Regulators walk very well when evaluating the AstraZeneca vaccine – POLITICO

The problems never end with the Oxford / AstraZeneca vaccine.

After all the struggles over contracts and deliveries, the latest challenge is the one facing European regulators: whether to recommend that national governments not administer the vaccine to the very young, citing a rare but sometimes fatal form of blood clotting.

Several countries have already taken that step and on Tuesday, the head of the European Medicines Agency’s vaccine strategy spoke out on the situation.

“It’s clear there is a link,” Marco Cavaleri told the Italian newspaper il Messaggero when asked if the vaccine causes the low platelet counts and blood clots found in some people who have received the vaccine.

“However, we still don’t know what causes this reaction,” Cavaleri said.

The EMA told POLITICO on Tuesday that Cavaleri’s comments were “preliminary personal comments,” while the agency is expected to make a more official announcement on the safety of the vaccine on Wednesday or Thursday.

Cavaleri’s comments were a notable change from the EU regulator, which has spent the last two months insisting that there was no reason for EU countries to restrict or stop using the vaccine, first in February, when concerns from that there was not enough data to use the vaccine in older people, and again in March due to early concerns about serious blood disorders.

The UK, which has boasted an enviable vaccination rate thanks in part to vaccine doses, is also seeing increasing reports of rare but serious blood clots. Channel 4 reported on Monday that British regulators are considering restricting the vaccine in young people, a potentially huge blow to the UK vaccination campaign, although the agency said it has not made any changes to its advice … “yet” .

Regulators are reluctant to limit use of the vaccine because, as Cavaleri noted, while there may well be a link between blood clots and the vaccine, its benefits still outweigh its risks.

A very small number of people could have serious side effects, but the vaccine is clearly saving thousands of people from dying from COVID-19.

“In summary, if you are currently offered a dose of the Oxford-AstraZeneca vaccine, your chances of staying alive and well will increase if you give the vaccine and will decrease if you don’t,” Adam Finn, professor of pediatrics at the University of Bristol wrote in a press release.

Cavaleri gave no indication whether the EMA would change course in the short term and advise against giving the vaccine to younger people. Instead, the decision could depend on each country weighing how cautious it wants to exercise.

“Above all, let’s not forget that the burden of COVID is different in different countries: in Italy, 500 people still die a day; in Norway almost none, ”said Cavaleri. “These factors justify different approaches.”

Considering that Europe is the most vaccine-skeptical continent in the world, and how cautious countries have been so far, EU countries are likely to continue to impose age restrictions on the British-Swedish vaccine, especially if they reports of blood clotting continue to pile up.

So while Europe waits to hear from the EMA this week, here’s a look at the main issues regulators are facing:

Is there a serious problem with the AZ vaccine?

European countries have distributed more than 40 million doses of the Oxford / AstraZeneca vaccine. The vast majority of people have had no problems; the most common side effects are simply pain where the needle was inserted and basic flu-like symptoms similar to other vaccines.

Still, there have been a very small, but growing, number of people who developed rare blood clotting problems about 14 days after receiving the injection.

Last week, Emer Cooke, the executive director of the EMA, said there were 62 reported cases of blood clots in the brain internationally, 44 of them in the European Economic Area, as of March 22. The UK, meanwhile, reported 22 cases of cerebral venous sinus thrombosis (CVST) and eight of low platelet-linked thrombosis as of March 24 (both conditions involve blood clots). Germany reported 31 cases of blood clots in the brain on March 30.

Some regulators have reported cases of thrombocytopenia, which is when a person has an unusually low level of platelets in the blood (which stop bleeding by clumping together and forming plugs in blood vessel lesions). Thrombosis is a broad term for a blood clot anywhere in the body, while cerebral venous sinus thrombosis (CVST) – confusingly, sometimes referred to as cerebral sinus vein thrombosis (CSVT) – is when produces a clot in the venous sinuses of the brain, preventing blood from draining out of the brain and causing a stroke.

These events tend to be more common in younger women. Most of the reports sent to European regulators concerned women between the ages of 22 and 50, although some women were between the ages of 50 and 60, Cavaleri said. About 20 percent of the cases were men in their 40s.

How unusual is this?

Peter English, former chairman of the British Medical Association’s Committee for Public Health Medicine, told reporters that British reports of CVST events amount to about 1.2 cases out of one million doses used.

The EMA said that, on average, there are between 2 and 5 cases of CVST in 1 million people. Still, the incidence rate varies by study. Given that the rate cited by the UK regulator, the Medicines and Healthcare Products Regulatory Agency (MHRA), last week is not far behind the typical number of cases a country would see in a given year anyway, English wrote that the cases linked to Oxford / AstraZeneca vaccine is “far from strong evidence of causation.”

English also warned about information bias. Now that doctors know about the problem and are actively looking for it, they may find more. “Remember, it is a ‘difficult diagnosis’, which suggests that it can often be overlooked, and if you look for it more closely in one group than another, you are likely to find more cases in the group in which you observe with more attention “, English said.

Why did the EU countries stop using the vaccine?

Austria discontinued a batch of the Oxford / AstraZeneca vaccine on March 7 after one woman died and another became ill after being vaccinated, both citing blood clotting problems. Other European countries followed suit, first suspending specific batches and then restricting their use to younger people. By the end of the month, at least nine EU countries had stopped using the vaccine entirely in younger populations due to blood clotting problems.

However, on March 31, the EMA said there was no evidence to support these restrictions, but that the agency’s safety committee would continue to review the reports. The announcement prompted most EU countries to lift their restrictions.

But reports of blood clotting kept coming in. Reports in the UK increased from 5 to 30 in a week from March 24. Canada, which has not reported any blood clotting problems, also stopped the vaccine in people under the age of 55 at the end. March, citing worrying reports from Europe.

Where is the EU now?

While most of the countries that suspended the use of jabs reversed their decisions when the EMA gave its cautious nod on March 18, several Nordic countries, along with France, took a more cautious approach and continued at least partial suspensions.

In Finland, a total suspension only started after the EMA announcement, after two cases of blood clots in the brain. Their National Institute of Health and Welfare said March 24 that they would only use the vaccine for those 65 and older as investigations continued. Iceland also did not fully restart jab vaccination, limiting its use to more than 70 years. Sweden only resumed the vaccine for the age group 65 and older, and France allowed access to the vaccine for those 55 and older. Estonia has also recommended prioritizing the jab for those over 60.

Norway and Denmark continued with the total suspension of the jab, and Denmark said on March 25 that it would extend the ban for another three weeks.

Germany then initiated a second wave of restrictions, announcing on March 30 that after 31 cases of blood clots in the brain, it would limit the use of the jab to those under the age of 60. North Macedonia did the same the next day and the Netherlands did the same on April 2. The Slovenian Vaccination Advisory Group recommended a similar measure.

Why don’t we stop using the vaccine?

Despite mounting evidence that the Oxford / AstraZeneca vaccine is linked to these rare blood clotting conditions, the vaccine has clearly prevented thousands of people from ending up in hospital or dying from COVID-19. Public Health England, for example, estimated that the nearly 18 million Oxford / AZ needles used in late March prevented more than 6,100 deaths in people over the age of 70.

On Tuesday, the World Health Organization continued to say there was “no link” between the vaccine and blood clotting events.

“At the moment there is no evidence that it is necessary to change the benefit-risk assessment of the vaccine and we know from data from countries like the United Kingdom and others that the benefits are really important in terms of reducing mortality in populations that are being vaccinated, ”said Rogerio Pinto de Sá Gaspar, director of the WHO regulation and prequalification unit.

Gaspar concluded that “we tend to overemphasize the risk” rather than the benefit of the vaccine.

The EMA’s Cavaleri was also clear when asked if “the risk-reward ratio was still in favor of the vaccine.” He answered with a clear “Yes”.

“This week we will begin to establish some preliminary definitions, but it is unlikely that we will indicate age limits as several countries have done,” Cavaleri said.

Then the agency will continue with a more detailed analysis of the different population groups.

Regardless of what the EMA says this week, each EU country could end up making its own decision.

“The public health agencies that run the various vaccination campaigns have different options and can use them however they see fit,” Cavaleri said. “Many hope that the EMA will solve the problem for everyone, but it is not that simple.”

In the UK, meanwhile, “no decision has yet been made on any regulatory action,” according to the MHRA. “People should continue to get their vaccine when invited to do so.”


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