AstraZeneca, Under Fire for Vaccine Safety, Releases Trial Blueprintshttps://www.nytimes.com/2020/09/19/health/astrazeneca-vaccine-safety-blueprints.htmlExperts are concerned that the company has not been more forthcoming about two participants who became seriously ill after getting its experimental vaccine....
experts noted that transverse myelitis is rare, diagnosed in only about one in 236,000 Americans a year. The trial in Britain involved only about 8,000 volunteers, a spokesman for the Oxford researchers said last month.AstraZeneca revealed details of its large coronavirus vaccine trials on Saturday, the third in a wave of rare disclosures by drug companies under pressure to be more transparent about how they are testing products that are the world’s best hope for ending the pandemic.
Polls are finding Americans increasingly wary of accepting a coronavirus vaccine. And scientists inside and outside the government are worried that regulators, pressured by the president for results before Election Day on Nov. 3, might release an unproven or unsafe vaccine.
Experts have been particularly concerned about AstraZeneca’s vaccine trials, which began in April in Britain, because of the company’s refusal to provide details about serious neurological illnesses in two participants, both women, who received its experimental vaccine in Britain. Those cases spurred the company to halt its trials twice, the second time earlier this month. The studies have resumed in Britain, Brazil, India and South Africa, but are still on pause in the U.S. About 18,000 people worldwide have received AstraZeneca’s vaccine so far.
AstraZeneca’s 111-page trial blueprint, known as a protocol, states that its goal is a vaccine with 50 percent effectiveness — the same threshold that the Food and Drug Administration has set in its guidance for coronavirus vaccines. To determine with statistical confidence whether the company has met that target, there will have to be 150 people ill with confirmed coronavirus among participants who were vaccinated or received placebo shots..
... Dr. Topol said AstraZeneca’s plan, like those of Moderna and Pfizer, had a problematic feature: All count relatively mild cases of Covid-19 when measuring efficacy, which may hamper efforts to determine whether the vaccine prevents moderate or severe illness.The company has released few details about the two cases of serious illness in its trial. The first participant received one dose of the vaccine before developing inflammation of the spinal cord, known as transverse myelitis, according to a participant information sheet for AstraZeneca’s vaccine from July. The condition can cause weakness in the arms and legs, paralysis, pain and bowel and bladder problems.
The case prompted a pause in AstraZeneca’s vaccine trials to allow for a safety review by independent experts. A company spokeswoman told the Times last week that the volunteer was later determined to have a previously undiagnosed case of multiple sclerosis, unrelated to the vaccine, and that the trial resumed shortly thereafter.
Transverse myelitis can sometimes be the first sign of multiple sclerosis, which involves more complex symptoms. But the
myelitis alone can also occur after the body encounters an infectious agent like a virusThe company said it had not confirmed a diagnosis in the second case, a participant who got sick after the second dose of the vaccine. A person familiar with the situation who spoke with The Times on the condition of anonymity said the participant’s illness had been pinpointed as transverse myelitis. The trial was paused again on Sept. 6 after she fell ill.
“If there are two cases, then this starts to look like a dangerous pattern,” said Mark Slifka, a vaccine expert at Oregon Health and Science University. “
If a third case of neurological disease pops up in the vaccine group, then this vaccine may be done.”A participant information sheet dated Sept. 11 on
AstraZeneca’s trial in Britain lumped the two volunteers’ cases together, stating the illnesses were “unlikely to be associated with the vaccine or there was insufficient evidence to say for certain that the illnesses were or were not related to the vaccine,” based on safety reviews. The next day, AstraZeneca announced that it had resumed the trial in Britain.
But the F.D.A. has so far not allowed the company to start up again in the United States.
A spokesman for the F.D.A. declined to comment. The National Institutes of Health said in a statement that it “remains to be seen” whether the onset of illness in trial participants was coincidental or tied to the vaccine, adding that “pausing to allow for further evaluation is consistent with standard practice.”
Dr. Mark Goldberger, an infectious disease expert at the Global Antibiotic Research and Development Partnership and a former F.D.A. official, said he found
the rapid restarting of trials abroad to be “a little disturbing,” especially given the lack of details around the patients’ symptoms and the ambiguity around their connection to the vaccine. “Maybe this is the best they could do — it may not be possible to get more certainty at this time,” he said. “It is a question mark as to what’s going .
The company did not immediately inform the public about the neurological problems of either participant. Nor did it promptly alert the F.D.A. that it was again pausing its trials after the second U.K. volunteer developed illness and an independent safety board in the United States called for a temporary halt, according to multiple people familiar with the situation. The company’s chief executive told investors about the problems but did not discuss them publicly until the information was leaked and reported by STAT.
“The communication around it has been horrible and unacceptable,” said Dr. Peter Jay Hotez, a virologist with Baylor College of Medicine in Houston. “This is not how the American people should be hearing about this.”
Dr. Hotez also criticized obtuse statements released by government officials, including U.K. regulators who he said failed to supply a rationale for resuming their trials.
“Tell us why you came to that decision,” he said.
Dr. Paul Offit, a professor at the University of Pennsylvania and a member of the F.D.A.’s advisory committee on vaccines, said that it’s unclear how the company — or the U.K. government — determined that the second case was not related to the vaccine.
Scientists want public confidence. The White House wants an October Surprise. The FDA wants to avoid looking political. Big Pharma wants a win. You’re in the middle.https://www.wired.com/story/the-943-dimensional-chess-of-a-trustworthy-covid-19-vaccine/ampAstraZeneca protocols
https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-cece903592b9/D8110C00001_CSP-v2.pdfAstraZeneca internal report
https://www.cnn.com/2020/09/17/health/astrazeneca-vaccine-trial-document/index.htmlDrug companies basically never try to push back against getting expedient approval of their products, because they’re for-profit businesses trying to sell stuff. Yet here they’re trying to distance themselves from politically motivated, unsafe Emergency Use Authorizations from the FDA.
Policy experts sometimes describe the process of industries controlling the agencies that oversee them through lobbying or other influence peddling as “regulatory capture.” Now the pharma companies seem to be worried about the direct inverse of that—political capture by leadership up the line that could threaten the market standing of the companies, not to mention the lives of their customers.
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