may have been based on outdated and incomplete information about the vaccine’s effectiveness, an extraordinary blow to the credibility of an already embattled vaccine.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that has been helping to oversee AstraZeneca’s U.S. trial had “expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data.”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 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.”
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 on Monday without conducting the full analysis the board requested, possibly casting its vaccine in an overly favorable light.
AstraZeneca defended the data it released on Monday, which it said showed the vaccine was 79 percent effective at preventing Covid-19. The company said on 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 on 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.
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 Dr. 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.
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..