been slow and methodical, hindered by the natural resistance of an industry dependent on oversight and were worried that a new way of doing things might mean a less compliant way of reaching their goals.
But CROs have seen these technological innovations as the potential for speeding up clinical trials – critical in an industry where time translates into millions in hard-fought fundraising capital – and for increasing access for patients.
Now, what were just curiosities to much of the drug development world six months ago are becoming the standard practices in an era are more focused than ever on clinical trials and drug development.
“It absolutely has acted as a floodgate in terms of accessibility of virtual trial approaches,” said Jessica Perry, Iqvia’s director of operations for clinical trials. “One of the things that we’ve really seen is that there really is a need to be able to provide solutions that allow for patients to be able to participate from their home.”
But the executives running these new trials at the Triangle’s largest CROs say they do not expect them to disappear in the post-Covid world. Rather, they expect virtual or remote offerings to become a permanent feature of the industry.
“What we’ve seen is a complete flip of the paradigm,” said Claudia Christian, FHI Clinical’s senior vice president of clinical operations. “The activities are really being driven by the site managers, and the clinical research associates are just sort of sprinkling in some field activities when it’s possible. … Really they’re now acting like site managers because you know it’s either that or they’re unemployed.”
Changing the model
The windfall for virtual clinical trials has come out of necessity since clinical studies came to a dramatic halt since the pandemic began.
Iqvia (NYSE: IQV), in an earnings call April 28, reported that at the peak of disruption some 80 percent of its trial sites in the world were shut down, and that expectations of continued disruption would last throughout the year.
Its guidance for revenue for the second quarter of the year was $2.36 billion, a far cry from the company’s anticipation of $2.84 billion for its first quarter.
At FHI Clinical, Christian said at least 95 percent of the company’s clinical trials were “either stopped, or significantly slowed down” due to the pandemic.
PRA officials say the low point during the pandemic saw a 90 percent reduction in global enrollment.
But, thanks to the rapid adoption of virtual trials, Christian notes the company is hiring a long list of new employees to meet new demand.
“This has already been shifting in the industry, mostly probably driven by cost and time with the quality question mark,” she said. “But now I think we’re proving more so faster than we would have before now that the quality is there.”
In fact, the drug companies and government sponsors have become so suddenly comfortable with the modality that at PRA, Thoelke said. “100 percent of new business requests have had some component of virtual trials.”
That change in attitude from sponsors is, to say the least, drastic according to Thoelke. At the same time last year, he estimates maybe 15 percent of new business requests had any virtual or remote aspect to them.
Josh Rose, Iqvia’s general manager and vice president of virtual trials, said Covid-19 will be “transformational” for many industries, but especially so for the jump to virtual work in trials.
Comparing it to how World War II brought an increase in women in the workforce, he said the need for virtual trials will show sponsors how valuable it can be.
“Our view is that there was pent-up demand within the industry to adopt a more decentralized or more patient-friendly approaches, and Covid was one of those events that basically created the opportunity for pharma to be able to say, ‘Now it’s legitimate,’” he said.
Prior to Covid-19, Iqvia was already bullish on the concept of virtual components of clinical trials. Rose said they projected by 2022 somewhere around 40 percent of clinical trials would have a virtual component.
But that has quickly changed. Rose said he recently polled a panel of CRO experts and most predicted the percentage of future virtual trials would be above 60 percent.
Rose and Perry both predict that by 2022 the figure will be at least 80 percent.
At PRA (Nasdaq: PRAH), Chief Medical Information Officer Greg Licholai said it’s at least 50 percent. Thoelke says the trials that do not require things like imaging and radiology components that cannot be collected from home will be quickest to transform, but even those that do will see a change.
“Highly complex trials will likely be virtual hybrid trials as opposed to 100 percent virtual,” he said. “So I expect hybrid models will be the bulk of what we do.”
The target of the virtual transformation is a well-studied issue in clinical trials: hardly anyone is participating in them.
Despite the thousands of patients that enroll in trials each year, researchers say the overwhelming majority of patients are left out, potentially skewing data and limiting certain populations to cutting-edge therapeutics.
According to Iqvia, just 5 percent of eligible patients participate in clinical research. And that’s despite 60 percent of eligible patients that report being interested.
“The bulk of patients that have access to clinical trials and novel therapeutics tend to be people that are in socio-economic statuses that have jobs where they can afford to take paid time off to go to a clinical trial three or four times in a week to have procedures done and participate in trials,” Thoelke said. “The reality is that 65-plus percent of the U.S. population does not live anywhere near a tertiary center or an academic medical center, and certainly doesn’t have the luxury of having a job that will allow them paid time off to participate in a clinical trial.”
He said virtual trials have the potential to “democratize access to health care and clinical trials as a care option that doesn’t exist today.”
In the least cumbersome way – completely virtual – patients receive “care packages” with tablets and necessary items paired with medical wearable technology in order to report results. Therapeutics that may be involved in the trial can be mailed or, if necessary, delivered by home care nurses or monitored remotely.
But even more involved trials, “remote” or “hybrid” trials, meanwhile patients may have to show up in person for some of the trial, much of the monitoring can be done remotely, lowering both the number of time researchers and patients have to commit to them.
Thoelke said even hybrid trials could reduce the burden on sites by as much as 50 or even 75 percent.
The concept is also projected to increase recruitment for rare and ultra-rare diseases, where the limited pool of patients are often dispersed across a massive geographic area.
Increased enrollment capability also means drastically reduced enrollment time – one of the longest and most costly processes in the traditional trial model.
“If you’re able to open your aperture – not only look at people within 10 miles of the site but now you can look at people within 200 miles, 1,000 miles – now your recruitment is a lot faster,” Rose said.
And collecting the data electronically, rather than through on-site visits, means the analysis “is a lot faster, so you can actually close your study quicker. Those end up as faster, and ultimately cheaper, studies.”
Licholai said PRA’s virtual trials are showing dramatic results in enrollment.
“Where traditional trials would have taken us six or nine months to get started, we are seeing trials start at a significant pace – within 30 to 60 days,” he said. “I don’t know how we go back.”
Emphasis on technology
But going forward means a fundamental change to the business model of CROs. Whereas researchers say the industry was led by clinical research associates (CRAs) on the ground at clinical sites, a virtual shift will put site managers, who once held support roles, in charge of the show.
Instead of using CRAs to go to sites to collect data, the remote monitoring found in the new models means that the data is automatically collected through electronic health records, providing more real-time data than ever.
“As you start to play this out in your head, the impact on our industry – while it won’t happen tomorrow – means that instead of hiring lots of research associates to go out to the site to do source-document verification, instead, we’re hiring people that are more focused on data,” Thoelke said.
He estimates that 60 to 70 percent of the data collected by CRAs are structured data points that can be pulled directly from electronic records, meaning it will “definitely change the future of how we hire and employ people.”
The change also means these companies will take another step further toward being technology companies.
“I suspect you’ll see more technology acquisitions than future CRO aggregation,” Thoelke said.
The potential of the virtual clinical trial model is what inspired Science 37 – an all-virtual CRO with dual headquarters in California and the Triangle – to launch years ago.
“Before Covid-19, the best way to characterize it was that sponsors were somewhat nervous to try a decentralized clinical trial model,” CEO David Coman said. “Because it’s different, and it’s not the way they’ve been doing it in the past.
“Today, sponsors are nervous not to do a decentralized clinical trial because of our ability to access patients in this world that is a little upside down from where it’s been in the past.”
Others in the industry may be concerned that less in-person oversight would lead to concerns about the control of the data, but industry officials say, if anything, virtual trials would probably be an improvement.
“We are looking at the actual medical records. … It’s not like when we go out to monitor a study we’re present at the time that those activities are occurring to that subject. We’re there two weeks later or three weeks later, so we’re trusting the medical records,” Christian said. “So it’s absolutely just as valid to look at the medical records. If anything we’re looking at them quicker because we’re having ongoing active access.”
In fact, part of the dramatic change that has enabled the quick transition to virtual trials is medical centers and health systems agreeing to grant access to their electronic medical records to CROs.
“This greatly helps us …if we’re able to access [electronic medical records] and verify those source records remotely, that saves time, money and effort on everybody’s part,” said Matt Healy, the vice president of clinical operations at Rho. “What I’m seeing is that some of our larger institutions in the country are opening their electronic health record systems to these types of monitoring and I don’t think that that is going to go away after the fact.”
On the regulatory side, government agencies, including the FDA, have been wholly behind the transformation in response to the pandemic, issuing guidance and support for the modality, and many of the national efforts to find a Covid-19 treatment have been approved with virtual methods.
“That’s one of the amazing things in how the world has changed. Who would have thought we’d be saying: ‘Yeah, it’s actually the government on the leading edge of innovation here,’ but that’s really true,” Licholai said.
Even if these current factors are not enough to fully solidify the industry’s permanent shift, the looming prospect of massive trials for Covid-19 vaccine testing will be a big statement of faith in the methods.
“The volume of patients required for those vaccine trials. …especially where we’re doing Covid testing and we’re still being relatively cautious about where potentially Covid-positive people are … we will not be able to do those trials without an incredibly robust mobile, virtual platform,” Licholai said.
For people such as Coman, who have been advocating about the potential public health benefits of increasing access and reducing costs, it’s been a long time coming.
“The ship is sailing now,” he said. “Every market has a catalyst to exponential growth and this has really unlocked the future.”
Original Article Source: Triangle Business Journal