There have been media reports suggesting that the independent commission that advises the German government on vaccination policy has recommended that the Oxford/AstraZeneca COVID-19 vaccine should only be given to people under the age of 65.
Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:
“The data from the OxfordAZ trials are not as clear cut as for the Pfizer and Moderna vaccines. However, this is my understanding of the arguments
1. It is true that the Oxford group did not include many people>55 years in their early trials as yet no definitive efficacy estimate in the over 60s group https://www-sciencedirect-com.uea.idm.oclc.org/science/article/pii/S0140673620326611.
2. However, we do know that antibody responses in older people is very little different to that in younger people and antibody levels seem to be a good predictor of protection
3. The estimate of only 6% is hugely uncertain. So far there were only 1 case in intervention and 1 case in control arms and no severe cases in the study arm information about when those infections occurred so the value. This data cannot be used to give even a rough estimate of efficacy.
4. We do know that the OxfordAZ is relatively poor at preventing infection even in younger people although it is much better at preventing symptomatic illness and even better at preventing severe disease https://www-sciencedirect-com.uea.idm.oclc.org/science/article/pii/S0140673620326611.
“The balance of evidence does support the continued use of the OxfordAZ vaccine and people in the older age groups should feel confidence about having whatever vaccine they are offered. I know I will take any of the vaccines when it is my turn to reach the top of the queue.”
Dr Doug Brown, Chief Executive of the British Society for Immunology, said:
“We are living through an unprecedented pandemic situation both in the UK and globally where governments need to make important policy decisions in the face of fast-moving situations where our knowledge of the underlying science is still evolving. We should not be surprised that this sometimes results in governments making different decisions from each other.
“The UK Medicines and Healthcare products Regulatory Authority (MHRA) will have carefully scrutinised the evidence on this COVID-19 vaccine before making their recommendation. As noted in their original report, there is “limited information available on efficacy in participants aged 65 or over” for the AstraZeneca/Oxford COVID-19 vaccine in the phase 3 trial data published so far. This reflects a need for more data to be gathered and published on the effectiveness of the vaccine in this age group but there is no data so far to indicate that the vaccine isn’t effective in people over the age of 65. It should also be noted that in all published reports, the AstraZeneca/Oxford COVID-19 vaccine shows a good safety profile.
“Since the start of the year, the UK has faced an extremely challenging situation with high levels of SARS-CoV-2 circulating in our communities together with the emergence of the new, more transmissible variant resulting extra pressure on healthcare services. Vaccination is our only way out of this pandemic and we are incredibly fortunate to have had several vaccines developed in less than a year. But we need the government and authorities to continue to generate and monitor data during the vaccine rollout so that they can make real time decisions on how to optimise the vaccination strategy to ensure the greatest benefit to public health.”
Prof Jason Oke, Senior Statistician and Prof Richard Stevens at the Nuffield Department of Primary Care Health Sciences, University of Oxford, said:
On the 6.3% figure:
“The figure (6.3%) quoted in the report is based on just two infections, one in the vaccine arm and the other in the control arm. Unethical is probably too strong a term but it would certainly be misleading to report a point estimate such as this without acknowledging the huge uncertainty due to the lack of data in this age-group. It is good practice to report uncertainty, especially when the results are inconclusive. This data tells us very little about the vaccine activity in this older age group. It is unlikely that the study was designed to be large enough to assess the effect of the vaccine is this age group separately. There are two ways to interpret this, 1) that there is no evidence that the vaccine works in this age group or 2) no evidence to suggest that vaccine activity in over 65’s is different from the overall effect (70%). The authors of the draft recommendation appear to interpret that there is no evidence that the vaccine works in this age group. Others may interpret it that there is no evidence to suggest the activity is different for older age groups.”
Dr Simon Clarke, Associate Professor in Cellular Microbiology at the University of Reading, said:
“After combing through the trials data in detail, STIKO have decided that there is insufficient evidence that the Oxford-AstraZeneca vaccine works in people over 65. It’s important to stress that this is not evidence that the vaccine does not work, merely that the evidence does not currently exist to satisfy the authorities in Germany.
“Supporters of the vaccine will point to the fact that it stimulates an immune response in over-65s. While that is positive, it does not guarantee protection against infection or disease. Having the right type of immune response is more important than its strength. We don’t yet know, in detail, what makes someone immune to Covid-19, so trying to measure it in a laboratory may be pointless.
“There will now be millions of older and more vulnerable people in the UK who have had the AZ jab, wondering, am I really protected? I would say to anyone over 65 who has had the AZ jab the same I would tell anyone who has had any covid jab. We already know that no vaccine available is 100 per cent protective against getting sick, and at the moment you should still behave as if you, and anyone around you, could be infected with Covid-19. We know that the AZ jab provides some protection, but because the trials recruited only a few hundred over 65s in the trials, the data are not clear enough to say for sure exactly how effective it is.”
An AstraZeneca Spokesperson, said:
On Germany STIKO recommendation:
“The latest analyses of clinical trial data for the AstraZeneca/Oxford COVID-19 vaccine support efficacy in the over 65 years age group. We await a regulatory decision on the vaccine by the EMA in the coming days.”
And on the data:
“Reports that the AstraZeneca/Oxford vaccine efficacy is low in adults over 65 years is not an accurate reflection of the totality of the data. The latest analyses support efficacy in this age group, which we expect to be published by the EMA in the coming days. The most recent Lancet publication has demonstrated that older adults showed strong immune responses to the vaccine, with 100% of older adults generating spike-specific antibodies after the second dose.”
Prof Paul Morgan, Director, Systems Immunity URI Cardiff, Cardiff University, said:
“Regarding STIKO’s (the German equivalent of the UK’s JCVI) conclusions around not recommending the AstraZeneca jab in those over 65, without more information as to how they arrived at this decision, it is hard to comment. But in the UK we now have very large numbers of people vaccinated and confirmatory data will be emerging soon.
“Regarding the figure of 6.3% in one of the tables in the document, nothing can be concluded from the data it refers to. It would be scientifically illiterate and wrong to quote significance on the basis of n=1 in each arm of the trial.”
Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:
“Every country is in a different situation. Advice on the use of a vaccine will depend on its availability and the availability of other vaccines.
“For the Oxford/Astra Zeneca vaccine, in Germany and the rest of the EU there is a shortage, as is well-known. It must be emphasised that this is not a regulatory decision, but draft advice on usage. It is in a context where supplies of the Pfizer/BioNTech vaccine, for which data in older people shows similar efficacy as in younger people, are relatively plentiful. In such a situation it is reasonable to prioritise younger people with one and older people with the other vaccine.
“It was well-known that the clinical data for this vaccine were limited for those aged 70 and over.
“In the preliminary randomised trial data from The Lancet paper, it was stated there “As older age groups were recruited later than younger age groups, there has been less time for cases to accrue and as a result, efficacy data in these cohorts are currently limited by the small number of cases, but additional data will be available in future analyses.” It may be recalled that during the summer of 2020 in the UK (where the older people were largely recruited) there was a fall-off in cases of Covid which meant the data are necessarily limited.
“The estimate of clinical efficacy based on extremely small numbers means it has enormous uncertainty and could be compatible with over 90% efficacy as well. It is so uncertain as to be meaningless.
“The UK regulator (and we will have to see if the EU follows suit), sensibly did not put an age limit on the use of the vaccine and JCVI have not given advice recommending use of one vaccine or the other in older people. Quite how a vaccine with extreme cold chain requirements would be delivered to UK care home residents might be an issue.
“The CEO of Astra Zeneca said “The issue with the elderly data is not so much whether it works or not. It´s that we have today a limited amount of data in the older population. You have to think that the program we have today was run by Oxford, it was the Oxford program. And Oxford is an academy group. They´re very ethical, and very academic. So they didn´t want to vaccinate older people until they had accumulated a lot of safety data in the 18 to 55 group. They said it was not ethical to vaccinate old people until they had enough safety data in younger people. Other companies took this risk, went ahead and vaccinated older people faster or earlier. If you start earlier, you have more data. Essentially, because Oxford started vaccinating older people later, we don´t have a huge number of older people who have been vaccinated. So that’s what the debate is. But we have strong data showing very strong antibody production against the virus in the elderly, similar to what we see in younger people. It’s possible that some countries, out of caution, will use our vaccine for the younger group.”
“He also said “There may also be local political considerations sometimes? I can’t say.”
“What is clear is that The Lancet paper made it clear that the blood test results (immunogenicity) does not suggest that there will be notably lower efficacy at older ages for the Oxford/Astra Zeneca vaccine. This was also true for the Pfizer and Moderna vaccines.
“There is no reason at all for anyone in the UK or elsewhere to think that this Oxford/AstraZeneca vaccine is ineffective at any age. Its ability to be delivered to people in GP surgeries and care homes makes it a vital component in the attempts to reduce hospitalisation and deaths, especially in the elderly.”
Prof Andrew Pollard, Director of the Oxford Vaccine Group, Department of Paediatrics, University of Oxford, said:
“The European Medicines Agency (equivalent of MHRA) recommendation on authorisation of the vaccine is expected in the next few days. Each country has its own JCVI-equivalent (STIKO in Germany), who will then decide how best to use the vaccines in their population once authorised.
“This is the information from the MHRA report:
“There is limited information available on efficacy in participants aged 65 or over, although there is nothing to suggest lack of protection. In this subpopulation, there were only two COVID-19 cases in the primary analysis. When considering all cases from dose 1, there were 2 cases on AZD1222 compared to 8 on control (VE=76%), although this result was associated with a wide confidence interval.”
“This is on page 33 here –
Public Assessment Report (publishing.service.gov.uk)”
Prof Jim Naismith, Director of the Rosalind Franklin Institute, and Professor of Structural Biology, University of Oxford, said:
“Science advances by experimental data. It is really important to read what has been said, German scientists conclude that the Oxford /AZ vaccine is safe and it is effective for under 65’s. Their assessment is that effectiveness is not yet demonstrated for over 65s. They have not said the vaccine is ineffective for over 65’s. Good faith discussions about what evidence is needed for vaccine effectiveness are really important. Experimental evidence and reasoned debate, not over heated rhetoric, will resolve this issue. There is no need to impugn the quality or character of the German scientists here, the UK’s MHRA advised by scientists of equal calibre have come to a different conclusion. Scientists often disagree about how much evidence is needed for any new advance and there is always more data to be secured. Normally this all happens out of sight of the glare of the media and not in a pandemic but such debates are an important part of the scientific process that is familiar to anyone who has ever been through peer review.”
All our previous output on this subject can be seen at this weblink:
Dr Doug Brown: “Prof Doug Brown is a Trustee of the Association of Medical Research Charities.”
Prof Stephen Evans: “No conflicts of interest. I am funded (one day per week) by LSHTM. They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator on any grants obtained from them. I am the statistician to the ‘meta-Data Safety and Monitoring Board’ for CEPI. I am paid for my attendance at those meetings and will be paid expenses for travel if that occurs. I am a participant in the Oxford/Astra Zeneca trial, and on 13th January 2021 learnt I had received the active vaccine.”
Prof Andrew Pollard: “Andrew Pollard is chair of the UK Department of Health and Social Care’s (DHSC) Joint Committee on Vaccination and Immunisation (JCVI), but does not chair or participate in the JCVI coronavirus committee, and is a member of the World Health Organization’s (WHO) Strategic Advisory Group of Experts. He has received research funding for coronavirus vaccine research from UKRI, CEPI and NIHR. Oxford University has entered into a partnership with Astra Zeneca for the development of a coronavirus vaccine.”
Prof Jim Naismith: “No conflicts.”
[Declarations of interest for AstraZeneca are implicit.]
None others received.