A leading coronavirus vaccine trial is on hold: scientists react

[NNadir]

This comes from the news section of the scientific journal Nature:

A leading coronavirus vaccine trial is on hold: scientists react

Subtitle: Scientists urge caution in global vaccine race as AstraZeneca reports ‘adverse event’ in a person who received the Oxford vaccine.

Nicky Phillips, David Cyranoski & Smriti Mallapaty Nature News September 9, 2020.

All Covid related papers and news items published by major scientific publishers are open sourced.

Enrolment in global trials of a leading coronavirus-vaccine candidate are on hold after a ‘suspected adverse event’ in a person who received the vaccine in the United Kingdom. Scientists say that it’s too soon to say what impact this might have on the global push to develop a vaccine, but that the news highlights the importance of waiting for the results of large, properly designed trials to assess safety before approving a vaccine for widespread use.

Researchers at the University of Oxford, UK, in collaboration with the pharmaceutical company AstraZeneca, are developing the vaccine, which is one of nine coronavirus vaccines in the final, ‘phase III’ stage of being tested.

Details of the adverse event, including how serious it is and when it happened, have not been reported by Oxford or AstraZeneca. But the trial’s pause comes amid concerns that US drug agencies might face political pressure to approve a vaccine before trials are completed, ahead of the US presidential election in November.

“The clinical hold shows that there are functioning checks and balances, in spite of political pressure,” says Marie-Paule Kieny, a vaccine researcher at INSERM, the French national health-research institute in Paris. “It might indeed remind everybody — even presidents — that for vaccines, safety is paramount,” she says.


Coronavirus vaccines leap through safety trials — but which will work is anybody’s guess

“I do hope that the adverse event is unrelated to the vaccine, since Oxford’s candidate seems quite promising so far,” says Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai in New York City. The decision to halt the trial shows that the process to evaluate vaccines works, and ensures that only safe and effective therapies make it to the market, he says...

...It is the second time that administration of the vaccine has been paused in the UK, according to two people who took part in the study and to information sheets uploaded to a clinical trial registry. Previously, a participant developed symptoms of transverse myelitis, an inflammation of the spinal cord which is often sparked by viral infections, according to an information sheet given to trial participants dated 12 July. After a safety review, the trial resumed. The individual was diagnosed with an “unrelated neurological illness”...

...Adverse events are not uncommon in clinical trials, and are often unrelated to the treatment being tested, says Paul Griffin, an infectious-disease researcher at University of Queensland in Brisbane, Australia, who has conducted large clinical trials. For instance, an adverse event would include a participant being admitted to hospital for any reason, and might automatically trigger the pausing of the trial even if the admission was unrelated to the vaccine...

...Researchers have been especially worried that COVID-19 vaccines could cause an ‘enhanced disease’ when people who receive the vaccine are exposed to the virus subsequently. Animal studies and early-phase human trials of COVID-19 vaccines, including the Oxford/AstraZeneca candidate, have so far reported no signs of enhanced disease.

The Oxford vaccine is a viral-vector vaccine that harnesses a cold-causing ‘adenovirus’ isolated from chimpanzees. The chimpanzee adenovirus has been modified such that it can no longer replicate in cells, and it expresses the ‘spike’ protein that the coronavirus uses to infect human cells...

I added the bold.

The greatest tragedy in all of this is the ongoing rise of the confusion of science with politics. This is not an isolated instant limited to Covid, of course, and it is not, regrettably, limited only to the political right, although the Trump cult is the problem reified.

[ihas2stinkyfeet]

1. that they are not providing details makes me suspicious.

hate to be that way, but these days...

[NNadir]

2. It would be very unusual for them to disclose the adverse event (AE).

Every clinical trial has exclusion criteria; rules about people having conditions or medical histories that may complicate results, but still, since it is not practical to completely genetically screen a large population, or to recognize any and all possible complicating factors, it often happens that people display symptoms that may not actually be involved with the drug or vaccine.

In fact, the approval of a drug will often weigh cost/benefits of known or discovered possible complications.

To stop a relatively large clinical trial for a single adverse event on an urgently needed vaccine suggests that there is a strong suspicion, but really no proof, that the adverse event, whatever it was, is a result of the treatment. It may, for example, be a cytokine storm or something of that nature, known from Covid-19. But it is possible to have this kind of immune response for other syndromes, after all people can and do die from viral infections that are much less lethal, overall, than Covid-19.

In an efficacy trial for a vaccine, one almost has to let the subjects out into the world where they will face a risk of infection. It would be unethical to deliberately expose people, so comparing a treated population with an untreated population is really the only way to test for efficacy. Therefore a patient could easily contract another disease, say a flu, to which they have a strong reaction.

I would be very surprised if this program was permanently halted based on my long experience with these kinds of trials.

Indeed, I have seen cases where I think pulling the drug for a series of known actual AE's may have lead to more deaths from the disease than the AE's would have.

Medicine is a statistical enterprise, and there are no definitive easy answers. I am pleased that Astra Zeneca is showing that they have not abandoned good science to rush into a positive result. It's a race, to be sure, and everyone is working hard. It reminds me of the time of AIDS before the approval of protease inhibitors.