Coronavirus: Experts call for clarity and caution over Oxford vaccine trial results

Experts have called for caution and clarity following the emergence of apparent irregularities in the vaccine trial data released by Oxford University and AstraZeneca earlier this week.

Investigations are ongoing into the preliminary results, which suggested that the Covid-19 jab was up to 90 per cent effective when administered as a half dose followed by a full dose.

Since unveiling the data on Monday, AstraZeneca has admitted this dosage initially applied in UK trial participants was a mistake. “The reason we had the half-dose is serendipity,” said Mene Pangalos, the head of AstraZeneca’s non-oncology research and development.

Side effects such as fatigue, headaches or arm aches were milder than expected in the volunteers, leading to the revelation that the doses were incorrect. Regulators were immediately notified of the error but signed off on the plan to continue testing the vaccine in different dosages.

More than two dozen different dosing regimens were used throughout the UK trial, with volunteers divided into groups dependent on age, as well as how much of the vaccine would be administered and when.

The group that was subject to the highly effective half-dose programme involved 2,741 volunteers. According to Professor Andrew Pollard, director of the Oxford Vaccine Group, this figure meets the “necessary statistical evidence as required by regulators”.

He said further evidence would probably be available next month but it was “a highly significant result even with the numbers that we have”.

However, the scientific head of the US’s Operation Warp Speed – the project to supply America with vaccines – later claimed that the dosing regime was only tested in people aged 55 and under.

Mr Pangalos later confirmed this, leading to concerns that responses to the jab among younger volunteers – who have stronger immune systems – may have been a factor in generating the high efficacy rate.

In another branch of the trial, in which 8,895 participants received two full doses, the vaccine was found to be 62 per cent effective at preventing disease.

As to why the large variation in the dosing programmes produced such different efficacy rates, scientists at AstraZeneca and Oxford University remain stumped. Sarah Gilbert, a professor of vaccinology who developed the vaccine, said it may be that the half-dose regimen “better mimics what happens in a real infection”.

Another point of confusion stems from how AstraZeneca and Oxford University were able to reach an overall average efficacy rate of 70 per cent for the vaccine, said David Salisbury, an associate fellow of the global health program at the Chatham House think tank.

“You’ve taken two studies for which different doses were used and come up with a composite that doesn’t represent either of the doses,” he said. “I think many people are having trouble with that.”

Mr Pangalos has defended AstraZenca’s handling of testing, the dosage mistake and its public disclosures.

Asked why the company had not shared the information with the public, he said: “I think the best way of reflecting the results is in a peer-reviewed scientific journal, not in a newspaper.”

Stephen Evans, a professor of pharmacoepidemiology at London School of Hygiene and Tropical Medicine, warned against jumping to conclusions over the revelations, insisting “there are many things that we still need to find out and we will have to wait for full publication”.

“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,” he added.

“We have good grounds for trusting that the regulation in this high profile area will be done as carefully or more carefully for these vaccines than for any others in the past.”

Peter Openshaw, professor of experimental medicine at Imperial College London, said that all speculation was for now based on a “limited data release”.

Questions have also been raised over the way in which Monday’s results were not drawn from a single, large-scale trial – as was the case for the data earlier presented by Pfizer and Moderna regarding their own vaccine candidates, both of which have been shown to be more than 90 per cent effective.

Instead, AstraZeneca pooled the results from two differently designed clinical trials in the UK and Brazil, which collectively involved more than 20,000 volunteers.

The two studies, which begin at different times, did not adopt the same standardised dosing schemes or provide the same “control” injections to volunteers who were not getting the experimental Covid vaccine.

Some experts also say it is unclear how many coronavirus cases were found in each arm of the trial, with AstraZeneca reporting that a total of 131 infections had been recorded among study participants.

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

A spokesman for AstraZeneca said: “Following established clinical trial standards, the data will be published in a peer-reviewed journal in due course.”

Eleanor Riley, a professor of immunology and infectious disease at the University of Edinburgh, described the media reports as “worrying”.

“Whether or not they are justified, and whether or not they affect the validity of the data released earlier in the week, they need to be answered clearly and completely,” she said. “Trust is at a premium when it comes to vaccines and we must not do anything that might in anyway undermine that trust.”

On Thursday Sir John Bell, Oxford’s regius professor of medicine and the UK government’s life sciences adviser, dismissed suggestions the trial had been improperly run. “We weren’t cooking this up as we went along,” he said.

Defending the trials, Sir John told a symposium run by the Faculty of Pharmaceutical Medicine: “[The] MHRA [Medicines and Healthcare Products Regulatory Authority] knew perfectly well what we were doing. They approved all the protocols.”

He said the vaccine, despite the apparent data irregularities, had still been shown to surpass the 60 per cent efficacy rate acquired for approval by most regulators.

A full data release and breakdown is expected to be provided in the coming days in the scientific journal The Lancet.