The First Dose is Good

WSJ: The Covid-19 vaccine developed by Pfizer Inc. and BioNTech SE generates robust immunity after one dose and can be stored in ordinary freezers instead of at ultracold temperatures, according to new research and data released by the companies.

The findings provide strong arguments in favor of delaying the second dose of the two-shot vaccine, as the U.K. has done . They could also have substantial implications on vaccine policy and distribution around the world, simplifying the logistics of distributing the vaccine.

A single shot of the vaccine is 85% effective in preventing symptomatic disease 15 to 28 days after being administered, according to a peer-reviewed study conducted by the Israeli government-owned Sheba Medical Center and published in the Lancet medical journal. Pfizer and BioNTech recommend that a second dose is administered 21 days after the first.

The finding is a vindication of the approach taken by the U.K. government to delay a second dose by up to 12 weeks so it could use limited supplies to deliver a single dose to more people, and could encourage others to follow suit. Almost one-third of the U.K.’s adult population has now received at least one vaccine shot. Other authorities in parts of Canada and Europe have prioritized an initial shot, hoping they will have enough doses for a booster when needed.

Preliminary data also suggest that the other widely used vaccine in the U.K. developed by AstraZeneca PLC and the University of Oxford could have a substantial effect after a first dose .

The Israeli findings came from the first real-world data about the effect of the vaccine gathered outside of clinical trials in one of the leading nations in immunization against the coronavirus. Israel has given the first shot to 4.2 million people—more than two-thirds of eligible citizens over 16 years old—and a second shot to 2.8 million, according to its health ministry. The country has around 9.3 million citizens.

…”This groundbreaking research supports the British government’s decision to begin inoculating its citizens with a single dose of the vaccine,” said Arnon Afek, Sheba’s deputy director general.

The Israeli study is here. Data from Quebec also show that a single dose is highly effective, 80% or higher (Figure 3) in real world settings.

It’s becoming clearer that delaying the second dose is the right strategy but it was the right strategy back in December when I first started advocating for First Doses First. Waiting for more data isn’t “science,” it’s sometimes an excuse for an unscientific status-quo bias.

Approximately 16 million second doses have been administered in the US. If those doses had been first doses an additional 16 million people would have been protected from dying. Corey White estimates that every 4000 flu vaccinations saves a life which implies 4000 lives would have been saved by going to FDF. COVID, of course, is much deadlier than the flu–ten times as deadly or more going by national death figures (so including transmission and case fatality rate)– so 40,000 deaths is back of the envelope. Let’s do some more back-of-the-envelope calculations. Since Dec. 14, there have been approximately 10 million confirmed cases in the United States and 200,000 deaths. There are 200 million adults in the US so 1/1000 adults has died from COVID, just since Dec. 14. If we use 1/1000 as the risks of a random adult dying from COVID, then an additional 16 million vaccinations would have saved 16,000 lives. But that too is likely to be an underestimate since the people being vaccinated are not a random sample of adults but rather adults with a much higher risk of dying from COVID. Two to four times that number would not be unreasonable so an additional 16 million vaccinations might have avoided 32,000-64,000 deaths. Moreover, an additional 16 million first doses would have reduced transmission. None of these calculations is very good but they give a ballpark.

It is excellent news that the vaccine is stable for some time using ordinary refrigeration. Scott Duke Kominers and I argue that there is lot of unused vaccination capacity at the pharmacies and reducing the cold storage requirement will help to bring that unused capacity online. The announcement is also important for a less well understood reason. If Pfizer is only now learning that ultra-cold storage isn’t necessary then we should be looking much more closely at fractional dosing.

When I said that we should delay the second dose, people would respond with “but the companies say 21 days and 28 days! Listen to the science!”. That’s not scientific thinking but magical thinking. Listening to the science was understanding that the clinical trial regimen was designed at speed with the sole purpose of getting the vaccines approved. The clinical trial was not designed to discover the optimal regimen for public health. Don’t get me wrong. Pfizer and Moderna did the right thing! But it was wrong to think that the public health authorities could simply rely on “the science” as if it were written on stone. Even cold-storage wasn’t written on stone!  Now that the public health authorities know that the clinical trial regimen isn’t written in stone they should be more willing to consider policies such as delaying the second dose and fractional dosing.

We are nearing the end in the US but delaying the second dose and other dose-stretching policies are going to be important in other countries.

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