Structural equation modeling for identifying the drivers of health-related quality of life improvement experienced by patients with migraine receiving eptinezumab.

BACKGROUND: As new migraine therapies emerge, it is crucial for measures to capture the complexities of health-related quality of life (HRQoL) improvement beyond improvements in monthly migraine day (MMD) reduction. Investigations into the correlations between MMD reduction, symptom management, and HRQoL are lacking, particularly those that focus on improvements in canonical symptoms and improvement in patient-identified most-bothersome symptoms (PI-MBS), in patients treated with eptinezumab. This exploratory analysis identified efficacy measures mediating the effect of eptinezumab on HRQoL improvements in patients with migraine. METHODS: Data from the DELIVER study of patients with 2-4 prior preventive migraine treatment failures (NCT04418765) were inputted to two structural equation models describing sources of HRQoL improvement via Migraine-Specific Quality-of-Life Questionnaire (MSQ) scores. A single latent variable was defined to represent HRQoL and describe the sources of HRQoL in DELIVER. One model included all migraine symptoms while the second model included the PI-MBS as the only migraine symptom. Mediating variables capturing different aspects of efficacy included MMDs, other canonical symptoms, and PI-MBS. RESULTS: In the first model, reductions in MMDs and other canonical symptoms accounted for 35% (standardized effect size [SES] - 0.11) and 25% (SES - 0.08) of HRQoL improvement, respectively, with 41% (SES - 0.13) of improvement comprising "direct treatment effect," i.e., unexplained by mediators. In the second model, substantial HRQoL improvement with eptinezumab (86%; SES - 0.26) is due to MMD reduction (17%; SES - 0.05) and change in PI-MBS (69%; SES - 0.21). CONCLUSIONS: Improvements in HRQoL experienced by patients treated with eptinezumab can be substantially explained by its effect on migraine frequency and PI-MBS. Therefore, in addition to MMD reduction, healthcare providers should discuss PI-MBS improvements, since this may impact HRQoL. Health technology policymakers should consider implications of these findings in economic evaluation, as they point to alternative measurement of quality-adjusted life years to capture fully treatment benefits in cost-utility analyses. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT04418765 ; EudraCT (Identifier: 2019-004497-25; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004497-25 ).

People get ready! A new generation of Alzheimer's therapies may require new ways to deliver and pay for healthcare.

The development of disease-modifying therapies (DMTs) for Alzheimer's disease (AD) has progressed over the last decade, and the first-ever therapies with potential to slow the progression of disease are approved in the United States. AD DMTs could provide life-changing opportunities for people living with this disease, as well as for their caregivers. They could also ease some of the immense societal and economic burden of dementia. However, AD DMTs also come with major challenges due to the large unmet medical need, high prevalence of AD, new costs related to diagnosis, treatment and monitoring, and uncertainty in the therapies' actual clinical value. This perspective article discusses, from the broad perspective of various health systems and stakeholders, how we can overcome these challenges and improve society's readiness for AD DMTs. We propose that innovative payment models such as performance-based payments, in combination with learning healthcare systems, could be the way forward to enable timely patient access to treatments, improve accuracy of cost-effectiveness evaluations and overcome budgetary barriers. Other important considerations include the need for identification of key drivers of patient value, the relevance of different economic perspectives (i.e. healthcare vs. societal) and ethical questions in terms of treatment eligibility criteria.

Estimating the Product Lifecycle Value of Trastuzumab Based on Registry Data in Sweden.

BACKGROUND AND OBJECTIVE: Trastuzumab was introduced in Sweden in 2000 for treatment of HER2-positive metastatic breast cancer (MBC) and later expanded to early breast cancer (EBC). The potential value of this innovative therapy was explored in economic evaluations; however, the extent to which these benefits were realised remains unknown. This study aims to estimate the lifecycle value of trastuzumab by combining randomised trial data with Swedish routine-care data. METHODS: Trastuzumab impact on costs and health outcomes was estimated with Markov models for MBC and EBC. Model inputs included progression/recurrence and breast cancer-related mortality data from international randomised clinical trials, and Sweden-specific non-breast cancer-related mortality, numbers treated, and costs and utilities based on data from National Registries and literature. Model predictions were validated by observed survival rates from the National Breast Cancer Registry. RESULTS: From 2000 to 2021, 3936 and 11,134 patients with HER2-positive MBC and EBC, respectively, were treated with trastuzumab, resulting in 25,844 life years and 13,436 per quality-adjusted life years (QALY) gained. Cost per QALY gained was lower in EBC (Swedish krona [SEK] 285,000/QALY) than MBC (SEK 554,000/QALY). The net-monetary value delivered (excluding drug costs) was SEK 13.714 billion, and society retained 62% of this. The modelled survival in trastuzumab-treated patients with EBC matched closely with actually observed survival in registry data. CONCLUSION: Trastuzumab provided substantial population-level health benefits for patients and society, with favourable cost effectiveness in MBC and EBC. There is some uncertainty around the magnitude of these benefits, mainly due to missing data on health outcomes and number of treated patients with MBC.

Effect of mortality in cost-effectiveness modeling of disease-modifying treatment for Alzheimer's disease.

INTRODUCTION: We examined (1) the magnitude of mortality attributed to Alzheimer's disease (AD), and (2) the effect of mortality in cost-effectiveness modeling of hypothetical disease-modifying treatment (DMT) in AD. METHOD: Data were derived from Swedish Dementia Registry (N = 39,308). Mortality was analyzed with survival analysis and multinomial logistic regression. A Markov microsimulation model was used to model the cost effectiveness of DMT using routine care as a comparator. Three scenarios were simulated: (1) indirect effect, (2) no effect on overall mortality, (3) indirect effect on AD-related mortality. RESULTS: Overall mortality increased with cognitive decline, age, male sex, number of medications used, and lower body mass index. Nearly all cause-specific mortality was associated with cognitive decline. DMT increased survival by 0.35 years in scenario 1 and 0.14 years in scenario 3. DMT with no mortality effect is the least cost effective. DISCUSSION: The results provide key mortality estimates and demonstrate influences on the cost effectiveness of DMT. Highlights: We describe cause-specific mortality in relation to disease severity in Alzheimer's disease (AD).We model different assumptions of disease-modifying treatment (DMT) on AD survival.DMT was the least cost effective when assuming no effect on AD survival.Cost effectiveness is mainly influenced by the relative cost of staying in each disease state.

The value of maintaining cognition in patients with mild cognitive impairment: The innovation headroom and potential cost-effectiveness of roflumilast.

INTRODUCTION: Early health-technology assessment can support discussing scarce resource allocation among stakeholders. We explored the value of maintaining cognition in patients with mild cognitive impairment (MCI) by estimating: (1) the innovation headroom and (2) the potential cost effectiveness of roflumilast treatment in this population. METHODS: The innovation headroom was operationalized by a fictive 100% efficacious treatment effect, and the roflumilast effect on memory word learning test was assumed to be associated with 7% relative risk reduction of dementia onset. Both were compared to Dutch setting usual care using the adapted International Pharmaco-Economic Collaboration on Alzheimer's Disease (IPECAD) open-source model. RESULTS: The total innovation headroom expressed as net health benefit was 4.2 (95% bootstrap interval: 2.9-5.7) quality-adjusted life years (QALYs). The potential cost effectiveness of roflumilast was k€34 per QALY. DISCUSSION: The innovation headroom in MCI is substantial. Although the potential cost effectiveness of roflumilast treatment is uncertain, further research on its effect on dementia onset is likely valuable.

The worldwide costs of dementia in 2019.

INTRODUCTION: Dementia is a leading cause of death and disability globally. Estimating total societal costs demonstrates the wide impact of dementia and its main direct and indirect economic components. METHODS: We constructed a global cost model for dementia, presenting costs as cumulated global and regional costs. RESULTS: In 2019, the annual global societal costs of dementia were estimated at US $1313.4 billion for 55.2 million people with dementia, corresponding to US $23,796 per person with dementia. Of the total, US $213.2 billion (16%) were direct medical costs, US $448.7 billion (34%) direct social sector costs (including long-term care), and US $651.4 billion (50%) costs of informal care. DISCUSSION: The huge costs of dementia worldwide place enormous strains on care systems and families alike. Although most people with dementia live in low- and middle-income countries, highest total and per-person costs are seen in high-income countries. HIGHLIGHTS: Global economic costs of dementia were estimated to reach US $1313.4 in 2019. Sixty-one percent of people with dementia live in low-and middle-income countries, whereas 74% of the costs occur in high-income countries. The impact of informal care accounts for about 50% of the global costs. The development of a long-term care infrastructure is a great challenge for low-and middle-income countries. There is a great need for more cost studies, particularly in low- and middle-income countries. Discussions of a framework for global cost comparisons are needed.

The Costs of Dementia in Europe: An Updated Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: The prevalence of dementia is increasing, while new opportunities for diagnosing, treating and possibly preventing Alzheimer's disease and other dementia disorders are placing focus on the need for accurate estimates of costs in dementia. Considerable methodological heterogeneity creates challenges for synthesising the existing literature. This study aimed to estimate the costs for persons with dementia in Europe, disaggregated into cost components and informative patient subgroups. METHODS: We conducted an updated literature review searching PubMed, Embase and Web of Science for studies published from 2008 to July 2021 reporting empirically based cost estimates for persons with dementia in European countries. We excluded highly selective or otherwise biased reports, and used a random-effects meta-analysis to produce estimates of mean costs of care across five European regions. RESULTS: Based on 113 studies from 17 European countries, the estimated mean costs for all patients by region were highest in the British Isles (73,712 EUR), followed by the Nordics (43,767 EUR), Southern (35,866 EUR), Western (38,249 EUR), and Eastern Europe and Baltics (7938 EUR). Costs increased with disease severity, and the distribution of costs over informal and formal care followed a North-South gradient with Southern Europe being most reliant on informal care. CONCLUSIONS: To our knowledge, this study represents the most extensive meta-analysis of the cost for persons with dementia in Europe to date. Though there is considerable heterogeneity across studies, much of this is explained by identifiable factors. Further standardisation of methodology for capturing resource utilisation data may further improve comparability of future studies. The cost estimates presented here may be of value for cost-of-illness studies and economic evaluations of novel diagnostic technologies and therapies for Alzheimer's disease.

Cost-effectiveness models for Alzheimer's disease and related dementias: IPECAD modeling workshop cross-comparison challenge.

INTRODUCTION: The credibility of model-based economic evaluations of Alzheimer's disease (AD) interventions is central to appropriate decision-making in a policy context. We report on the International PharmacoEconomic Collaboration on Alzheimer's Disease (IPECAD) Modeling Workshop Challenge. METHODS: Two common benchmark scenarios, for the hypothetical treatment of AD mild cognitive impairment (MCI) and mild dementia, were developed jointly by 29 participants. Model outcomes were summarized, and cross-comparisons were discussed during a structured workshop. RESULTS: A broad concordance was established among participants. Mean 10-year restricted survival and time in MCI in the control group ranged across 10 MCI models from 6.7 to 9.5 years and 3.4 to 5.6 years, respectively; and across 4 mild dementia models from 5.4 to 7.9 years (survival) and 1.5 to 4.2 years (mild dementia). DISCUSSION: The model comparison increased our understanding of methods, data used, and disease progression. We established a collaboration framework to assess cost-effectiveness outcomes, an important step toward transparent and credible AD models.

Health economic modeling for Alzheimer's disease: Expert perspectives.

The successful development of an economic model for the evaluation of future Alzheimer's disease (AD) interventions is critical to accurately inform policy makers and payers. As our understanding of AD expands, this becomes an increasingly complex and challenging goal. Advances in diagnostic techniques for AD and the prospect of disease-modifying treatments raise an urgent need to define specifications for future economic models and to ensure that the necessary data to populate them are available. This Perspective article provides expert opinions from health economists and governmental agency representatives on how future economic models for AD might be structured, validated, and reported. We aim to stimulate much-needed discussion about the detailed specification of future health economic models for AD.

Dementia prevention: The potential long-term cost-effectiveness of the FINGER prevention program.

INTRODUCTION: The aim of this study was to estimate the potential cost-effectiveness of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) program. METHODS: A life-time Markov model with societal perspective, simulating a cohort of people at risk of dementia reflecting usual care and the FINGER program. RESULTS: Costs were 1,653,275 and 1,635,346 SEK and quality-adjusted life years (QALYs) were 8.636 and 8.679 for usual care and the FINGER program, respectively, resulting in savings of 16,928 SEK (2023 US$) and 0.043 QALY gains per person, supporting extended dominance for the FINGER program. A total of 1623 dementia cases were avoided with 0.17 fewer person-years living with dementia. The sensitivity analysis confirmed the conclusions in most scenarios. DISCUSSION: The model provides support that programs like FINGER have the potential to be cost-effective in preventing dementia. Results at the individual level are rather modest, but the societal benefits can be substantial because of the large potential target population.

Costs of Inpatient Rehabilitation for Ischemic Stroke in Patients with Dementia: A Cohort Swedish Register-Based Study.

BACKGROUND: Stroke and dementia are frequent comorbidities. Dementia possibly increases total costs of stroke care, especially cost of institutionalization and informal medical care. However, stroke rehabilitation costs in dementia patients are understudied. OBJECTIVE: To estimate inpatient stroke rehabilitation costs for Swedish dementia patients in comparison with non-dementia patients. METHODS: A longitudinal cohort study with linked data from the Swedish Dementia Register and the Swedish Stroke Register was conducted. Patients diagnosed with dementia who suffered a first ischemic stroke between 2010 and 2014 (n = 138) were compared with non-dementia patients (n = 935). Cost analyses were conducted from a Swedish health care perspective. The difference of rehabilitation costs between the two groups was examined via simple linear regression (before and after matching by propensity scores of dementia) and multiple linear regression. RESULTS: Mean inpatient rehabilitation costs for dementia and non-dementia patients were SEK 103,693/$11,932 and SEK 130,057/$14,966, respectively (median SEK 92,183/$10,607 and SEK 106,365/$12,239) (p = 0.001). Dementia patients suffered from more comorbidities and experienced lower functioning, compared to non-dementia patients. The inpatient rehabilitation cost for patients with known dementia was 0.84 times the cost in non-dementia individuals. CONCLUSION: Dementia diagnosis was significantly associated with lower inpatient stroke rehabilitation costs. This might be explained by physicians' beliefs on the limited effectiveness of rehabilitation in dementia patients. Further research on cost-effectiveness of stroke rehabilitation and patients' satisfaction with stroke rehabilitation is necessary.

Assessing cost-effectiveness of early intervention in Alzheimer's disease: An open-source modeling framework.

INTRODUCTION: We develop a framework to model disease progression across Alzheimer's disease (AD) and to assess the cost-effectiveness of future disease-modifying therapies (DMTs) for people with mild cognitive impairment (MCI) due to AD. METHODS: Using data from the US National Alzheimer's Coordinating Center, we apply survival analysis to estimate transition from predementia to AD dementia and ordered probit regression to estimate transitions across AD dementia stages. We investigate the cost-effectiveness of a hypothetical treatment scenario for people in MCI due to AD. RESULTS: We present an open-access model-based decision-analytic framework. Assuming a modest DMT treatment effect in MCI, we predict extended life expectancy and a reduction in time with AD dementia. DISCUSSION: Any future DMT for AD is expected to pose significant economic challenges across all health-care systems, and decision-analytic modeling will be required to assess costs and outcomes. Further developments are needed to inform these health policy considerations.

Technology-Enabled Assessment of Functional Health.

The maturation of pervasive computing technologies has dramatically altered the face of healthcare. With the introduction of mobile devices, body area networks, and embedded computing systems, care providers can use continuous, ecologically valid information to overcome geographic and temporal barriers and thus provide more effective and timely health assessments. In this paper, we review recent technological developments that can be harnessed to replicate, enhance, or create methods for assessment of functional performance. Enabling technologies in wearable sensors, ambient sensors, mobile technologies, and virtual reality make it possible to quantify real-time functional performance and changes in cognitive health. These technologies, their uses for functional health assessment, and their challenges for adoption are presented in this paper.

Empowering aspects for healthy food and physical activity habits: adolescents' experiences of a school-based intervention in a disadvantaged urban community.

PURPOSE: This study aimed to describe adolescents' experiences of participating in a health-promoting school-based intervention regarding food and physical activity, with a focus on empowering aspects. Method: The school was located in a urban disadvantaged community in Sweden, characterized by poorer self-reported health and lower life expectancy than the municipality average. Focus group interviews with adolescents (29 girls, 20 boys, 14-15 years) and their teachers (n = 4) were conducted two years after intervention. Data were categorized using qualitative content analysis. RESULTS: A theme was generated, intersecting with all the categories: Gaining control over one's health: deciding, trying, and practicing together, in new ways, using reflective tools. The adolescents appreciated influencing the components of the intervention and collaborating with peers in active learning activities such as practicing sports and preparing meals. They also reported acquiring new health information, that trying new activities was inspiring, and the use of pedometers and photo-food diaries helped them reflect on their health behaviours. The adolescents' experiences were also echoed by their teachers. Conclusions: To facilitate empowerment and stimulate learning, health-promotion interventions targeting adolescents could enable active learning activities in groups, by using visualizing tools to facilitate self-reflection, and allowing adolescents to influence intervention activities.

Facilitators of Physical Activity: Voices of Adolescents in a Disadvantaged Community.

Despite increasing socioeconomic inequalities in the health and well-being of adolescents, the voices of adolescents in disadvantaged communities regarding facilitators of physical activity (PA) have received relatively little attention. In response, the purpose of this study was to illuminate what adolescents in a multicultural community of low socioeconomic status (SES) in Sweden convey concerning facilitators of PA. Adolescents (n = 53, aged 12-13 years) were recruited from a school in a multicultural community of low SES in Sweden. Following an interpretive approach, 10 focus group interviews were conducted to produce data for a qualitative content analysis. When the adolescents mentioned PA, they mostly referred to spontaneous PA rather than organized PA, and expressed that they enjoyed their PA engagement, which they stated was promoted by the variation of PA, available options for PA, their physical skills, and the presence of peers. They reported that social support from family and friends facilitated their PA, and they offered several suggestions regarding how the school environment could better support their PA. From the perspective of self-determination theory (SDT), the results stress the importance of facilitating intrinsic motivation with a supportive PA environment in which adolescents can satisfy their needs for autonomy, competence, and relatedness.

The worldwide costs of dementia 2015 and comparisons with 2010.

INTRODUCTION: In 2010, Alzheimer's Disease International presented estimates of the global cost of illness (COI) of dementia. Since then, new studies have been conducted, and the number of people with dementia has increased. Here, we present an update of the global cost estimates. METHODS: This is a societal, prevalence-based global COI study. RESULTS: The worldwide costs of dementia were estimated at United States (US) $818 billion in 2015, an increase of 35% since 2010; 86% of the costs occur in high-income countries. Costs of informal care and the direct costs of social care still contribute similar proportions of total costs, whereas the costs in the medical sector are much lower. The threshold of US $1 trillion will be crossed by 2018. DISCUSSION: Worldwide costs of dementia are enormous and still inequitably distributed. The increase in costs arises from increases in numbers of people with dementia and in increases in per person costs.