Projected economic burden of pancreatic cancer in Sweden in 2030.

BACKGROUND: Pancreatic cancer is predicted to become the second most common cause of cancer-related death by 2030. The objective of this study was to estimate the economic burden of pancreatic cancer for the years 2018 and 2030 based on changing demographics and incidence rates in Sweden. METHOD: The incidence of pancreatic cancer in Sweden and additional relevant data were obtained from official statistics. A linear regression model and the mean incidence rates 2008-2018 were applied to calculate the incidence in 2030. An economic model based on the human capital method was created to calculate the indirect cost of pancreatic cancer in 2018 and 2030. Costs associated with surgery, radiology, oncology, and palliative care constituted the direct costs. A sensitivity analysis was performed. RESULTS: The incidence of pancreatic cancer in Sweden in the year 2018 was 1352 patients and projected to between 1554 (+15%) and 1736 (+28%) in 2030. The total cost was calculated to €125 million in 2018 and between €210 million (+68%) and €225 million (+80%) in 2030. The indirect cost in the ≤65-year-old group was €328,344 in 2018 and between €380,738 and €382,109 per individual in 2030. CONCLUSIONS: The economic burden of pancreatic cancer is expected to increase in Sweden by 2030 due to the increasing incidence of the disease and changing demographics. Pancreatic cancer is a growing health care problem in urgent need of advancements in prevention, early detection, treatment, and control of the disease.

Swedish guidelines for device-aided therapies in Parkinson's disease -Economic evaluation and implementation.

OBJECTIVES: The National Board of Health and Welfare in Sweden published the national guidelines for Parkinson's Disease 2016. The aim of this study was to summarize this evidence review and development of the guidelines, focusing on the economic evaluation of device-aided therapies (deep brain stimulation, pump-based infusion of levodopa-carbidopa intestinal gel or apomorphine) for Parkinson's disease, and the rate of implementation after 3 years in Sweden. MATERIAL AND METHODS: The evidence review underlying the guidelines-including systematic literature searches of clinical and economic evidence, model-based economic evaluation, and formal analysis and guideline development-was examined, condensed, and translated. The impact of the guidelines was assessed with treatment use statistics from 2009 to 2019. RESULTS: All device-aided therapies were assigned high priority. Based on a relatively low proportion of device-aided therapies (30%) in Parkinson's disease, a 5-year increase of 500 patients was recommended. This was estimated to reduce total costs by SEK 14 million (€1.7 million). Follow-up data found an increase of 217 patients between 2017 and 2019, following the same trend as before the guidelines. CONCLUSION: Three years after the guidelines were published, the use of device-aided therapies has increased in Sweden, albeit not in pace with recommendations. One reason for slow implementation may be poor incentivization related to budget silos in which the costs for device-aided therapies are borne by the regions but the cost offsets (eg, reduced need for home care) are reaped by local stakeholders.

Dread and Risk Elimination Premium for the Value of a Statistical Life.

The value of a statistical life (VSL) is a widely used measure for the value of mortality risk reduction. As VSL should reflect preferences and attitudes to risk, there are reasons to believe that it varies depending on the type of risk involved. It has been argued that cancer should be considered a "dread disease," which supports the use of a "cancer premium." The objective of this study is to investigate the existence of a cancer premium (for pancreatic cancer and multiple myeloma) in relation to road traffic accidents, sudden cardiac arrest, and amyotrophic lateral sclerosis (ALS). Data were collected from 500 individuals in the Swedish general population of 50-74-year olds using a web-based questionnaire. Preferences were elicited using the contingent valuation method, and a split-sample design was applied to test scale sensitivity. VSL differs significantly between contexts, being highest for ALS and lowest for road traffic accidents. A premium (92-113%) for cancer was found in relation to road traffic accidents. The premium was higher for cancer with a shorter time from diagnosis to death. A premium was also found for sudden cardiac arrest (73%) and ALS (118%) in relation to road traffic accidents. Eliminating risk was associated with a premium of around 20%. This study provides additional evidence that there exist a dread premium and risk elimination premium. These factors should be considered when searching for an appropriate value for economic evaluation and health technology assessment.

Burden and costs of migraine in a Swedish defined patient population - a questionnaire-based study.

BACKGROUND: Migraine is a disabling, chronic neurological disease leading to severe headache episodes affecting 13.2% of the Swedish population. Migraine leads to an extensive socio-economic burden in terms of healthcare costs, reduced workforce and quality of life (QoL) but studies of the health-economic consequences in a Swedish context are lacking. The objective of this study is to map the health-economic consequences of migraine in a defined patient population in terms of healthcare consumption, production loss and QoL in Sweden. METHODS: The study is based on data from a web-based survey to members in the Swedish patients' association suffering from migraine. The survey was conducted in May 2018 and included people with migraine aged 18 years or older. The survey included questions on health resource consumption, lost production resulting from migraine-related absenteeism and presenteeism, and QoL as measured by the EuroQol 5 dimensions questionnaire (EQ-5D-5 L) and the Headache Impact Test (HIT-6). The results are presented in yearly costs per patient and losses in quality adjusted life years (QALYs). RESULTS: The results are based on answers from 630 individuals with migraine and are presented by number of migraine days per month. The total cost per patient and year increased with the number of migraine days per month (p < 0.001) and varied between approximately €5000 for those with less than 3 migraine days per month and €24,000 per year for those with 21-28 migraine days per month. Production loss represented the main part of the costs, approximately 80%. The average loss in QALYs per year also increased with the monthly number of migraine days (p = 0.023). CONCLUSIONS: Migraine leads to significant societal costs and loss of quality of life. There appears to be an unmet need and a potential for both cost savings and QoL benefits connected with a reduction in the number of migraine days.

Intraductal papillary mucinous neoplasms of the pancreas - a cost-effectiveness analysis of management strategies for the branch-duct subtype.

BACKGROUND: Branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) presents a clinical conundrum. Rigorous long-term surveillance or surgical resection is recommended. The economic consequences of the management have not been fully investigated. METHODS: A Markov decision model compared 4 strategies for low-risk BD-IPMN: I = upfront total pancreatectomy, II = upfront partial pancreatectomy, III = initial surveillance, IV = watchful waiting. Surveillance was based on the Swedish Guidelines for Pancreatic Cancer. Probabilities and costs were obtained from the participating unit and from the scientific literature. The incremental cost-effectiveness ratios (ICERs) were calculated and sensitivity analyses were performed by varying relevant parameters. Survival was reported in quality-adjusted life-years (QALYs). RESULTS: Strategy III was the most cost-effective strategy with an ICER of €31 682 compared to strategy IV. Strategy I was the most expensive but yielded the best QALY (9.32). Total number of years, annual risk of pancreatic cancer and annual risk of a low-risk BD-IPMN turning into a high-risk lesion had the greatest impact in the model. CONCLUSIONS: Initial surveillance seems to be the most cost-effective strategy in the management of low-risk asymptomatic BD-IPMN. However, the possibility of personalized approaches remains to be investigated.

Acute biliary pancreatitis: focus on recurrence rate and costs when current guidelines are not complied.

BACKGROUND: International guidelines recommend cholecystectomy within 2-4 weeks after mild to moderate acute biliary pancreatitis (ABP) to prevent recurrence. We aimed to investigate the compliance to guidelines concerning early cholecystectomy and the associated costs. METHODS: Admissions for ABP 2011-2013 were retrospectively reviewed. Classification was made according to the revised Atlanta classification. Treatment, time to surgery and recurrence, as well as cost analysis for both in-hospital costs and loss of production (LOP) were performed. RESULTS: In total, 254 patients were included. Some 202 of the ABP patients (80%) underwent definitive treatment during their first attack of ABP (68% cholecystectomy, 17% endoscopic retrograde cholangiopancreatography (ERCP), 15% both interventions) and 186 (73%) were treated within 1 month of discharge. Patients with ERCP alone were significantly older than cholecystectomy cases (p < .001), but no significant difference was observed between those who underwent ERCP or no treatment (p = .071). Mild ABP had intervention earlier (p < .001). In all, 52 patients (20%) had no intervention, out of which 15 were readmitted due to pancreatitis, compared to 3 patients of those treated at the initial admission (p < .001). The mean cost for hospital care and LOP in mild ABP was €6882 ± 3010 and €9580 ± 7047 for moderate ABP (p = .001). The cost for a recurrent episode was €16,412 ± 22,367. CONCLUSION: By improved compliance to current guidelines concerning the management of ABP, recurrence rate and associated costs can potentially be reduced.

Cost effectiveness of pomalidomide in patients with relapsed and refractory multiple myeloma in Sweden.

BACKGROUND: Multiple myeloma (MM) patients who have progressed following treatment with both bortezomib and lenalidomide have a poor prognosis. In this late stage, other effective alternatives are limited, and patients in Sweden are often left with best supportive care. Pomalidomide is a new anti-angiogenic and immunomodulatory drug for the treatment of MM. Our objective was to evaluate the cost effectiveness of pomalidomide as an add-on to best supportive care in patients with relapsed and refractory MM in Sweden. MATERIAL AND METHODS: We developed a health-economic discrete event simulation model of a patient's course through stable disease and progressive disease, until death. It estimates life expectancy, quality-adjusted life years (QALYs) and costs from a societal perspective. Effectiveness data and utilities were taken from the MM-003 trial comparing pomalidomide plus low-dose dexamethasone with high-dose dexamethasone (HIDEX). Cost data were taken from official Swedish price lists, government sources and literature. RESULTS: The model estimates that, if a patient is treated with HIDEX, life expectancy is 1.12 years and the total cost is SEK 179 976 (€19 100), mainly indirect costs. With pomalidomide plus low-dose dexamethasone, life expectancy is 2.33 years, with a total cost of SEK 767 064 (€81 500), mainly in drug and indirect costs. Compared to HIDEX, pomalidomide treatment gives a QALY gain of 0.7351 and an incremental cost of SEK 587 088 (€62 400) consisting of increased drug costs (59%), incremental indirect costs (33%) and other healthcare costs (8%). The incremental cost-effectiveness ratio is SEK 798 613 (€84 900) per QALY gained. CONCLUSION: In a model of late-stage MM patients with a poor prognosis in the Swedish setting, pomalidomide is associated with a relatively high incremental cost per QALY gained. This model was accepted by the national Swedish reimbursement authority TLV, and pomalidomide was granted reimbursement in Sweden.

Resource use in patients with psoriasis after the introduction of biologics in Sweden.

The introduction of biologics has changed treatment patterns as well as costs in patients with psoriasis. This study was performed to estimate direct and indirect costs of the psoriasis population in Sweden, and to analyse changes in costs between 2006 and 2009. The study population was identified in national registers. Direct costs included health care visits with primary psoriasis diagnoses in specialist care and drugs relevant for treating psoriasis. Productivity loss, including costs of long-term sick leave and disability pension, was estimated as the difference between psoriasis patients and matched controls from the general population. Total direct cost increased from SEK 348 million (~ €39) in 2006 to SEK 459 million (~ €51) in 2009, whereas the total productivity loss decreased from SEK 1,646 (~ €183) to 1,618 million (~ €180) between 2006 and 2009. Although direct costs, especially for biologic agents, have increased for patients with psoriasis over time, this study indicates that costs related to productivity loss are still more substantial.

Core discrete event simulation model for the evaluation of health care technologies in major depressive disorder.

OBJECTIVE: A review of existing economic models in major depressive disorder (MDD) highlighted the need for models with longer time horizons that also account for heterogeneity in treatment pathways between patients. A core discrete event simulation model was developed to estimate health and cost outcomes associated with alternative treatment strategies. METHODS: This model simulated short- and long-term clinical events (partial response, remission, relapse, recovery, and recurrence), adverse events, and treatment changes (titration, switch, addition, and discontinuation) over up to 5 years. Several treatment pathways were defined on the basis of fictitious antidepressants with three levels of efficacy, tolerability, and price (low, medium, and high) from first line to third line. The model was populated with input data from the literature for the UK setting. Model outputs include time in different health states, quality-adjusted life-years (QALYs), and costs from National Health Service and societal perspectives. The codes are open source. RESULTS: Predicted costs and QALYs from this model are within the range of results from previous economic evaluations. The largest cost components from the payer perspective were physician visits and hospitalizations. Key parameters driving the predicted costs and QALYs were utility values, effectiveness, and frequency of physician visits. Differences in QALYs and costs between two strategies with different effectiveness increased approximately twofold when the time horizon increased from 1 to 5 years. CONCLUSION: The discrete event simulation model can provide a more comprehensive evaluation of different therapeutic options in MDD, compared with existing Markov models, and can be used to compare a wide range of health care technologies in various groups of patients with MDD.

The C-terminus of Dpb2 is required for interaction with Pol2 and for cell viability.

DNA polymerase ε (Pol ε) participates in the synthesis of the leading strand during DNA replication in Saccharomyces cerevisiae. Pol ε comprises four subunits: the catalytic subunit, Pol2, and three accessory subunits, Dpb2, Dpb3 and Dpb4. DPB2 is an essential gene with unclear function. A genetic screen was performed in S. cerevisiae to isolate lethal mutations in DPB2. The dpb2-200 allele carried two mutations within the last 13 codons of the open reading frame, one of which resulted in a six amino acid truncation. This truncated Dpb2 subunit was co-expressed with Pol2, Dpb3 and Dpb4 in S. cerevisiae, but this Dpb2 variant did not co-purify with the other Pol ε subunits. This resulted in the purification of a Pol2/Dpb3/Dpb4 complex that possessed high specific activity and high processivity and holoenzyme assays with PCNA, RFC and RPA on a single-primed circular template did not reveal any defects in replication efficiency. In conclusion, the lack of Dpb2 did not appear to have a negative effect on Pol ε activity. Thus, the C-terminal motif of Dpb2 that we have identified may instead be required for Dpb2 to fulfill an essential structural role at the replication origin or at the replication fork.

Costs for stroke in Sweden 2009 and developments since 1997.

OBJECTIVES: The aim of this study was to estimate direct and indirect excess costs attributable to stroke in Sweden in 2009 and to compare these with similar estimates from 1997. METHODS: Data on first-ever stoke admissions in the first half of 2009 from the Swedish national stroke register (RS) were used for cost calculations and compared with results from 1997 also using RS data. A societal perspective was taken including the acute and follow-up phase, rehabilitation, stroke re-admissions, drugs, home- and residential care services for activities of daily life (ADL) support, and indirect costs for premature death and productivity losses (2009 prices). Survival was extrapolated to estimate the lifetime present value cost of stroke. RESULTS: The societal lifetime present value cost for stroke in 2009 was €68,800 per patient (ADL support: 59 percent; productivity losses: 21 percent). Women had higher costs than men in all age groups as a result from greater need for ADL support. Patients treated at a stroke unit indicated low incremental cost per life-year gained compared with those who had not. The total lifetime cost increased between 1997 and 2009. Hospitalization costs per patient were stable, while long-term costs for home- and residential care services increased. CONCLUSIONS: Changes in patient characteristics, longer expected survival, and possibly in the Swedish stroke care, have led to higher annual and lifetime costs per patient in 2009 compared with 1997. A comprehensive national stroke care performance register like RS may be suitable for health economic assessments.

Real-world evidence for coverage determination of treatments for rare diseases.

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

Modelling the benefits of early diagnosis of pancreatic cancer using a biomarker signature.

Pancreatic cancer (PC) has a poor prognosis, with a 5-year survival of 3-4%. This is mainly due to late diagnosis because of diffuse symptoms, where 80-85% of the patients are inoperable. Consequently, early diagnosis would be of significant benefit, resulting in a potential 5-year survival of 30-40%. However, new technologies must be carefully evaluated concerning effectiveness and healthcare costs. We have developed a framework for modelling cost and health effects from early detection of PC, which for the first time allowed us to analyse its cost-effectiveness. A probabilistic cohort model for estimating costs and quality adjusted life-years (QALY) arising from screening for PC, compared to a "wait-and-see"-approach, was designed. The test accuracy, Swedish survival and costs by tumour stage, expected life gain from early detection and pretest probabilities in risk groups, were retrieved from previous investigations. In a cohort of newly diagnosed diabetic patient (incidence 0.71%) the incremental cost per QALY gained (ICER) was €13,500, which is considered cost-effective in Europe. Results were mainly sensitive to the incidence with the ICER ranging from €315 to €204,000 (familial PC 35% and general population 0.046%, respectively). This is the first study focusing on clinical implementation of advanced testing and what is required for novel technologies in cancer care to be cost-effective. The model clearly demonstrated the potential of multiplexed proteomic-testing of PC and also identified the requirements for test accuracy. Consequently, it can serve as a model for assessing the possibilities to introduce advanced test platforms also for other cancer indications.

Acute pancreatitis--costs for healthcare and loss of production.

OBJECTIVE. Severity of acute pancreatitis (AP) can vary from a mild to a fulminant disease with high morbidity and mortality. Cost analysis has, however, hitherto been sparse. The aim of this study was to calculate the cost of acute pancreatitis, both including hospital costs and costs due to loss of production. MATERIAL AND METHODS. All adult patients treated at Skane University Hospital, Lund, during 2009-2010, were included. A severity grading was conducted and cost analysis was performed on an individual basis. RESULTS. Two hundred and fifty-two patients with altogether 307 admissions were identified. Mean age was 60 ± 19 years, and 121 patients (48%) were men. Severe AP (SAP) was diagnosed in 38 patients (12%). Thirteen patients (5%) died. Acute biliary pancreatitis was more costly than alcohol induced AP (p < 0.001). Total costs for treating mild AP (MAP) in patients ≤65 years old was lower (p = 0.001) and costs for SAP was higher (p = 0.024), as compared to older patients. The overall hospital cost and cost for loss of production was per person in mean €5,100 ± 2,400 for MAP and €28,200 ± 38,100 for SAP (p < 0.001). The costs for treating AP during the two-year-long study period were in mean €9,762 ± 19,778 per patient. Extrapolated to a national perspective, the annual financial burden for AP in Sweden would be €38,500,000; corresponding to €4,100,000 per million inhabitants. CONCLUSIONS. The costs of treating AP are high, especially in severe cases with a long ICU stay. These results highlight the need to optimize care and continue the identification and focus on SAP, in order to try to limit organ failure and infectious complications.

A candidate gene approach to ANCA-associated vasculitis reveals links to the C3 and CTLA-4 genes but not to the IL1-Ra and Fcγ-RIIa genes.

BACKGROUND/AIMS: The aim of the study is to search for associations between Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and polymorphisms in the genes of four key molecules possibly involved in different pathogenic pathways; complement C3, CTLA-4, Fcγ-RIIa and IL1-Ra. PATIENTS AND METHODS: Patients with AAV (n=105) subgrouped as microscopic polyangiitis or granulomatosis with polyangiitis (Wegener's granulomatosis) and myeloperoxidase (MPO) or proteinase 3 (PR3) ANCA positive were compared to a control group of 200 blood donors. Polymorphisms in the genes were analysed with PCR amplification of DNA. RESULTS: The diagnosis of AAV was confirmed in the 105 cases. The gene frequency of C3F was 0.27 in the PR3-ANCA subgroup (p=0.041) compared to 0,19 in the control group. The number of patients homozygous for the shortest 86 bp allele of CTLA-4 was significantly decreased in the whole group of patients (p=0.049). No differences were evident in the Fcγ-RIIa and IL1-Ra polymorphisms when compared to controls, neither in the whole group of patients, nor in any of the sub-groups. CONCLUSION: The aberrant gene frequency of the C3F allele among PR3-ANCA positive patients and the findings with the CTLA-4 polymorphism indicates that complement may be involved in pathogenesis and that T-cell activation also is of importance in these diseases.

Cost-effectiveness of specialised manual therapy versus orthopaedic care for musculoskeletal disorders: long-term follow-up and health economic model.

Background: Physiotherapy is usually the first line of treatment for musculoskeletal disorders. If pain persists, an appointment with an orthopaedic surgeon is indicated, but many disorders for which patients are placed on orthopaedic waiting lists cannot be treated in an orthopaedic clinic. Specialised manual therapy, although not mainstream, can be an effective alternative to orthopaedic care, although its cost-effectiveness beyond 12 months is unknown. Objectives: To perform an 8-year follow-up of the quality of life and costs of specialised manual therapy versus standard orthopaedic care for working-age patients with common nonsurgical musculoskeletal disorders referred to orthopaedic surgeons and to develop a health economic model. Design: Cost-effectiveness study using Markov modelling. Methods: The index group of a previously published pragmatic randomised controlled trial received a maximum of five treatment sessions of specialised manual therapy, while the control group received orthopaedic 'care as usual'. At 3, 6, 12 and 96 months, Health-Related Quality of Life and costs were measured with Short Form Health Survey 36, Short Form Health Survey 6D and Diagnostic Related Groups. An incremental cost-effectiveness ratio was calculated, a Markov model was developed and a sensitivity analysis was performed. Results: Overall, 95% (n = 75) of the participants completed the 8-year follow-up. Recovery rates during the first 3 months ('per protocol') in the index and control group were 69% and 58%, respectively. The index group had 0.159 more gains in quality-adjusted life years and cost 40,270 SEK (€4027) less per patient over 8 years. The sensitivity analysis results were consistent with the main results. Conclusion: Specialised manual therapy dominated standard care after 8 years. The results of this small but very first study are promising; therefore, further exploration within other health care professions, clinics and/or countries is required. Our study raises questions about the triaging of orthopaedic outpatients, cost-effectiveness and resource allocation. Registration: Not applicable per the information provided by ClinicalTrials.gov. Plain Language Summary: Specialised manual therapy is more cost-effective than 'care as usual' for working-age patients referred to an orthopaedist. This study provides an 8-year follow-up of the cost effects and quality of life of a previously published trial. Why was this study conducted? The standard care for musculoskeletal pain consists of exercises with a physiotherapist in primary care. If the pain persists, a referral to an orthopaedic clinic is often made. Many of these referrals are inappropriate because they concern pain from muscles and joints that do not benefit from surgery or the resources available in an orthopaedic clinic. There is a gap in competence and treatment between primary and specialised care that is costly, time- and resource-consuming and causes prolonged patient suffering. Although specialised manual therapy (MT) is effective, its use is not mainstream. Costs and effects after more than 12 months of treatment that may shorten waiting lists have never been evaluated. What did the researchers do? Quality of life and costs were compared in 75 patients with nonsurgical disorders referred to orthopaedic surgeons at 8 years after treatment with specialised MT or standard orthopaedic care. A health economics model for the probability of recovery was also developed and tested. What did the researchers find? Compared with the control group, the study participants treated with specialised MT had a better quality of life, required fewer health care interventions, underwent less surgery, incurred significantly lower costs and demonstrated an increased probability of recovery. What do these findings mean? It seems probable that using specialised MT for an old, well-known structural problem may yield better treatment effects at a significantly lower cost. Our study findings suggest that policy recommendations should focus on costs and effects rather than resource utilisation alone. The study is small and requires expansion using its economic health model.

A cross-country comparison of health-related quality of life in the United States, Sweden, and Norway during the first year of the COVID-19 pandemic.

BACKGROUND: Limited studies have directly compared health-related quality of life (HRQoL) in different countries during the COVID-19 global pandemic. The objective of this study was to evaluate the HRQoL outcomes in the US, Sweden, and Norway during the first year under the pandemic. METHODS: In April 2020, during early phase of the pandemic, separately in the US, Sweden, and Norway, we surveyed 2,734, 1,003 and 1,020 respondents, then again in January 2021, we collected 2,252, 1,013 and 1,011 respondents. The survey was first developed in English and translated into Swedish and Norwegian. Selected variables were used for the current study. We collected respondents' HRQoL using the EQ-5D-5L. Respondents' background information included their sociodemographic data, medical history, and COVID-19 status. We reported the EQ-5D-5L utility, EQ-VAS, and the proportion of problems with each of the EQ-5D-5L health subdomains. Population quality-adjusted life year (QALY) changes based on EQ-5D-5L utility scores were also calculated. Outcomes were stratified by age. One-way ANOVA test was used to detect significant differences between countries and Student's t-tests were used to assess the differences between waves. RESULTS: Respectively for the US, Sweden, and Norway, mean EQ-5D-5L utilities were 0.822, 0.768, and 0.808 in April 2020 (p < 0.001); 0.823, 0.783, and 0.777 in January 2021 (p < 0.001); mean EQ-VAS scores were 0.746, 0.687, and 0.692 in April 2020 (p < 0.001), 0.764, 0.682, and 0.678 in January 2021 (p < 0.001). For both waves, EQ-5D-5L utilities and EQ-VAS scores in the US remained higher than both Sweden and Norway (p < 0.001). Norwegians reported considerably lowered HRQoL over time (p < 0.01). Self-reported problems with anxiety/depression were highest for the US and Sweden, while Norwegians reported most problems with pain/discomfort, followed by anxiety/depression. The population QALYs increased in the US and Sweden, but decreased in Norway. CONCLUSIONS: In the first year of the pandemic, a rebound in HRQoL was observed in the US, but not in Sweden or Norway. Mental health issues during the pandemic warrant a major public health concern across all 3 countries.

Valuation of Treatments for Rare Diseases: A Systematic Literature Review of Societal Preference Studies.

INTRODUCTION: We sought to synthesize published empirical studies that elicited and characterized societal valuations of orphan drugs and the attributes that may drive different valuations for orphan drugs versus other treatments. METHODS: We conducted a systematic literature review (SLR) in MEDLINE and EMBASE databases up to November 2, 2020. Search terms covered societal preferences and attributes of orphan drugs (e.g., disease prevalence, severity, burden, unmet needs, and benefits). RESULTS: We identified 38 eligible publications: 33 societal preference studies and 5 reviews discussing societal valuations and attributes of orphan drugs. Most publications suggested that a majority of respondents favored allocating funds to more prevalent diseases. However, trade-off studies and discrete-choice experiments found that survey participants chose to allocate resources to orphan drugs even when the cost per unit of health benefit was greater than for therapies for more prevalent diseases. Overall, 19 of 27 studies assessing severity in treatment valuation revealed that respondents prioritized patients with severe diseases over those with milder ones for equal health benefits. Members of the general public tended to prefer treatments for diseases with no alternative or when existing alternatives had limited efficacy over diseases with clear therapeutic alternatives. There was evidence that individuals preferred sharing resources, so no patient was left without treatment. CONCLUSIONS: Our SLR indicates the general public typically attaches greater value to orphan drugs than to other treatments for common diseases. This is not because of rarity per se, but primarily because of disease severity and lack of therapeutic alternatives typically associated with rare diseases.

Orphan drugs are drugs serving a substantial public health need by treating life-threatening or chronically debilitating medical conditions affecting a small number of people with very high unmet needs. We reviewed 38 published studies looking at drug characteristics that may cause people to value orphan drugs differently versus treatments for common conditions. Most people surveyed in these publications favored health care funds going to more prevalent diseases. However, some people preferred funding orphan drugs even when the cost versus health benefit was higher compared with treatments for more common diseases. The majority of studies that investigated the impact of disease severity on the valuation of treatments found that people prioritized patients with severe disease over those with milder disease, for the same extent of health benefit. People also preferred funding treatments for diseases that have no alternative treatments, or treatments with limited benefits, over treatments for diseases with many treatments or more effective treatments. We also found evidence of a societal preference for shared resources, meaning that no patient would be left without treatment, including those who receive limited benefits from health care resources, even if this does not lead to the maximization of health benefits across society. In conclusion, our literature review indicated that the general public attaches greater value to orphan drugs versus treatments for more common diseases, not because of rarity per se, but largely because the rare diseases treated by orphan drugs are often severe and have no or few treatment options.

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.

Usage and impact of patient-reported outcomes in epilepsy.

BACKGROUND: The use of patient-reported outcomes (PRO) in clinical practice is gaining increasing attention. This study aimed to provide a critical assessment of the current state-of-the-art and beliefs about the use of PRO in the management of people with epilepsy across some European countries. METHODS: Structured interviews were conducted with European experts to collect insights about (I) the personal experience with PRO; (II) the value and impact of PRO in the decision-making process at the national level; and (III) the interest for and use of PRO by national health authorities. RESULTS: Nine neurologists (Austria, Belgium, Czechia, Denmark, France, Greece, Italy, Poland, and United Kingdom), three health economists (Portugal, Romania, and Sweden), and one epidemiologist (Slovakia) participated. They all stated that PRO are collected at their own countries in the context of clinical trials and/or specific projects. During everyday clinical practice, PRO are collected routinely/almost routinely in Austria and Sweden and only at the discretion of the treating physicians in Czechia, Denmark, France, Greece, and Portugal. There was complete consensus about the favorable impact that the PRO can have in terms of clinical outcomes, healthcare resources utilization, and general patient satisfaction. Only participants from Portugal and Sweden answered that the PRO are perceived as very important by the National Health Authorities of their respective countries. CONCLUSIONS: Differences exist in attitudes and perspectives about PRO in epilepsy across Europe. An active plan is warranted to harmonize the measurement of PRO and ensure they can be relevant to people with epilepsy and health services.