Almost all childhood vaccines are given in multiple doses a few months or years apart. It is conceivable that the length of the time interval between vaccine doses could increase or decrease the risk of adverse events.
Using a randomized trial, Pittman (2002) showed that the risk of adverse events was reduced if the second dose of subcutaneous anthrax vaccine, adsorbed, is given 4 months rather than 2 weeks after the first dose.
Early-Onset Adverse Events
The use of electronic health data is suitable for vaccine doses that are at most a few years apart. If the time between doses is too long, health plan data are less suitable, as only some members will have been enrolled long enough to have information about all the doses of interest.
For simplicity’s sake, first consider the situation where we want to evaluate the length of the time interval between the first two doses of the vaccine with respect to early-onset adverse events after the second dose. First, identify a cohort of children who received the first two doses of the vaccine. Exclude children that do not have a sufficiently long enrollment in the health plan to ensure that these are truly the first two doses. Note the number of days between the doses and whether they had an adverse event during a prespecified risk window after the second dose. For the statistical analysis, use logistic regression. The dependent variable is whether the potential adverse event was present in the risk window or not. The independent variable of interest is the number of days between the two doses. Adjust for gender, age at the second dose, calendar year, seasonality, study site, and any other potential confounders by including these as additional independent variables.
When one is looking at early-onset adverse events after the third dose, the same methods can be used for evaluating the length between the first and third dose or between the second and third dose. A single logistic regression can be used to evaluate both the time from the first to the third