Vaccines are first tested in people during phase 1 clinical trials. Phase 1 clinical trials assess the initial safety of the vaccine candidate and often compare different vaccine doses. Phase 1 clinical trials typically enroll dozens or hundreds of healthy adult volunteers.
If the results of the phase 1 clinical trials are promising, then the vaccine candidate will move on to phase 2 clinical trials. Phase 2 clinical trials are larger studies designed to continue to assess safety and to test the immune response to the vaccine in healthy people, often comparing those who are randomly assigned to receive the vaccine to those who remain unvaccinated. Typically, hundreds or thousands of volunteers participate in phase 2 clinical trials. Sometimes, phase 1 and phase 2 trials are combined into phase 1/2 clinical trials where the aims of both the phase 1 and phase 2 trials are achieved.
If the results of the phase 2 clinical trials are promising, then the vaccine candidate will move on to phase 3 clinical trials. Phase 3 clinical trials are so important, because they can provide the strongest evidence about how safe and protective the vaccine candidate is. In phase 3 clinical trials, thousand, tens of thousands, or sometimes more than 100,000 eligible volunteers participate and are randomly assigned to receive the vaccine or remain unvaccinated. Phase 3 clinical trials allow researchers to determine whether the vaccine protects those who are vaccinated from becoming sick compared to those who remain unvaccinated. By evaluating the evidence from phase 3 trials, we can understand a vaccine candidate's initial safety profile and how well the vaccine protects. Sometimes phase 2 and phase 3 trials are combined into phase 2/3 clinical trials where the aims of both the phase 2 and phase 3 trials are achieved.
If the evidence from phase 1, 2, and 3 clinical trials demonstrates that the vaccine is safe and effective, this evidence will be reviewed by national authorities and regulatory agencies who will decide whether the vaccine should be approved and authorized for use.
Even after completing phase 1, 2, and 3 trials, and even after vaccines are authorized for use, vaccines continue to be monitored to ensure that they remain safe and effective.
COVID-19 vaccine clinical trials are accepting volunteers in dozens of countries around the world. Find out which trials are underway in your country.
COVID-19 vaccine development progressed more rapidly than ever before because of significant funding, years of prior research, and the urgency of the pandemic
In the past, vaccines took years, or sometimes decades, to develop and test before enough evidence was available to demonstrate that they were safe and effective. The slow progress of the vaccine development process became the norm due to lack of adequate funding to advance more quickly, due to insufficient resources to accelerate the timeline, and due to the fact that only a small number of researchers and companies were working on vaccine development.
The urgency of the COVID-19 pandemic required rapid development of COVID-19 vaccines without delay. By devoting more resources, funds, and efforts than ever before, and by testing more vaccine candidates than ever before, COVID-19 vaccine development became the top priority for many countries, companies, research groups, and health organizations. As a result, the development process was accelerated – but not rushed! In fact, the technologies used to develop COVID-19 vaccines (including the mRNA platform) have been extensively studied for decades!
Vaccines are approved/authorized by national, regional, and global regulatory agencies based on an extensive review process
Vaccine candidates are extensively and rigorously tested in phase 1, 2, and 3 clinical trials before they can be authorized for use. Many countries, regional health authorities, and global organizations (like the World Health Organization) have a detailed process for reviewing evidence to determine whether a vaccine is safe and effective and whether it should be approved for use in their jurisdiction.
This review process differs by country and regulatory authority. However, many regulatory authorities publish summaries of the evidence about how safe and effective a vaccine is based on phase 1, 2, and 3 clinical trial results. This evidence supports the decision to approve a vaccine. Some countries rely on the decisions of regional or global regulatory authorities and adopt their recommendations.
There are many approval pathways and these also differ by country and regulatory authority. On our site, vaccines listed as approved include vaccines that have been approved, authorized, licensed, given emergency use authorization, given emergency approval, or made available for use via any mechanism recognized in that country. Consult the official health authority in each country to learn more about the process.
Vaccines given emergency use authorization also undergo extensive review to establish that they are safe and effective
Many countries have a process for authorizing vaccines for emergency use to ensure timely access to essential medical resources, like vaccines against COVID-19 during the pandemic. The specific pathway for authorizing a vaccine for use is country-specific, though most countries follow international standards and evaluate vaccines based on phase 3 clinical trials to assess whether the vaccine meets appropriate standards for safety, efficacy, and quality.
Emergency use authorizations are used in urgent situations typically when there are no approved and available alternative vaccines, and when the known and potential benefits of the vaccine in protecting people and keeping them healthy outweigh the known and potential side effects. Additionally, vaccines given emergency use authorizations, just like vaccines that are licensed or approved by other pathways, continue to be monitored as soon as vaccination campaigns begin to ensure that they remain safe and effective.
Find out more about which countries have approved each COVID-19 vaccine. As noted above, there are many approval pathways and these differ by country and regulatory authority. On our site, vaccines listed as approved include vaccines that have been approved, authorized, licensed, given emergency use authorization, given emergency approval, or made available for use via any mechanism recognized in that country. Consult the official health authority in each country to learn more about the process.
Vaccines are monitored continually to ensure that they continue to be safety and effective even after approval
Vaccines are tested in phase 1, 2 and 3 clinical trials to ensure that the benefits of vaccination outweigh any potential side effects. Evidence from clinical trials can help us learn about the most common side effects that can occur after vaccination, like a headache or a sore arm.
While clinical trials identify common side effects, vaccines must continue to be monitored during vaccination campaigns to check for very rare side effects. These unusual side effects are often so rare that they might only happen in one out of millions, or even tens or hundreds of millions, of vaccine doses. Health authorities are constantly reviewing the evidence to ensure that the benefits of vaccination far outweigh the potential risk of rare adverse events.
If you have questions about what to expect after vaccination, including questions about common or rare side effects, it is a good idea to talk to a health care professional to learn more about the latest evidence.
Vaccines can keep us healthy by preventing infection, transmission, symptomatic disease, hospitalization, and even death
COVID-19 vaccines teach our immune system to recognize SARS-CoV-2, the virus that causes COVID-19, so that if we are exposed to the virus, our immune system can leap into action and keep us healthy.
Vaccines can protect us from COVID-19 by preventing us from getting infected at all, and by preventing us from getting sick, ending up in the hospital, or dying even if we are infected. Vaccines can also prevent us from transmitting the virus to others.
In clinical trials, there are many outcomes that researchers can assess to determine how a given vaccine candidate works. COVID-19 vaccines can prevent some or all of these health outcomes and the evidence from clinical trials helps us understand how vaccines keep us healthy.
Most phase 3 clinical trials report the vaccine efficacy (VE) for symptomatic disease as the primary outcome. That tells us how well the vaccine prevents us from getting sick. Or, in other words, the vaccine efficacy tells us how much less likely a vaccinated person is to get sick compared to an unvaccinated person.
For example, if a COVID-19 vaccine’s efficacy is reported to be 95% against symptomatic disease, participants who received the vaccine were 95% less likely to experience symptoms of COVID-19, compared to participants in the control group (the group that did not receive the vaccine). A vaccine clinical trial can report a different outcome, or multiple outcomes, so it's important to ask what outcome the vaccine efficacy estimate refers to.
In addition to the primary outcome, vaccines can have multiple benefits. For example, in addition to preventing symptomatic disease (the most common primary outcome), many COVID-19 vaccine clinical trials showed that the vaccine was 100% effective in preventing severe disease (in particular, hospitalizations and deaths). In other words, none of the vaccinated individuals were hospitalized or died of COVID-19, a remarkable finding!
Finally, it’s important to distinguish between vaccine efficacy versus vaccine effectiveness. Vaccine efficacy is a measure of how well the vaccine works in a clinical trial, whereas vaccine effectiveness determines how well the vaccine works in real life. While these numbers are likely to be very similar, they may not be identical. Getting vaccinated is the single most effective decision you can make to prevent COVID-19. Yet, no vaccine has been proven to be 100% effective against all outcomes for all age groups and for all variants, so it's important to continue to follow all public health guidelines and continue to reduce the risk of SARS-CoV-2 infection even after vaccination.
Learn more about which health outcomes were evaluated in each clinical trial by reviewing a vaccine’s clinical trial records!