While the circumstances of each of the company’s vaccine missteps has varied, a common thread has run through them all: a perception that the company has been less than fully transparent. The widening credibility chasm facing the AstraZeneca vaccine has severely eroded confidence in a vaccine that much of the world is still depending on to help end the pandemic.

Opaque numbers

At least once before the company has been caught potentially shading its vaccine data in a press release to make its inoculation seem more effective. On November 23, when AstraZeneca and the University of Oxford announced the preliminary results of its U.K. and Brazilian clinical trials, the press release trumpeted a 70.4% efficacy against symptomatic COVID-19. It did so again when a fuller analysis was published on December 8. But that figure was only obtained using a “blended” average that included a large group that received the planned dosing schedule of two full doses, where there was a 62.1% efficacy, and a much smaller group that had been given a half-dose initially, where the vaccine seemed to be 90% effective.

It turned out this smaller half-dose group consisted only of people younger than 55, meaning that besides being a smaller sample, there were other reasons to think that high efficacy number might not be representative of how the vaccine would perform in the general population. This was especially concerning because COVID-19 is most dangerous to older people.

It certainly looked as though the company had bent over backwards to provide a better headline number for efficacy—one that might put their vaccine at least in the same state, if not the same zip code, as the results announced a month earlier by Pfizer and Moderna for their vaccines. Both companies reported near 95% efficacy for their vaccines. Those two vaccines both use messenger RNA technology, while AstraZeneca’s vaccine is based on modifying a chimpanzee virus to carry instructions into the human body for making copies of the coronavirus’s spike protein, which then prompts an immune response.

The picture got murkier still as medical experts and reporters tried to get to the bottom of why some trial participants had been given the initial half-dose, with those behind the vaccine seemingly struggling to get their story straight. Mene Pangalos, AstraZeneca’s head of biopharmaceuticals research and development, told reporters that the half-dose had been a “useful mistake,” the result of a measuring error. But the company’s CEO, Pascal Soriot, told Bloomberg, “it was not a mistake.” And two Oxford scientists who developed the vaccine, Sarah Gilbert and Adrian Hill, both told journalists that there hadn’t been an error. Gilbert told The Financial Times that there “wasn’t a mix-up in dosing,” while Hill told Reuters, “that is really not true” the Oxford team was unaware of the half-doses when it administered them.

Finally, after a few weeks, a fuller story emerged: there had been a problem with the method Oxford—which was running the U.K. clinical trial—used to verify the amount of chimpanzee virus particles in the doses a contract manufacturer had produced for it. This method meant the test showed twice as many virus particles as should have been in each vial, even though the manufacturer, using a different method, said its own test showed the vials contained the correct amount. Because at the time Oxford couldn’t be certain which measurement was correct, and because it didn’t want to delay the trial, it got permission from the U.K. medical regulator to just give volunteers half doses from that particular batch of vaccine. Why AstraZeneca and Oxford couldn’t have explained all this to begin with is less clear.

And these weren’t even the only transparency issues surrounding the half-dose trial. Reuters reported that while Oxford had informed the doctors running the clinical trial about the half-dose, telling them it was a planned change in the study protocol, and the U.K. medical regulator was fully informed, it hadn’t told the trial participants themselves. "Presenting the dosing variation as a planned change in the study is potentially a breach of trust if in fact the dosing resulted from an error,” Emma Cave, a professor of healthcare law at Durham University's law school, told the news agency.

The dosing confusion may hurt AstraZeneca’s efforts to obtain U.S. approval for its vaccine. The muddled results increased the chances that the FDA would not accept the results of the clinical trials conducted outside the U.S. as a basis for emergency use authorization for the vaccine.