News has emerged from Brazil that a participant of the Phase III clinical trial investigating the COVID-19 vaccine, ChAdOX1, has died.
ChAdOX1, developed at the University of Oxford's Jenner Institute in collaboration with the pharmaceutical company AstraZeneca, is being tested in various locations across the globe, including the United Kingdom and the United States. The Brazilian Phase III trial commenced back in June, and is set to enrol a total of 5,000 volunteers across the country. It's a single-blind trial, meaning only the invetigators conducting the study know exactly which participants have been allocated to receive the vaccine (active vaccine group), or placebo (control group).
Take a listen to our Opiniated Science Podcast episode, "COVID-19 Vaccines: Three Leading Candidates, Assessed", to learn more about ChAdOX1.
Whilst Brazilian health authorities have refrained from providing further details surrounding the death, the University of Oxford has shared the following statement: “All significant medical incidents, whether participants are in the control group or the COVID-19 vaccine group, are independently reviewed. Following careful assessment of this case in Brazil, there have been no concerns about safety of the clinical trial and the independent review in addition to the Brazilian regulator have recommended that the trial should continue.”
Confirmation that the trial will continue has led the scientific community to believe that the individual was allocated to the control group and did not receive the ChAdOx1 vaccine. Professor Ian Jones from the University of Reading said, “Without details it’s impossible to know what has happened in this case but as the trial is continuing, I think we can assume the circumstances of the death were such that it was clearly not vaccine related."
Clinical trials are designed to follow a strict study protocol that must receive approval from health authorities and ethics committees for the study to commence.
This protocol outlines a precise set of instructions for researchers to follow in the event that a trial participant falls unwell. Such events are often categorized as non-serious or serious adverse events (SAEs), depending on their nature and severity. If an adverse effect is confirmed to be related to the investigational new drug, it is known as an adverse drug reaction, or ADR.
Professor Trudie Lang, director of the Global Health Network at the Nuffield Department of Medicine explains, "The sad event of someone dying on a vaccine trial immediately triggers the actions defined in the trial protocol that are carefully set out for all serious events. Here the cause of death would be reviewed by an independent safety monitoring committee and the regulatory authorities. They may decide to "unblind" a case and see which vaccine the participant received, if they decide the nature of the event requires them to assess whether this specific event was related to the vaccine or not. It may not always be necessary to unblind the case, as it might be an event clearly unrelated, such as a road traffic accident."
The news of the participant's death comes several weeks after the Oxford trial was paused in September due to a reported side effect in a UK-based participant.
The nature of the beast?
Unfortunately, we still do not have a definitive answer as to when a vaccine against COVID-19 will be available. A large number of vaccines are now in human clinical trials, and will be put through rigorous testing to ensure their safety and efficacy. Clinical trials, particularly in the context of a global pandemic, are likely to encounter some challenges along the way due to their longevity; this includes adverse events. Professor Jones commented, "What we have to remember is that in any large trial the normal processes of morbidity and mortality are still operating and that sometimes an event will occur in a trial participant which would have occurred anyway, trial or not. The case will have been carefully examined and, as vaccine relatedness has presumably been ruled out, the trial should continue to bring the vaccine to a decision point as soon as possible.”
Professor Eleanor Riley from the University of Edinburgh added, “Details on this are very sketchy at present but Brazil currently has one of the highest per capita death rates in the world for COVID-19. So, whilst to be greatly regretted, a death from COVID-19 among clinical trial participants (if that is what has happened, as some media reports are suggesting) is not unexpected.”
The death of the participant should not lead to any assumptions regarding the safety of the vaccine, suggests Lang: "We do not know the details in this situation but the robust and independent oversight processes within all such vaccine trials would have reviewed this sad event and concluded that there is no requirement to stop the trials." She concludes, "Therefore there is no new evidence to suggest that this vaccine is not safe.”