Impact of mental health in persons living with rare disease: Findings from the AMCP Market Insights Program.

Within the framework of its Market Insights Program, AMCP convened a panel of experts representing diverse stakeholders to identify alterations to plan design and/or coverage options geared toward improving the diagnosis and treatment of mental health conditions among persons living with rare diseases (PLWRD). PLWRD face unique mental health challenges because of the misunderstood nature of their conditions, potential misdiagnosis, and limited treatment options. Economic burdens arise from increased medical needs, reliance on caregivers, and work disruptions. The interplay of these factors, along with health insurance coverage, creates a distinctive mental health landscape for PLWRD and a need to prioritize mental health support for this patient population. This article aims to (1) summarize expert perspectives on health care system challenges and areas of agreement concerning the management of mental health conditions and (2) advance payers' understanding of their role in supporting mental health care for patients with rare diseases. Addressing mental health needs of PLWRD presents multifaceted challenges. Managed care organizations play a pivotal role in supporting mental health care for PLWRD through their quality improvement initiatives and policies for coverage and reimbursement, which can impact both the rare disease treatment and mental health services PLWRD receive.

Innovations in Phenotyping and Diagnostics Create Opportunities for Improved Treatment and Genetic Counseling for Rare Diseases.

Genetic counseling and treatment options for rare developmental disabilities (DDs) have been revolutionized by the opportunities made possible by using massively parallel sequencing for diagnostic purposes [...].

Parents' expectations regarding case management for rare diseases in Switzerland: mixed-method findings from an online survey.

AIMS OF THE STUDY: This pilot study aims to enhance understanding by examining parents' specific views on the requirements, content and objectives of case management and advanced care coordination for children with rare diseases during childhood. The findings of this study are expected to offer valuable insights and recommendations for existing and future initiatives in clinical practice and research, with the goal of improving the comprehensive, child-centred and family-orientated approach to case management. METHODS: This pilot study is part of an ongoing prospective study (SPACE), involving parents and families from various networks in Switzerland. Participants were parents recruited from the Children with Rare Diseases (KMSK) network consisting of families with children with rare diseases. The survey questionnaire covered demographic information; expectations and perceived need for case management; assessment of their quality of life and their child's suffering; and evaluation of interprofessional and interdisciplinary communication. Qualitative data from free-response answers were analysed using Mayring's content analysis and descriptive statistics were used to analyse quantitative data from Likert-scale questions. RESULTS: The study included 108 respondent families from among the 775 in the KMSK, a 14% response rate. The age of their children ranged from 0.4 to 24 years (mean: 8) and their level of suffering in the past six months varied, with 31.5% indicating intense or very intense suffering. In terms of case management, 15.8% of families reported access while 32.4% expressed a need but did not have access to it. The study identified three categories of parental expectations regarding case management, emphasising the importance of interprofessional collaboration, effective communication and comprehensive support. CONCLUSIONS: The findings shed light on the high need for case management support with a current undersupply in Switzerland and an association with reduced parental quality of life, highlighting the necessity for diverse support and assistance to effectively manage the challenges faced by families with children with rare diseases.

Global health for rare diseases through primary care.

Rare diseases affect over 300 million people worldwide and are gaining recognition as a global health priority. Their inclusion in the UN Sustainable Development Goals, the UN Resolution on Addressing the Challenges of Persons Living with a Rare Disease, and the anticipated WHO Global Network for Rare Diseases and WHO Resolution on Rare Diseases, which is yet to be announced, emphasise their significance. People with rare diseases often face unmet health needs, including access to screening, diagnosis, therapy, and comprehensive health care. These challenges highlight the need for awareness and targeted interventions, including comprehensive education, especially in primary care. The majority of rare disease research, clinical services, and health systems are addressed with specialist care. WHO Member States have committed to focusing on primary health care in both universal health coverage and health-related Sustainable Development Goals. Recognising this opportunity, the International Rare Diseases Research Consortium (IRDiRC) assembled a global, multistakeholder task force to identify key barriers and opportunities for empowering primary health-care providers in addressing rare disease challenges.

[Update of the Pdta Net Observatory of the ReS Foundation with all regional Care Pathways approved until 2023.] / Aggiornato l'Osservatorio Pdta Net di Fondazione ReS con tutti i Pdta regionali approvati fino al 2023.

Pdta Net, established and managed by Research and Health Foundation (ReS), is a database aimed at gathering and analysing the Regional Care Pathways (CPs) approved in Italy. A comprehensive search was conducted within institutional websites to retrieve all CPs approved by Italian Regions and Autonomous Provinces until December 2023, by utilizing specific keywords. Compared to the previous year, 51 new approvals were recorded. By now, Pdta Net collects 856 CPs, of which 476 are for high-impact chronic diseases and 380 for rare diseases.

Registries or non-pharmacological observational studies? An operational attempt to draw the line and to provide some suggestions for the ethical evaluation of rare disease registries.

Originally established to evaluate the ethical aspects of clinical trials, Ethics Committees (ECs) are now requested to review different types of projects, including, among others, observational studies and disease registries. In Italy, clinical trials on medicinal products for human use and on medical devices are regulated by EU Regulation 536/2014, EU Regulation 2017/745, and 2017/746 while pharmacological observational studies are regulated by the Italian Medicines Agency guidelines of 2008 and by Ministerial Decree of November 30th, 2021. The other types of studies are not strictly regulated, causing discrepancies in their definition and assessment by the ECs, and slowdowns in the start of projects. The present contribution aims to propose definitions and distinctions between non-pharmacological observational studies and disease registries, which constitute different entities but are often assimilated by ECs, and to formulate suggestions for the evaluation of rare disease registries, which are an expanding research area of interest.

Invisible patients in rare diseases: parental experiences with the healthcare and social services for children with rare diseases. A mixed method study.

This study explores the experiences of Polish caregivers of children with rare disease (CRD) with health care and social services for CRD. A mixed-methods approach was employed, using an open-ended questionnaire with a convenience sample. Quantitative data presented through descriptive statistics, were complemented by thematic analysis applied to qualitative responses. Responses from 925 caregivers of 1002 children with CRD revealed that the duration of the diagnostic journey varied, spanning from 0 to 18 years, with an average time of 1.7 years. Similarly, the average number of physicians consulted before receiving the correct diagnosis was 4.8. The Internet was basic source of information about children's disease. Although caregivers were to some extent satisfied with the quality of health care for CRD, they complained at the accessibility of health care and social services, physicians' ignorance regarding RDs, the lack of co-ordinated care and financial and psychological support. To break the cycle of the diagnostic and therapeutic odyssey that may aggravate the condition of CRD, cause parental stress and financial burden there is a need to change our view on CRD from cure to family-oriented care. Multifaceted challenges and needs of CRD families should be prioritized.

Fair Funding Decisions: Consistency of the Time Horizons Used in the Calculation of Quality-Adjusted Life Years for Therapies for Very Rare Diseases by the National Institute for Health and Care Excellence in England.

The National Institute for Health and Care Excellence (NICE) in England uses quality-adjusted life years (QALYs) to assess the cost-effectiveness of treatments. A QALY is a measure that combines the size of the clinical benefit of a treatment with the time the patient benefits from it, i.e., the time horizon. We wanted to know how consistently QALY gains are calculated at NICE. Therefore, we have analysed information on the time horizons used for the QALY calculations of the concluded evaluations conducted under the Highly Specialised Technologies programme for treatments of very rare diseases at NICE. For treatments with final guidance published by December 2023 (n = 29), a time horizon of median 97.5 years (range: 35 to 125 years) was used to calculate the QALY gains. For most QALY calculations, the accepted time horizon was longer than either the expected treatment duration or the estimated life expectancy. In contrast, for the only technology with a final negative funding decision, i.e., afamelanotide for treating the lifelong chronic disease erythropoietic protoporphyria, a time horizon that was shorter than the expected treatment duration was used. The fairness and consistency of the evaluation process of treatments for very rare diseases at NICE should be reviewed.

Advance Care Planning for Children With Rare Diseases: A Pilot RCT.

BACKGROUND AND OBJECTIVE: Pediatric rare diseases are often life-limiting conditions and/or require constant caregiving. Investigators assessed the initial efficacy of the FAmily CEntered (FACE) pediatric advance care planning (pACP), FACE-Rare, intervention on families' quality of life. METHODS: A pilot-phase, single-blinded, intent-to-treat, randomized controlled clinical trial enrolled families from 1 pediatric quaternary hospital between 2021 and 2023. Intervention families received 3 weekly 60-minute (FACE-Rare pACP) sessions: (1) Carer Support Needs Assessment Tool or Action Plan, (2) Carer Support Needs Assessment Tol Action Plan Review, and (3) Pediatric Next Steps: Respecting Choices pACP. Controls received treatment as usual (TAU). Outcome measures were Beck Anxiety Inventory, Family Appraisal of Caregiving, Functional Assessment of Chronic Illness Therapy (FACIT)-Spirituality, and health care utilization. Generalized mixed effect models with γ response assessed the intervention effect at 3-month follow-up. RESULTS: Children (n = 21) were aged 1 to 10 years, 48% male, 24% Black; and 100% technology dependent. Primary family caregivers (n = 21) were aged 30 to 43 years, 19% male, 19% Black; and 27% household income below the Federal poverty level. Dyads underwent 1:1 randomization: 9 to FACE-Rare and 12 to TAU. TAU caregivers reported statistically lower meaning and peace than FACE-Rare caregivers (0.9, P = .03, confidence interval [CI]: 0.75-0.99). Black caregivers reported significantly less caregiver distress (0.7, P = .04, CI: 0.47-0.98) than non-Black caregivers. Poor families reported more anxiety (3.5, P = .002, CI: 1.62-7.94), more caregiver strain (1.2, P = .006, CI: 1.07-1.42); and less family well-being (0.8, P = .02, CI: 0.64-0.95). CONCLUSIONS: FACE®-Rare was feasible, acceptable, safe, and demonstrated initial efficacy, providing greater feelings of meaning and peace to caregivers. Poverty impacted well-being. A multisite trial is needed to determine generalizability.

My Digital Refuge.

In this narrative medicine essay, a medical ethicist discusses the complexity of juggling the interests of members in online forums dedicated to rare diseases after being blocked upon disclosing her affiliation with a medical school, thus barring her from the support and information she needed to manage her daughter's rare disease.

Infrastructuring precision medicine: Making gene therapies for rare diseases workable in practice.

Long viewed by social scientists as a future imaginary, precision medicine is now materializing in many healthcare systems in the form of new diagnostic practices and novel treatment modalities, such as gene therapies. Based on an ethnographic study of the introduction of the first two clinically available in-vivo gene therapies in the Danish healthcare system, we investigate what it takes to make these therapies workable in practice. Drawing on social science literature on infrastructuring, we describe the many forms of mundane work required to fit these therapies into regulatory frameworks, political processes and daily work practices in the healthcare system. Further, we observe how the processes of infrastructuring required to introduce the gene therapies into clinical practice had transformative implications as they redistributed roles and responsibilities among clinicians, pharmacists, procurement agencies and pharmaceutical manufacturers.

Video-based assessments of activities of daily living: generating real-world evidence in pediatric rare diseases.

INTRODUCTION: Preserving function and independence to perform activities of daily living (ADL) is critical for patients and carers to manage the burden of care and improve quality of life. In children living with rare diseases, video recording ADLs offer the opportunity to collect the patients' experience in a real-life setting and accurately reflect treatment effectiveness on outcomes that matter to patients and families. AREAS COVERED: We reviewed the measurement of ADL in pediatric rare diseases and the use of video to develop at-home electronic clinical outcome assessments (eCOA) by leveraging smartphone apps and artificial intelligence-based analysis. We broadly searched PubMed using Boolean combinations of the following MeSH terms 'Rare Diseases,' 'Quality of Life,' 'Activities of Daily Living,' 'Child,' 'Video Recording,' 'Outcome Assessment, Healthcare,' 'Intellectual disability,' and 'Genetic Diseases, Inborn.' Non-controlled vocabulary was used to include human pose estimation in movement analysis. EXPERT OPINION: Broad uptake of video eCOA in drug development is linked to the generation of technical and clinical validation evidence to confidently assess a patient's functional abilities. Software platforms handling video data must align with quality regulations to ensure data integrity, security, and privacy. Regulatory flexibility and optimized validation processes should facilitate video eCOA to support benefit/risk drug assessment.

Patient experiences of interprofessional collaboration and intersectoral communication in rare disease healthcare in Germany - a mixed-methods study.

BACKGROUND: Rare diseases are often complex, chronic and many of them life-shortening. In Germany, healthcare for rare diseases is organized in expert centers for rare diseases. Most patients additionally have regional general practicioners and specialists for basic medical care. Thus, collaboration and information exchange between sectors is highly relevant. Our study focuses on the patient and caregiver perspective on intersectoral and interdisciplinary care between local healthcare professionals (HCPs) and centers for rare diseases in Germany. The aims were (1) to investigate patients' and caregivers' general experience of healthcare, (2) to analyse patients' and caregivers' perception of collaboration and cooperation between local healthcare professionals and expert centers for rare diseases and (3) to investigate patients' and caregivers' satisfaction with healthcare in the expert centers for rare diseases. RESULTS: In total 299 individuals of whom 176 were patients and 123 were caregivers to pediatric patients participated in a survey using a questionnaire comprising several instruments and constructs. Fifty participants were additionally interviewed using a semistructured guideline. Most patients reported to receive written information about their care, have a contact person for medical issues and experienced interdisciplinary exchange within the centers for rare diseases. Patients and caregivers in our sample were mainly satisfied with the healthcare in the centers for rare diseases. The qualitative interviews showed a rather mixed picture including experiences of uncoordinated care, low engagement and communication difficulties between professionals of different sectors. Patients reported several factors that influenced the organization and quality of healthcare e.g. engagement and health literacy in patients or engagement of HCPs. CONCLUSIONS: Our findings indicate the high relevance of transferring affected patients to specialized care as fast as possible to provide best medical treatment and increase patient satisfaction. Intersectoral collaboration should exceed written information exchange and should unburden patients of being and feeling responsible for communication between sectors and specialists. Results indicate a lack of inclusion of psychosocial aspects in routine care, which suggests opportunities for necessary improvements.

'High hopes for treatment': Australian stakeholder perspectives of the clinical translation of advanced neurotherapeutics for rare neurological diseases.

INTRODUCTION: Advanced therapies offer unprecedented opportunities for treating rare neurological disorders (RNDs) in children. However, health literacy, perceptions and understanding of novel therapies need elucidation across the RND community. This study explored healthcare professionals' and carers' perspectives of advanced therapies in childhood-onset RNDs. METHODS: In this mixed-methodology cross-sectional study, 20 healthcare professionals (clinicians, genetic counsellors and scientists) and 20 carers completed qualitative semistructured interviews and custom-designed surveys. Carers undertook validated psychosocial questionnaires. Thematic and quantitative data analysis followed. RESULTS: Participants described high positive interest in advanced therapies, but low knowledge of, and access to, reliable information. The substantial 'therapeutic gap' and 'therapeutic odyssey' common to RNDs were recognised in five key themes: (i) unmet need and urgency for access; (ii) seeking information; (iii) access, equity and sustainability; (iv) a multidisciplinary and integrated approach to care and support and (v) difficult decision-making. Participants were motivated to intensify RND clinical trial activity and access to advanced therapies; however, concerns around informed consent, first-in-human trials and clinical trial procedures were evident. There was high-risk tolerance despite substantial uncertainties and knowledge gaps. RNDs with high mortality, increased functional burdens and no alternative therapies were consistently prioritised for the development of advanced therapies. However, little consensus existed on prioritisation to treatment access. CONCLUSIONS: This study highlights the need to increase clinician and health system readiness for the clinical translation of advanced therapeutics for RNDs. Co-development and use of educational and psychosocial resources to support clinical decision-making, set therapeutic expectations and promotion of equitable, effective and safe delivery of advanced therapies are essential. PATIENT OR PUBLIC CONTRIBUTION: Participant insights into the psychosocial burden and information need to enhance the delivery of care in this formative study are informing ongoing partnerships with families, including co-production and dissemination of psychoeducational resources featuring their voices hosted on the Sydney Children's Hospitals Network website SCHN Brain-Aid Resources.

Improving the care of children with GENetic Rare disease: Observational Cohort study (GenROC)-a study protocol.

INTRODUCTION: Around 2000 children are born in the UK per year with a neurodevelopmental genetic syndrome with significantly increased morbidity and mortality. Often little is known about expected growth and phenotypes in these children. Parents have responded by setting up social media groups to generate data themselves. Given the significant clinical evidence gaps, this research will attempt to identify growth patterns, developmental profiles and phenotypes, providing data on long-term medical and educational outcomes. This will guide clinicians when to investigate, monitor or treat symptoms and when to search for additional or alternative diagnoses. METHODS AND ANALYSIS: This is an observational, multicentre cohort study recruiting between March 2023 and February 2026. Children aged 6 months up to 16 years with a pathogenic or likely pathogenic variant in a specified gene will be eligible. Children will be identified through the National Health Service and via self-recruitment. Parents or carers will complete a questionnaire at baseline and again 1 year after recruitment. The named clinician (in most cases a clinical geneticist) will complete a clinical proforma which will provide data from their most recent clinical assessment. Qualitative interviews will be undertaken with a subset of parents partway through the study. Growth and developmental milestone curves will be generated through the DECIPHER website (https://deciphergenomics.org) where 5 or more children have the same genetic syndrome (at least 10 groups expected). ETHICS AND DISSEMINATION: The results will be presented at national and international conferences concerning the care of children with genetic syndromes. Results will also be submitted for peer review and publication.