Children's Hospital Colorado

Designing the Largest and Most Diverse Pediatric COVID-19 Vaccine Trial

COVID-19 Research | February 10, 2022

Children under 18 years old generally have milder disease than adults, but they carry COVID just as effectively, making up 20.8% of COVID cases and 22.2% of the U.S. population at large. In mid-December 2021, children were contracting COVID at a rate of nearly 200,000 new cases per week. They’re a crucial segment of the population to vaccinate.

In 2021, Children’s Hospital Colorado played a central role in the effort to clinically validate Pfizer’s COVID-19 vaccine for children, enrolling 252 participants altogether. It wasn’t just the largest study group, at 11% of the study population worldwide. It was also, very intentionally, the most diverse.

Pfizer pediatric COVID-19 vaccine trial draws public interest

“Typically at a pediatric academic institution we’re engaged in trials for rare disease, and it’s a specific medication or device,” says Erin Sandene, director of research operations at Children’s Colorado. “You don’t often have people chomping at the bit to be part of a research study.”

For its phase 3 trial of the Pfizer vaccine — the first to receive emergency authorization for use in children ages 5 to 11 from the Food and Drug Administration — Children’s Colorado received more than 5,000 initial applicants.

“That’s huge,” she says.

The slew of public interest presented an opportunity: For Pfizer, it was a chance to capture a large amount of pediatric data and lead the pack in making its vaccine available to the public. For Children’s Colorado, it was a chance to be part of something bigger, but also to advance a strategic priority that had been gathering steam all year: the effort to bring better representation to clinical research.

Covering all the bases

Pediatric infectious disease specialist Eric Simões, MD, has been leading clinical trials for decades. As a key player in the World Health Organization’s effort to help manage common pediatric conditions in low- and middle-income countries, he specializes in the prevention of long- and short-term effects of respiratory syncytial virus (RSV).  In fact, it was his role as primary investigator in a Pfizer RSV prevention trial that led to Children’s Colorado’s designation as a supersite for its COVID vaccine trial.

“They were asking questions about study design for the vaccine, and I helped with some of that,” he recalls. “And then they asked me if I wanted to do a large study here. They proposed 500 subjects. Immediately after I got off the phone with their Senior VP, I talked to Erin.”

“We’re talking about a randomized, blinded trial — it’s a lot more complicated than just here’s your shot,” says Sandene. “There’s a lot of moving parts, making sure you’re not unblinding, dispensing drug or placebo. It’s a huge amount of required documentation and regulations to consider. There’s no way one person could do it all.”

The team ultimately committed to enrolling 250 children to the trial — a massive effort in itself, representing 16% of the total enrolled population in the U.S. The project team included a 23-person staff, including a process improvement specialist, a project manager and an external vendor to help with scheduling. The goal: to enroll 25 children per day over the course of 10 days, eventually enrolling 252 children total. Pfizer agreed to pay the salaries of the staff necessary to support the effort.

“That’s kind of unheard of,” says Sandene. “Pharma companies usually see that kind of thing as a cost of doing business. But in this case, there were a lot of bases to cover.”

“I’ve been doing clinical trials for years,” says Chief Quality and Outcomes Officer Lalit Bajaj, MD, MPH, who served as executive sponsor for the trial. “Never have I been involved in something this quick, under this much scrutiny, involving so many people.”

Recruiting for representation 

The ZIP codes surrounding Children’s Colorado’s Anschutz Medical Campus, where the study would occupy a wing of the Outpatient Pavilion, are both racially and economically diverse. The team felt the study population should reflect that demography.

“We wanted to enroll populations that get often get excluded from studies like these,” Sandene says.

Dr. Simões and team centered recruitment efforts around pediatric practices that care for medically underserved communities from Longmont to Colorado Springs. Chief Legal Officer Michelle Lucero personally handed out materials in Spanish. And once the applications were in, Dr. Simões and team created a survey to ask applicants to self-identify their demographics. They used statistical methods to randomly select numbers that reflected the Colorado population.

And ultimately, they enrolled a population that was more than racially and ethnically diverse. They enrolled patients with autism spectrum disorder, Down syndrome, mental health challenges. They enrolled monolingual speakers of Spanish and Korean. They brought on interpretation services and a full-time child life specialist to help participants feel comfortable and informed.

“Dr. Simões was adamant,” adds Sandene. “He really influenced Pfizer in the view that we needed representation that met or exceeded our local demographics, because those were the populations that were most adversely affected by the pandemic. We helped shape Pfizer’s protocol.”

They also helped shape future protocols at Children’s Colorado. A pilot program built into the electronic medical record will collect cultural data moving forward, so research teams can better understand what their communities look like and work to correct disparities between clinical and research populations.

“I’m optimistic this isn’t going to be a decades-long effort,” says Dr. Bajaj. “In the next two or three years, we’re going to get better at this.”

The amazing part

One of the most surprising aspects of the study itself was just how effective Pfizer’s vaccine was in children.

“We were giving one-third the dose as in older children and getting the same immune response,” Dr. Simões says. “The study was actually not powered to show efficacy until 6 months out, but we were able to show efficacy by three months. That’s the amazing part.”

As the Delta variant surged, just three children in the vaccine group contracted COVID-19. Infections in the placebo group increased steadily.

The data were clear: Pfizer’s COVID-19 vaccine was safe and effective in children ages 5 to 11, and it received emergency use authorization from the FDA on October 29, 2021. Less than two weeks later, the team published their preliminary results in the New England Journal of Medicine.

The trial continues. The team followed participants through December, when they received a final blood draw to test for undetected infections and immune response. They’ll continue to follow for another year and a half. Currently, they’re gearing up for a modification of the trial beginning in February 2022, administering booster doses to participants at least 6 months from their initial dose to study their immune response.

Meanwhile, immediately following emergency use authorization, Children’s Colorado partnered with the Colorado Department of Public Health and Environment to stand up vaccine clinics at Children’s Colorado locations and through general pediatric practices in Children’s Colorado’s Pediatric Care Network. As of Dec. 7, 2021, those clinics had administered more than 22,000 doses, and that number continues to rise.

The study was so successful that the team was approached by Moderna to conduct a trial of similar proportions, although the team ultimately decided it was too much to absorb. That study eventually took place next door at the University of Colorado School of Medicine.

“One lesson we took from this is that staff hired under our Research Institute are usually committed to projects. We don’t have reserve staff that we can mobilize when something like this comes up,” says Dr. Simões. “We did it. We got the nurses, the research coordinators, the pharmacists. Everyone was fabulous, and we found the space. But one thing that would help in the future is having a core of uncommitted staff to take on something like this. I hope we can build that.”

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