Ask #BloemMomDoc

• How do vaccine trials work?
One of the most common concerns among people is that the COVID vaccines were developed “too fast.” I think to myself, what do these people think the appropriate time would then be for a vaccine trial to be? Do they even know what a vaccine trial is and what it entails?
Vaccines are developed, tested, and regulated very closely, just like medications. They are actually much better studied and safety-tested than medications on your pharmacy shelf because of the large number of participants in vaccine clinical trials.
So you can probably trust vaccines more than the unregulated vitamins you buy off the street.

While I am no vaccine researcher in any form, I researched it a bit, and I dumbed it down for myself to understand. So I thought I would explain how vaccine trials work to set some minds at ease.
• What are the phases of a clinical trial?•
• The exploratory and pre-clinical phase•
This is a very research-intensive stage. Intelligent people in labs try to figure out methods of producing an immune response the same way a virus or bacteria would in the human body. This can take a few years to get right since new technology needs to be developed. They then test it on tissue and cells in the labs and animals to check their immune response.
In the COVID vaccine’s instance, this could be achieved in months. More people focused their attention on using technology already known in other vaccines (thus cutting a lot of the research time) to use in a COVID vaccine.
There was much more funding from stakeholders due to it being a pandemic. More labs and scientists could focus their attention on the process.

• Phase 1 testing•
This phase is the first time the vaccine created in the lab is tested on humans. Usually, about 20-100 healthy adults are given the vaccine to test the safety and immune response they get from these vaccines. These candidates are fully aware of the clinical trials they enlist into and the risks involved. It is voluntary. This process can take up to a year to complete.
• Phase 2•
In this phase, scientists must try and figure out what the most effective dose is needed of the vaccine to create the best response, and in turn, is also safe. They look for expected reactions to the vaccine and serious events, which are usually rare. This is monitored throughout all the phases. This is something they do not skimp on and also takes about a year.
In this phase, they usually include many more healthy trial participants (1000 or more) of various ages, races, etc. They are checked for reactions a week after vaccination and a month after as well. They try to include participants that are at high risk of developing the disease.
• Phase 3a•
In this stage, they already know the safe dose to administer, so now they study the vaccine’s efficacy. We now know which dose of the vaccine is needed for maximal immune response. We know the vaccine is safe and how many doses to give due to the previous phases. Now we need to see if it is successful in preventing the infection or reducing the disease’s severity if they do get it.
More volunteers are recruited and of a more diverse nature: more ages, ethnicities, disease profiles, risk factors, etc. They also include people more vulnerable to the disease, in COVID’s case, those with co-morbidities and older age. We are talking about 10 000+ people here. They usually choose sites for the trial where the disease is very prevalent, and the chances of being infected are high.
In COVID’s case, all the epidemiologists and smart people knew where these hotspots were since everyone was tracking the disease so closely. They knew straight away where to test the vaccines.
All these study participants were tested for COVID, and if they were negative, they were divided into 2 groups. They are randomized, meaning the 2 groups’ people have the same characteristics. One group receives a placebo injection; the other gets the study vaccine. None of the participants know which group they are in. The people administering the vaccines also do not know if they are administering the vaccine or placebo. We call this a double-blinded study. Participants find out at the end of the trial the group they belonged to and if they received the vaccine or placebo.
They are then followed up if they experience any COVID symptoms, and again, monitor for any adverse effects. Even if they developed COVID, they are monitored to see if they develop mild, moderate, or severe disease or death. They are then compared with the severity of illness from people of the other placebo/vaccine group to see if there is a difference between them.
Since many participants will receive the vaccine in this phase than in previous phases, they can monitor much better for side effects, since they might not have occurred in the smaller number vaccinated in the earlier phases. If severe adverse events occur, or they see the vaccine’s impact is not really different, they have to stop the study and then change things before it can be restarted again.
This phase can take years due to getting enough study participants and waiting for the disease to actually affect (or not affect, hopefully!) the participants. In COVID’s case, people were standing in line to become study participants, and since the SARS-COV2 virus was so prevalent, they didn’t have to wait long for it to infect a few participants.
After a successful phase 3a, manufacturers now apply to regulatory bodies to get the vaccines approved. These bodies then go through all the data collected and safety profiles meticulously. They look at if every vaccine they produce is the same as the others, so all of them can induce immunity the same way.
• Phase 3b•
This is performed near the time of approval to accumulate additional findings, which may be required as a condition of regulatory body approval. In short, the manufacturer has jumped through all the hoops to prove it is safe and it works. Still, the approval bodies might want more info to expand their labelling or data.
In South Africa, the Jansen Johnson & Johnson vaccine is being rolled out in a Phase 3b study to our healthcare workers. We know it has gone through all the safety and efficacy tests. It is just awaiting approval from regulatory bodies to start mass production to get it to the rest of the world.
• Phase 4•
Even after approved, these regulatory bodies still monitor the vaccine process. They monitor production sites and vaccine contents. This is especially important when it comes to adverse effects as well. An example of this is the Vaccine Adverse Event Reporting System (VAERS).