Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
For the hundreds of thousands of people enrolling in clinical trials every year—and for whom experimental therapies can offer a last hope—a new report provides some welcome news: Enrollment in clinical studies in the United States is on the rebound after disruptions caused by the COVID-19 pandemic. But a fresh surge of coronavirus cases could once again scramble studies aimed at testing disease treatments.
In June, engagement of new patients in U.S. clinical trials was down 38% compared with prepandemic levels, found the analysis released last week by Medidata, a healthcare data services company. That’s still a significant improvement from April, when U.S. enrollments were much lower: down 70% at the 1500 trial sites tracked by the firm. Some hospitals, including the Memorial Sloan Kettering (MSK) Cancer Center in New York City, New York University’s Langone Health, and the medical center at the University of California, San Francisco (UCSF), have reopened almost all of their trials.
Internationally, the situation is better, the report finds. Clinical trials in France, Italy, and Spain—all of which were severely affected by the pandemic earlier in the year—have returned to baseline enrollment levels as coronavirus caseloads have normalized, according to the Medidata report.
A “new normal” for clinical research
The U.S. rebound isn’t coincidental. Investigators and sponsors have taken exhaustive efforts to “future-proof research … [by] reinvent[ing] the whole logistical side of trials,” says Bill Byrom, vice president of product strategy and innovation at Signant Health, a clinical trials support platform. Trial operators have distributed equipment to protect research staff, and made it easier for patients to reach trial sites by coordinating private transportation. To protect trial participants, operators have also arranged for shipment of trial medications directly to them, facilitated virtual monitoring through web-enabled devices and telehealth platforms, and organized follow-up blood tests and other trial assays options in community settings such as independent clinics rather than at research institutions.
“These aren’t your parents’ clinical trials anymore,” says Kent Thoelke, chief scientific officer at PRA Health Sciences, a contract research organization serving thousands of trial sites around the world. “We’ve virtualized the entire process.”
It’s not just well-resourced trial centers that are making changes. Nearly two-thirds of research sites monitored by WCG Clinical, a company that collects information on 93% of industry-sponsored trials across 3000 global institutions, have adopted telemedicine in some capacity to conduct trials during COVID-19. Before the pandemic, only about one-quarter of sites used virtual practices.
Cancer centers across the United States have sought to be particularly “nimble” because of the potential vulnerability of their patient population to COVID-19, says Michael Carducci, a prostate oncologist and associate director for clinical research at Johns Hopkins University’s (JHU’s) cancer center. Remote visits and other decentralized practices have become the “new normal” of clinical research, he says.
Nonetheless, the 38% enrollment shortfall reported by Medidata indicates that struggles persist. Some institutions, like JHU’s Kimmel Cancer Center, are still facing concerns from pharmaceutical sponsors about dropping certain traditional practices, such as in-person physical exams. Other institutions, including Columbia University’s Irving Comprehensive Cancer Center, have imposed hiring freezes that have led to enrollment constraints because of reduced staffing. These factors—among others—have forced trial delays and postponements.
Options limited for some patients
For individuals with diseases incurable by conventional therapies—such as end-stage cancer patients—loss of access to clinical trials implies “losing an important aspect of their care,” says Ezra Rosen, a breast oncologist at MSK. Although experimental medications are by no means guaranteed to be effective—fewer than 10% of drugs in phase I safety trials prove effective, and some 40% of drugs that advance to phase III efficacy trials fail—for some patients, “trial therapies can make a massive difference … [and] they can be life-altering,” Rosen says.
The pandemic has reduced choices for some patients facing deadly diseases, says Chloe Atreya, a gastrointestinal oncologist at UCSF. One of Atreya’s patients, Nathan Kelly, was diagnosed with stage 4 colon cancer in January 2018. His cancer was not responding to first-line chemotherapies, says Sarah Kelly, Nathan’s wife. So, he enrolled in a trial testing two novel monoclonal antibody drugs. But those medicines also didn’t work.
Nathan Kelly met with Atreya in February to review his few remaining options—which included enrolling in one of two trials. He elected to wait, hoping a second-line chemo regimen could “keep the cancer at bay,” Sarah Kelly says. Within 3 months, it became clear the regimen was ineffective, but by that time the two trials had stopped enrolling patients because of COVID-19.
Recently, Nathan Kelly was able to “jump on board” a planned third trial, Sarah Kelly says. But he “seems to be going downhill so fast,” she says. “I honestly don’t know if he will live” long enough to begin the trial.
Atreya is worried, too. “It’s a race against the clock right now,” she says.
Whether researchers in the United States will fully climb back to prepandemic clinical trial enrollment will depend, in large part, on regional COVID-19 caseloads. As states such as Texas and California have reinstituted lockdowns in recent weeks because of mounting caseloads, they either recommend—or require—hospitals preserve bed capacity for COVID-19 patients. That means once again restricting other visits, including those for clinical trials.
The White House this week reportedly warned 11 cities in other states, including Baltimore, Cleveland, Indianapolis, Las Vegas, Minneapolis, New Orleans, Pittsburgh, St. Louis, and Nashville, Tennessee, that they will need to take “aggressive” action to limit coronavirus infections to protect their health care systems. Overall, 18 states are now in the “red zone” for resurgent caseloads and may require imminent action, according to a 14 July document from the White House’s Coronavirus Task Force.
Doctors involved in research trials are watching these developments warily. “With a certain sequence of events in next few weeks,” Rosen says, “we could be back to square one.”