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The contribution of real-world evidence to cost-effectiveness analysis: case study of Dabigatran etexilate in France

The European Journal of Health Economics volume 21, pages 235–249 (2020)Cite this article

Abstract

Objective

The goal of this study was to assess the differences between an ex ante and an ex post cost-effectiveness analysis of Dabigatran etexilate vs VKAs for the prevention of thromboembolic events in non-valvular atrial fibrillation patients and to draw lessons on the design and use of real-world data for decision making.

Methods

The same model was used to calculate the cost-effectiveness ratio using two sets of parameters. One set included the efficacy and safety outcomes data from RE-LY, the pivotal trial comparing Dabigatran to warfarin; cost data came from an ex ante publication. Outcomes data for the second set came from real-world data studies. Cost data were a mix of real-world data and other sources. Two treatment strategies were compared: treatment initiation by either Dabigatran or VKAs, followed by either VKAs or Dabigatran. A crude comparison of results was performed; the impact of data differences was then assessed. Probabilistic sensitivity results of the two analyses were compared.

Results

With real-world evidence, Dabigatran at both dosages was more effective for the prevention of ischemic strokes, intra-cranial haemorrhages, with less major extra-cranial haemorrhages and a similar risk of myocardial infarction. Using clinical trial data, Dabigatran150 mg (resp. Dabigatran110 mg) as a first-line treatment vs VKAs yielded an ICER of € 8077/QALY (resp. € 13,116/QALY). Real-world evidence scenarios were cost-saving and more effective for both dosages.

Conclusion

The reassessment of outcomes and cost data had an impact on results, improving the efficiency of Dabigatran. We identify methodological issues which should be discussed if post-launch RWE based cost-effectiveness data become a standard in HTA decision making.

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References

  1. Garrison, L.P., Neumann, P.J., Erickson, P., et al.: Using real-world data for coverage and payment decisions: the ISPOR real-world data task force report. Value Health 10, 326–335 (2006)

    Article  Google Scholar 

  2. Connolly, S.J., Ezekowitz, M.D., Yusuf, S., Eikelboom, J., Oldgren, J., Parekh, A., Pogue, J., Reilly, P.A., Themeles, E., Varrone, J., Wang, S., Alings, M., Xavier, D., Zhu, J., Diaz, R., Lewis, B.S., Darius, H., Diener, H.C., Joyner, C.D., Wallentin, L.: RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 361(12), 1139–1151 (2009). https://doi.org/10.1056/nejmoa0905561

    Article  PubMed  CAS  Google Scholar 

  3. Chevalier, J., Delaitre, O., Hammès, F., de Pouvourville, G.: Cost-effectiveness of Dabigatranversus vitamin K antagonists for the prevention ofstroke in patients with atrial fibrillation: a French payer perspective. Arch. Cardiovasc. Dis. 107(6–7), 381–390 (2014)

    Article  Google Scholar 

  4. Lanitis, T., Cotté, F.E., Gaudin, A.F., Kachaner, I., Kongnakorn, T., Durand-Zaleski, I.: Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (Apixaban, Dabigatran, and Rivaroxaban), warfarin, and aspirin. J. Med. Econ. 17(8), 587–598 (2014)

    Article  CAS  Google Scholar 

  5. Sorensen, S.V., Kansal, A.R., Connolly, S., Peng, S., Linnehan, J., Bradley-Kennedy, C., Plumb, J.M.: Cost-effectiveness of Dabigatranetexilate for the prevention of stroke and systemic embolism in atrial fibrillation: a Canadian payer perspective. Thromb. Haemost. 105, 908–919 (2011)

    Article  CAS  Google Scholar 

  6. Kansal, A.R., Sharma, M., Bradley-Kennedy, C., et al.: Dabigatran versus Rivaroxaban for the prevention of stroke and systemic embolism in atrial fibrillation in Canada. Comparative efficacy and cost-effectiveness. Thromb. Haemost. 108(4), 672–682 (2012)

    PubMed  CAS  Google Scholar 

  7. Quinn, T.J., Dawson, J., Walters, M.R., Lees, K.R.: Functional outcome measures in contemporary stroke trials. Int. J. Stroke 4(3), 200–205 (2009)

    Article  CAS  Google Scholar 

  8. Fang, M.C., Go, A.S., Hylek, E.M., et al.: Age and the risk of warfarin-associated hemorrhages: the anticoagulation and risk factors in atrial fibrillation study. J. Am. Geriatr. Soc. 54, 1231–1236 (2006)

    Article  Google Scholar 

  9. Blin, P., de Pouvourville, G., Cottin, Y., Dureau-Pournin, C., Abouelfath, A., Lassalle, R., Bénichou, J., Droz-Perroteau, C., Mismetti, P., Moore, N.: Comparative effectiveness and medical cost of Dabigatranversus vitamin K antagonists from ENGEL 2: a french nationwide cohort of 100.000 patients with non-valvular atrial fibrillation. Value Health 20, 9 (2017)

    Google Scholar 

  10. Blin, P., Dureau-Pournin, C., Cottin, Y., Bénichou, J., Mismetti, P., Abouelfath, A., Lassalle, R., Droz, C., Moore, N.: Effectiveness and safety of 110 or 150 mg Dabigatran versus vitamin K antagonists in non-valvular atrial fibrillation. Br. J. Clin. Pharmacol. (2018). https://doi.org/10.1111/bcp.13815

    Article  PubMed  PubMed Central  Google Scholar 

  11. Blin, P., Dureau-Pournin, C., Bénichou, J., Cottin, Y., Mismetti, P., Abouelfath, A., Lassalle, R., Droz, C., Moore, N.: Comparative Real-Life Effectiveness and Safety of Dabigatranor Rivaroxaban vs. Vitamin K Antagonists: a High-Dimensional Propensity Score Matched New Users Cohort Study in the French National Healthcare Data System SNDS. Am. J. Cardiovasc. Drugs (2019). https://doi.org/10.1007/s40256-019-00359-z

    Article  Google Scholar 

  12. Grimaldi-Bensouda, L., Le Heuzey, J.Y., Ferrières, J., Leys, D., Davy, J.M., Martinez, M., Smadja, D., Ellie, E., Sablot, D., Nighoghossian, N., Benichou, J., Touzé, E., Abenhaim, L.: Non-valvular atrial fibrillation, VKA and non-VKA anticoagulants and stroke: the Stroke Prevention and Anticoagulants (SPA) case-control study. Eur. Heart J. 38, 769–770 (2017)

    Article  Google Scholar 

  13. Haute Autorité de Santé (HAS). Choix méthodologiques pour l’évaluation économique à la HAS. Guide méthodologique. http://www.has-sante.fr/portail/jcms/c_1120708/guide-choix-methodologiques-pour-l-evaluation-economique-a-la-has (2011). Accessed 31 Oct 2018

  14. de Pouvourville G, Karam P. Le coût hospitalier des événements cérébro-vasculaires associés à une fibrillation atriale en France. J Gestion Eco Santé 5 (2019) (in press)

  15. ATIH. ENC MCO. https://www.scansante.fr/referentiel-de-couts-mco-2015. Accessed 31 Oct 2018

  16. ATIH. ENC MCO. https://www.scansante.fr/referentiel-de-couts-ssr-2015. Accessed 31 Oct 2018

  17. Blin, P., Philippe, F., Bouée, S., Laurendeau, C., Torreton, E., Gourmelin, J., Leproust, S., Levy-Bachelot, L., Steg, P.G.: Outcomes following acute hospitalised myocardial infarction in France: an insurance claims database analysis. Int. J. Cardiol. 15(219), 387–393 (2016)

    Article  Google Scholar 

  18. Ministère des Solidarités et de la Santé. Les dépenses de santé en 2017. Résultats des comptes de la santé-Edition. https://drees.solidarites-sante.gouv.fr/etudes-et-statistiques/publications/panoramas-de-la-drees/article/les-depenses-de-sante-en-2017-resultats-des-comptes-de-la-sante-edition-2018 (2018). Accessed 31 Oct 2018

  19. Assurance Maladie. Coût des ALD en 2009. https://www.ameli.fr/l-assurance-maladie/statistiques-et-publications/donnees-statistiques/affection-de-longue-duree-ald/archives/cout-des-ald-en-2009.php (2009). Accessed 31 Oct 2018

  20. ATIH: Les coûts en établissement d’hébergement pour personnes âgées dépendantes. https://www.atih.sante.fr/resultats-de-l-enquete-de-couts-ehpad-2013 (2013). Accessed 31 Oct 2018

  21. Béjot, Y., Bailly, H., Graber, M., Garnier, L., Laville, A., Dubourget, L., Mielle, N., Chevalier, C., Durier, J., Giroud, M.: Impact of the ageing population on the burden of stroke: the Dijon Stroke Registry. Neuroepidemiology 52, 78–85 (2019)

    Article  Google Scholar 

  22. Lecoffre, C., de Peretti, C., Gabet, A., Grimaud, O., Woimant, F., Giroud, M., et al.: L’accident vasculaire cérébral en France: patients hospitalisés pour AVC en 2014 et évolutions 2008–2014. BEH 5, 84–94 (2017)

    Google Scholar 

  23. Pouvourville, G.: Anti-coagulants d’action directe: une revue de la littérature des études coût-efficacité en Europe. Arch. Cardiovasc. Dis. 8, 180–191 (2016)

    Google Scholar 

  24. Harenberg, J., Marx, S., Obermann, K., Frölich, L., Wehling, M.: Comparison of cost-effectiveness of anticoagulation with Dabigatran, Rivaroxaban and Apixaban in patients with non-valvular atrial fibrillation across countries. J. Thromb. Thrombolysis 37(4), 507–523 (2014)

    Article  Google Scholar 

  25. Kongnakorn, T., Lanitis, T., Lieven, A., Thijs, V., Marbaix, S.: Cost effectiveness of Apixaban versus aspirin for stroke prevention in patients with non-valvular atrial fibrillation in Belgium. Clin. Drug Investig. 34(10), 709–721 (2014)

    Article  CAS  Google Scholar 

  26. Langkilde, L.K., Asmussen, B.M., Overgaard, M.: Cost-effectiveness of Dabigatranetexilate for stroke prevention in non-valvular atrial fibrillation. Applying RE-LY to clinical practice in Denmark. J. Med. Econ. 15(4), 695–703 (2012)

    Article  Google Scholar 

  27. González-Juanatey, J.R., Álvarez-Sabin, J., Lobos, J.M., Martínez-Rubio, A., Reverter, J.C., Oyagüez, I., González-Rojas, N., Becerra, V.: Cost-effectiveness of Dabigatranfor stroke prevention in non-valvular atrial fibrillation in Spain. Rev. Esp. Cardiol. 65(10), 901–910 (2012)

    Article  Google Scholar 

  28. Rognoni, C., Marchetti, M., Quaglini, S., Liberato, N.L.: Apixaban, Dabigatran, and Rivaroxaban versus warfarin for stroke prevention in non-valvular atrial fibrillation: a cost-effectiveness analysis. Clin. Drug Investig. 34(1), 9–17 (2014)

    Article  CAS  Google Scholar 

  29. Verhoef, T., Redekop, W.K., Hasrat, F., de Boer, A., Maitland-van der Zee, A.H.: Cost effectiveness of new oral anticoagulants for stroke prevention in patients with atrial fibrillation in two different European healthcare settings. Am. J. Cardiovasc. Drugs 14(6), 451–462 (2014)

    Article  CAS  Google Scholar 

  30. Silva Miguel, L., Rocha, E., Ferreira, J.: Economic evaluation of Dabigatranfor stroke prevention in patients with non-valvular atrial fibrillation. Rev. Port. Cardiol. 32(7–8), 557–565 (2013)

    Article  Google Scholar 

  31. Kansal, A.R., Sorensen, S.V., Gani, R., Robinson, P., Pan, F., Plumb, J.M., Cowie, M.R.: Cost-effectiveness of dabigatranetexilate for the prevention of stroke and systemic embolism in UK patients with atrial fibrillation. Heart 98(7), 573–578 (2012)

    Article  CAS  Google Scholar 

  32. Pink, J., Lane, S., Pirmohamed, M., Hughes, D.A.: Dabigatranetexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses. BMJ (2011). https://doi.org/10.1136/bmj.d6333

    Article  PubMed  PubMed Central  Google Scholar 

  33. Davidson, T., Husberg, M., Janzon, M., Oldgren, J., Levin, L.Å.: Cost-effectiveness of dabigatran compared with warfarin for patients with atrial fibrillation in Sweden. Eur. Heart J. 34(3), 177–183 (2013)

    Article  Google Scholar 

  34. Pletscher, M., Plessow, R., Eichler, K., Wieser, S.: Cost-effectiveness of dabigatranfor stroke prevention in atrial fibrillation in Switzerland. Swiss Med. Wkly. 8, 143 (2013). https://doi.org/10.4414/smw.2013.13732

    Article  Google Scholar 

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Acknowledgements

Our thanks to Professor Maurice Giroud and Professor Yannick Béjot, Dijon Stroke Registry, for a free access to data; Professor Ariel Cohen, Hôpital Saint-Antoine, for his informed advice on clinical assumptions in the model; Katell Le Lay, Laura Luciani, Clément Le Diser, Samuel Seksik, from Boehringer Ingerlheim, for contributions and comments on the analysis and manuscript; Caroline Guilmet, François Bourhis, from Mapi Values, for their contributions in the adaptation of the model. Bruno Detournay, CEMKA, and Stephane Roze, HEVA HEOR for relevant comments on the first versions of the manuscript. The study was funded by a Boehringer Ingelheim grant to ESSEC Business School.

Funding

This research was funded by Boehringer Ingelheim France (FR) Grant number [316097 ADA -07/24/2017].

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Authors and Affiliations

  1. ESSEC Business School, 3, Avenue Bernard Hirsch, 95021, Cergy Pontoise Cedex, France

    Gérard de Pouvourville

  2. Bordeaux Pharmacoepi, Bâtiment du Tondu, 146 rue Léon Saignat, 33076, Bordeaux Cedex, France

    Patrick Blin

  3. PKCS, 7 rue de la Baie, 50300, Le Val Saint Père, France

    Pierre Karam

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  1. Gérard de Pouvourville
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Correspondence to Gérard de Pouvourville.

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de Pouvourville, G., Blin, P. & Karam, P. The contribution of real-world evidence to cost-effectiveness analysis: case study of Dabigatran etexilate in France. Eur J Health Econ 21, 235–249 (2020). https://doi.org/10.1007/s10198-019-01123-5

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  • DOI: https://doi.org/10.1007/s10198-019-01123-5

Keywords

  • Cost-effectiveness
  • Real-world evidence
  • Atrial fibrillation
  • Direct oral anticoagulants

JEL Classification

  • I11