The report details how the study volunteer, a previously healthy 37-year-old woman, “experienced confirmed transverse myelitis” after receiving her second dose of the vaccine, and was hospitalized on September 5.
Four days later, AstraZeneca dismissed media reports about the participant having a confirmed case of the rare neurological condition, in which the spinal cord becomes inflamed.
The document, which is labeled an “initial report,” describes how the study participant had trouble walking, weakness and pain in her arms, and other symptoms.
The internal safety report is dated September 10, and on September 11 it was sent out to doctors who are running the study’s clinical trial sites.
As the world closely watches the development process of a number of vaccines, hoping for an end to a deadly pandemic, some scientists say AstraZeneca’s communications about the patient’s condition have not been fully transparent.
A company spokesperson says, as the trial sponsor, they “cannot disclose medical information.”
In a press release last week, the pharmaceutical giant stated that “we are committed to the safety of our participants and the highest standards of conduct in our trials.”
‘Just a matter of time’ before trial resumes in the US
Fourteen days after receiving her second dose of the vaccine, the woman, who lives in the UK, “experienced confirmed transverse myelitis,” with symptoms including trouble walking and pain and weakness, the safety report said. Researchers were sufficiently concerned that they filed a SUSAR, or Suspected or Unexpected Serious Adverse Reaction report.
This is the report CNN obtained.
After the patient’s condition was reviewed by safety experts, the trial resumed in the UK and Brazil.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told CNN Tuesday that it is “just a matter of time” before the trial resumes in the United States.
He added that he considered the participant’s illness a “one-off” at this point, and that “it would be unusual to completely stop a trial on the basis of one single adverse event.”
He said doctors leading the trial sites in the US will be told to look out for similar symptoms.
“You have to be extra special careful and watch out to see if it happens again, and then if it does, it becomes an entirely different situation,” he said.
The “case narrative” contained in AstraZeneca’s report says the patient had the first dose of the coronavirus vaccine in early June and was fine. She received her second dose in late August.
On September 2, while running, the study participant “had a trip (not fall) with a jolt.” The report notes that she did not have any obvious injury to her cervical spine.
The next day, the report says, she had symptoms including difficulty walking, pain and weakness in her arms, pain and reduced sensation in her torso, a headache and reduced ability to use her hands.
The woman was hospitalized on September 5.
The AstraZeneca report mentions twice that the woman was diagnosed with “confirmed” transverse myelitis. It also says that a neurologist who consulted on her case “suggested the symptoms were consistent with the diagnosis of transverse myelitis.”
The report was sent to physicians who are leading study sites for the AstraZeneca vaccine. The cover sheet on the report, sent by a contractor hired by AstraZeneca, described her illness as “confirmed” transverse myelitis. The contractor requested that doctors, if required, submit the report to their Institutional Review Board or local ethics committee.
The report notes that the woman saw a neurologist, who stated the patient reported no past history of neurological symptoms or significant illnesses. At another point in the narrative, it said there was “limited information concerning the subject’s relevant medical history.”
No other similar cases had been diagnosed among other study volunteers, according to the report.
The neurologist noted that the study volunteer started to feel better.
“The resolution of her symptoms is quite rapid considering her illness started only four days ago,” according to the report. “Her symptoms were improving. Her strength and dexterity in her hands was getting better.”
Later that day, AstraZeneca addressed media reports.
”Reports claiming to be based on comments made earlier today by our CEO stating that we have confirmed that a participant in our clinical trial suffered from transverse myelitis are incorrect. He stated that there is no final diagnosis and that there will not be one until more tests are carried out. Those tests will be delivered to an independent safety committee that will review the event and establish a final diagnosis,” a spokesperson for the pharmaceutical giant said in a statement emailed to CNN on September 9.
That sheet refers to volunteers in the trial who “developed unexplained neurological symptoms including changed sensation or limb weakness.”
The document goes on to say that “after independent review, these illnesses were either considered 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.”
The sheet adds that “close monitoring of the affected individuals and other participants will be continued.”
It’s unclear why the Oxford patient safety sheet refers to “unexplained neurological symptoms” and does not mention transverse myelitis. It does not say whether the volunteer’s diagnosis was later changed.
When asked about this participant, a University of Oxford spokesperson wrote in an email to CNN that “we cannot disclose medical information about the illness for reasons of patient confidentiality.”
In a press release, a university spokesperson said, “we are committed to the safety of our participants and the highest standards of conduct in our studies and will continue to monitor safety closely.”
Oxford said in a statement that an “independent review process has concluded and following the recommendations of both the independent safety review committee and the UK regulator, the [Medicines and Healthcare products Regulatory Agency], the trials will recommence in the UK.”
In an email to CNN, an AstraZeneca spokesperson said, “the Company will continue to work with health authorities across the world, including the FDA in the US, and be guided as to when other clinical trials can resume.”
Last week, AstraZeneca’s Soriot said: “At AstraZeneca we put science, safety and the interests of society at the heart of our work. This temporary pause is living proof that we follow those principles while a single event at one of our trial sites is assessed by a committee of independent experts. We will be guided by this committee as to when the trials could restart, so that we can continue our work at the earliest opportunity to provide this vaccine broadly, equitably and at no profit during this pandemic.”
Moncef Slaoui, chief adviser to Operation Warp Speed, the US government’s effort to develop a Covid-19 vaccine, said Tuesday: “Upon reviewing the U.K. event, the U.S. trial will resume when the independent Data and Safety Monitoring Board overseeing the trial and the U.S. FDA determine that it is safe to proceed.”
Scientists question vaccine trial transparency
With tens of thousands of participants, it’s inevitable that during the course of a trial, some participants will fall ill with anything from a cold to cancer to heart attacks.
It’s not always clear whether an illness is connected to a vaccine.
How AstraZeneca communicated about this patient’s condition, and the condition of another who experienced symptoms during the trial, has caused some scientists to worry that the pharmaceutical company is not being fully transparent about the course of its coronavirus vaccine trial.
AstraZeneca “need[s] to be more forthcoming with a potential complication of a vaccine which will eventually be given to millions of people,” said Dr. Avindra Nath, intramural clinical director and a leader of viral research at the National Institute of Neurological Disorders and Stroke, an NIH division “We would like to see how we can help, but the lack of information makes it difficult to do so.
“The highest levels of NIH are very concerned,” Nath told KHN. “Everyone’s hopes are on a vaccine, and if you have a major complication the whole thing could get derailed.”
“The [Covid-19] vaccine companies haven’t been transparent; the stakes are big,” wrote Topol, executive vice president of Scripps Research in California.
Transparency and public trust are key to ending the pandemic and getting back to normal. If people don’t trust the vaccine, they might decide not to take it.
“People won’t get a vaccine if they don’t trust the science,” said Dr. Peter Hotez, a vaccinologist at Baylor College of Medicine and a CNN medical analyst.
Polls indicate there’s already a great deal of mistrust, including a CNN poll last month showing 40% of Americans won’t get a coronavirus vaccine when it comes out, even if it’s free and easy to get.
Hotez said AstraZeneca has shown a lack of transparency on several issues.
“It’s really unfortunate what they’re doing,” said Hotez, who is also developing a vaccine against Covid-19. “There needs to be transparency. This is just not acceptable.”
Hotez’s vaccine is not yet in human trials and has not received funding from Operation Warp Speed.
Questions still unanswered
Several factors have made some scientists question AstraZeneca’s transparency.
The company said that first participant was found to have had an “undiagnosed case of multiple sclerosis,” which was deemed to be unrelated to the vaccine. It did not explain how that conclusion was reached or why it waited more than a month to mention it publicly.
When asked why the UK arm of the trial was allowed to continue despite the woman’s recent illness, company spokespeople pointed CNN to the University of Oxford participant information sheet, which states independent reviewers recommended that vaccinations should continue.
In the UK, clinical trials are regulated by the Medicines and Healthcare products Regulatory Agency.
“We have now reviewed the data provided by the researchers and, after seeking independent expert advice from the Commission for Human Medicines (CHM), we agreed with the recommendation of the Data and Safety Monitoring Board that vaccination can restart,” according to a statement sent to CNN by Siu Ping Lam, director of licensing for the agency.
Covid-19 vaccines are a matter of “national security,” Hotez said.
“These are very sensitive issues, and Operation Warp Speed is ceding or delegating critically important communications that are vital to the national security interests of the nation,” Hotez said.
In response, Operation Warp Speed’s Slaoui told CNN on Tuesday that “questions regarding details and data on trial participants and trial pauses must be referred to the trial regulatory sponsors coordinating this process.”
Hotez added that incomplete communication about the trials, including participants who become ill, could have a dire effect not just on the AstraZeneca vaccine, but also on other coronavirus vaccines that have received federal funding.
“If they botch the communications on this, Americans will refuse to accept their vaccine, and this will have a spillover effect on the other Operation Warp Speed vaccines,” he said.