Vaccine safety and effectiveness: how is it tested?
The scale of the COVID-19 pandemic has shown how essential vaccination is for today’s world. It has also shown how quickly we can develop vaccines when we really need to: we can thank open international scientific collaboration, advances in vaccine technology, substantial investment and speedy regulatory review for the rapid development of COVID-19 vaccines.
The swift delivery of multiple COVID-19 vaccines surprised many people, including experts—but rapid development doesn’t mean cutting corners. All vaccines need to pass many tests and stages before they reach you, and COVID-19 vaccines are subject to the same thorough regulation and review processes as other vaccines.
We’ve previously explored what happens during clinical trials and why some people experience adverse events after vaccination. Here we look at how scientists and health authorities keep a close eye on the safety and effectiveness of vaccines, including after those vaccines are rolled out to the public.
The stages of clinical trials
Scientists spend a lot of time studying the pathogen that causes the disease and determining what might be the best ways to target it with a vaccine.
Once scientists develop a potential vaccine (called a ‘vaccine candidate’), it goes through preclinical assessment in a laboratory, usually using animals. If serious safety issues that may harm humans arise, work on the vaccine candidate is abandoned at this stage.
Eventually, a vaccine candidate gets tested in healthy adults during phase 1 clinical trials. Here, a small number of people, around 25–50, are given the vaccine to test its safety.
During phase 2 trials, the vaccine is given to hundreds of people to see how well it can do its job of stimulating the immune system and fighting the target disease. This is also where researchers further evaluate its safety and can work out the best dosage schedule to use.
In phase 3 trials, testing the vaccine’s efficacy and safety across thousands of people is the goal. Researchers check for adverse events as well as testing it in lots of different types of people: different ages, genders, and genetic and cultural backgrounds.
Efficacy vs effectiveness: what’s the difference?
Efficacy refers to how well a vaccine works under controlled conditions. Effectiveness refers to how well a vaccine works in the real world.
Efficacy refers to how well a vaccine does its job under controlled experimental conditions. That ‘job’ might be defined as preventing deaths, or preventing severe forms of the illness, or preventing people from developing any symptoms at all, which is how you can end up with multiple different efficacy statistics for the same vaccine. In the case of the AstraZeneca vaccine for COVID-19, for instance, a recent analysis found that the efficacy rate for preventing any symptoms of COVID-19 is 79%—but it’s 100% efficacious at preventing severe forms of the disease. That’s important, since we know that severe forms are more likely to result in serious long-term consequences, a higher chance of hospitalisation, and even death.
When vaccines get rolled out for use in the real world, though, it’s a different story. Suddenly, millions of people are involved, including those who may not have been represented in clinical trials such as people who are pregnant or chronically ill. In the case of COVID-19 vaccination, Australia has an advantage: with few active cases or very low rates of community transmission, we have been able to observe vaccines being deployed on a massive scale in other parts of the world, learning from their safety monitoring data in advance of our own larger rollouts.
The real world is messier and much more diverse than a controlled experimental trial: for example, someone might miss the second dose of a multi-dose vaccine, or the timing might not be quite right; someone might have a medical condition without realising, and so on. This is where a vaccine’s effectiveness comes into play—it looks at how well the vaccine works in the real world.
How vaccines are approved and monitored in Australia
Vaccine safety monitoring continues after the clinical trials are completed and for as long as vaccines are administered to the general population. Ongoing monitoring helps health authorities to discover any safety issues with a specific batch of vaccines, or very rare risks not picked up during clinical trials.
The Therapeutic Goods Administration (TGA) is responsible for overseeing vaccine approvals and safety monitoring in Australia. Even if a vaccine has been approved for use in other countries, and even if it’s been successful in clinical trials, the TGA always conducts its own assessment of the benefits and potential risks before a new vaccine is released for general use in Australia.
The first step is for the TGA to approve a vaccine. Here, the vaccine manufacturer provides the TGA with lots of data for review, especially about the vaccine’s safety, quality and effectiveness. For example, COVID-19 vaccines go through several stages of review and evaluation before they are finally approved for general use. These stages reflect the same assessments all vaccines go through, even when not being fast-tracked.
The safety testing doesn’t end there. Once a vaccine is approved and vaccination of the general population is underway, if someone experiences what is called an ‘adverse event’ after being vaccinated, that information gets collected, reported and analysed. Many reported adverse events that occur around the time of vaccination are not related to the vaccine at all and would have happened anyway, but they are still reported by health professionals, so that if a pattern of side effects related to the vaccine emerges, health authorities can investigate further. Adverse events shown to be related to the vaccine are sometimes only very mild, and if so, the vaccine continues to be used.
Health authorities can make the decision to temporarily stop giving a vaccine to people while they investigate whether a reported adverse event is a potential side effect related to the vaccine itself. For example, young children given a particular influenza vaccine in Australia in 2010 showed an increased risk of seizures. All flu vaccines in the children’s program were immediately stopped while health authorities investigated what was causing the problem. They found the culprit: one specific type of vaccine preparation was causing the issue. Health authorities were then able to reintroduce other flu vaccines that didn’t carry these risks. This also led to the development of AusVaxSafety, a system that enables fast vaccine safety monitoring using automatic SMS messages to gather feedback from vaccine recipients or their parents.
Sometimes we find extremely rare side effects after the approval and rollout of a vaccine. Finding them isn’t a reflection of a broken system, but rather one that is working as it should.
The aim of vaccination is to reduce the risk of people getting seriously sick and the risk of them dying—so scientists and health authorities collect as much information as possible and weigh up the benefits and risks to achieve this goal. All vaccines in use in Australia provide benefits that far outweigh any risks.
However, developing a good vaccine is only one part of the journey: it can only be fully effective when people actually receive their vaccines. The act of vaccination saves lives.