Surprise Oxford vaccine results due to manufacturing error

The makers of the vaccine candidate, Oxford University and AstraZeneca, confirmed the manufacturing error just days after releasing preliminary results that described the vaccine as ‘highly effective’.
 
Those results indicated that a group of volunteers who received a lower dose appeared to be better protected (90% efficacy) than those who were administered two full doses (62% efficacy).
 
Put together, the developers said this showed the vaccine appeared to be 70% effective.
 
However, the way in which researchers arrived at the results, and how those results were reported, has led to pointed questions from experts.
 
The latest vaccine statement released by Oxford University conceded the reason some volunteers got a half dose was because some of the vials used in the trial did not have the right concentration of vaccine.
 
The university said it discussed the problem with regulators and agreed to complete the late-stage trial with two groups.
 
The manufacturing problem has been corrected, according to the statement.
 
But the relatively small number of people who received a low dose means it is difficult to know if the effectiveness seen in the group is real or a statistical quirk; only 2741 people received a half dose of the vaccine followed by a full dose, AstraZeneca said, whereas 8895 people received two full doses.
 
Additionally, none of the people in the low-dose group were aged over 55, which may also have skewed the results – although Oxford University says phase 2 trials show the vaccine induces ‘similar’ neutralising antibody titres and T cell responses across all age groups from 18–70.  
 
Former director of immunisation at the UK’s Department of Health, Professor David Salisbury, said the decision to pool results from two groups of participants who received different dosing levels to reach an average 70% effectiveness has also led to confusion.
 
‘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 of the figure. ‘I think many people are having trouble with that.’
 
The partial results were taken from large ongoing studies in the UK and Brazil designed to determine the optimal dose of vaccine, as well as examine safety and effectiveness. Multiple combinations and doses were tried in the volunteers and were compared to others who were given a meningitis vaccine or a saline shot.
 
It is not know why a lower dose would result in greater efficacy, but Oxford researchers have said they are working to uncover the reason.
 
Professor Sarah Gilbert, one of the Oxford scientists leading the research, said the answer is likely related to providing exactly the right amount of vaccine to trigger the best immune response.
 
‘It’s the Goldilocks amount that you want, I think, not too little and not too much,’ she said. ‘Too much could give you a poor-quality response as well.
 
‘So you want just the right amount, and it’s a bit hit and miss when you’re trying to go quickly to get that perfect first time.’
 
Regardless of the reason, a more detailed breakdown of results is expected in the coming weeks. Those details should feature data that includes demographic and other information about who got sick in each group, therefore giving a more complete picture of the vaccine’s effectiveness.
 
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