Empirical evaluation of the sensitivity of background incidence rate characterization for adverse events across an international observational data network

ABSTRACT Background: incidence rates are routinely used in safety studies to evaluate the association of an exposure and an outcome. Systematic research on the sensitivity of background rates to the choice of the study parameters is lacking. We used 12 electronic health record and administrative claims data sources to calculate incidence rates of 15 adverse events. We examined the influence of age, race, sex, database, time-at-risk start (anchoring) event and duration, season and year, prior observation and clean window. For binary comparisons, we calculated incidence rate ratios and performed random-effect model meta-analysis. Background rates were highly sensitive to demographic characteristics of the population, especially age, with rates varying up to a factor of 1,000 across age groups. Rates varied by up to a factor of 100 by database. Incidence rates were highly influenced by the choice of anchoring (e.g., health visit, vaccination, or arbitrary date) for the time-at-risk start, especially at short times at risk, and less influenced by secular or seasonal trends. Therefore, comparing background to observed rates requires appropriate adjustment, and results should be interpreted in the context of design choices. Short Figure