title: User-only design to assess drug effectiveness in clinical practice: application to bisphosphonates and secondary prevention of fractures.
abstract: OBJECTIVE
  Different strategies applicable to control for confounding by indication in observational studies were compared in a large population-based study regarding the effect of bisphosphonates (BPs) for secondary prevention of fractures.
  
  
  METHODS
  The cohort was drawn from healthcare utilization databases of 13 Italian territorial units. Patients aged 55 years or more who were hospitalized for fracture during 2003-2005 entered into the cohort. A nested case-control design was used to compare BPs use in cohort members who did (cases) and who did not experience (controls) a new fracture until 2007 (outcome). Three designs were employed: conventional-matching (D1 ), propensity score-matching (D2 ), and user-only (D3 ) designs. They differed for (i) cohort composition, restricted to patients who received BPs straight after cohort entry (D3 ); (ii) using propensity score for case-control matching (D2 ); and (iii) compared groups of BPs users versus no users (D1 and D2 ) and long-term versus short-term users (D3 ).
  
  
  RESULTS
  Bisphosphonate users had odds ratios (95% confidence interval) of 1.20 (1.01 to 1.44) and 0.95 (0.74 to 1.24) by applying D1 and D2 designs, respectively. Statistical evidence that long-term BPs use protects the outcome onset with respect to short-term use was observed for user-only design (D3 ) being the corresponding odds ratio (95% confidence interval) 0.64 (0.44 to 0.93).
  
  
  CONCLUSIONS
  User-only design yielded closer results to those seen in RCTs. This approach is one possible strategy to account for confounding by indication.
authors.affiliation: Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, University of Milano-Bicocca, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Corrao
authors.forename: Arianna
authors.initials: A
authors.lastname: Ghirardi
authors.forename: Giulia
authors.initials: G
authors.lastname: Segafredo
authors.forename: Antonella
authors.initials: A
authors.lastname: Zambon
authors.forename: Gianluca
authors.initials: G
authors.lastname: Della Vedova
authors.forename: Francesco
authors.initials: F
authors.lastname: Lapi
authors.forename: Francesco
authors.initials: F
authors.lastname: Cipriani
authors.forename: Achille
authors.initials: A
authors.lastname: Caputi
authors.forename: Alberto
authors.initials: A
authors.lastname: Vaccheri
authors.forename: Dario
authors.initials: D
authors.lastname: Gregori
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gesuita
authors.forename: Annarita
authors.initials: A
authors.lastname: Vestri
authors.forename: Tommaso
authors.initials: T
authors.lastname: Staniscia
authors.forename: Giampiero
authors.initials: G
authors.lastname: Mazzaglia
authors.forename: Mauro
authors.initials: M
authors.lastname: Di Bari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D016208:Databases, Factual / Q000706:statistics & numerical data*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D006760:Hospitalization; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic / Q000379:methods*; D057216:Propensity Score; D012107:Research Design; D012189:Retrospective Studies; D055502:Secondary Prevention / Q000379:methods; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates
keywords: bisphosphonates; confounding; fracture; pharmacoepidemiology; propensity score; user-only design