- The hold on a trial was second incident for the AstraZeneca candidate vaccine.
- Earlier, the AstraZeneca/Oxford trial was also paused when a patient developed neurological symptoms.
- The trial was restarted after an independent committee determined the problems were not caused by the vaccine.
- Review board found the symptoms came from undiagnosed multiple sclerosis.
- If the adverse reaction were caused by the vaccine, millions of doses would be discarded.
- If the condition were to be linked to the vaccine, then scientists face another critical question.
- The problem could be caused by the vaccine technology - in this case, a harmless virus that causes colds in chimpanze.
- If it is related to the spike protein, that could be a bigger issue because most of the vaccines in development use the spike. to trigger the immune response.
Pharmaceutical giant AstraZeneca on Tuesday (September 8, 2020) suspended a late-stage trial of the experimental vaccine being developed with the University of Oxford against the novel coronavirus. The pause, triggered by a possible serious adverse event in one of the participants, has raised many questions.
Here are some answers:
Q: Why was the trial put on hold?
A: The multinational company headquartered in Cambridge, England, paused global trials of its coronavirus vaccine after a participant in its late-stage United Kingdom trial developed what was described as an "unexplained illness" that may or may not be related to the vaccination they received.
I'm not alarmed for a lot of reasons. In fact, I'm reassured. It tells me people are looking at things very, very carefully.
The company described the temporary hold as a "routine action" to allow an independent committee to investigate. Outside experts said the hold shows the systems designed to ensure the safety of participants are working.
"This is often a normal part of the process in vaccine trials, which involve tens of thousands of people," Charlie Weller, head of the Vaccines Program at Wellcome, a charity organisation funding vaccine research, said in a statement.
"It's critical to quickly understand whether the illness has any relationship to the vaccine or the placebo and to share data openly, as Oxford University and Astra-Zeneca have done."
The US National Institutes of Health (NIH) Director Francis Collins, testifying at a Senate hearing on Wednesday, said such an action was "not at all unprecedented."
Q: What is transverse myelitis, the condition believed to have been diagnosed in the study participant?
A: Collins described the condition as "transverse myelitis", although AstraZeneca said in a statement that "there is no final diagnosis and there will not be one until more tests are carried out."
Transverse myelitis is a rare inflammation of the spinal cord that can be caused by viral infections and has only rarely been associated with vaccinations.
The neurological disorder can damage the insulating material covering nerve cell fibers called "myelin". There are about 1,400 cases in the United States each year. Symptoms include pain, sensory problems, weakness in the legs and possibly the arms, and bladder and bowel problems, according to an NIH website.
Q: Do researchers know whether the adverse event is tied to the vaccine?
A: No. The investigation into the cause of the adverse event has just begun. AstraZeneca and the University of Oxford have said the decision to pause was the result of a "standard review" of the data, and the incident will be probed by an independent committee of experts.
"In large clinical trials, illnesses will happen by chance and must be independently reviewed," the company said in a statement.
Q: What happens next?
A: Outside experts, serving on an independent data and safety monitoring board that oversees the trial, will try to determine whether the condition was caused by the vaccine or was unrelated.
Susan Ellenberg, a biostatistician at the University of Pennsylvania who has served on such boards for other trials, said the process of determining whether an adverse event is related to the vaccine will delve into the individual's medical history, the timing of the illness and the biology of the vaccine.
"I'm not alarmed for a lot of reasons. In fact, I'm reassured," Ellenberg said. "It tells me people are looking at things very, very carefully."
Former Food and Drug Administration (FDA) commissioner Scott Gottlieb said on CNBC's "Squawk Box" on Wednesday that scientists will scrutinise records to see if there might have been any milder cases of the same condition that were missed.
"This was a 10,000-patient trial, so one case of a rare adverse event that could be associated with the vaccine is going to cause concern among regulators," he said.
Q: How common are adverse events in drug trials?
A: Ellenberg said that while a hold on a trial is "not terribly common, it's not earthshaking."
Earlier this summer, the AstraZeneca/Oxford trial was paused when a patient developed neurological symptoms.
The trial was re-started after an independent committee determined the problems were not caused by the vaccine, but were symptoms of undiagnosed multiple sclerosis, according to a company statement.
Q: What does this mean for the future of this vaccine and others being developed against the coronavirus?
A: Collins noted at the Senate hearing that the reason the government is investing in a half-dozen vaccines is because of the expectation that not all will work. He said if the adverse reaction were caused by the vaccine, millions of doses would simply be discarded.
But if the condition were to be linked to the vaccine, then scientists face another critical question. Vaccines would aim to train the body to recognize the coronavirus by exposing cells to the distinctive spiky protein on its surface, but they use different technologies to deliver that protein to the body.
The problem could be caused by the vaccine technology - in this case, a harmless virus that causes colds in chimpanzees. But if it is related to the spike protein, that could be a bigger issue because most of the vaccines in development use the spike to trigger the immune response.