Characteristics Of Rare Diseases Research Articles

Proposal of a Method for Transferring High-Quality Scientific Literature Data to Virtual Patient Cases Using Categorical Data Generated by Bernoulli-Distributed Random Values: Development and Prototypical Implementation

Teaching medicine is a complex task because medical teachers are also involved in clinical practice and research and the availability of cases with rare diseases is very restricted. Automatic creation of virtual patient cases would be a great benefit, saving time and providing a wider choice of virtual patient cases for student training. This study explored whether the medical literature provides usable quantifiable information on rare diseases. The study implemented a computerized method that simulates basic clinical patient cases utilizing probabilities of symptom occurrence for a disease. Medical literature was searched for suitable rare diseases and the required information on the respective probabilities of specific symptoms. We developed a statistical script that delivers basic virtual patient cases with random symptom complexes generated by Bernoulli experiments, according to probabilities reported in the literature. The number of runs and thus the number of patient cases generated are arbitrary. We illustrated the function of our generator with the exemplary diagnosis "brain abscess" with the related symptoms "headache, mental status change, focal neurologic deficit, fever, seizure, nausea and vomiting, nuchal rigidity, and papilledema" and the respective probabilities from the literature. With a growing number of repetitions of the Bernoulli experiment, the relative frequencies of occurrence increasingly converged with the probabilities from the literature. For example, the relative frequency for headache after 10.000 repetitions was 0.7267 and, after rounding, equaled the mean value of the probability range of 0.73 reported in the literature. The same applied to the other symptoms. The medical literature provides specific information on characteristics of rare diseases that can be transferred to probabilities. The results of our computerized method suggest that automated creation of virtual patient cases based on these probabilities is possible. With additional information provided in the literature, an extension of the generator can be implemented in further research.

The Value of Cardiac Magnetic Resonance Imaging in Identification of Rare Diseases Mimicking Hypertrophic Cardiomyopathy.

Background: The cardiac Magnetic Resonance Imaging (MRI) characteristics of rare diseases with the hypertrophic cardiomyopathy (HCM) phenotype are not well defined. Methods: Seventy-three sequential patients and 34 of their relatives, who have the HCM phenotype, were included. All subjects underwent cardiac MRI and genetic testing. Results: Of these 107 patients with phenotypic HCM, seven rare diseases were identified: four cases with LAMP2, one case with PRKAG2, one case with TTR mutation, and one case with senile systemic amyloidosis. Subjects with rare diseases had diffuse LGE, and the percentage of those with LGE was significantly higher than that of other HCM (median: 18.9%, interquartile range (IQR): 14.05 to 28.2% versus 7.8%, IQR: 4.41 to 14.56%; p = 0.003). Additionally, global T1 and ECV were significantly higher in subjects with rare diseases (global T1: 1423.1 ± 93.3 ms versus 1296.2 ± 66.6 ms; global ECV: 44.3 ± 11.5% versus 29.9 ± 4.5%; all p < 0.001). Conclusions: Cardiac MRI suggests the existence of distinct imaging characteristics, including via LGE and T1 mapping, among rare diseases that mimic HCM and HCM itself.

Characteristics of rare diseases in Zhejiang province, 2007-2017

Objective: To understand the characteristics of 24 388 inpatients with rare diseases in Zhejiang province during 2007-2017 and provide evidence for rare disease prevention and control. Methods: Inpatient data of rare diseases and the number of hospitalization in each year were collected in 10 hospitals of class Ⅲ (A) in Zhejiang province from 2007 to 2017, and descriptive statistical analysis was used. Results: A total of 24 388 cases of rare diseases were found, accounting for 2.69‰ (24 388/9 054 201) of total hospitalized cases. The top 3 types of rare diseases were "diseases of blood and blood-forming organs and certain disorders involving immune mechanism" (32.81%, 8 001/24 388), "congenital malformations, deformations and chromosomal abnormalities" (24.87%, 6 065/24 388) and "diseases of the nervous system" (19.01%, 4 635/24 388). The number of rare disease cases increased year by year from 2007 to 2017 with an average annual growth of 19.69%, however, the proportion of rare disease cases in the annual number of hospitalized cases only showed upward trend during 2016-2017, the time distribution of different types of rare diseases had different characteristics. The male to female ratio of rare diseases cases was 1.35∶1(13 990/10 398), "diseases of the digestive system" (4.45∶1, 1 180/265), "consequences of injury, poisoning and other external causes" (3.51∶1, 281/80) and "diseases of the nervous system" (2.26∶1, 3 213/1 422) had the highest male to female ratio. The distributions of rare disease types and diseases of different types in different age groups varied. The top 10 rare diseases accounted for 53.55% (13 060/24 388) of the total cases, and the top 3 diseases were adult idiopathic neutropenia (14.41%, 3 515/24 388), corticobasal degeneration (7.60%, 1 854/24 388) and henock-schoenlein purpura (6.01%, 1 466/24 388). Conclusion: The analysis on the characteristics of 24 388 rare disease cases in Zhejiang during 2007-2017 provided reference evidence for the promotion of rare disease research, monitoring, building registration database, and development of the prevention and control strategy for rare diseases in China.

Pharmacology and drug development in rare diseases: the attractiveness and expertise of the French medical pharmacology.

Developing drugs for rare disease can be challenging due to specific rare disease characteristics. The French Medical Pharmacology is structured and positioned to play a major role in orphan drug research and development due to the required expertise concentrated into pharmacology departments, exclusively implemented within the French university hospitals, public hospitals that are linked to a medical school (and often a pharmacy school) with numerous INSERM or CNRS labelled research units. In addition, these structures allow a close collaboration between researchers, academic institutions and biotech start-up (most of them being spin-off of the academic structures). Also, within university hospitals are located the clinical investigation centres, linking to the F-CRIN network and also to Inserm and hospitals, that enable care staff and researchers to be associated and clinical research protocols to be carried out on site, in full respect with ethic and regulatory aspects. As a consequence, this intra and multidisciplinary expertise offers all resource to elaborate a tailored approach for orphan drug development, in new entities as well as in repositioning. For preclinical development: drug screening, candidate selection (taking into account PK, metabolism, variability and potential toxicity) and preclinical models (iPS, animal models) that could allow a better translation to human research. For clinical development, we will mention here dose determination, safety evaluation and Orphan Drug Designation and Protocol Assistance preparation and submission. For post marketing evaluation and surveys, the pharmacovigilance, addictovigilance and pharmacoepidemiology expertise, combined with access to large databases allow a better approach to orphan drug use and safety. As outlined through two success stories (Charcot Marie Tooth, vascular Ehlers-Danlos syndrome), the added value of French Medical Pharmacology structures and expertise has been evidenced in the know-how, multidimensional and multidisciplinary approaches, allowing the development of numerous drugs that have been granted with Orphan Drug Designation and later Market Approval. Even if specific and possibly even more, the field of orphan drugs requires the respect of highest standards of safety and quality. French Medical Pharmacology intends to continue on this way and constantly improve his involvement in this field, committed to a single objective: answer the unmet medical need of patients with rare diseases.

Characteristics of rare diseases

Characteristics of rare diseases

PSY106 - To What Extent Do Disease and Treatment Characteristics Influence Hta-Based Recommendations for A Sample of Orphan Drugs In Three Countries, and Could These Indicate Whether Orphan Drugs Have A “Special Status”?

Routine HTA methods may not adequately capture all the important considerations of a treatment’s value and the impact of the condition on the patient given that evidence is often incomplete. This study aims to explore the influence of broader considerations of scientific and social value judgments on reimbursement decisions for a sample of orphan drugs. To identify and compare the extent to which these broader considerations not captured by the incremental cost-effectiveness ratio (ICER) influenced HTA decision-making process in three countries; and, on this basis, explore whether orphan drugs have a “special status”. Countries included were England, Scotland and Sweden. Ten drug-indication pairs with EMA orphan designation and all appraised by NICE were selected. Publicly available HTA reports were coded using thematic analysis to systematically identify and compare these broader considerations across countries using an existing analytical framework. 108 different other considerations were identified and grouped into 15 clusters based on the information provided. The most common related to the nature of the disease, and considerations based on rarity or unmet need. 52% were one of the main reasons for the decision, and in some cases, were also a pivotal factor in accepting high and uncertain ICERs. Categorising these as social or scientific value judgments was done to identify areas where further elicitation of societal preferences, and where more consistency and transparency in their use are needed, respectively. Each of these was then compared to determine whether they pertained specifically to orphan drug or rare disease characteristics. Considerable variation was seen in the application of these broader considerations. Identifying these is a way forward to highlight areas where more research, or consistency and transparency are needed. Some of these other considerations may also favour orphan drugs, furthering the debate around whether orphan drugs deserve special status.