Search

Background: Multiple sclerosis (MS) is a chronic autoimmune/neurodegenerative disease associated with progressing disability affecting mostly women. We aim to estimate transition probabilities describing MS-related disability progression from no disability to severe disability. Transition probabilities are a vital input for health economics models. In MS, this is particularly relevant for pharmaceutical agency reimbursement decisions for disease-modifying therapies (DMTs)., Methods: Data were obtained from Australian participants of the MSBase registry. We used a four-state continuous-time Markov model to describe how people with MS transition between disability milestones defined by the Expanded Disability Status Scale (scale 0-10): no disability (EDSS of 0.0), mild (EDSS of 1.0-3.5), moderate (EDSS of 4.0-6.0), and severe (EDSS of 6.5-9.5). Model covariates included sex, DMT usage, MS-phenotype, and disease duration, and analysis of covariate groups were also conducted. All data were recorded by the treating neurologist., Results: A total of N = 6369 participants (mean age 42.5 years, 75.00% female) with 38,837 person-years of follow-up and 54,570 clinical reviews were identified for the study. Annual transition probabilities included: remaining in the no, mild, moderate, and severe states (54.24%, 82.02%, 69.86%, 77.83% respectively) and transitioning from no to mild (42.31%), mild to moderate (11.38%), and moderate to severe (9.41%). Secondary-progressive MS was associated with a 150.9% increase in the hazard of disability progression versus relapsing-remitting MS., Conclusions: People with MS have an approximately 45% probability of transitioning from the no disability state after one year, with people with progressive MS transitioning from this health state at a much higher rate. These transition probabilities will be applied in a publicly available health economics simulation model for Australia and similar populations, intended to support reimbursement of a plethora of existing and upcoming interventions including medications to reduce progression of MS., Competing Interests: Declarations. Funding: Open Access funding enabled and organized by CAUL and its Member Institutions. This study was supported by Dr Julie Campbell’s MS Australia Research Fellowship number 19-0702 and the Australian Government, Medical Research Future Fund, emerging priorities in consumer driven research, EPCD000008. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Conflicts of interest: All authors declare that they have no conflict of interest Author contributions: Concept and Design: Campbell, Henson, Fuh Ngw, Ahmad, Palmer; acquisition of data: Campbell, Fuh Ngwa, Palmer, Taylor, Ahmad; analysis and interpretation of data: Campbell, Henson, Fuh Ngwa, Taylor, van der Mei, Palmer; drafting of the manuscript: Campbell and Henson; critical revision of the paper for important intellectual content: all authors; provision of study materials or patients: Taylor and MSBase Australian Researchers; obtaining funding: Campbell, Taylor, van der Mei, Palmer; administrative, technical or logistical support: Fuh Ngwa; supervision: Campbell, Taylor, van der Mei, Palmer. Ethics approvals: The use of MSBase as a research platform was approved by the Melbourne Health Human Research Ethics Committee and by the local ethics committees in all participating centres (or exemptions were granted according to local laws and regulations). Data availability: This study used MSBase registry data. Data approvals for access to the data used for this study can be sought through the corresponding authors who will then liaise with MSBase., (© 2024. The Author(s).)

Objectives: Studies have shown that people living with multiple sclerosis (PwMS) were substantially impacted by the COVID-19 pandemic. However, no study has compared the overall health-related quality of life impact of the COVID-19 pandemic on PwMS and the general population. Differences would have implications for crises/pandemic management policies. This study aimed to compare the prevalence and health-related quality of life impact of COVID-19-related adversity (such as deteriorations in mental or physical health) in PwMS and the general population., Methods: Cross-sectional data were obtained from the How Is Your Life Australian general population study (comprising subsamples with and without chronic disease) and the Australian MS Longitudinal Study from August to October 2020. Health-related quality of life was measured using health state utilities (HSUs; represented on a 0 [death] to 1 [full health] scale) generated by the EQ-5D-5L-Psychosocial. COVID-19-related adversity was measured via specialized survey items. Descriptive and multivariable regression analyses were conducted., Results: A total of 1020 general population individuals and 1635 MS participants entered the study (mean age 52.4 and 58.4; female 52.4% and 80.2%, respectively). COVID-19-related adversity prevalence was higher among PwMS compared to the general population with and without chronic diseases (PR: 1.430 [CI: 1.153, 1.774] and PR: 1.90 [CI: 1.56, 2.32], respectively). However, the HSU impact of COVID-19-related adversity was not dependent on disease status (p > 0.20, test for interaction)., Conclusion: This study found that PwMS were more likely to experience COVID-19-related adversity compared to the general population, though the health-related quality-of-life impact was similar. This demonstrates that PwMS require additional support during national and global crises., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Multiple sclerosis (MS) is a chronic neurological disease that causes substantial health economic impacts, however, the cost of informal care for MS is often excluded from health economic analysis. As a result there is a paucity of information for decision-making. This review aims to summarise, synthesise and where appropriate meta-analyse the global evidence regarding the health economics of informal care for people with MS. The findings will provide consolidated evidence that policymakers and other stakeholders can use to inform decisions, including the development of health economics models. This review was conducted with a pre-determined study protocol (PROSPERO- CRD42023396457). Biomedical and economic databases were searched. Costs were converted to 2022 United States dollars (USD). Mean cost was calculated and pooled with a random-effects model. Subgroup analysis and meta-regression was conducted for stratified variables such as country income level and Expanded Disability Status Scale (EDSS). Of 6,306 identified studies, 61 were retained for narrative synthesis and 50 for meta-analysis. Studies were conducted in 25 countries. Cost information was collected from the person with MS, not the caregiver. 83.6% of studies used the opportunity cost method. Average monthly caregiving time was 60.1 h. Informal care costs accounted for 15% of total societal cost of MS. Pooled mean annual cost of informal care per person was USD $6,308 (95% CI $5,022-7,594). Informal care costs were USD $6,797 and $1,478 in high- and middle-income countries. Costs for mild, moderate, and severe disability of the person with MS were $1,123, $6,643, and $15,855, respectively. Informal care cost contributes considerably to MS-related costs. Despite study heterogeneity, cost of informal care increases with MS-related disability severity, time attributed to care and country income level. These results can be used to inform health economic models for reimbursement decisions for MS. Future studies regarding the health economic burden of informal care should gather the data from the informal carers themselves., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Subjective wellbeing has been defined as an individual's personal appraisal of their quality of life. Subjective wellbeing is associated with positive health behaviours and improved coping abilities. This study aimed to investigate the subjective wellbeing of people living with multiple sclerosis (MS), using the novel Personal Wellbeing Index, and make comparisons with the general population., Methods: Cross-sectional data was obtained from the Australian Multiple Sclerosis Longitudinal Study and the How Is Your Life Australian general population study in August-October 2020. Subjective wellbeing was measured as life satisfaction using the Personal Wellbeing Index. This instrument measures life satisfaction globally and in seven life domains, allowing the importance of domain-specific life satisfaction to be explored. Descriptive and multivariable regression analyses were conducted., Results: One thousand six hundred eighty-three MS and 1,021 general population participants entered the study (mean age 52.4 and 58.6; female 79.9% and 52.4%, respectively). For people living with MS the most important life domains were standard of living and achieving in life. The domain of personal health was more influential for people living with MS (p < 0.01) than the general population. The life domains most susceptible to MS-related disability were personal health, achieving in life, and community connectedness (p < 0.01 for these domains)., Conclusion: Personal health and achieving in life are key domains through which the subjective wellbeing of people living with MS is modified. This study recommends the development of interventions to support healthy perceptions of illness and continued employment as paramount in improving the subjective wellbeing of people living with MS., (© 2024. The Author(s).)

Purpose: People living with multiple sclerosis (PwMS) in metropolitan Victoria, Australia, experienced a 112-day, COVID-19-related lockdown in mid-2020. Contemporaneously, Australian PwMS elsewhere experienced minimal restrictions, resulting in a natural experiment. This study investigated the relationships between lockdowns, COVID-19-related adversity, and health-related quality of life (HRQoL). It also generated health state utilities (HSU) representative of changes in HRQoL., Methods: Data were extracted from Australian MS Longitudinal Study surveys, which included the Assessment of Quality of Life-Eight Dimensions (AQoL-8D) instrument and a COVID-19 questionnaire. This COVID-19 questionnaire required participants to rank their COVID-19-related adversity across seven health dimensions. Ordered probits were used to identify variables contributing to adversity. Linear and logit regressions were applied to determine the impact of adversity on HRQoL, defined using AQoL-8D HSUs. Qualitative data were examined thematically., Results: N = 1666 PwMS (average age 58.5; 79.8% female; consistent with the clinical presentation of MS) entered the study, with n = 367 (22.0%) exposed to the 112-day lockdown. Lockdown exposure and disability severity were strongly associated with higher adversity rankings (p < 0.01). Higher adversity rankings were associated with lower HSUs. Participants reporting major adversity, across measured health dimensions, had a mean HSU 0.161 (p < 0.01) lower than participants reporting no adversity and were more likely (OR: 2.716, p < 0.01) to report a clinically significant HSU reduction. Themes in qualitative data supported quantitative findings., Conclusions: We found that COVID-19-related adversity reduced the HRQoL of PwMS. Our HSU estimates can be used in health economic models to evaluate lockdown cost-effectiveness for people with complex and chronic (mainly neurological) diseases., (© 2024. The Author(s).)

Background: No large-scale qualitative studies have investigated the lived experience of people living with multiple sclerosis (PwMS) during the pandemic according to their disability level. We used qualitative research methods to investigate the lived experience of a large cohort of Australians living with differing multiple sclerosis (MS)-related disability levels during the COVID-19 pandemic. We also provided useful contextualisation to existing quantitative work., Methods: This was a retrospective survey-based mixed-methods cohort study. A quality-of-life study was conducted within the Australian MS Longitudinal Study during the pandemic. Disability severity was calculated using the Patient Determined Disease Steps. Qualitative free-text data regarding COVID-19 impacts was collected/analysed for word frequency and also thematically (inductively/deductively using sophisticated grounded theory) using NVivo software. We also triangulated word frequency with emerging themes., Results: N=509 PwMS participated providing n=22 530 words of COVID-19-specific data. Disability severity could be calculated for n=501 PwMS. The word 'working' was important for PwMS with no disability, and 'support' and 'isolation' for higher disability levels. For PwMS with milder disability, thematic analysis established that multitasking increased stress levels, particularly if working from home (WFH) and home-schooling children. If not multitasking, WFH was beneficial for managing fatigue. PwMS with severe disability raised increased social isolation as a concern including prepandemic isolation., Conclusions: We found negative impacts of multitasking and social isolation for PwMS during the pandemic. WFH was identified as beneficial for some. We recommend targeted resourcing decisions for PwMS in future pandemics including child-care relief and interventions to reduce social isolation and suggest that these could be incorporated into some form of advanced care planning. As the nature of work changes postpandemic, we also recommend a detailed investigation of WFH for PwMS including providing tailored employment assistance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Health state utilities (HSU) are a health-related quality-of-life (HRQoL) input for cost-utility analyses used for resource allocation decisions, including medication reimbursement. New Zealand (NZ) guidelines recommend the EQ-5D instruments; however, the EQ-5D-5L may not sufficiently capture psychosocial health. We evaluated HRQoL among people with multiple sclerosis (MS) in NZ using the EQ-5D-5L and assessed the instrument's discriminatory sensitivity for a NZ MS cohort., Methods: Participants were recruited from the NZ MS Prevalence Study. Participants self-completed a 45-min online survey that included the EQ-5D-5L/EQ-VAS. Disability severity was classified using the Expanded Disability Status Scale (EDSS) to categorise participant disability as mild (EDSS: 0-3.5), moderate (EDSS: 4.0-6.0) and severe (EDSS: 6.5-9.5). Anxiety/depression were also measured using the Hospital Anxiety and Depression Score (HADS). In the absence of an EQ-5D-5L NZ tariff, HSUs were derived using an Australian tariff. We evaluated associations between HSUs and participant characteristics with linear regression models., Results: 254 participants entered the study. Mean age was 55.2 years, 79.5% were female. Mean (SD) EQ-5D-5L HSU was 0.58 (0.33). Mean (SD) HSUs for disability categories were: mild 0.80 ± 0.17, moderate 0.57 ± 0.21 and severe 0.14 ± 0.32. Twelve percent reported HSU = 1.0 (i.e., no problems in any domain). Participants who had never used a disease-modifying therapy reported a lower mean HSU. Multivariable modelling found that the HADS anxiety score was not associated with EQ-5D-5L., Conclusions: HRQoL for people with MS in NZ was lower than comparable countries, including Australia. We suggest a comparison with other generic tools that may have improved sensitivity to mental health., (© 2022. The Author(s).)

Background: Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease of the central nervous system which results in disability over time and reduced quality of life. To increase the sensitivity of the EQ-5D-5L for psychosocial health, four bolt-on items from the AQoL-8D were used to create the nine-item EQ-5D-5L-Psychosocial. We aimed to externally validate the EQ-5D-5L-Psychosocial in a large cohort of people with MS (pwMS) and explore the discriminatory power of the new instrument with EQ-5D-5L/AQoL-8D., Methods: A large representative sample from the Australian MS Longitudinal Study completed the AQoL-8D and EQ-5D-5L (including EQ VAS) and both instruments health state utilities (HSUs) were scored using Australian tariffs. Sociodemographic/clinical data were also collected. External validity of EQ-5D-5L-Psychosocial scoring algorithm was assessed with mean absolute errors (MAE) and Spearman's correlation coefficient. Discriminatory sensitivity was assessed with an examination of ceiling/floor effects, and disability severity classifications., Results: Among 1683 participants (mean age: 58.6 years; 80% female), over half (55%) had moderate or severe disability. MAE (0.063) and the distribution of the prediction error were similar to the original development study. Mean (± standard deviation) HSUs were EQ-5D-5L: 0.58 ± 0.32, EQ-5D-5L-Psychosocial 0.62 ± 0.29, and AQoL-8D: 0.63 ± 0.20. N = 157 (10%) scored perfect health (i.e. HSU = 1.0) on the EQ-5D-5L, but reported a mean HSU of 0.90 on the alternative instruments. The Sleep bolt-on dimension was particularly important for pwMS., Conclusions: The EQ-5D-5L-Psychosocial is more sensitive than the EQ-5D-5L in pwMS whose HSUs approach those reflecting full health. When respondent burden is taken into account, the EQ-5D-5L-Psychosocial is preferential to the AQoL-8D. We suggest a larger confirmatory study comparing all prevalent multi-attribute utility instruments for pwMS., (© 2022. The Author(s).)

Introduction: Generic multiattribute utility instruments (MAUIs) are efficient tools for determining and enumerating health-related quality of life. MAUIs accomplish this by generating health state utilities (HSUs) via algorithms. Minimal important differences (MIDs) assist with the interpretation of HSUs by estimating minimum changes that are clinically significant. The overall goal of the proposed systematic review and meta-analysis is the development of comprehensive guidelines for MID estimation., Methods and Analysis: This protocol defines a systematic review and meta-analysis of MIDs for generic MAUIs. The proposed research will involve a comprehensive investigation of 10 databases (EconLit, IDEAs database, INAHTA database, Medline, PsycINFO, Embase, Emcare, JBIEBP and CINAHL) from 1 June 2022 to 7 June 2022, and will be performed and reported in accordance with several validated guidelines, principally the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The quality of papers, considered for inclusion in the review, will be appraised using the COnsensus-based Standards for the selection of health Measurement INstruments, inter alia.Narrative analysis will involve identifying the characteristics of MIDs including methods of calculation, sources of heterogeneity, and validation. Meta-analysis will also be conducted. The descriptive element of meta-analysis will involve the generation of I 2 statistics and Galbraith plots of MID heterogeneity. Together with narrative analysis, this will allow sources of MID heterogeniety to be identified. A multilevel mixed model, estimated via restricted maximum likelihood estimation, will be constructed for the purposes of meta-regression. Meta-regression will attempt to enumerate the effects of sources of heterogeneity on MID estimates. Meta-analysis will be concluded with pooling of MIDs via a linear random-effects model., Ethics and Dissemination: Ethics approval is not required for this review, as it will aggregate data from published literature. Methods of dissemination will include publication in a peer-reviewed journal, as well as presentation at conferences and seminars., Prospero Registration Number: CRD42021261821., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)