title: Comparison of different approaches to confounding adjustment in a study on the association of antipsychotic medication with mortality in older nursing home patients.
abstract: Selective prescribing of conventional antipsychotic medication (APM) to frailer patients is thought to have led to overestimation of the association with mortality in pharmacoepidemiologic studies relying on claims data. The authors assessed the validity of different analytic techniques to address such confounding. The cohort included 82,012 persons initiating APM use after admission to a nursing home in 45 states with 2001-2005 Medicaid/Medicare data, linked to clinical data (Minimum Data Set) and institutional characteristics. The authors compared the association between APM class and 180-day mortality with multivariate outcome modeling, propensity score (PS) adjustment, and instrumental variables. The unadjusted risk difference (per 100 patients) of 10.6 (95% confidence interval (CI): 9.4, 11.7) comparing use of conventional medication with atypical APM was reduced to 7.8 (95% CI: 6.6, 9.0) and 7.0 (95% CI: 5.8, 8.2) after PS adjustment and high-dimensional PS (hdPS) adjustment, respectively. Results were similar in analyses limited to claims-based Medicaid /Medicare variables (risk difference = 8.2 for PS, 7.1 for hdPS). Instrumental-variable estimates were imprecise (risk difference = 8.8, 95% CI: -1.3, 19.0) because of the weak instrument. These results suggest that residual confounding has a relatively small impact on the effect estimate and that hdPS methods based on claims alone provide estimates at least as good as those from conventional analyses using claims enriched with clinical information.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA. khuybrechts@partners.org
authors.forename: Krista F
authors.initials: KF
authors.lastname: Huybrechts
authors.forename: M Alan
authors.initials: MA
authors.lastname: Brookhart
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Rothman
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Silliman
authors.forename: Tobias
authors.initials: T
authors.lastname: Gerhard
authors.forename: Stephen
authors.initials: S
authors.lastname: Crystal
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects*; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006707:Homes for the Aged / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D009026:Mortality; D015999:Multivariate Analysis; D009735:Nursing Homes / Q000706:statistics & numerical data*; D016017:Odds Ratio; D057216:Propensity Score; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D014150:Antipsychotic Agents