title: Comparison of high-dimensional confounder summary scores in comparative studies of newly marketed medications.
abstract: To compare confounding adjustment by high-dimensional propensity scores (hdPSs) and historically developed high-dimensional disease risk scores (hdDRSs) in three comparative study examples of newly marketed medications: (1) dabigatran vs. warfarin on major hemorrhage; (2) on death; and (3) cyclooxygenase-2 inhibitors vs. nonselective nonsteroidal anti-inflammatory drugs on gastrointestinal bleeds.
  
  
  
  In each example, we constructed a concurrent cohort of new and old drug initiators using US claims databases. In historical cohorts of old drug initiators, we developed hdDRS models including investigator-specified plus empirically identified variables and using principal component analysis and lasso regression for dimension reduction. We applied the models to the concurrent cohorts to obtain predicted outcome probabilities, which we used for confounding adjustment. We compared the resulting estimates to those from hdPS.
  
  
  
  The crude odds ratio (OR) comparing dabigatran to warfarin was 0.52 (95% confidence interval: 0.37-0.72) for hemorrhage and 0.38 (0.26-0.55) for death. Decile stratification yielded an OR of 0.64 (0.46-0.90) for hemorrhage using hdDRS vs. 0.70 (0.49-1.02) for hdPS. ORs for death were 0.69 (0.45-1.06) and 0.73 (0.48-1.10), respectively. The relative performance of hdDRS in the cyclooxygenase-2 inhibitors example was similar.
  
  
  
  hdDRS achieved similar or better confounding adjustment compared to conventional regression approach but worked slightly less well than hdPS.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street (Suite 3030), Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA. Electronic address: hik205@mail.harvard.edu.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Kumamaru
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street (Suite 3030), Boston, MA, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Gagne
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street (Suite 3030), Boston, MA, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.affiliation: Duke Clinical Research Institute, Duke University, 2400 Pratt St, Durham, NC 27705, USA.
authors.forename: Soko
authors.initials: S
authors.lastname: Setoguchi
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street (Suite 3030), Boston, MA, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015986:Confounding Factors, Epidemiologic; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D003627:Data Interpretation, Statistical; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D018570:Risk Assessment; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D014859:Warfarin
keywords: Administrative data; Comparative safety study; Confounding adjustment; Disease risk score; Historical cohort; Propensity score