title: Propensity score matching and persistence correction to reduce bias in comparative effectiveness: the effect of cinacalcet use on all-cause mortality.
abstract: OBJECTIVE
  The generalisability of randomised controlled trials (RCTs) may be limited by restrictive entry criteria or by their experimental nature. Observational research can provide complementary findings but is prone to bias. Employing propensity score matching, to reduce such bias, we compared the real-life effect of cinacalcet use on all-cause mortality (ACM) with findings from the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) RCT in chronic haemodialysis patients.
  
  
  METHODS
  Incident adult haemodialysis patients receiving cinacalcet, recruited in a prospective observational cohort from 2007-2009 (AROii; n = 10,488), were matched to non-exposed patients regardless of future exposure status. The effect of treatment crossover was investigated with inverse probability of censoring weighted and lag-censored analyses. EVOLVE ACM data were analysed largely as described for the primary composite endpoint.
  
  
  RESULTS
  AROii patients receiving cinacalcet (n = 532) were matched to 1790 non-exposed patients. The treatment effect of cinacalcet on ACM in the main AROii analysis (hazard ratio 1.03 [95% confidence interval (CI) 0.78-1.35]) was closer to the null than for the Intention to Treat (ITT) analysis of EVOLVE (0.94 [95%CI 0.85-1.04]). Adjusting for non-persistence by 0- and 6-month lag-censoring and by inverse probability of censoring weight, the hazard ratios in AROii (0.76 [95%CI 0.51-1.15], 0.84 [95%CI 0.60-1.18] and 0.79 [95%CI 0.56-1.11], respectively) were comparable with those of EVOLVE (0.82 [95%CI 0.67-1.01], 0.83 [95%CI 0.73-0.96] and 0.87 [95%CI 0.71-1.06], respectively).
  
  
  CONCLUSIONS
  Correcting for treatment crossover, we observed results in the 'real-life' setting of the AROii observational cohort that closely mirrored the results of the EVOLVE RCT. Persistence-corrected analyses revealed a trend towards reduced ACM in haemodialysis patients receiving cinacalcet therapy.
authors.affiliation: Amgen Ltd, Uxbridge, UK.
authors.forename: Iain A
authors.identifier: http://orcid.org/0000-0002-2265-9506
authors.initials: IA
authors.lastname: Gillespie
authors.affiliation: Division of Nephrology, Medizinische Klinik II, RWTH University Hospital Aachen, Aachen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: on behalf of Amgen Ltd, UK.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Gioni
authors.affiliation: Inserm Unit 1088, UFR de Médecine et de Pharmacie, Université de Picardie, Amiens, France.
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.affiliation: Servicio de Nefrología, Hospital Universitario Valdecilla, Universidad de Cantabria, Santander, Spain.
authors.forename: Angel L
authors.initials: AL
authors.lastname: de Francisco
authors.affiliation: Department of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Amgen Inc, Thousand Oaks, CA, USA.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Center for Nephrology, University College London, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: Amgen Europe GmbH, Zug, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Froissart
mesh_terms: D000328:Adult; D000368:Aged; D015982:Bias; D057966:Calcimimetic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality* / Q000628:therapy; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D064887:Observational Studies as Topic / Q000706:statistics & numerical data*; D010758:Phosphorus / Q000097:blood; D057216:Propensity Score; D006435:Renal Dialysis / Q000009:adverse effects*
chemical_list: D057966:Calcimimetic Agents; D010758:Phosphorus; D002118:Calcium; D000069449:Cinacalcet
keywords: bias; cinacalcet; haemodialysis; mortality; persistence; pharmacoepidemiology