Two Months Into Israel’s COVID Vaccination Drive, Most Comprehensive Study Yet Shows Level of Effectiveness

Asaf Ronel
Asaf Ronel
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A health worker prepares to administer a dose of the Pfizer-BioNtech vaccine in a Tel Aviv facility, on Wednesday.
A health worker prepares to administer a dose of the Pfizer-BioNtech vaccine in a Tel Aviv facility, on Wednesday.Credit: JACK GUEZ / AFP
Asaf Ronel
Asaf Ronel

The coronavirus vaccine developed by Pfizer and BioNTech provides very high protection against symptomatic illness, severe illness and death, closely approaching the level of protection the companies announced from their Phase III clinical trial. This is the clear conclusion of the most thorough, comprehensive study published to date.

It’s based on the medical data from 1.2 million patients belonging to Israel’s Clalit Health Services health maintenance organization – half of whom were vaccinated and half were not.

Three months after real-world coronavirus vaccinations began and two months after Israel's campaign started in late December, the vaccine’s safety is crystal clear, as tens of millions of people have received it with no worrisome side effects. But up to now, the question of whether it was really as effective against the coronavirus as the clinical trials showed remained unanswered.

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Israel wasn’t the first country to begin vaccinations. But the pace and scale of its vaccination campaign, coupled with the wealth of medical data from its HMOs and stored in a few central databases, made it a global test case of the vaccine’s effectiveness.

Consequently, all of the effectiveness studies published in the last two months have relied on Israeli data. They have used various methods to examine the vaccine’s effectiveness and most haven’t yet undergone peer review.

A woman receiving a coronavirus vaccination in Tel Aviv last week.Credit: Tomer Appelbaum

The latest study, published on Thursday in a leading journal, the New England Journal of Medicine, was conducted by researchers from the Clalit Research Institute. It used the most precise statistical methods available for analyzing real-world data to get as close as possible to the gold standard of clinical research.

The authors are Prof. Ran Balicer, Dr. Noa Dagan, Dr. Noam Barda, Dr. Eldad Kepten, Oren Miron, Shay Perchik and Prof. Mark Katz from Clalit, in addition to three senior researchers in the field from Harvard University – Miguel Hernan, Marc Lipsitch and Ben Reis.

The study found that the vaccine prevents 94 percent of cases of symptomatic illness on average; the full range is 87 to 98 percent. Because the study involved 1.2 million people, compared to only around 40,000 in the Phase III clinical trial, it also provides a clear answer to the question of how effective the vaccine is at preventing cases of serious illness – 92 percent.

From analyses carried out by the Clalit Research Institute based on the HMO’s updated data, after the article was written, they found that vaccinated people are 86 to 98 percent less likely to become seriously ill beginning from a week after the second dose. But the study also found that the vaccine starts having an effect even two weeks after the first dose, preventing 57 percent of cases of symptomatic infection and producing a 62 percent decline in the number of seriously ill patients.

The huge number of people in the study also enabled the researchers to determine how many deaths the vaccine prevented. It found that by day 27, the level of protection against death reaches 84 percent.

The later, unpublished data shows that the vaccine prevents 85 to 100 percent of deaths. In sum, “during each of the periods of time, the protection against death is equal to or greater than the protection against serious illness.”

Finally, the vaccine prevented 92 percent of cases of documented infection. This is not the same as the number of total infections it prevents, since to determine that, it would be necessary to test people randomly to detect asymptomatic carriers. Clalit is now doing precisely that and will publish the results later.

The biggest difference between the first and second doses is in this statistic: Until a week after the second dose, the vaccine is only 60 percent effective at preventing documented infections, but after that, it jumps to 92 percent.

Clalit’s research shows that the vaccine is extremely effective, but slightly less so than claimed by other studies published in recent weeks, including studies by the Israeli Health Ministry. The problem with the previous studies was that they didn’t take into account the significant differences between population groups that were more or less likely to get vaccinated. These differences, primarily socioeconomic, affect both their likelihood of contracting the virus and the likelihood of having preexisting conditions that exacerbate it.

A Clalit vaccination center in the Bedouin Negev town of Rahat.Credit: Eliyahu Hershkovitz

The basic problem with reaching conclusions about a vaccine’s real-world effectiveness, even with data from hundreds of thousands of people to draw on, is that no real-world study can meet the fundamental requirements of clinical trials.

First of all, in the real world, the division between the research group and the control group – i.e., the unvaccinated – is neither random nor controlled. There can be many differences between people who get vaccinated and those who don’t, and the researchers can’t control who is in which group.

Secondly, in the real world, vaccinated people know they’re getting the vaccine. Clinical trials are double-blind, meaning neither the researchers nor the subjects know who received the vaccine and who got a placebo – to prevent any possibility that this knowledge might distort the results. In real life, the knowledge that they have been vaccinated can alter people’s behavior, thereby altering their risk of infection with no connection to the vaccine’s biological impact.

To compensate for these problems, the Clalit researchers used sophisticated statistical tools to make their research and control groups as similar as possible. For each of the 600,000 vaccinated people, they found an unvaccinated “twin” in their databases whose demographic, health and socioeconomic characteristics were as similar as possible.

And the twins are not only similar in age and gender. For example, if there is a 56-year-old ultra-Orthodox vaccinated man who lives in a specific area of Tel Aviv, who has two underlying diseases and was vaccinated against the flu last year, the researches would “pair him” with a 56-year-old ultra-Orthodox man who lives in the same area who has the same two underlying diseases and was vaccinated last year against the flu – but was not vaccinated against the coronavirus.

Tracking virus statistics among these two groups allows the researchers to measure the vaccine’s effectiveness accurately while neutralizing most of the other factors that could influence the results.

Critical and clear evidence

The bottom line is that the Clalit study provides critical and clear scientific evidence of the effectiveness of the vaccines, but the study also makes clear that protection is not complete, and therefore we need to continue to conduct ourselves in a calculated and cautious manner with regard to those at the highest risk of serious illness, even if they are vaccinated.

Given this, will the vaccines ever enable us say goodbye to the coronavirus, and if so, when? What percentage of the population must be vaccinated to create herd immunity that will prevent the virus from spreading?

To answer this, we need to know to what degree the vaccine really entirely prevents people from getting infected (and therefore also infecting others). It is hoped that studies like the one Clalit is working on now will help answer this question, enabling us to better understand what we need to do to truly beat the virus.

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