NSBE Boston Professionals has curated insights from Dr. Sara Suliman, Instructor in Medicine, Immunobiologist to educate our communities about the importance of diversity in the COVID-19 vaccine clinical trials.
We would like to thank Dr. Sara Suliman for her insights
What is a clinical trial?
A clinical trial is a type of study where an experimental product, intervention or treatment is given to people to assess whether it could provide a clinical benefit. These studies in humans can only be approved after having sufficient evidence in laboratory tests, in cells and/or lab animals, to indicate a potential benefit and minimal side effects (also referred to as adverse events).
How is a vaccine clinical trial different from a drug trial?
Vaccine clinical trials tend to take much longer and require more people to be enrolled to have sufficient support for clinical benefit than drug trials. The reason for this is that vaccine trials are often tested in healthy individuals, and need enough individuals receiving the vaccine or the control (placebo) to compare the two groups. The vaccine efficacy is calculated as the probability that it reduces the number of infections in people who receive the vaccine compared to those in the control group. On the other hand, drug trials are conducted in people who already have a certain disease. Therefore, it needs fewer people in the two arms of the study to test whether the drug improves clinical outcomes, such as recovery or survival.
What are the different phases of clinical trials?
In phase I, also known as “first-in-human” trials, the aim is to test the vaccine safety, and basic “proof-of-concept” analyses of whether the product induces an immune response that is likely to provide protection against the infection. Importantly, this phase does not test whether the vaccine is efficacious, i.e. whether the vaccine “works”. The first phase usually only recruits healthy individuals considered to be at low-risk for the condition of interest.
Phase II expands on the first phase, and tests additional parameters such as the most effective dose and injection route of the vaccine. They also provide more data on the safety of the product since more individuals are tested. In this phase, additional groups with higher risk of the clinical condition can be included, such as older individuals or those with other risk factors.
Phase III is when the efficacy of the vaccine is tested, i.e. whether the vaccine “works”, and these trials often recruit in multiple communities or “clinical sites” simultaneously. In the case of COVID, a phase III clinical trial tests whether the vaccine can meaningfully prevent infection or disease severity. In efficacy trials, uninfected healthy volunteers are divided randomly into a control group that does not receive the vaccine, and a parallel experimental group that receives it. For a vaccine to be considered efficacious, the rate of infections in those who received the vaccine has to be significantly lower than the control group in the same population and setting. If the vaccine is safe and efficacious, it can now be licensed for marketing and clinical use.
Finally, phase IV is the post-marketing stage of testing. This is the “real world” test of the vaccine, where data continues to be collected by clinical providers in different settings to document any rare adverse events that may not have been recorded in the previous trials. Since this phase is usually “post-licensing”, the settings are not as controlled as they are in the previous phases. Thus, phase IV provides data of how well the vaccine works in real life.
How are vaccines licensed for use?
After phase III of clinical trials, the data is reviewed by oversight bodies including the vaccine sponsors and the Food and Drug Administration (FDA), who review the data carefully. The FDA, is an impartial federal entity with no financial interest in the product being tested. This allows for an unbiased assessment of the vaccine trial data. The process is described in detail here.
What is happening with COVID vaccines? Why are they taking too long?
There are currently over 100 vaccine candidates in development and testing, with at least 10 in active clinical trials in humans. According to clinicaltrials.gov, an international registry of ongoing clinical trials, there are at least 188 clinical trials of candidate COVID vaccines at different phases around the world.
It may seem that these trials are taking too long, but the process from development to marketing can traditionally take up to 10 years. The fact that some COVID vaccines are in phase III testing less than a year since the beginning of the pandemic shows the global commitment to accelerate development and deployment of a COVID vaccine. However, it is important to establish that these vaccines are safe and efficacious before administering them to the public.
If I participate in a trial, does that mean I get the vaccine?
Not necessarily. Clinical trials, especially phase III, are usually randomized and double-blinded. Randomization means that you will have an equal chance of receiving the vaccine or the control product (placebo). Double-blinded means that both the clinical provider who administers the product and the person receiving it do not know whether the product is a vaccine or a placebo. This is important to mitigate any bias from either side, and to prevent behavioral changes influenced by the perception that the vaccine would now prevent infection with SARS-CoV2.
Is it safe to participate in a vaccine trial?
Vaccine trials are overseen by a data safety and monitoring (DSM) board that monitors any symptoms or clinical events that occur in anyone who participates in the trial. Any safety concerns have to be reported to the DSM immediately. Trials that do not comply are forced to discontinue. The clinical trial investigators are obligated to clearly explain the study and any potential risks, in order to inform the participant so they can make a decision on whether to consent to participate. This is also a voluntary process, and you have the right to withdraw at any point if you feel any discomfort or change your mind for any reason about participation. Clinical trials are governed by ethical principles called “good clinical practice” guidelines, which ensure that the rights of the participants are protected.
Why should you participate?
The more individuals participate in the trials, the faster the vaccine can be licensed. There are also indications that rates of SARS-CoV2 infections and COVID19 disease are higher in vulnerable populations, including black communities. Therefore, it is important to collect data on populations that are most affected by the virus and the disease, since they may respond differently to the vaccine than other groups. Your rights will be protected, and your health will be carefully monitored to ensure that this experience will pose minimal risk, and provide benefit to the communities now grappling with the infection and disease.
Courtesy of Dr. Sara Suliman, Instructor in Medicine, Immunobiologist and NSBE Boston member since 2019