Exposure misclassification as a result of free sample drug utilization in automated claims databases and its effect on a pharmacoepidemiology study of selective COX-2 inhibitors

Purpose Free drug samples are widely used in clinical practice. We were concerned about free sample drug utilization as a source of misclassification in pharmacoepidemiology research using claims data that may result in biased effect estimates. Methods We investigated the magnitude of potential bias with sensitivity analyses based on a published study that examined cardiovascular risk associated with selective cyclooxygenase 2 (COX-2) inhibitors. We derived an estimate of free sample drug utilization with market data for rofexcoxib and calculated sensitivity of the exposure ascertainment method using claims data. We corrected the incidence rate ratio assuming the observed unexposed incidence rate was actually a weighted average rate of the truly unexposed and free sample drug users. The impact of exposure misclassification measured as the percentage change from a corrected to the reported crude incidence rate ratio was examined under a range of free sample drug utilization proportions and unexposed cohort sizes. Results The proportion of free sample drug utilization of all rofecoxib use in our base case scenario was 15.48%, resulting in sensitivity of 84.52% for exposure ascertainment. The magnitude of bias was an underestimation of the unadjusted incidence rate ratio by 0.03%. With a free sample drug utilization proportion of 1.48% and the same unexposed cohort size of 237 975 person-years, the underestimation was 0.003%. If the unexposed cohort were 975 person-years given a 15.48% proportion, the underestimation was 8.82%. Conclusions In the pharmacoepiderniology study, we examined that uses claims data to ascertain drug exposure, our results suggest that adjustment for free sample drug utilization is probably not warranted. Copyright (C) 2004 John Wiley Sons, Ltd.