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


METHODS
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.


CONCLUSIONS
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.
Leibniz Institute for Prevention Research and Epidemiology-BIPS, Department Biometry and Data Management, Achterstr. 30, Bremen 28359, Germany. Electronic address: kollhorst@bips.uni-bremen.de.
Bianca
B
Kollhorst
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, 1020 Pine Avenue West, Montreal H3A 1A2, Québec, Canada; Division of Clinical Epidemiology, McGill University Health Centre Royal Victoria Hospital, 687 Pine Avenue West, Montreal H3A 1A1, Québec, Canada.
Michal
M
Abrahamowicz
Leibniz Institute for Prevention Research and Epidemiology-BIPS, Department Biometry and Data Management, Achterstr. 30, Bremen 28359, Germany; Faculty of Mathematics and Computer Science, University of Bremen, Bibliothekstraße 1, Bremen 28359, Germany.
Iris
I
Pigeot
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D016208:Databases, Factual; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D008297:Male; D010818:Practice Patterns, Physicians'; D012189:Retrospective Studies
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors
COX-2 inhibitors; Confounding by indication; German Pharmacoepidemiological Research Database; Instrumental variables; Physician's preference; Two-stage least squares