Questions over '90 per cent effective' vaccine after error in trial

Following a test failure, a new global trial will likely be conducted on the vaccine from Oxford University and AstraZeneca.

AstraZeneca will likely take further steps to assess the effectiveness of its vaccine after a surprising result found that 90 percent protection was achieved when people were given a half dose followed by a full dose.

The company acknowledged that the finding was due to a dosing error.

However, it says it does not expect a new trial to hold up regulatory approval in countries, including the UK.

But as he addressed some of the claims made to AstraZeneca and Oxford tonight at a press conference in Downing Street, Chris Whitty, England’s Chief Medical Officer said, “The simple answer to this is that there is always a scientific debate on just about everything. is to leave this to the regulator, the excellent MHRA regulator.

“They will be making an assessment with a lot of data that is not currently in the public domain on efficacy and safety, and we will see the articles published in peer-reviewed journals, allowing us to make a decision about what to do.

“We have to keep that process going. I think it’s always a mistake to judge early before we have enough information.”

One scientist said the “dosing error raises some issues” – and there were some concerns about a lack of detail about the trials.

Another said it raises the need for caution regarding the vaccine’s effectiveness for older people.

Paul Hunter, a professor of medicine at the University of East Anglia, told PA: “Since many vaccines are less effective in older people, we need to be even more careful to consider this 90 percent efficacy at first glance, at least for older people. . “

However, many scientists have defended the work done – and one even said that half the dose could ultimately be more effective.

The overall effectiveness of two different dosing regimens in a phase three study was announced last week at a combined figure of 70 percent.

According to a subset of data, a half dose followed by a full dose was found to be 90 percent effective.

However, the effectiveness was 62 percent for people who received two full doses.

Earlier this week, Moncef Slaoui, the scientific chief of US Operation Warp Speed ​​- the program to provide America with vaccines – told the media that the half-dose regimen was only given to people over 55.

This may be problematic as scientists want to find vaccines that work in older people most at risk from Covid-19.

Results from an earlier phase two study published in The Lancet Medical Journal showed that the vaccine had a strong response in all age groups.

Professor Andrew Pollard, director of the Oxford Vaccine Group, told reporters last week that the finding of 90 percent effectiveness already met the “necessary statistical evidence as required by regulators.”

He said more evidence would likely be available next month, but it is “a very significant result, even with the numbers we have.”

The 90 percent effectiveness was based on a dosing regimen for 2,741 people.

The other regimen – with two doses – involved 8,895 people.

However, neither AstraZeneca nor Oxford disclosed at the briefing that the 90 percent figure was based on adults aged 55 and under.

Some US scientists have questioned an alleged lack of detail in the results published by AstraZeneca and Oxford last week.

Some experts have asked questions about using two differently designed clinical trials in the UK and Brazil, and about pooling analyzes of both.

They also said it is unclear how many Covid cases were found in each group of the trial.

The New York Times also said AstraZeneca’s Menelas Pangalos had to defend the way the company handles testing and its public disclosures.

John Moore, professor of microbiology and immunology at Weill Cornell Medical College, told the New York Times, “The press release raised more questions than it answered.”

Mr Pangalos said the half dose finding “could become a pretty useful mistake”, adding, “What is there to disclose? It doesn’t really matter whether it was done on purpose or not.”

The Oxford vaccine costs £ 2 to £ 3 per dose.

It is easier to store than Pfizer / BioNTech and Moderna vaccines, which require very low temperatures.

The shot is being reviewed by the Medicines and Healthcare products Regulatory Agency (MHRA) for use in the UK.

In an interview with the PA news agency last week, Tom Keith-Roach, president of AstraZeneca UK, said there were “very statistically significant efficacy results across all subgroups … so I think regulators will get it on that basis. see”.

Helen Fletcher, professor of immunology at the London School of Hygiene and Tropical Medicine (LSHTM), said: “What’s remarkable is that Oxford University and AstraZeneca have gone from the first to 100 million doses in less than a year.

“Unsurprisingly, some manufacturing issues were still ironed out when they started clinical trials, but early-stage studies are all about safety, and the safety data we’ve seen was very robust.”

She said it was important to wait for the full dataset to be published.

“I also think it is possible that a lower initial vaccination dose could result in higher vaccine effectiveness,” she said.

“More is not necessarily better when it comes to vaccines and immunotherapies. You have to stimulate an immune response, but if you push too hard you can get into a negative feedback loop where the immune system tries to control and dampen the response.

“It is also possible that a strong immune response to the first vaccine could effectively block an immune response to the second injection of the same vaccine – but we should be able to see evidence of that when the data is published.”

Stephen Evans, professor of pharmaco-epidemiology at LSHTM, said, “The idea that no protocol has been published (by Oxford and AstraZeneca) is simply not true.”

He added: “The variety of age groups and dosing regimens is a hallmark of a number of vaccine studies and not just the Oxford AstraZeneca vaccine.

“The way in which the data is compiled is specified in the protocol and examined very carefully by regulators to ensure that there is no cherry picking of the results.”

Joy Leahy of the Royal Statistical Society said the scientific community was “rightly looking for more data in the form of a peer-reviewed paper.”

She said a press release was issued due to the risk to financial markets due to too many people knowing the results pending publication by peer review.

She said the “dosing error raises some problems” and that the 90 percent result found may be due to random statistical variation.

“There are also some other complications when looking at this subgroup as they were all in one location and apparently were not representative of the full age profile in the trial,” she added.

An AstraZeneca spokesperson told PA on Thursday, “When the development of the vaccine was scaled up to the Oxford-sponsored Phase II / III trial, the measurement used for previous studies showed the strength of the dose in the new larger batches, thereby administering half a dose of the vaccine.

“This was reviewed by the independent Data Safety Monitoring Board and the UK regulator, who both approved the continuation of this dosing regimen and the regulator publicly confirmed there were ‘no concerns’.

“All other regulators were informed that we would continue to monitor and study this cohort. Given the high efficacy we have now seen with the different dosing regimens, it is of great value to further investigate these findings to determine the most effective dosing regimen.

“We are in talks with regulators around the world to evaluate these findings and we look forward to the publication of the peer-reviewed results, which have now been submitted to the journal.”

Oxford University said it would not comment pending the data appearing in a peer-reviewed publication.