Modeling Approaches in Cost-Effectiveness Analysis of Disease-Modifying Therapies for Relapsing–Remitting Multiple Sclerosis: An Updated Systematic Review and Recommendations for Future Economic Evaluations
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Numerous cost-effectiveness analyses (CEAs) of disease-modifying therapies (DMTs) for relapsing–remitting multiple sclerosis (RRMS) have been published in the last three decades. Literature reviews of the modeling methods and results from these CEAs have also been published. The last literature review that focused on modeling methods, without country or time horizon in the inclusion criteria, included studies published up to 2012. Since then, new DMTs have become available, and new models and data sources have been used to assess their cost effectiveness.
The aim of this systematic review was to provide a detailed and comprehensive description of the relevant aspects of economic models used in CEAs of DMTs for RRMS, to understand how these models have progressed from recommendations provided in past reviews, what new approaches have been developed, what issues remain, and how they could be addressed.
EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), the National Health System (NHS) Economic Evaluations Database, the Health Technology Assessment (HTA) Database, and EconLit were searched for cost-effectiveness studies of DMTs for RRMS that used decision-analytic models, published in English between 1 January 2012 and 24 December 2017. The inclusion criteria were as follows: being a full economic evaluation, a decision-analytic model was used, the target population concerned adult patients with RRMS, and being available in full-text format. Studies were not excluded based on the methodological quality. The background information of the included studies, as well as specific information on the components of the economic models related to the areas of recommendation from previous reviews were extracted.
Twenty-three studies from ten countries were included. The model structure of these studies has converged over time, characterizing the course of disease progression in terms of changes in disability and the occurrence of relapses over time. Variations were found in model approach; data sources for the natural course of the disease and comparative efficacy between DMTs; number of lines of treatment modeled; long-term efficacy waning and treatment discontinuation assumptions; type of withdrawal; and criteria for selecting adverse events. Main areas for improvement include using long-term time horizons and societal perspective; reporting relevant health outcomes; conducting scenario analyses using different sources of natural history and utility values; and reporting how the model was validated.
The structure of economic models used in CEAs of DMTs for RRMS has converged over time. However, variation remains in terms of model approach, inputs, and assumptions. Though some recommendations from previous reviews have been incorporated in later models, areas for improvement remain.
The authors would like to thank David January, PhD, Lead Market Access Writer at Evidera, for his contribution to resolve the disagreements between the reviewers during the abstract and full-text screening.
Luis Hernandez was the leading author who conducted the study design, literature search, data extraction, and writing of the manuscript, and will serve as guarantor for the content of the manuscript. Malinda O’Donnell participated in the literature search, data extraction, and writing of the manuscript. Maarten Postma participated in the study design and review of the manuscript.
Compliance with Ethical Standards
No funding was received for this study or manuscript.
Conflict of interest
Luis Hernandez and Malinda O’Donnell are employees of Evidera, a company that provides consulting and other research services to pharmaceutical, device, government, and non-government organizations. As part of his role at Evidera, Luis Hernandez has provided consulting services to pharmaceutical companies, manufacturers of disease-modifying therapies covered in this review. Maarten Postma is a Professor and researcher at the University of Groningen. Maarten Postma has received grants and honoraria from various pharmaceutical companies all unrelated to this research, but sometimes in the area of multiple sclerosis and from companies developing, producing, and marketing multiple sclerosis drugs.
- 4.Campbell JD, Ghushchyan V, Brett McQueen R, Cahoon-Metzger S, Livingston T, Vollmer T, et al. Burden of multiple sclerosis on direct, indirect costs and quality of life: national US estimates. Mult Scler Relat Disord. 2014;3(2):227–36. https://doi.org/10.1016/j.msard.2013.09.004.CrossRefPubMedGoogle Scholar
- 6.Multiple Sclerosis International Federation (MSIF). Atlas of MS 2013: Mapping multiple sclerosis around the world. 2013. https://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf. Accessed December 23 2017.
- 12.National Multiple Sclerois Society UK. What is MS? Types of MS. https://www.mssociety.org.uk/what-is-ms/types-of-ms. Accessed December 23 2017.
- 13.National Multiple Sclerois Society US. What is MS? Types of MS. https://www.nationalmssociety.org/What-is-MS/Types-of-MS. Accessed December 23 2017.
- 14.Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci. 2008;31:247–69. https://doi.org/10.1146/annurev.neuro.30.051606.094313.CrossRefPubMedGoogle Scholar
- 15.National Multiple Sclerois Society US. Treating MS: Medications. https://www.nationalmssociety.org/Treating-MS/Medications. Accessed December 23 2017.
- 19.US Food and Drug Administration (FDA). FDA News Release: FDA approved new drug to treat multiple sclerosis [ocrelizumab]. 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm549325.htm. Accessed December 23 2017.
- 20.European Medicines Agency (EMA). Press release: New medicine for multiple sclerosis [ocrelizumab]. 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm549325.htm. Accessed December 23 2017.
- 28.School of Health and Related Research (ScHARR): University of Sheffield—Center for Bayesian Statistic in Health Economics. Cost effectiveness of beta interferons and glatiramer acetate in the management of multiple sclerosis: Final report to the National Institute for Clinical Excellence. 2002. https://www.nice.org.uk/guidance/ta32/documents/assessment-report-on-the-use-of-beta-interferon-and-glatiramer-acetate-for-multiple-sclerosis-scharr-report2. Accessed December 28 2017.
- 32.Allen F, Montgomery S, Maruszczak M, Kusel J, Adlard N. Convergence yet continued complexity: a systematic review and critique of health economic models of relapsing-remitting multiple sclerosis in the United Kingdom. Value Health. 2015;18(6):925–38. https://doi.org/10.1016/j.jval.2015.05.006.CrossRefPubMedGoogle Scholar
- 34.Ebers GC, Heigenhauser L, Daumer M, Lederer C, Noseworthy JH. Disability as an outcome in MS clinical trials. Neurology. 2008;71(9):624–31. https://doi.org/10.1212/01.wnl.0000313034.46883.16.CrossRefPubMedGoogle Scholar
- 41.Hernandez L, Guo S, Kinter E, Fay M. Cost-effectiveness analysis of peginterferon beta-1a compared with interferon beta-1a and glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis in the United States. J Med Econ. 2016;19(7):684–95. https://doi.org/10.3111/13696998.2016.1157080.CrossRefPubMedGoogle Scholar
- 46.Dembek C, White LA, Quach J, Szkurhan A, Rashid N, Blasco MR. Cost-effectiveness of injectable disease-modifying therapies for the treatment of relapsing forms of multiple sclerosis in Spain. Eur J Health Econ. 2014;15(4):353–62. https://doi.org/10.1007/s10198-013-0478-z.CrossRefPubMedGoogle Scholar
- 48.La Rosa Sánchez-De. R, Sabater E, Casado MA, Arroyo R. Cost-effectiveness analysis of disease modifiying drugs (interferons and glatiramer acetate) as first line treatments in remitting-relapsing multiple sclerosis patients. J Med Econ. 2012;15(3):424–33. https://doi.org/10.3111/13696998.2012.654868.CrossRefGoogle Scholar
- 49.Montgomery SM, Kusel J, Nicholas R, Adlard N. Costs and effectiveness of fingolimod versus alemtuzumab in the treatment of highly active relapsing-remitting multiple sclerosis in the UK: re-treatment, discount, and disutility. J Med Econ. 2017;20(9):962–73. https://doi.org/10.1080/13696998.2017.1345748.CrossRefPubMedGoogle Scholar
- 50.Montgomery SM, Maruszczak MJ, Slater D, Kusel J, Nicholas R, Adlard N. A discrete event simulation to model the cost-utility of fingolimod and natalizumab in rapidly evolving severe relapsing-remitting multiple sclerosis in the UK. J Med Econ. 2017;20(5):474–82. https://doi.org/10.1080/13696998.2016.1276070.CrossRefPubMedGoogle Scholar
- 51.Nikfar S, Kebriaeezadeh A, Dinarvand R, Abdollahi M, Sahraian MA, Henry D, et al. Cost-effectiveness of different interferon beta products for relapsing-remitting and secondary progressive multiple sclerosis: decision analysis based on long-term clinical data and switchable treatments. DARU, J Pharmaceut Sci. 2013. https://doi.org/10.1186/2008-2231-21-50.CrossRefGoogle Scholar
- 54.Hernandez L, Guo S, Toro-Diaz H, Carroll S, Syed Farooq SF. Peginterferon beta-1a versus other self-injectable disease-modifying therapies in the treatment of relapsing-remitting multiple sclerosis in Scotland: a cost-effectiveness analysis. J Med Econ. 2017;20(3):228–38. https://doi.org/10.1080/13696998.2016.1247712.CrossRefPubMedGoogle Scholar
- 58.Maruszczak MJ, Montgomery SM, Griffiths MJS, Bergvall N, Adlard N. Cost-utility of fingolimod compared with dimethyl fumarate in highly active relapsing-remitting multiple sclerosis (RRMS) in England. J Med Econ. 2015;18(11):874–85. https://doi.org/10.3111/13696998.2015.1056794.CrossRefPubMedGoogle Scholar
- 61.National Institute for Health and Care Excellence. Teriflunomide for treating relapsing-remitting multiple sclerosis: Final appraisal determination. 2013. https://www.nice.org.uk/guidance/ta303/documents/multiple-sclerosis-relapsing-teriflunomide-final-appraisal-determination3. Accessed March 2016.
- 62.National Institute for Health and Care Excellence. Dimethyl fumarate for treating relapsing-remitting multiple sclerosis: Final appraisal determination. 2014. https://www.nice.org.uk/guidance/gid-tag340/resources/multiple-sclerosis-relapsingremitting-dimethyl-fumarate-final-appraisal-determination-document2. Accessed March 2016.
- 63.Biogen Idec Ltd. Dimethyl Fumarate for the Treatment of Adult Patients with Relapsing Remitting Multiple Sclerosis (TA320). Manufacturer submission of evidence to NICE. London. London: National Institute for Health and Care Excellence; 2013.Google Scholar
- 66.National Institute for Health and Care Excellence. Alemtuzumab for treating relapsing-remitting multiple sclerosis: Final appraisal determination. 2014. https://www.nice.org.uk/guidance/ta312/documents/multiple-sclerosis-relapsingremitting-alemtuzumab-fad-document2. Accessed March 2016.
- 67.National Institute for Health and Clinical Excellence. Natalizumab for the treatment of adults with highly active relapsing-remitting multiple sclerosis: Final appraisal determination. 2007. https://www.nice.org.uk/guidance/TA127/documents/multiple-sclerosis-natalizumab-for-the-treatment-of-adults-with-highly-active-relapsingremitting-multiple-sclerosis-final-appraisal-determination3. Accessed March 2016.
- 68.National Institute for Health and Clinical Excellence. Fingolimod for the treatment of highly active relapsing-remitting multiple sclerosis: Final appraisal determination. 2012. https://www.nice.org.uk/guidance/TA254/documents/multiple-sclerosis-relapsingremitting-fingolimod-final-appraisal-determination-document2. Accessed March 2016.
- 69.North American Registry for Care and Research in Multiple Sclerosis (NARCRMS). 2017. http://www.narcrms.org/overview/. Accessed March 11 2018.
- 73.Tolley K, Hutchinson M, You X, Wang P, Sperling B, Taneja A, et al. A network meta-analysis of efficacy and evaluation of safety of subcutaneous pegylated interferon beta-1a versus other injectable therapies for the treatment of relapsing-remitting multiple sclerosis. PLoS One. 2015;10(6):e0127960. https://doi.org/10.1371/journal.pone.0127960.CrossRefPubMedPubMedCentralGoogle Scholar
- 74.Fogarty E, Schmitz S, Tubridy N, Walsh C, Barry M. Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: systematic review and network meta-analysis. Mult Scler Relat Disord. 2016;9:23–30. https://doi.org/10.1016/j.msard.2016.06.001.CrossRefPubMedGoogle Scholar
- 75.Siddiqui MK, Khurana IS, Budhia S, Hettle R, Harty G, Wong SL. Systematic literature review and network meta-analysis of cladribine tablets versus alternative disease-modifying treatments for relapsing-remitting multiple sclerosis. Curr Med Res Opin. 2017. https://doi.org/10.1080/03007995.2017.1407303.CrossRefPubMedGoogle Scholar
- 84.Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829–39. https://doi.org/10.1016/S0140-6736(12)61768-1.CrossRefPubMedGoogle Scholar
- 85.Calabresi PA, Kieseier BC, Arnold DL, Balcer LJ, Boyko A, Pelletier J, et al. Pegylated interferon beta-1a for relapsing-remitting multiple sclerosis (ADVANCE): a randomised, phase 3, double-blind study. Lancet Neurol. 2014;13(7):657–65. https://doi.org/10.1016/S1474-4422(14)70068-7.CrossRefPubMedGoogle Scholar
- 88.Calabresi PA, Radue EW, Goodin D, Jeffery D, Rammohan KW, Reder AT, et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(6):545–56. https://doi.org/10.1016/S1474-4422(14)70049-3.CrossRefPubMedGoogle Scholar
- 91.Biogen. Biogen and AbbVie Announce the Voluntary Worldwide Withdrawal of Marketing Authorizations for ZINBRYTA® (daclizumab) for Relapsing Multiple Sclerosis. http://media.biogen.com/press-release/autoimmune-diseases/biogen%C2%A0and-abbvie-announce%C2%A0-voluntary%C2%A0worldwide-withdrawal-marketi. Accessed March 3 2018.
- 93.Meyer-Moock S, Feng YS, Maeurer M, Dippel FW, Kohlmann T. Systematic literature review and validity evaluation of the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Functional Composite (MSFC) in patients with multiple sclerosis. BMC Neurol. 2014;14:58. https://doi.org/10.1186/1471-2377-14-58.CrossRefPubMedPubMedCentralGoogle Scholar
- 95.Cohen JA, Reingold SC, Polman CH, Wolinsky JS. International Advisory Committee on Clinical Trials in Multiple S. Disability outcome measures in multiple sclerosis clinical trials: current status and future prospects. Lancet Neurol. 2012;11(5):467–76. https://doi.org/10.1016/S1474-4422(12)70059-5.CrossRefPubMedGoogle Scholar
- 103.Cadavid D, Phillips G, Dong-Si T, Tran J, Xu L. Efficacy and safety of anti LINGO-1 for the treatment of relapsing forms of multiple sclerosis: design of the phase 2 SYNERGY trial (P3.154). Neurology. 2014;82(10 Supplement):154. http://n.neurology.org/content/82/10_Supplement/P3.154. Accessed 3 Mar 2018.
- 104.Mellion M, Edwards KR, Hupperts R, Drulović J, Montalban X, Hartung H-P. Efficacy results from the phase 2b SYNERGY study: treatment of disabling multiple sclerosis with the anti-LINGO-1 monoclonal antibody opicinumab (S33.004). Neurology. 2017;88(16):S33.044. http://n.neurology.org/content/88/16_Supplement/S33.004. Accessed 3 Mar 2018.
- 107.Guo S, Hernandez L, Saint-Laurent Thibault C, Proskorovsky I, Phillips GA. Predicting the long-term clinical effectiveness of daclizumab in relapsing-remitting multiple sclerosis: a new modeling framework using discrete event simulation. Value Health. 2013;16(3):A101. https://doi.org/10.1016/j.jval.2013.03.478.CrossRefGoogle Scholar
- 109.Novartis Pharmaceuticals UK Ltd. Fingolimod for the Treatment of Relapsing-Remitting Multiple Sclerosis in Adults (TA254). Manufacturer submission of evidence to NICE. London: National Institute for Health and Clinical Excellence; 2011.Google Scholar
- 113.Biogen Idec Ltd. Natalizumab (Tysabri®) for the Treatment of Adults with Highly Active Relapsing Remitting Multiple Sclerosis (TA127). Manufacturer submission of evidence to NICE. London: National Institute for Health and Clinical Excellence; 2007.Google Scholar
- 114.Thompson JP, Noyes K, Dorsey ER, Schwid SR, Holloway RG. Quantitative risk-benefit analysis of natalizumab. Neurology. 2008;71(5):357–64. https://doi.org/10.1212/01.wnl.0000319648.65173.7a.CrossRefPubMedPubMedCentralGoogle Scholar
- 117.Bell C, Graham J, Earnshaw S, Oleen-Burkey M, Castelli-Haley J, Johnson K. Cost-effectiveness of four immunomodulatory therapies for relapsing-remitting multiple sclerosis: a Markov model based on long-term clinical data. J Manag Care Pharm. 2007;13(3):245–61. https://doi.org/10.18553/jmcp.2007.13.3.245.CrossRefPubMedGoogle Scholar
- 120.Genzyme. Teriflunomide for the Treatment of Relapsing-Remitting Multiple Sclerosis in Adults (TA303). Manufacturer submission of evidence to NICE. London: National Institute for Health and Care Excellence; 2013.Google Scholar
- 121.Hutchinson M, Fox RJ, Havrdova E, Kurukulasuriya NC, Sarda SP, Agarwal S, et al. Efficacy and safety of BG-12 (dimethyl fumarate) and other disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis: a systematic review and mixed treatment comparison. Curr Med Res Opin. 2014;30(4):613–27. https://doi.org/10.1185/03007995.2013.863755.CrossRefPubMedGoogle Scholar
- 122.Phillips JT, Giovannoni G, Lublin FD, O’Connor PW, Polman CH, Willoughby E, et al. Sustained improvement in Expanded Disability Status Scale as a new efficacy measure of neurological change in multiple sclerosis: treatment effects with natalizumab in patients with relapsing multiple sclerosis. Mult Scler. 2011;17(8):970–9. https://doi.org/10.1177/1352458511399611.CrossRefPubMedGoogle Scholar
- 123.Genzyme. Alemtuzumab for the Treatment of Relapsing Remitting Multiple Sclerosis in Adults (TA32). Manufacturer submission of evidence to NICE. London: National Institute for Health and Care Excellence; 2013.Google Scholar