Multicriteria Decision Analysis to Support Health Technology Assessment Agencies: Benefits, Limitations, and the Way Forward.

OBJECTIVE: Recent years have witnessed an increased interest in the use of multicriteria decision analysis (MCDA) to support health technology assessment (HTA) agencies for setting healthcare priorities. However, its implementation to date has been criticized for being "entirely mechanistic," ignoring opportunity costs, and not following best practice guidelines. This article provides guidance on the use of MCDA in this context. METHODS: The present study was based on a systematic review and consensus development. We developed a typology of MCDA studies and good implementation practice. We reviewed 36 studies over the period 1990 to 2018 on their compliance with good practice and developed recommendations. We reached consensus among authors over the course of several review rounds. RESULTS: We identified 3 MCDA study types: qualitative MCDA, quantitative MCDA, and MCDA with decision rules. The types perform differently in terms of quality, consistency, and transparency of recommendations on healthcare priorities. We advise HTA agencies to always include a deliberative component. Agencies should, at a minimum, undertake qualitative MCDA. The use of quantitative MCDA has additional benefits but also poses design challenges. MCDA with decision rules, used by HTA agencies in The Netherlands and the United Kingdom and typically referred to as structured deliberation, has the potential to further improve the formulation of recommendations but has not yet been subjected to broad experimentation and evaluation. CONCLUSION: MCDA holds large potential to support HTA agencies in setting healthcare priorities, but its implementation needs to be improved.

Budgetary Impact of Medicinal Therapies for Rare Diseases in Bulgaria.

BACKGROUND: Rare diseases have been continually outlined as one of the causes for the National Health Insurance Fund's (NHIF) deficit spending in Bulgaria. AIM: To estimate the budgetary impact of rare disease medicinal therapies from NHIF perspective for 2014 and 2016. MATERIALS AND METHODS: Budgetary impact of rare diseases is calculated as a percentage of NHIF total pharmaceutical spending. Total expenditure per ICD-10 code, mean annual number of patients reimbursed and mean annual cost per patient are analysed. RESULTS: Budgetary impact of rare diseases reached a plateau of about 9% of NHIF total pharmaceutical spending for 2014-2016. Mean number of patients reimbursed and mean annual cost per patient increased by median rates of 4.27% and 2.54%, respectively. Glycogen storage disease, neuropathic heredofamilial amyloidosis and C1 esterase inhibitor deficiency stood out, as they had the second, fourth and fifth most expensive medicinal treatment cost. While accounting for only 92 patients in 2016, these three conditions contributed for 22.89% of NHIF total expenditure on rare disease medicinal therapies. For comparison, coagulation defects, with the biggest total cost per indication, had a similar budgetary impact - 24.88%, but for 277 patients reimbursed. CONCLUSIONS: Our study does not support the concerns about uncontrolled growth of expenditures for rare disease medicinal therapies. Nevertheless, there is a need for enhanced post-marketing surveillance and performance-based payment of these treatments. Development, collection and analysis of local real-world data have been increasingly applied as a tool to advance these health policy goals.

Health Technology Assessment and Appraisal of Therapies for Rare Diseases.

Innovative rare disease therapies and health technology assessment (HTA) share a lot of similarities. Both represent cases of interaction of epidemiology and health economics. Both are relatively new topics in public health practice. And both pose a lot of challenges to rare disease stakeholders who are currently looking for tools to support the timely access to innovative treatments while putting budget spending in order. This is why optimisation of assessment and appraisal of new rare disease therapies is a fundamental issue in rare disease health policy. Rare disease patients and caregivers expect prolonged life expectancy and improved quality of life and they perceive innovative health technologies as a rightful way to achieve these objectives.Multi-criteria decision analysis (MCDA) provides a structured, transparent approach to identify preferred alternatives by means of combined calculation of relative importance of different criteria and performance of the alternatives on these criteria. The labyrinth of competing interests and numerous stakeholders involved is why innovative rare disease health technologies make an excellent case study of the integration between HTA and MCDA. This kind of formalisation of decision-making is perceived as fair and legitimate, leading to a balance and agreement. MCDA provides a stage for a debate of policy priorities, health system specifics and societal attitudes, while also addressing the impact of rarity on all criteria and considerations.

Economic Burden And Health-Related Quality Of Life Of Patients With Cystic Fibrosis In Bulgaria.

OBJECTIVE: 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 cystic fibrosis (CF) in Bulgaria. MATERIALS AND METHODS: We conducted a cross-sectional study of 33 patients with CF and 17 caregivers from Bulgaria. Data on socio-demographic characteristics, health resource utilisation, informal care, labor productivity losses and HRQOL were collected from questionnaires completed by patients or their caregivers. HRQOL was evaluated with the EuroQol 5-domain (EQ-5D-3L) questionnaire. RESULTS: Median annual costs of CF in Bulgaria were € 24 152 per patient in 2012 as a reference year. Median annual costs for children were found to be significantly higher than those for adults - € 31 945 vs. € 15 714 (p = 0.012). This outcome came from statistically significant differences in costs for main informal carer (p < 0.001) and costs for other informal carers (p = 0.022). As a single cost item, drugs had the biggest monetary impact. Median annual drug costs were € 13 059. Bulgarian CF patients showed low HRQOL results - 50 median VAS score and 0.592 median health utilities. A quarter of patients even rated their health state as worse than death. CONCLUSION: CF patients from Eastern Europe remain a vulnerable population with risk factors for worse health outcomes. Our study provided a state-of-the art analysis that facilitates the elaboration, adoption and application of targeted public health policies to tackle CF-related problems at national and European level.

Preeclampsia Management and Maternal Ophthalmic Artery Doppler Measurements between 19 and 23 Weeks of Gestation.

Background: The ophthalmic Doppler is a reliable and impartial way to assess the severity of preeclampsia (PE). The study aimed to assess the potential utility of Doppler measurements of the maternal ophthalmic arteries during the weeks 19-23 of gestation, both independently and in combination with established biomarkers for PE. Methods: A prospective cohort study was conducted involving women who were recruited from a variety of standard appointments, including booking, scanning, and regular prenatal visits. A total of 200 women that were divided into high-risk and low-risk groups for developing PE were involved during the period between April 2023 and November 2023. Results: The ophthalmic ratio had significantly higher values in high-risk patients than in low-risk women (p = 0.000). There was a significant relationship between PSV2/PSV1 and gestational age at birth in women with PE compared to the ones who did not develop PE. Conclusions: An ophthalmic artery Doppler can play a crucial role in the early detection of PE, allowing for timely intervention and management. Incorporating the ophthalmic artery Doppler as a screening tool for PE in Bulgaria has the potential to improve early detection, risk stratification, and overall maternal and fetal health outcomes.

Willingness to pay for an mRNA-based anti-cancer treatment: results from a contingent valuation study in Israel.

BACKGROUND: mRNA technology is currently being investigated for a range of oncology indications. We assessed the willingness to pay (WTP) of the general population in Israel for a hypothetical novel mRNA-based treatment for oncology indications. METHODS: We used a contingent valuation methodology to elicit WTP using a web-based questionnaire. A sample of adult participants were presented with a hypothetical scenario in which an mRNA-based intervention increased the likelihood of a cure for various cancer types from 20% to 40% (half of the sample), or 60% (the other half of the sample). RESULTS: 531 respondents completed the questionnaire. The mean, median and mode WTP for the proposed hypothetical treatment in both scenarios were ILS65,000 (± ILS114,000), ILS20,000 and ILS50,000, respectively (1USD = 3.4ILS). The WTP was skewed towards zero, and 9.6% of the respondents were not willing to pay any amount. WTP higher amounts was significantly associated with higher income (p < 0.01), self-reported good health (p < 0.05), supplementary health insurance (p < 0.05), Jews compared to other populations (p < 0.01), interest in technology (p < 0.001) and a tendency to adopt medical innovations (p < 0.001). No statistical difference between the 40% vs. the 60% potential cure scenarios was found. Logistic and OLS regressions indicated that age, religion, income, and interest in adopting medical innovations were the best predictors of respondents' WTP. CONCLUSION: Despite the scientific breakthroughs in oncology treatment over the last few decades, many types of cancer are still incurable. Given the expected development of innovative mRNA-based treatments for cancer, these results should inform policymakers, the pharmaceutical industry and other stakeholders on the future coverage and reimbursement of these technologies incorporating patients' and societal views. To date, WTP considerations have not been given much weight in prioritization of drug reimbursement processes, neither in Israel nor in other countries. As a pioneer in adoption of the mRNA technology, Israel can also lead the incorporation of WTP considerations in this field.

Family Planning and Preconception Care Service Management: The Key Role of Bulgarian GPs.

Assisting women in attaining their reproductive goals is crucial for improving the well-being of families and children. As the first point of contact for healthcare, general practitioners (GPs) are ideal for family planning (FP) and preconception care (PCC). However, primary care interventions' efficacy is unclear. The aim of this study was to examine GPs' knowledge, attitudes, and perspectives on FP and PCC service management. Most GPs were aware of FP and PCC services and held a firm conviction that they should be primarily accountable together with obstetrician-gynaecologists. However, it is worth noting that less than 50% of respondents reported receiving thorough and comprehensive knowledge of their respective specialities. Those with general medicine qualifications demonstrated a high level of commitment to providing such services. The women's GPs and those with training in general medicine prescribed birth control pills and emergency contraception three times more frequently than the other doctors who suggested condoms or traditional methods or referred patients to another specialist (p < 0.05). In conclusion, PCC is of the utmost importance, and its effective implementation demands the collaboration of policymakers, healthcare providers, and individuals. GPs are essential in managing FP and PCC. They must incorporate more in-depth PCC into their clinical practice.

Navigating Gene Therapy Access: The Case of Bulgaria in the Context of the EU Regulatory Landscape.

Gene therapies (GTs) have recently emerged as revolutionary personalized therapeutic options. Despite their promising potential, challenges such as uncertainty regarding long-term health benefits and safety, along with extreme price tags, pose significant obstacles to patient access. Within the EU, the European Medicines Agency plays a pivotal role with regards to GT market authorization. However, national authorities are responsible for pricing and reimbursement, which results in fragment patient access within the EU. This study aimed to provide an overview of the complex landscape of post-market authorization accessibility for GT products in Bulgaria, comparing it with neighboring EU countries. We applied a mixed-methods approach, including desk research, public data requests, and list price comparisons. As of 1 April 2023, 14 GTs had a valid market authorization at the EU level. In Bulgaria, Kymriah® was the only GT included in the Positive Drug List (PDL), with an official list price of EUR 335,636.94. Similar results were found in Romania, whereas five GTs were included in Greece's PDL. Additionally, Zolgensma® was found accessible in Bulgaria through an alternative individual access scheme at an estimated price of EUR 1,945,000.00. In conclusion, this study emphasized targeted policy interventions to address health inequalities and to ensure timely access to GTs within the EU.

Availability and Access to Orphan Drugs for Rare Cancers in Bulgaria: Analysis of Delays and Public Expenditures.

Rare cancers are defined by an annual incidence of fewer than 6 per 100,000. Bearing similarities to rare diseases, they are associated with substantial health inequalities due to diagnostic complexity and delayed access to innovative therapies. This situation is further aggravated in Southeastern European countries like Bulgaria, where limited public resources and expertise underscore the need for additional policy and translational research on rare cancers. This study aimed to explore the availability and access to orphan drugs for rare cancers in Bulgaria for the period of 2020-2023. We cross-compared data from both the European Union and national public sources to evaluate the number of available and accessible orphan drugs for rare cancers, the delay from market authorization to reimbursement, the dynamics of public expenditures, and regional disparities in access across the country. We juxtaposed the main characteristics of oncological and non-oncological orphan drugs as well. Only 15 out of 50 oncological orphan drugs that were authorized by the European Medicine Agency were accessible for rare cancer patients in Bulgaria. The median delay between market authorization and inclusion in the Bulgarian Positive Drug List was 760 days. The total expenditures for all orphan drugs for rare cancers amounted to EUR 74,353,493 from 2020 to 2023. The budgetary impact of this group rose from 0.24% to 3.77% of total public medicinal product expenditures for the study period. Rare cancer patients represent a vulnerable population that often faces limited to no access to treatment. We call for targeted European and national policies to address this major inequality.

Are the European reference networks for rare diseases ready to embrace machine learning? A mixed-methods study.

BACKGROUND: The delay in diagnosis for rare disease (RD) patients is often longer than for patients with common diseases. Machine learning (ML) technologies have the potential to speed up and increase the precision of diagnosis in this population group. We aim to explore the expectations and experiences of the members of the European Reference Networks (ERNs) for RDs with those technologies and their potential for application. METHODS: We used a mixed-methods approach with an online survey followed by a focus group discussion. Our study targeted primarily medical professionals but also other individuals affiliated with any of the 24 ERNs. RESULTS: The online survey yielded 423 responses from ERN members. Participants reported a limited degree of knowledge of and experience with ML technologies. They considered improved diagnostic accuracy the most important potential benefit, closely followed by the synthesis of clinical information, and indicated the lack of training in these new technologies, which hinders adoption and implementation in routine care. Most respondents supported the option that ML should be an optional but recommended part of the diagnostic process for RDs. Most ERN members saw the use of ML limited to specialised units only in the next 5 years, where those technologies should be funded by public sources. Focus group discussions concluded that the potential of ML technologies is substantial and confirmed that the technologies will have an important impact on healthcare and RDs in particular. As ML technologies are not the core competency of health care professionals, participants deemed a close collaboration with developers necessary to ensure that results are valid and reliable. However, based on our results, we call for more research to understand other stakeholders' opinions and expectations, including the views of patient organisations. CONCLUSIONS: We found enthusiasm to implement and apply ML technologies, especially diagnostic tools in the field of RDs, despite the perceived lack of experience. Early dialogue and collaboration between health care professionals, developers, industry, policymakers, and patient associations seem to be crucial to building trust, improving performance, and ultimately increasing the willingness to accept diagnostics based on ML technologies.

Landscape analysis of available European data sources amenable for machine learning and recommendations on usability for rare diseases screening.

BACKGROUND: Patient registries and databases are essential tools for advancing clinical research in the area of rare diseases, as well as for enhancing patient care and healthcare planning. The primary aim of this study is a landscape analysis of available European data sources amenable to machine learning (ML) and their usability for Rare Diseases screening, in terms of findable, accessible, interoperable, reusable(FAIR), legal, and business considerations. Second, recommendations will be proposed to provide a better understanding of the health data ecosystem. METHODS: In the period of March 2022 to December 2022, a cross-sectional study using a semi-structured questionnaire was conducted among potential respondents, identified as main contact person of a health-related databases. The design of the self-completed questionnaire survey instrument was based on information drawn from relevant scientific publications, quantitative and qualitative research, and scoping review on challenges in mapping European rare disease (RD) databases. To determine database characteristics associated with the adherence to the FAIR principles, legal and business aspects of database management Bayesian models were fitted. RESULTS: In total, 330 unique replies were processed and analyzed, reflecting the same number of distinct databases (no duplicates included). In terms of geographical scope, we observed 24.2% (n = 80) national, 10.0% (n = 33) regional, 8.8% (n = 29) European, and 5.5% (n = 18) international registries coordinated in Europe. Over 80.0% (n = 269) of the databases were still active, with approximately 60.0% (n = 191) established after the year 2000 and 71.0% last collected new data in 2022. Regarding their geographical scope, European registries were associated with the highest overall FAIR adherence, while registries with regional and "other" geographical scope were ranked at the bottom of the list with the lowest proportion. Responders' willingness to share data as a contribution to the goals of the Screen4Care project was evaluated at the end of the survey. This question was completed by 108 respondents; however, only 18 of them (16.7%) expressed a direct willingness to contribute to the project by sharing their databases. Among them, an equal split between pro-bono and paid services was observed. CONCLUSIONS: The most important results of our study demonstrate not enough sufficient FAIR principles adherence and low willingness of the EU health databases to share patient information, combined with some legislation incapacities, resulting in barriers to the secondary use of data.

Insight into reimbursement decision-making criteria in Bulgaria: implications for orphan drugs.

OBJECTIVE: This article's objective is to critically assess the Bulgarian legislation on health technology assessment (HTA). It analyses how innovative therapies and orphan drugs in particular would respond to the regulators' decision-making criteria for reimbursement. MATERIALS AND METHODS: The study features critical analysis of current decision-making criteria for drug reimbursement in Bulgaria, as well as hypothetical scenario planning for orphan medicinal products. RESULTS: The approval for inclusion into the Positive Drug List (PDL) (which is a must for reimbursement) has been reorganised into an assessment scoring system with decision-making criteria (presence of therapeutic alternative, clinical effectiveness, safety, pharmacoeconomics and societal value) divided into weighted indicators. An explicit threshold has been set--a medicinal product must score 60 points at least to be included in PDL. Under the currently defined reimbursement decision-making criteria a hypothetical middle-of-the-road scenario planning shows that an orphan drug would score 20 points for therapeutic alternative, 28 for clinical effectiveness and 12 for safety. It would take no points for pharmacoeconomics and societal value. This leaves the orphan drugs with a total score of 60 points, making the final outcome of real-life assessment and decision-making heavily dependent on small fluctuations. CONCLUSIONS: The current reimbursement decision-making framework in Bulgaria seems to be generalised and not sufficiently transparent. It is unable to precisely assess innovative health technologies. The availability of a therapeutic alternative emerges as a key reimbursement decision-making criterion for orphan drugs, as these innovative products nominally provide the first medicinal therapy alternative to rare diseases.

Willingness to pay for cancer prevention, screening, diagnosis, and treatment: a systematic review.

INTRODUCTION: Willingness to pay (WTP) studies examine the maximum amount of money an individual is willing to pay for a specified health intervention, and can be used to inform coverage and reimbursement decisions. Our objectives were to assess how people value cancer-related interventions, identify differences in the methodologies used, and review the trends in studies' publication. AREAS COVERED: We extracted PubMed and EconLit articles published in 1997-2020 that reported WTP for cancer-related interventions, characterized the methodological differences and summarized each intervention's mean and median WTP values. We reviewed 1,331 abstracts and identified 103 relevant WTP studies, of which 37 (36%) focused on treatment followed by screening (26), prevention (21), diagnosis (7) and other interventions (12). The methods used to determine WTP values were primarily discrete-choice questions (n = 54, 52%), bidding games (15), payment cards (12) and open-ended questions (12). We found a wide variation in WTP reported values ranged from below $100 to over $20,000. EXPERT OPINION: The WTP literature on oncology interventions has grown rapidly. There is considerable heterogeneity with respect to the type of interventions and diseases assessed, the respondents' characteristics, and the study methodologies. This points to the need to establish international guidelines for best practices in this field.

What is the awareness of rare diseases among medical students? A survey in Bulgaria.

BACKGROUND: Rare diseases (RDs) are life-threatening or chronically debilitating and offer a high level of complexity. The aim of this study is to assess medical students' knowledge and awareness of RDs as well as their perceptions of potential measures to boost training in RDs. The cross-sectional survey was conducted at the Medical University of Plovdiv, Bulgaria, in 2019. The questionnaire contained 12 questions, divided into three main categories: (1) sociodemographic profile; (2) knowledge and awareness of RDs; and (3) attitudes about potential measures to improve training in RDs. RESULTS: A total of 1189 medical students completed the survey with an overall response rate of 56.4%. Only 13% of participants knew the correct definition of RDs, and a low overall level of awareness was found with regard to orphan drugs (20.3%) and genetic counselling and testing (0.5%). Respondents believed that society as a whole was largely unaware of RDs as a major public health issue. Students suggested elective courses, and invited lectures by RDs experts, and participation in research projects as the most preferred measures to improve undergraduate training. CONCLUSIONS: It is crucial to address the gaps in medical students' knowledge and awareness of RDs. University curricula should consider incorporating different RDs training modalities. It is essential to encourage various stakeholders to play a more proactive role and to collaborate in these activities. Involvement of patient organisations and advocacy groups might enhance students' knowledge of the challenges faced by people with RDs. Not least, the media should be partners in this important endeavour as well.

Preconception-Health-Related Attitudes of Bulgarian Women of Reproductive Age.

Preconception care (PC) is relatively new area of practice. While the volume and quality of PC activities depend on local settings, the awareness of women is critical for the successful promotion of PC services. The aim of this study was to examine the preconception-health-related attitudes and experiences of Bulgarian women of reproductive age. A qualitative study conducted among 20 women aged 18 to 49 years was performed between May and July 2022. Two focus groups were used with mixed samples of nulligravida, pregnant, and postpartum women. The participants thought that the Internet and their obstetrician-gynecologist were the only places where they could learn about getting pregnant. Only two of them discussed their PC plans with their physicians. Women pointed out that general practitioners (GPs) need to be more proactive in promoting PC. All respondents outlined the need for a web-based educational platform that could serve as a primary source of health information for future families. The role and functions of GPs in the continuum of PC should be reconsidered. We recommend targeted educational measures for all stakeholders, including women and GPs. In this regard, an easily accessible, knowledge-based web platform could enhance Bulgarian women's awareness and perceptions of PC.

Challenges in mapping European rare disease databases, relevant for ML-based screening technologies in terms of organizational, FAIR and legal principles: scoping review.

Background: Given the increased availability of data sources such as hospital information systems, electronic health records, and health-related registries, a novel approach is required to develop artificial intelligence-based decision support that can assist clinicians in their diagnostic decision-making and shorten rare disease patients' diagnostic odyssey. The aim is to identify key challenges in the process of mapping European rare disease databases, relevant to ML-based screening technologies in terms of organizational, FAIR and legal principles. Methods: A scoping review was conducted based on the PRISMA-ScR checklist. The primary article search was conducted in three electronic databases (MEDLINE/Pubmed, Scopus, and Web of Science) and a secondary search was performed in Google scholar and on the organizations' websites. Each step of this review was carried out independently by two researchers. A charting form for relevant study analysis was developed and used to categorize data and identify data items in three domains - organizational, FAIR and legal. Results: At the end of the screening process, 73 studies were eligible for review based on inclusion and exclusion criteria with more than 60% (n = 46) of the research published in the last 5 years and originated only from EU/EEA countries. Over the ten-year period (2013-2022), there is a clear cycling trend in the publications, with a peak of challenges reporting every four years. Within this trend, the following dynamic was identified: except for 2016, organizational challenges dominated the articles published up to 2018; legal challenges were the most frequently discussed topic from 2018 to 2022. The following distribution of the data items by domains was observed - (1) organizational (n = 36): data accessibility and sharing (20.2%); long-term sustainability (18.2%); governance, planning and design (17.2%); lack of harmonization and standardization (17.2%); quality of data collection (16.2%); and privacy risks and small sample size (11.1%); (2) FAIR (n = 15): findable (17.9%); accessible sustainability (25.0%); interoperable (39.3%); and reusable (17.9%); and (3) legal (n = 33): data protection by all means (34.4%); data management and ownership (22.9%); research under GDPR and member state law (20.8%); trust and transparency (13.5%); and digitalization of health (8.3%). We observed a specific pattern repeated in all domains during the process of data charting and data item identification - in addition to the outlined challenges, good practices, guidelines, and recommendations were also discussed. The proportion of publications addressing only good practices, guidelines, and recommendations for overcoming challenges when mapping RD databases in at least one domain was calculated to be 47.9% (n = 35). Conclusion: Despite the opportunities provided by innovation - automation, electronic health records, hospital-based information systems, biobanks, rare disease registries and European Reference Networks - the results of the current scoping review demonstrate a diversity of the challenges that must still be addressed, with immediate actions on ensuring better governance of rare disease registries, implementing FAIR principles, and enhancing the EU legal framework.

Prospects for Expansion of Universal Newborn Screening in Bulgaria: A Survey among Medical Professionals.

Determining the scope of a newborn screening program is a challenging health policy issue. Our study aimed to explore the attitudes of specialists in pediatrics, neonatology, medical genetics, and biochemistry regarding the prospects for expanding the panel of diseases for universal newborn screening in Bulgaria. We conducted an online survey in March-May 2022. The questionnaire listed 35 disorders that could potentially be included in the Bulgarian panel for universal newborn screening. If endorsing a specific condition, participants had to justify their position by judging its performance against the ten principles of Wilson and Jungner. We found a high degree of knowledge about the current universal newborn screening program in Bulgaria. An overwhelming majority (97.4%) supported the expansion of the panel to include more conditions. Four disorders obtained more than 50% approval for inclusion: cystic fibrosis (87.0%), thalassemia (72.7%), spinal muscular atrophy (65.6%), and classical galactosemia (59.1%). The perception of the condition as an important health problem was the most significant factor in this support. The costs of diagnosis and treatment appeared to be the main source of concern. We recommend country-specific economic evaluations and research on the views of other stakeholders, including the government, payers, and patient organizations, to better understand and manage the complex nature of newborn screening policymaking.

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems.

Socio-Economic Burden of Myasthenia Gravis: A Cost-of-Illness Study in Bulgaria.

Background: Myasthenia gravis (MG) is a chronic autoimmune disorder, which is characterized by fatigable muscle weakness with frequent ocular signs and/or generalized muscle fatigue, and occasionally associated with thymoma. MG patients and their families face a significant socio-economic burden. This population is often experiencing unemployment, unwilling job transfers and decreased income. Objective: This study aimed to estimate the annual costs from a societal perspective in a triple dimension of direct health care costs, direct non-health care costs (formal and informal care) and labor productivity losses in MG patients from Bulgaria, as well as to identify the main clinical and demographical cost drivers. Methods: A bottom-up, cross-sectional, cost-of-illness analysis of 54 adult MG patients was carried out in 2020. To collect data on demographic characteristics, health resource utilization, informal care and productivity losses, questionnaires were administered to and completed by patients. Results and Conclusion: Median annual costs of MG in Bulgaria were 4,047 EUR per patient. Direct costs slightly outweighed indirect costs, with drugs cost item having the biggest monetary impact. Despite the zero-inflated median, hospitalizations also influenced the direct costs by an estimated amount of 1,512 EUR in the 3rd quartile. Social services and professional caregiver costs were found to be almost missing, with the vast majority of patients reporting reliance on informal caregivers. Severe generalized disease, disease crises, and recurrent infections were confirmed as statistically significant cost driving factors. There were no severe generalized MG patients in the bottom quartile of the total costs distribution. It should be noted that in both cases of crises or infections, the overall increase in the total costs was mainly due to higher indirect costs observed. Reliance on family members as informal caregivers is routine among Bulgarian MG patients. This phenomenon is likely due to the lack of access to appropriate social services. Moreover, it is directly related with higher disease burden and significant inequalities. There is a need for further research on MG in Bulgaria in order to design targeted health policies that meet the needs and expectations of these patients.

Autistic Adult Services Availability, Preferences, and User Experiences: Results From the Autism Spectrum Disorder in the European Union Survey.

There is very little knowledge regarding autistic adult services, practices, and delivery. The study objective was to improve understanding of current services and practices for autistic adults and opportunities for improvement as part of the Autism Spectrum Disorder in the European Union (ASDEU) project. Separate survey versions were created for autistic adults, carers of autistic adults, and professionals in adult services. 2,009 persons responded to the survey and 1,085 (54%) of them completed at least one of the services sections: 469 autistic adults (65% female; 55% <35 years old), 441 carers of autistic adults (27% female; 6% <35 years old), 175 professionals in adult services (76% female; 67% in non-medical services). Top choices by autistic adults, carers or professionals for services best suiting their current needs were: residential services: "help in own home" (adults, carers of high independent adults, professionals), "fulltime residential facility" (carers of low independent adults); employment services: "job mentors" (adults, carers of high independent adults, professionals), "Sheltered employment" (carers of low independent adults); education services: "support in regular education setting" (all groups); financial services: financial support in lieu of employment ("Supplementary income for persons unable to have full employment" for adults, "full pension" for carers of low independent adults) or to supplement employment earnings for carers of high independent adults and professionals; social services: "behavior training" (adults) and "life skills training" (carers and professionals). Waiting times for specific services were generally < 1 month or 1-3 months, except for residential services which could be up to 6 months; most professionals were uninformed of waiting times (>50% responded "don't know"). Five of seven residential services features recommended for autistic adults were experienced by <50% of adults. The knowledge of good local services models that work well for autistic adults was generally low across all services areas. The variation in services experiences and perceptions reported by autistic adults, carers, or professionals underscore the need to query all groups for a complete picture of community services availability and needs. The results showed areas for potential improvement in autistic adult services delivery in the EU to achieve recommended standards.