How does the trial work?

The study we have embarked on in SA is for a vaccine that was developed by the Jenner Institute at the University of Oxford. It’s what is known as a nonreplicating vector based Covid-19 vaccine trial.

The study came about when I reached out to the principal investigator at the University of Oxford, whom I’ve known for over 20 years, to find out if there was any interest in including SA as part of the clinical development plan for the vaccine. The short answer was yes, provided we conducted the study on our own, including raising the funding for it.

The agreement with Oxford University preceded a subsequent agreement it has entered into with AstraZeneca, the pharmaceutical company responsible for the further clinical development of the vaccine and future manufacturing. Pre-clinical studies of this vaccine candidate, including in nonhuman primates, have demonstrated initial evidence of its safety as well as its ability to protect against Covid-19 disease.

Why SA?

The main reason is that the legacy of vaccines shows that they don’t necessarily work similarly across different populations. So if we want to be one of the early adopters, in terms of implementing vaccination against Covid-19 as part of our immunisation programme, we really need to generate data applicable to the local context.

A number of past vaccines have been shown to be highly efficacious in high-income settings, but when they’ve gone on to be evaluated in low-and middle-income settings they were found to be much less efficacious and, at times, not efficacious at all.

So if we want to make informed decisions at an early stage about whether these vaccines are going to be of benefit to people in SA, it’s critical that we undertake the clinical evaluation during the start of the entire programme, rather than at the latter stage. Waiting for results to come in from other studies would just lead to a lag in terms of the timing of the introduction of vaccines in SA as well as other low-and middle-income countries.

This has been the experience for many other life-saving vaccines, where it has taken between five and 20 years from their availability in high-income countries to being available in low-and middle-income countries.

How are participants chosen for the trial?

Participation is completely voluntary.

Participants typically come to inquire about the study at clinics. We sit down with them and explain what the study is all about – what the criteria for joining are, and to find out what the expectations of the volunteers are, because the study has quite intense requirements in terms of being able to come for regular visits. And volunteers obviously need to be agreeable that when they participate in the study, if they do develop signs and symptoms suggestive of Covid-19 they would come forward to be investigated. This is critical for us to be able to determine whether this vaccine protects against the virus.

In addition, we would do some blood tests on volunteers to ensure that they don’t have any medical conditions we would want to exclude.

If they’re found to be eligible, we randomly allocate them to one of two groups. Half will receive the vaccine, and the other half a control substance, which in our case is a placebo. This is important for two reasons. It allows us to provide robust data in terms of the safety profile of the vaccine. And the control group enables us to determine whether the vaccine actually does have any impact in protecting against Covid-19.

Is there any reason people should be sceptical of the trial?

The short answer is no. The narrative that Africans are being used as guinea pigs is fundamentally incorrect. Rather, it’s a case of us wanting to generate robust scientific data to be able to make informed decisions about whether those vaccines actually do protect South Africans – and possibly Africans more generally – against developing Covid-19.

What are the next steps?

Right now we are enrolling people into the clinical trial. We’ve just reached the 200 mark out of the 2,000 participants we plan to enrol. We expect to have completed enrolment of all the volunteers over the next three to four weeks.

After that we will keep in touch with all of the participants at least every two weeks, including sending weekly SMS messages to determine whether they are experiencing any signs or symptoms of Covid-19. And if they are, they will be asked to come in to be investigated to determine whether they are infected or not.

The endgame of the study is twofold. One is obviously to evaluate the safety of the vaccine, which is something that is ongoing almost on a daily basis.

The second part is that once we have about 42 individuals who have developed Covid-19 at least about a month after they’ve received the first dose of either the vaccine or the placebo we will be able to do an analysis to determine whether the vaccine actually does protect against the virus. Specifically, we will be testing if the vaccine efficacy is at least 60%; that is, whether by being vaccinated your risk for developing Covid-19 will be reduced by at least 60%, if not more.

We expect we will probably be able to provide an answer as to whether this vaccine works and protects against Covid-19 by the end of November this year. In the worst-case scenario it might take us a bit longer, probably into the second quarter of next year.

What about managing expectations?

It’s very exciting to be involved such a clinical development of the vaccine. But we need to be guarded in terms of our expectations of what the result will be.

The fact that we’re embarking on a clinical trial doesn’t mean that we’re going to have a vaccine that’s going to protect against Covid-19. Only about 10% of vaccines that go into clinical trials are eventually licensed for use. Right now approximately 200 vaccines are being developed for Covid-19. It would be a huge accomplishment if, over the next 12 to 18 months, we are successful showing that even one out of every 20 (or 5%) of the vaccines that go into human studies are safe and provide some protection against Covid-19.

So even though there’s a huge amount of work taking place around vaccines, at least for the next 12 months the only tools we’ve got available to us to try to protect people is adherence to physical distancing, the wearing of face masks in public, the avoiding of mass gatherings and making sure that you’re in adequately ventilated settings when in public spaces.

*Madhi is a professor of vaccinology and director of the MRC Respiratory and Meningeal Pathogens Research Unit at the University of the Witwatersrand. The article was first published on The Conversation and is an edited version of a podcast, in which Madhi is interviewed by the Conversation Africa’s health and medicine editor Ina Skosana

NOTE: Anyone living in South Africa who is interested in participating in the study can e-mail vidacov19@rmpru.co.za for more information.

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