If you want to find seashells, go to a sand bar. If you want to test a coronavirus vaccine, go to a crowded bar

Some COVID-19 vaccine candidates being tested are in phase 3 of clinical trials. NCSE Executive Director Ann Reid helps decipher what that means.

crowded bar

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One of the great strengths of science is that it can save you a lot of work by giving you a predictive framework. We don’t have to shoot hundreds of satellites into space at different speeds in the hope that one will end up in orbit. We use physics to predict exactly how to propel the object to the right place. Similarly, if we want to find fossils of the transitional forms between fish and tetrapods, we don’t have to dig around at random; we can use evolutionary science and geology to identify where the likeliest fossil-bearing strata are. (If your students are struggling with the “it’s just a theory” misconception about evolution, you might have them watch evolutionary biologist Neil Shubin describe how he found a very specific and important fossil: Tiktaalik.)

Image by Zina Deretsky, National Science Foundation

Science can also guide you when it comes to testing vaccines. Now that several coronavirus vaccine candidates have reached the stage of phase 3 clinical trials, it seems like a good time to talk about how such trials are designed to provide the most possible information in the least amount of time. You can read about earlier phases in the process, but know that phase 3 is the big enchilada: the test of whether the vaccine protects people under normal, everyday circumstances.

The phase 3 trial of the first U.S. vaccine candidate, called mRNA-1273, developed by Moderna, Inc., is beginning this week and is slated to last for two years. Researchers are hopeful, though, that enough information will be gained in just three to four months to justify beginning to administer the vaccine on a mass scale.

This particular phase 3 trial will enroll 30,000 participants. Half will be given two doses of the vaccine, 28 days apart. The other half will receive shots containing a placebo. The participants will be carefully followed for two years, with regular blood tests to check for antibodies against the virus. Participants who become infected will be followed to determine the severity of their symptoms.

Phases 1 and 2 were designed to demonstrate that the vaccine was safe and that it stimulated an immune response. Phase 3 is designed to determine efficacy—that is, whether that immune response actually protects you from catching the disease. Efficacy is measured as the “percent reduction in incidence (of disease or infection) among the vaccinated” as compared to the unvaccinated. For example, if you give the vaccine to 100 people and a placebo to 100 people and none of the vaccinated people get the disease and all of the placebo recipients get the disease, the measured efficacy is 100%. But if 50 people from each group become infected, the measured efficacy is 0%.

In the real world, such clean-cut results—and such high infection rates—are unlikely. That’s why phase 3 trials need to be so big, and why mRNA-1273 in particular is being tested with 30,000 people.

It now appears at least possible that a vaccine will be ready within just one year from January 2020, when coronavirus began to spread widely.

Phase 3 vaccine trials go a lot faster when the target disease is spreading rapidly, so the unfortunate current situation in the U.S. of multiple hot spots of coronavirus spread has at least this one silver lining: the efficacy of the mRNA-1273 vaccine should become clear much more quickly than it would if we had the virus under control. The 30,000 participants are being recruited from places where the virus is prevalent, and from groups, like healthcare and other frontline workers, who are at higher risk of encountering the virus. If significantly fewer of these highly exposed workers who receive the vaccine become infected than those who receive the placebo, we will know that the vaccine is truly protective.

And if that proves to be the case, good! The next step in the process—manufacturing and distributing millions of doses—is already under way. Under normal circumstances, a vaccine producer would not invest the millions of dollars needed to build a production facility and begin making a vaccine until its effectiveness was more thoroughly established. But given the urgency of the coronavirus pandemic, large-scale production of the vaccine began as soon as the first safety and immunogenicity results were in. The government has guaranteed the manufacturer that it will cover the costs of production, even if the vaccine does not prove effective in phase 3.

Back in April 2020, I suggested that 18 months was the bare minimum for the production and distribution of a vaccine. It now appears at least possible that a vaccine will be ready within just one year from January 2020, when coronavirus began to spread widely. Vaccines don’t always prove effective in phase 3 trials, and even if this one does, we will not know for quite some time how long the immunity provided by the vaccine will last. But even a vaccine that provides only imperfect or short-term immunity would save lives, and therefore is something we can be deeply grateful for.

NCSE Executive Director Ann Reid
Short Bio

Ann Reid is the Executive Director of NCSE.

reid@ncse.ngo

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