The UK regulator has released a statement following suspensions of the Oxford-AstraZeneca COVID-19 vaccine by some countries over suspected blood clots.
Dr Craig Hartford, member of the Faculty of Pharmaceutical Medicine (FPM) Policy and Communications Group (and reviewed by a panel if FPM experts in vaccines, medicines and pharmacovigilance, including Dr Gillies O’Bryan-Tear, Dr Sheuli Porkess, Dr Neil Snowise, Dr Penny Ward), said:
“All COVID-19 Vaccines approved for use in the UK by the MHRA have met strict safety standards. The regulator has said that the vaccine works well and that you can have the vaccine – indeed it is the major way for all of us to get out of this COVID-19 pandemic, preventing and reducing further disability and deaths, helping the recovery of our economy and enabling your life to return to normal.
“Vaccines’ safety is assessed extensively at all stages of development, including: pre-clinical testing in research laboratories; large clinical studies; and, once the vaccine is made available to the public, by close monitoring and evaluation of the vaccines in clinical use. COVID-19 vaccines’ efficacy, safety and quality are comprehensively evaluated, as for other vaccines and medicines.
“Early reports from Public Health England suggest that both the COVID-19 vaccines authorised for use in the UK (Oxford-AZ and Pfizer-BioNTech) are highly effective at preventing hospitalisation for COVID-19 and may in addition reduce infection rate and potential transmission.
“All medicines and vaccines can have some side effects, but serious side effects are unusual – most side effects are typically mild and do not last long. In the case of both vaccines, the most frequent side effects are those linked to the injection and to stimulation of the immune system (which is the intended effect of the vaccines), such as pain at the site of injection and ‘flu-like’ symptoms including chills, mild fever, tiredness and muscle/joint pain.
“The MHRA are proactively monitoring all the safety events that are reported to them following vaccination, via the Yellow Card Scheme and other systems. Events can be reported by members of the public who have been vaccinated or by healthcare professionals. All of these events are carefully evaluated to assess whether any may be caused by a vaccine or not.
“When assessing a safety event for whether it may be related to a vaccine or not, numerous factors have to first be looked at and taken into account. For example: what is the timing of the safety event in relation to the vaccine administration? Is the vaccine likely to produce such a safety event based on its known actions? Is there any information in the pre-clinical or clinical development data that also suggests that the safety event may be being caused by the vaccine? Does the person with the safety event have other medical reasons, not related to the vaccine, for the event happening to them? Is the safety event more frequent than that normally expected in the same population? And many, many other pieces of information must be considered first!
“If a safety event is considered to be likely to be caused by the vaccine, the information for patients and prescribers will be updated to provide advice to enable effective management and prevention of the side effect in people at particular risk of the side effect. Even if a safety event is caused by a vaccine, that does not automatically mean you should not have a vaccine! As for all medicines, the benefits of the vaccine versus the risks of having the vaccine are weighed up, including the risks of not having the vaccine – such as acquiring COVID-19 disease, disease symptoms and the risk of hospitalisation that are caused by the virus itself, the risk of transmitting COVID-19 to others and the potential for long-lasting virus effects or “long-COVID”. On average, individuals becoming infected with COVID-19 have an approximately 1 in 100 (1%) risk of dying.
“The UK’s regulator (MHRA) and the EU’s regulator (European Medicine Agency- EMA) have comprehensively reviewed all the available information on the “clotting” events reported with the Oxford-AZ vaccine. “Clotting events” is a broad term but can include for example “deep vein clots” such as in the calves, clots associated with low levels of platelets (elements in the blood that help it to clot), and the rare but serious clots of the sinus vein that drains blood from the brain. Based on all currently available information, these clotting events are NOT regarded as being caused by the vaccine(s). The MHRA and EMA regulators will continue to monitor and evaluate clotting events reported with the vaccines, to determine if they are caused by the vaccines. They have also provided advice on how to minimise the potential risks of the rare clotting events. The MHRA and the EMA, and the World Health Organization, have concluded, based on all the currently available information, that the benefits of the vaccine outweigh the potential risks and outweigh the known risks of the vaccines and you should continue to receive the vaccine(s).
“In the UK you can report suspected side effects to COVID-19 vaccines at https://coronavirus-yellowcard.mhra.gov.uk/.”
Prof Gino Martini, Chief Scientist at the Royal Pharmaceutical Society, said:
“I hope that any concerns about potential links between the Oxford-AstraZeneca Covid-19 vaccine and regular blood clots can now be discarded given the positive verdicts delivered by the EMA, the MHRA and the WHO, who have all now said the vaccine is safe, effective and can continue to be used. The vaccine is playing a crucial role in protecting vulnerable groups from hospitalisation and death and helping to decrease infection rates across the UK.
“The MHRA is renowned as a world-class regulator of medicines and vaccines. They are continuing to monitor the Oxford/AstraZeneca vaccine closely as part of a ‘rolling review’ approach to COVID-19 jabs, through rigorous checks and processes, as they would for any other vaccine or medicine. Regulators are continuing to monitor and investigate some very rare instances of a blood clot in the brain.
“As trusted health professionals, pharmacists are playing a key role in administering COVID-19 vaccinations and have contributed enormously to the success of the programme so far. We have full confidence in these vaccines and can confidently state that pharmacists can continue administering them to patients. It is so important that we get all those at risk from the virus vaccinated as soon as possible.”
Prof Sir David Spiegelhalter, Chair, Winton Centre for Risk and Evidence Communication, University of Cambridge, said:
“The MRHA are investigating these five serious events that happened after 11,000,000 AZ vaccines.
“Let’s suppose the link is causal, although this is so far unproven. So assume there is around 1 in 2,000,000 chance of this severe event.
“Suppose 2,000,000 AZ vaccines are given in a week to middle-aged people, say 50-year-olds who are not at high risk from COVID-19. We would expect one such serious adverse event.
“But suppose these 2,000,000 people did not get their vaccine that week. At current UK rates, we might expect 2,000 to catch the virus – this would be higher elsewhere in Europe. As these are at lower risk, we might expect 20-30 to be hospitalised, and around 5 to die. So even for the week of the vaccination, the benefits far outweigh the risks.
“But that’s just one week. These unvaccinated people continue to have that risk for every subsequent week that their vaccination is delayed.
“So the benefit/risk balance seems firmly in favour of the vaccine, even if these events do turn out to be tied to the vaccine itself.”
Dr Andrew Garrett, Executive VP, Scientific Operations, ICON Clinical Research, said:
“The statement from MHRA can be viewed as describing a hierarchical evaluation of the available evidence. Their view is that overall the evidence does not support a causal relationship between the Oxford/AstraZeneca vaccine and the occurrence of venous blood clots, but that for a specific rare subset of venous blood clotting – sinus vein thrombosis – their review will continue. In other words, more data is needed to make a stronger statement with regard to this rare disease. Furthermore, as a sensible precaution, those vaccinated should seek medical attention if they observe potential signs and symptoms post-vaccination of sinus vein thrombosis. So in effect the MHRA is raising awareness of a potential event, will gather more data and will continue to monitor the situation closely – including taking into account evidence from other countries. Overall the recommendation is that vaccination program should continue unchanged based on the benefit/risk ratio.”
Prof Ian Douglas, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:
What is the process behind this work and how does the MHRA reach a decision like this?
“A detailed assessment will have been made of the individual case reports, taking into account things like patterns in the time to onset since vaccination and possible alternative explanations based on the medical history of the person affected. Cases in otherwise young and/or healthy people, with a consistent pattern could give cause for concern. The cases will have been reviewed by people with a wide range of expertise in different medical disciplines to make sure all angles are considered. But on the whole, it is often very difficult to conclude that a vaccine was the cause in an individual case, because we know that these kinds of events happen all the time. To help with this the MHRA have also looked to see whether the number of cases reported is more than would be expected under normal circumstances, without the vaccination campaign. So far, it’s clear we are not seeing more cases than might normally be expected.
Work is ongoing on the more specific rare case of blood clot in the cerebral veins (sinus vein thrombosis) occurring together with lowered platelets (thrombocytopenia) – what would you say to people worried about the vaccine and this condition?
“The MHRA and other regulators will examine these reports in detail to see if there is anything about them that suggests a possible causal link. Two things we know for certain are that the number of cases reported is very low and so if there is any causal link, it must be very rare. But more importantly we know for certain that the vaccine will actually prevent severe COVID-19 illness, which can itself include clotting problems.
What do they mean by benefits vs. risks of getting a vaccine?
“This is where we weigh up all the evidence we have on the possible side effects of a vaccine and we decide whether the risk of these is outweighed by the known benefits. In this instance, we know that the vaccine gives us substantial protection against severe COVID-19 and death. Individually, this means our personal risk of becoming ill or dying is drastically reduced. To balance this, we know from the randomised trials and our experience so far from >30 million people being vaccinated in the UK that the side effects people might experience are not serious and seem to be short lived. But on top of this, it means that as more and more of us are vaccinated, the rate of infection with the coronavirus in the community goes down. This is a vital step on the pathway to returning to some kind of normality. Most of us would tend to think the benefits we will get from the vaccine outweigh these risks by a long way.
How common are side effect from the AZ vaccine? What should people do if they have side effects?
“People are being given a leaflet when they receive the vaccine to tell them what side effects might occur. This is a really helpful resource for people to refer to. Some people will have no side effects, whilst others may have one or more. Importantly, although some side effects are pretty common, they are almost all not serious (with the exception of anaphylaxis). For example, quite a lot of people report having a sore arm, or flu like symptoms. If people think they are having a side effect that fits with the description in the leaflet, they will tend to be able to manage this themselves at home e.g. by taking paracetamol. If someone has side effects that get worse over time or continue for several days, they should seek medical assistance either by calling 111 or their general practitioner.”
Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:
“A major problem is discerning whether there is a possibility that this rare brain clotting condition was caused by Covid-19.
“Exactly these sort of conditions have been seen in patients with Covid-19 prior to the vaccines being available. So, unless it is ABSOLUTELY certain that the patients could not have had Covid-19 then it may not be the vaccine.
“There have been cases of this rare brain clotting problem with no apparent Covid symptoms, and some who test negative on repeat testing, but are later shown to have had SARS CoV-2 virus antibodies, who end up with the condition. Those who are vaccinated may get infected, either before getting the vaccine or in the period when the vaccine is not expected to work, and may then be unaware that they have been infected and it is assumed that the vaccine is the cause. It is clearly possible that it is the cause, but the possibility of it being Covid-19 disease being the cause must also be considered.”
All our previous output on this subject can be seen at this weblink:
Dr Craig Hartford: “Dr Hartford owns shares in pharmaceutical companies including Pfizer and is a Pfizer past employee. Dr Hartford is employed by Pharmaceutical Company(s).”
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. I have received one dose of the Oxford/AstraZeneca vaccine as part of the UK vaccination program.”
Prof Ian Douglas: “Research grants and shares in GSK.”
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.”
None others received.