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said Tuesday that the encouraging results that AstraZeneca announced about its Covid-19 vaccine may have been based on outdated and incomplete information about the vaccine’s effectiveness, an extraordinary blow to the credibility of an already embattled vaccine.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 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that has been helping to oversee AstraZeneca’s U.S. trial had “expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data.”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 exact nature of the institute’s concerns — and the effect they might have on how effective the vaccine appears to be — was unclear. But it is highly unusual for such a dust-up about the integrity of a clinical trial, especially one as high-profile as this, to be aired in public.
“This is really what you call an unforced error,” Dr. Anthony S. 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.”
AstraZeneca defended the data that it released on Monday, which showed the vaccine was 79 percent effective at preventing Covid-19. The company said in a statement on Tuesday that the interim results, which were current as of Feb. 17, 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 on Monday seemed encouraging — 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.
But the statement from the National Institute of Allergy and Infectious Diseases, which is part of the National Institutes of Health, raised the prospect that the company was presenting an overly optimistic interpretation of the data.
In recent days, the independent monitoring board’s analysis was delayed several times because the board had to ask for revised reports from those handling trial data on behalf of the company, according to a person familiar with the matter who was not authorized to discuss it publicly.
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 on 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 the 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 AstraZeneca released on 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 F.D.A. with a more comprehensive, recent set of data than what it disclosed on 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.
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 worldwide, 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 on 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 American 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 American officials’ trust in the company.
Last summer, at least some top F.D.A. officials learned only from news reports that AstraZeneca had paused its Phase ⅔ 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 the U.S. authorities.
The U.S. study was ultimately paused for seven weeks last fall, in part because AstraZeneca was slow to provide the F.D.A. 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.
Sheila Kaplan contributed reporting.
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