Another front-running team in the race to develop a COVID-19 vaccine has put a late-stage trial on hold after a reported “unexplained illness” in one of the trial volunteers. Here’s a look at the two pauses and what they mean for the quick development of a COVID-19 vaccine.
What kind of vaccine trials got put on hold?
Both pauses included Phase 3 clinical trials for the same class of vaccine, non-replicating viral vector vaccines.
Phase 3 is the largest type of clinical trial, requiring thousands of volunteers, and is the last of three stages of human testing before a vaccine can be approved for use. Its main goals are to:
Test the efficacy of the vaccine at preventing the disease compared with a placebo
Get a better idea of possible side-effects and how often they happen, including rare side-effects that might not show up in smaller trials.
The two vaccine makers that paused the trials are:
- The University of Oxford and pharmaceutical company AstraZeneca, which announced their pause on Sept. 8. The company is running Phase 3 trials involving thousands of people in the United Kingdom and smaller numbers of people in Brazil and South Africa. It is also recruiting 30,000 people in the United States for its largest study. The trials have since resumed in the U.K., Brazil and South Africa, but regulators have not yet approved them to resume in the U.S.
- Janssen Pharmaceutical Companies, a subsidiary of Johnson & Johnson, which announced their pause on Oct. 12. The company is running both early and late-stage clinical trials and did not say which the volunteer participated in. However, Johnson & Johnson said it was pausing all its COVID-19 vaccine trials. That includes a Phase 3 trial that started in late September and aimed to enroll 60,000 volunteers in Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa and the U.S.
Canada has deals to purchase tens of millions of doses of vaccine from each of the two companies if they make it through clinical trials and are approved.
Why were the trials suspended?
Both companies blamed an “unexplained illness” in one of the volunteers. That would have triggered a “standard review process,” intended to ensure safety when that happens. The pause allows the incident to be investigated by independent reviewers not involved in the trial.
What kind of illness was it?
Johnson & Johnson declined to reveal any more details about the illness, citing the participant’s privacy.
In AstraZeneca’s case, the company acknowledged that the patient had neurological symptoms associated with a spinal inflammatory disorder called transverse myelitis.
That involves localized inflammation of the spinal cord, which can cause symptoms such as weakness, loss of sensation or even paralysis of the arms and legs. It can be caused by autoimmune diseases, viral, bacterial or fungal infections or parasites, but it has also been reported as potentially a rare side-effect of vaccinations for diseases such as hepatitis B, influenza or measles-mumps-rubella.
The diagnosis was later confirmed by an internal report on the incident, CNN reported.
However, researchers who have studied transverse myelitis note that it’s difficult to confirm or exclude the link between the disease and vaccination, since it can occur coincidentally as a result of other causes after vaccination.
The U.S.-based Mayo Clinic said that the association so far is not strong enough to warrant limiting any vaccine.
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What is the goal of the review?
It will try to determine whether the illness was related to the vaccine.
Because trials like this are typically double-blinded, the researchers don’t know whether a given volunteer received the vaccine or a placebo. That’s one of the reasons why the review needs to be conducted by an independent committee that is not doing other analyses in the study.
Even if the volunteer received the vaccine, the timing of the illness could still be coincidental and unrelated to the vaccine.
Dr. Sumon Chakrabarti, an infectious disease specialist at Trillium Health Partners in Toronto, told CBC News Network that if the patient does have transverse myelitis, he or she will likely be tested for different types of infections to see if a cause can be determined.
“I’ve seen many of these cases myself, and we often come up with viral causes,” he said.
If that happens, the review may be able to rule out the vaccine as the cause and allow the trial to resume.
WATCH | Dr. Sumon Chakrabarti explains pauses in vaccine trials:
Dr. Sumon Chakrabarti, infectious diseases specialist at Trillium Health Partners, said safety is paramount in vaccine clinical trials, and temporary suspensions are not unusual to evaluate any unexplained illness in a participant. 4:31
How often do pauses like this happen?
On the one hand, they’re not triggered by “mild” side-effects, and there haven’t been any publicized for any COVID-19 vaccine trials so far, despite the large number underway. However, following the September pause, AstraZeneca disclosed that it had briefly paused a COVID-19 vaccine trial in July after a study volunteer was found to have multiple sclerosis. An independent review panel concluded the illness was not related to the vaccine.
Dr. Samir Gupta, associate professor of medicine at the University of Toronto, said that “it’s not a routine thing to stop a massive trial mid-course like this.”
However, AstraZeneca CEO Pascal Soriot said Thursday that such pauses are “very common actually.”
“Many experts will tell you this,” he said. “The difference with other vaccine trials is that the whole world is not watching them of course so they stop, they study and they restart.”
Such an event is not unexpected, given the size of the trial, said Dr. Michael Gardam, an infectious disease specialist at Women’s College Hospital in Toronto.
“I would argue for probably every vaccine that’s ever come to market, there’s been an event like this,” Gardam said.
“When you’re giving vaccine to tens of thousands of people, something’s going to happen to one of them. And chances are it’s happenstance … it’s not linked to the vaccine. But each time, you have to investigate it.”
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Will the pause slow down development of a vaccine?
“Not necessarily, it depends on what they find when they do the investigation,” British Health Secretary Matt Hancock said on Wednesday.
Gardam said he doesn’t think it will cause a significant delay.
Investigators will try to figure out “a reasonable explanation” for the cause of the illness, Gardam said, which may take some time.
A pause occurred during the Phase 1 trial of a Canadian-made Ebola vaccine in 2014 after several volunteers reported joint pain. An investigation found that the side-effect was likely caused by the vaccine, and the study resumed three weeks later with a lower dose.
In this case, Gardam said he thinks it will be hard to draw any conclusion based on one illness and that the University of Oxford researchers will be able to “quite quickly get back up and running again.”
However, they will need to collect more data to see if others show similar illnesses. If that happens, he said, “then that’s a completely different story.”
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How worried should we be about these pauses?
If it turns out that this is a potential adverse effect of this vaccine, “that would obviously be a substantial showstopper for this vaccine,” said Dr. Andrew Morris, an infectious disease specialist at Sinai Health, the University Health Network and the University of Toronto, following the University of Oxford/AstraZeneca pause.
He’s concerned there wouldn’t be access to the vaccine, which is in advanced stages of development. It’s also one that many countries are pinning their hopes on, with substantial investment from and billions of doses reserved by governments around the world and by the COVAX Facility, which aims to provide access to 172 countries, including many in the developing world. The company says it is close to having the capacity to produce three billion doses around the world to prevent governments from restricting distribution.
Morris said he’s also concerned that the media coverage will discourage people from enrolling in vaccine studies or increase anti-vaccination hype.
“Any step back is really a setback for all of us,” he said.
But at the same time, researchers such as Gardam say in some ways, the pause should ease people’s concerns, as it shows that the system is working and highlights the importance of Phase 3 clinical trials to ensure the safety of vaccines.
“This in and of itself isn’t a big deal,” he said. “This is what is supposed to happen…. This gives me some comfort.
“The fact that this has been stopped appropriately, it’ll be investigated. We’ll learn about it and then presumably the trial will start up again. That’s exactly what’s supposed to happen.”
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