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Authors: Kirsten Perrett, Kim Jachno, Terry Nolan, Murdoch Chil
Journal: JAMA Pediatrics (2019)

In Reply We thank Rosenbauer et al and Vajravelu et al for their comments on our Research Letter. 1 Rosenbauer et al requested more details of the statistical methods.We used an interrupted time-series analysis (ITS) 2 on the incidence of newly diagnosed type 1 diabetes (T1D) in children aged 8 years before and after the May 2007 introduction of routine infant oral rotavirus (RV) vaccination.Counts of new T1D cases by age were modeled as Poisson random variables.Publicly available population data for each age group and sex combination in each year were included as an offset in the model, and inference was on the relative change in incidence rates averaged over the preperiod and postperiod.We used annual counts of new cases of T1D from the Australian Institute of Health and Welfare and population numbers from the Australian Bureau of Statistics.The rate of T1D exhibits year-on-year variation (a cyclical trend), which makes selection of any set change point problematic.This is a challenge for small data sets because it is possible to obtain highly variable results for time trends and changes in averaged rates depending on the inclusion of more or fewer data points at the peak, middle, or trough of any cycle.In their review of ITS in drug utilization research, Jandoc et al 3 recommend a minimum of 9 data points preintervention and postintervention, at least 100 observations per data point, and suggest maximum power to detect an effect is achieved when numbers preintervention and postintervention are balanced.An acknowledged limitation of our data set is that it consisted of only 16 annualized counts for each age group, although these were balanced from 8 preintroduction and 8 postintroduction years and included more than 335 observations per data point.Analysis at other yearly change points would result in unbalanced observations.At the suggestion of Rosenbauer et al, we performed a change point analysis on our data set.We found a similar result with a change point after 2007, 2008, or 2009 and no effect if after 2004, 2005, or 2006, supporting our initial findings.Vajravelu et al commented that our data show an abrupt decrease in T1D incidence around the time of RV introduction.We hope our additional analysis corrects this possible misunderstanding.Vajravelu et al also commented that ITS is most appropriately used with short-term outcomes, which we acknowledge.However, the uptake of RV vaccination was high and prompt, and other factors that would explain the observed changes in T1D incidence rates in children aged 0 to 4 years but not in older age groups are not apparent.Further, T1D diagnosis is standardized in Australia, and there was no systematic change in case definition or ascertainment during the study period.Additionally, we report a coding error 4 that affected the reported T1D rates but not the overall findings in our study.A casual association between RV vaccination and T1D cannot be established from this ecologic study.However, this new evidence of a decline in incidence of T1D after the introduction of RV vaccine into a routine national immunization should encourage further research in other jurisdictions to test this hypothesis.