An analysis of the exclusion criteria used in observational pharmacoepidemiological studies

The application of exclusion criteria in pharmacoepidemiological studies could have a major impact on the findings but there appears to have been no previous research to examine the types of exclusion criteria applied.

We searched the literature and identified 10 senior pharmacoepidemiologists who had published five or more relevant papers between 1999 and 2004. All their published drug safety studies during this period were reviewed. A classification system was developed to categorise the exclusion criteria, with 5 categories and 11 sub-categories. The categories were: (1) data quality and validation, (2) disease-related, (3) exposure-related, (4) patient characteristics and (5) miscellaneous reasons. Within each sub-category, only the first exclusion criterion identified for that study was counted.

We identified 200 studies, from which a total of 752 exclusion criteria sub-categories had been applied (mean 3.8 per study; between-author range of means 2.8-5.1). At the category level, exclusion criteria relating to data quality and validation were the most commonly applied (87% of publications), followed by patient characteristics (75%), disease-related (69%), exposure-related (38%) and miscellaneous (3%). The main categories for which research practice appeared to differ were those relating to diseases and exposures. The application of sub-category 'risk factors and alternative causes' varied between authors from 0% to 81% of studies, and for the sub-category 'medication of interest' it varied from 5% to 93%.

There are important differences between investigators in the application of exclusion criteria in pharmacoepidemiological studies. It is likely that a substantial part of the observed variation reflects different research practices of investigators.