Societal costs of multiple sclerosis in Ireland

Aims: This paper evaluates the impact of multiple sclerosis (MS) in Ireland, and estimates the associated direct, indirect, and intangible costs to society based on a large nationally representative sample.

Materials and methods: A questionnaire was developed to capture the demographics, disease characteristics, healthcare use, informal care, employment, and wellbeing. Referencing international studies, standardized survey instruments were included (e.g. CSRI, MFIS-5, EQ-5D) or adapted (EDSS) for inclusion in an online survey platform. Recruitment was directed at people with MS via the MS Society mailing list and social media platforms, as well as in traditional media. The economic costing was primarily conducted using a ‘bottom-up’ methodology, and national estimates were achieved using ‘prevalence-based’ extrapolation.

Results: A total of 594 people completed the survey in full. The sample had geographic, disease, and demographic characteristics indicating good representativeness. At an individual level, average societal cost was estimated at €47,683; the average annual costs for those with mild, moderate, and severe MS were calculated as €34,942, €57,857, and €100,554, respectively. For a total Irish MS population of 9,000, the total societal costs of MS amounted to €429m. Direct costs accounted for just 30% of the total societal costs, indirect costs amounted to 50% of the total, and intangible or QoL costs represented 20%. The societal cost associated with a relapse in the sample is estimated as €2,438.

Limitations and conclusions: The findings highlight that up to 70% of the total costs associated with MS are not routinely counted. These “hidden” costs are higher in Ireland than the rest of Europe, due in part to significantly lower levels of workforce participation, a higher likelihood of permanent workforce withdrawal, and higher levels of informal care needs. The relationship between disease progression and costs emphasize the societal importance of managing and slowing the progression of the illness.     

The impact of increasing neurological disability of multiple sclerosis on health utilities: a systematic review of the literature

Abstract

Background: Multiple sclerosis (MS) is a debilitating disease, accompanied by neurological symptoms of varying severity. Utilities are a key summary index measure used in assessing health-related quality of life in individuals with MS.

Objectives: To provide a systematic review of the literature on utilities of relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) patients and to review changes in utilities associated with the increasing neurological disability of different stages of MS, as measured by the Expanded Disability Status Scale (EDSS).

Methods: Employing pre-defined search terms and inclusion/exclusion criteria, systematic searches of the literature were conducted in EMBASE, MEDLINE, PsycINFO, the Health Economic Evaluation Database (HEED), and the NHS Economic Evaluations Database (NHS/EED). Proceedings for the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), the European Society for Treatment and Research in MS (ECTRIMS), the American Society for Treatment and Research in MS (ACTRIMS), and the Latin American Society for Treatment and Research in MS (LACTRIMS) were reviewed in addition to the UK National Institute for Health and Clinical Excellence website and the table of contents of PharmacoEconomics and Value in Health.

Results: This review identified 18 studies reporting utilities associated with health states of MS. Utilities ranged from 0.80 to 0.92 for patients with an EDSS score of 1, from 0.49 to 0.71 for patients with an EDSS score of 3, from 0.39 to 0.54 for patients with an EDSS score of 6.5, and from –0.19 to 0.1 for patients with an EDSS score of 9.

Limitations: Several of the studies reviewed relied on data from patient organizations, which may not be fully representative of the general patient populations. Additionally, the majority of the studies relied on retrospective data collection.

Conclusions: Utilities decrease substantially with increasing neurological disability. Cross-country differences are minimal with utility scores following a similar pattern across countries for patients at similar disease severity levels. This consistency in findings is noteworthy, as there is a reliable evidence base for selecting utility values for economic evaluation analyses. However, more research is needed to explore potential differences in utilities between RRMS and SPMS patients.     

The burden of multiple sclerosis in Japan

Aims: Multiple sclerosis (MS) is a disabling autoimmune disease affecting the central nervous system. Few studies have examined the effect of MS on patient outcomes in Japan. The study aim was to quantify MS burden in Japan by comparing MS respondents to matched controls on patient outcomes.

Materials and methods: Data from seven administrations of the nationally representative Japan National Health and Wellness Survey (2009–2014 and 2016) were used (n?=?181,423). Respondents self-reporting MS diagnosis were compared with respondents not reporting MS. Matched controls were selected using propensity scores. Respondents with MS and matched controls were compared on health-related quality-of-life (HRQoL), work productivity and activity impairment, healthcare resource utilization, and costs. Comparisons were made using Chi-square tests or one-way ANOVAs.

Results: A total of 96 respondents with MS and 480 matched controls were included in the analyses. MS respondents reported worse mental (44.35 vs 47.51, p?p?p?p?p?p?p?Limitations: Japan NHWS data are cross-sectional, and causal relationships cannot be established. Due to the self-reported nature of the data, responses could not be independently verified.

Conclusions: Results suggest MS in Japan is associated with poorer HRQoL and greater work and activity impairment, healthcare resource use, and costs. Improved MS management could benefit both patients and society.     

Economic burden of amyotrophic lateral sclerosis in the United Kingdom

Abstract

To assess the economic burden of amyotrophic lateral sclerosis (ALS) in the United Kingdom, yearly direct medical costs were determined for four defined ALS health states (mild, moderate, severe and terminal disease stages). Resource utilisation patterns for each health state were obtained from United Kingdom neurologists and local costs (1996/97) were attached to the resources. The annual direct cost of the health states increased from £1185.20 in mild disease to £3127.51 in the terminal state. Hospitalisation was a major contributor to total cost in mild (43.3%), severe (31.6%) and terminal (45.1%) states. In contrast, in moderate disease the impact of hospitalisation was minimal (0.8%) compared to physician remuneration costs (59%). The economic burden of ALS is therefore directly related to the severity of the disease. The study identifies the major cost drivers in current ALS care and provides a means for determining how potential therapeutic interventions might affect the overall cost of the disease.     

Cost-minimization analysis of alemtuzumab compared to fingolimod and natalizumab for the treatment of active relapsing-remitting multiple sclerosis in the Netherlands

Aim: In active relapsing remitting multiple sclerosis (RRMS) patients requiring second-line treatment, the Dutch National Health Care Institute (ZiN) has not stated a preference for either alemtuzumab, fingolimod, or natalizumab. The aim was to give healthcare decision-makers insight into the differences in cost accumulation over time between alemtuzumab—with a unique, non-continuous treatment schedule—and fingolimod and natalizumab for second-line treatment of active RRMS patients in the Netherlands.

Methods: In line with ZiN’s assessment, a cost-minimization analysis was performed from a Dutch healthcare perspective over a 5-year time horizon. Resource use was derived from hospital protocols and summaries of product characteristics, and validated by two MS specialists. Unit costs were based on national tariffs and guidelines. Robustness of the base case results was verified with multiple sensitivity and scenario analyses.

Results: Alemtuzumab results in cost savings compared to fingolimod and natalizumab from, respectively, 3.3 and 2.8 years since treatment initiation onwards. At 5 years, total discounted costs per patient of alemtuzumab were €79,717, followed by fingolimod with €110,044 and natalizumab with €122,238, resulting in cost savings of €30,327 and €42,522 for alemtuzumab compared to fingolimod and natalizumab, respectively. Key drivers of the model are drug acquisition costs and the proportions of patients that do not require further alemtuzumab treatment after either two, three, or four courses.

Limitations: No treatment discontinuation and associated switching between treatments were incorporated. Consequences of JC virus seropositivity while continuing natalizumab treatment (e.g. additional monitoring) were omitted from the base case.

Conclusion: The current cost-minimization analysis demonstrates that, from the Dutch healthcare perspective, treating active RRMS patients with alemtuzumab results in cost savings compared to second-line alternatives fingolimod and natalizumab from ～3 years since treatment initiation onwards. After 5 years, alemtuzumab’s cost savings are estimated at €30k compared to fingolimod and €43k compared to natalizumab.     

Employment and absenteeism in working-age persons with multiple sclerosis

Aims: To better understand the impact of the clinical course of multiple sclerosis (MS) and disability on employment, absenteeism, and related factors.

Materials and methods: This study included respondents to the North American Research Committee on Multiple Sclerosis Registry spring 2015 update survey who were US or Canadian residents, aged 18–65 years and reported having relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS). The RRMS and SPMS participants were combined to form the relapsing-onset MS (RMS) group and compared with the PPMS group regarding employment status, absenteeism, and disability. Multivariable logistic regression was used to examine the relationship between employment-related outcomes and factors that may affect these relationships.

Results: Of the 8004 survey respondents, 5887 (73.6%) were 18–65 years of age. The PPMS group (n?=?344) had a higher proportion of males and older mean age at the time of the survey and at time of diagnosis than the RMS group (n?=?4829). Female sex, age, age at diagnosis, cognitive and hand function impairment, fatigue, higher disability levels, ≥3 comorbidities, and a diagnosis of PPMS were associated with not working. After adjustment for disability, the employed PPMS sub-group reported similar levels of absenteeism to the employed RMS sub-group.

Limitations: Limitations of the study include self-report of information and the possibility that participants may not fully represent the working-age MS population.

Conclusions: In MS, employment status and absenteeism are negatively affected by disability, cognitive impairment, and fatigue. These findings underscore the need for therapies that prevent disability progression and other symptoms that negatively affect productivity in persons with MS to enable them to persist in the workforce.     

Valuing Environmental Health Effects – An Economic Perspective

This paper provides an overview of some of the issues involved in comparing benefit-cost analysis and cost-effectiveness analysis based on quality-adjusted life-years as alternative approaches to assessing environmental policies that affect human health. It concludes that: (i) although QALYs have the advantage of reflecting policy impacts on both health status and longevity in a single scalar measure, they are not consistent with utility theory unless individuals’ preferences satisfy some restrictive conditions; (ii) they do not capture other important aspects of the valuation of changes in mortality and morbidity; (iii) cost-effectiveness analysis based on QALYs as a measure of effectiveness omits non-health related effects of environmental policy; and (iv) it leaves unanswered the important question of what level of environmental regulation is appropriate.     

Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims

Abstract

Objective:

Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data.

Methods:

A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated.

Results:

Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p?<?0.001). Alternative algorithms did not improve on the predictive value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability.

Conclusions:

The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.     

The economic burden of end-of-life care in metastatic breast cancer

Objective: To assess end-of-life (EOL) total healthcare costs and resource utilization during the last 6 months of claims follow-up among patients with metastatic breast cancer (MBC) who received systemic anti-neoplastic therapy.

Methods: Newly diagnosed females with MBC initiating treatment January 1, 2003–June 30, 2011 were identified in a large commercial claims database. Two cohorts were defined based on a proxy measure for EOL 1 month prior to the end of last recorded follow-up within the study period: patients who were assumed dead at end of claims follow-up (EOL cohort) and patients who were alive (no-end-of-life [NEOL] cohort). Proxy measures for EOL were obtained from published literature and clinical expert opinion. Cost and resource utilization were evaluated for the 6 months prior to end of claims follow-up. Baseline variables, resource utilization, and costs were compared between cohorts with univariate statistical tests. Adjusted relative risks were calculated for resource utilization measures. A covariate-adjusted generalized linear model evaluated 6-month total healthcare costs.

Results: Of the 3,878 females included, 18.5% (n?=?718) met the criteria for EOL. Mean observational time (MBC onset to end of claims follow-up) was shorter for the EOL cohort (EOL, 32 months vs NEOL, 35 months; p?p?2 times higher in the EOL cohort (p?Conclusions: Potential EOL presented a greater economic burden in the 6 months prior to death. EOL month-to-month costs increased precipitously in the last 2 months of life and were driven by acute inpatient care.     

The cost-effectiveness of disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis

Background: The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs.

Aims: To compare the cost-effectiveness of current DMTs for patients with RRMS in the US.

Materials and methods: A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e.g. relapses, disease progression) and costs of natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20?mg daily), and subcutaneous interferon beta-1a (IFN, 44?mcg), respectively, over 10 years. RRMS and secondary-progressive MS (SPMS) EDSS state transitions were predicted in 3-month cycles in which patients were at risk of death, relapse, or discontinuation. Upon DMT discontinuation, natural history progression and relapse rates were applied. Incremental cost-effectiveness ratios (ICERs) were estimated for the cost per relapse avoided, relapse-free years gained, progression avoided, and progression-free years gained. The impact of model parameters on outcomes was evaluated via one-way sensitivity analyses.

Results: Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs. Variability in drug costs and parameters that affected drug cost accrual (e.g. discontinuation rates and the decision to drop out after SPMS conversion) had a considerable impact on ICERs.

Limitations: Several simplifying assumptions were made that may represent potential limitations of this analysis (e.g. a constant treatment effect over time was assumed).

Conclusions: The results from this analysis suggest that the NTZ, DMF, and PEG are cost-effective DMT choices compared to FIN, GA, and IFN, respectively. The actual impact on a particular plan will vary based on drug pricing and other factors affecting drug cost accrual.     

Glatiramer acetate and interferon beta-1a for intramuscular administration: a study of outcomes among multiple sclerosis intent-to-treat and persistent-use cohorts

Abstract

Objective:

To study outcomes of multiple sclerosis (MS) patients treated with either glatiramer acetate (Copaxone) or interferon beta-1a for once-weekly, intramuscular administration (Avonex).

Methods:

An ‘intent-to-treat’ (ITT) cohort (n?=?1282) was established, consisting of patients diagnosed with MS who began therapy on either glatiramer acetate (GA) or intramuscular interferon beta-1a (IFN beta-1a-IM) and had continuous insurance coverage from 6 months before to 24 months after the date when they began taking the medication. A ‘persistent use’ (PU) cohort (n?=?639) was also constructed, consisting of individuals who, in addition to the criteria listed above, had a claim for GA or IFN beta-1a-IM within 28 days of the end of the 2-year post-period. Data were obtained from the i3 InVision Data Mart Database from July 2001 to June 2006. Multivariate regressions were used to examine both the 2-year total direct medical costs and the likelihood of relapse associated with the use of each of these alternative MS medications. A relapse was defined as either being hospitalized with a principal diagnosis of MS or having an outpatient visit with a MS diagnosis followed within 7 days by a claim for a corticosteroid. All regressions controlled a wide range of factors that may potentially affect outcomes.

Results:

In the ITT cohort, patients who started therapy on GA had a significantly lower 2-year risk of relapse (10.01 vs. 5.18%; p?=?0.0034) as well as significantly lower 2-year total medical costs ($44,201 vs. $41,121; p?=?0.0294). In the PU cohort, patients who used GA also had a significantly lower 2-year risk of relapse (7.25 vs. 2.16%; p?=?0.0048) as well as significantly lower total medical costs ($67,744 vs. 63,714; p?=?0.0445).

Limitations:

The analyses relies on an administrative claims database of an insured population and hence, may not be generalizeable to other populations. In addition, such a database precludes measurement of lost work time, unemployment, caregiver burden or other costs associated with MS.

Conclusions:

Results from this study indicate that the use of GA is associated with significantly lower probability of relapse as well as significantly lower 2-year total direct medical costs than IFN beta-1a-IM.     

Cost-effectiveness analysis of glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis

SUMMARY

We have developed an economic model around the patient level data from the pivotal clinical trial for Copaxone® (glatiramer acetate), combined with published cost and natural history data, to demonstrate cost-effectiveness in relapsing-remitting multiple sclerosis (RRMS). Based upon analysis over 8 years, the cost per relapse avoided and cost per disability unit avoided was £11,000 and £8,862 respectively. To facilitate comparison with other therapies and across other disease areas we also calculated the cost per quality adjusted life year (QALY). Dependent upon the assumed utility loss associated with duration of relapse, the cost per QALY ranged between £22,586 and £64,636 over 8 years analysis. Given the nature of the disease and compared to accepted standards of cost-effectiveness in the UK, this analysis shows that glatiramer acetate is demonstrably cost-effective versus best supportive care alone.

Copaxone is a registered trademark of Teva Pharmaceutical Industries, Israel     

A discrete event simulation to model the cost-utility of fingolimod and natalizumab in rapidly evolving severe relapsing-remitting multiple sclerosis in the UK

Objective: Two disease-modifying therapies are licensed in the EU for use in rapidly-evolving severe (RES) relapsing-remitting multiple sclerosis (RRMS), fingolimod and natalizumab. Here a discrete event simulation (DES) model to analyze the cost-effectiveness of natalizumab and fingolimod in the RES population, from the perspective of the National Health Service (NHS) in the UK, is reported.

Methods: A DES model was developed to track individual RES patients, based on Expanded Disability Status Scale scores. Individual patient characteristics were taken from the RES sub-groups of the pivotal trials for fingolimod. Utility data were in line with previous models. Published costs were inflated to NHS cost year 2015. Owing to the confidential patient access scheme (PAS) discount applied to fingolimod in the UK, a range of discount levels were applied to the fingolimod list price, to capture the likelihood of natalizumab being cost-effective in a real-world setting.

Results: At the lower National Institute of Health and Care Excellence (NICE) threshold of £20,000/quality-adjusted life year (QALY), fingolimod only required a discount greater than 0.8% of list price to be cost-effective. At the upper threshold of £30,000/QALY employed by the NICE, fingolimod was cost-effective if the confidential discount is greater than 2.5%. Sensitivity analyses conducted using fingolimod list-price showed the model to be most sensitive to changes in the cost of each drug, particularly fingolimod.

Conclusions: The DES model shows that only a modest discount to the UK fingolimod list-price is required to make fingolimod a more cost-effective option than natalizumab in RES RRMS.     

Exploring the variability of patient costs in disease management programs: a hierarchical modelling approach

Disease management programs include a wide variation of patients with different chronic diseases and different health care utilization. The aim of this article was to identify factors on patient-level and organizational-level that explain the variability in costs of patients with different chronic diseases enrolled in a DMP by employing a rigorous analytical model. A generalized linear mixed model (GLMM) was specified to perform a multi-level analysis of cross-sectional hierarchical data from 16 DMPs in the Netherlands. Multiple imputation, sub-group analysis per disease and analysis from both the health care and the societal perspectives were also performed. Our model showed that age, the presence of cardiovascular disease, multi-morbidity and payments on top of the payment for the usual care had positive relation with costs, while better quality of life was associated with lower health care costs. In the COPD sample, physical activity and employment were associated with health care costs. Our study showed that there is great variability in health care costs among patients included in DMPs and identified patient and organizational explanatory factors. The findings are relevant to the design of future DMPs and their payment schemes.     

Kidney involvement in tuberous sclerosis complex: the impact on healthcare resource use and costs

Abstract

Objective:

Tuberous sclerosis complex (TSC) is associated with non-malignant kidney lesions—angiomyolipomata—that may be associated with chronic kidney disease (CKD). This study investigated the relationship between renal angiomyolipomata and CKD in TSC, including the impact on healthcare resource utilization (HCRU) and costs.     

Health-related quality of life,work productivity and costs related to patients with inflammatory bowel disease in Austria

Abstract

Objective

Inflammatory-Bowel-Disease (IBD) is a lifelong illness with significant impact on health-related quality of life (HRQoL). The disease-burden causes work productivity impairment, such as sick-leave and restriction of leisure time activities. From a societal perspective, productivity loss often contributes significantly to the total costs. The aim of the study is to analyze the impact of disease-burden on work productivity, daily activities, and HRQoL.     

A cost utility model of interferon beta-1b in the treatment of relapsing-remitting multiple sclerosis

SUMMARY

This study estimates the long-term cost effectiveness of Betaferon®, (interferon beta-1b) in the treatment of relapsing-remitting multiple sclerosis (RRMS). Clinical trial data, natural disease history information, and costs and quality of life (EQ-5D) data, are linked using disease severity levels, via a model that accounts for the number, severity and duration of relapses, and the probability and speed of disease progression. Previous attempts at modeling the cost effectiveness of beta interferon have produced very estimates of costs per QALY gained (CQG). Increasing data availability enables the modification or replacement of many of the assumptions underlying these models. In particular, longer term modeling and the consideration of wider societal costs is appropriate in the context of this chronic disease. The evidence presented here provides much lower, and more precise, estimates of CQG. The base case 20-year model estimates a CQG of £8,100. These new estimates are in line with other recent estimates and demonstrate the cost effectiveness of beta interferon.