We've had some great questions since our vaccine efficacy announcement and the data that goes with it. Many of these are answered in today's publication in the Lancet, and we've provided some additional information here.
Could you explain your efficacy result?
In our peer reviewed publication in the Lancet we are pleased to report full details of our interim trial analysis. We have undertaken a pooled analysis which combines the information from trials in Brazil and the UK, and includes two sub-groups in our UK trial, one who received two full doses of the vaccine, and one who received a half dose of the vaccine followed by a full dose of the vaccine. We agreed the pooling approach with national and international regulators and when we broke the code we found the overall efficacy is 70.4% from this combined analysis. We’ve discovered that the half dose followed by full dose regimen gives an efficacy of 90%, whereas the regimen where volunteers received two full doses gave 62%.
Why are there three different numbers?
The newly published data in the Lancet show that the 70.4% is a weighted average of different dosing regimens across all of the trials. The 90% figure relates to a sub-group of volunteers who received a half dose of the vaccine followed by a full dose of the vaccine, and the 62% to those who received two full doses of the vaccine.
Why are you using the 70% number?
The 70.4% efficacy reported is a weighted average from a pooled analysis of our data that combined information from our trial sites around the UK and in Brazil. Before we looked at the data and began our analysis, we agreed the approach to this analysis with regulators. The pooling was considered appropriate as it improved the generalisability of the findings, by including different regions and populations and because the immune responses appeared similar across the different groups.
How and when did you spot that some doses were lower than expected?
There are two methods used to measure the concentration of the vaccine in a vial: spectrophotometry and PCR.
Our review of the concentration of the vaccine between spectrophotometry and PCR showed some differences between the two.
We discussed the results with the regulators and agreed to use the same dosing approach used in the Phase I trials, spectrophotometry, as this was likely to be result in more consistent performance.
There were no problems with manufacturing the vaccine, however, due to slight differences in the materials used in the production process the spectrophotometry over-estimated the dose, so that after adjustment a lower dose was produced.
This unplanned lower dosing regimen became apparent following our investigations into the different methods of dose estimation, and when we observed the lower vaccine dose was better tolerated by our volunteers than expected, this confirmed that the dose needed to be adjusted to the standard dose agreed in the trial protocol.
This was immediately discussed with the regulators, who agreed to allow our trial protocol to be updated to allow us to follow this scientifically interesting group of volunteers.
This is detailed further in the paper published in the Lancet.
How do you know it won’t happen again? Could you have given people too much vaccine?
The half dose group was unplanned, but we did know in advance that there was a discrepancy in the dose measurements and discussed this with the regulators. We chose the approach to dosing that was logical and safe, as there was never any risk of overdose.
Subsequently, we have worked with our global manufacturing partners AstraZeneca to establish a suite of tests to allow consistency across all batches of vaccine.
If you knew the doses were too low, why did you continue the trial?
When we realised that the dose was better tolerated by the volunteers in our trial, we discussed this with regulators and independent data safety monitoring board and agreed that in a time of a global pandemic, it would be valuable to global health and still scientifically appropriate to continue to follow this sub-group of volunteers.
These are small trials; how do you know this is ‘real’?
The pooled analysis meets the pre-specified criteria for declaring efficacy and is supported by the results of the individual trials and trial arms. The results meet the criteria set in advance for submission to regulators and so we have met our goal for an accessible and highly effective vaccine. The trials continue and we will have more data in the future to provide further insight evidence
The range of the small dose seems very close to the range of the full dose. How do you know this is a ‘real’ effect?
The data are compelling, but we will continue to collect more information about all the participants in the trials
There’s a big variation in when people got their booster vaccine. Does that impact the data?
Our early investigations of the efficacy did not find statistically significant differences between groups receiving their booster at different times, but we will investigate this possibility further.
Which vaccine will I get? The 62%, 70% or 90% effective one?
We have a lot of data on our planned dosing regimen of two full doses and we will provide extensive information for the regulators to consider.
Your data covers 18-55 year olds, the majority of whom are white. How do I know that this vaccine will work for me?
Our early investigations of immune system response in older adults suggest that the vaccine is well-tolerated and generates a similar level of immune response to those at other ages, and we’re optimistic that this means our vaccine is equally effective in older adults, but await further data on this. Our studies in Brazil also include older adults, and Astra Zeneca have a large trial in the USA which provide further evidence in older adults. Our global trials, and those of Astra Zeneca will provide further information to assess how the vaccine performs in different populations around the world.
Why are you only giving this information now, and not in your initial press release?
Normally, we would communicate all findings first through publication in peer review literature. As we are partnered with AstraZeneca, they are required to release High Level Results as is standard for any new medicine under development in order to make key data available in the public domain as soon as possible.
We’re delighted to now be able to share the full interim data in a peer reviewed journal. Both the University of Oxford and our partners AstraZeneca believe it is important to publish as much detail as possible about our studies, through the independently verified method of scientific peer-review literature, and we’re happy to see these results published in The Lancet.
Were there any pauses to the trial because of safety incidents?
Yes. Regulators reviewed and then restarted the trials confident it was safe to do so.
Of nearly 24,000 trial volunteers, and over 74,000 ‘person-months’ of safety follow up, only three from 175 reported serious adverse events were possibly related to the vaccine.
Of these, one was considered ‘possibly related’ to the ChAdOx1 nCoV-19 vaccine, one occurred in the control group, and a further case of severe fever in the vaccinated group was considered to be an expected vaccine-related event.
Safety is our absolute priority in our trials and so our protocol requires the chief investigator to pause the study if there are any unexplained illnesses that occur in the clinical trial. These are expected to occur in any population of more than 20,000 people, but when they do, the greatest scrutiny should be undertaken by independent experts and the regulators to check that it is safe for the trials to proceed.
Which vulnerable groups were included in the trial? When will you include more?
Our Phase III trials were open to people with many underlying health conditions, and these are represented in the trial, and further trials are designed to specifically recruit from these vulnerable groups.
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