Analyses modelled the first incidence of each event or class of event (e.g., respiratory

events) as the response variable. The RR for the main effect (or a covariate) was estimated by eβ where β is the regression coefficient for the specific effect or covariate of interest. The ninety five percent confidence intervals for the RR were calculated using a normal approximation, with the variance derived from the appropriate diagonal element of the estimated covariance matrix. In a conservative approach, statistical significance was declared if either the exact method or the Cox Selleckchem BIBF-1120 model showed statistical significance. A statistically significant increased risk associated with LAIV vaccination was declared if the lower bound of the exact 95%CI or the CI constructed from the Cox proportional model was >1.00. Likewise, a statistically significant decreased risk associated with LAIV vaccination was declared if the upper bound of either 95%CI was <1.00. Statistical significance was determined before rounding. The corresponding P values were also provided. When the control group had a zero event, the RR or HR was not estimable owing to a zero value of the denominator. If the P value was available, statistical significance was declared according to the MLN0128 nmr P value at the significance level of 0.05. According to the prespecified data analysis plan, CIs were constructed

without multiplicity adjustment. To facilitate interpretation of the results, a post Cell press hoc analysis was conducted using the Bonferroni method and statistical significance was declared at the adjusted significance level of 0.000002. The sample size of 20,000 per age group provided ≥90% power within each age group to observe a statistically significant increased RR if the true RR was ≥2.0 for events that occurred at a rate of 1 in 500 or if the true RR was ≥2.5 for events that occurred at a rate of 1 in 1000. For events that occurred at rates of 1 in 100 or 1 in 50, the study provided ≥90% power to observe a statistically significant increased RR if the true RR was ≥1.4 or ≥1.25, respectively, in

each age cohort. All analyses were performed using SAS® statistical software, version 8.2 (SAS Institute, Inc., Cary, NC, USA). A total of 43,702 unique subjects 5–17 years of age were vaccinated with 53,369 doses of Ann Arbor strain LAIV during the 5 study seasons. A similar number of TIV-vaccinated subjects receiving 48,683 vaccine doses and 53,366 unvaccinated subjects were used as matched controls. Subject characteristics are summarized in Table 2. A total of 3 deaths from all causes within 180 days of LAIV vaccination were observed during the entire study period. Deaths included a 17-year-old who died in an automobile accident, a 13-year-old who died from asphyxiation after choking on food, and an 11-year-old who died in a house fire. All were considered by the investigator to be unrelated to LAIV.