In making the announcement, AstraZeneca emphasised that this is a “routine action” which is part and parcel of any vaccine trial. It said that a participant in the United Kingdom leg of the trial had become ill, but provided no further details on the illness or its cause. It said the participant is expected to recover and the illness may well be unrelated to the trial.
Vaccine trials are overseen by an independent data and safety monitoring committee. The committee for this particular vaccine trial recommended that AstraZeneca should pause further vaccination for the time being. This would enable the committee to thoroughly assess why the United Kingdom participant fell ill and then recommend the best, safest way forward.
This has implications for South Africa. Wits University together with AstraZeneca, Oxford University and the Jenner Institute have been running a trial of this particular potential vaccine in Gauteng and the Western Cape since 24 June 2020.
The South African study is overseen by the same independent data and safety monitoring committee and has therefore paused further vaccination.
In a message to participants, the research team from Wits University said those who were due to receive either a first or second dose of the vaccine will be told in the coming days when vaccinations might restart. The team reassured participants that as this step shows, the well-being of participants is of “highest priority”.
“Pausing vaccination to review safety is evidence of the application of sound clinical practice and demonstrates the rigour of the independent oversight process under which this trial is being conducted,” says Professor Shabir Madhi. He leads the vaccine trial and is a Professor of Vaccinology at Wits University as well as the Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit.
“Assessing the safety of the vaccine is the reason why studies such as these are essential in South Africa, before there is widespread use of the vaccine,” he explains.
A number of leading South African health experts have said that this pause is no need for concern as it is part of normal procedure and shows that the trial takes safety very seriously.
All vaccine trials have an independent committee of experts called a Data, Safety and Monitoring Board, who will look over the shoulders of the research team, explains Professor Helen Rees.
She is the chairperson of the South African Health Products Regulatory Authority (SAHPRA) and executive director of the Wits Reproductive Health and HIV Institute. She is also on the World Health Organisation’s expert committee on Covid-19 vaccines.
This committee is set up before the trial begins and not when a problem arises. “It is there all the time and the role of this board is to periodically look at safety. Their role first and foremost is safety … They are able to look at the data and it is completely confidential. They don’t tell the research team what they’re seeing, but if they see a safety signal, they will advise the research team on how to respond,” she explains.
In addition, a trial cannot be approved before plans are in place to monitor safety. This includes reporting and monitoring any and all possible side effects.
She explains that with such big phase-three vaccine trials – in this case 30,000 people – researchers know that when they’re following up with so many people over such a long period of time “someone is going to get something because that’s life”.
What is then important is a proper assessment of the side effect. “If someone goes into hospital with some other complication then that will be investigated very seriously to say: is this just life? Is this what happens when you have a large number of people that you follow up with in the community and it has nothing to do with the vaccine? Or is this side effect related to the vaccine? That is what’s happening now – they are evaluating the report and deciding whether or not they think that there’s any causality or not,” she explains.
Trials will have “stopping rules” which include “pauses” such as this if an issue of safety arises, explains Professor Linda-Gail Bekker. She is the Deputy Director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town and the Chief Operating Officer of the Desmond Tutu HIV Foundation.
“This is a ‘normal’ set of events in trials and is designed to ensure the safest, most cautious approach,” she says.
This particular trial is periodically reviewed by the independent international data and safety monitoring committee, the South African Health Products Regulatory Authority and the University of the Witwatersrand Human Research Ethics Committee.
A report also goes to a country’s regulatory approval body, explains Prof Rees. This provides an extra layer of oversight and input on whether or not it is appropriate to continue the trial. The resumption of the South African trial depends on the decisions made in the United Kingdom, as this is where it was initially paused.
The continued evaluation of safety is part and parcel of any vaccine trial, says Dr Glenda Gray. She is the President and CEO of the South African Medical Research Council. She is also a participant in this vaccine trial.
“All vaccine trials have built-in evaluations to enhance safety. These processes are reviewed regularly by the South African Health Products Regulatory Authority and our ethics committees. I have full faith in these processes,” she said.
Another medical expert, Professor Francois Venter, agrees that it is a positive indication that the trial takes safety so seriously. He is the Deputy Executive Director of Wits Reproductive Health & HIV Institute and is a participant in the vaccine trial.
“It is great they are being so careful and not rushing this. Other vaccines are super-safe and we need to be certain the Covid-19 ones are the same – we will be potentially giving this vaccine to billions of people,” he said.
Another trial participant, Lawyers for Human Rights member Sharon Ekambaram, echoed these sentiments. “I feel gutted at the prospect of the trial being suspended but it’s reassuring that there is incredible oversight and monitoring to ensure safety of volunteers.
“I have had two doses and I have no fears for my personal safety and have not had any side effects since I was vaccinated 50 days ago. The team deserves credit and has my full confidence.”
The vaccine is in late-stage trials in South Africa, the United States, Britain and Brazil, with additional trials planned for Japan and Russia. so far, 1,814 people have been enrolled in the trial in South Africa. It has been described by the World Health Organisation as probably the world’s leading candidate and the most advanced in terms of development. DM/MC
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