Incidence in pharmacoepidemiology-Basic definitions and types of misclassification

The definition of a new case is a vital step in incidence studies in both epidemiology and pharmacoepidemiology, although with significant differences in methodology between the fields. We define and apply a framework for two different types of new cases of drug use, first-ever and recurrent, and show how the associated misclassifications related to length of run-in period can be expressed by the positive predictive value (PPV). In the study, we consider individual-level dispensations of statins 2006-2019 for 1,017,058 individuals with at least one dispensation in 2019 in Sweden. The incidence proportion for statins for both sexes of all ages in Sweden 2019 varied from 17.4/1000 with a run-in of 8 months, 9.45/1000 with 5 years and 8.4/1000 with 10 years. The PPV was 49% with 8 months and 89% for 5 years using 10 years as gold standard. We conclude that the interpretation of incidence and thus the selection of an appropriate run-in period, in pharmacoepidemiology, depends on whether first-ever use, recurrent treatment or both together (new cases) is the focus of the research question studied. At least five different misclassifications can be introduced depending on how incidence is defined.