Patient organisations play an increasingly crucial role in the pharmaceutical sector, yet their impact on innovation remains unexplored. In this article the impact of patient organisations on R&D activity in the context of rare diseases in Europe using a proprietary dataset that maps clinical trials from discovery to phase III across 29 countries, 1893 indications, and 30 years (1990-2019) is estimated. By applying difference-in-differences and event study methodologies to a panel of 1,646,910 unique R&D observations, is found that country-indication pairs with at least one operating patient organisation have a higher rate of R&D activity compared to those without, with stronger effect in more prevalent rare diseases compared to ultra-rare conditions. This article suggests that patient organisations play an important role in steering R&D efforts in rare diseases. Further research is needed to better understand mechanisms driving this effect and the potential impact of patient organisations on existing health inequities. Read the full article here.
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ORPHAcodes use for the coding of rare diseases: comparison of the accuracy and cross country comparability
Estimates of rare disease (RD) population impact in terms of number of affected patients and accurate disease definition is hampered by their under-representation in current coding systems. This study tested the use of a specific RD codification system (ORPHAcodes) in five European countries/regions (Czech Republic, Malta, Romania, Spain, Veneto region-Italy) across different data sources over the period January 2019-September 2021.
Overall, 3133 ORPHAcodes are used to describe RD diagnoses, mainly corresponding to the disease/subtype of disease aggregation level of the Orphanet classification (82.2%). More than half of the ORPHAcodes (53.6%) described diseases having a very low prevalence (< 1 case per million), and most commonly captured rare developmental defects during embryogenesis (31.3%) and rare neurological diseases (17.6%). ORPHAcodes described disease entities more precisely than corresponding ICD-10 codes in 83.4% of cases.
ORPHAcodes are found to be a versatile resource for the coding of RD, able to assure easiness of use and inter-country comparability across population and hospital databases. Future research on the impact of ORPHAcoding as to the impact of numbers of RD patients with improved coding in health information systems is needed to inform on the real magnitude of this public health issue. Read the full article here.
Gaucher disease (GD) is a rare autosomal recessive inherited disorder caused by the lysosomal enzyme acid β-glucosidase deficiency. Many patients experience a critical delay in the diagnosis of up to 8-10 years due to its rarity and variability in signs and symptoms, with the consultation of several specialists.
This prospective observational study analyzed the prevalence of GD in 600 patients with monoclonal gammopathy of uncertain significance (MGUS) from January 2018 until February 2022.
The clinical heterogeneity of GD and frequent lack of awareness among physicians often lead to diagnostic delays and severe clinical manifestations. The role of MGUS in the presence of at least one clinical sign, such as low platelet count, organomegaly, bone pain, or bleeding tendency, could aid in initiating GD screening with DBS, thus reducing the period between symptom onset and the diagnosis of this rare disease. Read the full article here.
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”. 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. Read the full article here.
Rare disease drug development is wrought with challenges not the least of which is access to the limited data currently available throughout the rare disease ecosystem where sharing of the available data is not guaranteed. Most pharmaceutical sponsors seeking to develop agents to treat rare diseases will initiate data landscaping efforts to identify various data sources that might be informative with respect to disease prevalence, patient selection and identification, disease progression and. Such data are often difficult to come by for highly prevalent, mainstream disease populations let alone for the 8000 rare disease that make up the pooled patient population of rare disease patients. The future of rare disease drug development will hopefully rely on increased data sharing and collaboration among the entire rare disease ecosystem. One path to achieving this outcome has been the development of the rare disease cures accelerator, data analytics platform (RDCA-DAP) funded by the US FDA and operationalized by the Critical Path Institute. Read the full article here.
Autosomal dominant leukodystrophy (ADLD) is an ultra-rare, slowly progressive neurodegenerative disorder associated with the loss of white matter in the central nervous system (CNS). Several years after its first clinical description, ADLD was found to be caused by variants in the LMNB1 gene that cause its overexpression in at least the brain of patients. LMNB1 encodes for Lamin B1, a protein of the nuclear lamina. Lamin B1 regulates many cellular processes such as DNA replication, chromatin organization, and senescence. However, its functions are not fully characterized yet. Nevertheless, Lamin B1 together with the other lamins that constitute the nuclear lamina has firstly the key role of maintaining the nuclear structure. Being the nucleus a dynamic system subject to both biochemical and mechanical regulation, it is conceivable that changes to its structural homeostasis might translate into functional alterations. Under this light, this review aims at describing the pieces of evidence that to date have been obtained regarding the effects of LMNB1 overexpression on cellular morphology and functionality. Moreover, further investigation on ADLD morpho-functional consequences is essential to better understand this complex disease and, possibly, other neurological disorders affecting CNS myelination are suggested. Read the full article here.
Phenotype-driven approaches to enhance variant prioritization and diagnosis of rare disease
Rare disease diagnostics and disease gene discovery have been revolutionized by whole-exome and genome sequencing but identifying the causative variant(s) from the millions in each individual remains challenging. The use of deep phenotyping of patients and reference genotype-phenotype knowledge, alongside variant data such as allele frequency, segregation, and predicted pathogenicity, has proved an effective strategy to tackle this issue. In this article the numerous tools that have been developed to automate this approach and demonstrate the power of such an approach on several thousand diagnosed cases from the 100,000 Genomes Project are reviewed. Finally, the challenges that need to be overcome to improve detection rates and help the majority of patients that still remain without a molecular diagnosis after state-of-the-art genomic interpretation are discussed. Read the full article here.
An extremely rare case of simultaneous adenocarcinoma and carcinoid of the sigmoid colon in the background of Barrett’s esophagus
According to GLOBOCAN 2018, colorectal cancer is the third most common cancer in the world. In 2018, the incidence of colon cancer worldwide is about 2 million, and the number of deaths is close to 1 million. The great morbidity, in combination with the high mortality and its late diagnosis, determine its social importance.
The most common symptoms include iron-deficiency type anemia, change in defecation rhythm, weight reduction, and manifestations of intestinal obstruction. However, the first manifestation of clinical symptoms is not always from the large intestine but also from other organs outside the digestive system. In these cases, colon cancer is usually incurable due to the development of extracolonic dissemination and corresponding organ failure. Genetic factors, sedentary lifestyle, obesity, consumption of red meat, alcohol, smoking, and some metabolic diseases are considered the main risk factors for its occurrence.
We present the case of a 47-year-old woman with histologically verified simultaneous adenocarcinoma and carcinoid of the sigmoid colon, as well as the background of asymptomatic gastroesophageal reflux disease complicated by precancer of the esophagus and stomach – Barrett’s esophagus. Read the full article.
The need to provide palliative care for patients and their families is key to alleviating their pain and suffering as well as preserving the possibility of a dignified end to their earthly journey. The lack of focus on the part of the legislator for the adoption of a comprehensive regulatory framework, which includes the forms, methods, and ways of providing and financing palliative treatment and care for terminally ill patients, creates a feeling of absence of the state and provokes patients and their families themselves to seek support and help to alleviate pain and suffering.
The purpose of the present analysis is to present the existing regulatory framework, based on which palliative treatment and care are provided in the Republic of Bulgaria. To summarize the comprehensiveness of the normative definition as well as make relevant recommendations for optimization of the regulation in view of the gaps found in it. Read the full article here.
Cancer diseases, as a group of pathological entities, represent a significant social and health problem. However, the consideration of all cancers in a single category in health policymaking has been subject to criticism. Due to their clinical and epidemiological characteristics, patients with rare cancers face obstacles in their access to innovative medicines, combined with a lack of expertise in the diagnostic and treatment processes. The establishment of specific policies for these patients requires a precise definition of the concept.
This article aims to provide a chronological overview of the definition of “rare cancer” in the context of health policy development. A narrative literature review based on the keywords “rare cancers”, “rare tumors”, and “rare neoplasms” was conducted in the PubMed/MEDLINE, ScienceDirect, and Google Scholar databases. The identified articles were organised into three main contextual categories: clinical-based definitions, epidemiological-based definitions, and definitions used in pediatric oncology. Read the full article here.