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Health economic consequences of Multiple Sclerosis in Australia

Ahmad, H ORCID: 0000-0002-2580-9856 2021 , 'Health economic consequences of Multiple Sclerosis in Australia', PhD thesis, University of Tasmania.

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Multiple sclerosis (MS) is a complex autoimmune/neurodegenerative disease in which the myelin sheath covering nerve fibres in the central nervous system (brain, optic nerves and spinal cord) is damaged, leading to increasing disability over time, which in turn, negatively impacts individuals’ health-related quality of life (HRQoL) and poses a significant economic burden to patients and society in terms of both direct (healthcare) and indirect costs (from lost productivity). Whilst some past studies have investigated the HRQoL and costs of MS in Australia, the studies suffered from methodological limitations and/or relied on data that are now more than a decade old and lacked information that are important to the detailed, comprehensive and contemporary health economic analyses of MS. Additionally, no previous studies in MS-specific disability progression in Australia have been published to document the transition probabilities of changing disability levels (measuring the likelihood of an individual moving from one disability state to another over a discrete period of time).
The current landscape of MS in Australia differs substantially from that at the time of publication of previous studies measuring the human and economic burden for Australians with MS. For example, Australians now have access to a range of higher efficacy and more expensive disease modifying therapies (DMTs) for relapsing-remitting MS, bringing potential impacts on health outcomes for people with MS, and hence, the costs. There is also a strong focus on earlier MS diagnosis (due to application of new diagnostic criteria) and treatment (due to therapeutic advances and growing evidence of the long-term benefits of early effective treatment). All of this may contribute to differences in the health and economic burden of MS over time. Moreover, country-specific health economic evaluation models of available treatment options guide evidence-based reimbursement decisions, with health state utility values (HSUVs), costs and transition probabilities being important inputs to these modelled evaluations. The correct implementation of multi-state health economic evaluation models requires reliable and robust estimation of these input parameters. In order to ensure that health economic evaluation models are representative of reality, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) has recommended the use of model input parameters that are locally derived.
Thus, the estimation of updated key input parameters (i.e.: HSUVs, costs and transition probabilities of disability progression) from an Australian population of people with MS at varying levels of disability severity is needed: 1) to improve our understanding of the key drivers of the health economic burden of MS and MS-related disability progression in Australian and similar populations; and 2) in the ongoing development and refining of a goldstandard health economics model of MS (currently under construction by our research group) for the estimation of life expectancy, quality-adjusted life years, and total lifetime costs, and to identify cost-effective MS interventions (to facilitate policy development, priority setting, advocacy, and management of public health) in Australian and similar populations.
This research thesis (comprised of four key studies) aims to bridge these important research gaps using the best available data (from the Australian Multiple Sclerosis Longitudinal Study [AMSLS], the Tasmanian MS Longitudinal Study [TasMSL] and the Ausimmune Longitudinal Study [AusLong]) and methodological framework. The first analytical study (reported in Chapter 3 of this thesis) presents a comprehensive contemporary analysis of the direct and indirect costs of MS in Australia from a societal perspective and examines how the cost landscape has changed over time. Annual costs per person with MS increased 17% from 2010 to $68,382 in 2017, driven largely by increased direct costs (from $16,306 in 2010 to $30,346 in 2017) (particularly those related to DMTs, hospitalizations, consultations, and medical tests), but offset by decreased costs of lost wages (from $29,030 in 2010 to $21,858 in 2017) as a result of recent positive shifts in the employment landscape for Australians with MS. Costs increased with increasing disability severity: $30,561 (95% confidence interval [CI]: $25,672-$35,451), $55,815 (95%CI: $47,503-$64,126), $76,915 (95%CI: $68,866-$84,964), and $114,813 (95%CI: $102,252- $127,374) for no, mild, moderate and severe disability, respectively. The total costs for all people with MS in Australia in 2017 were $1,751 million, which were $503 million (41%) higher than 2010 costs. Whilst costs did increase significantly from 2010 to 2017, over half ($295 million) of this increase was due to increased prevalence of MS in Australia. The current economic data on MS provided in this chapter are important for policy development, priority setting and public health management, particularly in this new era of increased access to higher efficacy DMTs, early MS diagnosis, and improved management of MS.
The second study (reported in Chapter 4 of this thesis) presents the HRQoL of Australians with MS (in the forms of HSUVs and health dimension scores) using a preferentially sensitive multi-attribute utility instrument (the Assessment of Quality of Life-8-Dimension [AQoL-8D]) and presents the impacts of disability on HRQoL. The mean overall HSUV for Australians with MS was 0.61 (95% CI: 0.60-0.62), 0.18 units lower than the Australian general population norm. HSUV decreased with increasing disability severity: 0.81 (95% CI: 0.80-0.83), 0.65 (95% CI: 0.63-0.67), 0.54 (95% CI: 0.52-0.56) and 0.48 (95% CI: 0.46-0.50) for no, mild, moderate and severe disability, respectively. Lower HRQoL was primarily driven by reduced scores on Independent living, Pain, Relationships, Coping, and Self-worth. These findings suggest that effective pain management and support to maintain independent living, relationships, and self-worth may improve the HRQoL of people with MS. Early diagnosis and affordable access to effective treatments to slow or prevent disability accumulation may also be helpful.
The third study (reported in Chapter 5 of this thesis) examines the differences between progressive-onset MS (PROMS) and relapse-onset MS (ROMS) in relation to HRQoL using the AQoL-8D. The study specifically examines if HSUVs differ significantly between onset types, in which health dimensions the differences are most pronounced, and whether these differences remain when HSUVs were stratified by disability severity. Adjusted mean overall HSUV of PROMS cohort was 0.55, which was 0.07 units lower than that of ROMS cohort. The mean physical and psychological super dimension scores for PROMS participants were 0.51and 0.28, which were 0.07 and 0.06 units lower than for ROMS participants, respectively. For the individual health dimensions, the largest difference between two groups was seen in independent living (0.17 units), followed by relationships (0.07units) and self-worth (0.07 units). However, when we stratified HRQoL estimates by disability severity, the differences between onset types disappeared. Our results suggest that disability severity-specific HSUV estimates based on an overall sample of people with MS equally apply to both onset types, suggesting that we do not need to develop separate HSUV inputs for economic evaluation models of each MS onset type.
The fourth study (reported in Chapter 6 of this thesis) presents the annual probabilities of changing disability levels in Australians with relapsing-remitting MS. We found that a very high proportion of people with MS remained in the same disability states across the course of follow-up (93% no/mild, 91% moderate and 100% severe), indicating that on average, MS progresses slowly. From no/mild disability, 6.4% (95% CI: 4.7-8.4) and 0.1% (0.0-0.2) progressed to moderate and severe disability annually, respectively. From moderate disability, 6.9% (1.0-11.4) improved (to no/mild state) and 2.6% (1.1-4.5) worsened. From severe disability, 0.0% improved to moderate and no/mild disability. Male sex, age at onset, longer disease duration, not using immunotherapies greater than 3 months and a history of relapse were related to higher probabilities of worsening. The probabilities of changing disability levels presented in this chapter will be helpful in health economic evaluation models aimed at predicting long-term disease outcomes and identifying cost-effective MS interventions.
In summary, this thesis presents a range of studies that were conducted to address the substantial knowledge gaps in improving our understanding of the key drivers of the health economic burden of MS and MS-related disability progression in Australian and similar populations. The disability severity-specific estimates of MS-related costs and HSUVs, as well as the probabilities of changing disability levels in MS provided here can be used to populate future health economic models of MS for the estimation of life expectancy, quality-adjusted life years, and total lifetime costs, and to identify cost-effective interventions for the management of MS.

Item Type: Thesis - PhD
Authors/Creators:Ahmad, H
Keywords: Multiple Sclerosis, health economics, cost of illness, health-related quality of life, Australia
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