Nevertheless, the news here is good: Another vaccine works. While Pfizer/BioNTech’s and Moderna’s trials went about as perfectly as possible, AstraZeneca’s announcement demonstrates how an honest mistake, a confusing trial design, and a lack of transparency can compound one another to create unnecessary confusion at a time when vaccines are under heightened scrutiny. “At the scale at which we’re planning to deploy these vaccines, we don’t want to leave any room for doubt,” says Natalie Dean, a biostatistician at the University of Florida who specializes in infectious disease and vaccine-study design. In an ideal world, many effective vaccines, deployed in tandem, would bring the global pandemic to a timely end, but each vaccine candidate is unique and needs to be evaluated individually.
Before vaccine manufacturers can give any experimental shots, they have to decide the number of people they will enroll in the trial, their definition of effectiveness (for example, will the vaccine be judged on its ability to prevent symptoms, or severe death, or transmission?), and the statistical analyses they will use. Changing the study protocol after it’s set is usually frowned upon because it can muddy the results, which is exactly what happened with the dosing error in AstraZeneca/Oxford’s vaccine. After U.K. scientists discovered the manufacturing error that created the weak doses, they got permission to modify the protocol and keep going.
This unusual change might require extra transparency, but that didn’t happen here. The original press releases neither acknowledged that the half dose was originally a mistake nor explained the full data behind the 90 percent efficacy number. A company spokesperson said that a peer-reviewed study with more details is forthcoming. But even in these very splashy initial press releases the company has been less transparent, Dean notes, than Pfizer/BioNTech and Moderna. Those two companies released results based on predetermined milestones laid out in published and detailed U.S. trial protocols; AstraZeneca has shared similarly detailed protocols for its U.S. trial, but the data undergirding last week’s announcement came from the U.K. and Brazil. The U.K. component of this vaccine trial alone has 28 arms, an unusually large number, where participants are divided by age and various dosing regimens. The Brazilian trial has a simpler design. (Moderna’s trial, in comparison, has two arms: vaccine and placebo.) The AstraZeneca announcement pooled data from the U.K. and Brazil without specifying how the groups might be different.
Thus the confusion when more information began to trickle out—but not from the company itself. On Tuesday, the day after AstraZeneca’s announcement, Moncef Slaoui, the head of Operation Warp Speed, the U.S. government’s vaccine effort, told reporters that only people younger than 55 got the half dose, while the full-dose group included people older than 55. That presented a problem: Younger people have immune systems that tend to respond more robustly to a vaccine, so the 90 percent and 62 percent efficacy in those two groups is not directly comparable. Moreover, only 2,741 of the more than 23,000 people whose data were included in the announcement got the half dose, so it’s unclear if the seeming benefit of the smaller dose will hold up in a larger trial. AstraZeneca is now eyeing a new trial to validate its half-dose regimen.