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A preprint, an unpublished non-peer reviewed study, assesses the effectiveness of one dose of the Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines against hospitalisations in the over 80s.
This Roundup accompanied an SMC Briefing.
Dr Peter English, Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:
“This is another excellent paper confirming the efficacy of the two Covid-19 vaccines in use, to date, in the UK. The paper confirms that both vaccines are highly effective in people aged 80 or more, including in patients who have other medical conditions.
“It is only 12 weeks since (on 8 Dec 2020) we started to use the Pfizer-BioNTech (Pfizer) vaccine in the UK; and 8 weeks since (on 4 Jan 2021) we started to use the Oxford-AstraZeneca (AstraZeneca) vaccine against Covid-19 in England. Yet already there are a number of papers looking at the effectiveness of the vaccines against a range of outcomes and in different population groups.
“We are still feeling our way in confirming the optimum approach to vaccination. The UK has taken a lead by prioritising a single dose of vaccination to as many people as possible initially, with the booster dose being given at 12 weeks, rather than the three- or four-week prime-boost intervals used for the Pfizer and AstraZeneca phase III trials. (We must remember that the phase III trials were a best-guess for rapid protection – they were never going to be the be-all and end-all of optimum efficacy. The best doses and prime-boost intervals will only emerge over time. The trials were a starting point; they were never set in stone as the perfect approach.)
“One of the outstanding questions from the phase III trials was the efficacy of vaccines in older people. We know that older people generally mount a poorer immune response to vaccinations or infection than younger people. But older people are also at much greater risk of serious disease and death from covid-19 infection, so it is particularly important to protect them with vaccination if this is achievable. This new study from Bristol specifically looks at the efficacy of vaccination in people over the age of 80.
“There are a number of ways of evaluating the effects of an exposure – whether it’s the harmful effects of smoking, or the benefits (or harms) of vaccination. The two main approaches can be categorised as prospective studies, where you compare groups who are exposed and who are not exposed, and follow them up to see what outcomes arise; and case control studies, where you start with the outcomes (e.g. people who have and who do not have the condition you are interested in), and look back to compare their previous exposures.
“To use a different example, we know with certainty that MMR vaccine does not cause autism because – apart from a lack of biological plausibility – extremely large studies have been done. Some were prospective studies: they took people who were vaccinated with MMR, and followed them up to see how many in each group developed autism (it was the same, as the MMR vaccine does not cause autism: people given the vaccine were no more likely to develop autism than people who were not vaccinated). Others were case-control studies: they took people with autism and comparable people without autism, and compared them to see what the odds were that they’d been vaccinated. Again, they found no difference: people with autism were no more likely to have received the MMR vaccine than people without autism.
“The Bristol paper – drawing on data from the ongoing “AvonCAP” surveillance project – uses a case-control approach. They looked at all the people who, on 1st March 2021, will be aged 80 or older, and who were admitted to the hospitals in Bristol during the study period, and identified all those who had signs or symptoms of respiratory illness, such as pneumonia. All the patients included in the study were tested for Covid-19. Those who tested positive were the “cases”, and those who tested negative were the “controls”.
“They checked to see whether the patients had been vaccinated against Covid-19, and the date on which this had been done.
“They were then able to calculate the proportion of the patients in the case and control groups had been vaccinated at least 14 days previously. Comparing these proportions – the odds of having been vaccinated – gives the “odds ratio”, from which you can get a good estimate of the protective effect of the vaccines.
“That, in broad terms, is what they did. It was actually a lot more complicated than that. Researchers who collected the vaccination data were “blinded” – they did not know about the people admitted or whether they had tested positive for Covid-19 or not; and the researchers collecting information on the patients did not know about the patients’ vaccination status. (This was done to reduce bias.) They collected a lot of information about each case, including on comorbidities – other illnesses or conditions patients might have, such as frailty, dementia, diabetes, cancer. They also collected information on socioeconomic indicators.
“As you would expect, the Pfizer vaccine was rolled out first, initially to people in care homes; and the AstraZeneca vaccine was rolled out later, in such a way that people who were living independently (and therefore likely to be less ill) were more likely to get the AstraZeneca vaccine. This can be seen in the comorbidity data for the two vaccine groups.
“The analysis was also complicated by the fact that the proportion of the population getting ill varied over time, and this could have influenced the findings. To compensate for this, they did the analysis separately for each week. They will also have been able to look at the time since the first dose was given – the authors make it clear that these are initial findings, and that the study is ongoing, so, over time, we can expect to see a lot more data, and to be able to draw increasingly clear conclusions about a lot of research questions.
“In the meantime, however, this is very strong evidence that both vaccines are very effective – and indistinguishably effective – even in people who are aged over 80 and who have other illnesses.
“These data should help other countries make decisions about whom to vaccinate, and which vaccine to use (the answer to the latter being – the one you can get hold of!).
Dr Andrew Garrett, Executive VP, Scientific Operations, ICON Clinical Research, said:
“This important study adds to the body of evidence that supports the view that single dose vaccination has been highly effective at reducing severe disease due to the SARS CoV2 virus in the UK elderly. In comparison to the large PHE study reported on 1st March, the Bristol study is smaller but more detailed. This trade-off is helpful since overall conclusions are more robust if consistent results are obtained from different study designs and datasets.
“The Bristol case-control study has collected data from every adult patient admitted to two Bristol NHS hospitals with evidence of acute lung disease. In total there were 136 cases and 298 controls from 18th December 2020 to 26th February 2021, and for each patient it was determined whether they had been vaccinated, and with which vaccine, and whether they were infected with SARS CoV2 (case) or not (control). Adults must have been eligible for vaccination (i.e. aged at least 80 years by end March 2021). Like the PHE study, and other recent studies, it is observational in design and there remains potential for bias. However the consistency of the results with other studies is quite remarkable. The authors draw sensible conclusions and carefully analyze the data in weekly intervals to account for anticipated time trends in infection prevalence, vaccine prioritization, etc. Account has also been taken of other known confounders, such as social deprivation and sex. As expected, more case-control data are available for the Pfizer/BioNTech vaccine (404 patients) than for the Oxford/AstraZeneca vaccine (126 patients), and the latter had more patients sent from care homes due to the timing of the respective vaccine roll-outs.
“From separate analyses, the Vaccine Effectiveness (VE) was 71.4% (95% confidence interval 46.5, 90.6) for Pfizer/BioNTech and 80.4% (95% CI 36.4, 94.5) for Oxford/AstraZeneca, although when a like-for-like time period was used for the Pfizer/BioNTech vaccine, VE increased to 79.3% (95% CI 47.0, 92.5). All in all, impressive results for both vaccines.
“There is now overwhelming evidence that single dose vaccination has been highly effective in the short-term to reduce severe COVID-19 disease, regardless of the approved vaccine administered. The optimal approach to developing long-term immunity to SARS CoV2 and its variants is still to be determined, although a randomised trial is underway in the UK to explore the varying immunological response to different dosing intervals and different vaccine combinations.”
Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:
“Observational studies of vaccine effectiveness are never simple to undertake, analyse and interpret. Most recent studies have relied on information in population-based databases with linkage to vaccination and outcome data. Traditionally many studies were done using a particular form of case-control study called a ‘test-negative design’ which can be done using a database but may also be carried out using prospective data collection, especially in a hospital setting. The AvonCAP study is an example of such a study. It is useful to have a variety of studies which can have different biases so that an overall picture of vaccine effectiveness does not rely on similar designs which may have similar biases.
“This study is a very useful addition to the surveillance of effectiveness of vaccines, and although not nationally based provides reasonably reliable answers.
“The exact estimates of effectiveness should not be the headline, since there is considerable uncertainty in the exact value related to the numbers of patients in the study, but also due to the possibility of inevitable biases in any observational study. What is clear is that these results provide further evidence that the vaccines are effective both in an older age-group less studied in the trials and for an outcome which was rarer in the trials than in ‘real-world’ use, namely hospitalisations.
“There is a particular bias that this design avoids that is related to patients seeking healthcare differently when they have been vaccinated. This study looks at all those being hospitalised for acute respiratory disease and examines the vaccination status of those who test negative for the presence of the SARS CoV-2 virus.”
Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:
“This is a well-conducted case control study looking at the impact of vaccination on older populations in the south-west of the UK. Different study types can be used to look at vaccine effectiveness. A clinical trial involves prospective recruitment of participants who are then administered a vaccine or placebo. A case control study looks back at ‘what has already happened’, so is an appropriate method for examining ‘real-world’ data. This study covered patients admitted to hospital, aged >80, and with a diagnosis of respiratory disease. The cases had a positive test for COVID-19, the controls had a negative test. The researchers then assessed levels of vaccination between the two groups.
“One of the key aims of the vaccination roll-out is to reduce hospitalisation and death from COVID-19 in vulnerable populations, since this has posed a massive burden on the NHS over much of the last 12 months.
“This case control study estimates high levels of protection in older populations after one dose of either the Pfizer or Oxford vaccine. There are limitations, such as the wide confidence intervals around both the Pfizer and Oxford AstraZeneca data, indicating uncertainty as to the true level of protection given by the vaccine. However, the results here are underpinned by similar findings from the emerging body of evidence that covers clinical trials and analyses of real-world data.
“Overall, this looks like further good news around COVID-19 vaccines. There has been a very high uptake so far in priority groups. The excellent effectiveness should result in fewer COVID-19 admissions and thus an easing of the huge pressures on the NHS over the coming months. The key beyond this will be to ensure high uptake in younger populations. This is important for various reasons, including to lower the incidence of long COVID that can occur with mild infection, to reduce onward transmission to susceptible individuals who haven’t got full protection, and to reduce the risks of new variants emerging that may lower the impact of vaccine effectiveness.”
Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:
“This latest paper by Hyams and colleagues from Bristol is a test-negative case-control study of hospitalised patients with respiratory disease. In essence they compare patients admitted with respiratory symptoms with a positive COVID test against those patients admitted with respiratory symptoms who then test negative for COVID. This study design (sometimes known as a case-case study) is a well established design and has the benefit of relatively easy recruitment of the control group which these days can often pose great difficulties. This type of study design is not without its problems, however. The main issue is that because the control group also has a disease any risk factors for that disease could appear to give significant negative associations with the outcome of interest. However, given that it is unlikely that immunization would affect the risk of non-COVID disease this is not likely to have had an important impact here. The other issue is that false negative tests would lead to incorrect allocation of cases to the control group and so reduce the apparent effectiveness of vaccine but again these are likely to represent only a small proportion of cases.
“In any event, this study provides important additional evidence that both the Oxford AstraZeneca and the Pfizer vaccine are both highly effective at keeping people out of hospital and so presumably keeping people alive. As with the recent pre-print from Public Health England Oxford AstraZeneca vaccine seems to perform marginally better than the Pfizer vaccine at keeping people out of hospital although much of the apparent benefit of Oxford over Pfizer seems to be because of the fact that Pfizer was being used earlier and when analyses were restricted to the same weeks when both vaccines were being used much of this apparent benefit was reduced.
“So the main conclusion from this study is that a single dose of either the Oxford AstraZeneca or the Pfizer vaccine are both roughly equally effective at keeping elderly and frail people out of hospital and so reducing risk of death. Furthermore the balance of evidence is very strongly that both vaccines are roughly equally effective with the Oxford AstraZeneca maybe having a slight edge (though we will have to wait for much more date to know that for certain).”
Preprint: ‘Assessing the effectiveness of BNT162b2 and ChAdOx1nCoV-19 COVID-19 vaccination in prevention of hospitalisations in elderly and frail adults: a single centre test negative case-control study’ by Catherine Hyams et al.
All our previous output on this subject can be seen at this weblink:
www.sciencemediacentre.org/tag/covid-19
Declared interests
Dr Peter English: “No COI.”
Dr Andrew Garrett: “I am employed by ICON which is a Contract Research Organization. ICON provides pharmaceutical services to the pharmaceutical and biotechnology industries. ICON conducts clinical trials on behalf of Sponsors, including vaccine trials. I am a member of the UK Statistical Authority’s (UKSA) Research Accreditation Panel.”
Prof Stephen Evans: “I have been present at discussions on this research project through membership of a PHE group looking at multiple studies looking at vaccine effectiveness
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.”
Dr Michael Head: No COI
None others received.