Just hours after AstraZeneca announced encouraging news on Monday about the effectiveness of its Covid-19 vaccine, a group of medical experts tasked with overseeing the company’s clinical trial made a highly unusual accusation: AstraZeneca essentially had it Dates selected to make the vaccine look better.
The allegation, in a two-page letter sent to the company and federal officials on Monday, was a new blow to the credibility of a vaccine whose low price and relatively easy storage have made it critical to the global fight against the coronavirus pandemic.
The private letter, described by people who read it, accused AstraZeneca of compromising the integrity of a closely watched clinical trial.
“Decisions like these undermine public confidence in the scientific process,” the regulator wrote.
The letter prompted the National Institute for Allergies and Infectious Diseases to issue a sharply worded statement shortly after midnight on Tuesday, exposing the panel’s concerns.
The battle is about the level of effectiveness of a vaccine that is undeniably effective.
While AstraZeneca said its vaccine appeared 79 percent effective in preventing Covid-19 on Monday, the panel of independent experts said the real figure could be between 69 percent and 74 percent. The mass availability of a vaccine with as much as 69 percent effectiveness could help the world defeat the coronavirus.
However, the public broadcast of a conflict between a pharmaceutical company and a board member overseeing a clinical trial is virtually unknown. It is certain that the Food and Drug Administration and other regulatory agencies will trigger an additional review of the vaccine if AstraZeneca is expected to obtain approval for emergency use in the US.
Repeated problems with the data provided by AstraZeneca have shaken the confidence of American regulators and threaten to throw a global cloud over the company’s vaccine.
“Unfortunately, such things could lead to a lack of confidence in the process,” said Dr. Anthony S. Fauci, the nation’s leading infectious disease expert.
Fears that the vaccine could cause rare but serious side effects had led more than a dozen countries, mostly in Europe, to temporarily stop using the shot. European regulators confirmed the vaccine’s safety last week. The results of Monday’s US study, which provided the cleanest and most complete picture of the vaccine’s effectiveness, seemed to confirm the European decision and made the vaccine look more effective than previous studies.
In short, it strengthened the credibility of arguably the most important vaccine in the world, approved in more than 70 countries. However, the institute’s overnight announcement immediately raised new questions about him and AstraZeneca.
“If they keep making these casual mistakes it will damage confidence and seriously affect our ability to fight this pandemic,” said Dr. Peter J. Hotez, vaccine expert at Baylor College of Medicine.
The question is whether the publication of data should count recently confirmed cases of Covid-19 among the participants. The board of directors urged AstraZeneca representatives last week to go through a backlog of potential cases and classify whether or not they were Covid-19. This had the potential to affect the vaccine’s rate of effectiveness for better or for worse.
The requested analysis found that the vaccine was between 69 and 74 percent effective, according to regulatory letters.
When AstraZeneca announced its interim results on Monday, the company did not count these reclassified Covid-19 cases. As a result, it was reported that the vaccine appeared to be 79 percent effective in preventing the disease.
March 23, 2021, 6:19 p.m. ET
Federal officials were stunned to discover on Monday that AstraZeneca had released the results, despite the fact that the monitoring body had been pushing for and eventually receiving updated data for days. Until then, Dr. Fauci publicly welcomed the results at a White House briefing, and the company had been showered with positive media coverage. AstraZeneca’s shares rose around 4 percent on Monday.
AstraZeneca on Tuesday defended its actions, saying the interim results appeared to be “consistent” with more recent data collected during the trial. The company announced that it would immediately share its latest data with the Monitoring Board and republish more comprehensive results within 48 hours.
The company’s shares fell 3.5 percent on Tuesday.
Dr. H. Cody Meissner, an infectious disease expert at Tufts University School of Medicine, said he had never seen such a series of events with a vaccine developer before. “They know the anti-vaccine community will use this as fodder to argue that drug companies are always fooling,” he said.
Dr. Meissner, who serves on a panel that advises the FDA on vaccine approval, predicted that if AstraZeneca were to apply for such approval, board members would examine the hundreds of pages of data even more carefully than usual.
“I’ll make sure I don’t skip a word,” he said.
Dr. Eric Topol, a clinical trial expert at Scripps Research in San Diego, said it was “very infrequent” to see such public friction between a supervisory board and a drug company.
“I’ve never seen anything like it,” he said. “It’s so, so unsettling.”
AstraZeneca’s relationship with the US authorities has been very strained almost since the clinical trial began last summer. Senior health officials complained that the company was not open about the design of its clinical trials, its results, and safety issues.
Last week, an apparent delay in the release of the vaccine’s interim results sparked suspicion among federal officials.
When asked by the New York Times, an AstraZeneca spokeswoman, who refused to name the company, replied Friday that any back-and-forth between the company and the Supervisory Committee was a normal dialogue.
“As is so often the case,” she said, “supervisory bodies can request new or clarification analyzes of data from the study.” This would enable them to ensure the robustness of their provisions. “
With more than 32,000 participants, the US trial, funded by the National Institutes of Health, was the largest test of its kind for the shot. The results, AstraZeneca released Monday, reflected an interim look at the data after 141 Covid-19 cases occurred in volunteers, a third of whom were given a saline placebo. Those were enough cases to assess whether the vaccine was effective in preventing the disease.
The impact of the study extends beyond the US, which ordered 300 million doses of the vaccine.
AstraZeneca’s application for emergency approval may take longer to review than companies that have already received approval. If there is no apparent need for the vaccine in the US at the time of the FDA evaluation, it may be less urgent for regulators to complete their review.
Monday’s results had the potential to allay concerns in Europe and other parts of the world that are counting on hundreds of millions of affordable, permanent doses of the AstraZeneca vaccine. Regulators in Europe said the shot was “safe and effective” last week after conducting a review after a small number of people who had recently been vaccinated developed blood clots and abnormal bleeding. The US trial showed no evidence of such problems.
Millions of people have received the AstraZeneca shot worldwide, including more than 17 million in the UK and the European Union, almost all without serious side effects. To increase public confidence, many European political leaders have received the injections in the past few days. The AstraZeneca vaccine was also given to executives in South Korea, Taiwan and Thailand last week.
“If you get the call, get the bump,” urged UK Health Secretary Matt Hancock on Monday. In the UK, more than 11 million doses of AstraZeneca have been administered, almost all without serious side effects. The vaccination campaign has reduced hospital stays and helped the country get out of a terrible winter wave of infections.
Even if AstraZeneca convinces American regulators to approve its vaccine, it is not clear whether the Biden administration will use it here. By the end of May, federal officials said the three already approved groups of manufacturers – Pfizer and BioNTech, Moderna, and Johnson & Johnson – will have delivered enough doses to cover all American adults.
The mopping up of US data is the latest in a string of mistakes and communication errors by AstraZeneca, whose vaccine, developed with Oxford University, was once a frontrunner in the race for safe and effective vaccination.
In September, key federal officials, including then-FDA Commissioner Dr. Stephen Hahn, only from the news media, that the vaccine trials worldwide were halted after a volunteer in the UK developed worrying neurological symptoms. AstraZeneca officials had a conference call with the FDA just hours before the news broadcast, but they neglected to mention the safety issue.
The US study was interrupted last fall, partly because AstraZeneca was slow to provide the FDA with evidence that the vaccine had not caused the neurological symptoms. Investigators concluded that the symptoms could not be linked to the vaccine.
However, due to the nearly seven-week delay, AstraZeneca lagged behind the three authorized manufacturers.
Sheryl Gay Stolberg and Sheila Kaplan contributed to the coverage.