with MMR and the measles, mumps, rubella, and varicella (MMRV) vaccine (Klein et al., 2010). There are also several such examples of less severe adverse events like fever and rash. The adverse event may be serious enough to warrant the withdrawal of the vaccine from the market, as with the rotavirus vaccine, or it may be mild enough to keep using the vaccine, as with MMR. A midlevel alternative option is to revise the vaccination schedule to minimize the number of adverse events or to contraindicate the vaccine in a certain age group. Knowledge of the relative and attributable risk of the adverse event as a function of age is one important component when deciding between these options, together with other important factors, such as how the immunogenicity varies by age. This paper discusses only methods for obtaining knowledge about the former and not how to weight different sources of information to arrive at a final decision.


In two different studies, Gargiullo et al. (2006) and Rothman et al. (2006) evaluated the effect of age on the excess risk of intussusceptions after vaccination with the rotavirus vaccine (RotaShield). In a more recent study, Rowhani-Rahbar et al. (2012) evaluated the effect of age on the risk of febrile seizures after vaccinations with MMR and MMRV. All three studies found that the risk of the adverse event varied greatly by age.


EMRs from health plans and health insurance claims from health plans are ideally suited for studying this question. It is also possible to use data from a case-control study. VAERS data cannot easily be used since VAERS does not contain information about the age distribution of vaccinated children. Too few data are available from premarketing randomized because such trials are too small and typically do not include individuals over a wide enough range of ages. In light of existing observational data, specifically designed postmarketing randomized trials could be unethical, depending on the nature of the known adverse event.


The first key step is to determine the time between the vaccination and the adverse event as precisely as possible. Some children will, just by chance, have the adverse event soon after vaccination. To maximize the precision of our age estimates, we want to exclude as many of them as possible, by counting only the adverse events occurring in the true risk window. An efficient way to determine the appropriate risk window is to

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