Needs and Experiences With Health Care Providers of Adult Rare Disease Patients and Caregivers of People With Rare Diseases: Protocol for a Qualitative Study.

BACKGROUND: Rare diseases in Europe are defined as diseases with a prevalence of less than 5 per 10,000 people. Despite their individual rarity, the total number of rare diseases is considerable. Rare diseases are often chronic and complex, affecting physical, mental, and neurological health. People with rare diseases face challenges such as delayed diagnosis, limited medical support, and financial burden. Caregivers, usually family members, bear significant physical and emotional burdens. Understanding the experiences of patients with rare disease and their caregivers is critical to effective care, but this is still underresearched. Better support and understanding of the challenges faced by both patients and caregivers is clearly needed. Our study will explore the experiences and needs of people with rare diseases and caregivers of people with rare diseases in relation to accessing health services. OBJECTIVE: This study aims to explore the experiences of patients with rare disease and their caregivers with Slovenian health care providers and to create a theoretical model of needs and experiences. METHODS: This is a qualitative thematic analysis study, using the codebook approach. The study will conduct semi-open-ended interviews to understand the experiences and needs of people with rare diseases and caregivers of people with rare diseases in relation to accessing health services. The interview questions will be based on an extensive literature review. Data from the interviews will be analyzed using thematic analysis to identify patterns and build a thematic map. Data will be analyzed by at least 2 coders. To ensure reliability, respondent validation will be conducted and negative cases investigated. Any discrepancies will be resolved by consulting the entire research team until a consensus is reached. RESULTS: This study was not specifically funded. However, author TC is supported by grant number P3-0339 from the Slovenian Agency for Research and Innovation. This study was approved by the Medical Ethics Committee of the Republic of Slovenia (0120-47/2022/3), and recruitment is expected to begin in May 2024, with data analysis results anticipated by the end of 2025. CONCLUSIONS: This study will fill an important research gap in Slovenia by exploring the needs and experiences of people living with rare diseases and their caregivers. The results will contribute to the broader field of rare diseases and add knowledge that can inform future research processes and intervention strategies. It also aims to identify neglected areas that have a significant impact on the lives of people with rare diseases. This study is important not only because it addresses the immediate needs of the Slovenian rare disease community, but also because it contributes to a discussion on patient-centered care, health policy design, and the inclusion of psychosocial components in health care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/53362.

Recommendations for optimal interdisciplinary management and healthcare settings for patients with rare neurological diseases.

BACKGROUND: In 2017, the German Academy for Rare Neurological Diseases (Deutsche Akademie für Seltene Neurologische Erkrankungen; DASNE) was founded to pave the way for an optimized personalized management of patients with rare neurological diseases (RND) in all age groups. Since then a dynamic national network for rare neurological disorders has been established comprising renowned experts in neurology, pediatric neurology, (neuro-) genetics and neuroradiology. DASNE has successfully implemented case presentations and multidisciplinary discussions both at yearly symposia and monthly virtual case conferences, as well as further educational activities covering a broad spectrum of interdisciplinary expertise associated with RND. Here, we present recommendation statements for optimized personalized management of patients with RND, which have been developed and reviewed in a structured Delphi process by a group of experts. METHODS: An interdisciplinary group of 37 RND experts comprising DASNE experts, patient representatives, as well as healthcare professionals and managers was involved in the Delphi process. First, an online collection was performed of topics considered relevant for optimal patient care by the expert group. Second, a two-step Delphi process was carried out to rank the importance of the selected topics. Small interdisciplinary working groups then drafted recommendations. In two consensus meetings and one online review round these recommendations were finally consented. RESULTS: 38 statements were consented and grouped into 11 topics: health care structure, core neurological expertise and core mission, interdisciplinary team composition, diagnostics, continuous care and therapy development, case conferences, exchange / cooperation between Centers for Rare Diseases and other healthcare partners, patient advocacy group, databases, translation and health policy. CONCLUSIONS: This German interdisciplinary Delphi expert panel developed consented recommendations for optimal care of patients with RND in a structured Delphi process. These represent a basis for further developments and adjustments in the health care system to improve care for patients with RND and their families.

Healthcare costs for patients with rare diseases: Evidence from China.

OBJECTIVE: Rare diseases cause a huge financial burden to countless patients and families. It is an important public health issue that requires widespread attention. This study analyzes medical expenses composition and the change in trends of out-of-pocket (OOP) expenses for patients with Amyotrophic lateral sclerosis (ALS) and explores the factors influencing these changes. METHODS: Data were obtained from the Chinese Medical Insurance Department database from 2018 to 2020, including 857 patients with ALS in 60 cities across 30 provinces. We used descriptive methods to analyse the baseline characteristics and medical expenses of outpatients and inpatients with ALS. And we used quantile regression to analyse the differences in patient OOP ratio and the factors influencing them. RESULTS: In China, 80.3% of ALS patients chose tertiary hospitals, with an annual direct medical cost of 11,339.7 RMB per patient and an OOP ratio of 41.6%. The annual medical cost for outpatients was 345.1 RMB per patient, with an OOP ratio of 36.7%. The annual medical cost for inpatients was 28,139.8 RMB per patient, with an OOP ratio of 41.7%. Compared to outpatients, inpatients had higher medical costs but lower actual reimbursement rates. The OOP ratio of ALS patients decreased, then increased over time. And the OOP ratio was influenced by medical institution, medical insurance, and age (p < 0.05). Patients who chose tertiary hospitals, those who were covered by the urban resident basic medical insurance and younger patients had relatively higher OOP ratio. CONCLUSION: In recent years, although China has begun to pay attention to the rights and interests of patients with rare diseases, the government has provided some healthcare security to patients with rare diseases. However, the level of medical insurance coverage was still low, the equity of protection was still insufficient and the financial burden on patients was high. Therefore, the government should further improve the healthcare system to provide full life-cycle and affordable healthcare services to patients with rare diseases.

Healthcare access and health equity: intricate challenges for rare diseases.

No abstract available.

Are We Capturing the Socioeconomic Burden of Rare Genetic Disease? A Scoping Review of Economic Evaluations and Cost-of-Illness Studies.

BACKGROUND AND OBJECTIVES: Rare diseases have a significant impact on patients, families, the health system, and society. Measuring the socioeconomic burden is crucial to valuing interventions for rare diseases. Healthcare system costs are significant, but so are costs to other government sectors, patients, families, and society. To understand the breadth of costs captured in rare disease studies, we examined the cost categories and elements of socioeconomic burden captured in published studies. METHODS: A scoping review was conducted using five electronic databases to identify English language economic evaluations and cost-of-illness studies of interventions for rare diseases (2011-21). We mapped costs using a previously developed evidence-informed framework of socioeconomic burden costs for rare disease. RESULTS: Of 4890 studies identified, 48 economic evaluations and 22 cost-of-illness studies were included. While 18/22 cost-of-illness studies utilized a societal perspective, only 7/48 economic evaluations incorporated societal costs. Most reported cost categories related to medical costs, with medication and hospitalizations being the most common elements for both study designs. Costs borne by patients, families, and society were reported less among economic evaluations than cost-of-illness studies. These included: productivity (10% vs 77%), travel/accommodation (6% vs 68%), government benefits (4% vs 18%), and family impacts (0% vs 50%). CONCLUSIONS: Contrary to cost-of-illness analyses, most of the included economic evaluations did not account for the hidden burden of rare diseases, that is, costs borne by patients, families, and societies. Including these types of costs in future studies would provide a more comprehensive picture of the burden of disease, providing empirical data to inform how we value and make decisions regarding rare disease interventions, health policy, and resource allocation.

Assessment highlights need for improvement in standards of development of core outcome sets for rare genetic diseases.

OBJECTIVES: A rare disease is classified as such if it affects less than one person in 2,000. The Core Outcome Set STandards for Development (COS-STAD) is a set of standards that represent the minimum recommendations to be considered in the process of core outcome set (COS) development. The aim of this study was to provide a baseline assessment of COS development standards for rare genetic diseases. STUDY DESIGN AND SETTING: Core Outcome Measures in Effectiveness Trials (COMET) database contains nearly 400 published COS studies according to the latest systematic review. Studies focusing on COS development for rare genetic diseases were eligible for inclusion and were assessed by two independent evaluators. RESULTS: Nine COS studies were included in the analysis. Eight different rare genetic diseases were investigated. None of the studies met all the standards for development. The number of standards met ranged from 6 to 10, and the median was 7. CONCLUSION: This study is the first study to assess COS-STAD for rare genetic diseases, and it highlights a great need for improvement. First in terms of numbers of rare diseases considered for COS developments, second in methodology, particularly regarding the consensus process, and third in reporting of the COS development studies.

Developing a Framework of Cost Elements of Socioeconomic Burden of Rare Disease: A Scoping Review.

BACKGROUND AND OBJECTIVE: Rare diseases place a significant burden on patients, families, the healthcare system, and society. Evidence on the socioeconomic burden of rare disease is limited and mostly reflects diseases where treatments are available. We developed a framework encompassing recommended cost elements for studies of the socioeconomic burden of rare diseases. METHODS: A scoping review, conducted in five databases (Cochrane Library, EconLit, Embase, MEDLINE, and APA PsycINFO), identified English language publications from 2000 to 2021 presenting frameworks developed for determining, measuring or valuing costs for rare or chronic diseases. Cost elements were extracted and used to develop a literature-informed framework. Structured feedback was gathered from experts in rare diseases, health economics/health services, and policy research to revise the framework. RESULTS: Of 2990 records identified, eight papers were included and informed our preliminary framework; three focused on rare disease and five on chronic disease. Following expert input, we developed a framework consisting of nine cost categories (inpatient, outpatient, community, healthcare products/goods, productivity/education, travel/accommodation, government benefits, family impacts, and other), with several cost elements within each category. Our framework includes unique costs, added from the expert feedback, including genetic testing to inform treatment, use of private laboratories or out-of-country testing, family involvement in foundations and organizations, and advocacy costs for special access programs. CONCLUSIONS: Our work is the first to identify a comprehensive list of cost elements for rare disease for use by researchers and policy makers to fully capture socioeconomic burden. Use of the framework will increase the quality and comparability of future studies. Future work should focus on measuring and valuing these costs through onset, diagnosis, and post-diagnosis.

Enhancing Equitable Access to Rare Disease Diagnosis and Treatment around the World: A Review of Evidence, Policies, and Challenges.

This document provides a comprehensive summary of evidence on the current situation of rare diseases (RDs) globally and regionally, including conditions, practices, policies, and regulations, as well as the challenges and barriers faced by RD patients, their families, and caregivers. The document builds on a review of academic literature and policies and a process of validation and feedback by a group of seven experts from across the globe. Panelists were selected based on their academic merit, expertise, and knowledge regarding the RD environment. The document is divided into five main sections: (1) methodology and objective; (2) background and context; (3) overview of the current situation and key challenges related to RDs covering six dimensions: burden of disease, patient journey, social impact, disease management, RD-related policies, and research and development; (4) recommendations; and (5) conclusions. The recommendations are derived from the discussion undertaken by the experts on the findings of this review and provide a set of actionable solutions to the challenges and barriers to improving access to RD diagnosis and treatment around the world. The recommendations can support critical decision-making, guiding efforts by a broad range of RDs stakeholders, including governments, international organizations, manufacturers, researchers, and patient advocacy groups.

Gene-targeted therapies: Towards equitable development, diagnosis, and access.

Genomic and gene-targeted therapies hold great promise in addressing the global issue of rare diseases. To achieve this promise, however, it is critical the twin goals of equity in access to testing and diagnosis, and equity in access to therapy be considered early in the life cycle of development and implementation. Rare disease researchers and clinicians must simultaneously recognize the life-altering potential of early diagnosis and administration of gene-targeted therapeutics while acknowledging that not everyone who experiences a rare disease and needs these therapies will be able to afford or access them. Achieving equity in the development of and access to gene-targeted therapies will not only require innovations in research, clinical, regulatory, and reimbursement frameworks, but will also necessitate increased attention to the ethical, legal, and social implications when establishing research paradigms and the translation of research results into novel interventions for rare genetic diseases. This article highlights and discusses the growing importance and recognition of health equity across the spectrum of rare disease research and care delivery.

HTA challenges for appraising rare disease interventions viewed through the lens of an institutional multidimensional value framework.

INTRODUCTION: Evaluating rare disease interventions poses challenges for HTA agencies, including uncertainties and ethical issues and tensions. INESSS has recently adopted a Statement of Principles and Ethical Foundations which proposes a multidimensional approach to value appraisal as well as five principles to frame the evaluation process. AREAS COVERED: Our aim was to identify and analyze HTA challenges for appraising interventions for rare diseases, using the Statement's approach to value appraisal as an analytical framework, and outline how the Statement's principles can help address these challenges. Challenges, covering a diversity of aspects, were identified by leveraging institutional experience in diverse domains of expertise and consolidated through narrative literature review. Challenges were categorized by value dimension (clinical, populational, economic, organizational, and sociocultural), which allowed to pinpoint how each challenge affects the ability to appraise the value of an intervention. Key ethical tensions across dimensions were also identified. Specific approaches to addressing these challenges - related to knowledge mobilization and integration, deliberation, and recommendation-making - were outlined on the basis of the principles promulgated in the Statement. EXPERT OPINION: A multidimensional approach can be fruitful for analyzing challenges for appraising the value of rare disease interventions and help guide approaches to tackle them.

Improving Insurance Protection for Rare Diseases: Economic Burden and Policy Effects - Simulation of People With Pompe Disease in China.

BACKGROUND: The economic burden of Pompe disease (PD) is under-researched. This study aimed to fill this gap and provide evidence-based suggestions for policy improvement based on policy simulation. METHODS: Data were derived from a nationally based cross-sectional survey on rare diseases in early 2018. Answers from 92 PD patients were used for data analysis and simulation. Catastrophic health expenditure (CHE) and impoverishment due to illness (IDI) were adopted to measure PD patients' economic burden. Two typical reimbursement patterns, a dosage-based model and a cost-based model, in China were simulated. RESULTS: Twenty-four pediatric and 68 adult PD patients were investigated. Families with pediatric PD patients on average had lower annual household incomes than families with adult PD patients (RMB 37 890 vs. RMB 66 120). The direct medical expense and out-of-pocket expenses were almost double for pediatric patients compared with adult patients (RMB 120 050 vs. RMB 66 350; RMB 112 710 vs. RMB 57 940, respectively). The direct non-medical expense for patients was almost six times the expense of adult patients (RMB 73 790 vs. RMB 13 080, respectively). About 88.24% of families with pediatric PD patients and 67.21% of families with adult PD patients suffered from CHE. Around 84.21% of families with pediatric PD patients and 45.90% of families with adult PD patients were forced to live in poverty due to illness. The simulation indicated that, although the two current reimbursement schemes helped reduce CHE, they almost had no effect on reducing IDI; the dosage-based model was more sensitive to changes in policy parameters. CONCLUSION: Our study highlighted the alarmingly high disease burden faced by PD patients with first-hand patient-reported evidence. Our series of simulations could be a good reference for China and other countries to improve their reimbursement policy regarding PD.

Improving Interpretation of Evidence Relating to Quality of Life in Health Technology Assessments of Rare Disease Treatments.

Rare diseases are often severe, debilitating, life-limiting conditions, many of which occur in childhood. These complex conditions have a wide range of clinical manifestations that have a substantial impact on the lives of patients, carers and families and often produce heterogeneous clinical outcomes. Therefore, the evaluation of quality-of-life (QoL) impacts is important. In health technology assessment (HTA), patient-reported outcome measures (PROMs) and/or health state utility values (HSUVs) are used to determine QoL impacts of new treatments, but their use in rare diseases is challenging due to small and heterogeneous populations and limited disease knowledge. This paper describes challenges associated with the use of patient-reported outcomes (PROs)/HSUVs to evaluate QoL in HTA of rare disease treatments (RDTs) and identifies five recommendations to ensure appropriate interpretation of QoL impacts. These were derived from mixed methods research (literature reviews, appraisal document analyses, appraisal committee observations and interviews) examining the use of PROs/HSUVs in HTA of RDTs. They highlight that HTAs of RDTs must (1) understand the QoL impacts of the disease and of treatments; (2) critically assess PRO data, recognising the nuances in development and administration of PROMs/HSUVs, considering what is feasible and what matters most to the patient population; (3) recognise that lack of significant effect on a PRO does not imply no QoL benefit; (4) use different forms of evidence to understand QoL impacts, such as patient input; and (5) provide methodological guidance to capture QoL impacts on patients/carers.

Health Policies for Rare Disease Patients: A Scoping Review.

OBJECTIVE: To identify and map the available evidence on the implementation of public health policies directed at individuals with rare diseases, and to compare the implementation of these health policies between Brazil and other countries. METHOD: A scoping review guided by the PRISMA-ScR and JBI checklists. The search for articles was conducted in eight electronic databases, MEDLINE/Pubmed, Embase, Cochrane Library, Web of Science, Scopus, CINAHL, PsycINFO, and LILACS, using controlled descriptors, synonyms, and keywords combined with Boolean operators. All steps of this review were independently conducted by two researchers. The selected studies were classified by evidence hierarchy, and a generic quantitative tool was used for the assessment of the studies. RESULTS: A total of 473 studies were identified, of which 13 which met all the inclusion criteria were selected and analyzed. Of these studies, 61.5% (n = 8) had final scores equal to or greater than 70%, i.e., they were classified by this tool as being well-reported. The comparative analysis of international rare diseases demonstrates that public authorities' priorities and recommendations regarding this topic also permeate and apply to the Brazilian context. CONCLUSIONS: The evaluation and monitoring of public policies directed at rare disease patients are urgent and necessary to improve and implement such policies with less bureaucracy and more determination for this unique population that requires timely and high-quality care.

'Advocacy groups are the connectors': Experiences and contributions of rare disease patient organization leaders in advanced neurotherapeutics.

INTRODUCTION: Biomedical progress has facilitated breakthrough advanced neurotherapeutic interventions, whose potential to improve outcomes in rare neurological diseases has increased hope among people with lived experiences and their carers. Nevertheless, gene, somatic cell and other advanced neurotherapeutic interventions carry significant risks. Rare disease patient organizations (RDPOs) may enhance patient experiences, inform expectations and promote health literacy. However, their perspectives are understudied in paediatric neurology. If advanced neurotherapeutics is to optimize RDPO contributions, it demands further insights into their roles, interactions and support needs. METHODS: We used a mixed-methodology approach, interviewing 20 RDPO leaders representing paediatric rare neurological diseases and following them up with two online surveys featuring closed and open-ended questions on advanced neurotherapeutics (19/20) and negative mood states (17/20). Qualitative and quantitative data were analysed using thematic discourse analysis and basic descriptive statistics, respectively. RESULTS: Leaders perceived their roles to be targeted at educational provision (20/20), community preparation for advanced neurotherapeutic clinical trials (19/20), information simplification (19/20) and focused research pursuits (20/20). Although most leaders perceived the benefits of collaboration between stakeholders, some cited challenges around collaborative engagement under the following subthemes: conflicts of interest, competition and logistical difficulties. Regarding neurotherapeutics, RDPO leaders identified support needs centred on information provision, valuing access to clinician experts and highlighting a demand for co-developed, centralized, high-level and understandable, resources that may improve information exchange. Leaders perceived a need for psychosocial support within themselves and their communities, proposing that this would facilitate informed decision-making, reduce associated psychological vulnerabilities and maintain hope throughout neurotherapeutic development. CONCLUSION: This study provides insights into RDPO research activities, interactions and resource needs. It reveals a demand for collaboration guidelines, central information resources and psychosocial supports that may address unmet needs and assist RDPOs in their advocacy. PATIENT OR PUBLIC CONTRIBUTION: In this study, RDPO leaders were interviewed and surveyed to examine their perspectives and roles in advanced neurotherapeutic development. Some participants sent researchers postinterview clarification emails regarding their responses to questions.

[Sustainable reimbursement of the B­centres for rare diseases in Germany-status quo and solution approaches]. / Nachhaltige Vergütung der B­Zentren für Seltene Erkrankungen in Deutschland ­ Status quo und Lösungsansätze.

BACKGROUND: To ensure specialized care of patients with rare diseases, numerous centres for rare diseases were funded over the past few years. The reimbursement of patients' ambulatory care in hospitals, however, is characterized by a plurality of forms of care and payment. There is some evidence of deficits in the reimbursement of care of patients suffering from a rare disease from studies on individual rare diseases. OBJECTIVES: To investigate current forms of care provision and reimbursement of centres for rare diseases and to develop future approaches for sustainable compensation. MATERIALS AND METHODS: Initially, centres for rare diseases in Germany were asked to provide information about their forms of care and reimbursement using questionnaires. Subsequently, two focus group interviews and one expert interview with representatives from centres for rare diseases, health insurance, health politics and patients were conducted to discuss current and future meritocratic forms of care provision and reimbursement. The data were evaluated using content analysis. RESULTS AND CONCLUSIONS: Thirty-nine centres for rare diseases participated in the questionnaire survey. Of those, 38% receive a flat fee/allowance for university outpatient departments, the amount of which varies notably, and 41% obtain a mixed payment comprising an allowance for university outpatient departments and other forms of reimbursement. An under-recovery of costs in centres for rare diseases and its impact on patient care were mentioned in the interviews. In this context, a need to further develop forms of care provision and reimbursement has been identified. Participants prefer a special flat fee/allowance for rare diseases that covers the time-consuming care for patients with rare diseases.

Evaluating discrete choice experiment willingness to pay [DCE-WTP] analysis and relative social willingness to pay [RS-WTP] analysis in a health technology assessment of a treatment for an ultra-rare childhood disease [CLN2].

BACKGROUND: Conventional cost-effectiveness analysis [CEA] using cost per QALY thresholds may counteract other incentives introduced to foster development of treatments for rare and ultra-rare diseases. Therefore, alternative economic evaluation methods were explored, namely Discrete Choice Experiment Willingness to Pay (DCE-WTP) and Relative Social Willingness to Pay (RS-WTP), to value interventions for an ultra-rare childhood disease, Neuronal Ceroid Lipofuscinosis type 2 (CLN2). RESEARCH DESIGN AND METHODS: Treatment for CLN2 was valued from a citizen's ('social') perspective using DCE-WTP and RS-WTP in a survey of 4,009 United Kingdom [UK] adults. Three attributes (initial quality of life, treatment effect, and life expectancy) were used in both analyses. For DCE-WTP, a cost attribute (marginal income tax increase) was also included. Optimal econometric models were identified. RESULTS: DCE-WTP indicated that UK adults are willing to pay incremental increases through taxation for improvements in CLN2 attributes. RS-WTP identified a willingness to allocate >40% of a pre-assigned healthcare budget to prevent child mortality and approximately 15% for improved health status. CONCLUSIONS: Both techniques illustrate substantive social WTP for CLN2 interventions, despite the small number of children benefitting. This highlights a gap between UK citizens' willingness to spend on rare disease interventions and current funding policies.