IRDiRC: The International Rare Disease Research Consortium
“The goal of this initiative: designating resources for RD research that have received recognition by researchers in the RD community.”
The International Rare Disease Research Consortium (IRDiRC) was created in 2011 to increase research in rare diseases (RD) and contribute to the development of over 200 new diagnoses and therapies. This organization promotes the need for collaboration in rare disease research and effective circulation of current findings. In 2015, the IRDiRC produced a quality indicator for rare disease research called the IRDiRC Recognized Resources. The goal of this initiative: designating resources for RD research that have received recognition by researchers in the RD community.1 All resources under this label undergo a review process through independent researchers and the members of the IRDiRC Scientific Committee.
There are two mandatory criteria that need to be met by each of the proposed resources. First, it needs to be within the mission of the IRDiRC in that it is functional and accessible to all researchers. It also needs to have multinational connectivity in terms of having a maintenance team, quality control protocol, scientific peer review process, financially visible, and adheres to ethical requirements.1 Some of these resources include bioinformatics platforms, software, and RD biospecimen collections. There are also a number of important resources used in the field but have been excluded from the IRDiRC Recognized Resources, such as commercial resources, national, regional or institutional registries for RD and biobanks, and resources that are primarily designed for broader uses but can be used in RD research. Some examples of these would include partnerships with highly specialized vendors, partnerships with site advocacy groups, and biostatistical and data management experts. These are excluded since these resources are not primarily designed for RD research and focus more on the commercialization aspect of the field.1
“ It has allowed for matchmaking efforts that have enabled the identification of new disease genes and undiagnosed syndromes, thereby facilitating the publication of over 700 peer-reviewed scientific publications since 2004.”
Over the past year, there have been a total of 13 resources accepted into the IRDiRC Recognized Resources. These can be grouped into four categories: facilitating international data sharing for discovery, knowledge organization and ontologies, networking patient registries and therapeutic development. One of the core objectives of the IRDiRC is creating a global network for data exchange between researchers in the rare disease field, which is why resources that facilitate international data sharing are critical to this organization. For example, PhenomeCentral is a private and matchable platform for secure sharing of a patient’s genotypic and phenotypic data within the field.1 However, it can also be used as a public record to facilitate collaboration between clinicians globally. The record remains private unless the submitter accepts to share the information with researchers and other users.2 The database is also able to match the record to similar profiles based mainly on gene-level information. Software within the program called Exomiser is used to identify prioritized candidate genes that can be examined to determine causation for certain diseases or traits in future clinical trails. All phenotypic information is left more general to protect the submitter.2 Another example would be DECIPHER, which is a platform used to share and analyze possible phenotype linked pathologies in patients with rare diseases. It has allowed for matchmaking efforts that have enabled the identification of new disease genes and undiagnosed syndromes, thereby facilitating the publication of over 700 peer-reviewed scientific publications since 2004.3 Both DECIPHER and PhenomeCentral are part of the Matchmaker Exchange Initiative, which is a collaboration between the Global Alliance for Genomics and Health and the IRDiRC. This initiative will provide the basis for further research in the RD field and support the goal of identifying 200 diagnoses and therapies by 2020.1
“An inventory of rare diseases has been maintained since 1997 in order to provide an exhaustive list of terms designating rare diseases.”
Furthermore, a second goal of the IRDiRC is to establish effective knowledge organization strategies and ontologies to effectively disseminate information to researchers within the field and make sense of the current findings. If there is a lot of research circulating in different countries but a lack of communication or understanding to piece it together, the research becomes unusable. Two databases have been identified to improve access to RD data. The first one is Orphanet, which is a portal for information on orphan drugs and rare diseases. An orphan drug is essentially any drug that is commercially undeveloped due to limited profitability from its use. This system encompasses multilingual terminology, multi-hierarchical classification, and classes of genes and manifestations. An inventory of rare diseases has been maintained since 1997 in order to provide an exhaustive list of terms designating rare diseases.4 It is updated monthly with changes that include new disorders, updating preferred terms for certain disorders, expanding the synonyms for a disorder and creating newly designated entities.
The second is the Online Mendelian Inheritance in Man (OMIM), which is also a database of phenotypes and genes with over 23,000 entries. This is a primary resource in cataloguing current relationships between diseases and genes, and for describing rare Mendelian diseases. 1 MIMmatch is a new OMIM service initiated in 2013 to follow and receive updates for entries they find interesting. It also allows them to network with researchers in their field and obtain daily updates on new phenotype-gene relationships established in the database. 5
Also, ontologies improve the dissemination of information by creating a consistent language for science and medicine. For instance, the Orphanet Rare Disease Ontology (ORDO), provides a structured vocabulary for rare diseases and can identify relationships between genes and diseases.1 This ontology organizes rare diseases based on their phenome type and allows for complex queries including epidemiological data, such as prevalence, mode of inheritance and age of onset for the disease.6
Finally, international patient registries are essential to the IRDiRC’s goal since they allow for natural history studies of these diseases and provide access to patient data for recruitment into clinical trials. The only resource included in the IRDiRC Recognized Resources is the TREAT-NMD, which is an international registry that provides access to patients with rare neuromuscular diseases worldwide. Currently, there are not enough clinical trials examining potential therapies for neuromuscular diseases. The TREAT-NMD Advisory Committee for Therapeutics (TACT) was created to provide guidance for the development of novel therapies for these rare diseases. It aids in collecting meaningful data that can be implemented in the use of future therapies.6 This will enhance the efficiency of recruitment for these clinical trials and allow for the creation of future diagnoses and therapies.1
In conclusion, the IRDiRC Recognized Resources has started to fill the gaps in the tools needed to further RD research such as access to patient registries, data sharing for new findings, effective knowledge organization, and therapeutic development. As of now, there are only 13 resources included in the recognized resources. However, collaboration with other international projects such as the Human Variome Project will help in expanding the techniques used in RD research. Through successful integration of RD communities around the world, standardized tools and platforms established will advance future developments in this field.
Works Cited:
1. Lochmuller H, Cam L, Jonker H, et al. IRDiRC Recognized Resources: a new mechanism to support scientists to conduct efficient, high-quality research for rare diseases. European Journal of Human Genetics. 2017;25:162-165. http://doi:10.1038/ejhg.2016.137.
2. Buske J, Girdea M, Dumitriu S, et al.PhenomeCentral: A Portal for Phenotypic and Genotypic Matchmaking of Patients with Rare Genetic Diseases. Human Mutation. 2015;36(10):931-940. http://doi:10.1002/humu.22851
3. Chatzimichali A, Brent S, Hutton B, et al. Facilitating Collaboration in Rare Genetics Disorders Through Effective Matchmaking in DECIPHER. Human Mutation. 2015;36(10):941-949. http://doi:10.1002/humu.22842.
4. Rath A, Olry A, Dhombres F, et al. Representation of rare diseases in health information systems: The orphanet approach to served a wide range of end users. Human Mutation. 2012;33(5):803-808. https://doi.org/10.1002/humu.22078.
5. Amberger S, Bocchini A, Schiettecatte F, et al. OMIM.org: Online Mendelian Inheritance in Man (OMIM), an online catalog of human genes and genetic disorders. Nucleic Acids Research. 2015;43:789-798. http://doi.org/10.1093/nar/gku1205.
6. Vasant D, Chanas L, Malone J, et al. ORDO: An Ontology Connecting Rare Disease. Epidemiology and Genetic Data. 2014. http://www.orphadata.org/cgi-bin/inc/ordo_orphanet.inc.php
7. Heslop E, Csimma C, Straub V, et al. The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development. Orphanet Journal of Rare Diseases. 2015;10:49-55. https://doi.org/10.1186/s13023-015-0258-1
Cite This Article:
Ravi R., Chan G., Lewis K., Palczewski K., Ho J. IRDiRC: The International Rare Disease Research Consortium. Illustrated by K Ala. Rare Disease Review. November 2019.
DOI: 10.13140/RG.2.2.11395.66087.
