Results of AstraZeneca’s main US trial of its COVID-19 vaccine issued by press release Monday morning exceeded expert expectations. But less than a day later, U.S. health officials questioned the results, which have not yet been published in full.
In a test with the participation of more than 32,000 volunteers, about two-thirds of whom received the vaccine, the shots had a 79% effectiveness in preventing symptomatic COVID-19, the company said. This was based on 141 cases of the disease that occurred through the vaccine and placebo arms of the trial. There were no cases of serious illness requiring hospitalization among people who received the vaccine, compared with five of the placebo arm, Said Monday at a White House press conference the head of the National Institute of Allergy and Infectious Diseases (NIAID), Anthony Fauci.
“The good news is also that there was a comparable effectiveness between ethnicity and age,” Fauci said.
But Tuesday morning, NIAID issued a very unusual statement questioning the company’s report on its results. The company “may have included obsolete information from this trial,” the statement said, “which may provide an incomplete view of the efficacy data.”
The statement said that by the end of Monday, the Data Security Monitoring Board, the independent group of medical experts in charge of overseeing AstraZeneca’s trial in the United States, notified NIAID and other health officials that it “Concerned” by the way the results had been presented.
On Tuesday morning, AstraZeneca responded to concerns raised by the independent expert group. “The numbers published yesterday they were based on a pre-specified interim analysis with a February 17 data limit, “the company wrote.” We reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis. We are now completing the validation of the statistical analysis ”.
The company pledged to “collaborate immediately” with the independent group to “share our core analysis with the most up-to-date performance data,” saying it would issue results in the next two days.
“As a member of the FDA advisory committee, I want to see all the data, all the data that has been collected. Any experience with that. Anything that is relevant to the decision,” said vaccine expert Paul Offit of the Philadelphia Children’s Hospital, which is part of the FDA’s vaccine advisory committee. “Because the most important thing we take into account with these vaccines is safety. Security, safety, security “.
Appears Good morning America on Tuesday, Fauci said the DSMB wrote a “rather harsh note” to AstraZeneca, copying Fauci, saying they felt the data in the press release “in fact, could be a bit misleading.”
“It’s really unfortunate that this is happening,” Fauci said. “That’s really what you call an unforced error, because the fact is, it’s very likely to be a very good vaccine.”
Other experts expressed similar concerns about how the company had presented its data.
“It’s a good vaccine, but this kind of thing about public relations makes it a little more messy and complicated. It’s harder for the public to analyze what’s going on. We just want a clean, simple process that is easy to interpret, ”Natalie Dean, a biostatistician at the University of Florida, told BuzzFeed News. “It simply came to our notice then. But only the appearance of all this does no favor to anyone.
The NIAID statement surprised many scientists.
“We are in an unknown territory. DSMBs don’t usually do things like that,
and the bar for a federal agency to issue a statement of concern
about a high-profile corporate trial is very, very high, ”John Moore, a virologist at Weill Cornell Medical College in New York, told BuzzFeed News by email.
The statement by U.S. health officials is just the latest in a series of problems the AstraZeneca COVID-19 vaccine trials have faced.
Previous results from trials conducted in the UK and Brazil, led by Oxford University, which developed the vaccine, had indicated around 70% efficacy overall. But scientists were critical of these trials, which had included a number of experimental subgroups with patients of different age ranges, doses, and intervals between the two shots of the vaccine, which made it very difficult to interpret the numbers.
This also meant that the Oxford team had not been able to gather enough data to answer a key question: Does the vaccine protect older people who are more vulnerable to COVID-19 from getting sick? This caused some nations, initially including Germany, to delay vaccine authorization for use in older age groups.
The new trial finally has enough data to answer that question, according to the company’s statement. Analysis of outcomes among people 65 years of age or older indicated 80% efficacy in the prevention of symptomatic COVID-19.
“These results confirm previous results observed in AZD1222 trials in all adult populations, but it is exciting to see similar efficacy results in people over 65 for the first time,” said Ann Halsey of the University’s School of Medicine. Rochester, AstraZeneca, said in the company statement.
Crucially, the new trial, held in the United States and several other countries, is one much simpler design than those led by the Oxford team, with only two experimental groups. Volunteers were given two doses of the vaccine four weeks apart or two saline injections as a placebo control.
Moore, who has been a prominent critic of the Oxford trials, last week described the U.S. trial in BuzzFeed News as a “rigid protocol” that should produce conclusions that are easier to assess.
The company has not yet published any data beyond the results summarized in its press release, but said a document “will be submitted for publication in a peer-reviewed journal.” The results will also be presented as the central axis of AstraZeneca’s request to the FDA to authorize the vaccine for emergency use in the U.S.
“We are preparing to submit these findings to the U.S. Food and Drug Administration and for the deployment of millions of doses across America if the vaccine is granted U.S. emergency use authorization,” he said. said Mene Pangalos, AstraZeneca’s executive vice president for biopharmaceuticals, in Monday’s statement. .
These results suggest that the AstraZeneca two-dose vaccine is slightly more effective in preventing COVID-19 than the single-shot vaccine manufactured by Johnson & Johnson, 66% effective in disease prevention in its main trial. Both appear to be less effective than the two-shot vaccines manufactured by Pfizer / BioNTech and Moderna, which exceeded 90% efficacy. All four vaccines appear to provide very strong protection against severe COVID-19.
The new test results come after a security scare against the AstraZeneca vaccine last week, when many European countries temporarily withdrew the vaccine from its use after reports of rare but severe blood clots.
The European Medicines Agency then analyzed data from almost 20 million people who received the vaccine, finding 18 cases. cerebral venous sinus thrombosis (CVST), which can prevent drainage of blood from the brain and cause bleeding, and seven cases of disseminated intravascular coagulation (DIC), which causes clots in tiny blood vessels throughout the body. Although the agency could not rule out any link to the vaccine, it said the benefits of the vaccine in preventing COVID-19 far exceeded the risk of these serious but very rare conditions, and it is recommended to resume vaccination.
AstraZeneca said it did not find any CVST case in its trial. This was expected as the disease is very rare and only about 21,000 people received the vaccine during the trial.
Even before Tuesday’s statement by U.S. health officials, some experts were concerned that the conflicting history of the vaccine would make it less appealing to the American public than the alternatives already available.
“Now the FDA has to make a decision, but even if this vaccine is approved, it could be difficult to convince the public to take it,” Moore told BuzzFeed News Monday. “Perception can come true in situations like this, and public confidence may simply not be there.”
Last week, the He announced the administration of Biden which would provide millions of prefabricated doses of the AstraZeneca vaccine in Canada and Mexico, where it has already been approved.
Dan Vergano has contributed to the notification of this story.