The European Medicines Agency (EMA) have concluded that the benefits of the Oxford-AstraZeneca COVID-19 vaccine still outweigh the risks despite possible link to rare blood clots with low blood platelets.
Prof Ian Douglas, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:
“The approach taken by the EMA seems sensible. They have restated that the AZ COVID-19 vaccine is safe and effective, and have concluded there is currently no evidence of a causal link with venous thromboembolism. They have also been honest and open about their continued investigation into other clotting related disorders including disseminated intravascular coagulation and sinus vein thrombosis. This doesn’t mean a link with the vaccine is likely to be causal, but that they are taking these reports seriously. This is a sign of a well-prepared response to the vaccine role out which was always going to be accompanied by safety worries. What matters is that they are thoroughly investigated and that the findings are communicated as soon as possible. This is likely to involve formal studies using electronic health records to see whether people who have been vaccinated are more likely to develop these problems than people who haven’t been vaccinated and will probably take weeks to months to complete.”
Professor Andrew Pollard, Chief Investigator on the Oxford Vaccine Trial, said:
“I welcome the news that both the MHRA and EMA have reiterated that the vaccine’s benefits continue to outweigh any potential risks, and the vaccine should continue to be administered.
“Thousands of cases of COVID-19 are occurring across Europe every day, the rate of covid is rising in many countries on the continent and vaccination remains a central component of our fight against the pandemic virus.
“It is important that public health bodies monitor the roll out of the vaccine, and safety has to be paramount with any new medicine. Importantly, real-world data shows the clear impact of the vaccine on public health – with far fewer cases and hospitalisations from coronavirus in those who have been vaccinated.”
Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:
“The EMA have finished their investigations into the Oxford AstraZeneca vaccine and its possible association with thromboembolic events. They did not find a causal link in this investigation. The EMA will continue to investigate this safety signal.
“It is good to see the EMA reaffirm their continued recommendation of this vaccine. This backs up other comments this week from the WHO, and other regulators such as the UK MHRA. The key message has to be that the Oxford AstraZeneca vaccine is safe and effective.
“If the world is to put an end to this pandemic, then vaccines will be the key tool that underpins the global response. We need several safe and effective vaccines to help us do that. We have plenty of data on this AstraZeneca vaccine, including over 10 million doses administered here in the UK and almost 20 million doses in total across Europe.
“It is absolutely right that countries investigate safety signals as soon as they are observed. This is a hugely important part of any vaccine campaign. However, I’m still not clear why the decision of several countries was to withdraw the vaccine from use. It is entirely possible to continue the roll-out whilst adverse events are investigated.
“Withdrawing a vaccine during a pandemic will have other consequences, including leaving people unprotected against COVID-19 when they may otherwise have been immunised. There may also be a rise in vaccine hesitancy, and that may be difficult to overcome in the short to medium term. We don’t want a situation where people wait for another vaccine to arrive, or worse still, prefer not to get vaccinated at all.”
Dr Peter English, Retired Consultant in Communicable Disease Control, Former Editor of Vaccines in Practice Magazine, Immediate past Chair of the BMA Public Health Medicine Committee, said:
“The problem with rare conditions, is that they are very common.
“That sounds like an oxymoron; but the reality is that there are lots of different rare conditions. When I trained as a GP I was told that roughly one in every 15 consultations would relate to a very rare medical condition.
“This is a huge problem when trying to establish whether an apparent excess of a rare condition following vaccination is a consequence of vaccination – there is a “causal link”; or if it’s just due to chance.
“The usual cut-off for “significance” is if something is likely to have occurred by chance less than once in 20 times. That’s why you commonly see 95% confidence intervals on graphs…
“But if there are two possible outcomes to consider, and you’re wondering whether either one of them might have occurred by chance – well, obviously, the chance that one of two things will happen is twice the chance of just one thing happening. So when you’re analysing data with multiple outcomes, you use a different cut-off. One of the ways of doing this, statistically, is to use the “Bonferroni correction”.
“When you’re looking at population-related data, however, it’s harder. There are thousands of rare conditions that might (by chance) show an excess in people who have been vaccinated. If you use a cut-off or 95% probability – well, there will be excesses in lots of them.
“So regulators will look to see how big the excess is (if they can identify one at all); and consider the biological plausibility of a link. (The girl who died in a car crash when her mum was driving her home after her HPV jab clearly didn’t die as a result of the vaccine per se).
“From the evidence I’ve seen to date, it looks far more likely that the association of a rare clotting disorder with a particular Covid-19 vaccine is mere chance, rather than causally related.
“But what if – worst case and very unlikely scenario- it is causally related? What’s the best thing to do?
“Covid-19 causes clotting disorders. If you’re susceptible to the clotting disorder, and the vaccine increases your likelihood of it happening to you by a tiny amount, so small it’s not obviously a causal link to the vaccine, just think how much more likely it is that the disease itself will cause the clotting disorder.
“It’s like Guillain-Barré syndrome (GBS) and flu. We know that flu causes GBS. It has been suggested that flu vaccination might possibly cause GBS – but so infrequently that it’s really difficult to be sure if it’s just a chance finding. If you want to avoid getting GBS, you should choose to be vaccinated (unless you’re going to be living somewhere so remote you won’t be exposed to flu). The low risk of GBS from flu is still so much higher than any possible risk from the vaccine, that the odds of getting flu AND getting GBS as a result are much higher than the odds of the vaccine causing it; and the vaccine makes you much less likely to get the flu, thereby hugely reducing the overall risk of GBS.
“This scare about clotting disorders and Covid-19 vaccines is the same. The vaccines are very unlikely to cause clotting disorders; but if they do, they do so far less often than the disease does, so the best way to avoid getting a clotting disorder is to get vaccinated.”
Dr Doug Brown, Chief Executive of the British Society for Immunology said:
“When developing a new vaccine, the two most important factors are safety and effectiveness. All vaccines have to go through rigorous clinical trials before they are approved for use and they are then monitored during subsequent rollout by the appropriate safety authorities, which in the UK is the Medicines Healthcare products Regulatory Agency (MHRA). The approved COVID-19 vaccines in the UK have all been through this thorough process.
“Over the last few days, a number of countries decided to pause the rollout of the AstraZeneca/Oxford COVID-19 vaccine to double check that having the vaccine is not linked to any cases of blood clots. These reports can sound worrying but we need to put the risk into perspective. As we all know, people fall ill for a multitude of reasons. As has happened in this case, it is right the medicines regulators review the evidence to work out what the cause is behind the rare reports of blood clots and whether it is linked to having been given the vaccine or not. We must remember that COVID-19 is a disease that can have serious consequences in its own right, including the development of coagulation problems. In the case of the AstraZeneca/Oxford vaccine, the European Medicines Agency have concluded the vaccine is safe and effective and recommend the continuation of the vaccine rollout, a viewpoint backed up by the UK regulator, the MHRA.
“Vaccines are our route out of this pandemic. Whilst safety is always the foremost concern, this episode shows that the monitoring systems are working as they should. Vaccination is the safest and most effective way to protect yourself from falling ill with COVID-19.”
All our previous output on this subject can be seen at this weblink:
Prof Ian Douglas: “Research grants and shares in GSK.”
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.”
Dr Michael Head: “No COI.”
Dr Peter English: “No COI.”
Dr Doug Brown: “Trustee of the Association of Medical Research Charities.”