The recent breakthrough in vaccine efficacy for the Pfizer and Moderna vaccines has become daily news. But many are confused by what this efficacy measure really means, and how it is calculated. In this short essay, I look at what a vaccine efficacy (VE) rate really means, and what it implies about the ultimate impact on human deaths.
The recent Phase 3 clinical trials of the vaccines were conducted by taking a sample of 30,000 individuals, and randomizing half of them to receive the vaccination (“treatment group”) and the other half to receive the placebo (“control group”). After a certain time horizon, or when enough subjects from both groups reach a critical threshold number of infections, the number of cases are counted in each group. The VE is then calculated as:
A recent study of the efficacy of the Pfizer vaccine (which necessitates two doses of the vaccine) appeared in the New England Journal of Medicine. It reports that the number of cases of COVID after just the first dose of the Pfizer vaccine were: 39 cases in the treatment group, 82 cases in the control group. This implied an efficacy rate of 52% after one dose. After the second dose, the number of cases of COVID were: eight cases in the treatment group and 162 in the placebo group, or an efficacy rate of 95%. So the
VE rate is the percentage reduction in COVID cases for those receiving the vaccine versus those who received the placebo.
Why should we care much about the VE rate for a disease with a fairly low death rate? A disease’s death rate is simply the percentage of those confirmed cases who end up dying. According to the Centers for Disease Control and Prevention (CDC), the known case fatality rate attributed to COVID in the U.S. is about 335,000, while the number of confirmed cases is slightly above 19 million — for a death rate of 1.76%. Globally, the number of confirmed cases is slightly more than 80 million, while the number of deaths is about 1.8 million — for a global death rate of 2.19%. In comparison, the CDC reported that influenza in the U.S. in 2019-20 resulted in an overall death rate of only about 0.06%. In this regard, we see that the COVID disease is about 20 to 30 times deadlier than a typical seasonal flu outbreak. Furthermore, the flu vaccine has a VE of about 40 to 60% (depending on how good the vaccine matches the actual virus).
How Vaccine Efficacy Affects COVID-19 Deaths
To get an idea of how variations in a vaccine’s VE has real effects, let’s make some back-of-the-napkin estimates on the number of deaths caused by the COVID pandemic under two vaccine scenarios. Let’s compare a vaccine that is around 50% effective (like the flu vaccine) versus a vaccine that is around 90% effective (like the Pfizer vaccine), and see how this difference in efficacy affects the expected number of deaths. In this thought experiment, we will use the most recent CDC data on the U.S. and the world. (Reuters recently did a similar fact check on the effects of VE on death rates.)
If our experiences with COVID over the past nine months were to continue over the next nine months, a vaccine with a 50% VE means that the U.S. could expect another 9.5 million cases, whereas a vaccine with a VE of 90% would result in only an additional 1.9 million cases. This implies that this more effective vaccine could reduce the number of American cases by about 7.6 million. Now, let’s translate this into the expected numbers of deaths from the pandemic. Using the current U.S. death rate of 1.8%, a 50% vaccine would result in an additional 171,000 deaths (instead of another 335,000) while the number of deaths under a 90% effective vaccine would be only another 34,000 deaths. This higher efficacy rate alone could result in about 137,000 fewer lives lost (and much fewer than the more than 300,000 lives lost over the past nine months)!
Continuing this hypothetical exercise using the global data, we see an even greater impact on human lives. A 50% VE would result in 40 million cases (instead of 80 million cases) while a 90% VE would result in 8 million cases. Given the global death rate is 2.19%, the 50% VE would result in about 880,000 deaths (instead of 1.8 million). While under the 90% VE, the number of deaths would be about 175,000. Again, we see that the size of a vaccine’s VE has a large and significant impact on human lives.
One lesson learned here is that it suggests an easy explanation for the logic of the federal government involvement in the Operation Warp Speed program. This program directed almost $11 billion in federal aid to accelerate the development and delivery of COVID vaccines. The program called for government approval of any new vaccine that surpassed a minimum VE threshold of 50%. Utilizing results on messenger RNA (developed under earlier vaccine research) had the benefit of pushing the two vaccine’s VE to over 90%, potentially resulting in a significantly greater impact on lives saved. But perhaps an even more important task for the Warp Speed program is that we must ultimately get the vaccine into people’s arms, for every day of delay is costing lives.