A Fast Path from Innovation to Safe and Effective Medicines

"SHARE. CARE. CURE." – A EUROPEAN REFERENCE NETWORK FOR RARE INFECTIOUS DISEASES

Rare diseases are frequently life-threatening or chronically debilitating and the impact on the quality of life of affected patients and their family members is thus significant. However, drug development for these conditions has been limited by a lack of understanding of the underlying mechanisms of disease and the relative unavailability of subjects for clinical trials, as well as the prohibitive cost of investing in a novel pharmaceutical agent with poor market potential. Nevertheless, the introduction of Orphan Drug legislations has provided important incentives for the development of orphan drugs (i.e. drugs that have been abandoned or 'orphaned' by major drug companies). Moreover, recent studies on rare diseases, including inherited immunodeficiencies and metabolic disorders, have served not only to alleviate the plight of patients with rare diseases, but also yielded valuable information on biological processes of relevance for other, more common conditions. These lessons, along with the crucial importance of cooperation between academic institutions, pharmaceutical companies, patient advocacy groups and society in the elucidation of rare diseases, are highlighted in the present review.

Standards for Child and Adolescent Immunization Practices

Significance of Patient Registries for Dermatological Disorders

Diagnosis, treatment and management of rare diseases (RD) pose unique challenges due to their complex nature, significantly impacting the daily experiences of researchers and healthcare professionals working in this field. Despite increasing awareness and progress in the field of RD worldwide in recent years, a significant gap remains in our understanding of the specific barriers that these professionals face in their work with RD. This study provides a detailed survey analysis that sheds light on the challenges that researchers and healthcare professionals face in diagnosing, treating, managing and conducting research on RD. We developed a national online survey with three RD stakeholder groups (Researchers, Healthcare professionals and researcher-healthcare professionals) to identify the main challenges and needs in Türkiye for the diagnosis, treatment and follow-up processes of rare and undiagnosed diseases. The survey was completed by 363 participants, revealing that participants face key challenges such as the need to refer patients to specialized centers, financial burdens, limited access to necessary tests, inadequate support for rare disease research and a lack of interdisciplinary collaboration. Participants also noted that RD are inherently difficult to conduct research on with small cohorts. Survey results also suggest a number of policy improvements to accelerate research on RD: increased funding, establishment of robust surveillance systems, and development of comprehensive national action plans and guidelines on RD. To the best of our knowledge, this is the first study to be conducted in Türkiye. This study contributes to the understanding of the needs of professionals in rare disease research and highlights the urgent need for system improvements to support them.

Healthcare professionals need to continuously improve their knowledge, skills and performance to effectively function in an ever-changing healthcare environment. They depend on continuing professional development programs (CPD), either within or outside their institutions, to reflect on and update their clinical practice. Professional growth requires more than knowledge transfer; it requires curiosity, humility, self-awareness and a motivation for mastery. Educators can build on these factors and create effective learning experiences to develop complex skills including communication, interprofessional collaboration, teamwork, leadership and reflective practice. CPD program leaders should adopt an evolved approach to program design that leverages adult learning principles, active learning and longitudinal curricula, while identifying and overcoming system barriers to change, and targeting meaningful behaviour and health outcomes. In this article, we describe principles and strategies that CPD leaders can apply to their own programs, categorized under three steps: (1) Program design, (2) Program implementation and (3) Program evaluation. Under each step, we provide theoretical principles as well as practical tips, focusing on strategies that can motivate and facilitate change.

Harmonizing legal and ethical standards for interactions between health care providers and industry

Patients with rare diseases often encounter significant challenges, including poor coordination of healthcare services. The UK Rare Disease Framework emphasizes key priorities such as faster diagnoses, greater awareness among healthcare professionals, improved care coordination, and better access to specialist care. This National Health Service (NHS) project, based in the North East and Yorkshire Genomic Medicine Service (GMS), aimed to improve care coordination for patients with rare genetic diseases in primary care. The project focused on developing a generic clinical pathway to improve care coordination and transitions of care that could be applied to a range of rare diseases. Additionally, it sought to strengthen the integration between genomic services and primary care, fostering a more cohesive approach to patient management. The project mapped clinical care pathways for two exemplar rare genetic diseases, Achondroplasia and Neurofibromatosis type 1 (NF1), this paper describes the NF1 pathway and broader learning from this project. The pathways focussed on identifying common clinical touchpoints with primary care and transitions between primary and specialty care. Key findings included the identification of gaps in care coordination, particularly during the transition from paediatric to adult services, and the development of a set of principles and a template for mapping other rare diseases. Feedback from a wide range of stakeholders, including clinicians across specialties and patient representatives, informed the refinement of the pathways. This project illustrates a systematic approach to enhancing care coordination for patients with rare genetic diseases through the mapping of clinical pathways and the development of primary care resources. The principles and template created can be adapted for other rare diseases, enabling the development of concise, disease-specific pathways. By prioritizing care coordination and transitions, and engaging a wide range of stakeholders in the process, this approach offers significant potential to improve the management of rare disease patients, especially during the critical transition from paediatric to adult care.

BackgroundRare and complex diseases can have a significant impact on family life, and managing the reproductive aspects of patients of childbearing age with rare diseases is often difficult and complex.A European Reference Network (ERN) Transversal Working Group (WG) on Pregnancy and Family Planning was created to join forces to promote and address issues on these topics in rare and low-prevalence diseases.ObjectiveTo outline the challenges and the good practices related to pregnancy and family planning in rare and complex diseases for healthcare professionals (HCPs).MethodsA survey on state of the art and unmet needs was created by a co-design group of both clinicians and patients’ representatives from 20 ERNs. The survey was uploaded in English on the online platform “EU Survey” and disseminated by respective ERNs and learned societies. Seven transversal domains were explored in the survey by using closed and open-ended questions: fertility preservation, pre-conceptional counselling, family planning counselling, pre-implantation diagnosis, prenatal diagnosis, pregnancy monitoring and post pregnancy monitoring, lactation monitoring/counselling and newborn management. The questions investigated for each topic were the following: level of importance, activities performed by the centre, clinical challenges, good practice and educational activities.ResultsA total of 197 answers were collected from 24 different countries. Unmet needs for HCPs included: the need to improve communication between different HCPs, the lack of predefined organizational pathways, the lack of availability of expert HCPs for some pregnancy-related issues and the need to streamline the care provided among different countries. In addition, the survey underlined the need to improve the educational activities provided to rare disease patients.ConclusionsPhysicians and patients need to be educated on the emerged unmet needs in order to standardize the information for both HCPs and patients with rare diseases. Educational activities should be considered to help to disseminate information.

People with rare lung diseases often suffer the burden of delayed diagnosis, limited treatment options, and difficulties in finding expert physicians. One of the reasons for the delay in diagnosis is the limited training for healthcare practitioners on rare diseases. This review explores the main concerns and needs for education on rare lung diseases from the perspectives of both patients and professionals. Despite the increasing interest in rare lung disorders and some recent breakthrough developments on the management of several diseases, healthcare professionals, including general practitioners and hospital workers, receive little education on this topic. Nonetheless, many healthcare professionals show much interest in receiving further training, especially on diagnosis. Patients and families want easier access to high-quality education materials to help them manage their own disease. Well-educated patients are better equipped to deal with chronic diseases, but patient education can be challenging as patients’ individual health issues, and diverse backgrounds can create significant barriers. Raising more awareness for rare lung diseases and further development of patient-centred international expert networks like the European Reference Network on Rare Lung Diseases (ERN-LUNG), which includes both experts and patient representatives, are essential for improving care and education on rare lung diseases. Initiatives such as the Rare Disease Day, have been successful in increasing awareness for rare conditions. The development of online tools for accessing information has had positive effects and should be further supported and extended in the future.

A rare disease is defined as any life-limiting or chronically debilitating disease affecting <1 person in 2000, with many rare diseases affecting <1 person per 100 000. There are approximately 8000 rare diseases, with recent analysis suggesting a conservative prevalence of 3.5–5.9%.1 Over the last decade, tremendous advances have been made in rare disease identification, treatment, and support. This has been largely driven by an increasingly vehement consolidated patient voice and an EU directive (2009) that all member states required a rare disease plan/strategy by 2013. In 2013, the UK strategy for rare disease was published,2 followed by the launch of rare disease implementation plans for the devolved nations (Scotland in 2014;3 Northern Ireland in 2015;4 Wales in 20175). Rare diseases have major unmet medical needs. Healthcare professionals and rare disease charities often hear tragic stories of patients with rare life-threatening diseases where responsible doctors have been unable to help as they have never heard of the condition, nor seen a similar case presentation, nor found relevant knowledge and expertise online. More than 80% of individuals report difficulty in accessing relevant information and >70% of GPs struggle to identify or manage rare diseases. A long diagnostic odyssey is common, with patients often feeling misunderstood, isolated, vulnerable, receiving …

Health authorities worldwide have invested in digital technologies to establish robust information exchange systems for improving the safety and efficiency of medication management. Nevertheless, inaccurate medication lists and information gaps are common, particularly during care transitions, leading to avoidable harm, inefficiencies, and increased costs. Besides fragmented health care processes, the inconsistent incorporation of patient-driven changes contributes to these problems. Concurrently, patient-empowerment tools, such as mobile apps, are often not integrated into health care professional workflows. Leveraging coproduction by allowing patients to update their digital shared medication plans (SMPs) is a promising but underused and challenging approach. This study aimed to determine the value propositions of a digital tool enabling patients, family caregivers, and health care professionals to coproduce and co-manage medication plans within Switzerland's national eHealth architecture. We used an experience-based co-design approach in the French-speaking region of Switzerland. The multidisciplinary research team included 5 patients as co-researchers. We recruited polypharmacy patients, family caregivers, and health care professionals with a broad range of experiences, diseases, and ages. The experience-based co-design had 4 phases: capturing, understanding, and improving experiences, followed by preparing recommendations and next steps. A qualitative, participatory methodology was used to iteratively explore collaborative medication management experiences and identify barriers and enabling mechanisms, including technology. We conducted a thematic analysis of participant interviews to develop value propositions for digital SMPs. In total, 31 persons participated in 9 interviews, 5 focus groups, and 2 co-design workshops. We identified four value propositions for involving patients and family caregivers in digital SMP management: (1) comprehensive, accessible information about patients' current medication plans and histories, enabling streamlined access and reconciliation on a single platform; (2) patient and health care professional empowerment through the explicit co-ownership of SMPs, fostering coresponsibility, accountability, and transparent collaboration; (3) a means of supporting collaborative interprofessional medication management, including tailored access to information and improved communication across stakeholders; and (4) an opportunity to improve the quality of care and catalyze digital health innovations. Participants discussed types of patient involvement in editing shared information and emphasized the importance of tailoring SMPs to individual abilities and preferences to foster health equity. Integrating co-management into the clinical routine and creating supportive conditions were deemed important. Coproduced SMPs can improve medication management by fostering trust and collaboration between patients and health care professionals. Successful implementation will require eHealth interoperability frameworks that embrace the complexity of medication management and support diverse use configurations. Our findings underscored the shared responsibility of all stakeholders, including policy makers and technology providers, for the effective and safe use of SMPs. The 4 value propositions offer strategic guidance, while highlighting the need for further research in different health care settings.

ObjectiveSeizure forecasting algorithms have become increasingly accurate and may reduce the morbidity and mortality caused by seizure unpredictability. Translating these benefits into meaningful health outcomes for people with epilepsy requires effective data visualization of algorithm outputs. To date, no studies have investigated patient and physician perspectives on effective translation of algorithm outputs into data visualizations through health information technology.Materials and MethodsWe developed front-end data visualizations as part of a Seizure Forecast Visualization Toolkit. We surveyed 627 people living with epilepsy and caregivers, and 28 epilepsy healthcare providers. Respondents scored each visualization in terms of international standardized software quality criteria for functionality, appropriateness, and usability.ResultsPeople with epilepsy and caregivers ranked hourly radar charts highest for protecting against errors in interpreting forecasts, reducing anxiety from seizure unpredictability, and understanding seizure patterns. Accuracy in interpreting visuals, such as a risk gauge, was dependent on seizure frequency. Visuals showing hourly/daily forecasts were more useful for patients who experienced seizure cycling than those who did not. Hourly line graphs and monthly heat maps were rated highest among clinicians for ease of understanding, anticipated integration into clinical practice, and the likelihood of clinical usage. Epilepsy providers indicated that daily heat maps, daily line graphs, and hourly line graphs were most useful for interpreting seizure diary patterns, assessing therapy impact, and counseling on seizure safety.DiscussionThe choice of data visualization impacts the effective translation of seizure forecast algorithms into meaningful health outcomes.ConclusionThis effort underlines the importance of incorporating standardized, quantitative methods for assessing the effectiveness of data visualization to translate seizure forecast algorithms into clinical practice.

Data Needs for Economic Evaluations of Screening in Pediatric Primary Care: A Research Framework.

BackgroundGiven the inherent complexity of rare paediatric diseases and the sensitive emotional context of the situations they create (due to the patients’ age and the tense uncertainty surrounding the progression of the disease), communication between the adults involved is a key tool in the efforts to provide these children and youths a better quality of life. We conducted ten interviews with families of children with rare diseases, in the aim of exploring how communication between doctors and patients affect their daily lives.All participants, members of FEDER (a Spanish federation of associations of patients with rare diseases) were invited by phone or email to participate in a semi-structured interview including questions on clinical information, communication experiences with healthcare professionals, and the impact these had on the interviewees’ relationships with them. To analyse these interviews, we used the ‘grounded theory’ methodology and open and axial text coding techniques, in addition to those identifying the properties and dimensions of the categories formulated.ResultsThe core category we have proposed is ‘adjustment of mutual trust’, with said category describing the attitude and behaviour of doctors who inspire trust in the parents of paediatric patients diagnosed with a rare disease. More specifically, said behaviours or sources of trust are: appearing human, sensitive and empathetic; showing transparency and communicative openness; being supportive of parental proactivity; and being available to families at all times.ConclusionsTrust is the cornerstone of parent-doctor communication in the field of children with rare diseases. If the sources of trust are present, they create a degree of trust that bolsters both parties in the search for a common goal: providing the child with the best possible care.