Like most things in healthcare, clinical trials have been slow to evolve in recent decades. But the COVID-19 pandemic has forced clinical trial research teams to become more efficient, patient-centered and inclusive.
Much is at stake as the pandemic has already caused significant clinical trial disruption. EY estimates that the COVID-19 impact on Phase 3 studies for the top pharma and biopharma companies could cost the industry $35 billion by 2024.
The potential disruption to clinical trials for drug development, fillings and launching could last for years, if not decades, according to the white paper “The Growing Value of RWE” from IQVIA, which serves as a contract research organization and offers consulting services to the pharmaceutical industry.
“Almost all of our studies were impacted,” said Barbara Arone, VP of global medical affairs category lead at IQVIA. The majority of clinical trials Arone witnessed “had to change something about how they were operationalizing, and that goes from the interventional-type post-approval studies all the way through to observational studies.”
Researchers looked to repurpose existing drugs to battle severe COVID-19 infections in the early days of the pandemic. Their work led them to dexamethasone, an injectable corticosteroid, and remdesivir, an antiviral first developed as an Ebola treatment. Remdesivir, developed by Gilead Sciences (NASDAQ: GILD), ultimately became the first FDA-approved COVID-19 treatment.
But the question of how the industry can convert pipeline drugs to commercialization in a COVID-19 landscape is frequently thorny.
More patient-friendly trial designs could be a COVID-19 silver lining
The pandemic meanwhile has forced research teams to modify clinical trial designs and embrace concepts such as remote patient monitoring, virtual trial designs and direct-to-patient assessments that could be beneficial for clinical trial volunteers.
Clinical trial organizers have modified their trial designs in a way that is less burdensome for patients. “Maybe they’re giving up a couple questions or rearranging a few assessments to make it as streamlined as possible,” Arone said.
A growing number of clinical trials research teams are launching remote studies or reducing in-person patient visits. In rare disease studies, for instance, it is generally necessary to have in-person patient visits, but it is often possible to limit their frequency.
COVID-19 has “forced people to really look at how to use patients’ time most efficiently,” Arone said.
Overcoming clinical trial data gaps
While streamlined clinical trials can have benefits for patients, many studies struggle to gather optimal data volumes. An EY study found that 81% of clinical trial professionals were concerned about patient availability.
Real-world evidence (RWE) can help fill in the gaps, Arone said. One example where RWE is gaining ground in the clinical development lifecycle is the use of electronic medical records (EMRs) or patient-generated data for cell and gene therapy long-term follow-up, which can last as long as 15 years.
“Those patients usually have a one-time cell or gene therapy treatment, and then they go back to their treating physicians,” Arone said. “So the opportunity to follow those patients becomes really challenging.”
External comparators, also known as “synthetic control data,” can provide contextual information to such single-arm studies that are unable to use a placebo or an active comparator arm. The technique can supplement clinical trials with external data that can provide contextual information. External comparators have a long history in studying rare diseases where it is impractical or unethical to randomize patients to a placebo group. In cases like this, “you might get a comparator arm from a real-world data set,” Arone said. “And that’s something that we’ve been doing for a long time.”
What is different now is the growing use of the technique in contexts such as oncology. “As the oncology space is getting more and more personalized, and you have more opportunities for single-arm studies.”
There is also a broader trend of clinical trials incorporating patients’ real-world data to limit the need for in-patient visits. “We’re seeing it come into play in a lot of different little places, mostly because of need,” Arone said. Examples include incorporating electronic health record data to augment clinical trial data, virtual physician physicians and the use of wearable devices to monitor patients’ vital signs remotely.
Will the new normal provide a long-term improvement?
The new techniques have allowed many clinical trials to resume during the pandemic. “I would say that most studies that we’re operationalizing have come to an uneasy truce with the pandemic and now have practices in place to allow them to continue to follow their patients,” Arone said.
One trend to watch is the degree that such clinical trial changes become permanent as the pandemic fades into the background. “I like to think that they will, because a lot of these approaches are very patient-centric,” Arone said. The benefit of collecting data directly from patients, for instance, was apparent in the past, but “it might have taken this pandemic for people to get comfortable with the idea,” she added.