With several vaccines against COVID-19 in late-phase testing, the business of measuring efficacy is front and center.
Determining the efficacy, or how well a vaccine works in a randomized, controlled trial, gives a sense of how much a vaccine could help alleviate the suffering caused by COVID-19. The U.S. Food and Drug Administration recommends vaccines tested against COVID-19 reach an efficacy of 50 percent, at minimum. That means at least a 50 percent reduction in cases of COVID-19 disease in those who are vaccinated compared with those who receive the placebo.
Johnson & Johnson, Moderna, Pfizer and AstraZeneca have each begun phase III trials of their vaccines in the United States. These late-phase trials, which will each assess safety and efficacy in tens of thousands of people, randomly assign some participants to receive vaccinations and others a placebo. The companies and the U.S. government, working together as part of Operation Warp Speed, have set a goal of having initial doses of a vaccine available by January 2021 (SN: 7/10/20). It won’t be clear how well any of these vaccines do their job until the companies report full results from those trials; some preliminary results may come out as early as October.
The FDA setting a minimum recommendation for efficacy doesn’t mean vaccines couldn’t perform better. The benchmark is also a reminder that COVID-19 vaccine development is in its early days. If the first vaccines made available only meet the minimum, they may be replaced by others that prove to protect more people. But with more than 1 million deaths from COVID-19 worldwide — and U.S. deaths surpassing 200,000 — the urgency in finding a vaccine that safely helps at least some people is at the forefront.
“You want to set the bar [for efficacy] high enough so that it is clinically and epidemiologically significant, but low enough that a ‘good enough’ vaccine can be licensed until something better comes along,” says Kawsar Talaat, a vaccine researcher at the Johns Hopkins Bloomberg School of Public Health.
The World Health Organization has also set a minimum target of 50 percent efficacy for vaccines tested against COVID-19, but its “preferred efficacy” is at least 70 percent.
Efficacy specifically applies to how a vaccine works in a clinical trial. For the four vaccine candidates now in phase III trials in the United States, the primary goal is not necessarily to stop an infection but to prevent a person from experiencing symptoms of COVID-19 or, in Johnson & Johnson’s case, to guard against moderate to severe illness. Researchers will count cases of symptomatic COVID-19 in the vaccinated group and in the placebo group (who get injections of saline, for example) and calculate how much of a reduction there was with vaccination.
“At least with the first generation of vaccines,” Talaat says, “what we’re really trying to do is prevent severe disease and hospitalization and death.”
A vaccine that prevents people from developing symptoms may not stop them from becoming infected and passing the virus to others. If such a vaccine gets approved, what the vaccine does and doesn’t do would need to be communicated very clearly, says Maria Bottazzi, a vaccinologist at the Baylor College of Medicine in Houston. People would still need to wear masks and practice social distancing to help keep the virus from spreading, she says.
The efficacy results won’t be the final word on how effective the vaccine is in the real world. That’s one reason “why it’s always a good idea to have a more diverse population in your trials,” says Saad Omer, a vaccine researcher at Yale University. That way, researchers can gather data on how the vaccine works for different people in a variety of scenarios.
Studies of other vaccines in which a trial took place in different locations have reported different results based on the incidence of disease in those areas; some vaccines haven’t worked as well in populations where the risk of exposure is higher. In this pandemic, Black and Latino Americans are disproportionately represented in the essential jobs that can’t be done at home, putting them at risk for more exposures to the coronavirus (SN: 7/2/20).
A person’s age also affects how well a vaccine will work. Our immune system “ages as we age too,” says Bottazzi. When older adults get the flu vaccine, for example, the shot doesn’t elicit as strong an immune response as it does in younger adults. In the United States, adults ages 65 and older can get specially formulated flu vaccines that create a stronger immune response and better protection for this age group.
For the COVID-19 vaccine trials, the FDA has strongly encouraged “enrollment of populations most affected by COVID-19, specifically racial and ethnic minorities.” The agency also states that the phase III trials should include enough older adults and people with certain underlying medical conditions, two groups at increased risk for COVID-19, to be able to evaluate efficacy for them.
How well the first COVID-19 vaccines work, and for whom, will influence who is initially prioritized to receive the vaccine. The Advisory Committee on Immunization Practices of the U.S. Centers for Disease Control and Prevention issues guidance on the use of vaccines in the general population. To recommend a COVID-19 vaccine for older adults, for example, there has to be data to show that it works for them.
There are other COVID-19 vaccines in development and testing; some aren’t very far behind the front runners. Even if one or more of the vaccines now in phase III trials gets the green light, “the story wouldn’t be over,” says Omer. “It would be the end of the beginning.”