AstraZeneca, one of the front runners for a vaccine for Covid19, working with Oxford University, admitted that two participants in its stage 3 vaccine trial have experienced serious adverse effects, diagnosed as transverse myelitis, a severe potentially disabling adverse effect listed on the package insert of a number of vaccines already in use.
Vaccine companies already have immunity from prosecution for any adverse effects that may occur as a result of vaccines and are therefore not incentivized to ensure safety. Further, the “volunteers” for these trials are generally young and healthy people, and not the stated target group of the elderly and immune compromised, for whom the vaccine might be more harmful.
In response to the adverse effects, AstraZeneca briefly suspended its global trials, however, less than a week later it was back in action in all countries except the USA. At that time, the company reported that one of the participants affected had a “previously undiagnosed case of multiple sclerosis”, while according to the New York Times, there has been no statement about the second case.
The article states the following:
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 virus.
The 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.
The condition is rare, but serious, and experts said that finding even one case among thousands of trial participants could be a red flag. Multiple confirmed cases, they said, could be enough to halt AstraZeneca’s vaccine bid entirely.
“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 on.”
Ethical Issues of Challenge
The issue of the ethics of drug and vaccine research was discussed in the New York Review of Books back on July 2nd. An article called “An Ethical Path to a Covid Vaccine” reviewed a book called “Adverse Events, Inequality, and the Testing of New Pharmaceuticals.” It recounted that the history of drug research has been full of examples where the poor, prisoners, prostitutes, psychiatric patients, soldiers and others who either had little choice or, for economic reasons, were persuaded by money, to participate in drug research. The article also discusses the ethical issue involved in a “challenge study”, in which researchers give healthy people a new vaccine and then infect them with the pathogen being tested, in this case the SARS-Cov-2. The general view is that this wouldn’t be ethical as there is no accepted treatment for COVID19, but the author of the article discussed the growing call for challenge studies to be introduced for COVID19 vaccine trials, including potentially, elders in nursing homes who may well not survive the experience. The author uses this as a possible example of how previous drug research has often profoundly crossed the line of medical ethics and human rights. There is another specific issue relating to challenge in a corona virus trial. When the SARS-1 trial challenged the animals in the trial, they became fatally ill, despite having developed measurable antibodies. In the seventeen years since SARS-1 a successful vaccine for a corona virus has never been developed.
Nonetheless, in the race for the COVID19 vaccine, this ethical line has already been crossed and permission has been given for the AstraZeneca / Oxford trial to challenge the trial participants after they have received doses of the experimental vaccine.
It is interesting that in the USA, the FDA seems concerned enough about the safety of this vaccine to halt further trials, while the British government seem less concerned and are re-starting the trials. Both these companies are locked into a $multi-billion race to bring their product to market, so it’s difficult to know whether the official responses are based on loyalty to their respective candidates, and political and financial issues are taking precedent over safety.
AstraZeneca seem determined to hide any serious adverse effects from their vaccine. To state that one participant had an undiagnosed case of multiple sclerosis unrelated to the vaccine should raise eyebrows. The subjects had been pronounced healthy by the trial’s criteria before the vaccine was given. The first serious adverse effect occurred in July and in September a second participant was reported to have similar symptoms of transverse myelitis. Despite this condition being very rare in the population at large, the company has still dismissed a possible connection with the vaccine.
The British government should halt the trial until more evaluation is done, but there is too much at stake. The need to be the first to bring the vaccine to market, the huge amount of money already invested in both the research and the manufacture, makes this a vaccine too big to fail.
In turn the British media is disturbingly quiet about this recent development, while the US media is reporting it widely. But then it is a competition and the volunteers, across the world, will be considered collateral damage in the race.