t takes a convergence of disciplines, community participation and clinical excellence to test a vaccine under normal circumstances. But, these days, life is far from normal.

With COVID-19 deaths exceeding 200,000 in the U.S. alone, six months into the coronavirus pandemic millions of people are hoping — and waiting — for a safe and effective vaccine that will stop the virus in its tracks, creating immunity, preventing sickness and mitigating spread.

UNC Associate Professor Cindy Gay ’98 (M.D.), ’99 (M.P.H.) is part of a dedicated team of doctors, nurses, medical assistants, research specialists, pharmacists, data and project managers from different areas of expertise at Carolina, united in the common goal to find a vaccine for COVID-19. Committed to doing their part to save lives, they have prioritized this effort in order to run Carolina’s phase 3 clinical trial of the mRNA-1273 vaccine developed by pharmaceutical company Moderna.

As the primary investigator of the study, Gay’s motivation for pivoting from HIV research to a COVID-19 vaccine trial is the urgency of the moment.

“It is just so needed,” she said. “This is a global tragedy that has impacted our lives on so many levels. As a physician I hear about the stress and the fear, the uncertainty and the anxiety from my patients and colleagues.

The big picture

Testing the efficacy and safety of a potential vaccine is a three-phase process. During phases 1 and 2, small groups of people receive the trial vaccine. By phase 3, the vaccine trial is expanded to include thousands of participants. If the vaccine proves effective and safe in a phase 3 trial, it can move along to the FDA approval process.

The phase 3 clinical trial of the Moderna vaccine at Carolina is taking place at the Clinical and Translational Research Center — one of more than 90 sites testing the vaccine across the U.S. The overall goal of the national study is to enroll 30,000 volunteers from a myriad of backgrounds with various levels of day-to-day potential exposure to the virus.

These sites will continue to enroll participants until they meet that goal. By gathering such a large and varied pool of volunteers, researchers hope to determine if there’s a significantly different rate of infection in the placebo and vaccine groups and whether the vaccine is at least 50% effective.

So far, the UNC team has more than 100 participants who have given their informed consent, and they are working around the clock to move each eligible volunteer through the enrollment process.

“Our UNC goal is to enroll as many qualified volunteer participants as possible,” added Miriam Chicurel-Bayard, a clinical trial research nurse involved in the study. “There’s so much interest in the community, so we’re ramping up our staff internally so we can see the number of people who are interested and eligible to participate.”

Ramping up staff

After a participant is screened through a national registry or directly by the research team and determined eligible to participate in the vaccine trial at UNC-Chapel Hill, a clinical trial research nurse calls them to verify their eligibility and go through the consent process.

Friday, September 11, was Alex Bradley’s first day in the clinic, but he had spent the previous day on the phone with participants answering questions about the study and verifying informed consent on behalf of the local trial. A former nurse at a hospital in Goldsboro, North Carolina, Bradley moved to the area and joined the UNC team as a clinical trial research nurse.

“The work we do before the office visit is a lengthy process, but it’s rewarding to be a part of all this,” Bradley said.

Like Bradley, many staff members working on this trial are new hires.

“We’re at the front edge of research, so we’re having to start up quickly and develop our clinical flow and strategies as we go. Then we assess how things are going to move forward,” said Chicurel-Bayard, who’s been working on HIV treatment and prevention trials and studies for years.

“Everyone on our original team pivoted from what they were doing before COVID-19,” added Gay. “We are hiring new staff as fast as we can to support the trial and the participants in it.”

The volunteers

After the consent process is complete, participants come in for office visits. Gay or her colleagues physically examine each participant and answer any outstanding questions.

“Honestly, the best part is meeting the people willing to come in and volunteer and hearing their reasons why,” shared Gay.

One patient told Gay that he is participating in the study because his parents need the vaccine. Another participant, a working mom trying to home school her kids, said she is eager for her children to be able to safely go back to school. A health care worker is worried he’ll end up infecting his family.

Asking volunteers to intentionally expose themselves to the virus is, of course, unethical, which is why researchers seek to enroll volunteers with high-risk jobs or lifestyles.

“Ideally we are looking for participants who have frequent contact with others or who are living with someone who does — people who work at grocery stores or plants, health care workers, staff at nursing homes or prisons, first responders,” Gay explained. “We have one participant who is a health care worker whose wife is a physician, and they have kids in daycare — that’s several family members who are in contact with other people on a regular basis.”
 

After the physical examination, Gay reviews a detailed eligibility checklist, documents the exam, signs off that everything is in order, then places an order for the study injection, which goes to the Investigational Drug Services pharmacy at UNC Hospitals. The study injections are administered to participants by nurses or medical assistants on the unblind side of the study.

“It’s a randomized study, so none of the staff who are involved in any kind of health and wellness assessments of the participants has any idea who is getting placebos and who is getting vaccines,” Gay explained.

Randomly assigning the placebo or vaccine helps ensure that participants aren’t altering their behavior or putting their own safety at risk by thinking they’re immune. All volunteers are instructed to continue to follow guidelines in place to mitigate the spread of the virus.

Tracking health and wellness

Once the patient has been randomized and Gay orders the study injection, a research specialist, like Carolina Pastrana-Medina ’18, meets with the patients to help them download and install a special app to track their daily health. The app entries are linked to the participants’ study numbers and go directly into a database monitored by the clinical trial team at UNC-Chapel Hill.

“The app asks questions about how you feel, if you’re getting headaches or have joint pain, or have a temperature,” explained Pastrana-Medina.

Participants consult the app every day for a week after the first and second injections — the trial requires two injections spaced about a month apart — and then once a week throughout the course of the study. Pastrana-Medina and the clinical trial research nurses monitor data from the app and make follow up calls to check on participants routinely and as needed.

The Moderna study is Pastrana-Medina’s first clinical trial. A Carolina graduate who majored in sociology, she is currently pursuing a master’s in clinical operations and health care management at George Washington University.

“When this pandemic started, I was scared,” she shared. “I didn’t want to work in a setting where there was a lot of contact. But when I had the opportunity to interview here, even though I was scared, I knew it was a great chance to join this team. I’ve been wanting to help out with a clinical trial and am finally doing it.”

Behind the scenes

Supporting Dr. Gay and the clinical trial research nurses are Certified Medical Assistants Centhla Washington, who started in mid-August, and Dynesha Perry, whose first day was Friday, September 11. As CMAs, Washington and Perry are on the unblind side of the study, so their patient interaction is minimal.

“We get here before the first patient arrives and verify the paperwork. We grab their files and bring them to the clinic rooms, that we sterilize,” said Washington, who shared that she is fascinated by the vaccine trial process.

Further behind the scenes of participant interactions are Data Manager Mandy Tipton and Project Manager Samantha Earnhardt ’04, ’08 (M.P.H.).

Tipton requests randomization for each eligible participant and helps create and manage the flow of the medical charts among the medical assistants, nurses, Gay and the coordinators who enter the data and ensure the data is clean.

“When the charts are done, they come back to me,” said Tipton. “I do quality control to make sure everything is filled out completely and accurately.”

Tipton has been a data manager for seven years, normally working on smaller industry studies. “Before that I was a nurse in the infectious disease clinic. That combination has helped me do this job really well. I know what looks right and what doesn’t as far as medical histories and medications.”

She would normally work off-site but as the team is randomizing so many participants on a daily basis, having a data manager onsite during the day is essential.

Earnhardt joined the team just as they started enrolling participants. “I basically jumped in. The original team got the project going, and I’m helping transition the new people to come in and help keep everything growing. I’m so impressed with this group. Since most of them have been working together a long time, everyone interacts seamlessly.”

As the project manager, Earnhardt oversees the various teams, troubleshoots any issues that arise, ensures the clinic has adequate coverage for each team’s needs and onboards new staff. She has worked in clinical trial research for 10 years and has been in the research field for 15 — all at UNC-Chapel Hill — and she completed her undergraduate studies at Carolina. Laughing, she shared that her whole career started because of an ad in The Daily Tar Heel for a data collector.

“They needed someone who could speak English and Spanish and who could talk to people about being in studies, and here I am!”

Overcoming challenges

Conducting a vaccine trial of this magnitude and importance comes with a number of challenges. Enrollment is a concern as some people have reservations about vaccines in general, and a lot of people aren’t used to participating in research, Gay said.

Gay’s team is reaching out to communities that researchers haven’t reached out to before for participation in the trial — including African American and Hispanic/Latino communities.

“There’s a lot you need to do in explaining why you’re reaching out. It’s important given where we are in the country around these issues. Maybe it’s a silver lining that this horrible pandemic is giving us the motivation to do a better job with this, but it needs to be done in a sensitive and understanding way, so we can try to bring these vaccines to the people who are most impacted.”

The research team shares some of the basic concerns most health care professionals encounter: not having enough personal protective equipment and the struggle to get reagents for testing. Other hurdles include the tremendous need to quickly hire staff and provide childcare so staff members can work onsite. The team is also challenged to find space off campus.

“We need to lease space off campus because it’s more convenient and we simply need more space,” said Gay. “People have anxiety and want to be able to park right outside and go in. So we find ourselves leasing additional space without a guarantee of how to fund it over the next few years — but we can’t do the studies without it.”

The University launched the UNC COVID-19 Research Accelerator Fund to provide immediate, flexible support to Carolina’s critical research teams focused on COVID-19 testing, treatment and prevention. The fund is designed to help fill gaps in existing and evolving research so Carolina can better execute its rapid response to this global pandemic.

“Any assistance from donors would be hugely appreciated by a lot of people,” Gay stated. “The acceleration comes not in skipping any of the safety steps of three-phase trials but in speeding up all the other research components.”

What’s next

The big picture goal is to get a vaccine available and with clear data to show that it does or doesn’t work.

Gay can’t really say how quickly a vaccine will be available, but she is confident it will happen. Her team will be taking on at least one more large-scale COVID-19 vaccine trial in the near future. In the meantime, “we’ve certainly learned a lot about how to be prepared for such a pandemic.”
 

 
Cynthia “Cindy” Gay, M.D., M.P.H, is an associate professor in the Division of Infectious Diseases in the UNC School of Medicine Department of Medicine, and medical director at the UNC HIV Cure Center. The Clinical and Translational Research Center is a research space located in the Burnett-Womack Building on the campus of UNC-Chapel Hill. The space is part of the research support services provided by NC TraCS, a grant-funded institute founded as a service to the research community.