Task 1.1: Organisation of the Kick-off meeting/workshop and additional F2F meetings
Leader: INSERM Contributors: all partners
Start date: M1 End date: M4
Ahead of the kick-off workshop, a detailed workplan containing a description of all activities of the project, milestones and deliverables to be approved during the kick off meeting will be prepared, and the logistics organised. A report/executive summary will be published out of that workshop. The Kick-off Workshop will be held at Month 5 in Paris.
One additional workshop will be organised in year 2 (and a final workshop if budget allows it), time will be dedicated also to discuss ongoing developments and collaborative strategies.
Task 1.2: Follow-up of the activities
Leader: INSERM Contributors: all Orphanet country coordinators
Start date: M1 End date: M31
The Management Board composed of National coordinators will monitor the progress achieved (compliance with the milestones and timetable validated during the kick-off meeting) and address the possible difficulties and opportunities arising during the project. Dissemination issues will also be discussed and validated by the Management board. Conference calls will be organised for MB meetings every two months.
Task 1.3: Ensure communication and information exchange amongst project participants
Leader: INSERM, Contributors: all partners
Start date: M1 End date: M31
An internal newsletter will be edited every 2 months in order to ensure a smooth communication among participants. Where necessary in between newsletters, emails and conference calls will be organized. It aims to inform the partners on the conclusions of the Monitoring meetings. It will also ensure circulation of information, among all partners, relating to each team’s activities and outputs in order to facilitate the acquisition of comprehensive knowledge by the network.
Task 1.4: Reporting to the Chafea and the DG SANTE
Leader: INSERM, Contributors: all partners
Start date: M1 End date: M31
The project coordinator will act as the official representative towards the Chafea and DG SANTE. The project coordinator will provide them one interim and a final report, assisted by the Financial Officer.

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Lead partner : Inserm
Role of participants: MB will validate the material produced within WP2.
The main channels of dissemination to be used include:
1. Publication of at least 4 articles in the Newsletter of the rare disease community Orphanews; this newsletter (Produced in English, French and Italian) counts more than 26,000 subscribers altogether (multi-stakeholder audience including patients).
2. Publication of all the outputs in Orphanet website. These website has a monthly 1 Mo visitors (of which 46% of health professionals and 25% of patients and their entourage) :
3. Scientific communication: At least two abstract presentations in a scientific conference (ECRD 2020 or ESHG 2021).
Task 2.1. To set up and maintain Orphanet dissemination tools
Start date: M1 End date: M31; Leader: INSERM
In this task, mandatory leaflets and layman reports will be prepared. Articles to be submitted to OrphaNews, the RD community newsletter, will be prepared. Dissemination material will be submitted to the MB for validation. Social networks will also also be used as dissemination tools: (Facebook, Twitter accounts)
Task 2.2 Communication in conferences and workshops
Start date: M1 End date: M31; Leader: INSERM Contributors: all participants
Slides and poster layouts will be produced and made available for Orphanet network members. They will be encouraged to communicate about Orphanet at different events in their respective countries by adapting and translating eventually the material in order to increase awareness of the Orphanet resource nationally, and internationally, so as to benefit from the added-value of the extensive Orphanet network. Furthermore communication budget centralised at the coordinating level can be used to facilitate partners attendance to congresses for results presentation of Orphanet results and/or booths if needed according to Management Board decision. Abstracts will be submitted to at least two conferences (European Conference on Rare Diseases 2020 and/or European Society of Human Genetics 2021).

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Leader: Inserm
Start date: M1 End date: M31
Overall project evaluation will be based on measure of KPI indicators (achievements of tasks and deliverables compared to plans) as well as measuring the process, output, outcome and impact indicators as described in section 2.2.
Task 3.2: Elaborate Satisfaction surveys/stakeholder survey
Leader: MUW Contributors: Inserm
Start date: M1 End date: M31
Online satisfaction surveys will be made available to measure satisfaction of partners project (regarding coordination and dissemination activities) as well as satisfaction surveys for the end-users of the deliverables and satisfaction surveys of the Orphanet website. Survey content will be discussed with the MB. These surveys will include a section for improvement suggestions in order to further discuss them by the MB and implement them if relevant.
Orphanet Stakeholders survey approved by the European Commission SGPP and BoMS chairs : A stakeholder satisfaction survey will be proposed to the European Commission for approval before sending proactively to representatives of all stakeholders in the field of RD in all Member States (MS), as well as to members of the SGPP (the Steering Group on Health Promotion, Disease Prevention and Management of Non-Communicable Diseases) and of the BoMS (the Board of Member States for European Reference Networks), in order to assess Orphanet knowledge and satisfaction within the different groups and to explore funding opportunities.

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Task 4.1: Maintain and expand the Orphanet rare diseases nomenclature and classification
Task Leader :INSERM Contributors: Sciensano, MHH, CIBER, OPBG, DGS, IPCDZ
Start date: M1 End date: M31
During this task, the inventory and classification of RD annotated with genes cross-referenced with other resources will be expanded and maintained so as to provide the RD community, from healthcare to research, with a well-structured hierarchy specific for RD with different degrees of granularity so as to allow linking data coming from healthcare (i.e. clinical diagnosis in health records) to data coming from research (i.e. genetic entities in databases).
The nomenclature and classification will be maintained and expanded, so as to follow the evolution of knowledge. The methodology involves a comprehensive and regular literature survey. It also includes taking into account the input from the RD community in a more systematic way through a web-based curation platform (www.curation.orphanet.org) and through direct contacts with expert groups, and in particular, ERNs. For each new or modified entity in the Orphanet nomenclature a definition will be produced in WP5, and specific annotation characterizing the disease (typology, the fact that it is a historical entry, deprecation or obsolescence of entries); the sources for decisions will be traced. Semantic relationships between entities in the nomenclature will be created to build the classification and every entity removed from the nomenclature will be referred to an entity in use in order to ensure the use of the nomenclature overtime.
Translations of the rare diseases nomenclature and classification are currently carried out in France, Belgium, Czech Republic, Italy, Germany, Portugal, Spain and Poland and will be maintained. Additional translations will be encouraged as a national effort in each country.
Orphanet nomenclature is made available to be downloaded in Orphadata, and as dedicated Orphanet Report Series published every 6 months in 8 languages.
Task 4.2 To maintain and update mappings between the Orphanet nomenclature of RD with other medical terminologies.
Task Leader: INSERM; Start date: M1 End date: M31
Mappings to ICD10, OMIM, SNOMED CT, UMLS, MeSH, MedDRA and ICD11 will be maintained and updated according to a methodology adapted to each target terminology and comprising a combination of semi-automated and manually curated alignments. In particular, Orpha-ICD11 mappings will give rise to new proposals for addition/corrections in ICD11, and alignments between Orphacodes and ICD11 URIs will be made available together with the Orphanet nomenclature when ICD11 is released. Mappings are expert-curated together with the annotation if the alignment is exact or partial.
Alignments will be delivered together with the nomenclature in a re-usable format through Orphadata as well as displayed in each specific disease page in the Orphanet website.
Task 4.3 Genetic annotations and interoperability with genetic databases
Task Leader: INSERM ; Start date: M1 End date: M31
In order to provide interoperability between the Orphanet nomenclature and gene-related resources, links between genetic RD and genes based on the survey of most recent peer-reviewed publications will be continuously updated, as will the cross-referencing with other genetic databases (OMIM, HGNC, and others) in use in patient registries and mutation databases, which is made by semi-automatic cross-reference each month. The role of genes in the aetiology of RD will also be provided (causative, major susceptibility factor, modifier, major role in the phenotype, etc) and validated according to published validation criteria and to expert validation, in particular through the Genetic Advisory Board, but also during the update of the encyclopaedia (cross-talk with WP5).

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Task 5.1 Produce and update epidemiological data on RD
Leader: Inserm ; Start date: M1 End date: M31
Epidemiological figures are produced proactively through literature review, as well as by survey of prevalence and incidence figures produced by registries. Data comprise: point prevalence, incidence, birth prevalence, lifetime prevalence, and number of cases/families per geographical area. Figures are submitted to expert validation and used to update the epidemiology section of summary information on RD (Orphanet encyclopaedia) produced in Task 5.3. A compilation of point prevalence and incidence average figures will be produced as an Orphanet Report Series (ORS) twice a year. Crude data will be made available and updated in a monthly basis through Orphadata for re-use under Data Transfer Agreement for research.
Task 5.2 Maintain updated information on orphan designation and drugs linked to the RD nomenclature
Leader: Inserm ; Start date: M1 End date: M31
Orphan designations and drugs are retrieved through monthly survey of European Medicines Agency and Food and Drugs Administration, linked to the corresponding RD in the nomenclature and enriched with metadata (indications, sponsor, dates of designation/approval etc) and linked to clinical trials when applicable. Data are registered in the database, then summarized in compiled reports (Orphanet Report Series on orphan drugs in Europe) and available as downloadable files under Data Transfer Agreement on Orphadata for analysis.
Task 5.3 Orphanet encyclopaedia maintenance and update
Leader: Inserm Contributors: all participants; Start date: M1 End date: M31
Subtask 5.3.1 Abstract/definition production
Textual information for each rare disease completes the Orphanet nomenclature and produces the Orphanet encyclopedia of RD. In particular, this task will produce a definition for each new rare disease in the database (that will be disseminated together with the Orphanet nomenclature of RD in order to ease coding RD; Task 4.1), and up-to-date structured abstracts for the less rare diseases, by developing a strategy for updating currently available abstracts through the web-based curation platform. Definitions and abstracts are produced by medical writers based on literature reviews and reviewed by internationally recognized experts. A strategy producing new and updated information on RD will be adapted so as to optimise the use of other sources of information avoiding duplicating efforts (i.e. expert networks, and in particular ERNs, learned societies, etc). The writing activities can be shared inside the Orphanet network if dedicated resources can be allocated by Orphanet teams: in the context of the previous JA, a new, decentralized organization was initiated to share the medical writer and medical validation activities, that showed the difficulty recruiting medical writers at national level. However the medical validation was successfully distributed to the teams: currently Lithuanian and Slovenian teams are part of the international editorial team as medical validators. This distributed organisation of work allows progressing faster and will continue and encouraged in this task.
Translations of the Orphanet encyclopaedia is currently carried out in France, Belgium, Italy, Germany, Portugal, Spain and Poland. Translations will be encouraged as a national effort in each country.
Subtask 5.3.2 External content acquisition
Task leader: Inserm Contributors: all participants; Start date: M1 End date: M31
Orphanet Network members will contribute identifying and assessing relevant articles in every MS language according to Orphanet’s quality standards, using quality assessment charts. Selected articles, including layperson articles, and clinical practice guidelines will be published in the website after obtaining the copyright holder permission in order to increase the coverage of information available per each disease in as many languages as possible, independently of the fact that
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Task 6.1. Expand and update the directory of expert resources in all the countries of the Orphanet network.
Task Leader: INSERM Contributors: MUW, SCIENSANO, BAPES, CUNI, MHH, UT, CIBER, Rinnekoti, PHE, KDB, OTH, HSE, OPBG, VUHSK, CCUH, DHIR, LUMC, IPCZD, DGS PT, UMF IASI, IMGGI, KI, UMCL, OUS-BAR, Center of medical genetics and primary health Armenia, GeRaD, the Chaim Sheba Medical center, McGill University, TRI, HUG
Start date: M1 End date: M31
Data collection on expert resources in MS provides a unique source of added-value information to meet two different needs: to allow for the identification of the appropriate resources for a given disease/group of diseases in a given country, therefore improving referrals and facilitating cross-border care, and to allow for analysis of the situation of the offer of resources par disease or group of diseases in a given country.
More particularly, this task will continue identifying expert centres and networks of expert centres (in particular European Reference Networks) so as to reflect healthcare offer at national and European level; identifying patient registries; identifying clinical laboratories performing diagnostic testing including NGS, including their coverage in terms of diseases and genes; identifying patient organisations across Europe and beyond.
During this project, the collect methodology will be based in the establishment of partnerships or agreements with data source holders, in order to ensure the data are as complete and up-to-date as possible, and compliant with the Orphanet Standard operating procedures. Cooperation with ERNs will be reinforced towards this aim. In addition, all the professionals already registered in the database will be invited annually to update their activities registered in Orphanet using the Orphanet registration tool.

Collected resources are linked to the appropriate level of granularity in the classification allowing users to find the data in the Orphanet website by disease or by group of diseases. Data are annotated with metadata, including the last date at which the professional has updated them.
A special attention will be focused at the representation of activities related to ERNs in a user-friendly way.

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Task 7.1: To increase the capacity of the teams populating the database to produce database content according to the Orphanet standards of quality, thus improving Orphanet’s transparency and traceability;
Task Leaders: INSERM ; Start date: M1 End date: M31
The quality of the database relies on three pillars: clear and transparent procedures; well-trained teams; overarching quality control.
Orphanet has put in place a Quality management System (SMQ), which methodologies and tools aim at implementing the standard ISO9001 approach. It is based on a number of quality management principles including a strong end-users (customer) focus, the motivation and implication of top management, the process approach and continual improvement.
Within this general frame, this task will continue the work initiated in RD-ACTION, identifying each process involved in the population of the database with a end-users focus. Clear written procedures will be produced or updated and disseminated in the network (Subtask 7.1.1), and will constitute the basis for training cycles (both at distance and face-to-face) of all the teams in the network (Subtask 7.1.2). Training sessions will be assessed and repeated if necessary. Sources and dates of data production will be published to increase traceability.

Furthermore, subtask 7.1.3 will set up a strategy for overarching quality control, in order to ensure, as much as possible, internal consistency and accuracy of the database. All teams will be involved in correcting errors identified through quality control, and preventive measures will be derived for the future, and will give raise to improvement of the procedural documents, so as to establish a continuous improvement dynamic in the network.
Task 7.2 Tooling development and improvement for a better data management in the Orphanet database
Task Leaders: INSERM ; Start date: M1 End date: M31
This task aims to provide overarching database data management tools and IT support. The evolution of the Orphanet IT system towards a more flexible knowledge base will be continued during this project, in order to stick to most up-to-date data management technologies and to allow smoother partnerships and development sharing, to ease data collection, edition and quality control, as well as exploitation of data. This evolution contributes to enhance the position of Orphanet by allowing a better interaction with the (bio)informatics environment, and to enable partnerships.
During this task, tooling will be further improved and adapted to better fit the data collection, edition, validation process and quality control.
During this project the French based IT team will become international as a bioinformatician based in the Irish team will join the team.

Task 7.3 Enhancing the Orphanet network and Orphanet national teams
Task Leaders: INSERM Contributors: all participating members
Start date: M1 End date: M31
This task will set up a two-layer organisation in order to keep a good level of cohesion within the Orphanet network, which is constantly growing (41 countries including associated countries). It is important to ensure that the internal culture, missions and strategic objectives are equally shared across the network and that targeted actions are taken to address the specificities of each country situation, in order to consolidate the position of Orphanet as national-level reference database and information service for rare diseases. In the last year of RD-ACTION an Operating Committee (OOC) has approved by the Management Board (MB): it is composed of country coordinators representing geographical areas covering 4 countries; each representative works closer with his/her group of countries to analyse the situations, the needs to be addressed at the local level and the proposed actions to improve Orphanet visibility and position. OOC will meet regularly by teleconferences and face-to-face and actions plans are proposed to the MB, with the ultimate goal of promote sust
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