Methods

First consider the scenario in which there is a known increased risk of the adverse event in the population as a whole and we want to know if the excess risk is more severe among children in a specific group. By use of the temporal scan statistic, first determine the true risk window for the adverse event, as described above. Suppose that we have an excess risk in the 7 to 10 days after vaccination. We now define the study population as those who received the vaccine and who had an adverse event in some longer time period, such as 1 to 42 days after vaccination. In a logistic regression model, the dependent variable is whether they had the adverse event inside or outside the true risk window. The independent variables are the various health status variables that we want to examine as potential risk modifiers. Several of these can be included in the same logistic regression, but doing several univariate analyses may be a suitable first step. As long as the baseline risk for the adverse event is fairly constant over the longer time period, it is not necessary to adjust for age. Note that since all subjects had the vaccine and all subjects had the adverse event, there is no actual interaction term in the logistic regression model.

If we do not have a known adverse event but still want to evaluate possible vaccine–health status interaction terms, we can still use the same approach with a reasonable guess of a wider risk interval. For example, the risk interval may be 1 to 42 days, while the comparison interval is 43 to 84 days.

Late-Onset Adverse Events

The approach described above cannot be used to study late-onset adverse events. Instead, we first determine if a vaccinated child had the health condition of interest at the time of vaccination. We then compare the number of late-onset events between the children that did and those that did not. This design is more prone to bias than the self-controlled design described above. One way to partially adjust for this is to include only children that had both the vaccine and the potential adverse event of interest, at any time, and compare the children who had the vaccination at the same time as the health event with those that had them at different times.

VACCINE-VACCINE INTERACTION Background

In the CDC-recommended vaccine schedule, many different vaccines are given on the same day. It is plausible that two vaccines, if given separately



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