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There are more than 7,000 rare diseases, is this number objective and accurate? The lack of a reliable understanding of the specific number of rare diseases and the number of people affected by rare diseases will limit the path to reduce the burden of rare diseases.
is used to define the phenotypic, genetic, and environmental characteristics of a particular disease, usually determined in different demographic characteristics, regions, or environments. Multiple observations in different subgroups are often required to support the definition of relevant diseases and to support standardized diagnostic capabilities and treatments.
However, the possibility of such evidence for rare diseases is much lower. Before , there is a lack of consensus on the definition of rare diseases, and the definition is imperfect. Objectively, it will affect the number of patients, diagnosis and treatment methods, and will affect the research of rare diseases and potential therapies. It is estimated that patients with rare diseases account for 10% of the population. Therefore, the development of rare disease diagnosis and treatment is facing increasing social pressure. There is an urgent need to more accurately define rare diseases, improve access to accurate information on relevant diseases, and achieve the goal of providing accurate medical services to affected patients. However, the current situation is that even a few rare diseases can not be accurately stated.
Recently, from the Oregon Health and Science University (Oregon Health & Science University, OUSU) Dr. Mellisa Haendel of the Oregon Institute of Clinical and Translational Sciences, etc. In Nature Reviews Drug DiscoveRy sent a paper to discuss related issues.
▲Mellsa Haendel (Image source: OHSU official website)
What kind of rare disease is considered “rare”?
The common definition of rare diseases is the development, funding and supervision of drug regulatory agencies for (called orphan drugs) The qualification criteria used for incentives. The relevant definitions vary by country and region. For example, in the United States, the definition of a rare disease is based on the 1983 Orphan Drug Act (Orphan Drug Act of 1983) 200,000 people (condition). Similar legislation introduced by the European Union defines a rare disease as a disease that affects less than one person per 2,000 people.
▲The definition of rare patient groups in different countries and regions (Source: References [4], Medicine Mingkang Content Team Mapping)
In addition, some diseases are “rare” in some populations or regions, but not in others. For example, Tay-Sachs disease is rare in the general population, but among the Ashkenazi Jews, the carrier frequency is 1/25. Tuberculosis is rare in the United States, but according to the World Health Organization, tuberculosis is one of the top ten causes of death worldwide. Obviously, the “rare” of rare diseases depends on the specific context.
What is a rare disease?
Rare Mendelian diseases (including on how to define the disease), reach an agreement; the definition of the incidence of disease should also be agreed at the same time.
At present, there is a large overlap between terms, models, and metadata used to identify rare diseases and classify rare diseases; data integration of proteins and genes that may represent therapeutic targets is increasing, and similar situations exist. Difficulties in the definition of certain diseases seem inevitable. However, there is an urgent need for a computational representation that can integrate multiple resources
Image Source: Pixabay
How many rare diseases exist?
Regulators, scientists, clinicians, and patient rights groups often refer to about 7,000 rare diseases, and there are 5,000 to 8,000 rare diseases. The difference in the estimated number of rare diseases, why is it so big ? One reason is that, as mentioned earlier, in defining individual diseases ; while other terms do not cover environmental causes A rare disease, such as a rare disease caused by exposure to toxins. Estimating the number of rare diseases did not explicitly define the inclusion/rejection criteria when considering the calculation of attributes, nor did it indicate whether the relevant counts included more general disease categories or even how they were defined.
Image Source: monarchinitiative.org
Recently, the parties have brought together a large number of terminology resources to unify the diseases in the Monarch Disease Ontology (Mondo) of the Monarch Disease Ontology (span class=”text-remarks” label=”Remarks”> definition. Although this consensus process is still ongoing, the author currently estimates that there are more than 10,000 rare diseases. This number is obtained using a hierarchical structure of existing disease terms. In the absence of a widely accepted definition of a rare disease, the initial practical method is to calculate the most specific term in the disease hierarchy (ie “leaves” The term “leaf terms” , while excluding higher level terms.
For example, consider Mondo’s specific rare disease term “span class=”text-remarks” label=”remarks”>(tetralogy of Fallot, TOF) Instead of the previous term “congenital heart disease.” When coming from the main source of knowledge about rare diseases (including Orphanet, OMIM, GARD, DOID, and NCI Thesaurus (NCIt, National Cancer Institute Synonym)) such information (see below), through algorithm combination and content management in Mondo, a total of 10,393 rare disease “leaf terms” can be identified. Most of them, 6,370 rare diseases, exist in 3 Of the 3 or more sources, and the remaining 4,023 rare diseases are single sources. This preliminary analysis suggests that the number of rare diseases currently may be much higher than is usually assumed. Drug discovery and treatment have a significant impact. However, it should be emphasized that a more rigorous analysis is needed to determine if this is indeed a more accurate estimate.
Image Source: The WuXi PharmaTech Content Team is organized according to the reference [5]
▲Mondo analysis results (Source: Reference [7])
Call for action
It’s clear that the industry must act together globally through clinical and computing resourcesTo collect, consolidate and manage the most reliable and up-to-date knowledge of rare diseases. For example, OMIM adds more than 200 new diseases to its database each year. It is also important to coordinate these sources of knowledge on a regular basis.
The authors of the article call on funding agencies and regulatory agencies, patient interest groups, and all other organizations in the rare disease area to support a coordinated, concerted effort to determine what is a rare disease in a neutral, geopolitical manner. .
A set of globally consistent standards that accurately define rare diseases, which will allow you to count rare diseases based on existing knowledge and use rapidly growing genomic knowledge to clarify current unknown or poorly characterized The molecular basis of rare diseases. These efforts will lay the foundation for more effective diagnosis, treatment and care of patients with rare diseases and the development of new treatments. Conversely, if knowledge about rare diseases cannot be collected and planned more effectively, many patients with rare diseases will still be in a state of lack of medical care and will not receive the attention of the health care system.
Disclaimer: This article is for informational purposes only. The views in this article do not represent WuXi PharmaTech’s position, nor On behalf of WuXi PharmaTech supports or opposes the views in the text.
References:
[1] WHO. Tuberculosis. Oct 17, 2019. Retrieved Nov 6, 2019 from https://www.who.int/news-room/fact-sheets/detail /tuberculosis
[2] Daniel J O’Connor. Orphan drug designation — Europe, the USA and Japan. Feb 13, 2013. Retrieved Nov 6, 2019 from https://www .tandfonline.com/doi/pdf/10.1517/21678707.2013.769876
[3] Christopher J. Mungall, Julie A. McMurry, Sebastian Köhler, et al. The Monarch Initiative: an integrative data and analytic platform connecting phenotypes to genotypes across species. Nucleic Acids Res. 2017 Jan 4; 45 (Database Issue): D712–D722. Published online 2016 Nov 29. doi: 10.1093/nar/gkw1128
[4] RF. Orphan Drug Regulations: A Global Perspective. V1, No. 3, 2018. Retrieved Nov 2, 2019 from https://learningportal.raps.org/ Products/1509/rf-article-series-orphan-drug-regulations-a-global-perspective
[5] Melissa Haendel, Nicole Vasilevsky, Deepak Unni, et al. How many rare diseases are there? Nature Reviews Drug Discovery. NOV 5, 2019. doi: 10.1038/d41573 -019-00180-y
[6] Haendel, MA, Chute, CG & Robinson, PN Classification, ontology, and precision medicine. N. Engl. J. Med. 379, 1452–1462 (2018 )
[7]Unni, Deepak; Joachimiak, Marcin; Shefchek, Ken, et al. Rare Disease analysis in Mondo. Oct 10, 2019. doi: 10.5281/zenodo.3477634
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