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European countries put AstraZeneca vaccine on pause – Expert Reaction

Ireland has joined a growing list of European countries pausing their use of the Oxford/AstraZeneca Covid-19 vaccine after reports of blood clotting.

The vaccine manufacturer says its review of the reports show the jab does not increase the risk of blood clotting. New Zealand agreed to purchase enough of the vaccine to immunise 3.8 million people, alongside agreements it made with three other suppliers.

Local and international experts have commented on the reports.

Professor David Murdoch, Dean and Head of Campus, University of Otago, Christchurch, and Co-Director, One Health Aotearoa, comments:

“Over recent days, several European countries have temporarily suspended administration of the AstraZeneca COVID-19 vaccine following reports of serious blood clotting events in a relatively small number of recipients. This very cautionary approach has been taken while awaiting further information, particularly from the European Medicines Agency (EMA), the agency responsible for safety monitoring of medicines in the European Union.

“This sort of pause is not unusual with the introduction of new vaccines, and is a sign that the adverse reaction monitoring system is working. A key task is to investigate whether these clotting events might be related to the vaccine or whether they have occurred by chance. Very large numbers of people are being vaccinated for COVID-19 at the moment, many of whom have pre-existing health conditions. In this situation, we expect a number of illnesses are going to happen following vaccination by chance alone.

“At present, there is no evidence that clot-related illnesses are happening more frequently than usual among populations receiving COVID-19 vaccines. This is reassuring. However, safety is of critical importance and it is essential that we continue to rigorously monitor the safety of vaccines.”

Conflict of interest statement: Member, COVID-19 Vaccine Strategy Taskforce, NZ Government. Member, COVID-19 Vaccine Strategy Scientific and Technical Advisory Group, NZ Government. Member, Advisory Group, Vaccine Alliance Aotearoa New Zealand (VAANZ). Independent Member, Clinical Trials Steering Committee, University of Oxford COVID-19 Vaccine. Member, COVID-19 Expert Advisory Network, Ministry of Health.

Professor Graham Le Gros, Immunologist, Director Malaghan Institute of Medical Research; Programme Director Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo (VAANZ), comments:

“The AstraZeneca vaccine has been rolled out in quite a large number of people. You’ve got to remember, if you have 500,000 people and someone gets the vaccine and they walk out the door and they have a heart attack and die – is it because of the vaccine or is it because with 500,000 people at any one time on the planet, 5 or 10 people are going to have a heart attack and die? The particular cases that are being talked about right now – some blood clotting issues – they may just be the chance event you have when you have such a large number of people. But because of the very precautionary approach we’re taking with these vaccines, because we don’t know everything about them, things get stopped, and we look at the data and investigate to make sure we’re not making something worse. It’s standard procedure.”

Conflict of interest statement: Professor Le Gros is Programme Director of the Government-funded Vaccine Alliance Aotearoa New Zealand – Ohu Kaupare Huaketo, a partnership between the Malaghan Institute, the University of Otago and Victoria University of Wellington.

Excerpted comments gathered by the UK SMC today, 15 March:

Prof Adam Finn, Professor of Paediatrics, University of Bristol, comments:

“Given the clear evidence we now have of real-world effectiveness of this vaccine against severe COVID-19 and against SARS CoV2 infection and the continuing widespread circulation of the virus in most if not all European countries, the potential public health consequences, both direct and reputational, of taking a stop-start approach need to be considered very carefully. In order to use vaccines effectively to help gain control over the pandemic there needs to be vaccine supply, vaccine delivery and vaccine acceptance. Getting all three lined up and in place at the same time is not easy and cannot be taken for granted while the need for rapid progress is obvious. If clear evidence of serious or life threatening side-effects emerges that will have important consequences. However so far it hasn’t and it’s highly undesirable to disrupt a complex and urgent programme every time people develop illnesses after receiving vaccine that may be coincidental and not causally related. Making the right call in situations like this is not easy but having a steady hand on the tiller is probably what is needed most.”

Conflict of interest statement: “AF is an investigator in clinical trials of the Oxford AZ vaccine and other COVID-19 vaccines.  He is a member of JCVI, member of WHO SAGE working group on COVID-19 vaccines and chair of the WHO Euro technical advisory group of experts on immunization.”

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, comments:

“Blood clots and subsequent brain haemorrhages are a rare condition.

“However, what these authorities do not make clear is that these coagulation disorders are very common in patients with Covid-19. Unless we are sure that those who suffered these unfortunate events very definitely did not have COVID-19 then it would seem to be premature to suggest it was the vaccine that caused these events.

“It has been well known for over a year that coagulation disorders, both clotting causing strokes, and bleeding (thrombocytopenia, which is a reduced number of platelets in the blood), are very common in patients with COVID-19.  Early reports from China noted over 30% of patients reaching hospital had thrombocytopenia.

“It is also a principle of regulatory action that when action is taken in regard to a particular product, that the alternatives definitely do not have the same problem. There was a case of thrombocytopenia in the US trial for the Pfizer vaccine, but detailed investigation made it clear that the vaccine was not the cause. The publicly available information on the AstraZeneca vaccine lists a total of 35 cases of thrombocytopenia reported on “Yellow Cards” in the UK up to 8th March 2021. This is a very small proportion of the yellow card reports which total over 54,000 in the context of nearly 10 million vaccinations delivered. For the Pfizer vaccine there are a total of 22 reports of thrombocytopenia out of 33,000 reports and well over 10 million vaccination doses. It is clear that the proportion of reports for this bleeding disorder is not different in the two vaccines.

“Covid definitely causes coagulation disorders and each of the vaccines prevents Covid disease, including more severe cases. Therefore, it is extremely likely that the benefit of the vaccine notably outweighs any risk for coagulation disorders and the vaccine prevents other consequences of Covid including deaths from other causes.

“It is entirely reasonable that detailed studies are done on the vaccines in regard to coagulation disorders, but it seems a step too far in taking precautions that would stop people getting vaccines that would prevent disease.”

Conflict of interest statement: “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.”

Excerpted comments gathered by the Australian SMC, Friday 12 March:

Professor Julie Leask, Susan Wakil School of Nursing and Midwifery, University of Sydney, comments:

Note: Julie is a social scientist whose research focuses on infectious disease and immunisation controversies and communication.

“Vaccine safety is important. This issue is now being carefully examined by the European Medical Agency’s safety committee.

“Our Australian regulator and vaccine safety experts are keeping a close eye on the outcomes of the rapid review. At this stage it appears that the blood clots may have occurred in these people anyway and that the vaccine did not cause them, but investigations will continue. Regulators look at things like biological plausibility, evidence from the trials, what is happening in other countries, and background rates to see if there is an unexpected rise in blood clot events.

“So far, the EMA note that ‘As of 9 March 2021, 22 cases of thromboembolic events had been reported among the 3 million people vaccinated with COVID-19 Vaccine AstraZeneca in the European Economic Area.’ The EMA state that this is not higher than in the general population.

“Countries around the world have set up systems to monitor for what are known as ‘adverse events following immunisation’. WHO defines this as, ‘Any untoward medical event that follows immunization and that does not necessarily have a causal relationship with the usage of the vaccine.’

“Once an adverse event is detected, regulators and vaccine safety experts will investigate whether the event is thought to be caused by the vaccine or not. This is a normal part of any vaccine program. It demonstrates a system is open, transparent and responsive. Governments want to ensure they are giving people safe vaccines.

“Some countries will be extremely cautious and pause the vaccine program while they investigate. Others will still investigate but keep the vaccine program going. This may reflect how much the decision makers in a country tolerate temporary uncertainty about vaccine safety and balance that against the vaccine’s undoubted benefits of protection from COVID-19.

“These are the dilemmas that leaders face when vaccine safety events occur. When vaccines are suspended due to such events, it can take a while for public confidence to return, even if the problem is later found to be unrelated. So these are never easy decisions.”

No conflict of interest declared.

Emeritus Professor Gerry Fitzgerald, public health expert, Queensland University of Technology (QUT), comments:

“The countries that have suspended the use of the AstraZeneca vaccine have acted with extreme caution by suspending vaccination, until such time as the risk can be assessed.

“Blood clots are extremely common. For example, the CDC in the US reports 60-100,000 deaths per year from lung blood clots. These are more common again in the elderly and those with chronic disease who are the people who are the target of the early vaccination programs.

“We also need to keep any risk in perspective. So far more than 2.5M people have died of COVID 19 and 8,000 to 10,000 people are dying each day around the world. More than 320 million people worldwide have already been vaccinated. More than 11 m people in the UK alone have been vaccinated with the AstraZeneca vaccine.

“The scientifically conducted clinical trials of the vaccines prior to their approval did not identify any increased risks associated with the vaccine. The scientific community has not had the time to test these new vaccines over prolonged periods and in large populations but on the present knowledge there is no evidence of significant increased risk.

“The seriousness of the disease we are trying to control means that we need to move quickly to roll out the vaccines to save lives and to restore social and economic activity. If the disease were to get out of control in Australia as it did in much of Europe and the USA, then we can expect between 30,000 and 40,000 people to die in Australia.”

No conflict of interest declared.

Excerpted comments gathered by the UK SMC, Friday 12 March:

Dr Andrew Garrett, Executive VP, Scientific Operations, ICON Clinical Research, comments:

“The vaccine clinical trials themselves were very large – much larger than for most clinical development programs for treatments – so they actually had a much higher chance than usual of detecting very rare adverse events whilst characterising common events (like injection site reactions) very well.  For instance, the chances of observing at least one “1-in-10,000” very rare event is 78% with 15,000 participants in a clinical trial receiving an experimental vaccine.  So there is a good chance of observing rare and very rare events prior to a vaccine being approved, and the clinical trials have the advantage of a control group to compare the frequency of events objectively.  Furthermore the safety data from these reported clinical trials are still accumulating since participants in these studies are followed for two years.”

Conflict of interest statement: “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.”