Vaccine Effectiveness Studies

CDC’s COVID-19 Vaccine Effectiveness Program

In collaboration with public health partners, CDC evaluates vaccine effectiveness through multiple observational studies that employ a variety of methods and use information collected through surveillance platforms, electronic health records, and prospective studies. Vaccine effectiveness studies utilize multiple sources of vaccine history data (e.g., medical records, state and jurisdiction vaccine registries, vaccination cards) to minimize bias.

Several factors influence vaccine effectiveness, including:

Collecting information on these factors and adjusting for important epidemiologic confounders allow CDC to minimize bias in measuring vaccine effectiveness. Vaccine effectiveness may differ in certain populations, such as older individuals or those with immunocompromising conditions. To account for these differences, effectiveness estimates are often presented by age group, by presence of immunocompromising conditions, or among other populations at increased risk for severe COVID-19, such as long-term care facility residents. Vaccine effectiveness can also differ by the type of vaccine product, total number of vaccine doses received, and how long it has been since the most recent vaccine dose was received.

Guiding principles for monitoring vaccine effectiveness

When monitoring vaccine effectiveness, CDC is guided by the following principles:

Outcomes of interest for vaccine policy

Preventing severe COVID-19 is the priority for the U.S. COVID-19 vaccination program. The U.S. Advisory Committee on Immunization Practices uses a standard Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework to review vaccine effectiveness studies systematically. The GRADE framework considers quality of evidence on vaccine effectiveness against patient-important outcomes. CDC’s vaccine effectiveness program monitors these outcomes in the evaluations it conducts to generate evidence most relevant for COVID-19 vaccine policy:

Terms for vaccine effectiveness

Vaccine effectiveness is a measure of how well vaccination protects people against health outcomes such as infection, symptomatic illness, hospitalization, and death. Vaccine effectiveness is generally measured by comparing the frequency of health outcomes in vaccinated and unvaccinated people. Absolute vaccine effectiveness is a term that can be applied when the study compares vaccinated people to unvaccinated people.

Sometimes vaccine effectiveness is measured by comparing the frequency of health outcomes in people who received one type of vaccine to people who received a different vaccine or by comparing people who received more vaccine doses to people who received fewer doses. Relative vaccine effectiveness is the term used when the study measures vaccine effectiveness by comparing people who have received one vaccine type or regimen to those who received a different vaccine type or regimen. In addition, vaccine effectiveness measures comparing people who received more doses to those who received fewer doses can be referred to as incremental vaccine effectiveness.

• Measuring relative and incremental vaccine effectiveness can help vaccine policy makers decide whether people who have already been vaccinated may benefit from receiving a new vaccine product or an extra dose.
• For example, CDC studies measured relative vaccine effectiveness of the updated (bivalent) COVID-19 booster by comparing people who received original (monovalent) COVID-19 vaccines plus an updated (bivalent) booster dose to people who had only received original (monovalent) COVID-19 vaccines.
• In these studies, relative vaccine effectiveness can be interpreted as the additional protection provided by an updated (bivalent) booster among people who already received monovalent COVID-19 vaccines.

Vaccine Effectiveness Evaluations by Outcome

Below are descriptions of some of the vaccine effectiveness evaluations CDC conducts with partners. The descriptions include the data collection platform, outcome, population, and participating sites. Links to online resources detailing the evaluation designs are included when possible.

Hospitalization for COVID-19 or medically attended COVID-19

Hospitalization is a widely recognized measure of severe COVID-19. The limitations of this measure as a marker of severe disease include the challenge in distinguishing hospitalizations due to COVID-19 from hospitalizations in which SARS-CoV-2 infection is incidentally identified, which can lead to differences in vaccine effectiveness estimates generated across various platforms.

CDC works with partners to evaluate vaccine effectiveness in preventing hospitalizations and emergency department and urgent care visits for COVID-19 using the following platforms: VISION, IVY, and Overcoming COVID.  These platforms also collect information on severity of COVID-19-associated hospitalizations and COVID-19-associated deaths.

Post-COVID Conditions and related conditions

Understanding vaccine effectiveness in reducing the occurrence of these outcomes is especially important as they can occur after relatively mild acute infections. The broad spectrum of PCCs, including its various manifestations and lack of standard case definitions across surveillance platforms, makes it challenging to evaluate vaccine effectiveness against these outcomes and interpret findings across studies. CDC has included follow-up of participants to measure PCC in many of its vaccine effectiveness platforms.

Symptomatic SARS-CoV-2 infection

The primary goal of the COVID-19 vaccination program is to prevent severe illness and death. Monitoring vaccine effectiveness against infection provides useful insight into effectiveness against new variants or be an early signal of waning of vaccine effect. Studies monitoring vaccine effectiveness against SARS-CoV-2 infection can be subject to bias due to changes in testing practices, including increased use of at-home testing, or different testing practices among vaccinated and unvaccinated individuals. CDC employs multiple study designs and various statistical methods to account for influence of such factors on measured vaccine effectiveness.

Vaccine effectiveness against SARS-CoV-2 infection is monitored using the following platforms: ICATT, HEROES/RECOVER, PROTECT, and PREVENT.