title: A comparative analysis of models used to evaluate the cost-effectiveness of dabigatran versus warfarin for the prevention of stroke in atrial fibrillation.
abstract: BACKGROUND
  A number of models exploring the cost-effectiveness of dabigatran versus warfarin for stroke prevention in atrial fibrillation have been published. These studies found dabigatran was generally cost-effective, considering well-accepted willingness-to-pay thresholds, but estimates of the incremental cost-effectiveness ratios (ICERs) varied, even in the same setting. The objective of this study was to compare the findings of the published economic models and identify key model features accounting for differences.
  
  
  METHODS
  All aspects of the economic evaluations were reviewed: model approach, inputs, and assumptions. A previously published model served as the reference model for comparisons of the selected studies in the US and UK settings. The reference model was adapted, wherever possible, using the inputs and key assumptions from each of the other published studies to determine if results could be reproduced in the reference model. Incremental total costs, incremental quality-adjusted life years (QALYs), and ICERs (cost per QALY) were compared between each study and the corresponding adapted reference model. The impact of each modified variable or assumption was tracked separately.
  
  
  RESULTS
  The selected studies were in the US setting (2), the Canadian setting (1), and the UK setting (2). All models used the Randomized Evaluation of Long-Term Anticoagulation study (RE-LY) as the main source for clinical inputs, and all used a Markov modelling approach, except one that used discrete event simulation. The reference model had been published in the Canadian and UK settings. In the UK setting, the reference model reported an ICER of UK£4,831, whereas the other UK-based analysis reported an ICER of UK£23,082. When the reference model was modified to use the same population characteristics, cost inputs, and utility inputs, it reproduced the results of the other model (ICER UK£25,518) reasonably well. Key reasons for the different results between the two models were the assumptions on the event utility decrement and costs associated with intracranial haemorrhage, as well as the costs of warfarin monitoring and disability following events. In the US setting, the reference model produced an ICER similar to the ICER from one of the US models (US$15,115/QALY versus US$12,386/QALY, respectively) when modelling assumptions and input values were transferred into the reference model. Key differences in results could be explained by the population characteristics (age and baseline stroke risk), utility assigned to events and specific treatments, adjustment of stroke and intracranial haemorrhage risk over time, and treatment discontinuation and switching. The reference model was able to replicate the QALY results, but not the cost results, reported by the other US cost-effectiveness analysis. The parameters driving the QALY results were utility values by disability levels as well as utilities assigned to specific treatments, and event and background mortality rates.
  
  
  CONCLUSIONS
  Despite differences in model designs and structures, it was mostly possible to replicate the results published by different authors and identify variables responsible for differences between ICERs using a reference model approach. This enables a better interpretation of published findings by focusing attention on the assumptions underlying the key model features accounting for differences.
authors.affiliation: United BioSource Corporation, 7101 Wisconsin Avenue, Suite 600, Bethesda, MD 20814, USA. Sonja.sorensen@unitedbiosource.com
authors.forename: Sonja V
authors.initials: SV
authors.lastname: Sorensen
authors.forename: Siyang
authors.initials: S
authors.lastname: Peng
authors.forename: Brigitta U
authors.initials: BU
authors.lastname: Monz
authors.forename: Carole
authors.initials: C
authors.lastname: Bradley-Kennedy
authors.forename: Anuraag R
authors.initials: AR
authors.lastname: Kansal
mesh_terms: D001281:Atrial Fibrillation / Q000150:complications* / Q000191:economics / Q000517:prevention & control; D001562:Benzimidazoles / Q000191:economics* / Q000494:pharmacology; D003362:Cost-Benefit Analysis / Q000379:methods*; D000069604:Dabigatran; D016527:Drug Costs; D017048:Health Care Costs; D006801:Humans; D018803:Models, Economic; D019057:Quality-Adjusted Life Years; D020521:Stroke / Q000150:complications / Q000191:economics* / Q000517:prevention & control*; D014859:Warfarin / Q000191:economics* / Q000494:pharmacology; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000191:economics / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D015091:beta-Alanine; D014859:Warfarin; D000069604:Dabigatran