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Application of Multicriteria Decision Analysis to Determine the Value of Prophylaxis Relative to On-Demand Treatment in Hemophilia A and Emicizumab versus Replacement Therapy in the Greek Healthcare Setting

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Abstract

Background and Objective

Hemophilia A (HA) is a rare disease that is characterized by congenital underproduction or dysfunction of the endogenous coagulation factor VIII (FVIII). The aim of the present study was to determine the value of prophylaxis versus on-demand treatment strategies for moderate to severe HA (MtSHA) patients and the value of emicizumab in the prophylaxis of MtSHA in Greece, compared with short half-life (SHL) FVIII and extended half-life (EHL) FVIII through multicriteria decision analysis (MCDA).

Methods

A literature review was performed to identify a set of criteria relevant to the therapeutic approaches and therapies under investigation. A performance matrix was populated by two literature reviews and meta-analyses. The criteria selected were hierarchically classified by allocating weights on a 0–100 scale. The performances of therapies were scored at the 100-point scale. The value judgments utilized for weighing and scoring were sourced via a survey among independent multidisciplinary system stakeholders. A linear additive value function was used for the calculation of total value estimates.

Results

The participants ranked ‘annual number of bleedings per patient’ and ‘percentage of target joint bleeds’ as the most important criteria, while the least important criterion was the ‘annual treatment cost’ for both assessments. Based on the weights elicited and the performance in each criterion, the overall value score was higher for prophylaxis treatment (58.27) compared with on-demand treatment (40.13). In the other comparison, the most valued treatment was emicizumab (77.05) followed by EHL FVIII (71.52) and SHL FVIII (19.88). According to the participants, the most important factors for managing MtSHA patients are those related to successful management of bleeding events given their contribution to improved quality of life (QoL) and reduced morbidity.

Conclusions

This MCDA has shown that the prophylaxis strategy was perceived as a more valuable option for managing MtSHA patients when compared with the on-demand strategy. Moreover, emicizumab adds higher value and improves patient QoL compared with replacement therapy for MtSHA in Greece. Emicizumab addresses important unmet needs due to its improved efficacy and mode of administration.

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References

  1. World Federation of Hemophilia. Report on the Annual Global Survey, 20th Anniversary. World Federation of Hemophilia; 2019. www.wfh.org/publications/files/pdf-1731.pdf. Accessed 20 Jan 2020

  2. Srivastava A, Brewer A, Mauser-Bunschoten E, et al. WFH guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1–47.

    Article  CAS  Google Scholar 

  3. Greek Ministry of Health. Haemophilia Greek treatment guidelines 2018. 2020. http://www.moh.gov.gr/articles/health/domes-kai-draseis-gia-thn-ygeia/kwdikopoihseis/therapeytika-prwtokolla-syntagografhshs. Accessed 25 Jan 2020.

  4. Manco-Johnson MJ, Kempton CL, Reding MT, et al. Randomized, controlled, parallel-group trial of routine prophylaxis vs. on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART). J Thromb Haemost. 2013;11(6):1119–27.

    Article  CAS  Google Scholar 

  5. Valentino LA, Mamonov V, Hellmann A, et al. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. J Thromb Haemost. 2012;10(3):359–67.

    Article  CAS  Google Scholar 

  6. Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535–44.

    Article  CAS  Google Scholar 

  7. European Medicines Agency. Assessment report: Hemlibra International non-proprietary name: emicizumab. Procedure No. EMEA/H/C/004406/0000. 2018. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004406/WC500244745.pdf. Accessed 14 Jan 2020.

  8. Mahlangu J, Oldenburg J, Paz-Priel I. Emicizumab prophylaxis in patients who have hemophilia A without inhibitors. N Engl J Med. 2018;379(9):811–22.

    Article  CAS  Google Scholar 

  9. Oldenburg J, Mahlangu J, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809–18.

    Article  CAS  Google Scholar 

  10. Annemans L, Aymé S, Le Cam Y, et al. Recommendations from the European Working Group for value assessment and funding processes in rare diseases (ORPH-VAL). Orphanet J Rare Dis. 2017;12(1):50.

    Article  Google Scholar 

  11. Angelis A, Kanavos P. Value-based assessment of new medical technologies: towards a robust methodological framework for the application of multiple criteria decision analysis in the context of health technology assessment. Pharmacoeconomics. 2016;34(5):435–46.

    Article  Google Scholar 

  12. Thokala P, Devlin N, Marsh K, et al. Multiple criteria decision analysis for health care decision making—an introduction: report 1 of the ISPOR MCDA emerging good practices task force. Value Health. 2016;19(1):1–13.

    Article  Google Scholar 

  13. Thokala P, Duenas A. Multiple criteria decision analysis for health technology assessment. Value Health. 2012;15(8):1172–81.

    Article  Google Scholar 

  14. Moher D, Liberati A, Tetzlaff J. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006–12.

    Article  Google Scholar 

  15. Collins P, Faradji A, Morfini MM, et al. Efficacy and safety of secondary prophylactic vs. on-demand sucrose-formulated recombinant factor VIII treatment in adults with severe hemophilia A: results from a 13-month crossover study. J Thromb Haemost. 2010;8(1):83–9.

    Article  CAS  Google Scholar 

  16. Gringeri A, Leissinger C, Cortesi PA, et al. Health-related quality of life in patients with haemophilia and inhibitors on prophylaxis with anti-inhibitor complex concentrate: results from the Pro-FEIBA study. Haemophilia. 2013;19(5):736–43.

    Article  CAS  Google Scholar 

  17. Mahlangu J, Powell JS, Ragni MV, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014;123(3):317–25.

    Article  CAS  Google Scholar 

  18. Kavakli K, Yang R, Rusen L, et al. Prophylaxis vs. on-demand treatment with BAY 81–8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II). J Thromb Haemost. 2015;13(3):360–9.

    Article  CAS  Google Scholar 

  19. Mahlangu J, Kuliczkowski K, Karim FA, et al. Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A. Blood. 2016;128(5):630–7.

    Article  CAS  Google Scholar 

  20. Giangrande P, Andreeva T, Chowdary P, et al. Clinical evaluation of glycoPEGylated recombinant FVIII: efficacy and safety in severe haemophilia A. Thromb Haemost. 2017;117(2):252–61.

    Article  Google Scholar 

  21. Tarantino MD, Collins PW, Hay CR, et al. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia. 2004;10(5):428–37.

    Article  CAS  Google Scholar 

  22. Marsh K, Thokala P, Youngkong S, et al. Incorporating MCDA into HTA: challenges and potential solutions, with a focus on lower income settings. Cost Eff Resour Alloc. 2018;16:43.

    Article  Google Scholar 

  23. Marsh K, Sculpher M, Caro JJ, et al. The use of MCDA in HTA: great potential, but more effort needed. Value Health. 2018;21(4):394–7.

    Article  Google Scholar 

  24. Marsh K, Lanitis T, Neasham D, et al. Assessing the value of healthcare interventions using multi-criteria decision analysis: a review of the literature. Pharmacoeconomics. 2014;32(4):345–65.

    Article  Google Scholar 

  25. Angelis A, Kanavos P. Multiple Criteria Decision Analysis (MCDA) for evaluating new medicines in Health Technology Assessment and beyond: the advance value framework. Soc Sci Med. 2017;188:137–56.

    Article  Google Scholar 

  26. Zozaya N, Martínez-Galdeano L, Alcalá B, et al. Determining the value of two biologic drugs for chronic inflammatory skin diseases: results of a multi-criteria decision analysis. BioDrugs. 2018;32(3):281–91.

    Article  CAS  Google Scholar 

  27. Wagner M, Khoury H, Bennetts L, et al. Appraising the holistic value of Lenvatinib for radio-iodine refractory differentiated thyroid cancer: a multi-country study applying pragmatic MCDA. BMC Cancer. 2017;17(1):272–272.

    Article  Google Scholar 

  28. Garau M, Hampson G, Devlin N, et al. Applying a Multicriteria Decision Analysis (MCDA) approach to elicit stakeholders’ preferences in italy: the case of obinutuzumab for rituximab-refractory indolent non-hodgkin lymphoma (iNHL). PharmacoEconomics Open. 2018;2(2):153–63.

    Article  Google Scholar 

  29. González N, Moreno J, Vega A. Multi-criteria decision analysis in healthcare—its usefulness and limitations for decision-making. Madrid: Fundación Weber; 2018. ISBN 978-84-947703-8-8. https://weber.org.es/wp-content/uploads/2021/03/libro_admc_17_x_24_ingles_digital.pdf. Accessed 5 Nov 2021

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Authors and Affiliations

  1. Department of Public Health Policy, School of Public Health, University of West Attica, Athens, Greece

    George Gourzoulidis

  2. ECONCARE LP, Athens, Greece

    George Gourzoulidis, Garyfallia Stefanou & Georgia Kourlaba

  3. 1st Pediatric Department, Aristotle University Thessaloniki, Hippocratio Hospital, Thessaloniki, Greece

    Marina Economou

  4. 2nd Propedeutic Department of Internal Medicine, Hippokration General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Sofia Vakalopoulou

  5. Greek Haemophilia Society, Athens, Greece

    George Filippidis

  6. Laiko General Hospital, Athens, Greece

    George Soultatis

  7. Panhellenic Pharmaceutical Association, Athens, Greece

    Dimitrios Kontos

  8. Roche Hellas S.A, Athens, Greece

    Sotiria Tzima, Fotis Ntemousis & Angeliki Fassa

Authors
  1. George Gourzoulidis
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  2. Garyfallia Stefanou
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  4. Sofia Vakalopoulou
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Corresponding author

Correspondence to George Gourzoulidis.

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Conflict of Interest

Fotis Ntemousis, Sotiria Tzima and Angeliki Fassa were Roche Hellas employees at the time of the study. George Gourzoulidis, Garyfallia Stefanou, Marina Economou, Sofia Vakalopoulou, George Filippidis, George Soultatis, Dimitrios Kontos, and Georgia Kourlaba have no conflicts of interest to declare.

Funding

This study was funded by Roche Hellas.

Ethical approval

This study is an MCDA and does not involve human subjects. Input data included human material or human data derived from other published studies performed with the approval of an appropriate Ethics Committee. Therefore, no ethics approval arises for the performance of this MCDA.

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Not applicable.

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Not applicable.

Availability of data and materials

All data used to conduct this study are included in this published article.

Code availability

Not applicable.

Author contributions

GG and GS conducted the SLRs and developed the MCDA models. GS conducted the meta-analyses and GG wrote the manuscript. All other authors have confirmed the appropriateness of the data used in the models and contributed to the discussion of the results. All authors have read and approved the final manuscript.

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Gourzoulidis, G., Stefanou, G., Economou, M. et al. Application of Multicriteria Decision Analysis to Determine the Value of Prophylaxis Relative to On-Demand Treatment in Hemophilia A and Emicizumab versus Replacement Therapy in the Greek Healthcare Setting. Clin Drug Investig 42, 75–85 (2022). https://doi.org/10.1007/s40261-021-01108-4

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