BioPharma, Policy

Clinical trial sites anticipate disruption due to Covid-19; FDA issues guidance for trials amid pandemic

In a survey of 170 sites, Continuum Clinical found that around one-third of sites anticipate impacts on their ability to recruit and retain participants. The FDA guidance listed considerations patient protection and conduct of trials during the pandemic.

A member of the medical staff at La Paz Hospital in Madrid waves from the intensive care unit as Spain prepares for a nationwide lockdown to combat the spread of the novel coronavirus.

Only days ago, the Phase I clinical trial of Moderna’s vaccine against the Covid-19 virus dosed its first participant, and trials of potential antiviral treatments like Gilead Sciences’ remdesivir are continuing apace as well. But a new survey of clinical trial sites indicates that the pandemic could be bad news for trials in general, and the Food and Drug Administration is also stepping in to offer guidance.

Northbrook, Illinois-based Continuum Clinical released initial results of the survey, showing that among 170 clinical trial sites in the U.S., 30% said the SARS-CoV-2 pandemic would have a “big” or “extremely big” impact on their ability to recruit patients for new trials and to keep those already enrolled compliant. Meanwhile, 39% said they believe patients will be less likely to enroll in new trials, while 25% said currently enrolled patients would be less willing to continue participation. The survey was conducted between March 12-13.

“Even at this early stage, where school closures and life disruptions have only just begun, study sites are bracing for a recruitment and retention problem,” Continuum Clinical President Neil Weisman said in a statement. “We want to uncover these trends and, when possible, mitigate their potential impact in an effort to help our sponsor and [contract research organization] partners understand what they need to be watching for as this pandemic unfolds.”

As of Wednesday afternoon, the number of confirmed infections stood at more than 214,000, including 7,323 in the U.S., according to Johns Hopkins University. Globally, 8,727 have died. Several locations in the U.S. have implemented restrictions on movement and business activity, including six counties in the San Francisco Bay Area that have collectively issued a shelter-in-place order, with talk of a potentially similar order for New York.

On Wednesday, the FDA released a guidance for running clinical trials during the pandemic, issuing the final document instead of issuing a draft guidance to solicit public comment, as it usually does.

The agency said it recognized that Covid-19 may require sponsors to modify trial protocols, while illness and control measures related to the disease may make protocol deviations unavoidable.

As such, the FDA said, it is “critical” that trial participants be kept abreast of study changes and monitoring plans that could affect them. Trial sponsors, investigators and institutional review boards establish policies and procedures or revise existing ones to describe how they will protect participants and manage study conduct that could arise from Covid-19.

The guidance listed some ways that trial sponsors can change how they conduct trials to account for Covid-19. While they are still required to report protocol changes to do things like eliminate or limit hazards like exposure to the virus, they can implement them without institutional review board approval and before filing amendments with the FDA. Indeed, protecting patients’ safety could mean either continuing their participation per protocol, halting administration of a product or dropping them altogether, but even those who lose access to a product may require additional safety monitoring. Methods of assessing patients remotely should be considered if patients cannot physically go to sites, along with alternative methods of delivering products, when feasible. Optimizing use of central and remote monitoring programs should be considered to maintain oversight of trial sites if on-site monitoring visits are no longer possible.

The agency also provided ideas for how sponsors can make up for potential challenges to data collection. They may consider delaying assessments for trials, for example. But changes made due to restrictions related to Covid-19 should be documented, and any missing information due to changes in visit schedules, missed visits or discontinuations should be explained, including its potential relationship to the pandemic. Sponsors should consult with appropriate review divisions about protocol modifications for collection of efficacy endpoints like virtual assessments, assessment delays and alternative specimen collection, while reasons for failing to collect efficacy endpoints should be documented. Protocol changes that lead to amendments to data management or statistical analysis plans should be made in consultation with the FDA, and sponsors should address in their analysis plans how Covid-19-related deviations will be handled for prespecified analyses.

Photo: Pablo Blazquez Dominguez, Getty Images