The results of AstraZeneca’s top US study on its COVID-19 vaccine, released in a press release Monday morning, exceeded the experts’ expectations. Less than a day later, U.S. health officials questioned the results, which have not yet been fully released.
In a study of more than 32,000 volunteers, roughly two-thirds of whom received the vaccine, the shots had 79% effectiveness in preventing symptomatic COVID-19, the company said. This was based on 141 cases of the disease occurring in the vaccine and placebo arms of the study. There were no cases of serious illness that required hospitalization in people given the vaccine, compared with five cases in the placebo arm, Anthony Fauci, chief of the National Institute of Allergy and Infectious Diseases (NIAID), said during a news conference at White House on Monday.
“Also, the good news is that there was comparable efficacy in terms of ethnicity and age,” said Fauci.
However, early Tuesday morning, NIAID released an extremely unusual statement that cast doubt on the company’s earnings report. The company “may have included out of date information from this study,” the statement said, “which may have provided an incomplete view of the efficacy data.”
The statement said the Data Safety Monitoring Board, the independent panel of medical experts tasked with overseeing AstraZeneca’s US study, notified NIAID and other health officials late Monday that it was “concerned” about the Way is how the results were presented.
On Tuesday morning, AstraZeneca responded to the concerns of the independent panel of experts. “The numbers released yesterday are based on a pre-determined interim analysis with a February 17th data cut-off date,” the company wrote. “We checked 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 promised to contact the independent panel immediately to “share our primary analysis with the most recent efficacy data” and publish the results within the next two days.
“As a member of the FDA Advisory Committee, I want to see all of the data – all of the data that has been collected. Any experience with it. Anything relevant to the decision, ”said Paul Offit, a vaccines expert at Philadelphia Children’s Hospital who sits on the FDA’s Vaccine Advisory Board. “Because the most important thing we consider with these vaccines is safety. Security, security, security. “
When Fauci appeared on Good Morning America Tuesday, he said the DSMB AstraZeneca wrote a “pretty harsh note” copying Fauci and saying the data in the press release “might actually be a bit misleading”.
“It is really unfortunate that this happened,” said Fauci. “This is really what you call an easy mistake because the fact is, this is very likely to be a very good vaccine.”
Other experts expressed similar concerns about how the company presented the data.
“It’s a good vaccine, but this kind of outreach makes things a little more chaotic and complicated. It’s harder for the public to figure out what’s going on. We just want a clean, straightforward process that is easy to interpret, ”Natalie Dean, biostatistician at the University of Florida, told BuzzFeed News. “We don’t really have any details. But just the look of it all doesn’t do anyone a favor. “
NIAID’s statement surprised many scientists.
“We are in uncharted territory. DSMBs usually don’t do such things.
and the bar for a federal agency to make a statement raising concerns
John Moore, a virologist at Weill Cornell Medical College in New York, told BuzzFeed News via email.
The statement from U.S. health officials is only the latest in a series of issues faced by the AstraZeneca COVID-19 vaccine studies.
Previous results from studies in the UK and Brazil conducted by Oxford University, which developed the vaccine, showed an overall effectiveness of around 70%. However, the scientists criticized those studies that included a number of experimental subgroups with patients of different ages, doses, and intervals between the two vaccine shots, which made the numbers very difficult to interpret.
It also meant the Oxford team couldn’t collect enough data to answer a key question: does the vaccine protect older people, who are most susceptible to COVID-19, from disease? This resulted in some nations, originally including Germany, delaying approval of the vaccine for use in older age groups.
According to the company’s press release, the new study finally has enough data to answer that question. Analysis of the results in people aged 65 and over found 80% effectiveness in preventing symptomatic COVID-19.
“These results confirm previous results seen in AZD1222 studies in all adult populations, but it is exciting to see similar efficacy results for the first time in people over 65,” said Ann Halsey of the University of Rochester School of Medicine, AstraZeneca, who jointly directed the study, said in the company’s press release.
Crucially, the new experiment, which is being carried out in the US and several other countries, is much simpler than the Oxford team’s experiment with just two experimental groups. The volunteers received either two doses of the vaccine four weeks apart or two injections of saline as a placebo control.
Moore, who was a prominent critic of the studies conducted by Oxford, described the US study to BuzzFeed News last week as a “rigid protocol” designed to provide results that are easier to evaluate.
The company has not yet released data beyond what is summarized in its press release, but said a paper “will be submitted for publication in a peer-reviewed journal.” The results will also be submitted as the centerpiece of AstraZeneca’s application to the FDA to approve the emergency vaccine in the United States.
“We are preparing to present these results to the US Food and Drug Administration and the launch of millions of doses across America should the vaccine receive US emergency approval,” said Mene Pangalos, executive vice president for biopharmaceuticals at AstraZeneca, in Monday’s press release.
These results suggest that AstraZeneca’s two-dose vaccine is slightly more effective at preventing COVID-19 than Johnson & Johnson’s single vaccine, which was 66% effective at preventing disease in its main study. Both appear to be less effective than the two-shot vaccines from Pfizer / BioNTech and Moderna, which were over 90% effective. All four vaccines appear to offer very strong protection against severe COVID-19.
The new trial results come after a safety crisis for the AstraZeneca vaccine last week when many European nations temporarily withdrew the vaccine from use after reports of rare but serious blood clots.
The European Medicines Agency then analyzed data for nearly 20 million people who were given the vaccine and found 18 cases of cerebral venous sinus thrombosis (CVST), which can prevent blood from draining 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 a link to the vaccine, the vaccine’s usefulness in preventing COVID-19 far outweighed the risk of these serious but very rare diseases and recommended resuming vaccination.
AstraZeneca said it didn’t find any cases of CVST in its study. This was expected because the condition is very rare and only about 21,000 people received the vaccine in the study.
Even ahead of the U.S. health officials’ statement on Tuesday, some experts were concerned that the vaccine’s troubled history might make it less attractive to the U.S. public than the alternatives already available.
“The FDA has a decision to make now, but even if this vaccine is approved, it could be difficult to convince the public to take,” Moore told BuzzFeed News Monday. “In situations like this, perception can become a reality and the public’s trust just may not be there right now.”
Last week, the Biden government announced it would loan millions of pre-made doses of the AstraZeneca vaccine to Canada and Mexico, where it has already been approved.
Dan Vergano contributed to the coverage of this story.