Parkinson's disease in Sweden-resource use and costs by severity.

OBJECTIVES: To estimate resource use and costs, including direct and indirect costs, in relation to levels of severity in individuals with Parkinson's disease (PD) in a Swedish setting. MATERIALS AND METHODS: Patients with idiopathic PD registered in the National Parkinson's Disease Patient Registry (PARKreg), with registrations of Hoehn and Yahr (H&Y) and "off time" in the Skåne Region, were included. Annual costs of healthcare contacts, drugs, formal and informal care, and productivity loss associated with PD were estimated using data from PARKreg linked with regional and national healthcare registers between 2013 and 2019. RESULTS: In total, 960 patients and 1324 observations (patient-years) were included. Total average cost per patient-year was SEK 168,982 (EUR 15,958) and ranged from SEK 62,404 (EUR 5893) for H&Y stage I to SEK 1,056,324 (EUR 99,755) in H&Y stage V. The dominating part of total costs for early stages were indirect costs accounting for 50-60% while formal care made up for 55% and 81% of total costs in H&Y IV and V, respectively. Total mean costs for formal care, informal care, and productivity loss also increased with increasing off-time. CONCLUSION: Advanced and late stages of PD are associated with significant societal costs as patients in those stages often require resource-intensive and costly formal care. Thus, there are potential savings to be made, by optimizing the pharmacological and surgical symptomatic treatment of patients with advanced disease.

Distributional consequences of including survivor costs in economic evaluations.

Medical interventions that increase life expectancy of patients result in additional consumption of non-medical goods and services in 'added life years'. This paper focuses on the distributional consequences across socio-economic groups of including these costs in cost effectiveness analysis. In that context, it also highlights the role of remaining quality of life and household economies of scale. Data from a Dutch household spending survey was used to estimate non-medical consumption and household size by age and educational attainment. Estimates of non-medical consumption and household size were combined with life tables to estimate what the impact of including non-medical survivor costs would be on the incremental cost effectiveness ratio (ICER) of preventing a death at a certain age. Results show that including non-medical survivor costs increases estimated ICERs most strongly when interventions are targeted at the higher educated. Adjusting for household size (lower educated people less often live additional life years in multi-person households) and quality of life (lower educated people on average spend added life years in poorer health) mitigates this difference. Ignoring costs of non-medical consumption in economic evaluations implicitly favors interventions targeted at the higher educated and thus potentially amplifies socio-economic inequalities in health.

Practical Guidance for Including Future Costs in Economic Evaluations in The Netherlands: Introducing and Applying PAID 3.0.

OBJECTIVES: A consensus has been reached in The Netherlands that all future medical costs should be included in economic evaluations. Furthermore, internationally, there is the recognition that in countries that adopt a societal perspective estimates of future nonmedical consumption are relevant for decision makers as much as production gains are. The aims of this paper are twofold: (1) to update the tool Practical Application to Include Future Disease Costs (PAID 1.1), based on 2013 data, for the estimation of future unrelated medical costs and introduce future nonmedical consumption costs, further standardizing and facilitating the inclusion of future costs; and (2) to demonstrate how to use the tool in practice, showing the impact of including future unrelated medical costs and future nonmedical consumption in a case-study where a life is hypothetically saved at different ages and 2 additional cases where published studies are updated by including future costs. METHODS: Using the latest published cost of illness data from the year 2017, we model future unrelated medical costs as a function of age, sex, and time to death, which varies per disease. The Household Survey from Centraal Bureau Statistiek is used to estimate future nonmedical consumption by age. RESULTS: The updated incremental cost-effectiveness ratios (ICERs) from the case studies show that including future costs can have a substantial effect on the ICER, possibly affecting choices made by decision makers. CONCLUSION: This article improves upon previous work and provides the first tool for the inclusion of future nonmedical consumption in The Netherlands.

Costs and benefits of early response in the Ebola virus disease outbreak in Sierra Leone.

BACKGROUND: The 2014-2016 Ebola virus disease (EVD) outbreak in West Africa was the largest EVD outbreak recorded, which has triggered calls for investments that would facilitate an even earlier response. This study aims to estimate the costs and health effects of earlier interventions in Sierra Leone. METHODS: A deterministic and a stochastic compartment model describing the EVD outbreak was estimated using a variety of data sources. Costs and Disability-Adjusted Life Years were used to estimate and compare scenarios of earlier interventions. RESULTS: Four weeks earlier interventions would have averted 10,257 (IQR 4353-18,813) cases and 8835 (IQR 3766-16,316) deaths. This implies 456 (IQR 194-841) thousand DALYs and 203 (IQR 87-374) million $US saved. The greatest losses occurred outside the healthcare sector. CONCLUSIONS: Earlier response in an Ebola outbreak saves lives and costs. Investments in healthcare system facilitating such responses are needed and can offer good value for money.

Disease burden attributed to alcohol: How methodological advances in the Global Burden of Disease 2013 study have changed the estimates in Sweden.

AIM: The Global Burden of Disease (GBD) study continuously refines its estimates as new data and methods become available. In the latest iteration of the study, GBD 2013, changes were made related to the disease burden attributed to alcohol. The aim of this study was to briefly present these changes and to compare the disease burden attributed to alcohol in Swedish men and women in 2010 using previous and updated methods. METHODS: In the GBD study, the contribution of alcohol to the burden of disease is estimated by theoretically assessing how much of the disease burden can be avoided by reducing the consumption of alcohol to zero. The updated methods mainly consider improved measurements of alcohol consumption, including less severe alcohol dependence, assigning the most severe injuries and removing the protective effect of drinking on cardiovascular diseases if combined with binge drinking. RESULTS: The overall disease burden attributed to alcohol in 2010 increased by 14% when using the updated methods. Women accounted for this overall increase, mainly because the updated methods led to an overall higher alcohol consumption in women. By contrast, the overall burden decreased in men, one reason being the lower overall alcohol consumption with the new methods. In men, the inclusion of less severe alcohol dependence resulted in a large decrease in the alcohol attributed disease burden. This was, however, evened out to a great extent by the increase in cardiovascular disease and injuries. CONCLUSIONS WHEN USING THE UPDATED GBD METHODS, THE OVERALL DISEASE BURDEN ATTRIBUTED TO ALCOHOL INCREASED IN WOMEN, BUT NOT IN MEN.

Budget impact models for lung cancer interventions: A systematic literature review.

BACKGROUND: Budget impact models (BIMs) forecast the financial implications of adopting new technologies and the potential need for budget reallocation, thus playing a crucial role in reimbursement decisions. Despite the importance of accurate forecasts, studies indicate large discrepancies between estimates and reality. We are developing an artificial intelligence-based clinical decision tool to identify patients with non-small cell lung cancer who are most likely to benefit from immunotherapy. OBJECTIVE: To evaluate the budgetary implications and describe a systematic literature review of published lung cancer BIMs. METHODS: We searched PubMed and EMBASE for studies published between 2010 and 2023 that include BIMs that describe lung cancer interventions. Forward and backward reference searches were performed for all qualifying studies. We extracted author and publication year, country, interventions, disease stages, time horizon, analytical perspective, modeling methods used, types of costs included, sensitivity analyses conducted, and data sources used. We then evaluated adherence to the Professional Society for Health Economics and Pharmacoeconomics Research best-practice guidelines. RESULTS: A total of 25 BIMs were identified, spanning 14 different countries. Model structure could not be ascertained definitively for nearly half of the models. The cost calculator approach was most common among the others. Time horizons ranged from 1 to 5 years, in line with recommendations. Most models compared drugs, 4 compared nondrug interventions, and 7 compared diagnostic technologies. Assumptions about market uptake were poorly documented and poorly motivated. Inclusion of cancer-related costs was rare. Adherence to best practices was variable and did not appear to improve over time. CONCLUSIONS: The number of published BIMs for lung cancer exceeded expectations. There were modest trends toward publication frequency and model quality over time. Our analysis revealed variability across the models, as well as their adherence to best practices, indicating substantial room for improvement. Although none of the models were individually suitable for the purpose of evaluating an artificial intelligence-based treatment selection tool, some models provided valuable insights.

The Relationship between PDQ-8 and Costs in Parkinson's Disease-A Swedish Register-Based Study.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with substantial costs which increase with progression state. However, few studies have investigated the association between costs and health related quality of life. Objectives: To estimate the relationship between costs and health related quality of life, measured by the Parkinson's disease Quality of Life Questionnaire (PDQ)-8 from a societal perspective, partial societal perspective (excluding productivity loss), and a health care perspective. Methods: The Swedish Parkinson's Disease registry was linked to health care data registries to estimate annual costs. A generalized linear model was used to assess the relationship between instrument items and costs. Results: The results suggest that PDQ-8 captures the increase of costs by PD severity, particularly for costs within the broader societal perspective. From the best to worst PDQ-8 quartile, we observed approximately 7-fold increases within the societal perspective (39,400 to 274,300 SEK) and the partial societal perspective (31,800 to 219,400 SEK), and the increase within the health care perspective more than doubled (21,900 to 49,700 SEK). The PDQ-8 dimensions "mobility," "activities of daily living" and "social support" were associated with high costs in all perspectives. Conclusion: Using a disease-specific measure reflecting the patient's perspective, we found an increase of costs with worsening severity of PD, particularly for costs within the broader societal perspective. High costs were associated with not only motor symptoms, but also the dimension "Social support."

Clinical Impression of Severity Index for Parkinson's Disease and Its Association to Health-Related Quality of Life.

Background: Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD) is a simple tool that can easily be used in clinical practice. Few studies have investigated the relationship between health-related quality of life and the CISI-PD. Objective: To analyze the association of CISI-PD scores with those of generic (EQ-5D-5L) and Parkinson's disease (PD) disease-specific (Parkinson's Disease Questionnaire-8 [PDQ-8]) health-related quality of life assessments. Methods: Persons with idiopathic PD in the Swedish Parkinson's Disease registry with simultaneous registrations of CISI-PD and EQ-5D-5L and/or PDQ-8 were included. Correlations with EQ-5D dimensions were analyzed. The relationships between the CISI-PD, EQ-5D-5L, and PDQ-8 were estimated by linear mixed models with random intercept. Results: In the Swedish Parkinson's Disease registry, 3511 registrations, among 2168 persons, fulfilled the inclusion criteria. The dimensions self-care, mobility, and usual activities correlated moderately with the CISI-PD (r s = 0.60, r s = 0.54, r s = 0.57). Weak correlations were found for anxiety/depression and pain/discomfort (r s = 0.39, r s = 0.29) (P values < 0.001). The fitted model included the CISI-PD, age, sex, and time since diagnosis. The CISI-PD had a statistically significant impact on the EQ-5D and PDQ-8 (P values < 0.001). Conclusions: The CISI-PD provides a moderate correlation with the EQ-5D and could possibly be useful as a basis for defining health states in future health economic models and serving as outcomes in managed entry agreements. Nonetheless, the limitation of capturing nonmotor symptoms of the disease remains a shortcoming of clinical instruments, including the CISI-PD.

Impact of age at onset on symptom profiles, treatment characteristics and health-related quality of life in Parkinson's disease.

Parkinson's disease (PD) is typically considered an age-related disease, but the age at disease onset can vary by decades between patients. Aging and aging-associated diseases can affect the movement system independently of PD, and advanced age has previously been proposed to be associated with a more severe PD phenotype with accelerated progression. In this work, we investigated how interactions between PD progression and aging affect a wide range of outcomes related to PD motor and nonmotor symptoms as well as Health Related Quality of Life (HRQoL) and treatment characteristics. This population-based cohort study is based on 1436 PD patients from southern Sweden followed longitudinally for up to approximately 7.5 years from enrollment (3470 visits covering 2285 patient years, average follow-up time 1.7 years). Higher age at onset was generally associated with faster progression of motor symptoms, with a notable exception of dyskinesia and other levodopa-associated motor fluctuations that had less severe trajectories for patients with higher age at onset. Mixed results were observed for emergence of non-motor symptoms, while higher age at onset was generally associated with worse HRQoL trajectories. Accounting for these identified age-associated differences in disease progression could positively impact patient management and drug development efforts.

High risk of developing dementia in Parkinson's disease: a Swedish registry-based study.

Dementia have substantial negative impact on the affected individual, their care partners and society. Persons living with Parkinson's disease (PwP) are also to a large extent living with dementia. The aim of this study is to estimate time to dementia in PD using data from a large quality register with access to baseline clinical and patient reported data merged with Swedish national health registries. Persons with Parkinson's disease in the Swedish Neuro Registries/Parkinson's Disease Swedish PD Registry (PARKreg) in Sweden were included and linked to national health registries and matched by sex and age to controls without PD. Time to dementia was analysed with Cox regression models assuming proportional hazards, with time since diagnosis as the underlying time variable. In this large prospective cohort study, PwP had approximately four times higher risk of developing dementia as compared to age and sex-matched controls, a finding which remained after adjusting for potential confounders. The present results underline the high risk of dementia in PD and further emphasize the importance of developing symptomatic and ultimately disease modifying strategies to counteract this part of the non-motor symptomatology in PD.

Patient Utilities in Health States Based on Hoehn and Yahr and Off-Time in Parkinson's Disease: A Swedish Register-Based Study in 1823 Observations.

BACKGROUND: Cost-effectiveness models in Parkinson's disease often include health states based on Hoehn and Yahr (H&Y) and time in 'off'. Few studies have investigated utilities in these health states. OBJECTIVE: The aim of this study was firstly to explore utilities in health states based on H&Y and off-time, and secondly to investigate to what extent H&Y and off-time correlated with EQ-5D dimensions. METHODS: Patients with idiopathic Parkinson's disease in the National Parkinson's Disease Patient Registry (PARKreg) in Sweden with observations of EQ-5D-3L, H&Y and off-time were included. Correlations with EQ-5D dimensions were analyzed. The relationship between the EQ-5D-3L and H&Y and off-time were estimated by a linear mixed-model with random intercept. RESULTS: Among patients in PARKreg, 1823 observations fulfilled inclusion criteria. The dimensions 'self-care', 'mobility' and 'usual activities' correlated moderately with H&Y (rs = 0.45, rs = 0.46, rs = 0.45). Weak correlations were found for 'anxiety/depression' and 'pain/discomfort' (rs = 0.24, rs = 0.22) (p values < 0.001). All dimensions correlated weakly with off-time. The fitted model included H&Y, time in 'off', and sex. All H&Y stages were found to be significant and had large and monotonous impact on EQ-5D. Off-time was not significant, but improved the model goodness of fit. Predicted values ranged from 0.733 to - 0.106. CONCLUSION: This study provides utilities for health states reflecting the current modeling practice of interventions targeting motor symptoms in Parkinson's disease. Future research should investigate patient utilities in health states that also capture non-motor symptoms of the disease, as the management of and options for treatments targeting these symptoms increases.

Estimating the costs of non-medical consumption in life-years gained for economic evaluations.

Including the costs of non-medical consumption in life years gained in economic evaluations of medical interventions has been controversial. This paper focuses on the estimation of these costs using Dutch data coming from cross-sectional household surveys consisting of 56,569 observations covering the years 1978-2004. We decomposed the costs of consumption into age, period and cohort effects and modelled the non-linear age and cohort patterns of consumption using P-splines. As consumption patterns depend on household composition, we also estimated household size using the same regression modeling strategy. Estimates of non-medical consumption and household size were combined with life tables to estimate the impact of including non-medical survivor costs on an incremental cost-effectiveness ratio (ICER). Results revealed that including non-medical survivor costs substantially increases the ICER, but the effect varies strongly with age. The impact of cohort effects is limited but ignoring household economies of scale results in a significant overestimation of non-medical costs. We conclude that a) ignoring the costs of non-medical consumption results in an underestimation of the costs of life prolonging interventions b) economies of scale within households with respect to consumption should be accounted for when estimating future costs.

Cost-Effectiveness of Canagliflozin Added to Standard of Care for Treating Diabetic Kidney Disease (DKD) in Patients with Type 2 Diabetes Mellitus (T2DM) in England: Estimates Using the CREDEM-DKD Model.

INTRODUCTION: On the basis of reductions in diabetic kidney disease (DKD) progression and major adverse cardiovascular events observed in the landmark CREDENCE trial, canagliflozin 100 mg received an extension to its EU marketing authorisation in July 2020 to include the treatment of DKD in people with type 2 diabetes mellitus (T2DM) making it the first pharmacological therapy to receive regulatory authorisation for treatment of DKD since the RENAAL and IDNT trials in nearly 20 years. Efficient allocation of limited healthcare resources requires evaluation not only of clinical safety and efficacy but also economic consequences. The study aim was to estimate the cost-effectiveness of canagliflozin when added to current standard of care (SoC) versus SoC alone from the perspective of the NHS in England. METHODS: A microsimulation model was developed using patient-level data from CREDENCE, including risk equations for the key clinical outcomes of start of dialysis, hospitalisation for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. DKD progression was modelled using estimated glomerular filtration rate and urinary albumin-to-creatinine ratio evolution equations. Risk for kidney transplant was sourced from UK-specific sources given the near absence of events in CREDENCE. Patient characteristics and treatment effects were sourced from CREDENCE. Unit costs (£2019) and disutility weights were sourced from the literature and discounted at 3.5% annually. The time horizon was 10 years in the base case, and sensitivity analysis was performed. RESULTS: Canagliflozin was associated with sizable gains in life-years and quality-adjusted life-year (QALYs) over 10 years, with gains increasing with simulation duration. Cost offsets associated with reductions in cardiovascular and renal complications were sufficient to achieve overall net cost savings. The findings were generally confirmed in the sensitivity analyses. CONCLUSION: Model results suggest that adding canagliflozin 100 mg to SoC can improve patient outcomes while reducing overall net costs from the NHS perspective in England. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02065791.

Costs and benefits of interventions aimed at major infectious disease threats: lessons from the literature.

Pandemics and major outbreaks have the potential to cause large health losses and major economic costs. To prioritize between preventive and responsive interventions, it is important to understand the costs and health losses interventions may prevent. We review the literature, investigating the type of studies performed, the costs and benefits included, and the methods employed against perceived major outbreak threats. We searched PubMed and SCOPUS for studies concerning the outbreaks of SARS in 2003, H5N1 in 2003, H1N1 in 2009, Cholera in Haiti in 2010, MERS-CoV in 2013, H7N9 in 2013, and Ebola in West-Africa in 2014. We screened titles and abstracts of papers, and subsequently examined remaining full-text papers. Data were extracted according to a pre-constructed protocol. We included 34 studies of which the majority evaluated interventions related to the H1N1 outbreak in a high-income setting. Most interventions concerned pharmaceuticals. Included costs and benefits, as well as the methods applied, varied substantially between studies. Most studies used a short time horizon and did not include future costs and benefits. We found substantial variation in the included elements and methods used. Policymakers need to be aware of this and the bias toward high-income countries and pharmaceutical interventions, which hampers generalizability. More standardization of included elements, methodology, and reporting would improve economic evaluations and their usefulness for policy.