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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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Abstract

Background

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.

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. Evidera, 500 Totten Pond Road, Suite 500, Waltham, MA, USA

    Luis Hernandez & Malinda O’Donnell

  2. Department of Health Sciences, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands

    Luis Hernandez & Maarten Postma

  3. Unit of Pharmacotherapy, -Epidemiology and -Economics, University of Groningen, Groningen Research Institute of Pharmacy (GRIP), Groningen, The Netherlands

    Maarten Postma

  4. Department of Economics, Econometrics and Finance, Faculty of Economics and Business, University of Groningen, Groningen, The Netherlands

    Maarten Postma

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  1. Luis Hernandez
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Contributions

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.

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Correspondence to Luis Hernandez.

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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.

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Hernandez, L., O’Donnell, M. & Postma, M. 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. PharmacoEconomics 36, 1223–1252 (2018). https://doi.org/10.1007/s40273-018-0683-9

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