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Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1524-1529. doi: 10.1073/pnas.1612833114. Epub 2017 Feb 1.

Estimating the population-level impact of vaccines using synthetic controls.

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Department of Epidemiology of Microbial Diseases, Yale University School of Public Health, New Haven, CT 06520.
Sage Analytica, Portland, ME 04101.
Department of Statistics, University of California, Riverside, CA 92521.
Department of Pediatrics, Yale School of Medicine, New Haven, CT 06520.
Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520.
Milken Institute School of Public Health, George Washington University, Washington, DC 20052.
Department of Public Health, University of Copenhagen, 1017 Copenhagen, Denmark.
Department of Epidemiology of Microbial Diseases, Yale University School of Public Health, New Haven, CT 06520;


When a new vaccine is introduced, it is critical to monitor trends in disease rates to ensure that the vaccine is effective and to quantify its impact. However, estimates from observational studies can be confounded by unrelated changes in healthcare utilization, changes in the underlying health of the population, or changes in reporting. Other diseases are often used to detect and adjust for these changes, but choosing an appropriate control disease a priori is a major challenge. The "synthetic controls" (causal impact) method, which was originally developed for website analytics and social sciences, provides an appealing solution. With this approach, potential comparison time series are combined into a composite and are used to generate a counterfactual estimate, which can be compared with the time series of interest after the intervention. We sought to estimate changes in hospitalizations for all-cause pneumonia associated with the introduction of pneumococcal conjugate vaccines (PCVs) in five countries in the Americas. Using synthetic controls, we found a substantial decline in hospitalizations for all-cause pneumonia in infants in all five countries (average of 20%), whereas estimates for young and middle-aged adults varied by country and were potentially influenced by the 2009 influenza pandemic. In contrast to previous reports, we did not detect a decline in all-cause pneumonia in older adults in any country. Synthetic controls promise to increase the accuracy of studies of vaccine impact and to increase comparability of results between populations compared with alternative approaches.


Streptococcus pneumoniae; observational study; pneumococcal conjugate vaccines; program evaluation; synthetic controls

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