The proportion of all previous patients was a potential instrument for patients' actual prescriptions of nonsteroidal anti-inflammatory drugs

Abstract

Objectives: To investigate whether physician's prescribing preference is a valid instrumental variable (IV) for patients' actual prescription of selective cyclooxygenase-2 (COX-2) inhibitors in the German Pharmacoepidemiological Research Database (GePaRD).

Study design and setting: We compared the effect of COX-2 inhibitors vs. traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) on the risk of gastrointestinal complications using physician's preference as IV. We used different definitions of physician's preference for COX-2 inhibitors. A retrospective cohort of new users was built which was further restricted to subcohorts. We compared IV-based risk difference estimates, using a two-stage approach, to estimates from conventional multivariate models.

Results: We observed only a small proportion of COX-inhibitor users (3.2%) in our study. All instruments, in the full cohort and in the subcohorts, reduced the imbalance in most of the covariates. However, the IV treatment effect estimates had a highly inflated variance. Compared to the most recent prescription, the proportion of previous patients was a stronger instrument and reduced the variance of the estimates.

Conclusion: The proportion of all previous patients is a potential IV for comparing COX-2 inhibitors vs. tNSAIDs in GePaRD. Our study demonstrates that valid instruments in one health care system may not be directly applicable to others.

Keywords: COX-2 inhibitors; Confounding by indication; German Pharmacoepidemiological Research Database; Instrumental variables; Physician's preference; Two-stage least squares.