Can Clinical Trials Continue in Age of COVID-19?

The coronavirus pandemic and the imperative to protect researchers and research subjects has interrupted clinical trials across multiple diseases. Directives that curtail clinical trials and guidance that suggest possible means of mitigation have been issued by national regulatory agencies, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), but many trials are now on hold, or have been discontinued.

"Clinical trials require years to design, fund, conduct, and complete but are essential for improving health and preventing disability," Mary McDermott, MD, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago IL, and Anne Newman, MD, Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh PA, pointed out in their viewpoint column in JAMA.

"The effects of the coronavirus pandemic on randomized trials hopefully will be short-lived, relative to the long-term benefits of these trials to millions of people who will continue to live with debilitating medical diseases after the crisis ends," McDermott and Newman added.

Large pharmaceutical companies like Eli Lilly and Company and Bristol Myers Squibb, as well as smaller companies have announced that they are suspending screening and enrollment, postponing starting new studies, and interrupting ongoing studies; while trying to maintain efforts toward developing treatment for coronavirus disease 2019 (COVID-19).

"Lilly is working hard to alleviate some of the pressure that the global COVID-19 pandemic has placed on our healthcare system. We have repurposed our laboratories to conduct diagnostic testing for patients and we are researching potential therapeutics," announced Tim Garnett, Lilly's chief medical officer.

"By delaying most new study starts and pausing enrollment of new patients or healthy volunteers in most ongoing studies, we hope to ease the burden on participating healthcare facilities and allow physicians to focus more of their efforts on combating COVID-19," Garnett explained.

Moderna, Cambridge MA, is 1 biotechnology company that is both involved with vaccine research, including for COVID-19, and encountering challenges with proceeding in the current conditions. Among the projects in infectious disease that they are closely monitoring against potential interruptions are a phase 2 cytomegalovirus and phase 1 Zika clinical trials. The company has suspended new enrollment of participants in an hMPV/PIV3 study, which had been actively enrolling seropositive pediatric participants.

"The COVID-19 pandemic has created unprecedented challenges and we are committed to ensuring the health and safety of all participants in our and our partners' clinical trials, our clinical trial site teams, vendors and our employees," said Stéphane Bance, Moderna's Chief Executive Officer. "We are also focused on responding to the pandemic through our work on our vaccine candidate against COVID-19, mRNA-1273."

Gilead Sciences, Foster City CA, is proceeding with clinical testing of remdesivir for COVID-19, despite current challenges, and has facilitated emergency, compassionate use access to the product while test results and regulatory review are pending.

"We are still on track to provide data for remdesivir in the coming weeks," assured Chris Ridley, senior director, Media Relations for Gilead, in comment to Contagion® on March 31.

In an open letter on March 28, Gilead Chairman and CEL Daniel O'Day described the access programs that are in place and being expanded while the product remains investigational. "This 'compassionate use' program is typically reserved for a small number of individual cases but there is nothing typical about this crisis and to date we have provided remdesivir to more than 1000 patients."

O'Day indicated that Gilead is expanding beyond the traditional protocols of compassionate use which require, among other procedures, a review of each individual application. "With expanded access, hospitals or physicians can apply for emergency use of remdesivir for multiple severely ill patients at a time," O'Day announced.

The editors of Alzheimer's & Dementia note not only the disruption of important clinical research by the COVID-19 pandemic, but the particular vulnerability of the older adults who are often the subjects, and the beneficiaries of these trials.

"Clinical research in AD (Alzheimer's disease), whether observational or interventional, includes some of the longest and most complex studies ever designed and deployed," the editors pointed out.

"Many of these studies cannot be feasibly re-funded or restarted. Therefore, given the enormous investment made by research participants, family members, investigative teams, and research sponsors, every effort should be made to preserve the integrity and value of this critical ongoing research while balancing the dynamic risks associated with study participation during an outbreak," they argued.

McDermott and Newman offer several means to mitigate the disruption to clinical trials, including prioritizing outcomes which most need to be preserved; facilitating interventions that can be safely adhered to without leaving home; and employing technology to remotely screen potential participants rather than conducting baseline in-person visits.

"To maximize public health benefits, creativity and persistence are required," McDermott and Newman urged, "especially during these unprecedented and uncertain times."