High-dimensional versus conventional propensity scores in a comparative effectiveness study of coxibs and reduced upper gastrointestinal complications
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High-dimensional propensity score (hd-PS) adjustment has been proposed as a tool to improve control for confounding in pharmacoepidemiological studies using longitudinal claims databases. We investigated whether hd-PS matching improved confounding by indication in a study of Cox-2 inhibitors (coxibs) and traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) and their association with the risk of upper gastrointestinal complications (UGIC).
In a cohort study of new users of coxibs and tNSAIDs we compared the effectiveness of these drugs to reduce UGIC using hd-PS matching and conventional propensity score (PS) matching in the German Pharmacoepidemiological Research Database.
The unadjusted rate ratio (RR) of UGIC for coxib users versus tNSAID users was 1.21 [95 % confidence interval (CI) 0.91–1.61]. The conventional PS matched cohort based on 79 investigator-identified covariates resulted in a RR of 0.84 (0.56–1.26). The use of the hd-PS algorithm based on 900 empirical covariates further decreased the RR to 0.62 (0.43–0.91).
A comparison of hd-PS matching versus conventional PS matching resulted in improved point estimates for studying an intended treatment effect of coxibs versus tNSAIDs when benchmarked against results from randomized controlled trials.
KeywordsNSAIDs Upper gastrointestinal complications Confounding by indication Propensity score High-dimensional propensity score
This study was conducted as one subproject of The Safety of Nonsteroidal Anti-inflammatory Drugs (SOS) project (http://www.sos-nsaids-project.org/) which has received funding from the European Community’s Seventh Framework Programme under grant agreement number 223495—the SOS project. The authors are grateful to all statutory health insurance providers that provided data for this study, namely the Allgemeine Ortskrankenkasse (AOK) Bremen/ Bremerhaven, the DAK–Gesundheit, the Techniker Krankenkasse (TK), and the hkk. S. Schneeweiss was supported by grants from the National Library of Medicine (RO1-LM010213), the National Center for Research Resources (RC1-RR028231), and the National Heart Lung and Blood Institute (RC4-HL106373).
Conflict of interest
E. Garbe has received consulting fees by Novartis Pharma GmbH, Bayer AG and TEVA GmbH unrelated to this project and is member of a Scientific Advisory Board of Nycomed, unrelated to this project. S. Schneeweiss is Principal Investigator of the Brigham and Women’s Hospital DEcIDE Center on Comparative Effectiveness Research and the DEcIDE Methods Center, both funded by AHRQ, and of the Harvard–Brigham Drug Safety and Risk Management Research Center, funded by the Federal Drug Administration. S. Schneeweiss is consultant to WHISCON LLC and Booz & Co, and his research is partially funded by investigator-initiated grants from Pfizer, Novartis, and Boehringer–Ingelheim unrelated to the topic of this study. The remaining authors declare no conflict of interest.
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