The COVID-19 pandemic is still an ongoing global problem, with the current death toll worldwide of almost 1’000’000 people and over 5’000 people in just the last 24 hours (as of 27.09.2020) [1]. Hence, we are in need of an effective solution to be able to fight the SARS-CoV-2 virus.

One of the possible remedies for this pandemic could be a vaccine, which once administered would provide immunity against the virus without actually getting infected by it. At the moment, many companies are working on the development of a vaccine, and 42 are being currently tested in clinical trials [2]. Unfortunately, one of them was the target of a social discussion as one of the patients displayed an adverse event. Furthermore, this study was put on hold to verify the reasons why this patient became sick [3].  The investigation showed that there is no evidence that the vaccine was responsible for causing the illness and research was resumed. This information triggered another social backlash from people who were already opponents of vaccinations, as visible in the comments section of one of the journals that covered this topic [4].

The aim of this article is to explain the concept and stages of clinical trials. It will be followed up by a second article in which we will discuss the current state of the COVID-19 vaccines in more detail.

While side effects and adverse events are not desired in any drug or vaccine, their proper identification is part of the clinical trial [5]. The process is divided into three distinct phases in the pre-approval period:

1. Phase I – the main goal at this stage is to assess the safety of the studied drug or vaccine on people without any underlying condition. That is why it usually contains 20 to 80 healthy voluntary participants who are closely monitored for any possible adverse events. It is usually the shortest phase and lasts several months [6, 7].
2. Phase II – the main goal at this stage is still the safety of the studied medication, mostly with regard to the treatment dosage and the method of application. When testing vaccines, the efficacy is the second primary goal of this phase. To further assess the safety of the tested medication, this phase contains a few hundred healthy individuals (in case of vaccine studies) or patients with a disease (in case of drug studies) to closely monitor any possible side effects or adverse events related to the studied medication. This phase lasts longer, from several months to even a few years, depending on the study [6-8].
3. Phase III – this phase is significantly bigger in regard to the number of enrolled individuals, as it contains tens of thousands of participants. In the case of the studies for vaccinations, the patients are still healthy individuals. This is the first phase in which the efficacy of the studied medication is the primary goal while still monitoring its safety. During this phase, the assessment of the ratio between risks and benefits takes place. Hence, it is possible to present that the studied medication is advantageous for the intended use. This is usually the longest phase and can take from one to a few years [6, 7, 9].

With all that in mind, it is important to understand that the main goal of clinical trials is to test the safety of the studied medication in a safe and controlled environment which allows fast access to medical care in case of a potential side effect or adverse event during the trial.

Moreover, it is important to remember that clinical trials can be run on tens of thousands of individuals, which is still a small number when compared to a few billion people around the world. That is why Phase IV of clinical studies is very often conducted to monitor the safety and efficiency of the medication after it is approved for the general use. This way, it is possible to monitor any rare adverse event that may occur after using the studied medication [5, 6, 9, 10]. Furthermore, when a medication is licensed for public use after clinical trials, all the adverse events and side effects are publicly available and can also be reported by patients on a specific website. In the case of European Union citizens, it can be found under this address: http://www.adrreports.eu/en/index.html, while US citizens can find it under this address: https://vaers.hhs.gov/index.html.

Adverse events and side effects often happen during clinical trials, as their role is to find, identify, and solve possible issues. While some are impossible to eliminate, it is important to remember that every medication can be released for public use only if the ratio of the benefits to risks is greatly in the favor of the benefits.