What Does Vaccine Efficacy Mean?

By Sheeva Azma and Nidhi Parekh

Photo by Artem Podrez on Pexels.com

In the past few weeks, both Pfizer and Moderna have released the results of their Phase 3 clinical trials.  Both companies state that their vaccines are 95% effective — but what exactly does that mean?

What does vaccine efficacy mean? Find out in this post.

We’ve previously written about how the clinical trials process works and how various COVID-19 vaccines under development work.  Read on to learn more about vaccine efficacy and the vaccine clinical trials results.

Despite Accelerated Vaccine Efforts, Safety and Efficacy Remain Paramount

Operation Warp Speed (OWS) has hastened vaccine development efforts.  OWS is an initiative developed by the U.S. federal government to distribute 300 million doses of vaccines for the novel coronavirus by 2021.  The mission of OWS is to condense the vaccine clinical trials process — which can take years — into an accelerated timeline of just over a year.  The goal of OWS is to do so while ensuring vaccine effectiveness and safety, which are the two most important goals for any clinical trial.  The role of OWS in COVID-19 vaccine development is to “leverage the full capacity of the U.S. government to ensure that no technical, logistic, or financial hurdles hinder vaccine development or deployment.”  The vaccines that are part of OWS are the most safe and effective vaccine technologies currently available.  They are also vaccines which can be rapidly developed and deployed due to the urgent need to bring us a step closer to overcoming the COVID-19 pandemic.

The vaccines under development in OWS include both novel (e.g., mRNA vaccines) and tried-and-true (e.g., inactivated vaccines) vaccine technologies which are currently considered to be the best candidates in terms of safety and efficacy.  You can read about the most promising COVID-19 vaccines in late-stage clinical trials here.  It’s important to note that not all vaccines currently in development are part of OWS; for example, the Pfizer/BioNTech vaccine is being developed independently from OWS.  The U.S. federal government, which established OWS, has, however, paid Pfizer for some amount of vaccine doses that it will purchase from the pharmaceutical company.

What Is Vaccine Efficacy?

One of the main criteria OWS used to select vaccines was the ability for vaccine developers to begin Phase 3 clinical trials and report data on vaccine efficacy by the end of 2020. Vaccine efficacy is the measured effectiveness of the vaccine to prevent disease as determined by clinical trials.  Vaccine efficacy is different from vaccine effectiveness, which is the actual ability of the vaccine to prevent disease in the population.

How is Vaccine Efficacy Measured?

The definition of vaccine efficacy is the percent reduction in disease in a vaccinated group, compared to an unvaccinated group, in optimal experimental conditions, such as a randomized controlled trial.  On the other hand, vaccine effectiveness refers to the ability of the vaccine to prevent disease in the “real world.”

In a vaccine clinical trial, there are two groups — one group that receives the experimental COVID-19 vaccine candidate, and another group that receives a placebo vaccine.  The reason that both groups receive some sort of vaccine is so that there is not a major difference in post-injection symptoms such as muscle soreness or pain or a low-grade fever.

In the COVID-19 vaccine trials, vaccine efficacy is measured by comparing the number of people who develop COVID-19 in each experimental group.  The difference between the fraction of people who develop COVID-19 in the vaccine group versus the control group is called efficacy.  As the New York Times explains, “If there’s no difference between the vaccine and placebo groups, the efficacy is zero.  If none of the sick people had [received the experimental vaccine], the efficacy is 100 percent.”

Vaccine efficacy is a way to estimate how effective a vaccine will be in the real world.  As such, Operation Warp Speed has baked-in guidelines for the minimum efficacy of the vaccines under development.  Recognizing the need for a rapidly-developed COVID-19 vaccine, the U.S. Food and Drug Administration (FDA) released a set of guidelines for the vaccines currently under development.  The FDA guidelines set the vaccine efficacy threshold at 50%.

Vaccine efficacy is a way to estimate how effective a vaccine will be in the real world.

It’s important to note here that even if a vaccine does not entirely prevent disease, it can still provide indirect protection.  For example, vaccines can lessen the severity of disease and reduce infectiousness by reducing symptoms such as coughing or sneezing that could spread the virus.  Therefore, a vaccine that is not 100% effective can still reduce the spread of a disease and improve outcomes by making symptoms less severe. In other words, vaccines do not have to be 100% effective to have protective properties – a 50% rate is large in the grand scheme of things, as it would still provide protection in 50% of all people who receive the vaccine thereby bringing infection rates down. 

Pfizer and Moderna Vaccines’ Phase 3 Results Both Show High Efficacy

The two COVID-19 vaccines which are furthest along in the clinical trials process both rely on new technology — they are both mRNA-based vaccines.  The Moderna and Pfizer/BioNTech vaccines released their Phase 3 clinical trials results in November, both boasting 95% efficacy.  In other words, for both of these vaccines, most of the people who got sick from COVID-19 were in the control group — that is, they did not receive the COVID-19 vaccine candidates, but instead received the placebo.  

Pfizer/BioNTech Vaccine Efficacy: 95%

“There were 10 severe cases of COVID-19 observed in the trial, with nine of the cases occurring in the placebo group and one in the BNT162b2 vaccinated group,” Pfizer reports.  While a late-comer to the vaccine race, Pfizer and BioNTech’s candidate has been the fastest-progressing vaccine in the race.  After its Phase 3 clinical trials reported 95% efficacy, the Pfizer/BioNTech vaccine was the first candidate to file for an FDA Emergency Use Authorization (EUA) on November 20, 2020. The FDA will review Pfizer’s application on December 10, 2020. If approved, it would be the first COVID-19 vaccine — not to mention the first mRNA vaccine ever to obtain FDA approval — on the commercial market.

Moderna Vaccine Efficacy: Also 95%
 

Moderna’s vaccine was the fastest to be developed, and was the second, after Pfizer, to announce Phase 3 clinical trial results, including vaccine efficacy.  Moderna also reported a 95% vaccine efficacy.  According to a press release from the U.S. National Institutes of Health, “90 of the [COVID-19] cases occurred in the placebo group and 5 occurred in the vaccinated group. There were 11 cases of severe COVID-19 out of the 95 total, all of which occurred in the placebo group.”  Moderna will, in the coming days, also apply for an EUA from the FDA so that its vaccine can begin to be used in the real-world population.

So, What’s Next?

What’s next for the COVID-19 vaccine race?  Pfizer/BioNTech and Moderna’s vaccines, which have demonstrated impressive efficacy, are likely to obtain EUA by the end of 2020, and begin being administered to the highest-risk populations — including healthcare workers.  Many of these COVID-19 vaccines in development, including both the Pfizer vaccine and the Moderna vaccine, require two doses, which are typically administered a few weeks apart.  Therefore, full immunity for the first groups of vaccine recipients may not be established until early spring 2021.

Other vaccines, such as that in development by Oxford/AstraZeneca, are also expected to report their Phase 3 clinical trial results, including vaccine efficacy, by the end of 2020.  The Johnson and Johnson (J&J) vaccine only requires a single dose, but Phase 3 trials for the J&J vaccine started in late September 2020, so J&J vaccine efficacy results may not become available until early 2021.

While the vaccines under development appear very promising, experts have cautioned that the world will not return to normal until the end of 2021.  Some countries, such as the UK, already have a vaccine distribution plan in place.  While a distribution plan has not been finalized in the United States, it is highly likely that vaccines will be distributed according to need and risk.  For example, people most at risk of contracting COVID-19 will be highest priority — healthcare workers, other essential workers, and the elderly.  Young, healthy people will be low on the priority list.

A COVID-19 Vaccine Is Just the Beginning of the End to the COVID-19 Pandemic

Experts have cautioned that vaccines will not bring an end to the pandemic.  It will take time for the vaccines to be administered on a large-scale basis.  Currently, experts believe that the world will not return to life-as-we-know-it until the end of 2021.  Also, communication about vaccine safety and efficacy is increasingly becoming important with each passing day as more promising news about the COVID-19 vaccines in development are released.  Anti-vax rhetoric threatens to undermine the global efforts by spreading misinformation.

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