dose, it is more suitable to define them according to a predefined age range. For example, the study may include only children who had all the doses of interest before 18 months of age and would consider only adverse events for which the incident diagnosis occurred between ages 2 and 6 years. That will prevent bias due to age-varying incidence rates.

If suitable health plan data are not available, a case-control approach can be used instead. The first step is then to select children with an incident diagnosis during a predefined age range, together with a set of controls matched by age, gender, calendar month, study site, and other covariates of interest. The next, more challenging step is to obtain the vaccination history of each of the children. This could be done by contacting all the health plans or all the pediatricians that the child has had. The dose interval length is then compared between those children with and without the adverse event.



Several vaccines are contraindicated for children with specific health problems. For example, live attenuated influenza vaccine should not be given to 2- to 4-year-old children who have had wheezing during the past 12 months (CDC, 2012). This means that the vaccine schedule may have to be modified for some children on the basis of their personal disease history. To know if and when that is necessary, one needs to study the interaction effects between vaccines and preexisting health conditions.

The study of interaction effects between vaccines and health conditions is especially important when there is a known excess risk of an adverse event. If it is possible to pinpoint that the adverse events are due to an interaction effect, then the number of adverse events can be reduced by contraindicating the vaccine for children with the health condition in question. For example, if the risk of seizures after vaccination with MMR is higher among children with a recent well-defined disease episode, then MMR may potentially be postponed by 3 months for those children.

Early-Onset Adverse Events


Electronic health plan data are suitable for early-onset adverse events.

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