Skip to main content

Economic Evaluation of Stiripentol for Dravet Syndrome: A Cost-Utility Analysis

PharmacoEconomics volume 36, pages 1253–1261 (2018)Cite this article

Abstract

Background

Dravet syndrome is a catastrophic form of pediatric treatment-resistant epilepsy with few effective treatment options. Stiripentol is approved for use in Canada for treatment of Dravet syndrome, but the associated long-term costs and benefits have not been well-studied and its cost effectiveness is unclear.

Objective

The aim of this study was to evaluate the cost effectiveness of stiripentol as an adjunctive treatment to clobazam and valproate for treatment of Dravet syndrome from the perspective of the Canadian public healthcare payer.

Methods

A cost-utility analysis was performed to estimate the costs and quality-adjusted life-years (QALYs) associated with adjunctive stiripentol treatment compared with clobazam and valproate alone in children with Dravet syndrome. Transition probabilities, drug efficacy, utility weights, and costs were obtained from a review of the literature. Probabilistic analyses were conducted using a Markov model with health states related to seizure frequency. A 10-year horizon was used. The incremental cost per QALY gained (incremental cost-effectiveness ratio [ICER]) for adjunctive use of stiripentol was calculated, and assumptions were explored in scenario analyses. All costs are expressed in 2017 Canadian dollars ($Can).

Results

Compared with clobazam and valproate alone, the adjunctive use of stiripentol is associated with an ICER of $Can151,310. At a willingness-to-pay threshold of $Can50,000, the probability that stiripentol was the optimal treatment was 5.2%. The cost of stiripentol would need to be reduced by 61.4% for stiripentol to be cost effective.

Conclusion

From the perspective of the Canadian public healthcare payer, stiripentol is not cost effective at its current price at a willingness-to-pay threshold of $Can50,000. Funding stiripentol will be associated with important opportunity costs that bear consideration.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

49,54 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Durá-Travé T, Yoldi-Petri ME, Gallinas-Victoriano F. Epilepsy in children in Navarre, Spain: epileptic seizure types and epileptic syndromes. J Child Neurol. 2007;22:823–8.

    Article  Google Scholar 

  2. Wu YW, Sullivan J, McDaniel SS, Meisler MH, Walsh EM, Li SX, et al. Incidence of Dravet syndrome in a US population. Pediatrics. 2015;136:e1310–5.

    Article  Google Scholar 

  3. Dravet C, Oguni H. Dravet syndrome (severe myoclonic epilepsy in infancy). Handb Clin Neurol. 2013;111:627–33.

    Article  Google Scholar 

  4. Wallace A, Wirrell E, Kenney-Jung DL. Pharmacotherapy for Dravet syndrome. Paediatr Drugs. 2016;19:197–208.

    Article  Google Scholar 

  5. Brigo F, Igwe SC. Antiepileptic drugs for the treatment of infants with severe myoclonic epilepsy. Cochrane Database Syst Rev. 2015;10:CD010483.

    Google Scholar 

  6. Chiron C, Marchand MC, Tran A, Rey E, D’Athis P, Vincent J, et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO Study Group. Lancet. 2000;356:1638–42.

    CAS  Article  Google Scholar 

  7. Guerrini R, Tonnelier S, D’Athis P, Rey E, Vincent J, Pons G, et al. Stiripentol in severe myoclonic epilepsy in infancy (SEMI): a placebo-controlled Italian trial [poster no. P496]. Epilepsia. 2002;43(Suppl. 8):155.

    Google Scholar 

  8. Biocodex, Product monograph: Diacomit (stiripentol). Gentilly: Biocodex; 2012.

    Google Scholar 

  9. Common Drug Review. Pharmacoeconomic review report - Diacomit. Ottawa: CADTH; 2015. https://www.cadth.ca/sites/default/files/cdr/pharmacoeconomic/sr0360_diacomit_pe_report.pdf. Accessed 8 May 2018.

  10. CADTH. Guidelines for the economic evaluation of health technologies: Canada. 4th ed. Ottawa: CADTH; 2017.

    Google Scholar 

  11. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Value Health. 2013;16:e1–5.

    Article  Google Scholar 

  12. National Institute for Health and Care Excellence (NICE). Appendix R: economic evaluation of AEDs used as monotherapy and adjunctive therapy in the treatment of children with focal seizures. London: NICE; 2012. pp. 55–76. https://www.nice.org.uk/guidance/cg137/evidence. Accessed 8 May 2018.

  13. Inoue Y, Ohtsuka Y. Long-term safety and efficacy of stiripentol for the treatment of Dravet syndrome: a multicenter, open-label study in Japan. Epilepsy Res. 2015;113:90–7.

    CAS  Article  Google Scholar 

  14. Briggs AH, Ades A, Price MJ. Probabilistic sensitivity analysis for decision trees with multiple branches: use of the Dirichlet distribution in a Bayesian framework. Med Decis Mak. 2003;23:341–50.

    Article  Google Scholar 

  15. Cooper MS, Mcintosh A, Crompton DE, McMahon JM, Schneider A, Farrell K, et al. Mortality in Dravet syndrome. Epilepsy Res. 2016;128:43–7.

    Article  Google Scholar 

  16. Fleurence RL, Hollenbeak CS. Rates and probabilities in economic modelling. Pharmacoeconomics. 2007;25:3–6.

    Article  Google Scholar 

  17. Verdian L, Oyee J, Heyes A, Tolley K, Yi Y. Eliciting preferences for health states associated with Lennox-Gastaut syndrome (LGS) [abstract no. 1.352]. 62nd meeting of the American Epilepsy Society; 5–9 Dec 2008; Seattle. https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/8833. Accessed 8 May 2018.

  18. Edlin R, Mccabe C, Hulme C, Hall P. Cost effectiveness modelling for health technology assessment: correlated parameters and the Cholesky decomposition. In: Edlin R, Mccabe C, Hulme C, Hall P, Wright J, editors. Cost effectiveness modelling for health technology assessment: a practical course. Cham: Springer; 2015.

    Chapter  Google Scholar 

  19. Jacoby A, Buck D, Baker G, McNamee P, Graham-Jones S, Chadwick D. Uptake and costs of care for epilepsy: findings from a UK regional study. Epilepsia. 1998;39:776–86.

    CAS  Article  Google Scholar 

  20. Jennum P, Christensen J, Ibsen R, Kjellberg J. Long-term socioeconomic consequences and health care costs of childhood and adolescent-onset epilepsy. Epilepsia. 2016;57:1078–85.

    Article  Google Scholar 

  21. Whittington MD, Knupp KG, Vanderveen G, Kim C, Gammaitoni A, Campbell JD. The direct and indirect costs of Dravet syndrome. Epilepsy Behav. 2018;80:109–13.

    Article  Google Scholar 

  22. Strzelczyk A, Schubert-Bast S, Reese JP, Rosenow F, Stephani U, Boor R. Evaluation of health-care utilization in patients with Dravet syndrome and on adjunctive treatment with stiripentol and clobazam. Epilepsy Behav. 2014;34:86–91.

    Article  Google Scholar 

  23. Wijnen BFM, van Mastrigt GAPG, Evers SMAA, Gershuni O, Lambrechts DAJE, Majoie MHJM, et al. A systematic review of economic evaluations of treatments for patients with epilepsy. Epilepsia. 2017;58:706–26.

    Article  Google Scholar 

  24. Common Drug Review. Stiripentol (Diacomit): for severe myoclonic epilepsy in infancy (Dravet syndrome): CDEC final recommendation. 2014. http://www.ncbi.nlm.nih.gov/books/NBK349324/. Accessed 8 May 2018.

  25. Jetté N, Quan H, Faris P, Dean S, Li B, Fong A, et al. Health resource use in epilepsy: Significant disparities by age, gender, and aboriginal status. Epilepsia. 2008;49:586–93.

    Article  Google Scholar 

  26. Wilmshurst JM, Burman R, Gaillard WD, Cross JH. Treatment of infants with epilepsy: common practices around the world. Epilepsia. 2015;56:1033–46.

    CAS  Article  Google Scholar 

  27. Panju AH, Bell CM. Policy alternatives for treatments for rare diseases. CMAJ. 2010;182:E787–92.

    Article  Google Scholar 

  28. Clarke JTR. Is the current approach to reviewing new drugs condemning the victims of rare diseases to death? A call for a national orphan drug review policy. CMAJ. 2006;174:189–90.

    Article  Google Scholar 

  29. McCabe C, Edlin R, Round J. Economic considerations in the provision of treatments for rare diseases. In: de la Paz MP, Groft S, editors. Rare Disease Epidemiology, Chapter 13. Dordrecht: Springer; 2010. pp. 211–22.

    Chapter  Google Scholar 

  30. Coyle D, Cheung MC, Evans GA. Opportunity cost of funding drugs for rare diseases: the cost-effectiveness of eculizumab in paroxysmal nocturnal hemoglobinuria. Med Decis Mak. 2014;34:1016–29.

    Article  Google Scholar 

  31. Ontario Municipal Benchmarking Initiative (OMBI). Emergency medical services (EMS): 2013 OMBI performance measurement report. Dundas: OMBI; 2013. p. 2013.

    Google Scholar 

Download references

Acknowledgements

JE is supported by an Ontario Graduate Scholarship and is a trainee in the Drug Safety and Effectiveness Cross-Disciplinary Training (DSECT) program, funded by the Canadian Institutes of Health Research.

Author information

Affiliations

  1. School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada

    Jesse Elliott, Tammy Clifford, George A. Wells & Doug Coyle

  2. Department of Paediatrics, University of Toronto, Toronto, ON, Canada

    Bláthnaid McCoy

  3. Division of Neurology, The Hospital for Sick Children, Toronto, ON, Canada

    Bláthnaid McCoy

  4. CADTH, Ottawa, ON, Canada

    Tammy Clifford

  5. Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, ON, Canada

    George A. Wells

Authors
  1. Jesse Elliott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bláthnaid McCoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tammy Clifford
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George A. Wells
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Doug Coyle
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All of the authors contributed to the conception and planning of the study, the analysis and/or interpretation of the data; drafting and critical revision of the manuscript; and approved the version of the manuscript submitted for publication.

Corresponding author

Correspondence to Jesse Elliott.

Ethics declarations

Funding

No specific funding was received for this study.

Conflict of interest

Bláthnaid McCoy is principal investigator in a study of cannabinoids for Dravet syndrome. Tammy Clifford is employed by CADTH (Canadian Agency for Drugs and Technologies in Health). She had no role in the review of stiripentol that was undertaken by the Common Drug Review. Jesse Elliott, George Wells, and Doug Coyle have no conflicts of interest to declare.

Data availability statement

All data generated or analyzed during this study are included in this published article (and its online supplementary information files). The Markov model used in this analysis was provided for peer review.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 515 kb)

Supplementary material 2 (DOCX 33 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Elliott, J., McCoy, B., Clifford, T. et al. Economic Evaluation of Stiripentol for Dravet Syndrome: A Cost-Utility Analysis. PharmacoEconomics 36, 1253–1261 (2018). https://doi.org/10.1007/s40273-018-0669-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40273-018-0669-7