There were other dosing issues, too, that haven’t been explained even though dosing is the centerpiece of the press release. There are many different regimens in these trials—the UK study has more than two dozen arms, meaning the volunteers were divided into that many groups according to age and how much of the vaccine would be administered and when. The doses are measured by the number of altered viral particles they contain, and the developers decided that the standard dose would be 5 x 1010 viral particles. But for many of those arms in the UK trial—as well as everyone who got the vaccine in the Brazilian trial—publicly available trial information shows that the standard dose could be between 3.5 and 6.5 × 1010 viral particles. The lower end of that range isn’t far off from a half-dose.

How did Oxford-AstraZeneca end up with this patched-together analysis instead of data from a single, large trial? After all, this vaccine went into Phase 3 testing before either BNT-PFizer’s or Moderna’s did. But in the UK, where that testing started, the Covid-19 outbreak happened to be receding. That meant results would be coming in very slowly.

A month later, a second Phase 3 trial for the vaccine started in Brazil. That one was for healthcare workers, for whom the risk of being exposed to Covid was far higher than it was for the people in the UK trial. But the two trials had other substantive differences. In the UK, for example, the volunteers who did not get the experimental Covid vaccine were injected with meningococcal vaccine; in Brazil, those in the comparison group were given a saline injection as a placebo.

Meanwhile, BNT-Pfizer and Moderna began Phase 3 trials for their coronavirus vaccines on the same day in July: Both planned to include 30,000 volunteers at the time, and both trial plans were approved by the FDA. Oxford-AstraZeneca then announced they, too, would run a 30,000-person trial in the US.

But that research on the Oxford-AstraZeneca vaccine quickly fell behind the others’. The US trial was approved by the FDA, but it didn’t start recruiting people until the end of August; and just a week later, it was put on hold so the FDA could investigate a serious adverse event in the UK trial. It wasn’t clear what caused the volunteer to get sick, but the FDA did not give the all-clear for Oxford-AstraZeneca’s US trial to resume until Oct. 23. By then the protocol for the trial had been publicly released. It says the plan is to inject the vaccine in two standard doses, a month apart; and two people will be vaccinated for every one who gets a placebo saline injection.

So here we are at the end of November. BNT-Pfizer and Moderna have offered up a masterclass in how to do major vaccine trials quickly in a pandemic, while Oxford-AstraZeneca has, for the moment, only an assortment of smaller ones ready to look at.

Read all of our coronavirus coverage here.

But wait, more red flags! Last week, Oxford-AstraZeneca published some results from earlier in the development of the UK trial. That paper included a trial protocol for the UK study, attached as an appendix. Deep in that document, and apparently overlooked by reporters and commentators, was an eyebrow-raising suggestion: Under a section marked “Interim and primary analyses of the primary outcome,” the trialists outline a plan to combine and analyze data from four clinical trials (only half of which are Phase 3), carried out in different ways on three different continents. The plan, they wrote, was to pull out results only for the people across these four trials who had gotten “two standard-dose vaccines,” and then pool those together for what’s called a meta-analysis.


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