Who should be at the front of the line if an effective COVID-19 vaccine emerges from testing? The answer depends on what we learn from the kind of field trials Russia is skipping.
Some vaccines might not be that good at preventing infection, but would prevent severe cases. Those should be given to those most likely to die from the disease — older people or those with conditions associated with death from COVID-19.
But if a vaccine actually prevents transmission, then priority should go to those who transmit the disease most often: younger adults. Getting protected with a vaccine is a way of protecting others, since you can't give anyone the disease if you never get it. And starting with younger people could be the fastest route to herd immunity — that phenomenon by which the virus is slowed by a lack of susceptible hosts.
Why give the vaccine to the people most likely to spread the disease rather than to the people most likely to die from it? Virologist David Sanders of Purdue explains that it's likely that COVID-19 vaccines it won't work as well in people with poorly functioning immune systems — those most vulnerable to the disease. That's often the case with flu shots and other vaccines. But those people can still be protected if enough healthy people get vaccinated to drive infections way down. "Immunization is not about protecting the individual — it's about protecting society," he says.
But here's the rub: If young, healthy people unlikely to die from the disease are being asked to step up and get vaccinated, the odds of any serious side effects have to be extremely low. And that's why field testing is so important.
Skipping that kind of extensive field testing, as Russia is doing, could foil our chance to end the pandemic. Infectious disease specialist Paul Offit of the Children's Hospital of Philadelphia says the early phases of the FDA's required testing offer limited information. Phase 1 determines the optimal dose for a vaccine. Phase 2 enrolls hundreds of people, which can reveal common side effects and determine whether the vaccine prompts the body's immune system to produce antibodies or T-cells capable of disabling the virus.
Those early trials have already revealed transient side effects, especially fever and the malaise that goes with it. But given the number of people dying from the disease, that's probably going to be considered tolerable.
Phase 3 is the time-consuming part, where a vaccine is compared to a placebo in the real world. Even with the expected 30,000 volunteers for each of several front runners, that could take a few months, depending on how much transmission is going on. At least a few people in the placebo group need to get infected to demonstrate efficacy.
This is the phase Russia is skipping, and it's only during this phase that researchers can tell if people who get vaccinated can still develop a mild or silent infection and transmit to others. The vaccines generally prompt your body to produce antibodies to just one of the viral proteins, but the virus makes four proteins, and a natural infection will leave you with distinct, detectable antibodies to all of them.
Still, even enrolling tens of thousands of people in those trials may not be enough to reveal rare side effects, says Offit. The live polio vaccine caused a few children to get polio — about 1 in 2.4 million. A swine flu vaccine deployed in 1976 caused a rare neurological disorder called Guillain-Barre Syndrome. About one in 100,000 people developed the condition, and while most recovered, a few died or suffered permanent paralysis. A further data-gathering phase — sometimes called Phase 4 — would have a better chance of catching anything that rare, and reduce any risk that a vaccine could hurt the healthy people being asked to get it.
Phase 4 isn't part of the testing regimen required for licensure, but refers to post-licensure surveillance, said Harvard public health professor Barry Bloom, speaking at a Zoom press conference. Purdue's Sanders says this phase should include health care workers and military personnel, since they can be closely tracked to provide crucial information.
It might seem counterintuitive to do extra testing in a situation this urgent it has prompted Russia to deploy a vaccine without the critical field testing the FDA requires. But additional testing wouldn't have to slow down the benefits of a vaccine. Think of it as a hybrid between a final trial and the rollout itself, configured to gather important data.
This additional layer of testing could help prevent problems that might get in the way of widespread adoption of a COVID-19 vaccine. Offit says he's worried that people will come to believe in severe side effects that don't exist. Out of the millions who eventually get the vaccine, a few will likely have heart attacks or strokes or develop multiple sclerosis or some other disease that wasn't caused by the vaccine but happened close enough in time to seem that way. Such temporal associations, as he calls them, have created the longstanding, false perception that childhood vaccines caused autism.
A Phase 4 trial could prevent these problems, and help convince enough healthy, young people — those with the least to individually gain from a vaccine — that getting a coronavirus vaccine is both safe and their civic duty.
Faye Flam is a Bloomberg Opinion columnist. She has written for the Economist, the New York Times, the Washington Post, Psychology Today, Science and other publications. She has a degree in geophysics from the California Institute of Technology.
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