By Benjamin Ross 

April 2, 2020 | The reality of the novel coronavirus (COVID-19) has presented numerous challenges for society—and these challenges extend to clinical research as well. While some trials for a COVID-19 vaccine have already begun, it will take some time before any progress is made for a publicly available drug. 

And in the meantime, clinical trials not dedicated to the pandemic are struggling to remain operational. 

Recent guidance from the U.S. Food and Drug Administration (FDA) has attempted to provide clarity to the situation, offering solutions to challenges such as quarantines, site closures, travel limitations, and possible interruptions to the supply chain. 

However, these provisions highlight fundamental issues with how clinical researchers and pharmaceutical companies execute their trials, argues Ed Seguine, CEO of clinical trial technology company Clinical Ink. 

It’s an argument made by former FDA director Scott Gottlieb, who, in a March 2019 statement lamented how opportunities to “harness the full potential of science to reduce the suffering, death, and disability caused by complex human illnesses” is often “delayed or stymied by a clinical research enterprise that is often extraordinarily complex and expensive.” 

“Unfortunately, we’ve seen a continued reluctance to adopt innovative approaches among sponsors and clinical research organizations,” Gottlieb stated. “In some cases, the business model adopted by the clinical trial establishment just isn’t compatible with the kind of positive but disruptive changes that certain innovations can enable.” 

This incompatibility between business model and innovation is clear when looking at the industry’s options to respond to COVID-19, Seguine tells Clinical Research News. 

“The FDA guidelines recommend some targeted activities like virtual visits, etc... But if you didn’t build that into your protocol in the first place, implementing that during the trial is going to be a total mess.” 

Despite the dramatic and rapid advance in the science, the business model for executing clinical trials hasn’t changed in decades, Seguine says, leading to nothing more than surface-level innovation. 

“We haven’t fundamentally changed how we run trials,” Seguine said. “And as a consequence, we can’t fundamentally change other operational activities to monitor and review data remotely or to simplify the complex demands on sites.” 

Seguine fears that sponsors and CROs don’t have a pragmatic focus when it comes to innovation.  

“It’s much more enticing to put out dramatic statements about how the future will be different and say, ‘If we just deployed sensors on all clinical trials’ or ‘If we just integrate with EMRs [Electronic Medical Records], we’ll have so much more data and we’ll see it all the time.’ But guess what? That hasn’t happened for years, and we’re not meaningfully closer now,” Seguine said. “Now, there’s a pragmatic approach that says certain studies focused on certain disease areas would benefit from sensors, such as diabetes and glucose monitoring. But just wiring up Apple Watches and talking about how that’s going to change the world is naïve.” 

Despite the industry talking about the potential of innovation, Seguine says it has to come down to the mundane discussion of data storage. If not, researchers left with a platform that doesn’t enable change to their business model, a mandatory step to restructuring trials in the wake of COVID-19. 

Seguine believes it’ll be difficult for trials using the current business model to implement alternative processes, saying it’s like trying to put spilled milk back in the jug. But the broader point, Seguine stresses, is that events like COVID-19 provide the opportunity to look at the structural dynamic of how clinical research is done. 

Innovation on the Fly 

The novelty of the virus is causing researchers in the U.S. to learn on the fly, Zach Gobst, CEO of the patient advocacy company Leapcure, tells Clinical Research News.  

“Today, we’re still figuring out the unknown,” Gobst said. “We know that China and Italy are weeks and months ahead of us, but we don’t really understand what the new normal is going to look like, or even if it will go back to normal or will change. So understanding what site behaviors are going to be and what patients are going to be interested in joining now versus later is an adaptive learning process.” 

Gobst says patient recruitment companies are used to working with this mindset, giving them a unique perspective into what steps can be taken to ensure trials generate participation from patients. 

“As a [patient recruitment] company, we’re used to understanding which research sites are most likely to be able to enroll patients and have the capacity for them in terms of staff and resources, and we have to adapt where we target accordingly,” said Gobst. “What we’re seeing in some ways is absolutely a new challenge, but in some ways it’s something we’re always dealing with, which is figuring out where we need to find patients to move research forward.” 

Recruiting patients for COVID-19 requires a shift in mindset from the industry. As Laurent Schockmel noted at the recent Summit for Clinical Ops Executives (SCOPE), the industry has worked under the assumption that if they provide the trials, patients will naturally flock to them. Gobst says a new approach follows a consumer marketing trend. 

“We’re moving from cold-outreach distribution to permission marketing and partnership marketing where you’re reaching out to the folks that want to participate instead of putting your media into a billboard, where you’re paying for impressions to people where it’s completely irrelevant,” said Gobst. 

One way this is evolving is in conversion-based adaptive recruiting, Gobst says. 

“In a lot of cases, when you’re trying to find people for clinical trials and you want to make sure they’re going to make sure they meet the basic inclusion/exclusion criteria, you’ll put together a digital pre-screener where you’ll ask important criteria questions that can influence the quality of a patient for a site,” Gobst explained. 

Instead of looking at marketing outreach’s success by the number of clicks or views on a given pre-screener, conversion-based adaptive recruiting looks at the cost of finding a patient that meets a trial’s criteria and converts that into optimal ads that ensure the right patients complete the pre-screener, which can lead to a referral, being scheduled, consented, and enrolled. 

Researchers tend to think of their media outreach as one big blast and getting economies to scale by reaching as many people as possible with the same message. “That’s actually not what works best for recruitment,” Gobst said. “For recruitment, you want to get in front of the right people because your site coordinator already has a day job when they get a patient that comes in. If the first fifteen or twenty of them aren’t a fit for their study, then they’re going to stop following up with those patients. So you need to make sure you’re finding the patients that are the most likely going to participate, and getting those people in front of the researcher is imperative in a time like this.” 

This approach reduces the number of referrals it takes to fill a study, Gobst says, saving the site both time and money. It also ensures that the patients found are the most invested in moving research forward. And in the case of COVID-19 trials, Gobst says both elements are keys to success. 

“Lifestyle plays a big part in this,” Gobst said. “We’re trying to figure out what everything looks like, and it’s constantly evolving. So it’s important to find both affected and healthy patients that are going to be the most likely to participate.” 

“No Pressure, No Diamonds” 

Gobst says COVID-19 presents a unique scenario where the industry can begin to heavily adopt alternative methods at every phase of clinical trials, from patient recruitment to sample collection. 

Where the innovation is going to happen in this space is hard to pinpoint, he says. “Who knows exactly whether it’s going to be adopting advocacy, patient influencers, or refining recruitment. . . But I think the folks focused on mobile and virtual trials are going to be where we see a lot of innovation.” 

Sanguine Biosciences is one of those companies finding ways to enable mobile trials, offering services to serve as a conduit for both the patient and the researcher. 

Sanguine’s co-founder and CEO, Brian Neman, tells Clinical Research News that COVID-19 has grinded the traditional model of running a clinical trial to a halt. 

“Overall, there’s a tension when having to go to the doctor’s office,” Neman said. “. . . For the most part, when it’s an investigational drug that we’re not sure what the effects are, the likelihood of dropping out of a trial is [high].” 

The reason for dropouts is two-fold, Neman says. People want to avoid going out to the visit the sites for obvious reasons, and caregivers—often the children of elderly patients—want to avoid physical contact with their parents. 

“[COVID-19] is forcing the patients to stay home, and it puts the researchers and pharmaceutical companies in a tough position where they say, ‘We need to finish this study ASAP. If the patients aren’t going to come to the site, then we need to find another way [to conduct our trials],” says Neman. 

Virtual visits and telemedicine are established ways to navigate these hurdles, but Neman says Sanguine takes it a step further with at-home visits, data collection, and sample processing according to study protocols. 

“It’s pretty clear you can’t give a blood draw over the phone,” said Neman. “What we’re offering is a suite of services in the home setting that’s enabling us to collect as many samples as possible and engage with as many research organizations as possible.” 

Sanguine interacts with patients and researchers on three fronts: patient engagement, home visits, and data collection and processing. 

“We find patients over the internet, through social media and patient advocacy groups, and they sign electronic informed consent forms and medical record authorization—so basically online recruiting and scheduling,” Neman explained. “We perform the home visits, we collect the medical record data and samples and synthesize them, and then we deliver it to the researchers.” 

Sanguine also stores the patients’ medical records through their Trial Match platform, giving them the ability to link patients to additional trials. 

Trial Match will scan through a patient’s medical records, comparing specific data points with other clinical trial enrollment criteria. The platform then gives both the patient and their doctor a report on the best-matched trials and will assist in the enrollment process. On average, Sanguine helps enroll patients in 3-4 trials per year. 

Neman’s noticed an uptick in business since COVID-19, saying Sanguine’s received twenty requests from pharmaceutical companies in the 72 hours prior to our conversation, including a company working on a COVID-19 study. 

“I think the industry is responding with solutions that can be long lasting and can improve outcomes and effectiveness over time,” Neman said. “It’s unfortunate that [COVID-19] is the catalyst that has gotten us here, but I think once we start to see home visits increase the capacity for safety and decrease the burden for patients, I think it’s going to be tough to go back to the old ways.”