Published NOVEMBER 26, 2020
Updated NOVEMBER 26, 2020
LONDON — The announcement this week that a cheap, easy-to-make coronavirus vaccine appeared to be up to 90 per cent effective was greeted with jubilation. “Get yourself a vaccaccino,” a British tabloid celebrated, noting that the vaccine, developed by AstraZeneca and the University of Oxford, costs less than a cup of coffee.
But since unveiling the preliminary results, AstraZeneca has acknowledged a key mistake in the vaccine dosage received by some study participants, adding to questions about whether the vaccine’s apparently spectacular efficacy will hold up under additional testing.
Scientists and industry experts said the error and a series of other irregularities and omissions in the way AstraZeneca initially disclosed the data have eroded their confidence in the reliability of the results.
Officials in the United States have noted that the results were not clear. It was the head of the flagship federal vaccine initiative — not the company — who first disclosed that the vaccine’s most promising results did not reflect data from older people.
The upshot, the experts said, is that the odds of regulators in the United States and elsewhere quickly authorising the emergency use of the AstraZeneca vaccine are declining, an unexpected setback in the global campaign to corral the devastating pandemic.
“I think that they have really damaged confidence in their whole development program,” said Mr Geoffrey Porges, an analyst for the investment bank SVB Leerink.
In an interview Wednesday, Dr Menelas Pangalos, the AstraZeneca executive in charge of much of the company’s research and development, defended the company’s handling of the testing and its public disclosures.
He said the error in the dosage was made by a contractor, and that, once it was discovered, regulators were immediately notified and signed off on the plan to continue testing the vaccine in different doses.
Asked why AstraZeneca shared some information with Wall Street analysts and some other officials and experts but not with the public, he responded, “I think the best way of reflecting the results is in a peer-reviewed scientific journal, not in a newspaper.”
The regimen that appeared to be 90 per cent effective was based on participants receiving a half dose of the vaccine followed a month later by a full dose; the less effective version involved a pair of full doses.
AstraZeneca disclosed in its initial announcement that fewer than 2,800 participants received the smaller dosing regimen, compared with nearly 8,900 participants who received two full doses.
The biggest questions were, why was there such a large variation in the effectiveness of the vaccine at different doses, and why did a smaller dose appear to produce much better results? AstraZeneca and Oxford researchers said they did not know.
Crucial information was also missing. The company said that the early analysis was based on 131 symptomatic Covid-19 cases that had turned up in study participants.
But it did not break down how many cases were found in each group of participants — those who received the half-strength initial dose, the regular-strength initial dose and the placebo.
Bigger problems soon surfaced.
Dr Pangalos told Reuters on Monday that the company had not intended for any participants to receive the half dose. British researchers running the trial there had meant to give the full dose initially to volunteers, but a miscalculation meant they were mistakenly given only a half dose.
Dr Pangalos described the error as “serendipity,” allowing researchers to stumble onto a more promising dosing regimen.To many outside experts, that undercut the credibility of the results because the closely calibrated clinical trials had not been designed to test how well a half-strength initial dose worked.
The company’s initial announcement didn’t mention the accidental nature of the discovery.
Then, on Tuesday, Dr Moncef Slaoui, the head of Operation Warp Speed, the US initiative to fast-track coronavirus vaccines, noted another limitation in AstraZeneca’s data. On a call with reporters, he suggested that the participants who received the half-strength initial dose had been 55 years old or younger.
Dr Pangalos confirmed that Wednesday, saying the participants received the half-strength dose over a matter of weeks before the error was discovered.
The fact that the initial half-strength dose wasn’t tested in older participants, who are especially vulnerable to Covid-19, could undermine AstraZeneca’s case to regulators that the vaccine should be authorised for emergency use.
AstraZeneca has not been testing the promising half-strength initial dose in its ongoing US trial. The company said it would work with the agency to add it as quickly as possible to that trial.Dr Pangalos said the company is planning a global trial to compare the two dosing regimens. The number of participants it will enroll hasn’t yet been determined, but it will be in the thousands.
“The only way they’re going to find out is by specifically and deliberately testing this serendipitous observation,” Dr Moore said. “The onus is on them to prove the speculation.” THE NEW YORK TIMES
Read more at https://www.nytimes.com/2020/11/25/business/coronavirus-vaccine-astrazeneca-oxford.html