Table 1.

Summary of advantages and disadvantages of different target populations in a cohort study of vaccine effectiveness, using PCV13 as an example.

Age of inclusion	Target group	Advantages	Disadvantages	Direction of Bias	Comment
4–52 weeks	Post-neonatal infants	High recruitment of deceased infants	Includes vaccine ineligible infants	Overestimated VE	Includes infants who have not had the opportunity to be vaccinated (non-outstanding), therefore leading to higher vaccine effectivenessa
6–52 weeks	Any dose age-eligible infants	Relatively high recruitment of deceased infants	High proportion of unvaccinated infants	Overestimated VE
14–52 weeks	Fully vaccinated infants: age-eligible for final dose	Relatively high recruitment of deceased infants	Low vaccine coverage and protection	Unclear direction of bias	May decrease VE as vaccinated but unprotected infants are considered vaccinated. Or may increase VE as untimely vaccination leads to more unvaccinated infants being included
16–52 weeks	within 2 weeks of recommended week as a strict cut-off	Per guidelines definition of vaccination	Low vaccine coverage	Unclear direction of bias
18–52 weeks	within the recommended month as a moderate cut-off	Moderately high vaccine coverage	Low recruitment of deceased infants	Inconclusive VE	Using later cut-offs will decrease recruitment of deceased infants, reducing the power
20–52 weeks	within 6 weeks of the recommended month as a moderate cut-off	Moderately high vaccine coverage	Low recruitment of deceased infants	Inconclusive VE
26–52 weeks	by 6 months of age as a liberal cut-off	High vaccine coverage	Low recruitment of deceased infants	Inconclusive VE

PCV13: 13 valent pneumococcal conjugate vaccine; VE: vaccine effectiveness.

^aIn this scenario, infants who were not age-eligible for all doses but died before they had the opportunity to receive all doses would still be included in the analysis as either unvaccinated or partially vaccinated, increasing the apparent vaccine effectiveness.