Pfizer-BioNTech vaccine performs as well in the real world as in clinical trials, new study concludes

Pfizer and BioNTech’s Covid-19 vaccine performed as well in the real world as it did in the clinical trial that led to its use, a large study conducted in Israel concluded.

The study, published Wednesday in the New England Journal of Medicine, is the largest to date assessing the effectiveness of the vaccine, comparing all illness, severe illness, and hospitalizations as well as deaths between 600,000 pairs of vaccinated and unvaccinated people.

That a vaccine will perform as well in the real world as it does in the highly controlled setting of a clinical trial is not a given, noted senior author Ran Balicer, director of the Clalit Research Institute of Israel.

“The vaccine fulfilled the promise that was there. And it was somewhat of a surprise to see that in a real-world setting, a vaccine was able to perform as well as it did in the very controlled setting of a clinical trial, where cold-chain is perfect and the people are being carefully selected,” said Balicer, who also chairs an expert panel that advises the Israeli government on the pandemic.

But he warned that while the vaccine performed very well — it was 94% protective against symptomatic Covid, across all age groups, even older adults — some fully vaccinated people did develop severe illness and some died. During the period of the study, nine people who were fully vaccinated died from Covid-19, compared to 32 people who had not yet been vaccinated.

“These vaccines are not a force field around you that negates the chance that you will have an illness or that you will have a severe illness,” Balicer said, noting that while two doses of the vaccine offer substantial protection against severe Covid infection and death, “there is residual risk.”

“And so I think continuing precautions, especially among those populations at risk … at a time when community spread is evident and is massive, as in the case in Israel, would be the prudent thing to do, even for those who are fully vaccinated,” he said.

Kathleen Neuzil, director of the Center for Vaccine Development at the University of Maryland School of Medicine, found the results of the study encouraging.

“This was a well-done study, and the findings support an impact of the vaccine on multiple important outcomes — any infection, symptomatic infection, hospitalizations and deaths,” she said. “The rapidity with which we are seeing impact after introduction of the SARS-CoV-2 vaccines … provides hope that with enough vaccine supply, we can get this pandemic under control.”

The authors of the study, from several institutions in Israel as well as Harvard School of Public Health and Boston Children’s Hospital, reported some data that will likely play into the ongoing debate about whether it would be safe to delay the second dose of the Pfizer vaccine to give a first dose more quickly to more people.

The Pfizer vaccine is a two-dose vaccine that is meant to be given 21 days apart. Health authorities in Britain have already decided to delay giving the second dose, and some experts in the United States are pushing for this country to follow suit. But to date the Food and Drug Administration has resisted the calls to change the dosing schedule for the virus.

Almost everyone in Israel who got the vaccine received their second dose on time, so that study cannot answer the question of how well the protection induced by the first dose of vaccine would last if it was not boosted at the appropriate time.

But the analysis showed that from day 14 after the first shot — the point at which protection is seen to start to take effect — to day 20, the day before the second dose, there was moderate protection against any infection but better protection against serious disease.

During that narrow window of time, protection against documented Covid infection after one dose was 46% — below the FDA’s stipulated cut off of 50% efficacy. But for symptomatic infection, hospitalization, and severe illness, the protection for that period was 57%, 74%, and 62% respectively.

The authors estimated that one dose of vaccine was 72% protective against death from Covid in that seven-day period, though because of the numbers of deaths was small, it’s difficult to draw firm conclusions.

The study also found the vaccine worked well in people with significant health problems — another real-world test that vaccines don’t always pass with flying colors.

Noa Dagan, an author also from the Clalit Research Institute, said that for people with one or two health conditions that increased their risk of severe Covid illness, the vaccine worked as well as it did for people who were healthy.

Even in people with three or more health conditions, the vaccine’s protection appeared to be strong, with about 89% effectiveness, she said.

As Covid vaccines start to be used more broadly, there will be a multitude of studies looking at how well the vaccines work and whether some work better in certain segments of the population than others. Such data are badly needed as the world tries to figure out how best to use vaccines that will be in scarce supply for months or longer.

“I think the results are useful, in that we can start to leverage large observational datasets to fill in gaps in our understanding, primarily by enabling finer breakdowns by age, comorbidity, and time since vaccination, as they have done here,” said Natalie Dean, a biostatistician at the University of Florida.