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Background: For novel migraine therapies, economic evaluations will be required to understand the trade-offs between additional health benefit and additional cost. The purpose of this study was to conduct a systematic literature review (SLR) to identify previous economic evaluations in migraine from the United Kingdom or Irish perspective to critically appraise these evaluations and to propose, if necessary, a novel modelling approach that can be used for future economic evaluations of migraine therapies. Methods: An SLR was conducted to identify previous economic evaluations of preventive migraine treatments. Key opinion leaders were consulted to determine the criteria for a robust migraine economic evaluation. Economic evaluations identified in the SLR were appraised against these criteria, and a novel cost-effectiveness model structure was then proposed. Results: Eight records reporting on published economic evaluations were identified and critically appraised for general quality. Expert consultation provided 6 recommendations on the ideal model structure for migraine that is both clinically and economically meaningful. A decision-tree plus Markov structure was then developed as a cost-effectiveness model for migraine therapies where each health state is associated with a patient distribution across monthly migraine day (MMD) frequencies. Conclusions: Future migraine economic evaluations should allow for assessments across the full spectrum of migraine, a response-based stopping rule, and the estimation of benefits and resource costs based on MMD frequency. The approach proposed in this paper captures all of the desired elements for an economic evaluation of migraine therapy and is suitable to assess new migraine therapies.

Background Secondary progressive multiple sclerosis (SPMS) is a subtype of multiple sclerosis (MS), which is a chronic neurological disease, characterised by inflammation of the central nervous system. Most of MS patients eventually progress to SPMS. This study estimates the prevalence of SPMS in the United States of America, Europe, Canada, Australia, and Brazil. Methods A systematic literature search of the Medline and Embase databases was performed using the OVID™ SP platform to identify MS epidemiological studies published in English from database inception to September 22, 2020. Studies reporting the prevalence of MS and proportion of SPMS patients in the included population were selected. The pooled prevalence of SPMS was calculated based on the proportion of SPMS patients. The Loney quality assessment checklist was used for quality grading. A meta-analysis of the proportions was conducted in RStudio. Results A total of 4754 articles were retrieved, and prevalence was calculated from 97 relevant studies. Overall, 86 medium- and high-quality studies were included in the meta-analysis. Most studies were conducted in European countries (84 studies). The estimated pooled prevalence of SPMS was 22.42 (99% confidence interval: 18.30, 26.95)/100,000. The prevalence of SPMS was more in the North European countries, highest in Sweden and lowest in Brazil. A decline in SPMS prevalence was observed since the availability of oral disease-modifying therapies. We also observed a regional variation of higher SPMS prevalence in urban areas compared with rural areas. Conclusion High variability was observed in the estimated SPMS prevalence, and the quality of the studies conducted. The influence of latitude and other factors known to affect overall MS prevalence did not fully explain the wide range of inter-country and intra-country variability identified in the results.

0%. Percentage change in accuracy when validated on dataset with transformations was: RF=6.59%, GBL=0.31%, GLM=0.1%, GBT=0.1%, SVM=-0.1%. Conclusions: (1) All algorithms can extract data patterns and maintain their predictive performance under extreme transformations. (2) Boosting and treebased algorithms drastically outperform SVM and LASSO algorithms in noise-free data (3) SVM and LASSO face no decrease in performance, while Tree-based algorithms can be rendered unusable by heavy noise. (4) Ability to identify the source and degree of noise in the validation dataset is necessary to select appropriate classification algorithm. (5) Data-specific tuning is critical to assure high performance even under heavy noise.

Objective The study aim was to evaluate the cost effectiveness and budget impact of siponimod compared to interferon beta-1a for adult patients with secondary progressive multiple sclerosis (SPMS) with active disease, from a Swiss health insurance perspective. Methods We conducted an analysis using a Markov cohort model with a cycle length of 1 year, life-long time horizon, and discount rate of 3% for cost and health outcomes. We used a matching-adjusted indirect comparison to estimate clinical outcomes using data from the EXPAND randomised controlled trial of siponimod vs placebo and the Nordic SPMS randomised controlled trial of interferon beta-1a vs placebo as the basis for estimates of disability progression and relapse outcomes. We used 6-month confirmed disability progression results to estimate disability progression in the base-case analysis. We calculated quality-adjusted life-years (QALYs) based on an external study that administered the EQ-5D-3L questionnaire to European patients with multiple sclerosis. We included costs (Swiss Franc (CHF), year 2020) of drug acquisition/administration, adverse events and disease management. We also performed a budget impact analysis to estimate the cost over the first 3 years of introducing siponimod. Results For the base case, siponimod resulted in mean incremental costs of CHF 84,901 (siponimod: CHF 567,838, interferon beta-1a: CHF 482,937) and mean incremental QALYs of 1.591 (siponimod: 7.495, interferon beta-1a: 5.905), leading to an incremental cost-effectiveness ratio of CHF 53,364 per QALY gained. In the probabilistic sensitivity analysis, the probability of the cost effectiveness of siponimod assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained was 90%. Siponimod was projected to result in drug administration costs for siponimod of CHF 23,817,856 in the first 3 years after introduction, accompanied by large cost offsets in drug acquisition of other multiple sclerosis drugs. Considering drug administration, monitoring and adverse event management costs, it was estimated to result in additional healthcare costs in Switzerland of CHF 2,177,021. Conclusions In the base-case analysis, we found that siponimod may be cost effective for treating Swiss adult patients with SPMS with active disease. The results of the cost-effectiveness analyses are valid under the assumption that the efficacy of siponimod and the comparators on disability progression for the overall SPMS population would be the same in the active SPMS population. Clinical Trial Identifier NCT01665144. This economic evaluation was based on the EXPAND trial. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-021-01023-8.