For pharmaceutical companies, the first sign last year that the pandemic was going to have a major impact on R&D was when nothing started happening.
The usual stream of clinical data simply dried up as people hunkered down into their homes. Patients stopped signing up for trials. Clinic visits were canceled. Clinical researchers—crucial to every clinical trial that’s ever been run—jumped from their studies to help out in COVID clinics.
Forced into a virtual world
Clinical trials are the lifeblood of any pharmaceutical company or biotech. What happens when a pandemic sends the world into lockdown? Fierce Biotech investigates
|How pharma R&D bounced back from a once-in-a-lifetime pandemic|
|Can the tech that kept pharma R&D going through the pandemic tackle trial diversity, too?|
|Novartis brings trials to the patient|
|UCB gets out of the driver’s seat|
|J&J's Janssen offers a la carte flexibility|
|At Medidata, things got real quiet|
|Takeda hunts for COVID's silver linings|
Clinical trials are the lifeblood of any pharmaceutical company or biotech. Without clinical research, drugs do not get approved or sold. Many companies, of course, launched into completely new research on COVID-19 vaccines and therapeutics. But all pharma companies were left wondering: What about everything else? “We were all in shock,” said Kim Doggett, head of site engagement for UCB. “With other pharma companies in the industry, we were all like, ‘Oh my gosh, is this really happening?’”
“We saw a lot of stuff fall apart in clinical trials, and I think it's kind of a proxy for stuff that fell apart in healthcare,” said Glen de Vries, co-CEO of Medidata, a software company that supports clinical trials for many of the largest pharmaceutical companies.
The healthcare system is based on the assumption that a doctor and patient can see each other face to face, de Vries said.
Before the pandemic, many biotechs and pharmas were already using or at least exploring decentralized clinical trials and telemedicine as a way to make studies more efficient and broaden their reach. But these tools suddenly became the only way to keep research going in the early days of the pandemic.
Companies had to virtualize as much of the trials process as possible and cut down on clinic visits—and do it fast.
High school chemistry
The disruption happened in several different ways, according to PwC’s Greg Rotz, U.S. pharmaceuticals and life sciences advisory leader for the consulting firm. Ongoing clinical trials stopped or ended up with longer timelines, and trials that were expected to get underway were put on hold or canceled altogether.
A Medidata study including thousands of clinical trials and study sites found a 20% decline in new patients entering clinical trial sites in August last year compared to pre-COVID numbers. The report also found that 31% of sites had to delay a study; 13% canceled a study; 32% had to extend patient visit windows; 27% began shipping medicines to patients; 14% switched to home visits; and 40% had to switch patients to virtual.
The TMF Futures 2021 report similarly found that 41% of life sciences companies had to delay or cancel a study, and 41% of those delayed trials will now run in 2021.
The report also found that 65% of surveyed members planned to continue running clinical trials remotely after the pandemic.
“At the end of the day, I think the feeling was that we can't let the patients down just because we're dealing with COVID issues,” said Craig Tendler, M.D., vice president of clinical development and global medical affairs, oncology, for Johnson & Johnson’s Janssen unit. “We have to continue to support the patients in the studies and also continue to pursue some of these novel treatments that could ultimately have a major benefit.”
Novartis and J&J quickly pivoted to mailing medicines and offering home health visits to keep patients at home. UCB and Takeda halted all of their trials—a completely unprecedented but necessary jolt to their clinical research programs as they figured out a way to protect patients in existing trials.
Companies faced tricky questions depending on the type of medication in a given trial, according to Rotz. For instance, for behavioral health meds, would a virtual visit be sufficient for the doctor to observe the patient’s demeanor?
Clinical studies are very regimented; everything that happens needs to be carefully documented and submitted to the relevant regulatory agency before beginning. So that meant Novartis, UCB and their peers could not just suddenly alter a study to make it fit into the fluctuating environment of the pandemic.
“I wish I could tell you that it was super easy to take a bunch of clinical trials that we're running and start to convert them to use technologies like that. It's not,” de Vries said. “It's like a high school chemistry experiment. You take your lab notebook and you write down in pen what you're going to do, because that's good science. Then you do it and then you write out the conclusion as well.”
Doggett and her team, for instance, documented everything. When they did have to change study protocols, they wrote it down and reached out to regulatory agencies to communicate the update.
Rotz said the regulators knew the challenges companies were up against to keep trials going.
“There was a fast response from the industry and an understanding view from the regulators realizing that we still need to have high quality science,” Rotz said.
The FDA made some accommodations as fast as they could, but, in some instances, companies had no time to wait for permission.
“We didn't have the luxury of being able to wait on regulatory agencies to say, ‘Okay this is the way you do telemedicine, this is the way you do home nursing,’” said Badhri Srinivasan, head of global development operations for Novartis.
One critical issue companies had to overcome was obtaining informed consent from patients participating in trials—a critical step in the enrollment process. The FDA rolled out the COVID MyStudies App as a free platform for investigators to securely get the consent they need to run trials.
For its part, the FDA told Fierce Biotech the agency started a running guidance document in March 2020 with the latest information. The document was updated multiple times as new questions came in from industry about ongoing trials and new starts.
An email inbox set up to take industry questions has garnered 600 hits from industry, investigators, healthcare providers, patients and consumer groups involved in clinical trials. The FDA responded to all of them.
What's normal, anyway?
The R&D chiefs and industry watchers agree, there is no such thing as normal anymore as research has resumed.
“In the immediate term, a return to uninterrupted operations is critical,” Rotz said. But once the pace of research picks up again, he said companies will have to consider how to fit all the advances they launched during the pandemic into new clinical trials.
Novartis, for one, wants to make the changes permanent.
“Disruption is now going to become the fabric of how we do business,” Srinivasan said. “So we will invest and make sure that risk management is something we follow.”
De Vries remembers one client who, prior to the pandemic, was setting up a clinical trial that allowed patients to participate remotely or in person. When the world shut down, that trial kept going.
Decentralized trials could increase the speed and quality of research, but Rotz said they come with some risks around data collection and flow. It's also tough to ensure that everything is done the same way across the trial population.
“The faster we can get through the trial without any delays, the sooner we can get on the market, which is good for the patients,” Rotz said.The FDA said that many of the flexible arrangements they offered during the public health crisis will remain in place.
"The FDA is working closely with our stakeholders and actively continuing our efforts to provide the clarity needed to help ensure the safety of clinical trial participants, maintain compliance with good clinical practice and minimize risks to trial integrity during the COVID-19 pandemic," said FDA spokeswoman Chanapa Tantibanchachai. "These activities, and further lessons learned during the COVID-19 public health emergency, has FDA well positioned to address and advance access to clinical trials going forward."
"We blew it"
Bigger companies were better equipped to handle the disruption, while smaller biotechs may not have had the resources to adapt, Rotz said. The TMF report found that 49% of life sciences organizations reported that the cost of clinical trials has increased since the pandemic began.
Novartis, Janssen, UCB and others said these new trial technologies are unlikely to cut costs for clinical trials, but the benefits may be worth it.
With the delta variant continuing to spread and new guidance from the Centers for Disease Control and Prevention for vaccinated individuals to mask up indoors once again, Rotz warns that the pandemic is not over yet. While the situation in the U.S. is—or at least was—improving with the rollout of vaccines, other countries that traditionally host clinical trials may not be in the same boat. That means companies may have to reconsider where they start new trials in countries outside the U.S.
Had companies had a better handle on where the virus was going in the early days, Rotz said trial sites could have been selected more carefully and companies could have better predicted enrollment challenges. The pandemic underscored the need for better data analytics in setting up trials.
De Vries hopes the industry will take a hard look at other ways to prepare for the next pandemic. For him, that means more collaboration among pharmaceutical and biotech companies and collection of hard data that could send up a red flag when something starts spreading like COVID-19 did.
“I don't know how else to say it politely,” de Vries said. “We kind of blew it, in terms of how the Big Pharma companies of the world and the biotechs of the world could have collaborated and really helped get the planet through the pandemic faster.”