Federal health officials said Tuesday that the encouraging results that AstraZeneca announced about its COVID-19 vaccine may have been based on outdated and incomplete information about the vaccine’s effectiveness, an extraordinary blow to the credibility of an already embattled vaccine.
In a statement released shortly after midnight, the National Institute of Allergy and Infectious Diseases said that an independent panel of medical experts that has been helping to oversee AstraZeneca’s U.S. trial had “expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data.”
The public airing of a conflict between a pharmaceutical company and a board overseeing a clinical trial is highly unusual. It is almost certain to trigger extra scrutiny of the vaccine by the Food and Drug Administration and other regulators if AstraZeneca seeks emergency authorization of its vaccine in the United States.
“This is really what you call an unforced error,” Dr. Anthony Fauci, the nation’s leading infectious-disease expert, said on “Good Morning America” on Tuesday morning. “Because the fact is: This is very likely a very good vaccine, and this kind of thing does, as you say, do nothing but really cast some doubt about the vaccines and maybe contributes to the hesitancy.”
The friction with the independent monitoring board revolved around how AstraZeneca was determining whether participants in the clinical trial had possible or actual cases of COVID-19, according to a person familiar with the situation. The independent monitoring board twice pushed AstraZeneca to take a more rigorous approach, telling the company it had sufficient information to determine how many trial participants had the disease. That had the potential to reduce the vaccine’s apparent effectiveness.
But AstraZeneca unveiled its interim results Monday without conducting the full analysis the board requested, possibly casting its vaccine in an overly favorable light.
AstraZeneca on Monday defended the data it released, which it said showed the vaccine was 79% effective at preventing COVID-19. The company said Tuesday that the interim results appeared to be “consistent” with more recent data collected during the trial. AstraZeneca said it would immediately share its latest efficacy data with the monitoring board. The company said it would reissue fuller results within 48 hours.
The results that AstraZeneca announced Monday were a badly needed dose of good news, especially because they came at a moment when concerns about the vaccine’s safety had led more than a dozen countries, mostly in Europe, to temporarily suspend the shot’s use over concerns about possible rare side effects. The results not only affirmed the vaccine’s safety but also made the vaccine look more effective than it appeared in earlier trials.
The news sent AstraZeneca shares up about 4% Monday.
But members of the independent monitoring board were surprised by the company’s announcement.
“They got concerned and wrote a rather harsh note to them and with a copy to me, saying that in fact they felt that the data that was in the press release were somewhat outdated and might in fact be misleading a bit and wanted them to straighten it out,” said Fauci, who runs the National Institute of Allergy and Infectious Diseases.
That prompted the overnight statement from the infectious-disease institute, which is part of the National Institutes of Health.
AstraZeneca’s stock fell more than 3.5% in early trading Tuesday.
Companies sponsoring drug or vaccine trials typically wait for the monitoring board to review analyses and conclude that the study has yielded an answer before they announce trial results. Company executives do not see the results of the study until the monitoring board reports their study data back to the company. The monitoring board ultimately conveyed the results of the study to AstraZeneca in a meeting over the weekend, leading to the company’s announcement Monday morning.
The monitoring board’s slow progress fueled concerns among federal officials that AstraZeneca may have been sitting on the data or that the monitoring board had concerns about the way the data it was reviewing had been presented.
An AstraZeneca spokeswoman, whom the company declined to name, said Friday that it was “completely incorrect” that the trial data had formatting problems or had not been submitted to the monitoring board in a clean fashion.
“As is often the case,” the spokeswoman said, monitoring boards “can request new or clarifying analyses of data from the trial. This would enable them to ensure the robustness of their determinations.”
The national institute’s statement, issued shortly after midnight, stunned experts. Dr. Eric Topol, a clinical trials expert at Scripps Research in San Diego, said it was “highly irregular” to see such a public display of friction between a monitoring board and a study sponsor, which are typically in close concordance.
“I’ve never seen anything like this,” he said. “It’s so, so troubling.”
AstraZeneca’s relationship with U.S. authorities has been fraught since last year, when senior health officials believed the company was not being forthright about the design of its clinical trials, its results and safety issues. That skepticism carried over to last week, when senior officials at a number of federal health agencies grew suspicious about why AstraZeneca had not announced data from its U.S. study.
That U.S. trial, which involved more than 32,000 participants, was the largest test of its kind for the shot. The results that AstraZeneca released Monday were from an interim look at the data after 141 COVID-19 cases had turned up among volunteers.
The company had not disclosed until Tuesday how up-to-date those data were. That information is important, because sometimes a more current look at clinical trial results can present a different effectiveness and safety.
If the analysis was conducted on data from a month or two ago, it is possible that a more current look would present a different picture of the vaccine’s effectiveness and safety. The company has said it will provide the FDA with a more comprehensive, recent set of data than what it disclosed Monday. Although no clinical trial is large enough to rule out extremely rare side effects, AstraZeneca reported that its study turned up no serious safety issues.
The fresh data may have arrived too late to make much difference in the United States, where the vaccine is not yet authorized and is unlikely to become available before May. By then, federal officials predict, there will be enough vaccine doses for all of the nation’s adults from the three vaccines that have already been authorized: Pfizer-BioNTech, Moderna and Johnson & Johnson.
Even so, the better-than-expected results were seen as a heartening turn for AstraZeneca’s shot, whose low cost and simple storage requirements have made it a vital piece of the drive to vaccinate the world.
The results were also thought to ease concerns about the AstraZeneca vaccine in Europe. Regulators there said last week that the shot was “safe and effective,” having conducted a review after a small number of people who had recently been inoculated developed blood clots and abnormal bleeding. The U.S. trial did not turn up any sign of such problems, although some safety issues can only be detected in the real world, once a drug or vaccine has been widely used.
Many millions of people have received the AstraZeneca shot, including more than 17 million in Britain and the European Union, almost all without serious side effects. In an effort to increase public confidence, many European political leaders have gotten the injections in recent days. The AstraZeneca vaccine has also been administered in the past week to leaders in South Korea, Taiwan and Thailand.
AstraZeneca said Monday that it would continue to analyze the new data and prepare to apply in the coming weeks for emergency authorization in the United States. The vaccine has already been approved in more than 70 countries, but clearance from U.S. regulators would bolster its global reputation.
The statement from the infectious disease institute comes after a series of miscues and communication blunders by AstraZeneca dating to last year that have eroded U.S. officials’ trust in the company.
Last summer, at least some top FDA officials learned only from news reports that AstraZeneca had paused its Phase 2/3 vaccine trial in Britain after a participant developed neurological symptoms. Then in September, after another participant in the British study fell ill with similar symptoms, AstraZeneca halted its trials globally but failed to promptly notify U.S. authorities.
The U.S. study was ultimately paused for seven weeks last fall, in part because AstraZeneca was slow to provide the FDA with evidence that the vaccine had not caused the neurological symptoms. Investigators ultimately concluded that the illnesses could not be linked to the vaccine. Still, the delay was a key reason that AstraZeneca fell so far behind the three other manufacturers whose vaccines have been granted emergency authorization in the United States.