NIH Concerns of Side Effects in Coronavirus Vaccine Trial


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The Food and Drug Administration is weighing whether to follow British regulators in resuming a coronavirus vaccine trial when a participant suffered spinal cord damage, even as the National Institutes of Health reported the case Investigation should be started.

“The highest levels of NIH are very concerned,” Dr. Avindra Nath, NIH Division’s National Institute for Neurological Disorders and Stroke, a leader of viral research, Dr. Avindra Nath said. “Everyone’s expectations are on a vaccine, and if you have a big complication the whole thing can derail.”

To the frustration of those following the progress of the vaccine trial, there remains a great deal of uncertainty about what happened to the unnamed patient. AstraZeneca, which is conducting a global trial of vaccines produced with the University of Oxford, said the trial volunteer has recovered from severe spinal cord inflammation and is no longer hospitalized.

AstraZeneca has not confirmed that the patient was suffering from transverse myelitis, but Nath and another neurologist said they understood the case. Transverse myelitis produces a group of symptoms involving inflammation along the spinal cord that can cause pain, muscle weakness, and paralysis. The Medicines and Healthcare Products Regulatory Agency, a UK regulatory body, reviewed the case and allowed the trial to resume in the United Kingdom.

AstraZeneca “required[s] With the potential complication of a vaccine to be more forthcoming, which will eventually be given to millions of people, “Nath said. We would like to see how we can help, but the lack of information makes it difficult to do so. “

Any decision about whether to continue testing is complicated because it is difficult to assess the cause of a rare injury that occurs during a vaccine test – and because scientists and authorities risk unusual side effects against a vaccine that curbs the epidemic. Can be applied. .

“So many factors go into these decisions,” Nath said. “I’m sure everything is on the table. The last thing you want to do is hurt healthy people.”

The NIH has not yet received tissue or blood samples from a British patient, and its investigation is “in the planning stages,” Nath said. US scientists can look at samples from other vaccinated patients to see if any antibodies generated in response to coronovirus attack the brain or spinal cord tissue.

He said that such studies may take one or two months. The FDA declined to comment on how long it would take before proceeding.

A Georgetown University professor and physician, Dr. Jesse Goodman, who was the chief scientist and principal vaccine regulator at the FDA during the Obama administration, said the agency would review the data and possibly consult with British regulators before being allowed to resume the US study. The bus started as soon as the injury was reported. Two other coronavirus vaccines are also in late trials in the US

If it determines that the injury in the British trial was caused by the vaccine, the FDA may stop the test. If it allows it to resume, regulators and scientists will certainly monitor similar symptoms in other trial participants.

A volunteer in the first phase of the AstraZeneca trial experienced a similar side effect, but investigators found that he had multiple sclerosis that was unrelated to vaccination, Dr. Director of the Multiple Sclerosis and Neurominology Center at the University of Texas. According to Elliot Frohman. .

Neurologists studying diseases such as transverse myelitis say they are rare – perhaps at a rate of 1 in 250,000 people – and strike the most frequently as a result of the body’s immune response to the virus. Less often, such episodes have also been linked to vaccines.

The exact cause of the disease is critical to the decision by authorities as to whether to resume testing. Sometimes an underlying medical condition is “unmasked” by a person’s immune response to the vaccine, causing the disease, as happened to a patient with MS. In that case, the test may be continued without fear, as the disease was not specific to the vaccine.

More worrying is a phenomenon known as “molecular mimicry”. In such cases, some small pieces of the vaccine may resemble brain or spinal cord tissue, resulting in an immune attack on that tissue in response to the vaccine component. If this is the case, there will be another possibility of transverse myelitis if the trial resumes, Drs. William Scheffner, an infectious disease specialist at Vanderbilt University School of Medicine. A second case will close the trial.

In 1976, the massive swine flu vaccination program was halted when doctors began diagnosing Guillain-Barre syndrome, a similar disorder in people receiving the vaccine. At the time no one knew how common GBS was, so it was difficult to tell whether the episodes were vaccine-related.

Eventually, scientists found that the vaccine increased the risk of the disorder by an additional one case per 100,000 vaccinated patients. Specific seasonal flu vaccination increases the risk of GBS in approximately one additional case per 1 million people.

“It’s very, very difficult” to determine whether a rare event was caused by a vaccine, Scheffner said. “How can you increase the risk of one in a million people?”

Goodman said that before allowing the US tests to resume, the FDA wants to see why the company and an independent Data and Safety Monitoring Board (DSMB) in the UK felt it was safe to continue. The AstraZeneca Trial has a separate safety board in the United States.

FDA officials will be required to review the full details of the case and may decide to request more information about the affected volunteer before the US trial is allowed to continue. They may also require AstraZeneca to update the security information provided to the participants to study.

It is possible that the volunteer’s health problem was unrelated to the vaccine, a senior scholar at the Johns Hopkins Center for Health Security, Dr. Amesh Adalja said. Studies are usually not discontinued on a single health problem, even if it is severe.

Yet many health leaders have expressed disappointment that AstraZeneca has not released much information about the health problem that has led to its UK trial being halted.

“There is little information about whether it is impossible to understand what the diagnosis was or why DSMB and the sponsors were convinced” it was safe to continue, Goodman said.

AstraZeneca has said it is unable to provide more information about the health issue, saying it would violate patient privacy, although it did not reveal how.

Scientists say there is an extraordinary need for transparency in a political environment with hesitation of the vaccine and mistrust of the Trump administration’s response, which is a response to COVID-19.

“Although I respect the critical need for patient privacy, I think it would be really useful to know what their assessment of these issues was,” Goodman said. “What was the diagnosis? If there was no clear diagnosis, what made them feel that the test could be resumed? There is so much interest and potential concern about the COVID-19 vaccine that there may be more information Provided, that the more it is assured. ”

The FDA will need to balance any potential risk from the experimental vaccine with the threat posed by COVID-19, which has killed approximately 35,000 Americans.

“There are also possible consequences of stopping a study,” Goodman said.

If the AstraZeneca vaccine fails, the US government is supporting six other COVID vaccines in the hope that at least one will be successful. Adalja said the potential problems with the AstraZeneca vaccine is a wise investment.

“It’s just part of the idea of ​​not being a vaccine candidate,” he said. “It gives you a little more insurance.”

Scheffner said that researchers need to remember that vaccine research is unpredictable.

“Investigators have inadvertently hypnotized their own vaccine,” Scheffner said. “Oxford investigators this summer were saying, ‘We will get there first.’ But this is exactly like the reason… Dr. [Anthony] Fauci and the rest of us have been saying, ‘You never know what will happen once in a large scale to mankind’.

This story by KHN was first published on California Healthline, a service of the California Healthline Foundation.

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