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How Do Clinical Trials Work?

Updated: Mar 1, 2021

Vaccines are the most effective way to prevent infectious diseases. Their development involves an extensive set of rigorously designed procedures to ensure safety and efficacy before they are given to many people. In other words, when a vaccine is released to the market, they already went through a long and careful examination to make sure it will not hurt the population while still protecting from disease.

Each country or region has its own agency that regulates and makes sure that the vaccine development process is rigorously done. In the USA, the agency is called U.S. Food and Drug Administration (FDA), in Europe it is known as the European Medicines Agency (EMA), in Mexico, it is called the Comision Federal para la Protección contra Riesgos Sanitarios (COFEPRIS), etc.

The process of vaccine development is divided into different phases, in which different parameters are assessed. Each stage has different goals and provides different information. At each stage, the data are assessed by government regulators to give permission to move to the next stage. A vaccine is released to the market after a Phase 3 clinical trial is passed and the results are thoroughly reviewed

Vaccine development and clinical testing happens in various phases. Each phase serves its own purpose and all phases together are conducted in such a way that safety can be assured

The general process of vaccine development

The general stages of the development cycle of a vaccine are (according to the CDC):

  • Exploratory stage - Design of the vaccine and experiments in cells

  • Pre-clinical stage - Experiments in animals

  • Clinical development - Clinical Trials Phase 1 to Phase 4

  • Regulatory review and approval - All data from earlier stages is evaluated

  • Manufacturing - Reproduction of the exact same product that was approved

  • Quality control - Every step of manufacturing and distribution is recorded and verified

The exploratory and the pre-clinical stage are done in the laboratory by research scientists. They design the vaccine (not as easy as it sounds) and test it in cells and animals to assess for vaccine safety and immunogenicity (i.e., the ability of the vaccine to produce an immune response). After these stages are done, we know if the vaccine is safe in animals and if it is able to induce an immune response.

The clinical stages

After the initial tests in cells and animals, the clinical stages of the process are done with human volunteers. They include:

Phase 1

(Is the vaccine safe in humans? What type of immune response is it inducing?)

Goal: to assess safety and the type and extent of the immune response. Participants: a small group of adults (between 20-100 healthy volunteers).

Phase 2

(Is the vaccine safe? For how long can it induce an immune response? Which vaccine doses should be used to induce an immune response? Is a vaccine booster necessary?)

Goal: to assess safety, immunogenicity, dosing, and schedule.

Participants: between 50 to several hundred people.

Phase 3

(Is the vaccine safe? Can the vaccine prevent the disease?)

Goal: to assess efficacy (i.e., the reduction of disease in the vaccinated group compared to an unvaccinated group receiving a placebo (fake drug)) and further study of the safety.

Participants: thousands to tens of thousands of people (e.g. Moderna trials >30,000 participants and Pfizer >40,000 participants)

Phase 4

(Is the vaccine safe?)

Goal: to follow up on the safety, looking for long term effects

Participants: people who received the vaccine after it was released to the market

In the different stages, the candidate vaccine is tested against a placebo, which is usually an inert substance with no therapeutic value (such as a saline injection). This comparison allows scientists to observe how many people naturally contract the virus in the absence of the vaccine, and to rule out any psychological and behavioral effects caused by thinking that you were vaccinated.

Since Phase III Trials are done in big groups of participants, it is possible to detect rare side effects that are too infrequent to be identified in the other trial phases.

Once all the trials are completed, the information is reviewed by independent regulators who are not related to the groups and companies that developed the vaccine. Once carefully evaluated, the vaccine is approved and can be used in that country.

COVID-19 vaccine development is following all these standards. However, given the urgency to develop vaccines fast to combat the pandemic, some changes to this standard protocol have been made. First, multiple phases were partially conducted overlapping another, to allow for continuation into the next phase before all analyses of previous phases have been finished. Second, regulatory authorities have evaluated the data from Phase III trials before authorizing the use of these vaccines for the public. This means that monitoring continues but all safety and efficacy requirements have been met.

COVID-19 vaccines are safe and will protect you against the disease. Getting vaccinated is important. Just do it!

Further Reading

Contributed by: Text: Nilda Vanesa Ayala Nunez, Illustration: Christina Nowicki

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