The AstraZeneca vaccine and over-65s: we may not have all the data yet, but limiting access could be counterproductive


Kylie Quinn, RMIT University

Last week, a German vaccine advisory committee recommended the AstraZeneca vaccine only be used in 18-64-year-olds, citing a lack of data on the efficacy of the vaccine in people over 65.

Subsequently, the European regulator, the European Medicines Agency, conditionally approved the vaccine for anyone over 18.

What can we make of this? Should we be giving this vaccine to older people or not?

While we don’t yet have all the data we’d like, we don’t have reason to believe this vaccine won’t be at least somewhat effective in older adults. To exclude them from receiving it wouldn’t necessarily be the right approach.

The recommendation

STIKO, a German vaccine advisory committee that reports to the country’s government, was responsible for the draft recommendation which caused the stir. It released a similar final recommendation at the weekend.

While the German government may elect to follow STIKO’s advice or the European Medicines Agency’s guidelines, the latter’s approval carries significant weight. Equivalent to the Therapeutic Goods Administration (TGA) in Australia, this body decides which vaccines may legally be supplied in Europe.

The AstraZeneca vaccine has already received approvals, not singling out older age groups, from multiple international regulators, including those in the United Kingdom, India and Mexico.




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Why did STIKO make this recommendation?

STIKO’s advice is based on the fact it didn’t have enough data to definitively say whether the vaccine will work in older people — not because it won’t.

According to the data we have so far from AstraZeneca’s phase 3 trials, only two out of 660 people in the trial aged over 65 got sick with COVID-19. Two sick people isn’t enough for a strong statistical analysis.

AstraZeneca initially enrolled younger people in its trials, with older people enrolled only later. So data on older people in the original trials and another trial in the United States are still on the way.

A doctor prepares to vaccinate a grey-haired woman.
AstraZeneca’s early trials didn’t include as many older people as younger people.
Shutterstock

What do we know about the vaccine?

We have very good safety data for the AstraZeneca vaccine in older people. Older people actually have significantly lower levels of early side effects after vaccination. This makes sense, as older people’s immune systems don’t tend to react as strongly to vaccines, which would reduce many of these early side effects.

But the vaccine has been shown to induce strong immune responses in older people, which are likely to provide a degree of protection. The European Medicine Agency’s press release on their decision refers to a reasonable likelihood of protection based on this data.

So, just looking at immune responses, it’s reasonable to anticipate the AstraZeneca vaccine will be of some benefit, at least, to older people.




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What do we know from other vaccines?

Often, vaccines aren’t as effective in older people as compared to younger people, because their immune responses can be less robust. For example, in 2010-2011 in the US, the flu vaccine was 60% effective in the general population, but only 38% effective in people over 65.

There’s more information on efficacy in older people for other COVID-19 vaccines. Notably, the Pfizer vaccine maintained efficacy of 93.7% for people over 55, compared to 95% overall. Accordingly, it would be reasonable to prioritise the Pfizer vaccine for older people.

But we’re beginning to see that vaccine supply and distribution can be unpredictable, with supply issues for Pfizer and AstraZeneca starting to affect vaccine rollout.

Importantly, all COVID-19 vaccines assessed so far, including the AstraZeneca vaccine, provide a high level of protection against severe disease and death across variants of the SARS-CoV-2 virus.

A health-care worker administers a vaccine to a senior man.
Older people are more susceptible to the coronavirus.
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Limiting access limits options for older people

The question that advisory committees and regulators are weighing up is, should the AstraZeneca vaccine, or any vaccine, be recommended for older people if we know:

  • the vaccine has low risk of side effects

  • the vaccine has a fair but unconfirmed likelihood of providing some benefit

  • COVID-19 has a higher likelihood of severe disease and death in the demographic.

This is tricky to navigate and advice may differ across different vaccines and countries. For example, China is delaying vaccine rollout to older people while it waits for more data.

But conditional approval is a reasonable path to take. It allows for some uncertainty and maintains contact with the manufacturer. It also recognises that the likely benefit of giving older people any available vaccine could outweigh the hypothetical risk that it might not work in the midst of a crushing pandemic.




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In any case, approvals from regulators, such as the European Medicines Agency and the TGA, have the most impact — defining who the vaccine can be supplied to in a country.

If regulatory guidelines are kept open to all age groups above 18, it will facilitate access to vaccines for many people who could benefit from them. The next steps are distributing these vaccines, and educating and updating the public with the latest information as it comes to hand.

Crucially, we should support older people in vaccine decisions with two things; good information and easy access to an array of safe, protective vaccines.The Conversation

Kylie Quinn, Vice-Chancellor’s Research Fellow, School of Health and Biomedical Sciences, RMIT University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Halting the Oxford vaccine trial doesn’t mean it’s not safe – it shows they’re following the right process



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Nigel William Crawford, Murdoch Children’s Research Institute and Jim Buttery, Monash University

Only days after the federal government announced a A$1.7 billion vaccine deal to roll out COVID-19 vaccines to Australians in 2021, one of the two candidates has halted its phase 3 trials after a participant became ill.

The AZD1222 vaccine, considered one of the frontrunners in the global race for a COVID-19 vaccine, was developed by the University of Oxford and has been undergoing testing with British-Swedish pharmaceutical company AstraZeneca.

Melbourne-based biotechnology company CSL has committed to producing and supplying more than 30 million doses of the vaccine to Australians if it’s found to be safe and effective.

But this pause in the trials doesn’t necessarily mean it’s not safe. Rather, it indicates the testing is progressing as it should, with due consideration of safety.

What happened?

There’s been no official statement on the nature of the incident that caused the trial to be halted. We only know it was a suspected adverse reaction in a participant in the UK. (Phase 3 trials for the AZD1222 vaccine have been taking place in several countries.)

The New York Times has reported the participant was diagnosed with transverse myelitis, an inflammatory condition than affects the spinal cord and can be sparked by viral infections.

Transverse myelitis is very rare, with between one and eight new cases per million people per year.

Most people will recover, but may be left with some symptoms such as weakness.




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In the world of vaccine safety, transverse myelitis is one of several conditions collectively known as a serious acute neurological episode (SANE) temporally associated with vaccination. Others include Guillain-Barré syndrome and acute disseminated encephalomyelitis.

“Temporal” suggests they occasionally occur some time after vaccination, but we don’t know whether the relationship is one of cause and effect. Unfortunately, it’s not always easy to find what caused these conditions, and it’s important to look for other infections that may be associated with the diagnosis.

There are a couple of things worth noting in this case. First, in the UK branch of the trial, not all participants were receiving the AZD1222 vaccine. To ascertain its effectiveness, researchers have given a control group a type of meningococcal vaccine (MenACWY) that has already been licensed. As the trial is double-blinded, we don’t yet know whether the affected participant received the COVID-19 vaccine.

Second, AZD1222 is not a “live-attenuated” vaccine — it’s not made from live SARS-CoV-2 virus. (It does use a chimpanzee adenovirus vector, but this doesn’t replicate or cause disease in humans.) It’s not impossible the transverse myelitis — if confirmed as a diagnosis — was related to the vaccine. But it wouldn’t be possible for the vaccine to cause a COVID-19 infection, which could then spark the myelitis.

Further, phase 2 and 3 trials involve much broader populations than the young, healthy adults who typically participate in early testing. The UK trial of AZD1222 includes people 70 years and older, which naturally increases the risk of temporally associated adverse events.

So what next?

AstraZeneca will already be investigating the incident, with input from external regulatory bodies such as the study’s data safety monitoring board, the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

These independent bodies will review all parts of the investigation, such as an MRI on the participant to confirm the diagnosis, and look at which of the groups the person was in (whether they received AZD1222 or the other vaccine).

They will try to find out what caused the illness, but this may not be possible. It will be particularly hard to prove the vaccine caused the illness with only one case. Illnesses like transverse myelitis, although rare, have a “background rate” of occurrence already in the community.

The World Health Organisation provides a framework to assess the cause of an adverse event following immunisation. AstraZeneca and the independent bodies monitoring their processes will follow this or similar frameworks to evaluate the event.

Once they’ve reviewed the incident, they will decide whether to resume the trial. Given the impetus to move quickly with this, we’d expect this to happen in a matter of days.




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It’s not a bad thing

This halt on the trial doesn’t indicate the vaccine isn’t safe — we’ll need to see further evidence before we can ascertain this.

But it does reflect robust processes for a clinical trial. In a sense, this is what phase 2 and 3 clinical trials are designed for — to pick up any potential safety issues and investigate them further.

These sort of things happen occasionally in other clinical trials too. We just don’t hear about it. There’s perhaps never been so much attention on a single clinical trial as there is on the trial of this and other potential COVID-19 vaccines.

We’re not sacrificing safety for speed

In the course of this pandemic, we’ve often heard that fast can’t be safe in the context of a vaccine. We don’t feel that’s the case here.

The reason these trials are moving so fast is largely because recruitment is happening quickly. The phase 3 trials of AZD1222 will have 40,000-50,000 participants in total.

Beyond the AZD1222 vaccine, we’re seeing open disclosure of processes and transparency around any issues. This includes a pledge from the major pharmaceutical companies to keep safety at the forefront when evaluating COVID-19 vaccines.

Of course, there are exceptions to this — notably the Russian vaccine, which has published some phase 1 data but reportedly gone into widespread use before completing all of the standard safety and effectiveness checks.




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In Australia, we follow certain steps to assess the safety of new vaccines. If the trial of the Oxford/AstraZeneca vaccine resumes and it proves safe and effective, Australia’s Therapeutic Goods Administration (TGA) will see the data and interact closely with regulatory bodies around the world to ensure it’s safe to use.

The TGA is also responsible for post-marketing surveillance, which we regard as phase 4. When the vaccine is being rolled out, we continue to monitor for adverse events, and follow these up using both jurisdictional vaccine safety units, such as SAEFVIC in Victoria, and active surveillance systems, such as Smartvax and Vaxtracker.The Conversation

Nigel William Crawford, Associate Professor, Murdoch Children’s Research Institute and Jim Buttery, Professor of Paediatric Epidemiology, Monash University

This article is republished from The Conversation under a Creative Commons license. Read the original article.