Manuel Posada-de-la-Paz

Delphi approach to select rare diseases for a European representative survey. The BURQOL-RD study

OBJECTIVES The BURQOL-RD project is intended to develop a disease based model capable of quantifying the socio-economic burden and health-related quality of life for patients with rare diseases (RDs) and their caregivers in Europe. We described the methodology used to select a set of 10 RDs to be approached in a pilot study. METHODS BURQOL-RD project includes 23 partners from 8 European countries: Spain, UK, France, Germany, Sweden, Italy, Hungary and Bulgaria. A two-round Delphi panels in combination with Carroll diagram was used to generate consensus in the selection of the 10 RDs among the project participants. RESULTS The two Delphi rounds yielded a prioritised list, to which the Carroll diagram was applied, taking into account three determinants: prevalence, availability of effective treatment and need for carer. The final set of RD to be studied was obtained: cystic fibrosis, Prader-Willi syndrome, haemophilia, duchenne muscular dystrophy, epidermolysis bullosa, fragile X syndrome, scleroderma, mucopolysaccharidosis, juvenile idiopathic arthritis and histiocytosis. CONCLUSIONS This methodology permitted the generation of an equilibrated set of RDs for the pilot study of BURQOL-RD project. The model will be suitable for application in a wide range of RDs.

Social economic costs and health-related quality of life in patients with systemic sclerosis in Spain.

Cost‐of‐illness analysis is the main method of providing an overall vision of the economic impact of a disease. Such studies have been used to set priorities for health care policies and inform resource allocation. The aim of this study was to determine the economic burden from a societal perspective and health‐related quality of life (HRQOL) of patients with systemic sclerosis (SSc; scleroderma) in Spain.

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

ObjectiveTo 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.MethodsA 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.ResultsFive 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.ConclusionOur 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 in patients with Prader-Willi syndrome in Europe

ObjectiveThe aim of this study was to determine the economic burden from a societal perspective and health-related quality of life (HRQOL) of patients with Prader-Willi syndrome (PWS) in Europe.MethodsWe conducted a cross-sectional study of patients with PWS from Spain, Bulgaria, Hungary, Germany, Italy, the UK, Sweden and France. Data on demographic characteristics, healthcare resource utilisation, informal care, labour productivity losses and HRQOL were collected from questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire.ResultsA total of 261 patients completed the questionnaire. The average annual costs ranged from € 3937 to € 67,484 between countries; the reference year for unit prices was 2012. Direct healthcare costs ranged from € 311 to € 18,760, direct non-healthcare costs ranged from € 1269 to € 44,035, and loss of labour productivity ranged from € 0 to € 2255. Costs were also shown to differ between children and adults. The mean EQ-5D index score for adult PWS patients ranged between 0.40 and 0.81 and the mean EQ-5D visual analogue scale score ranged between 51.25 and 90.00.ConclusionThe main strengths of this study lie in our bottom-up approach to costing and in the evaluation of PWS patients from a broad societal perspective. This type of analysis is very scarce in the international literature on rare diseases in comparison with other illnesses. We conclude that PWS patients incur considerable societal costs and experience substantial deterioration in HRQOL.

Social/economic costs and health-related quality of life in patients with juvenile idiopathic arthritis in Europe

ObjectiveThe 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 juvenile idiopathic arthritis (JIA) in Europe.MethodsWe conducted a cross-sectional study of patients with JIA from Germany, Italy, Spain, France, the United Kingdom, Bulgaria, and Sweden. Data on demographic characteristics, healthcare resource utilization, informal care, labor productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D-5L) questionnaire.ResultsA total of 162 patients (67 Germany, 34 Sweden, 33 Italy, 23 United Kingdom, 4 France, and 1 Bulgaria) completed the questionnaire. Excluding Bulgarian results, due to small sample size, country-specific annual health care costs ranged from €18,913 to €36,396 (reference year: 2012). Estimated direct healthcare costs ranged from €11,068 to €22,138; direct non-healthcare costs ranged from €7837 to €14,155 and labor productivity losses ranged from €0 to €8715. Costs are also shown to differ between children and adults. The mean EQ-5D index score for JIA patients was estimated at between 0.44 and 0.88, and the mean EQ-5D visual analogue scale score was estimated at between 62 and 79.ConclusionsJIA patients incur considerable societal costs and experience substantial deterioration in HRQOL in some countries. Compared with previous studies, our results show a remarkable increase in annual healthcare costs for JIA patients. Reasons for the increase are the inclusion of non-professional caregiver costs, a wider use of biologics, and longer hospital stays.

Recruitment procedures for descriptive socio-economic studies in rare diseases. The BURQOL-RD project

Background: Patient recruitment is a barrier that limits the power and validity of research findings in rare diseases (RD) research. We report the recruitment strategy carried out for the BURQOL-RD project in eight European countries with their corresponding results to gather socio-economic and health-related quality of life data of patients with 10 RD and their caregivers. Method: First, literature related to recruitment strategies for RD was reviewed, with a focus on descriptive studies and clinical trials. Second, the recruitment strategy for BURQOL-RD project was designed. Results: Findings from the literature showed that the most common recruiting strategies were the use of clinical and research networks and patient organizations (POs). The main BURQOL-RD recruitment strategy was driven, in every participant country, by the corresponding National Federation of RD by means of PO registries, e-mail and Internet-based questionnaires; providing a total of 3233 valid responses for the 10 selected RD in all participant countries. Conclusions: Our results provide inputs to improve the planning of recruitment activities in RD research. Internet-based questionnaires managed by POs using e-mail proved to be a useful strategy for patient recruitment.

Modified checklist for autism in toddlers cross-cultural adaptation for Argentina

Objectives: Early detection leads to early intervention and improvement in prognosis of autism spectrum disorder(ASD). Argentina does not rely on standardized ASD screening tools used among its health professionals.Therefore, the reliability of the Argentinian version of the Modified Checklist for Autism in Toddlers (M-CHAT) was tested. Methods: A sample of children from the general population between 18 and 24 months (n = 420) was used. Parents/caregivers completed the M-CHAT. The reliability, test-retest agreement between parents and Cronbachs alpha were estimated. Results: Results indicate that the M-CHAT version for Argentina showed satisfactory reliability values of: a test–retest with a Kappa index equal to 1, an agreement between parents that showed Kappa values of 0.79, and an internal consistence – Cronbachs alpha – of 0.76.Also, the adaptation of M-CHATs telephone follow-up interview (FUI) was included. Conclusions: It is a useful tool for its application in the Argentinian healthcare setting, in turn, prove beneficial for early diagnosis and intervention.

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

ObjectiveThe 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.MethodsWe 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.ResultsA 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.ConclusionThe 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.

Recommendations for Improving the Quality of Rare Disease Registries

Rare diseases (RD) patient registries are powerful instruments that help develop clinical research, facilitate the planning of appropriate clinical trials, improve patient care, and support healthcare management. They constitute a key information system that supports the activities of European Reference Networks (ERNs) on rare diseases. A rapid proliferation of RD registries has occurred during the last years and there is a need to develop guidance for the minimum requirements, recommendations and standards necessary to maintain a high-quality registry. In response to these heterogeneities, in the framework of RD-Connect, a European platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research, we report on a list of recommendations, developed by a group of experts, including members of patient organizations, to be used as a framework for improving the quality of RD registries. This list includes aspects of governance, Findable, Accessible, Interoperable and Reusable (FAIR) data and information, infrastructure, documentation, training, and quality audit. The list is intended to be used by established as well as new RD registries. Further work includes the development of a toolkit to enable continuous assessment and improvement of their organizational and data quality.