As the number of COVID-19 positive patients increase in the US, specialty organizations, hospitals and others are making changes to clinical trial visits that could translate into delayed clinical trial readouts and enrollments.
On March 18, FDA issued final guidance for sponsors of clinical trials in light of the COVID-19 outbreak. The guidance is largely in line with the recommendations from the individual institutions in terms of the delay of in person visits and the potential to shift these visits to remote data collection. It also suggests steps companies can take to best document any potential protocol changes related to the outbreak.
The US Centers for Disease Control and Prevention (CDC) website posted community mitigation plans for communities and healthcare facilities that recommend shifting elective surgeries, rescheduling “non-urgent” outpatient visits as necessary, and trying to move patients to telehealth options if needed. These recommendations also could impact enrollment into clinical trials or protocol-specified check-ins to gather data on primary and secondary endpoints in the studies.
Anticipating potential disruptions to clinical trials, the National Cancer Institute (NCI) has recommended different options that investigators could take to ensure patient safety, including the transfer of a patient’s care to a different participating study or a more local care provider to administer investigational IV agents as well as the allowance of the dispensing pharmacy to ship oral agents to patients directly.
However, according to the guidance, only the sites approved under the protocol can continue to enroll patients. The American Society of Clinical Oncologists (ASCO) has also issued specific treatment considerations for cancer patients, including a link to the NCI guidance on clinical trial procedures.
Some of the states most affected by the COVID-19 pandemic in recent days are also significant centers of research. According to the Johns Hopkins Coronavirus Resource Center, there were 7,323 confirmed cases of COVID-19 in the US as of March 18, with Washington state, California, New York, and Massachusetts reporting the highest numbers.
As a result of the outbreak, some academic research facilities are pausing clinical trial visits regardless of indication. For example, Columbia University posted on March 13 that “study procedures involving in-person contact with participants at a location in the greater New York area or participant travel for research purposes within the greater NY area are paused, effective immediately or as soon as can be implemented.”
The university recommended that study investigators consider telephone contact or remote monitoring for data collection.
Boston Medical Center has recommended that “most research activities involving in-person interactions with subjects must stop until further notice,” unless they would harm the subject’s well-being or deprive the subject of a potential direct benefit. Several other institutional review boards have put out similar guidance (Penn Medicine, University of Southern California, University of Minnesota).
Additionally, the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) issued advice on March 12 for the management of clinical trials in the wake of COVID-19. MHRA said there had already been reports of protocol deviations due to missed visits and recommended that trial sponsors “ensure they are well documented,” adding that “an increase in protocol deviations in relation to coronavirus will not constitute a serious breach, therefore there is no need to report this to us.”
As COVID-19 begins to disrupt routine medical care in US hospitals and research facilities, a spillover effect on clinical trials appears inevitable.
As of March 13, ClinicalTrials.gov included 9,071 interventional clinical trials in the US for investigational pharmaceuticals or medical devices that were sponsored by industry and were either recruiting patients or in the active stage, meaning recruitment was complete and patients were being studied for the primary and secondary outcomes.
HRI’s analysis of the studies in the four cities and states with the highest number of COVID-19 cases showed that nearly half of studies could be affected. Specifically, among the 9,071 studies, 4,327 (48%) are in California; 1,760 (19%) trials have sites in Washington state, including 1,172 in Seattle; New York state was home to 3,649 (40%) with 2,684 in New York City; and 2,505 (28%) trials have sites in Massachusetts, including 2,124 in Boston.
The proportion is similar among 4,350 cancer studies in the US, with about 44% of those trials having a site in New York City or California. Nearly 15% of the oncology clinical trials have a site in Seattle, and 28% have sites in Boston.
Clinical trial delays would be the latest lag effect from the COVID-19 outbreak for pharma life science (PLS) companies after the FDA said it would stop most foreign inspections through April.
One potential solution for PLS companies could be the use of digital tools to monitor treatment outcomes. A recent HRI survey of 100 global R&D executives found that the majority have used biometric sensor or wearables to capture clinical trial data as well as mobile apps to communicate with patients during trials.