Thursday , January 21 2021

AstraZeneca defends the dosing error in the COVID-19 trial

The CEO of AstraZeneca PLC withdrew on Wednesday against criticism that the company did not reveal enough data from a clinical trial of the Covid-19 vaccine earlier this week and acknowledged skepticism about the vaccine’s 90% effectiveness in a group of patients who were accidentally given a lower dose. than provided.

“I will not pretend that it is not an interesting result, because it is – but I definitely do not understand it and I think none of us understand that,” said Mene Pangalos, executive vice president of AstraZeneka for biopharmaceuticals research and development. . “It was a surprise for us.

The British company said on Monday that the vaccine it was developing with the University of Oxford was on average about 90% effective in preventing Covid-19 when volunteers were given half a dose, followed by a full dose a month or more later, but only 62% effective when two full doses are given. The data combined the results of surveys from the UK and Brazil.

U.S. regulators have banned vaccines from being approved at 50% effectiveness, but vaccines being developed by Moderna and partners Pfizer and Germany’s BioTech SE have set the benchmark even higher with study results showing greater efficiencies of 90%. These vaccines use new gene-based technology that, despite impressive clinical results to date, requires recordings to be stored at sub-zero temperatures. The AstraZeneca vaccine can be stored in a more standard refrigerator, which may make it more attractive to low- and middle-income nations.

In the days following the announcement of the results, independent scientists and US government officials said the data was further evidence that vaccines could prevent Covid-19, but they also warned that the 90% effectiveness rate could not be kept below further. analysis

AstraZeneka said in interviews with news media on Monday that the half-dose regimen was the result of a manufacturing error, which neither the company nor Oxford initially mentioned in their press releases announcing the results.

The dosing error was identified after an investigating researcher noticed that volunteers did not have such an inflammatory response to the shot that prompted researchers to analyze the vaccine supply and find that they had miscalculated the dose, Dr Pangalos said.

AstraZeneka and Oxford briefed regulators in the UK, US and European Union and changed the design of the study to include the half-dose group in their analysis.

“The mistake is actually irrelevant,” said Dr Pangalos. “No matter how you reduce the data – even if you only believe in full-dose, full-dose data…

Oxford researchers said Monday that lower doses may be more effective because they more accurately reflect the natural immune response to viruses, but that they will need to further examine the findings to know for sure.

Other factors may also play a role. The half-dose was given only to volunteers 55 and younger, while the full-dose group included older patients, said Dr. Moncef Slaoui, chief scientific adviser to the US government’s Speed ​​Speed ​​Initiative, on call. with reporters on Tuesday the first revelation of a shortage of older participants in the half-dose group. It is also possible that the difference between the groups is a statistical fraud and a result of chance, he said.

“There are a lot of variables that we need to understand,” Dr. Slawi said. “It is unlikely, but it may still be a random difference.”

AstraZeneca plans to test the half-dose regimen in a large, ongoing study in the United States, which is expected to enroll more than 30,000 volunteers, Dr. Pangalos said. The study has enrolled more than 11,000 volunteers and may soon yield results given the progression of the pandemic, Dr Slawi said.

Dr Pangalos said there was a theoretical explanation for why a lower first dose might work, but that he would not speculate until researchers looked at the data further. “I will not shake hands with immunologists,” he said. “Until I see some data that gives me some science behind it, I will say ‘I do not know.’

Some scientists have criticized AstraZeneca for not revealing key data from the test results, such as the number of infections that have occurred in groups of patients and broken down by age and severity of the disease – although the company says it has not developed patients receiving severe disease vaccine or required hospitalization.

“AstraZeneka provided very little real information for anyone to independently assess how vaccine trials are conducted,” said Shane Crotti, a vaccine and infectious disease researcher at the La Jola Institute for Immunology. “It’s perfectly reasonable for people to be skeptical.

Dr Pangalos said the researchers only received the data last weekend and were working to quickly publish the full data in a peer-reviewed journal. “The right way to publish and document the results is in a scientific journal and all this data will be published next week or so,” he said.

Write to Joseph Walker at [email protected] and eneni Strasbourg at [email protected]

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