Who and why has doubts about the data of the Astrazeneca anti Covid vaccine
The data of the anti Covid vaccine communicated by Astrazeneca, the questions of analysts and experts and the position of the pharmaceutical company in the analysis of the New York Times
This week's announcement that an inexpensive, easy-to-produce coronavirus vaccine appears to be up to 90% effective was greeted with jubilation. "Get a vaccine," celebrated a British tabloid, noting that the vaccine, developed by AstraZeneca and the University of Oxford, costs less than a cup of coffee.
But since presenting the preliminary results, AstraZeneca has acknowledged a key mistake in the vaccine dosage received by some study participants, which adds to the question of whether the vaccine's seemingly spectacular effectiveness will hold up under further testing. Scientists and industry experts said the error and a number of other irregularities and omissions in how AstraZeneca initially disclosed the data eroded their confidence in the reliability of the results, the NYT writes.
Officials in the United States noted the results were unclear. It was the head of the federal vaccine initiative – not the company – who first revealed that the most promising results from the vaccine did not reflect data from older people.
The result, experts said, is that the likelihood of regulators in the United States and elsewhere quickly authorizing emergency use of the AstraZeneca vaccine is decreasing, an unexpected setback in the global campaign to stem the devastating pandemic.
"I think they have really damaged confidence in their entire development program," said Geoffrey Porges, an analyst at investment bank SVB Leerink.
Michele Meixell, spokesman for AstraZeneca, said the experiments "were conducted to the highest standards".
In an interview on Wednesday, Menelas Pangalos, the AstraZeneca executive responsible for much of the company's research and development, defended test management and public disclosure. He said the dosing mistake was made by a contractor and that, once discovered, regulators were immediately notified and signed the plan to continue testing the vaccine in different doses.
When asked why AstraZeneca shared some information with Wall Street analysts and some other officials and experts, but not with the public, he replied: “I think the best way to reflect the findings is in a peer-reviewed scientific journal. -reviewed, not in a newspaper ".
AstraZeneca was the third company this month to report encouraging results on the first results of a coronavirus vaccine candidate. At first glance, on Monday morning, the results looked promising. Depending on the strength at which the doses were administered, the vaccine appeared to be 90% or 62% effective. The average effectiveness, the developers said, was 70 percent.
Almost immediately, however, there were doubts about the data.
The regimen that appeared to be 90% effective was based on the participants receiving a half dose of the vaccine followed by a full dose one month later; the less effective version involved a couple of full doses. AstraZeneca revealed in its initial announcement that fewer than 2,800 participants received the smaller dosage regimen, compared to nearly 8,900 participants who received two full doses. The biggest questions were: why was there such a large variation in vaccine efficacy at different doses and why a smaller dose seemed to produce so much better results? Researchers from AstraZeneca and Oxford said they didn't know.
Crucial information was also missing. The company said the initial analysis was based on 131 symptomatic cases of Covid-19 that emerged in the study participants. But he didn't break down how many cases were found in each group of participants – those who received the starting half dose, the regular starting dose, and the placebo.
"The press release raised more questions than answers," said John Moore, professor of microbiology and immunology at Weill Cornell Medical College. Adding confusion, AstraZeneca pooled the results of two differently designed clinical trials in Britain and Brazil, a break from standard practice in reporting drug and vaccine study results.
"I just can't understand where all the information comes from and how it fits together," said Natalie Dean, a biostatistician and an expert in vaccine trial design at the University of Florida. He tweeted that AstraZeneca and Oxford "score poorly for transparency and rigor when it comes to the vaccine trial results they reported."
With AstraZeneca's shares falling on Monday, company executives held several private conference calls with industry analysts in which they revealed details that weren't in the public announcement, including how the Covid-19 cases split. between the different groups. Such disclosures to analysts are not uncommon in the industry, but they often generate criticism as to why the details have not been shared with the public.
Bigger problems soon emerged.
Mr. Pangalos told Reuters on Monday that the company did not intend the participants to receive the half dose. The UK researchers who conducted the trial intended to initially administer the full dose to the volunteers, but a miscalculation meant that they were mistakenly given only half a dose. Mr. Pangalos described the mistake as "serendipity," allowing researchers to stumble upon a more promising dosing regimen.
For many outside experts, this undermined the credibility of the results because carefully calibrated clinical trials were not designed to test how well an initial half dose worked.
The company's initial announcement did not mention the accidental nature of the discovery.
"The reality is that it could end up being a pretty useful mistake," he said Wednesday in the New York Times interview. “He wasn't putting anyone in danger. It was a dosing mistake ”. Everyone was moving very fast. We corrected the error and continued with the study, without changes to the study, and agreed with the regulator to include those patients in the study analysis as well. "
He added: “What is there to reveal? It doesn't really matter if it was done on purpose or not ”.
In the statement attributed to Oxford, AstraZeneca spokesperson Ms. Meixell said the error stemmed from a problem, which has since been resolved, with the way some of the vaccine doses were manufactured.
Then, on Tuesday, Moncef Slaoui, the head of Operation Warp Speed, the US initiative to speed up coronavirus vaccines, noted another limitation in AstraZeneca's data. In a phone call with reporters, he suggested that the participants who received the initial half dose of the coronavirus were 55 or younger. Mr. Pangalos confirmed that Wednesday, saying participants received half a dose of strength within a few weeks before the error was discovered.
The fact that the initial half dose has not been tested in older participants, who are particularly vulnerable to Covid-19, could undermine AstraZeneca's case to regulators that the vaccine should be cleared for emergency use.
Stephanie Caccomo, a spokesperson for the Food and Drug Administration, declined to comment on whether the dosing error would harm the vaccine's chances of being licensed. The FDA said it expects the vaccines to be at least 50 percent effective in preventing or reducing disease severity, a bar the vaccine seems to have canceled even in the group that got the two full doses.
Shares of AstraZeneca fell roughly 5 percent this week, while broader equity indices rose to record highs. Investors appear to be disappointed with the murky results, especially when compared with much clearer data released by two of AstraZeneca's main rivals in the race for a coronavirus vaccine. Pfizer and Moderna said this month that their vaccines, which use a technology known as "messenger RNA," appear to be about 95 percent effective. Both offers seem almost certain to win FDA emergency clearance in the coming weeks.
The AstraZeneca vaccine, which uses a different approach involving a chimpanzee virus to provoke an immune response to the coronavirus, has all the hallmarks of a blockbuster. It's inexpensive – just a few dollars per dose – and easy to mass produce. Unlike Pfizer's and Moderna's vaccines, AstraZeneca's can be stored for months in regular refrigerators. The company has estimated that it will be able to produce around three billion doses next year, enough to vaccinate nearly a fifth of the global population.
Compared to most other major Covid-19 vaccine developers, AstraZeneca is inexperienced when it comes to vaccines. And even before the chaotic release of the results, the company was under scrutiny for handling the testing process. In September, AstraZeneca suspended clinical trials worldwide after one participant became ill – but the company did not promptly publicly announce the decision. AstraZeneca also came under fire for providing details on the nature of the disease in a private conference call with investors hosted by investment bank JP Morgan, rather than disclosing the information to the public. Both of these developments were first reported by STAT, which covers health and science news.
Ever since the Oxford-AstraZeneca team emerged as a leader in the race to develop a vaccine this spring, British Prime Minister Boris Johnson has embraced the effort. The government preordered 100 million doses and called the research one of the country's most important contributions to the fight against the pandemic.
Based on Monday's findings, Mr Johnson said the vaccine "has the makings of a wonderful British scientific achievement."
In the United States, which has ordered at least 300 million doses of AstraZeneca's vaccine, the regulatory path is unclear. AstraZeneca was cautious on Monday about its plans to get regulatory approval. The company said it would ask the Food and Drug Administration to formally submit its findings to apply for an emergency clearance.
AstraZeneca has not tested the promising starting half dose in its ongoing trial in the United States. The company said it would work with the agency to add it as quickly as possible to that trial.
Mr. Pangalos said the company is planning a global trial to compare the two dosing regimens. The number of participants he will register has not yet been determined, but will be in the thousands.
(Extract from the press review of Eprcomunicazione )
This is a machine translation from Italian language of a post published on Start Magazine at the URL https://www.startmag.it/mondo/vaccino-astrazeneca-covid-dati-dubbi/ on Sat, 28 Nov 2020 06:43:21 +0000.