Is it Safe? The never ending story...

of the AZ vaccine

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AZ vaccine restrictions

Channel 4 news reported tonight on the AZ vaccine, reporting that the JCVI and the MHRA are urgently scrutinising the AZ vaccine and its status ‘hangs in the balance’. Two senior sources are meant to have said to Channel 4 that, while the data is still unclear, there is a growing argument for offering younger people an alternative vaccine. You can watch the story here.

While this is presented as breaking news, this sort of discussion has been occurring in full public view for days.

Here’s Chris Whitty on the side effects of vaccines on the 1st of April (about 23 minutes in). He notes that the MHRA, CHM, and JCVI are all looking at this issue and that for anyone at significant risk of getting COVID-19, such as an 80 year old, the risk/benefit is ‘wildly in favour’ of vaccination. However…

‘The closer you get to someone who is right down at 20 [years of age] the more you have you think through this really very rare side effects that are severe because the risk/benefit might get to parity.’

‘the idea that there might be a point where actually there’s a group you wouldn’t look at from the beginning of this I’ve been really cautious about making a policy on children getting vaccines until we were really confident about adults and that’s not because I’m trying to protect children specifically, it’s just that children get so little problems with severe COVID that you have therefore got to have a very strong justification for vaccination. [.] So it’s always going to be a matter of risk against benefit for particular patient groups.’

And here’s Adam Finn from the JCVI discussing the use of COVID-19 vaccines in children that they are at lower risk, so the balance of benefits and harms is different.

These are exactly the discussions that will be occuring. The specific MHRA data on the cerebral venous sinus thrombosis (CSVT) risk was recently updated:

The risk of having this specific type of blood clot is very small. Up to and including 24 March, we had received 22 reports of cerebral venous sinus thrombosis (CVST) and 8 reports of other thrombosis events with low platelets, out of a total of 18.1 million doses of COVID-19 Vaccine AstraZeneca given by that date. There were no reports for the Pfizer/BioNTech vaccine. We have thoroughly analysed each and every report as soon as it has come in. To note the current analysis prints include data up to and including the 21 March.

That’s about 1 in 600,000, so still very rare. There is no data about age or gender, but a BBC article seems to suggest that it is a wide range of individuals (but not clear where they got that from).

Dr June Raine from the MHRA stated "‘The benefits… in preventing Covid-19 infection and its complications continue to outweigh any risks and the public should continue to get their vaccine when invited to do so.’ and EMA agreed despite more cases being found, with an age adjusted exposure of 1 in 100,000 in the under 60s. EMA also noted, ‘At present the review has not identified any specific risk factors, such as age, gender or a previous medical history of clotting disorders, for these very rare events. ‘

However, the French ANSM reported on 12 cases of rare atypical thromboses to AZ vaccine (1.93 million doses given, so that’s 1 in 160,000). Three-quarters were under 55 years of age, and mainly in women. These should be subset of the wider European data which EMA says shows no gender or age risk. Germany reported on 31 cases of CSVT, with all but two of the cases in women aged 20 to 63 (most of these cases would have been in the EMA review).

Despite all this, EMA still don’t agree with restricting the vaccine to any particular groups on the basis of the existing safety data, along with the MHRA. However, that could change in time.

There is clearly a safety signal, and the data has increased since it first came to attention. There are mechanisms being looked at. There is a causal story being developed as time progresses, but we aren’t there yet. Both EMA and the MHRA seem to be suggesting that there are no identifiable groups who can be singled out for caution with the vaccine, although that may change in the next week or so. The MHRA are in a rolling review, and EMA’s specialist committee (PRAC) will be addressing AZ vaccine issues between the 6-9th of April.

However, even if there are no special precautions for specific groups can be ascertained, there are two non-AZ vaccine factors that are important:

1. Some groups, as Chris Whitty noted, are at an extremely low risk of COVID-19 mortality.

2. The risk of infection is also falling.

3. We have an alternative vaccine, and possibly more coming for the period when the younger age groups will get access to vaccine.

So even if the mechanism of this rare side effect is unknown, even if we don’t have a proven causal link, and even if we don’t know the groups at risk, we could use the low risk of COVID-19 in some groups, and the availability of alternative vaccines, to make different decisions about AZ vaccine’s deployment.

It’s not impossible that both EMA and the MHRA/JCVI might make different decisions on the AZ vaccine based on careful consideration of new information and of the risk of disease to particular patient groups. Or they might not. But it would be better if those decisions were being taken in a calm scientific manner and communicated as a clear story, rather than appearing as something being urged by anonymous sources. The confusing messaging in the EU, which can’t be blamed on EMA who have been following their plans, seems to have undermined the use of AZ vaccine.

Whatever the outcome, both the EMA and the MHRA will need to have a clear set of reasoning for the decisions, and a message that can told to the public. For those who present any such decisions as ‘Oh look, the MHRA and EMA have changed their minds.’, that’s the point. They are meant to review data on an ongoing basis, and make changes (or not) on the basis of the data. As new data comes in, it either weakens or strengthens the safety signal, but it does not tell you that prior decisions were wrong.

There is a clear benefit to rolling out the vaccine in terms of lives saved at the moment, and decisions need to be finely balanced and cautiously taken.

That’s all and stay safe.

Anthony

Don’t forget to report your suspected adverse effects from medicines and vaccines. In the UK, this means using the Yellow Card Scheme.