After the U.S. Food and Drug Administration (FDA) authorizes a vaccine for emergency use or approves a vaccine, experts continue to assess how well the vaccine is working in real-world conditions. Clinical trials of the available COVID-19 vaccines are important for authorization and approval, but their results may not reflect how effective the vaccines are once administered beyond the clinical trial. CDC has established methods to monitor vaccine effectiveness in real-world conditions and address ongoing and future questions around how vaccines perform.
CDC uses several methods to evaluate COVID-19 vaccine effectiveness. These methods can contribute different information and build a base of evidence about how COVID-19 vaccines are working. The information collected through this combined approach enables CDC to monitor vaccine effectiveness over time. This can help inform public health action to continue to best
protect the population.
Vaccine Effectiveness Studies
Experts are working on many types of assessments to determine COVID-19 vaccine effectiveness in real-world conditions. These are known as vaccine effectiveness (“VE”) studies. The goal is to understand how a vaccine protects people outside of strict clinical trial settings, where storage and delivery are monitored and participants are usually healthy. Vaccine effectiveness measures vaccine protection in observational studies, which:
Include people with underlying medical conditions
Include people who have been given vaccines by different types of healthcare professionals under real-world conditions
Occur in settings where people may make different decisions about vaccination
There are several kinds of observational studies, which use different methods:
Case-control studies include cases (people who have COVID-19) and controls (people who do not have COVID-19). People who agree to participate in a case-control study provide information on whether they received a COVID-19 vaccine. Experts look back to see if cases were less likely to be vaccinated than controls, which would show the vaccine is working.
Some case-control studies use a test-negative design. These studies enroll people who are seeking medical care for symptoms that could be due to COVID-19. In this special type of case-control study, experts compare the COVID-19 vaccination status of those who test positive, meaning they have COVID-19, to those who test negative, who do not have COVID-19).
Cohort studies observe groups of people, both vaccinated and unvaccinated, then follow them for a period of time to see if they get COVID-19. Experts compare COVID-19 illness in the vaccinated and unvaccinated groups to measure how well COVID-19 vaccines protected against the disease. This can be done in real time (prospectively) or by looking back in time (retrospectively) using data already collected, such as information in participants’ medical records.
Screening method assessments look at vaccination status among a group of people infected with the virus that causes COVID-19 (for example, those detected through ongoing COVID-19 surveillance) and compare that with the vaccination coverage in the overall population where those cases arise (for example, people from the same state). By comparing vaccination coverage between these two groups, researchers can get an estimate of whether a vaccine is working as expected.
Ecologic analysis assessments look at groups of people—such as those in different locations or at different times—using different sources of data to see if there is an overall association between how many were vaccinated against COVID-19 and how many were diagnosed with COVID-19. These analyses may be hard to interpret broadly because an association that might appear at the group level might not exist on an individual level. Also, it is hard to control for differences in the different sources of data.
Cross-Agency Collaboration and Evaluating COVID-19 Vaccine Effectiveness
CDC coordinates with several other federal agencies to assess how COVID-19 vaccines work under real-world conditions after FDA authorization for emergency use or approval. These agencies include: