Vaccine trial halted - what does it mean?

Opinion: Dr Helen Petousis-Harris explains why the pause button has been hit on a late-stage Covid-19 vaccine trial, and why it's an appropriate and safe response.

An image shows vaccines bottles labelled "clinical trials Covid-19": With more than 200 Covid-19 vaccines now under development we are going to start seeing participants in the clinical trials have health events. Photo: iStock
With more than 200 Covid-19 vaccines now under development we are going to start seeing participants in the clinical trials have health events. Photo: iStock

Today AstraZeneca pushed the pause button on its late-stage trials of a Covid-19 vaccine. A clinical trial participant has experienced a serious health event and an investigation is underway to determine the cause.

What does this mean? It means the trial is being conducted cautiously; it has been halted to assess safety data. This is an appropriate action and it is not uncommon.

With more than 200 Covid-19 vaccines now under development we are going to start seeing participants in the clinical trials have health events. These events may or may not be completely unrelated to the vaccine under study. When you have what will ultimately be hundreds of thousands of people under observation in clinical trials, some will get sick, especially when you start recruiting older people into these studies. When this happens sometimes the trial will need to be halted while the event is investigated, and a lot of questions answered, briefly:

- Did the person receive the vaccine or a placebo?

- How long after the injection did this event occur?

- What sort of health event is this? For example, is it heart attack? An infection? An injury? A seizure? Something else?

- Is this event biologically plausibly explained by receipt of the vaccine?

What does the halting of a trial mean?
As the Covid-19 vaccine trials progress we are going to see periodic haltings. This is actually the second time the Oxford/AstraZeneca vaccine trials have paused. One reason for halting a trial is because a participant has had an adverse medical event. We must accept the possibility that one, or some, of these new vaccines may have safety problems and fail to progress further. We must also accept that if the event has been determined not caused by the vaccine the trial may resume. This is normal practice.

Who oversees the safety data on the trials?
Each clinical trial has a Data and Safety Monitoring Board (DSMB). This is an independent group of people who have expertise in the disease, the drug, statistics, or other relevant fields. While they will periodically review the study data for evidence of study-related adverse events, they can also make recommendations to the developer about continuing, modifying, or even terminating the study. When a serious event occurs, they are alerted and convene urgently. The data they review, and discussions are confidential.

In the case of Covid-19 vaccines, a large pool of safety-trained people have been recruited into a meta-DSMB. This team can liaise across all the individual DSMBs across all of the different vaccine products. This can help ensure the same level of rigour and standards are applied to all Covid-19 vaccines – at least those receiving support from CEPI (Coalition for Epidemic Preparedness Innovations).

The AstraZeneca COVID-19 vaccine
This vaccine was developed at Oxford University in partnership with Pharma giant AstraZeneca. The vaccine is called a non-replicating viral vector vaccine and it uses an adenovirus that has had the gene for the SARS-CoV-2 spike protein inserted into it. When injected, the vaccinee’s own cells will make the spike protein and the immune system generates a response that looks likely to be protective. There is some experience with viral vector vaccines in humans and so far, while reactogenic (i.e. sore arms and fevers are common), there are no particular safety concerns identified associated with this particular viral vector construct which is called ChAdOx1.

The adverse event
According to the New York Times, the adverse event is a case of transverse myelitis (but this has not yet been confirmed by the company). Transverse myelitis is an inflammatory condition that affects the spinal cord. Biologically speaking many infections, such as the herpes and influenza viruses are known to cause this condition. It has even been reported associated with Covid-19. Historically, there have been rare cases of such immune mediated inflammatory disorders associated with vaccines, but a firm causal link has never been established.

What does this mean for COVID-19 vaccines?
This event does not affect other trials, particularly those using different vaccine platforms. It also demonstrates that safety is being taken very seriously. We need to be patient and let the trials run their course.

A more detailed version of this article appears on Dr Petousis-Harris’s blog Diplomatic Immunity.

Dr Helen Petousis-Harris is a vaccinologist and associate professor in the Faculty of Medical and Health Sciences.

This article reflects the opinion of the author and not necessarily the views of the University of Auckland.

Used with permission from Newsroom Vaccine trial halted - what does it mean? 10 September 2020.

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