A Call to Action

Ensuring high standards and minority representation in fast-paced vaccine trials

In 2020, physician-scientists at the University of Miami Miller School of Medicine worked hard and fast to address the threat COVID-19 imposed on

humanity. UM partnered with the National Institutes of Health (NIH) COVID-19 Prevention Trials Network to test investigational vaccines against the deadly virus. Clinical trials began in July with the Moderna

vaccine, followed by the single-dose Janssen Pharmaceuticals product (Janssen is a subsidiary of Johnson & Johnson). Researchers in UM’s Department of Medicine partnered with the

Department of Pathology, Interdisciplinary Stem Cell Institute (ISCI), and Sylvester Comprehensive Cancer Center (SCCC) and moved with relentless speed to demonstrate vaccine efficacy and

safety. Despite the intensity of the race, the team

maintained high scientific standards following

strict protocols to ensure results were sound.

Above: Susan DobleckiLewis, M.D., M.P.H., speaking about the Phase 3 trial for a COVID-19 vaccine. The Miller School of Medicine’s participation in the clinical trial, part of the National Institutes of Health COVID-19 Prevention Trials Network, was one of 89 sites across the U.S.

“Absolutely no corners were cut in terms of the actual research. There were external monitors all the time, and we had our own set of monitors,” says Olveen Carrasquillo, M.D., M.P.H., professor of medicine and public health sciences and chief of the Division of General Internal Medicine. “We made sure that all the data collected was done per protocol, and we got it done quickly. I was really proud of the team.”

The Miller School’s long legacy of infectious disease treatment, prevention research, and clinical trials made it an ideal testing site. As a leader in HIV/AIDS research and a member of the NIH’s HIV Vaccine Trials Network, UM’s infrastructure was already in place to conduct COVID-19 clinical trials.

Susanne Doblecki-Lewis, M.D., M.P.H., clinical director for the Miller School’s Division of Infectious Diseases and principal

“Even though we have a very experienced team, this was still much bigger than anything we’ve put together before. It was a tough time but there was a need to move with lightning speed.”

— Susanne Doblecki-Lewis, M.D., M.P.H.

Data were analyzed to determine the efficacy of convalescent plasma on the severity and length of the COVID-19. investigator on the Moderna trial, says the bigger challenge, in fact, was keeping up with the pace and scope of the work during the most intense period of the pandemic. The staff had never experienced anything like it. “Even though we have a very experienced team, this was still much bigger than anything we’ve put together before. It was a tough time but there was a need to move with lightning speed,” says DobleckiLewis. “The staff did an amazing job.” According to Doblecki-Lewis, staff from all existing research areas were called in to work on this. It also helped that most of the nonCOVID-19 research had been paused due to the pandemic. “We reassigned everyone we had available and then pulled in people from other areas and hired individuals to work on the vaccine project. It was a heavy lift. Everyone worked extended hours and the staff was here every day,” she says.

Of utmost importance was ensuring vaccine equity among minority groups. Early CDC studies determined that black, Hispanic, and indigenous populations would more likely suffer the effects of COVID-19. It was critical, therefore, to recruit a large representation of Miami’s multicultural population to confirm the vaccines’ mass efficacy.

“We know what approaches to use to recruit these minority populations and we know how to reach them. That’s what we do. That’s our skill set,” says Carrasquillo. “Here we had a disease that was disproportionately affecting minority communities, and it looked like these individuals were not going to be well represented in the vaccine trials. Many of the landmark studies on diseases like diabetes, heart disease, and even cancer did not have adequate minority representation. I remember saying to myself, ‘This is not going to be like that.’”

For the first randomized, double-blind study, 300 participants braved the unknown. Half of the group received the Moderna vaccine upon enrollment and the other half received a placebo. Once the vaccine was proven effective and authorized by the FDA, individuals in the placebo group also received the vaccine.

“It was a huge team effort to get the trial off the ground,” says Doblecki-Lewis. “We were so very committed to recruiting participants that represented the diversity of Miami, and I’m pleased to say we did that well.”

Much of what the team learned from conducting the Moderna study paved the way for assessing Janssen’s vaccine product. UM’s team saw an even larger participant group, this time recruiting 1,000 participants within four to five months. They brought in 400 people in less than two months, or 20 to 25 patients per day. Sixty percent of those participants were black and Hispanic.

“This was an astronomical feat,” says Dushyantha Jayaweera, M.D., associate director of the Miami Clinical and Translational Science Institute (CTSI), professor of medicine and principal investigator for Janssen’s UM site. “The difficulty in these studies was that time was of the essence. It showed how well different parts of the University came together to achieve this.”

Jayaweera admits that, while successful, orchestrating the Janssen trial was a “logistical nightmare.” Sylvester Comprehensive Cancer Center’s pharmacy prepared the vaccine, maintaining a certain temperature and transporting the serum within 45 minutes. The patient’s arrival time and the time of injection required precise coordination. Any glitch with patient scheduling, data entry, lab shipments, or computer functioning further complicated the time- and resultssensitive situation.

“Sometimes people ask me, ‘Was it worth it?’ It was worth it because there is a certain duty that comes in a pandemic. You must step up to the plate. We worked like crazy to do that, and then it finally came through,” recalls Jayaweera.

One of the most impactful lessons came in August 2020, when the FDA issued an emergency use authorization to test the effectiveness of treating hospitalized COVID-19 patients with convalescent plasma, the antibody-rich blood product from survivors of the disease.

Convalescent plasma had been used anecdotally since the 1890s, but UM was one of the first medical schools in the country approved to conduct a clinical trial to confirm its efficacy at reducing the severity or length of the disease. For Jayaweera, asking patients to participate in this research was much more challenging than what he faced with the vaccine trials.

COVID-19 Research Funding

Samples 363,849

Plasma 1,368,618

Outreach 2,075,682

Drug 8,630,068

Vaccine

0 5M 10M

In Millions 19,183.428

15M 20M

“Here we had a disease that was disproportionately affecting minority communities, and it looked like these individuals were not going to be well represented in the vaccine trials.”

“The difficulty in these studies was that time was of the essence. It showed how well different parts of the University came together to achieve this.”

— Dushyantha Jayaweera, M.D.

The vaccine research studies conducted at the Miller School of Medicine were organized with “lightning speed” and mobilized faculty and staff from across the University. “That convalescent plasma study had to be done, and it was not easy,” Jayaweera says. “The most difficult thing with COVID-19 was that we had to see patients who were very sick and tell them, ‘I want to put you on a study.’ And people would respond, ‘I’m dying here… and you want to put me on a study!?’” Another challenging aspect was convincing patients to enroll in the study while also telling them there was a 50-50 chance of receiving a placebo. “Then I would have to tell them, ‘There is no treatment available. If we don’t do the studies, we won’t be able to find the cure.’”

Data on this work will be available in late summer 2021.

The trials confirmed that the Moderna vaccine, which uses a messenger RNA, is able to successfully mount a protective immune response. The presence of this COVID-19 mRNA prompts the body to produce antibodies against the novel coronavirus, Jayaweera explains.

The Janssen/Johnson & Johnson vaccine uses inactive particles of a cold virus (adenovirus) that contain COVID-19 spike protein DNA.

“When Janssen vaccine is injected into a person, the adenovirus particles enter the nucleus of the cells. An adenovirus acts as a delivery vehicle to carry the coronavirus genetic material (DNA). Within the nucleus, the DNA of the COVID-19 spike protein will prompt the cell to produce mRNA, which will signal the cell to make spike proteins. These will be identified by the immune system and make antibodies that will protect us from COVID-19”.

Both approaches provoked an immune response. But there was also extremely rare unanticipated developments and changes that would force the researchers to adjust. A complication from the Janssen/Johnson & Johnson vaccine posed such a challenge to UM’s team.

COVID-19 Research Grants by Division

General Medicine 9%

Division

General Medicine Infectious Disease

Infectious Disease 65% Pulmonary 26%

Pulmonary Grand Total

Grant Type

Outreach

Drug Outreach Plasma Samples Vaccine

Drug

Number of Grants

3

9 2 2 4 5

7

Total Cost

$1,960,915 1,918,953 114,767 1,368,618 363,849 18,760,678 6,711,115 $31,621,745

What occurred was that several female patients out of several million who received the Janssen/Johnson & Johnson vaccine developed blood clots—and one woman died—after receiving the vaccine.

“We had to change the protocol, and now anyone who has anything that remotely sounds like a blood clot has to be evaluated. Part of that is that the platelets go low, so now we’re checking the platelet levels in patients,” says Carrasquillo.

Most recently, the same vaccine has been linked to a small risk of developing GuillainBarré Syndrome, a condition where the body’s immune system attacks nerve cells.

The staff will follow participants over the next two years to monitor these kinds of developments and to study the drug’s efficacy. The follow-up period will allow researchers to learn how many vaccinated patients still contracted COVID-19. Patients have been asked to record their health data in a diary and return every few months for antibody tests. Despite these careful observations the science agrees that these vaccines are safe and the most effective way to alter the course of the pandemic. The pandemic wrote a dark history that the world was forced to read. Researchers at the Miller School of Medicine revised that story, promising a better ending for everyone, in every community, throughout the world.

Although the pandemic is not yet over, we know that vaccination needs to be the cornerstone of ebbing the tide. As we further understand the variant viruses that are affecting the population we know that the vaccines will save lives. We will need to consider the use of booster vaccines as more information is just around the corner.

“It was an incredible privilege to be part of such an important process,” says DobleckiLewis, “and to know it had a good chance of making a difference.”

Top: Roy Weiss, M.D., Ph.D., with University vaccination partner Walgreens’ employees/ representatives. Bottom: UMPresident Frenk with students at the vaccine clinic at the Shalala Student Center on the Coral Gables campus.

“It’s important to note that reports of breakthrough cases of COVID-19 in vaccinated people is not a sign that the vaccines don’t work. They do work. They are meant to prevent severe illness and keep infected individuals out of the hospital, and they are doing their job.”