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Covid-19: UK government asks regulator to assess Oxford vaccine as questions are raised over interim data

BMJ 2020; 371 doi: (Published 27 November 2020) Cite this as: BMJ 2020;371:m4670

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  1. Elisabeth Mahase
  1. The BMJ

The UK government has asked the Medicines and Healthcare Products Regulatory Agency (MHRA) to evaluate whether the University of Oxford and AstraZeneca vaccine can be authorised for temporary supply as soon as the data on safety, quality, and efficacy are submitted.

If approved, the UK could receive four million doses by the end of the year and 40 million by the end of March 2021. But the request comes as questions have been raised over the researchers’ data, and AstraZeneca said that it would run a new global trial to test the lower dosage of the vaccine.1

The Oxford team reported their interim phase III results on 23 November through a press release. They said that the vaccine was found to be 62% effective when given as two standard doses (8895 participants) one month apart, but it was 90% effective when a half dose was followed by a standard dose regimen (2741 participants).2

The analysis included 131 covid-19 cases, and no hospital admissions or severe cases were recorded in anyone who received the vaccine. However, the press release lacked much of the detail seen in the press releases on phase III results from Moderna and Pfizer, including information on participant age and ethnicity.

Dosing error

While the vaccine has been praised for its low price (around £3 a dose (€3.40; $4), compared with around £15 for Pfizer’s vaccine and £25 for Moderna’s) and its easy storage, concerns have been raised over the dosing, after the half dose regimen was revealed to be accidental and due to a dosing error.

Peter Openshaw, professor of experimental medicine at Imperial College London, said, “From what I have read, it seems that the calculation of the dose in the UK limb of the trial was out by a factor of 2 and that this resulted in the half dose, followed by full dose limb of the trial in the UK.

“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. We have to wait for the full data and to see how the regulators view the results of the phase III trials.

“The US and European regulators might possibly take a different view. All we have to go on is a limited data release. The protection from the Oxford-AstraZeneca vaccine may be less than that from the RNA vaccines, but we need to wait and see.”

A spokesperson from the University of Oxford told The BMJ, “When it was apparent that 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, allowing us to include both approaches in the phase III trial.”

Peer review

Other questions have been raised regarding differences between the arms run in the UK and Brazil, such as no standardised dosing scheme and the different control injections being used. Despite these differences the data from both trial arms were combined.3

Natalie Dean, assistant professor of biostatistics at the University of Florida, USA, has also raised concerns. She said, “I am guessing people think my objection is to ‘science by press release’ and that I want a peer reviewed publication. But no, not really. What I want is reliable and definitive evidence to inform policies impacting millions.

“If the answer is that AstraZeneca needs to go back and add a new half dose arm to their trials so that they can prospectively evaluate its efficacy in diverse subgroups, then we have to carefully consider the value of a peer reviewed publication at this moment.

“I am very encouraged by the prospect of multiple safe and effective vaccines, particularly cheaper and easier to store vaccines, but these results have major policy implications—and implications for the public’s trust. We have to make sure we get it right.”

Dean said her main concern was that, after the publication of the peer reviewed data, the public could be told that there is not enough evidence to support regulatory approval or to guide policy. This could “create confusion” and jeopardise researchers’ ability to collect the additional data they need if people are unwilling to conduct or participate in further trials, she said.

The University of Oxford confirmed to The BMJ that the interim phase III results have been submitted to a peer reviewed journal. They are expected to be published this weekend (28-29 November).

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