US health chiefs accuse AstraZeneca of providing 'outdated' information from its vaccine trial - when it claimed the shot was 79% effective - in a bid to get approval in America
US health chiefs have accused AstraZeneca of sending 'outdated information' as part of an application to get its Covid vaccine approved for use on Americans.
The drug giant, which is manufacturing Oxford University's jab, revealed yesterday that a US-specific trial found the vaccine prevented 100 per cent of hospital admissions and deaths from Covid, along with 79 per cent of all symptomatic infections. It said it hoped to get a licence from drug regulators within weeks.
The National Institute of Allergy and Infectious Diseases (NIAID) – a health authority headed up by Dr Anthony Fauci, America's top infectious disease expert – last night called on AstraZeneca to send US regulators the 'most accurate up-to-date' data 'as quickly as possible'.
It said the Data and Safety Monitoring Board — an independent watchdog panel of a dozen leading experts that it appointed to vet coronavirus vaccines — was 'concerned' that the firm may have 'provided an incomplete view of the efficacy data'.
The NIAID, a division of the US National Institutes of Health, made the 'unprecedented' call for more data in public — discussions usually happen behind closed doors. It asked the company to provide up-to-date figures 'as quickly as possible' but did not offer its own estimate of how well the vaccine works.
The hiccup is latest in a string of PR disasters for AstraZeneca, which has faced constant criticism over its jab with European officials first claiming it didn't work on older people and later that it caused blood clots – neither of which turned out to be true. UK and EU officials are now rowing over supplies.
Real-world data proves that the vaccine is protecting people against Covid in the UK, which has given the jab to over 13million people since it was approved in January. It means any updated figures are unlikely to change the regulator's decision but must be examined thoroughly.
Experts reacting to the NIAID's statement released last night described it as 'unusual' and said airing grievances in the public domain was 'unprecedented'. They criticised AstraZeneca for 'confusing' officials with the way it was sending its data.
AstraZeneca, whose North American headquarters (pictured left) are in Wilmington, Delaware, was asked Monday for more data. Pictured right, vials of the firm's vaccine
The full statement read: 'Late Monday, the Data and Safety Monitoring Board (DSMB) notified NIAID, BARDA, and AstraZeneca that it was concerned by information released by AstraZeneca on initial data from its Covid vaccine clinical trial.
'The DSMB expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data.
'We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible.'
Covid vaccines can't be rolled out in the US until they are approved by the Food and Drug Administration (FDA) and the Centers for Disease Control (CDC), who rely on independent committees such as the DSMB to rigorously review the evidence.
The DSMB — which is run through the NIAID — is made up of around 10 to 15 leading scientists and statisticians who have no ties to the Government or the drug firms making the jabs.
'It is not unknown for a [regulator] to disagree with investigators over interpretation of trial results but it is usually done in private, so this is unprecedented in my opinion,' said Professor Stephen Evans, a vaccines expert at the London School of Hygiene & Tropical Medicine.
'I have said frequently that "headline" estimates of efficacy being compared between trials is very unreliable.
'The DSMB [Data and Safety Monitoring Board] has responsibility essentially for safety of participants, not efficacy unless it is either so high or so low or negative that it is unethical to continue to randomise, so in some senses they might be seen to be exceeding their brief...
'One explanation might well be that this trial is currently being conducted when there is a large amount of a new variant about more recently, and, as might be expected, the efficacy against that variant might be less, so more recent data shows reduced efficacy. Of course the other vaccines may also show such reduced efficacy and we don’t know by how much.
'It does not leave me concerned particularly unless they had found a safety issue that was being hidden, which does not appear to be the case.'
Dr Peter English, former editor of Vaccines in Practice Magazine and a former British Medical Association official, said the statement was 'problematic in various ways'.
He said: 'In my opinion this is shamefully bad communication by NIH as with their lack of clarity they have left room for speculation which could be damaging for vaccine uptake.'
And Dr Stephen Griffin, an associate professor of medicine at the University of Leeds, said the issue 'highlights the importance of data being provided at the same time as summaries being made public'.
He added: 'Naturally, the news yesterday was taken in good faith and the issues raised by the DSMB may be a mere technicality, yet this won’t be clear until we have full disclosure.
'Nevertheless, we must ensure that issues such as this are dealt with appropriately and that idle speculation is not seized upon by groups seeking to undermine faith in vaccination programmes.'
Oxford University yesterday published interim results of a trial done in the US, Chile and Peru that found its jab prevented 100 per cent of severe Covid cases and 79 per cent of all symptomatic infections.
It had been carried out because US regulators the FDA wanted a trial done on Americans before it would approve the jab, choosing not to use data from Oxford's tests in the UK, South Africa and Brazil.
And the study found the vaccine works just as well in over-65s as it does in younger people – it was the largest one so far conducted on older people, including more than 6,000 of them.
The trial — which involved 32,000 people in total — also confirmed the vaccine doesn't increase the risk of blood clots, which is a confidence boost after safety concerns in Europe rattled public faith in the jab last week.
Two doses were given four weeks apart in the study and the effectiveness of a single dose was not reported. Full results from the trial are expected to be published later in the year.
Trump's administration made a deal with AstraZeneca last year for 300million doses and the federal government is currently sitting on nearly 30million which can't be used until the shot is authorized by the FDA.
But this process has been delayed now, too, with officials having to wait until AstraZeneca sends the specific data they want. It is unclear how much of a delay the issue will cause, but the authorisation had been expected in April.
Experts said the news about the hold-up was concerning.
Professor Francois Balloux, a biologist at University College London, said: 'This is a highly unusual statement by the US National Institute of Allergy and Infectious Diseases (NIAID).
'It comes close to accusing Oxford/AZ of having willfully misrepresented some results from their recent US vaccine trial.'
And Professor Angela Rasmussen, a virologist at Georgetown University, said: 'If nothing else Oxford/AstraZeneca continues their perfect record of sharing trial data in the most confusing way possible.'
AstraZeneca said it still expected to get approval for the vaccine and one of its vice-presidents, Ruud Dobber, said on CNBC yesterday: 'Assuming that the approval will take place in a fast way, we hope to deliver 30million doses instantly after the EUA [Emergency Use Approval] for Americans to get vaccinated.'
Oxford's Professor Andrew Pollard, who runs the vaccine trials, said the results were 'remarkable', and its inventor Professor Sarah Gilbert said she was 'very pleased'.
Dean of Brown University's School of Public Health, Dr Ashish Jha, called the results 'fabulous news' in a tweet and told the Today Show that the AstraZeneca shot is the 'best ticket towards vaccinating the world.'
The jab-makers were in need of good press after the past fortnight saw more than a dozen European countries shun the jab amid fears it could cause blood clots on the brain – on which most have now backed down, although Sweden, Denmark and Norway are still hesitating and refusing to use it.
Meanwhile, Boris Johnson is preparing to call for EU leaders to shun 'vaccine nationalism' amid fears they will ban exports of vaccines because AstraZeneca is delivery on expectations in Britain but not in Europe, where it has allegedly only provided a third of the number of doses that were expected by the end of March.
Britain will also have to cope with five million fewer doses of the jab than expected in April because an expected shipment from India has been cancelled.
This is expected to mean the vaccine drive, which gave out a record 844,285 jabs on Sunday, will have to stick mainly to second doses instead of new patients.
Some 32,449 people across all age groups took part in the phase three trial in the US, Chile and Peru, with a total of 141 cases of symptomatic Covid reported.
Around two thirds of all the participants had the real vaccine – 21,583 – and the rest had a fake jab so the effects could be compared. Full results of the trial have not yet been published.
The initial results showed that among people aged 65 and over, there was 80 percent protection against developing symptomatic Covid, Oxford said.
This comes after officials in Europe, who had smeared the vaccine on yet another occasion, claimed that the vaccine didn't work on people over 55 and tried to prevent it being used on elderly people.
The US trial initially found that the Oxford/AstraZeneca vaccine was more effective than expected after results from the UK trial – while both found it to be 100 percent effective at preventing hospital admission or death, the US one saw it prevent 79 percent of all infections compared to 76 percent in the UK
Overall the study, which officials said was incomplete, found that the effectiveness of the jab against symptomatic Covid was even higher than it had been in the original trials that took place in the UK, South Africa and Brazil.
'These results are great news as they show the remarkable efficacy of the vaccine in a new population and are consistent with the results from Oxford-led trials,' said Professor Pollard.
'We can expect strong impact against COVID-19 across all ages and for people of all different backgrounds from widespread use of the vaccine.'
AstraZeneca has not yet published the full results of the trial, but its press release does not address whether or not the US trial screened participants for variants.
The older 'wild-type' coronavirus is still dominant in the US, but the UK's B117 variant is gaining ground, and the Centers for Disease Control and Prevention (CDC) lists four additional variants as 'concerning.'
In prior trials, the AstraZeneca shot was equally effective against B117, and worked well in Brazil where the P1 variant is dominant.
But it performed poorly in South Africa, where the B1351 variant is dominant.
Nonetheless, US health authorities are eager to add a fourth vaccine to the American arsenal.
AstraZeneca's shot has already been authorized in more than 50 countries around the world, and has helped the UK's vaccination campaign to race ahead of the America's.
AstraZeneca's US trial got a late start compared to its other global tests, beginning on August 28.
Trials were also protracted after the death of a participant in Brazil last year.
American regulators dragged out the trial pause even after other countries resumed their tests. AstraZeneca's trial wasn't allowed to resume for more than six weeks.
After European leaders this month claimed people were developing brain blood clots and even dying after having the AstraZeneca vaccine, inspectors looked at the risk of blood clots and found it was not increased at all.
They looked at a specific condition that had scared officials in Germany, called cerebral venous sinus thrombosis, and found there wasn't a single case recorded in the clinical trial.
The European Medicines Agency itself – which first launched an investigation and triggered panic across the continent – last week admitted there was no proof of a link to blood clots and backed down on its warning.
Health officials around the world, including Britain's regulator the MHRA and the World Health Organization, have urged countries to keep using the vaccine to stamp out coronavirus.
Professor Sarah Gilbert, the Oxford scientist who invented the jab, said on BBC Radio 4 today: 'I’m very pleased to see these results.
'Another large trial in different countries to what we had before again reporting on the safety and high efficacy of this vaccine, so it’s really good news to see that.'
She added: '20 percent of people in this trial were over the age of 65 and there was no drop in protection for those people. It was just as good in the over-65s as it was in the younger people and that’s very clear from this trial.'
On Europe's concerns, Professor Gilbert said: 'I'd say the balance remains hugely in favour of using this vaccine. Across Europe there are thousands of deaths a day occurring from COVID.
'It's really important that we get the chance to protect people as quickly as possible, this vaccine is available for use in Europe and it will save lives.'
AstraZeneca said leaving an interval longer than four weeks – as is happening in the UK – can increase efficacy and 'accelerates the number of people who can receive their first dose'.
This is understood to be because it allows the body to cement the immunity from the first dose before the second – the booster dose – provokes a second, separate reaction and lets the already established protection strengthen itself.
As part of an agreement with Oxford, AstraZeneca is supplying the vaccine on a not-for-profit basis for the duration of the pandemic and in perpetuity for low and middle-income countries.
The news comes as polling for YouGov suggests confidence in the safety of the vaccine has dropped in the last two weeks in Spain, Germany, France and Italy.
Some 55 percent of Germans said the AstraZeneca vaccine is unsafe while 32 percent said it is safe.
AstraZeneca's vaccine was already seen as unsafe in France but concerns have increased even further, with 61 percent now saying it is unsafe while 23 percent say it is safe, according to the survey of almost 9,000 people in seven countries.
More than a dozen European countries suspended use of the vaccine over concerns about blood clots, although most have now resumed its use.
The European Medicines Agency and the World Health Organization (WHO) have ruled that the AstraZeneca jab is safe and effective.
