Chris Whitty, England’s Chief Medical Officer, refused to back Oxford’s vaccine
The Chief Medical Officer has dodged giving the AstraZeneca jab his full backing as the company revealed it will run a new Oxford vaccine trial.
Chris Whitty refused to back the injection when asked about the controversy surrounding data from its late-stage trials at a Downing Street press conference.
AstraZeneca will run a new trial because no one who got accidental low dose that had 90 per cent success rate was aged over 55.
There has been close scrutiny of the vaccine, after it was found to be 70 per cent effective on average, but 90 per cent effective with a low-dose jab followed by a standard booster injection.
This much higher result, based on a sub-group of around 2,700 people, was met with concern when it emerged no one in the group was reportedly aged over 55.
Now AstraZeneca, the firm manufacturing the vaccine, is understood to be considering ensuring that the lower dose of the vaccine is tried by older people in its ongoing US trials.
It is important to establish if the vaccine can work as well in over-55s, who face a greater threat from Covid and have higher death rates.
AstraZeneca has been planning to roll out the low-dose jab in its US trial of 40,000 people since the vaccine results emerged this week.
But the pharmaceutical company now faces added pressure to look at older people specifically.
AstraZeneca will likely run an entirely new trial to test the use of a half dose for the first injection of its coronavirus vaccine is most effective after the accidental regimen appeared to boost the efficacy of the shot in its original trial
Prof Whitty refused to back the jab when asked about the controversy surrounding data from its late-stage trials at a Downing Street press conference.
He said judgment about the vaccine’s efficacy and safety should be ‘left in the hands’ of the UK’s drugs watchdog, which will decide whether the jab is safe enough to dish out to millions of Britons in a matter of days.
He added: ‘The simple answer to this is there is always scientific debate about virtually everything. The key thing from our point of view is to leave this in the hands of the regulator, the excellent MHRA regulator.
‘They will make an assessment with lots of data that is not currently in the public domain on efficacy and on safety and we will see the papers published in peer reviewed journals, which will allow us to make a decision about what needs to happen.
‘We need to allow that process to go forward. I think it’s always a mistake to make judgement early before we have enough information.’
Sir Patrick Vallance, the Chief Scientific Adviser, was far less gun-shy when the question was put to him, saying: ‘The headline result is the vaccine works and that’s very exciting.’
Sir Patrick Vallance, the Chief Scientific Adviser, was far less gun-shy when the question was put to him, saying: ‘The headline result is the vaccine works and that’s very exciting’
Geoffrey Porges, an analyst at healthcare investment bank SVB Leerink, said he thought it unlikely the jab would get approval in the US after AstraZeneca ‘tried to embellish their results’, according to the Financial Times.
It was Moncef Slaoui, the scientific head of the US’s drive to manufacture and distribute vaccines, who reportedly revealed to US journalists that the half-dose regime was only given to people aged 55 and under.
But Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said: ‘The variety of age groups and dosing regimes is a feature of a number of the vaccine trials and not just the Oxford AstraZeneca vaccine.
‘The way the data are put together will have been specified in the protocol and scrutinised very carefully by regulators to ensure that there is no ‘cherry-picking’ of the results.’
Peter Openshaw, professor of experimental medicine at Imperial College London, said: ‘It has been reported in the media that this only included cases below the age of 55 – if this is true, it may mean we don’t have any information about this regimen in older adults’
Sir John Bell, Oxford’s regius professor of medicine, said yesterday: ‘All the protocols, all the designs were all approved – pre-approved – by the regulators, so we weren’t cooking this up as we went along.’
It is simpler to add the low-dose injection to the US trial of 40,000 people as only around 10,000 have been recruited so far.
The Oxford vaccine trial in the UK is ongoing, but does not have many volunteers left to bring in.
The surprise result that the Oxford vaccine worked better with a low-dose jab followed by a standard shot, rather than two standard injections, came after a mistake in which half the dose was wrongly prepared for trials.
But Oxford University said this was approved by the medicines regulator when it was added to the trial design.
Meanwhile the Government has formally asked the medicines regulator to approve the Oxford vaccine for temporary use as soon as it has received the necessary safety, quality and efficacy data.
Sir John Bell, Oxford’s regius professor of medicine, said yesterday: ‘All the protocols, all the designs were all approved – pre-approved – by the regulators, so we weren’t cooking this up as we went along’
‘I have a tiny sense of pride’: Volunteer in Oxford’s coronavirus vaccine trial hails ‘promising’ results
A volunteer in Oxford University’s coronavirus vaccine trial has revealed she felt a ‘tiny sense of pride’ at taking part in research that could finally beat the virus.
Sarah Hurst, 47, from South Oxfordshire, said it was a ‘great feeling’ after hearing on Monday that the vaccine could trigger an immune response in up to 90 per cent of those who receive the jab.
Jack Somers, 35, from London, who also took part, said he was ‘very happy’ and felt like his vaccine team had ‘just won’.
Sarah Hurst, 47, from Goring-on-Thames, who took part in the trials of the vaccine, said she had a ‘tiny sense of pride’ in helping to prove the jab worked
The pair, who both work as journalists, received two shots of either the experimental or placebo vaccine. Mr Somers said he suffered side-effects of a pain in his shoulder and slightly raised temperature, but Ms Somers said she didn’t experience any.
Ms Hurst, who works as a journalist, said: ‘It’s really the developers and everyone who’s done all the work, all the medical students who are constantly all day meeting the vaccine participants and testing them and being on the front line.
‘But it’s good, it’s a great feeling to help to make a vaccine.’
Jack Somers, 35, from London , who also took part, said he was ‘very happy’ and felt like his vaccine team had ‘just won’
Explaining why she signed up, she said: ‘I live near where it’s being done and they were looking for people in the Thames Valley. As soon as I saw that I wanted to get involved to help research a vaccine.’
She underwent health checks and blood tests before receiving her two shots, and filled in a diary to notify researchers of her movements over the course of the study, as well as any symptoms.
‘You have to treat it as if you were in the placebo group anyway, you wouldn’t go out and randomly expose yourself because you don’t know,’ she said.
Despite suffering no side effects, this doesn’t mean she received the placebo. The trial used the meningitis vaccine as a control, which scientists argued would elicit a similar response to the Covid-19 jab.
She said Monday’s results were ‘promising’ and noted ‘the fact it doesn’t need to be chilled at a very low temperature and is cheaper than the other vaccines will help in making it easier to distribute’.
‘You have to treat it as if you were in the placebo group anyway, you wouldn’t go out and randomly expose yourself because you don’t know,’ she said.
‘People have only been vaccinated for a few months so I would still want to know: what are going to be the results after a year? Is it going to be effective after a year?
‘That’s something you really just have to wait for.’
Mr Somers said he found it hard to believe how quickly scientists had developed the vaccine.
‘I can’t help but take my hat off to the scientists,’ said the freelance journalist from south-west London.
‘I remember six months ago sitting in a hospital watching a safety video, with Professor Matthew Snape at Oxford University talking in quite careful, deliberate, cautious terms about how this vaccine might work or it might not work.
‘Now it seems amazing that we’re here six months later and that jab is very effective at stopping coronavirus.
‘It’s not where I thought we’d be six months ago, it’s not even where I thought we’d be a month ago, but it’s testament to the work of so many people, so many extraordinary people.’
Volunteers receive no information about how the trial is going so have been following the progress in the media along with everybody else.
And Mr Sommers said that, while he had been very pleased to read about positive results from other vaccines such as that developed by Pfizer, there was a special feeling about this one.
In the Moderna and Pfizer vaccine trials – which are about 95 per cent effective – dosing regimens were tested on 10,000 volunteers and four in 10 were over 55.
The World Health Organization set a target of 50 per cent effectiveness for a Covid-19 jab, a threshold Oxford surpassed after its jab was 60 per cent effective in people receiving two full doses.
But despite this it is facing mounting criticism from scientists.
Hilda Bastian, an accomplished scientist turned writer who blogs for the British Medical Journal (BMJ), claimed yesterday data from the Oxford trials had been ‘patched together’ and excludes results from the groups most vulnerable to Covid.
Others have warned they ‘still don’t have all the information that is needed’ and that, based on current data, the jab may be rejected for emergency approval by US regulators.
Oxford’s candidate is seen as a potential silver bullet because it costs a fraction of the price of rivals made by Pfizer and Moderna and does not need to be stored in expensive fridges.
But, in a piece for Wired, Ms Bastian said the critical flaw was that a dosing error led to a huge boost in the success rate – experts accidentally gave some volunteers one-and-a-half doses of the jab rather than two full doses that people are meant to get.
The trials were also never designed to test this hypothesis, which leaves the door open to subconscious biases creeping into the study methods or data, making the study less rigorous.
She wrote: ‘This week’s ‘promising’ results are nothing like the others that we’ve been hearing about in November [the studies the results are based on were less rigorous] — and the claims that have been drawn from them are based on very shaky science.
‘The problems start with the fact that Monday’s announcement did not present results from a single, large-scale, Phase 3 clinical trial, as was the case for earlier bulletins about the BNT-Pfizer and Moderna vaccines…
‘The fact that they may have had to combine data from two trials in order to get a strong enough result raises the first red flag…. As far as we know, some of this analysis could hinge on data from just a few sick people.’
She said this means the findings could be a coincidence, or they could be ‘biased by other factors’.
The former president for global research at Covid-19 vaccine competitor Pfizere, John LaMattina, has warned based on the current data Oxford’s jab is unlikely to be approved for emergency-use in the US.
He tweeted it was it was ‘hard to believe’ that regulators would give the green light to a vaccine ‘whose optimal dose has only been given to 2,300 people’.
Professor Natalie Bean, a bio-statistician at the University of Florida, told the Financial Times they still ‘don’t have all the information we need to tell whether these results are reliable’.
‘We certainly don’t have enough information in the public domain to decide whether this half dose is really working,’ she added.
An investment analyst at SVB Leerink, Geoffrey Porges, told the FT the jab was likely to be rejected because the company had ‘tried to embellish their results’ by highlighting its effectiveness in a ‘relatively small subset of subjects in the study’.
But Professor Ian Jones, a virologist at the University of Reading, told MailOnline: ‘We need to keep the positives in mind, that the vaccine is safe and can provide protection.
‘It is also a fact that in order to see protection, a Phase 3 trial has to be done in an area of current infection and if the level of infection changes, there may be a need to add additional sites.’
He did concede, however, that ‘the issue of the dose is confusing’.
He added: ‘That 90 per cent protection was observed in the subset that received the supposed lower dose is really good but I think that would equate to only about 15 people in the 3,000 that received it which may be too low to convince regulators of efficiency, especially if it is not quite clear what the key difference is between it and the higher dose. All this should be much clearer when the full data are published.’
Oxford’s trials found that the jab has a nine in ten chance of working when administered as a half dose first and then a full dose a month later.
But efficacy drops to mere 62 per cent when someone is given two full doses a month apart.
Oxford has also claimed that its vaccine has an average efficacy of 70 per cent, based on the 62 and 90 per cent figures, which would put the Covid jab on par with good flu vaccines.
But there have been doubts about the reliability of the 70 per cent figure because it has been crudely calculated based on the two regimens, rather than everyone in the trials of all ages.
And because so far Oxford and AstraZeneca – which owns the rights to the jab – have only revealed the percentages in a press release, it is not clear how they arrived at those figures.
It means the analysis that could seal whether or not the jab is administered to millions of people globally could be based on data from a handful of people – which, again, leaves the door open for other factors to bias in the study.
For example, it has since been revealed that the people who received the reduced dose included no-one over the age of 55 – who are most vulnerable to falling seriously ill or dying from Covid, according to Ms Bastian.
That was not the case for the normal dosed group, raising questions about whether the demographic – rather than dosing – difference is the true driver behind the boosted efficacy.
The Oxford-AstraZeneca study appears to include few participants over the age of 55, even though the vaccine is being targeted at elderly people.
Wired reports that people in that demographic were not originally eligible to join the Brazilian trial at all – compared Pfizer’s trial, where 41 per cent were over 55.
Another flaw, according to Ms Bastian, came from the simple fact the results have been combined from two separate trials in the UK and Brazil, as opposed to one single large-scale study like Pfizer and Moderna’s vaccines.
Oxford originally planned to conduct a single trial in the UK when it launched its phase three study in May, but coronavirus began to fizzle out over summer which meant not enough volunteers were getting infected naturally.
A month later a second phase three trial was started in Brazil where transmission had begun to spike.
But the consequence of splitting the trial in half was that researchers could not control variables as tightly as they could in one single trial done by the same team.
There wasn’t a standardised dosing regimen across both trials and control groups in the studies were not given the same fake vaccine to compare to the Covid jab.
Participants in Brazil were given a saline injection as a placebo, whereas the British arm of the study were given a vaccine for meningitis – which creates an unfair comparison.
According to emergency-use vaccine guidance issues by Britain’s medical regulator, the MHRA, and the FDA in the US, jabs can be approved if they demonstrate safety and efficacy through a single Phase 3 clinical study.
Although early results from Oxford’s clinical trials were published on Monday, the study is not completed.
Oxford has started a 30,000-person phase 3 trial in the US to get more accurate and precise data about its vaccine – but the jab could be approved and rolled out within weeks before those results arrive.
Oxford researchers said they intend to publish the full results of the trial in a medical journal in the coming weeks and will then submit an application to the drugs regulator, the MHRA, for a licence to use the vaccine on members of the public.
This process could then take days or weeks for the MHRA to decide whether the jab is good enough to use before it can start to be given out – this is currently expected to be completed in December.
The vaccine uses a harmless adenovirus to deliver genetic material that tricks the human body into producing proteins known as antigens that are normally found on the coronavirus’s surface, helping the immune system develop an arsenal against infection.
A spokesman for AstraZeneca said: ‘There is strong merit in continuing to further investigate these findings in order to establish the most effective dosing regimen.’
Oxford University said: ‘We have different ways of measuring the concentration of the vaccine and when it was apparent a lower dose was used, we discussed this with the regulator, and agreed a plan to test both the lower dose-higher dose and higher dose-higher dose.’
HOW DO THE OXFORD, MODERNA AND PFIZER/BIONTECH VACCINES COMPARE?
Moderna and Pfizer/BioNTech have both released interim results of the final stage clinical trials of their vaccines, with both suggesting they are extremely effective.
Oxford University has published the findings from its second phase, which show the jab provokes an immune response and is safe to use – it is not yet clear how well it protects against coronavirus in the real world.
Here’s how they compare:
PFIZER (US) & BIONTECH (DE)
mRNA vaccine – Genetic material from coronavirus is injected to trick immune system into making ‘spike’ proteins and learning how to attack them.
mRNA vaccine – both Moderna’s and Pfizer and BioNTech’s vaccines work in the same way.
Recombinant viral vector vaccine – a harmless cold virus taken from chimpanzees was edited to produce the ‘spike’ proteins and look like the coronavirus.
94.5% effective (90 positive in placebo group, 5 positive in vaccine group) .
95% effective (160 positive in placebo group, 8 positive in vaccine group).
62% – 90% effective, depending on dosing.
Moderna confirmed it will charge countries placing smaller orders, such as the UK’s five million doses, between £24 and £28 per dose. US has secured 100million doses for $1.525billion (£1.16bn), suggesting it will cost $15.25 (£11.57) per dose.
The US will pay $1.95bn (£1.48bn) for the first 100m doses, a cost of $19.50 (£14.80) per dose.
Expected to cost £2.23 per dose. The UK’s full 100m dose supply could amount to just £223million.
UK has ordered five million doses which will become available from March 2021. Moderna will produce 20m doses this year, expected to stay in the US.
UK has already ordered 40million doses, of which 10million could be available in 2020. First vaccinations expected in December.
UK has already ordered 100million doses and is expected to be first in line to get it once approved.
What side effects does it cause?
Moderna said the vaccine is ‘generally safe and well tolerated’. Most side effects were mild or moderate but included pain, fatigue and headache, which were ‘generally’ short-lived.
Pfizer and BioNTech did not produce a breakdown of side effects but said the Data Monitoring Committee ‘has not reported any serious safety concerns’.
Oxford said there have been no serious safety concerns. Mild side effects have been relatively common in small trials, with many participants reporting that their arm hurt after the jab and they later suffered a headache, exhaustion or muscle pain. More data is being collected.