51. Propensity score matching and persistence correction to reduce bias in comparative effectiveness: the effect of cinacalcet use on all-cause mortality
- Author
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David C. Wheeler, Marc Froissart, Stefan D. Anker, Yumi Kubo, Iain A. Gillespie, Tilman B. Drüeke, Angel L.M. de Francisco, Jürgen Floege, Ioanna Gioni, and Universidad de Cantabria
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cinacalcet ,Epidemiology ,Calcimimetic Agents ,law.invention ,cinacalcet ,haemodialysis ,mortality ,persistence ,bias ,pharmacoepidemiology ,Persistence ,Randomized controlled trial ,Bias ,law ,Renal Dialysis ,Internal medicine ,Cinacalcet Hydrochloride ,Original Reports ,Original Report ,Medicine ,Humans ,Pharmacology (medical) ,Mortality ,Propensity Score ,Aged ,Intention-to-treat analysis ,business.industry ,Pharmacoepidemiology ,Hyperparathyroidism ,Hazard ratio ,Phosphorus ,Middle Aged ,Confidence interval ,3. Good health ,Surgery ,Haemodialysis ,Observational Studies as Topic ,Logistic Models ,Censoring (clinical trials) ,Cohort ,Propensity score matching ,Bias (Epidemiology) ,Kidney Failure, Chronic ,Calcium ,Female ,business ,medicine.drug - Abstract
Purpose: 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. Funding: DWreports having received research funding from Abbott,Genzyme and AstraZeneca and honoraria from Amgen,Abbott, Fresenius, Janssen, Otsuka, Shire and Vifor.
- Published
- 2015