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Dabigatran for the Prevention of Stroke and Systemic Embolism in Atrial Fibrillation: A NICE Single Technology Appraisal

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Abstract

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG). This article presents a summary of the manufacturer’s submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service. Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80 years are treated with dabigatran 150 mg twice daily (DBG150) and patients 80 years and over are given dabigatran 110 mg twice daily (DBG110). NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors. The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence. DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism. DBG110 was found to be non-inferior to warfarin. Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age. This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen. The economic evaluation compared the costs and outcomes of DBG110, DBG150 and DBG sequential against warfarin, aspirin, and aspirin plus clopidogrel. Across the three dosing regimens, dabigatran was associated with greater costs and better health outcomes than warfarin; however, DBG150 offered the most benefits and dominated DBG110 and DBG sequential (i.e. less costly and more effective). The cost-effectiveness of DBG150 was less favourable for patients well controlled on warfarin. In the first appraisal meeting, the committee issued a ‘minded no’ decision until additional analyses on the licensed DBG sequential regimen were presented by the manufacturer. These additional analyses indicated that the incremental cost-effectiveness ratio (ICER) of the DBG sequential regimen compared with warfarin ranged from £8,388 to £18,987 per quality-adjusted life year (QALY) gained depending on the level of monitoring costs assumed for warfarin. Patients on warfarin would need to be within therapeutic range 83–85 % of the time for the ICER to exceed £30,000 per additional QALY. Following consideration of the additional evidence and the responses from a large number of consultees and commentators, the committee recommended dabigatran as DBG sequential as an option for the prevention of stroke and systemic embolism in people with non-valvular AF with one or more risk factors for ischaemic stroke.

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Acknowledgments

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (project number 09/43) and was as part of a compendium of ERG articles in Health Technology Assessment (HTA). See the HTA programme website (http://www.hta.ac.uk) for further project information. This summary of the ERG report was compiled after the appraisal committee’s review and incorporates additional information and comment from the authors on the STA process and iterations of the NICE guidance not covered by the HTA report. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of NICE or the Department of Health. This summary has not been externally peer reviewed by PharmacoEconomics.

Conflict of Interest

Dr Derick Todd has received speaker fees from Boehringer Ingelheim and Bayer. The remaining authors have no conflicts of interest that are directly relevant to the content of this summary.

Author Contributions

Rita Faria was responsible for the preparation of the paper, contributed to the writing of the economic sections of the report and performed the economic modelling. Eldon Spackman reviewed the paper, contributed to the writing of the economic sections of the report and performed the economic modelling. Belen Corbacho reviewed the paper, contributed to the writing of the economic sections of the report and was involved in the economic modelling. Stephen Palmer reviewed the paper and supervised the health economics work. Jane Burch and Nerys Woolacott were the systematic reviewers who critiqued and wrote the clinical sections of the report and reviewed the paper. Dr Derick Todd and Dr Chris Pepper provided clinical advice and reviewed the paper.

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Authors and Affiliations

  1. Centre for Health Economics, Alcuin ‘A’ Block, University of York, Heslington, York, YO10 5DD, UK

    Rita Faria, Eldon Spackman & Stephen Palmer

  2. Centre for Reviews and Dissemination, University of York, Heslington, York, UK

    Jane Burch & Nerys Woolacott

  3. York Trials Unit, Department of Health Sciences, University of York, Heslington, York, UK

    Belen Corbacho

  4. Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital, Liverpool, UK

    Derick Todd

  5. Yorkshire Health Centre, Leeds General Infirmary, Leeds, UK

    Chris Pepper

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  1. Rita Faria
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Correspondence to Rita Faria.

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Faria, R., Spackman, E., Burch, J. et al. Dabigatran for the Prevention of Stroke and Systemic Embolism in Atrial Fibrillation: A NICE Single Technology Appraisal. PharmacoEconomics 31, 551–562 (2013). https://doi.org/10.1007/s40273-013-0051-8

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