AstraZeneca and Oxford University have given conflicting accounts of how they came upon the most effective dosing pattern for their COVID-19 vaccine, a rare instance of public dissension between major institutions collaborating on a pivotal project.
The discrepancy, reported for the first time by Reuters, centres on the regimen administered to a smaller group of volunteers in the late-stage trials, of half a dose followed by a full dose. This diverged from the original plan of two full doses, given to the majority of participants.
The half-dose pattern was found to be 90% effective, versus the 62% success rate of the two-full-dose main study, based on interim data.
AstraZeneca’s research chief told Reuters 10 days ago, when interim trial data was released, the half-dose was given inadvertently as a first shot to some trial participants, and emerged as a stroke of fortune – “serendipity” – that scientists expertly harnessed.
This narrative was refuted by a leading Oxford University scientist, however, who told Reuters on Monday that the half-dose shot was given deliberately after thorough consultations.
Uncertainty over how the dosing regimen came about raises questions about the robustness of the data, according to some experts who said it risked slowing down the process of gaining regulatory approval for the shot and denting public confidence.
“These differing accounts are worrying,” Eleanor Riley, a professor of immunology and infectious disease at the University of Edinburgh, told Reuters.
“Trust is at a premium when it comes to vaccines and we must not do anything that might in any way undermine it.”
There is also the potential impact on AstraZeneca, whose shares have underperformed rival vaccine developers that have also announced successful results, partly due to concerns from scientists about the relatively small sample size for the half-dose sub-group that led to the 90% efficacy finding.
AstraZeneca declined to comment about the conflicting accounts.
An Oxford University spokesman said that a media briefing would be held once the detailed interim trial results are peer-reviewed and published in a scientific journal.
“This will be the appropriate time to discuss the complicated intricacies of the global trial design,” he said.
OXFORD SCIENTIST: ‘THAT’S NOT TRUE’
More than 20 countries, including many poorer nations, have ordered the vaccine, which costs less than some rival shots and is easier to distribute.
The trial data was released on Nov. 23, when developers hailed “a vaccine for the world”. Hours later, AstraZeneca’s head of non-oncology research and development, Mene Pangalos, told Reuters the half-dose schedule had been a case of miscalculated dosing given to some volunteers.
It came to light, he said, after side effects in some participants turned out to be surprisingly mild.
“The reason we had the half dose is serendipity,” he said.
However, professor Adrian Hill, director of the Jenner Institute at the University of Oxford which co-developed the COVID-19 shot with AstraZeneca and led the UK trials, told Reuters in a phone interview on Monday that it was a conscious decision by researchers to administer a lower dose.
“There had been some confusion suggesting that we didn’t know we were giving a half dose when we gave it – that is really not true,” he said.
“What we were aware of was that we were using a different batch of a vaccine from a different manufacturer. We knew the measurements on it and we had been in discussions with regulators about how to move forward.”
“The dosing that we started with that new batch, was a half dosing compared to what we had used previously,” he added, without giving details about the different manufacturer.
Both AstraZeneca and Oxford University scientists said they had consulted health regulators and were given the go-ahead to continue with the half-dose among a limited group of volunteers in Britain, and to follow up with the full-dose booster shot at the scheduled time.
Britain’s Medicines and Healthcare products Regulatory Agency (MHRA) said its rolling review of the vaccine is ongoing and that any vaccine must undergo robust clinical trials in line with international standards.
“No vaccine would be authorised for supply in the UK unless the expected standards of safety, quality and efficacy are met,” a spokeswoman said. She did not comment on when the regulator was consulted about the half-dose regimen.