How many people need to be protected by a vaccine before it’s recommended for widespread use? Ideally, rates of disease will be 70 percent lower in vaccinated people than in unvaccinated people. The World Health Organization says a vaccine should be at minimum 50 percent effective, averaged across age groups. (We know from influenza that vaccines don’t always work as well on older adults whose immune systems have declined.)
This benchmark is crucial because a weak vaccine might be worse than no vaccine at all. We do not want people who are only slightly protected to behave as if they are invulnerable, which could exacerbate transmission. It is also costly to roll out a vaccine, diverting attention away from other efforts that we know work, like mask-wearing, and from testing better vaccines.
The last thing Phase III trials do is examine safety. Earlier trials do this, too, but larger trials allow us to detect rarer side effects. One of those rare effects researchers are paying attention to is a paradoxical phenomenon known as immune enhancement, in which a vaccinated person’s immune system overreacts to infection. Researchers can test for this by comparing the rates of disease severe enough to require hospitalization across the two groups. A clear signal that hospitalization is higher among vaccinated participants would mark the end of a vaccine.
The speed of the trials depends on how quickly we can detect a difference between the two groups. If two vaccinated people became sick versus 10 who got a placebo, it could be because of chance. But if it were 20 compared to 100, we would feel much more confident that the vaccine was working.
A key to getting a quick result is placing the trial in outbreak hot spots where people are most likely to be infected. We can even target the highest-risk people within those areas, using mobile teams to travel to neighborhoods, bringing the trial directly to the people. Some trials explicitly prioritize essential workers like health care workers or grocery employees. Others are simply focused on enrolling large numbers of participants as fast as possible.
Combining those efforts, it could take as little as three to six months to generate enough convincing safety and efficacy data for companies to apply for expedited review by the Food and Drug Administration.
There are ways for vaccines to be approved without definitive efficacy data, based on animal or immune response data instead, but the bar is extremely high, and for good reason. A precondition is that efficacy trials are not possible, typically because the disease is so rare or sporadic that it would require hundreds of thousands of participants to be followed for many years to tell if the vaccine is effective (rabies, for example). That is not the situation here.