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AstraZeneca Covid-19 vaccine: every suspected case is examined
Photo: Dan Kitwood / Getty Images
Coincidence or connection?
As early as Thursday, the European Medicines Agency (Ema) wants to give an initial assessment of whether AstraZeneca's Covid-19 vaccine can cause life-threatening thrombosis.
There is hardly any time for extensive studies or autopsy reports, so what do the expert teams rely on?
The European Medicines Agency Ema has prepared for such suspected cases.
If possible complications arise with an approved vaccine or drug - experts speak of a safety signal in this case - the so-called pharmacovigilance committee, or PRAC for short, meets.
This checks the information and finally makes a recommendation.
The search for the signal
A decisive instrument is the so-called observed-versus-expected-analysis, which in German means something like observed-versus-expected analysis.
Behind this is the following consideration: In the meantime, millions of people worldwide have already been vaccinated against Covid-19 with the AstraZeneca agent.
It was therefore to be expected that such a large number of people would become ill by chance.
The decisive factor, however, is: Does a certain disease accumulate conspicuously in vaccinated people?
Last week there were reports of thromboses that had occurred after vaccination with the AstraZeneca drug.
A 49-year-old nurse in Austria died as a result of severe coagulation disorders.
According to the Austrian Federal Office for Safety in Health Care, it has not yet been determined whether there is a connection with the vaccination.
An autopsy is in progress.
There were also reports that three soldiers died after the vaccination in Sicily, but that the vaccination could be ruled out as the cause of death in at least one of those affected.
Some countries paused vaccinations with AstraZeneca's drug after similar incidents.
Why the assessment changed in Germany
First, the Ema gave the all-clear.
"The number of thromboembolic events in vaccinated people does not seem to be higher overall than in the general population," said the agency earlier this week.
Thromboses in vaccinated people are even significantly less common than one would expect in the rest of the population, said Ema expert Peter Arlett on Tuesday afternoon during a press conference that was scheduled at short notice.
Arlett is Head of Pharmacovigilance and Epidemiology at Ema.
Meanwhile, the situation in Germany had changed.
The Paul Ehrlich Institute (PEI), which is responsible for vaccines in this country, found that cases of thrombosis in Germany were strikingly similar.
Germany also stopped vaccinations with the AstraZeneca substance.
Those affected not only developed thrombosis, they also had a platelet deficiency and bleeding was noted.
Seven such cases had been reported to the institute by Monday, and three of those affected died.
"It is a very serious disease that is also difficult to treat," said the PEI.
Such thromboses of the cerebral veins are much less common.
The observed-versus-expected analysis by the PEI experts showed that, measured against the 1.6 million AstraZeneca doses administered in Germany, only one case would have been expected, now there were seven.
A clear safety signal that automatically initiates a testing process.
How exactly the PEI came to this bill and when the cases occurred is still unclear.
(Read more about this here.)
The Ema experts are now checking whether this safety signal is also shown in other data.
The process is like laborious detective work.
Rare diseases in particular make epidemiological investigations difficult, says Ema expert Arlett.
There is little publication and the rate of expected cases is less clear.
"So the focus is much more on analyzing the clinical characteristics of each individual reported case," says Arlett.
National reporting systems would have to be evaluated.
The studies that are decisive for admission will be examined again.
The experts examine every single suspected case, work their way through the patient files, looking for clues as to whether there are other explanations for the thrombosis.
In Austria, a 58-year-old died in the queue for vaccinations
On the basis of this data, they carry out further observed-versus-expected analyzes.
However, there is no simple mathematical calculation behind this, the equation depends on many parameters.
If a disease is so rare, every reported case can have a significant impact on the calculation.
Chance also plays a role and it is difficult to calculate it out.
In Austria, for example, a 58-year-old collapsed in the queue for her Covid 19 vaccination, the broadcaster ORF reported on the weekend.
The woman died, why is not yet clear - a connection with the immunization is excluded, however, she was not yet vaccinated.
Had she died just a short time later, after the injection, her death should also have been investigated in connection with the vaccination.
In addition: With diseases that are so rare, it is not so easy to determine how often they actually occur.
Even the definition of the clinical picture can differ considerably.
For this reason, too, each individual case should now be checked again.
In the case of sinus vein thrombosis, for example, the PEI ranges from two to five cases per million people per year
off, other studies estimate the frequency many times higher.
One study comes to 13 cases per million people per year, another to 16 cases.
The stork paradox
Even if it should now be shown that thromboses in the brain are increasing in the vaccinated, this is not automatically proof that the vaccination is the cause.
There are many examples of bogus causalities in the history of science.
Probably the best known concerns storks.
A 2001 study showed that more children are born when there are more storks.
The number of human birth rates correlated significantly with the number of pairs of storks, the effect could be demonstrated in several regions of Europe.
The fact that storks bring babies has been scientifically refuted.
So the number of birds cannot have anything to do with the number of babies.
The explanation for the connection goes as follows: storks tend to live in the countryside and there tends to be more children per couple.
There could be a similar explanation for the incidents that have now been reported.
Women are three times more likely to be affected by sinus vein thrombosis than men.
They also work more often in nursing - and it is precisely these professional groups that received the vaccine from AstraZeneca in Germany, because initially only people under 65 years of age should be vaccinated with it.
In the UK, however, the vaccine was also used in the elderly from the start.
So far, only three cases of sinus vein thrombosis have been registered there - out of a total of eleven million inoculated doses.
Ema continues to convince: advantages with AstraZeneca vaccine outweigh risks
The experts will price all of these considerations into their recommendation.
In the end, therefore, there should not only be a simple mathematical calculation, but a weighing of the risks.
After all, stopping vaccinations also costs human lives.
It is currently unlikely that vaccinations with the AstraZeneca agent will be stopped permanently.
A current statement from the European Medicines Agency states: "Ema currently continues to believe that the benefits of the AstraZeneca vaccine in the prevention of Covid-19 with the associated risk of hospital stays and deaths outweigh the risks of side effects."
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