After highly encouraging results from its US clinical trials this week, AstraZeneca seemed set to recover from a series of research mishaps, public relations blunders and political misfortunes, writes MedicalBrief. Then the US National Institute of Allergy and Infectious Diseases raised concerns that its results data were outdated.
The NIAID officials put out a highly unusual statement saying that AstraZeneca’s results “may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data.”
The New York Times said the latest setback raises a new rash of knotty questions about its vaccine. The NYT’s Noah Weiland, who covers health care, said that AstraZeneca told American officials over the weekend that the company was about to announce promising results showing the vaccine had a stellar 79% efficacy rate – and then it released that data to the public.
“But it turns out the company was presenting a different data set than one that the independent oversight board overseeing the trial expected, with a higher efficacy rate,” Noah said. The experts said in their letter to the company that the vaccine’s efficacy might have been between 69% and 74%. “The real efficacy rate wasn’t likely that much lower, but it showed that the company’s representatives and independent experts monitoring the trial were on different pages,” Noah said. “With such an important trial and product, officials were shocked by the discrepancy.
AstraZeneca has defended the data it released. The company said that results were based on interim data that was current as of 17 February. AstraZeneca added that it had collected more data since then and that the new data appeared to be “consistent” with the interim data. The company said it would immediately share its latest efficacy data with the independent panel of experts and reissue fuller results within 48 hours.
The NYT notes that experts questioned only the data that demonstrated the vaccine’s effectiveness. AstraZeneca reported that its study turned up no serious safety issues – though experts point out that no clinical trial is large enough to rule out extremely rare side effects.
Scientists have said that the problem could yet turn out to be a technical matter that does not change their assessment of the vaccine. AstraZeneca’s filing “is really what you call an unforced error,” said Dr Anthony Fauci. “The fact is: This is very likely a very good vaccine.” However, he noted that the confusion could “cast some doubt about the vaccines and maybe contributes to the hesitancy.
The NYT’s Benjamin Mueller reported from London, that AstraZeneca's latest blunder has further eroded confidence across Europe, where many countries stopped administering the AstraZeneca vaccine because a very small number of recipients had developed unusual blood clots, although the issues are very separate.
The US regulators were concerned with overall efficacy data, while halts in Europe and elsewhere were because of worries about side effects. But ultimately this will most likely hinder efforts to rebuild trust in the AstraZeneca vaccine, whose low price and easy storage requirements have made it the backbone of many countries’ campaigns to end the pandemic.
AstraZeneca said that it would continue to analyse the new data and prepare to apply in the coming weeks for emergency authorisation in the US. Noah said that “it’s still unclear whether this changes how the vaccine might be evaluated by the US Food and Drug Administration.”
In interviews with CNN, several vaccine advisers to the US government did not cast doubt as to whether AstraZeneca's vaccine would ultimately gain emergency use authorisation from the FDA. They did, however, say the company's application will likely bring up issues that didn't arise when the three COVID-19 vaccines currently used in the US – made by Pfizer, Moderna and Johnson & Johnson – were considered for their own emergency use authorisations.
"It's clear more questions have been raised about the AstraZeneca vaccine than about any of the other vaccines which are now authorised in the US," said Dr Arnold Monto, acting chair of the FDA's Vaccines and Related Biological Products Advisory Committee, which reviews vaccine applications and advises the FDA on whether they should be authorized.
CNN reports that those advisers – who work at academic medical centres and not for the government – said the reports of blood clots after vaccination, which caused more than a dozen western European countries to suspend use of the AstraZeneca vaccine, are not the only issue. Questions have been raised about other aspects of AstraZeneca's efficacy and safety data, too.
"It does feel different, and it felt different even before the whole blood clot kerfuffle," said Dr William Schaffner, a liaison member of the CDC's Advisory Committee on Immunisation Practices. Monto, Schaffner and other government advisers said they look forward to receiving the "dossier" of data about a vaccine's safety and efficacy that FDA publicly releases when a pharmaceutical company applies for emergency use authorization.
Even before this latest stumble, the company had made missteps in reporting data and faced a blood-clot scare over its COVID-19 shot. According to a LA Times report, health officials worried that those issues could cause lasting harm to the reputation of the vaccine, which was developed in conjunction with Oxford University and has been regarded as key to global efforts to stop the pandemic.
“I doubt it was (US officials’) intention to deliberately undermine trust in the AstraZeneca vaccine,” said Dr Paul Hunter, a professor of medicine at the University of East Anglia in England. “But this will likely cause more vaccine hesitancy.”
The report says Hunter emphasised that it was unclear how significant this latest issue might be. But it’s not the first time the company has run into problems.
The LA Times reports that partial results from the vaccine’s first major trial – which Britain used to authorise the vaccine in December – were clouded by a manufacturing mistake that the researchers didn’t immediately acknowledge. Insufficient data about how well the vaccine protected older people also led some countries, including Germany and France, to initially restrict its use to younger populations.
In the US, officials suspended AstraZeneca’s study in 30,000 Americans for an unusual six weeks last fall, as frustrated regulators sought details about neurological problems reported in Britain. In the end, there was no evidence that the vaccine was to blame for those problems.
The LA Times notes that even if the company clears up the misunderstanding – and it’s not yet clear what the US experts are asking for – it could have a lasting impact. Julian Tang, a virologist at England’s University of Leicester, pointed to the decades-old controversy over the measles vaccine as a cautionary tale.
“There was absolutely no evidence to prove the (measles, mumps and rubella) vaccine caused autism,” he said. But despite the retraction of the paper that made the claim, Tang said some people still worry about the vaccine. He said AstraZeneca’s issues may be even tougher to overcome “because every week it seems like there’s some new concern.”
“This is unfortunately more about perception than it is the science,” said Dr Bharat Pankhania, an infectious-diseases specialist at the University of Exeter in southwest England.
“We have now seen, on several parameters, that the AstraZeneca vaccine provides protection and is safe,” he said. “But the narrative for the public has not been as clear,” he added, criticising politicians for undermining confidence in the vaccine without evidence.
Full New York Times report (Restricted access)
Full CNN report (Open access)
Full LA Times report (Open access)
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