By Melinda Young
Mere weeks into the United States’ experience with the coronavirus pandemic, many academic and research institutions have closed all, or part, of their usual activities.
IRBs have learned that their disaster plans did not prepare them for the effects of a fast-moving virus, COVID-19, that has demonstrated its far-reaching ability to shut down normal business and social interactions. This novel coronavirus, spread to more than 194,000 cases worldwide and 5,723 cases in the United States as of March 17. (Up-to-date figures are available at: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html.)
By March 15, 2020, the disease was declared a pandemic. It paralyzed Italy’s social and business enterprises, and threw the nation’s healthcare system into chaos with more patients needing intensive care and respiratory equipment than the system could handle.
The pandemic prompted closures of American universities, sporting events, schools, churches, entertainment venues, cruise ships, Disney properties, and many other businesses and sites for an indeterminate period.
The pandemic also is causing unfortunate challenges for clinical research, said Paul Biddinger, MD, MGH, endowed chair in emergency preparedness, director of the Center for Disaster Medicine, and vice chairman for emergency preparedness in the department of emergency medicine at Massachusetts General Hospital in Boston. Biddinger spoke at a web conference on March 13 that was co-sponsored by WIRB-Copernicus Group (WCG) and Accumen.
“It’s hard for us to support clinical encounters with patients if either the principal investigator or research assistant comes into contact with COVID-19, from a management or resources utilization standpoint,” Biddinger noted. “We cannot use a single piece of personal protective equipment that could be used by a clinician in clinical care.”
PPE Is Limited
Health systems and academic medical centers are experiencing a limited supply of personal protective equipment (PPE), and must only use it when necessary — or it will not be available when an influx of COVID-19 patients enter their system.
Research purposes are necessary — but not always during a national emergency. “We have to be careful how many people enter a room for a clinical encounter,” Biddinger explained. “We need to consume fewer masks, gloves, etc., so this is having an impact on clinical research capabilities.”
Despite an incredible need for knowledge and the intention to understand what is happening with the virus, research institutions should proceed with caution when it comes to human subjects research, he added.
“We need to continue to acquire knowledge, and we can’t put the entire site on hold for a year to stop medical knowledge,” Biddinger said. “But, we need to know when to start and stop research studies, looking at resources utilization and the importance of the project.”
Clinical Trial Guidance
On March 18, the FDA issued guidance for IRBs, investigators, and industry for conducting clinical trials during the pandemic. The guidance acknowledges challenges, such as quarantines, site closures, travel limitations, and interruptions to the supply chain for the investigational product. The FDA recommends that sponsors evaluate alternative methods for assessing participants, including phone contacts and virtual visits. Also, they should offer additional safety monitoring for trial participants who may no longer have access to investigational products. (The FDA guidance is available at: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-guidance-conducting-clinical-trials.)
Research organizations can conduct some elements off site such as remote assessments, said Mike Cioffi, senior vice president of clinical solutions and strategic partnerships at WCG MedAdvante-ProPhase. Cioffi spoke March 18 at a WCG webinar on clinical trials in the era of COVID-19.
IRBs and research organizations need to consider the scientific validity of collecting data remotely, Cioffi noted. “I encourage people to look at the type of data you’re collecting and see if it’s going to be valid,” he said.
Research organizations could leave decisions about whether to continue in-person monitoring of study participants to investigators, suggested Greg Poland, MD, professor of medicine and infectious diseases at Mayo Clinic, and director of Mayo Vaccine Research Group.
“They know those research subjects best and know how critical is what they’re doing,” Poland said. “If I’m testing a new antihypertensive and it requires blood tests, I would probably delay that trial because healthcare providers and that lab have maximal capacity for what they need to be doing.”
But if a researcher is conducting an oncology study, which may be more urgent, institutions and investigators need to decide jointly. Some are deciding to delay enrollment of new subjects, except for COVID-19 research, Poland added.
The COVID-19 pandemic highlights the importance of isolation ethics, such as avoiding doctor’s visits for minor illnesses and using telemedicine whenever possible, said Arthur L. Caplan, PhD, professor of bioethics and founding director, Division of Medical Ethics at NYU Langone Medical Center in New York City. Caplan also spoke at the WCG webinar.
Under this construct, it is unethical for researchers to continue clinical research if it poses a public health risk or a personal risk to research participants and staff.
“If someone is in a Phase III study and they’re getting efficacy for treating cancer, then there is a responsibility to talk with the sponsor and institution about continuing to provide care,” Caplan said.
But for a study that does not involve a life-and-death issue for participants, or that does not involve finding a cure or vaccine for COVID-19, continuing the clinical trial during a pandemic has less convincing ethical underpinnings.
All Eyes on Developing Vaccine, Treatments
The U.S. Department of Health and Human Services (HHS) has expanded and formed partnerships with pharmaceutical development companies to expedite development of a vaccine for COVID-19. One partnership is with Janssen Research & Development, part of Johnson & Johnson.
There also are some potential drugs for treating COVID-19 infection being studied in China and elsewhere, said Scott Gottlieb, MD, former FDA commissioner and current member of the boards of Pfizer and Illumina.
“There is an antibody-based prophylaxis, where you give monthly injections, for treatment of Ebola,” Gottlieb explained at the March 13 web conference. “This could be used for frontline healthcare workers who are going to be exposed to coronavirus — like people in nursing homes.”
If prophylaxis treatment is developed, and studies show it works with COVID-19, then it could be available by the end of summer. “It would provide a natural backdrop against transmission and reduce morbidity and mortality,” Gottlieb said.
Vaccine efforts are much further away: “We have to be realistic and believe a vaccine is two years away,” he said. While it would be possible to inoculate frontline healthcare workers first, this might not be the best strategy in the event the vaccine makes them more susceptible to the virus, he added.
HHS also offered development support for developing a high-throughput COVID-19 diagnostic test. The test could be used in a diagnostic system that processes up to 1,000 tests in 24 hours. It is receiving support from HHS Office of the Assistant Secretary for Preparedness and Response. The test can produce results in three hours. Its development is expected to be completed this spring, and it could be considered for the FDA’s emergency use authorization. (More information is available at: https://www.hhs.gov/about/news/2020/03/09/hhs-supports-development-of-first-high-throughput-covid-19-diagnostic-test.html.)
For IRBs and research offices that maintain some on-campus staffing and business, the CDC has published charts and toolkits on keeping the workplace safe, at: https://www.cdc.gov/coronavirus/2019-ncov/downloads/workplace-school-and-home-guidance.pdf. The CDC encourages people to:
• Practice good hygiene:
- Stop handshaking;
- Clean hands at the door and email handwashing reminders;
- Remind people to not touch their faces and to cover coughs and sneezes;
- Disinfect surfaces regularly;
- Increase ventilation through open windows or adjusting air conditioning.
• Use caution with meetings/travel:
- Use videoconferencing for meetings;
- Hold meetings in open, well-ventilated spaces;
- Adjust or postpone large meetings and gatherings;
- Assess business travel risks.
• Stay home if:
- Employees feel sick;
- They have a sick family member at home.
• Avoid crowding:
- Schedule appointments to stagger customer flow;
- Use online transactions when possible;
- Limit attendance at larger gatherings.
These measures, including the hundreds of closings of entertainment, tourist, travel, sporting events, festivals, conferences, and other events, are intended to flatten the pandemic’s curve, Biddinger said.
“We’ll continue to see rising numbers of cases, but perhaps all of our efforts are blunting the curve, keeping the peak as low as possible,” he explained. “The higher that peak, the more people we will see who need hospitalization and intensive care.” The higher the peak, the more likely the influx of very ill patients will overwhelm EDs and ICUs.
The rapid pace of the pandemic’s spread, and of the state and public response, gives public health officials and emergency preparedness workers hope that the United States’ experience with the pandemic will not be as overwhelming as Italy’s experience in early March 2020, Gottlieb said.
“The question is, ‘Will we look like Italy or South Korea?’” Gottlieb asked. “South Korea’s epidemic looks like it has peaked [by mid-March] and has declining cases, vs. Italy with 15,000 cases and over 1,000 deaths [by mid-March]; the two nations are similarly sized.”
South Korea took the right actions by enacting strict mitigation steps early on to have the public engage in social distancing. The nation also implemented broad-based diagnostic screening and identified people in clusters, getting them into quarantine, Gottlieb explained.
“They used tools to reduce the scope of the epidemic, while Italy was slow to implement mitigation steps and allowed the virus to spread in the country,” Gottlieb said. “Now, Italy’s healthcare system is overwhelmed, and the epidemic is on the brink of being out of control everywhere.”