Small, single-vaccine clinical trials may not provide sufficient evidence that a COVID-19 vaccine is effective enough to provide significant protection, writes a group of World Health Organization scientists, including the University of Florida’s Ira Longini, Ph.D., in a commentary published last week in the journal The Lancet.
“You need large numbers and multiple products in many different settings tested in many different kinds of people to assess whether they’re really safe and effective,” said Longini, a professor in the department of biostatistics in the UF College of Public Health and Health Professions and the UF College of Medicine.
Longini and the other Lancet commentary authors are working on the WHO Solidarity Trial, which will test multiple vaccines at possibly hundreds of sites in tens of thousands of participants to find vaccines with at least 50% efficacy, WHO’s recommendation to provide meaningful protection and help achieve herd immunity.
“There’s a misconception that once you test a vaccine, you’re finished,” Longini said. “The truth is vaccines are very complex products that may or may not be safe or protective. We want to ensure we have safe and effective vaccines as fast as possible.”
The authors caution that deploying vaccines with 30% or less efficacy could actually worsen the epidemic if people incorrectly assume they are protected and decide to discontinue other infection control behaviors. While a few phase III COVID-19 vaccine clinical trials are currently underway, they may not give scientists a full picture of their efficacy due to limitations in size and scope, says Longini, also a member of UF’s Emerging Pathogens Institute.
In contrast, the WHO Solidarity Trial will simultaneously test several COVID-19 vaccine candidates at multiple sites with sustained COVID-19 transmission, with more added as different disease hotspots are identified. Each vaccine will be tested in around 20,000 adult participants in a range of ages, with another 20,000 receiving a placebo. Coordinated analyses across all these sites will rapidly identify vaccines that hold promise and eliminate those that do not.
“High enrollment rates, facilitated by flexible trial design and hundreds of study sites in high-incidence locations, could yield results for each vaccine within just a few months of it entering the trial,” the authors write.
The Solidarity Trial expert group, made up of some of the researchers who designed the vaccine trial for the successful Ebola vaccine Ervebo, will evaluate prospective vaccines for inclusion in Solidarity based on a number of factors, including safety in animals and humans, preliminary efficacy and the ability to effectively produce and distribute large quantities of doses. More than 150 potential COVID-19 vaccines are in some stage of development, with about 30 at the clinical trial stage, Longini said.
“When successful vaccines are found, we are going to make sure they are vaccines that can be quickly ramped up for production of hundreds of millions or even billions of doses, and they will be distributed equitably throughout the planet,” Longini said.