Tenosynovial Giant Cell Tumor Observational Platform Project (TOPP) Registry: A 2-Year Analysis of Patient-Reported Outcomes and Treatment Strategies.

BACKGROUND: The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that -previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies. MATERIAL AND METHODS: TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and -Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment). RESULTS: A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy -(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year -follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained -Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy. CONCLUSION: These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088).

A prospective real-world study of the diffuse-type tenosynovial giant cell tumor patient journey: A 2-year observational analysis.

BACKGROUND AND OBJECTIVES: Diffuse-tenosynovial giant cell tumor (D-TGCT) is a rare, locally aggressive, typically benign neoplasm affecting mainly large joints, representing a wide clinical spectrum. We provide a picture of the treatment journey of D-TGCT patients as a 2-year observational follow-up. METHODS: The TGCT Observational Platform Project registry was a multinational, multicenter, prospective observational study at tertiary sarcoma centers spanning seven European countries and two US sites. Histologically confirmed D-TGCT patients were categorized as either those who remained on initial treatment strategy (determined at baseline visit) or those who changed treatment strategy with specific changes documented (e.g., systemic treatment to surgery) at the 1-year and/or 2-year follow-up visits. RESULTS: A total of 176 patients were assessed, mean diagnosis age was 38.4 (SD ± 14.6) years; most patients had a knee tumor (120/176, 68.2%). For the 2-year observation period, most patients (75.5%) remained on the baseline treatment strategy throughout, 54/79 patients (68.4%) remained no treatment, 30/45 patients (66.7%) remained systemic treatment, 39/39 patients (100%) remained surgery. Those who changed treatment strategy utilized multimodal treatment options. CONCLUSIONS: This is the first prospectively collected analysis to describe D-TGCT patient treatments over an extended follow-up and demonstrates the need for multidisciplinary teams to determine an optimal treatment strategy.

Assessing the Effect of Including Social Costs in Economic Evaluations of Diabetes-Related Interventions: A Systematic Review.

BACKGROUND: The economic burden of diabetes from a societal perspective is well documented in the cost-of-illness literature. However, the effect of considering social costs in the results and conclusions of economic evaluations of diabetes-related interventions remains unknown. OBJECTIVE: To investigate whether the inclusion of social costs (productivity losses and/or informal care) might change the results and conclusions of economic evaluations of diabetes-related interventions. METHODS: A systematic review was designed and launched on Medline and the Cost-Effectiveness Analysis Registry from the University of Tufts, from the year 2000 until 2018. Included studies had to fulfil the following criteria: i) being an original study published in a scientific journal, ii) being an economic evaluation of an intervention on diabetes, iii) including social costs, iv) being written in English, v) using quality-adjusted life years as outcome, and vi) separating the results according to the perspective applied. RESULTS: From the 691 records identified, 47 studies (6.8%) were selected. Productivity losses were included in 45 of the selected articles (73% used the human capital approach) whereas informal care costs in only 13 (when stated, the opportunity cost method was used in seven studies and the replacement cost in one). The 47 studies resulted in 110 economic evaluation estimations. The inclusion of social costs changed the conclusions in 8 estimations (17%), 6 of them switching from not cost-effective from the healthcare perspective to cost-effective or dominant from the societal perspective. Considering social costs altered the results from cost-effective to dominant in 9 estimations (19%). CONCLUSION: When social costs are considered, the results and conclusions of economic evaluations performed in diabetes-related interventions can alter. Wide methodological variations have been observed, which limit the comparability of studies and advocate for the inclusion of a wider perspective via the consideration of social costs in economic evaluations and methodological guidelines relating to their estimation and valuation.

The diffuse-type tenosynovial giant cell tumor (dt-TGCT) patient journey: a prospective multicenter study.

BACKGROUND: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive neoplasm arising from the synovium of joints, bursae, and tendon sheaths affecting small and large joints. It represents a wide spectrum ranging from minimally symptomatic to massively debilitating. Most findings to date are mainly from small, retrospective case series, and thus the morbidity and actual impact of this rare disease remain to be elucidated. This study prospectively explores the management of TGCT in tertiary sarcoma centers. METHODS: The TGCT Observational Platform Project registry was a multinational, multicenter, prospective observational study involving 12 tertiary sarcoma centers in 7 European countries, and 2 US sites. This study enrolled for 2 years all consecutive ≥ 18 years old patients, with histologically diagnosed primary or recurrent cases of diffuse-type TGCT. Patient demographic and clinical characteristics were collected at baseline and every 6 months for 24 months. Quality of life questionnaires (PROMIS-PF and EQ-5D) were also administered at the same time-points. Here we report baseline patient characteristics. RESULTS: 166 patients were enrolled between November 2016 and March 2019. Baseline characteristics were: mean age 44 years (mean age at disease onset: 39 years), 139/166 (83.7%) had prior treatment, 71/166 patients (42.8%) had ≥ 1 recurrence after treatment of their primary tumor, 76/136 (55.9%) visited a medical specialist ≥ 5 times, 66/116 (56.9%) missed work in the 24 months prior to baseline, and 17/166 (11.6%) changed employment status or retired prematurely due to disease burden. Prior treatment consisted of surgery (i.e., arthroscopic, open synovectomy) (128/166; 77.1%) and systemic treatments (52/166; 31.3%) with imatinib (19/52; 36.5%) or pexidartinib (27/52; 51.9%). Treatment strategies at baseline visits consisted mainly of watchful waiting (81/166; 48.8%), surgery (41/166; 24.7%), or targeted systemic therapy (37/166; 22.3%). Patients indicated for treatment reported more impairment compared to patients indicated for watchful waiting: worst stiffness NRS 5.16/3.44, worst pain NRS 6.13/5.03, PROMIS-PF 39.48/43.85, and EQ-5D VAS 66.54/71.85. CONCLUSION: This study confirms that diffuse-type TGCT can highly impact quality of life. A prospective observational registry in rare disease is feasible and can be a tool to collect curated-population reflective data in orphan diseases. Name of registry: Tenosynovial Giant Cell Tumors (TGCT) Observational Platform Project (TOPP). TRIAL REGISTRATION NUMBER: NCT02948088. Date of registration: 10 October 2016. URL of Trial registry record: https://clinicaltrials.gov/ct2/show/NCT02948088?term=NCT02948088&draw=2 .

Can the Consideration of Societal Costs Change the Recommendation of Economic Evaluations in the Field of Rare Diseases? An Empirical Analysis.

OBJECTIVES: To analyze whether the adoption of a societal perspective would alter the results and conclusions of economic evaluations for rare disease-related healthcare technologies. METHODS: A search strategy involving all the active substances considered as orphan drugs by the European Medicines Agency plus a list of 76 rare diseases combined with economic-related terms was conducted on Medline and the Cost-Effectiveness Registry from the beginning of 2000 until November 2018. We included studies that considered quality-adjusted life years as an outcome, were published in a scientific journal, were written in English, included informal care costs or productivity losses, and separated the results according to the applied perspective. RESULTS: We found 14 articles that fulfilled the inclusion criteria. Productivity losses were considered in 12 studies, the human capital approach being the method most frequently used. Exclusively, informal care was considered in 2 articles, being valued through the opportunity cost method. The 14 articles selected resulted in 26 economic evaluation estimations, from which incremental cost-utility ratio values changed from cost-effective to dominant in 3 estimates, but the consideration of societal costs only modified the authors' conclusion in 1 study. CONCLUSIONS: The presence of societal costs in the economic evaluation of rare diseases did not affect the conclusions of the studies except in a single specific case. In those studies where the societal perspective was considered, we did not find significant changes in the economic evaluation results due to the higher costs of treatments and the low quality-adjusted life-years gained.

The Burden of Spinal Muscular Atrophy on Informal Caregivers.

Spinal muscular atrophy (SMA) is one of the most common severe hereditary diseases of infancy and early childhood. The progression of this illness causes a high degree of disability; hence, a significant burden is experienced by individuals with this disease and their families. We analyzed the time taken to care for patients suffering from SMA in European countries and the burden on their informal caregivers. We designed a cross-sectional study recording data from France, Germany, Spain and the United Kingdom. The primary caregivers completed a self-administered questionnaire that included questions about the time of care, The Zarit Burden Interview, type of SMA and socio-demographic characteristics. Multivariate analyses were used to study the associations between the type of SMA, time of care and burden supported by informal caregivers. The caregivers provided 10.0 h (SD = 6.7) per day of care (the principal caregivers provided 6.9 h, SD = 4.6). The informal caregivers of patients with type I SMA had a 36.3 point higher likelihood (p < 0.05) of providing more than 10 h of care per day in comparison with caregivers of patients with type III SMA. The severity of the disease was associated with more time of care and a higher burden on the caregivers.

Considering the societal perspective in economic evaluations: a systematic review in the case of depression.

BACKGROUND: Depressive disorders are associated with a high burden of disease. However, due to the burden posed by the disease on not only the sufferers, but also on their relatives, there is an ongoing debate about which costs to include and, hence, which perspective should be applied. Therefore, the aim of this paper was to examine whether the change between healthcare payer and societal perspective leads to different conclusions of cost-utility analyses in the case of depression. METHODS: A systematic literature search was conducted to identify economic evaluations of interventions in depression, launched on Medline and the Cost-Effectiveness Registry of the Tufts University using a ten-year time horizon (2008-2018). In a two-stepped screening process, cost-utility studies were selected by means of specified inclusion and exclusion criteria. Subsequently, relevant findings was extracted and, if not fully stated, calculated by the authors of this work. RESULTS: Overall, 53 articles with 92 complete economic evaluations, reporting costs from healthcare payer/provider and societal perspective, were identified. More precisely, 22 estimations (24%) changed their results regarding the cost-effectiveness quadrant when the societal perspective was included. Furthermore, 5% of the ICURs resulted in cost-effectiveness regarding the chosen threshold (2% of them became dominant) when societal costs were included. However, another four estimations (4%) showed the opposite result: these interventions were no longer cost-effective after the inclusion of societal costs. CONCLUSIONS: Summarising the disparities in results and applied methods, the results show that societal costs might alter the conclusions in cost-utility analyses. Hence, the relevance of the perspectives chosen should be taken into account when carrying out an economic evaluation. This systematic review demonstrates that the results of economic evaluations can be affected by different methods available for estimating non-healthcare costs.

The Economic Impact and Health-Related Quality of Life of Spinal Muscular Atrophy. An Analysis across Europe.

Background: this study aimed to estimate the economic impact and health-related quality of life (HRQOL) of patients with spinal muscular atrophy (SMA) in three European countries. It was used a cross-sectional study carried out in France, Germany, and the United Kingdom. Data were collected from July 2015 to November 2015. Healthcare costs (hospitalizations, emergencies, medical tests, drugs used, visits to general practitioners (GPs) and specialists, medical material and healthcare transport), and non-healthcare costs (social services and informal care) were identified and valued. EuroQol instruments, the Zarit interview, and the Barthel Index were also used to reflect the burden and the social impact of the disease beyond the cost of healthcare. Results: we included 86 children with SMA, 26.7% of them had Type I, and 73.3% Type II or III. The annual average cost associated with SMA reaches €54,295 in the UK, €32,042 in France and €51,983 in Germany. The direct non-healthcare costs ranged between 79-86% of the total cost and the informal care costs were the main component of these costs. Additionally, people suffering from this disease have a very low health-related quality of life, and there are large differences between countries. Conclusions: SMA has a high socioeconomic impact in terms of healthcare and social costs. It was also observed that the HRQOL of affected children was extremely reduced. The figures shown in this study may help to design more efficient and equitable policies, with special emphasis on the support provided to the families or on non-healthcare aid.

What attributes should be included in a discrete choice experiment related to health technologies? A systematic literature review.

Discrete choice experiments (DCEs) are a way to assess priority-setting in health care provision. This approach allows for the evaluation of individuals' preferences as a means of adding criteria to traditional quality-adjusted life year analysis. The aim of this systematic literature review was to identify attributes for designing a DCE in order to then develop and validate a framework that supports decision-making on health technologies. Our systematic literature review replicated the methods and search terms used by de Bekker-Grob et al. 2012 and Clark et al. 2014. The Medline database was searched for articles dated between 2008 and 2015. The search was limited to studies in English that reflected general preferences and were choice-based, published as full-text articles and related to health technologies. This study included 72 papers, 52% of which focused on DCEs on drug treatments. The average number of attributes used in all included DCE studies was 5.74 (SD 1.98). The most frequently used attributes in these DCEs were improvements in health (78%), side effects (57%) and cost of treatment (53%). Other, less frequently used attributes included waiting time for treatment or duration of treatment (25%), severity of disease (7%) and value for money (4%). The attributes identified might inform future DCE surveys designed to study societal preferences regarding health technologies in order to better inform decisions in health technology assessment.

Using a stated preference discrete choice experiment to assess societal value from the perspective of patients with rare diseases in Italy.

BACKGROUND: Decision makers have huge problems when attempting to attribute social value to the improvements achieved by new drugs, especially when considering the use of orphan drugs for rare diseases. We present the results of a pilot study aimed to investigate patient preferences regarding public funding for drugs used to treat rare diseases. METHODS: An online questionnaire was used as a discrete choice experiment (DCE) survey to explore the preferences of patients with cystic fibrosis and haemophilia in Italy. The questionnaire focused on relevant issues that were defined in a review of the literature. A conditional logistic model showed preferences for specific attributes. RESULTS: A total of 54 questionnaires (20% response rate) were completed. The issues that received the greatest attention were improvement in health, treatment cost and value for money. However, disease severity and the availability of other treatments were important social values that could not be ignored. CONCLUSIONS: The findings presented here provide evidence as to what patients with cystic fibrosis or haemophilia think are the most important considerations on which to base decisions in health technology scenarios, and regarding the priorities for funding.

Health-related quality of life in type 1 diabetes mellitus pediatric patients and their caregivers in Spain: an observational cross-sectional study.

Objectives: This study assessed the health-related quality of life (HRQOL) of pediatric patients with type 1 diabetes mellitus (T1DM) and their caregivers.Methods: CHRYSTAL was an observational cross-sectional study conducted in Spain in 2014 on 275 patients under 18 years old diagnosed with T1DM. Patient/caregiver pairs were stratified by patients' HbA1c level (≥7.5% versus <7.5%) and by presence or absence of T1DM complications and/or comorbidities. EQ-5D and PedsQL questionnaires were administered to patients and caregivers.Results: On the EQ-5D, according to caregivers' perception, 17.7% of children experienced moderate pain or discomfort, 9.7% suffered problems performing usual activities, and 13.2% demonstrated moderate anxiety or depression. Mean EQ-5D index score was 0.95 and mean visual analog scale (VAS) score was 86.1. By HbA1c level (≥7.5% versus <7.5%), mean index scores were 0.94 and 0.95, and mean VAS scores were 82.8 and 89.2, respectively. Mean index scores were 0.91 for children with complications and/or comorbidities and 0.96 for children without. Mean VAS scores were 83.7 and 87.2, respectively. HRQOL per the PedsQL tool ranged from 68.1 (ages 2-4) to 73.1 (ages 13-18). EQ-5D index and VAS scores were significantly correlated (rho = 0.29-0.43) with several age groups of the PedsQL. EQ-5D scales showed significant moderate correlation between EQ-5D-Y and EQ-5D-3L proxy VAS score (rho = 0.45; p < .001).Conclusions: Patients with few complications and controlled HbA1c reported a relatively high HRQOL. The results suggest that parent-proxy EQ-5D ratings are valid for use as part of an overall health outcomes assessment in clinical studies of T1DM in pediatric patients.

Social/economic costs and health-related quality of life in patients with spinal muscular atrophy (SMA) in Spain.

BACKGROUND: The aim of this study was to determine the economic burden and health-related quality of life (HRQOL) of patients with Spinal Muscular Atrophy (SMA) and their caregivers in Spain. METHODS: This was a cross-sectional and retrospective study of patients diagnosed with SMA in Spain. We adopted a bottom up, prevalence approach design to study patients with SMA. The patient's caregivers completed an anonymous questionnaire regarding their socio-demographic characteristics, use of healthcare services and non-healthcare services. Costs were estimated from a societal perspective (including healthcare costs and non-healthcare costs), and health-related quality of life (HRQOL) was assessed using the EQ-5D questionnaire. The main caregivers also answered a questionnaire on their characteristics and on their HRQOL. RESULTS: A total of 81 caregivers of patients with different subtypes of SMA completed the questionnaire. Based on the reference unitary prices for 2014, the average annual costs per patient were € 33,721. Direct healthcare costs were € 10,882 (representing around 32.3% of the total cost) and the direct non-healthcare costs were € 22,839 (67.7% of the total cost). The mean EQ-5D social tariff score for patients was 0.16, and the mean score of the EQ-5D visual analogue scale was 54. The mean EQ-5D social tariff score for caregivers was 0.49 and their mean score on the EQ-5D visual analogue scale was 69. CONCLUSION: The results highlight the burden that SMA has in terms of costs and decreased HRQOL, not only for patients but also for their caregivers. In particular, the substantial social/economic burden is mostly attributable to the high direct non-healthcare costs.

Social economic costs of type 1 diabetes mellitus in pediatric patients in Spain: CHRYSTAL observational study.

AIMS: To estimate the social-economic costs of Type 1 Diabetes Mellitus (T1DM) in patients aged 0-17years in Spain from a social perspective. METHODS: We conducted a cross-sectional observational study in 2014 of 275 T1DM pediatric outpatients distributed across 12 public health centers in Spain. Data on demographic and clinical characteristics, healthcare utilization and informal care were collected from medical records and questionnaires completed by clinicians and patients' caregivers. RESULTS: A valid sample of 249 individuals was analyzed. The average annual cost for a T1DM patient was €27,274. Direct healthcare costs were €4070 and direct non-healthcare cost were €23,204. Informal (familial) care represented 83% of total cost, followed by medical material (8%), outpatient and primary care visits (3.1%) and insulin (2.1%). Direct healthcare cost per patient statistically differed by glycated haemoglobin (HbA1c) level [mean cost €4704 in HbA1c ≥7.5% (≥58mmol/mol) group vs. €3616 in HbA1c<7.5% (<58mmol/mol) group)]; and by the presence or absence of complications and comorbidities (mean cost €5713 in group with complications or comorbidities vs. €3636 in group without complications or comorbidities). CONCLUSIONS: T1DM amongst pediatric patients incurs in considerable societal costs. Informal care represents the largest cost category.

Pharmaceutical regulation in 15 European countries review.

In the context of pharmaceutical care, policy-makers repeatedly face the challenge of balancing patient access to effective medicines with affordability and rising costs. With the aim of guiding the health policy discourse towards questions that are important to actual and potential patients, this study investigates a broad range of regulatory measures, spanning marketing authorization to generic substitution and resulting price levels in a sample of 16 European health systems (Austria, Belgium, Denmark, England, Finland, France, Germany, Greece, Ireland, Italy, the Netherlands, Poland, Portugal, Scotland, Spain and Sweden). All countries employ a mix of regulatory mechanisms to contain pharmaceutical expenditure and ensure quality and efficiency in pharmaceutical care, albeit with varying configurations and rigour. This variation also influences the extent of publicly financed pharmaceutical costs. Overall, observed differences in pharmaceutical expenditure should be interpreted in conjunction with the differing volume and composition of consumption and price levels, as well as dispensation practices and their impact on measurement of pharmaceutical costs. No definitive evidence has yet been produced on the effects of different cost-containment measures on patient outcomes. Depending on the foremost policy concerns in each country, different levers will have to be used to enable the delivery of appropriate care at affordable prices.

Socioeconomic costs and health-related quality of life in juvenile idiopathic arthritis: a cost-of-illness study in the United Kingdom.

BACKGROUND: Juvenile idiopathic arthritis (JIA) refers to a number of rare chronic inflammatory diseases. Although JIA imposes a significant societal burden, limited data are available on the cost of JIA. The study's objective is to quantify the socioeconomic burden of JIA patients in the United Kingdom (UK), along with their health-related quality of life (HRQoL). METHODS: A bottom-up, cross-sectional, cost-of-illness analysis of 23 patients was carried out. To collect data on demographic characteristics, health resource utilization, informal care, productivity losses and HRQoL, questionnaires were administered to and completed by patients or their caregivers. The EuroQol five dimensions (EQ-5D) instrument was used to measure HRQoL. RESULTS: This study found that the average annual cost for a JIA patient was €31,546, with direct health care costs equalling €14,509 (46.0 % of total costs), direct non-health care costs amounting to €8,323 (26.4 %) and productivity losses being €8,715 (27.6 %). This was calculated using unit costs for 2012. The largest expenditures on average were accounted for by early retirement (27.0 %), followed by informal care (24.1 %), medications (21.1 %), outpatient and primary health care visits (13.2 %) and diagnostic tests (7.9 %). Important differences existed between JIA patients in need of caregiver assistance and those with no need (€39,469 vs. €25,452 respectively). Among adult JIA patients, mean EQ-5D index scores and visual analogue scale (VAS) scores were found to be 0.26 and 49.00 respectively; the same scores among caregivers were 0.66 and 67.14 respectively. CONCLUSION: JIA poses a significant cost burden on the UK society. Over half of the total average costs (54 %) are related to non-health care and productivity losses. HRQoL of JIA patients is considerably worse than the UK general population.

Social/economic costs and health-related quality of life in patients with histiocytosis in Europe.

OBJECTIVE: The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with histiocytosis in Europe. METHODS: We conducted a cross-sectional study of patients with histiocytosis from France, Germany, Italy, Spain, Bulgaria, the UK, and Sweden. Data on demographic characteristics, health resource utilisation, informal care, loss of labour productivity and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. RESULTS: A total of 134 patients (35 France, 32 Germany, 30 Italy, 24 Spain, 7 Bulgaria, 4 UK and 2 Sweden) completed the questionnaire. The average annual costs ranged from € 6832 to € 33,283 between countries, the year of reference being 2012. Estimated direct healthcare costs ranged from € 1698 to € 18,213; direct nonhealthcare costs ranged from € 2936 to € 17,622 and labour productivity losses ranged from € 1 to € 8855. The mean EQ-5D score for adult histiocytosis patients was estimated at between 0.32 and 0.85, and the mean EQ-5D visual analogue scale score was estimated at between 50.00 and 66.50. CONCLUSION: The main strengths of this study lie in our bottom-up approach to costing and in the evaluation of histiocytosis patients from a broad perspective (societal costs). This type of analysis is very scarce in international literature for rare diseases in comparison with other illnesses. We conclude that histiocytosis patients incur considerable societal costs and experience substantial deterioration in HRQOL.

Social/economic costs and health-related quality of life in patients with cystic fibrosis in Europe.

OBJECTIVES: Our goal was to provide data on the economic burden and health-related quality of life (HRQOL) of patients with cystic fibrosis (CF) and their caregivers in Europe. METHODS: A cross-sectional study was carried out on adults and children with CF in eight European countries. Patients completed an anonymous questionnaire regarding their socio-demographic characteristics, use of healthcare services and presence of a caregiver. Costs were calculated with a bottom-up approach using unit costs from each participating country, and HRQOL was assessed using EQ-5D. The principal caregiver also answered a questionnaire on their characteristics, HRQOL and burden. RESULTS: A total of 905 patients with CF was included (399 adults and 506 children). The total average annual cost per patient varied from €21,144 in Bulgaria to €53,256 in Germany. Adults had higher direct healthcare costs than children, but children had much higher informal care costs (P < 0.0001). Total costs increased with patients' level of dependence. In adults, mean utility fell between 0.640 and 0.870, and the visual analogue scale ranged from 46.0 to 69.7. There was no difference in caregiver HRQOL regardless of whether they cared for an adult or a child. However, caregivers who looked after a child had a significantly higher burden (P = 0.0013). CONCLUSIONS: Our study highlights the burden of CF in terms of costs and decreased HRQOL for both patients and their caregivers throughout Europe.

Social/economic costs and quality of life in patients with haemophilia in Europe.

OBJECTIVE: The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with haemophilia in Europe. METHODS: We conducted a cross-sectional study of patients with haemophilia from Bulgaria, France, Germany, Hungary, Italy, Spain Sweden and the UK. Data on demographic characteristics, health resource utilisation, informal care, loss of labour productivity and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. The costs have been estimated from a societal perspective adopting a bottom-up approach. RESULTS: A total of 401 questionnaires were included in the study, of which 339 were collected from patients with haemophilia and 62 from caregivers. The lowest average annual cost per person was reported in Bulgaria (€6,660) and the highest in Germany (€194,490). Our results demonstrate both a large difference from country to country in the average annual cost per patient in 2012 and the driving role of drugs in costs. Drugs represent nearly 90 % of direct healthcare costs in a majority of the countries analysed (Hungary, Italy, Spain and Germany). In Bulgaria, France and Sweden, however, healthcare services (visits, tests and hospitalisations) prevail. Costs are also shown to differ between children and adults. The mean EQ-5D index score for adult patients was 0.69 and mean EQ-5D VAS was 66.6. The mean EQ-5D index score for carers was 0.87 and mean EQ-5D VAS was 75.5. In the disability score, 60 % showed no disability and measuring caregiver burden with the Zarit Index produced an overall mean score of 25.3. CONCLUSION: We have shown that haemophilia is associated with a substantial economic burden and impaired HRQOL. Studies on cost of illness and HRQOL are important for haemophilia as the future of this disease is likely to change with the development of new innovative treatments. The introduction of these treatments will most likely impact future costs related to haemophilia.

Social/economic costs and health-related quality of life in patients with fragile X syndrome in Europe.

OBJECTIVE: To estimate the social/economic costs of fragile X syndrome (FXS) in Europe and to assess the health-related quality of life (HRQOL) of patients and caregivers. METHODS: A cross-sectional study was conducted in a sample of European countries. Patients were recruited through patients' associations. Data on their resource use and absence from the labour market were retrospectively obtained from an online questionnaire. Costs were estimated by a bottom-up approach and the EuroQol-5 Domain (EQ-5D) questionnaire was used to measure patients' and caregivers' HRQOL. RESULTS: Five countries were included in the analysis. The mean annual cost of FXS per patient varied from €4951 in Hungary to €58,862 in Sweden. Direct non-healthcare costs represented the majority of costs in all countries but there were differences in the share incurred by formal and informal care among those costs. Costs were also shown to differ between children and adults. Mean EQ-5D utility score for adult patients varied from 0.52 in France (n = 42) to 0.73 in Hungary (n = 2), while for caregivers this score was consistently inferior to 0.87. CONCLUSION: Our findings underline that, although its prevalence is low, FXS is costly from a societal perspective. They support the development of tailored policies to reduce the consequences of FXS on both patients and their relatives.

Social/economic costs and health-related quality of life of mucopolysaccharidosis patients and their caregivers in Europe.

OBJECTIVES: To assess the health-related quality of life (HRQOL) of patients with mucopolysaccharidosis (MPS) and their caregivers and to quantify the disease-related costs from a societal perspective. METHODS: In the context of a multi-country study of rare diseases (BURQOL-RD project), a cross-sectional survey was performed among MPS patients in seven European countries. Data on demographic characteristics, health resource utilization, informal care, and loss of labor productivity were collected. The EQ-5D, Barthel index (BI), and Zarit burden interview (ZBI) questionnaires were used to assess patients' and their informal caregivers' quality of life, patients' functional ability, and caregivers' burden, respectively. RESULTS: Altogether, 120 patients (children 62 %, females 40 %) and 66 caregivers completed the questionnaire. Patients' mean age was 16.5 years and median age at diagnosis was 3 years. Adult patients' average EQ-5D and EQ VAS scores varied across countries from 0.13 to 0.43 and 30.0 to 62.2, respectively, mean BI was 46.7, and ZBI was 32.7. Mean informal care time was 51.3 h/week. The mean total annual cost per patient (reference year 2012) was €24,520 in Hungary, €25,993 in France, €84,921 in Italy, €94,384 in Spain, and €209,420 in Germany. Costs are also shown to differ between children and adults. Direct costs accounted for most of the costs in all five countries (80, 100, 99, 98, and 93 %, respectively). CONCLUSIONS: MPS patients experience substantial loss of HRQOL and their families take a remarkable part in their care. Although utilization of health and social care resources varies significantly across countries, MPS incurs considerable societal costs in all the countries studied.