AGENDA - Europa · 2016-09-26 · automation) - Improve user-friendliness (e.g. providing autonomy to national teams, increasing online interactivity with Orphanet users) - Be sustainable

INFORMATION SCIENTISTS’TRAINING Rare Diseases Platform, 96 rue Didot, Paris, France

AGENDA

Monday 30 January 2012

Room Primevère (level0); breaks and lunch: Petunia(level-1)

11h30-13h00 General Orphanet Presentation (minutes-taker: Idoia G.)

13h00-14h00 Welcome lunch

14h00-15h30 Diseases database (minutes-taker: Ursula U.)

15h30-16h00 Coffee break

16h00-17h30 Translations (minutes-taker: Martina D.) 17h30-18h30 Technical Major Training (for current Major users only) 19h30 Dinner

Tuesday 31 January 2012 Rooms Primevère(Gr1) (level0) and Gardenia (Gr2) (level-1); breaks and lunch:

room Petunia(level-1 ) 8h30-10h00 Workshop 1

Group 1 Data collection of Patient care services ( minutes-taker: Rita T.)

Group2 Data collection of R&D (minutes-taker: Ana V.R.)


10h30-12h00 Workshop 2

Group 1 Data collection of R&D (minutes-taker: Konstantina M.)

Group2 Data collection of Patient care services (minutes-taker: Claude B.)

12h00-13h00 Lunch

13h00-14h30 Workshop “Validation process and Quality assurance” Group 1 and Group2 (minutes-taker: Maria Elena M.) 14h30-16h00 New procedures on quality assurance of Medical laboratories (minutes-taker: Bénédicte B.)

PARTICIPANTS

GROUP 1

Kristine Hovhannesyan (AM) Alexandra Ramssl-Sauer (AT)

Ursula Unterberger (AT) Sille Vahtra (EE) Rita Teek (EE)

Konstantina Merou (GR) Santa Rozite (LV)

Birute Burnyte (LT) Jaber Lyahyai (MA)

Nancy Anoja (QC/CA) Monica Panzariu (RO) Eszter Hegyiova (SK)

Ales Maver (SI)

GROUP 2

Elfriede Swinnen (BE) Ana Ruiz (CH)

Marek Turnovec (CZ) Mareike Derks (DE)

Maria Elena Mateo (ES) Leena Toivanen (FI) Claude Barrère (FR)

Bénédicte Belloir (FR) Idoia Gomez-Paramio (GB, IE)

Martina Di Giacinto (IT) Judith Carlier-de Leeuw van Weenen (NL)

Dorota Karczmarewicz (PL) Sandra Peixoto (PT)

Mayss Naccache (QC/CA) Maja Stojiljkovic (RS)

SPEAKERS: Ana Rath

Els Dequeker Virginie Hivert

Mariana Jovanovic-Lassalle Sylvie Maiella

Observers :

Patricia Posius (QC/CA) Gail Ouellette (QC/CA)

Natalia Ginaldi (FR)

mailto:[email protected]

Orphanet Europe Joint Action

(N°2010 22 06)

TRAINING REPORT

Paris, 30 & 31 January 2012

TABLE OF CONTENT

AGENDA ................................................................................................................................................ 2

Participants .......................................................................................................................................... 3

SESSION I ............................................................................................................................................. 4

1. GENERAL ORPHANET PRESENTATION ........................................................................................ 4

2. DISEASES DATABASE ................................................................................................................... 5

3. TRANSLATIONS ........................................................................................................................... 8

SESSION II .......................................................................................................................................... 10

1. DATA COLLECTION OF PATIENT CARE RESOURCES .................................................................. 10

2. DATA COLLECTION OF R&D ...................................................................................................... 13

3. VALIDATION PROCESS AND QUALITY ASSURANCE ................................................................. 15

4. NEW PROCEDURES ON QUALITY ASSURANCE OF MEDICAL LABORATORIES ......................... 16

AGENDA

Monday 30 January 2012

Room Primevère (level 0); breaks and lunch: Petunia (level -1)

11h30-13h00 General Orphanet Presentation (minutes-taker: Idoia G.)

13h00-14h00 Welcome lunch

14h00-15h30 Diseases database (minutes-taker: Ursula U.)


16h00-17h30 Translations (minutes-taker: Martina D.)

17h30-18h30 Technical Major Training (for current Major users only)

19h30 Dinner

Tuesday 31 January 2012 Rooms Primevère (Gr1) (level 0) and Gardenia (Gr2) (level -1); breaks and

lunch: room Petunia (level -1 ) 8h30-10h00 Workshop 1

Group 1 Data collection of Patient care resources (minutes-taker: Rita T.)

Group 2 Data collection of R&D (minutes-taker: Ana V.R.)


10h30-12h00 Workshop 2

Group 1 Data collection of R&D (minutes-taker: Konstantina M.)

Group 2 Data collection of Patient care resources (minutes-taker: Claude B.)

12h00-13h00 Lunch

13h00-14h30 Workshop “Validation process and Quality assurance” Group 1 and Group 2

(minutes-taker: Maria Elena M.)

14h30-16h00 New procedures on quality assurance of Medical laboratories (minutes-

taker: Bénédicte B.)

Participants

GROUP 1

Kristine Hovhannesyan (AM)

Alexandra Ramssl-Sauer (AT)

Ursula Unterberger (AT)

Sille Vahtra (EE)

Rita Teek (EE)

Konstantina Merou (GR)

Santa Rozite (LV)

Birute Burnyte (LT)

Jaber Lyahyai (MA)

Nancy Anoja (QC/CA)

Monica Panzariu (RO)

Eszter Hegyiova (SK)

Ales Maver (SI)

GROUP 2

Elfriede Swinnen (BE)

Ana Ruiz (CH)

Marek Turnovec (CZ)

Mareike Derks (DE)

Maria Elena Mateo (ES)

Leena Toivanen (FI)

Claude Barrère (FR)

Bénédicte Belloir (FR)

Idoia Gomez-Paramio (GB, IE)

Martina Di Giacinto (IT)

Judith Carlier-de Leeuw van Weenen (NL)

Dorota Karczmarewicz (PL)

Sandra Peixoto (PT)

Mayss Naccache (QC/CA)

Maja Stojiljkovic (RS)

SPEAKERS:

Ana Rath

Els Dequeker

Virginie Hivert

Mariana Jovanovic-Lassalle

Sylvie Maiella

Observers :

Patricia Posius (QC/CA)

Gail Ouellette (QC/CA)

Natalia Ginaldi (FR)

Guillaume Vaquer (FR)

mailto:[email protected]

Orphanet Europe Joint Action Training report – 30-31 January 2012 - Paris

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SESSION I

30 JANUARY 2012

1. GENERAL ORPHANET PRESENTATION (minutes taker: Idoia Gomez-Paramio)

Ana Rath gave an overview on Orphanet, a comprehensive portal for rare diseases and

orphan drugs.

The first part of this talk explained the origin of Orphanet in 1997, conceived to address the

needs in rare disease’s information, research and patient care at this time. Different grants

and contracts have allowed the further development (technical and geographical) of

Orphanet, which is used all over the world by patients and professionals.

In the second part, an overview regarding the inventory of Rare Diseases was given. This

inventory is linked to a multidimensional classification by medical specialty, based on

international literature and expert’s advice and updated monthly. The other additional

information provided, such as the links to other indexation systems, epidemiological data,

genes and relevant literature were also explained.

The third part focused on the Encyclopaedia that includes the abstracts/disease summaries,

review articles for professionals and patients and clinical guidelines. The coordinating team

is aware of the existence of excellent clinical guidelines in other countries. These already

available resources could be used for the global benefit of the rare disease community.

Therefore, it was encouraged to contact Ana Rath whenever we found high quality clinical

guidelines in our country; in case these fulfil our quality standards, the coordinating team

will provide advice about getting the necessary permission for their publication on Orphanet.

This topic was followed by a short description of the Orphanet Directory of resources (expert

centres, medical laboratories, patient organisations, research projects, patient registries,

mutation registries, biobanks, clinical trials and networks), the directory of orphan drugs, the

external (the Orphanet report series, OrphaNews) and internal communication tools

(OrphaNetWork) and the –positive- results of the satisfaction survey of English-speaking

users.

Very interesting was the information regarding the IT side of Orphanet; it gave an insight

about the different tasks daily addressed, the necessary servers, the technical infrastructure

and its new challenges.


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Later on, the Joint Action’s main objectives were described in detail; these are:

- Improve existing services (e.g. directory of expert resources by improving

procedures, training and supervision)

- Develop new services (e.g. Orphadata and national websites)

- Become the tool to serve national plans/strategies at country level and EU objectives

- Improve cost-effectiveness (e.g. development of Collector and increase of

automation)

- Improve user-friendliness (e.g. providing autonomy to national teams, increasing

online interactivity with Orphanet users)

- Be sustainable

- Establish the appropriate governance

Also the most useful Orphanet tools (Major, Plator, Orphadata, Arbor, Actor and

OrphaNetwork) were explained. Special attention was given to the new interface of Plator

and the new tool Orphadata.

The talk finished with information regarding the funding for this Joint Action that has been

provided by the European Commission, France and other partners.

The power point presentation of this session is available here.

2. DISEASES DATABASE (minutes taker: Ursula Unterberger)

In the database, each disease is linked to several kinds of data:

- ICD-10 (coding)

- terminologies (indexation – Thesaurus)

- multiaxial classifications

- identity card (for documentation)

ICD-10 only comprises around 500 rare diseases. Orphanet is currently working together

with the WHO on the revision of ICD-10 because each rare disease should have its own code

in the new classification system.

Another current project is the indexing of each disease with disability terms so that diseases

can be classified with respect to dysfunction.

Also, rare diseases are now documented with incidence/prevalence figures and with age of

onset/death, and mode of inheritance.

https://network.orpha.net/network/cgi-bin/articles.php?lng=en&pg=116


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Currently, Orphanet offers a comprehensive list of rare diseases; for each entity, there are 2

numbers:

1) ID# (identity in the database, „PatID“); this is connected to the

2) Orpha-number (displayed in the identity card of the disease; it will be connected to

ICD-11)

The diseases are also linked to genes. Abstracts are part of the identity card of a disease but

there may be other kinds of texts (either produced by Orphanet or used with permission)

linked in the “detailed information” section.

Edition process for the diseases database

First, a Pubmed search for the specific entity is performed for annotation/indexation/writing

of texts; this is sent to experts for validation. After that, the data is quality controlled for

completeness and coherence by the Orphanet coordinating team.

In principle, the database is updated (also) in response to the demands of the partner

countries: if a disease is missing in the database, partners should send an email to the

coordinating team ([email protected]). These requests will always be treated with priority!

Once a month, a disease meeting of MD Orphanet’s staff is held where decisions are made

concerning

- validity of a potential new entity, creation of new entries

- correction of mistakes (e. g. double entries), deletion of old entries

- revision of classifications

- which non-rare diseases should be included in the database (e. g. fibromyalgia); the

decision to include a non-rare disease in Orphanet is based on the need for

information; information on testing of susceptibility genes will also be included

(collection of data on genetic testing is considered a general task of Orphanet!). Non-

rare diseases can only be linked to genetic testing and patients’ organisations; other

entries will be deleted after validation by the coordinating team.

- for each entry, they decide on the nomenclature (preferred term and synonyms, key-

words (if needed)), the classification, and any attached information (type of text,

epidemiology, genes, OMIM#)

The information scientists then receive a disease meeting report with the Quality Assurance

review (also published on OrphaNetWork).

Another task of Orphanet is the production and the update of abstracts. These abstracts are

written for physicians, and are structured and expert-reviewed. They are primarily translated

to 6 languages. Beside abstracts, there are also short definitions (on extremely rare

conditions, or if the abstract is still pending).


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Methodology for classifications

A literature search is performed in addition to organized expert meetings; thus, the

Orphanet classification of rare diseases is created. It is multidimensional and updated on a

regular basis.

Currently, there are two kinds of classifications in the database:

- Orphanet and published classifications (the ones displayed on the website)

- functional classifications (not displayed but stored)

Linking expert centres to a group of diseases allow patients suffering from a ultra-rare

disease included in it to be oriented to a relevant service, even though there is no expert for

this disease because of its extreme rarity.

Sometimes, adjustments to classifications in Orphanet are made to better depict the reality

as a consequence of quality control meeting on expert resources.

Procedure to link diseases/tests etc.

Either check classifications on the website (but: as mentioned before, not everything is

displayed there, so this is not exactly the same as in Arbor), or using Arbor (it is

recommended, even if some difficulties using it can be encountered as the tool is no longer

updated, as it was not developed by the IT-team, but the classifications are updated).

How Arbor functions was described briefly

Genes in the database

Each webpage on a gene contains a list of diseases linked to the gene, plus the expert

resources linked to the gene.

Sources of information are Orphanews, Pubmed surveys, OMIM surveys (performed

monthly), and demands of the partner countries.

In Orphanet, genes are linked to gene testing, research projects, clinical trials if gene therapy

is involved, and mutation registries/databases. Genes and diseases have to be consistent

(when in doubt, check the literature; contact Orphanet, if a gene/disease is missing)!

Genes listed in Orphanet include causative genes (genes with constitutional or acquired

mutations, fusion genes), major susceptibility factors, genes with a major effect on the

phenotypes associated with chromosomal anomalies, and modifying genes.


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Next/ongoing projects

1) Make types of entities better identifiable (e. g. disease vs. syndrome etc.)

e. g. if there is proof in the literature that a condition is no longer a separate disease,

but part of a syndrome, there will be an automated text displayed on the website

that says „this entry has moved…“ or „this entry is described under…“

For „historical“entries (e.g. no publication within the last decade), no resources will

be linked; the texts are however kept.

2) Improvement of the representation of genes

(e.g. identifying genotype-phenotype correlation)

3) creation of new annotations


3. TRANSLATIONS (minutes taker: Martina DiGiacinto)

Increasing the language availability of the Orphanet website and related documents is one of the top priorities of the Orphanet Europe Joint action. Currently the only mandatory translation is the Orphanet National website in the national language, however if a National funding is identified, Orphanet National teams can also have the possibility to work on 5 different translation packages:

- Orphanet International website, including the website layout, list of diseases and thesaurus clinical signs and symptoms

- Encyclopaedia for professionals - Emergency guidelines - General public encyclopaedia - OrphaNews Europe.

In-depth of each package and some general considerations about translation were given.

The main ones are the following:

- translation can be performed by any Orphanet national team or people designated/appointed by the country coordinator

- regarding validation of the translation: • non medical translated content must be validated by the national team • medical translated content must be validated by the Country coordinator or a

physician designated by him/her; - Globally the national team is entirely responsible for the translation - There shall be one contact point for translation per team.

During the presentation, Sandra Peixoto from Orphanet Portugal shared her experience translating the Orphanet web site in Portuguese: it took her a month to translate the static pages and two months to translate the whole disease list (one person working full time); it is



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difficult to have the translations validated, it takes a long time because professionals are not willing to validate abstracts they didn’t write. She suggested that validators should be acknowledged to motivate their work. It was reminded that currently the validators of the translation can be acknowledged on the national website.

Maria Elena Mateo from Orphanet Spain highlighted that 4000 characters limit for abstracts in Major is a problem with Spanish language, in which words are longer than in English. In fact, when Spanish abstracts exceed this limit, she is forced to delete words in order to respect it. Ana Rath answered her saying that this bug will be solved with new procedure for abstract insertion. Abstracts cut in sections will expand this limit once the translation screen is developed. For the moment, even with the new Major abstracts-in-sections screen, the 4000 characters limitation is kept. In the part dedicated to general public encyclopaedia translation, Maria Elena Mateo related the Spanish experience: Orphanet Spain received a funding and so they are starting to translate 7 articles of this encyclopaedia, the ones of more interest.

At the end of the presentation, Martina Di Giacinto from Orphanet Italy spoke about the Italian translation of OrphaNews Europe, in particular she pointed out the difficulties in setting up the Editorial Board and familiarizing with html codes.




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SESSION II

31 JANUARY 2012

1. DATA COLLECTION OF PATIENT CARE RESOURCES (minutes taker: Claude Barrère and Rita Teek)

The aim is to have a comprehensive directory of expert resources for rare diseases in a given country.

In decreasing order of priority:

The points 1 to 3 above were analysed and explained in details please refer to the powerpoint presentation (available here).

Before collecting info:

- Identification of sources: • define the national sources of information • national sources of information should be transmitted to the coordination team and

advertised on the national website • funded networks are a priority source for collecting data

- Data selection • Should match the selection criteria depending on the type of data

Data collection:

HOW:

• partnerships with official sources • direct data retrieval or registration forms directly sent to professionals for non-

official sources

1 • Expert centres / Centres of expertise

2 • Diagnostic tests

3 • Patient organisations

4 • Clinical trials

5 • Patient registries

6 • Mutation registries / Biobanks

7 • Research projects



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WHO:

• Supranational information (such as EU-funded research networks or multinational clinical trials) is collected by the coordinating team – for Europe only

• National and regional information is collected at national level • Technical procedure available at:


Data registration:

• Handled by the coordinating team on behalf of the national team or by the national team if access to Major is granted

Expert centres

- Definition and selection criteria - Data collection of information about expert centres is top priority for Orphanet (think

also about Networks of Cns). For genetic counselling Cns: be as comprehensive as possible.

- For the definition of an expert centre if there is no official designation in the country; a new questionnaire for professionals was established on the basis of the EUCERD criteria, in addition to the registration form; in this questionnaire all questions should be answered.

- How to collect information: • information comes from Professionals or Patient Organisations, • registration is handled in Paris on behalf of the teams that do not have access to

MAJOR • registration forms are available on OrphaNetWork here , they can be translated in

national language • the forms have to be filled in by professionals and checked by national teams

Diagnostic tests

- Definition and inclusion criteria. - Quality management systems:

• Accreditation • External Quality Assessment

- Cytogenetic: Classical karyotyping analysis should be linked to "Joker disease" unless more specific analysis is performed.

- specific inclusion criteria depending on the type of test: it is important to know what kind of test was used, and what is the technical competence behind it.

Patient organisations

- Definition and selection criteria - Note: for general organisations for rare diseases, remind to link them to the "Rare

disease" entry (PatId) (not connected to the classification).




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General recommendations

All the information should be checked by the Information scientist and/or the country coordinator. Information on expert centres should be validated by the coordinator prior to publication. Mapping with diseases and genes is crucial: check the classification in Arbor!

If a disease or gene is missing, contact the coordinating team (important – the reason why you ask a creation and references!) All the questions will be discussed once a month during the disease meeting

Information about the expert link

- it gives access directly to the person’s data or to his/her activity. Common URL :

http://www.orpha.net//consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=

- AbsID: It is a unique and stable reference for any entry in the database (= Orpha number) - Data ID: for internal use only - You can find the AbsId that corresponds to the DataID in the AbsId file from Plator

https://www.orpha.net/plator/

Questions & Answers

Expert centres

Question: publishing information on the expert centre could be controversial. Is the questionnaire of help for those centres to be officially designated?

Answer: In France with officially designated centres, it's easier. Until official designation, you have the questionnaire to help you selecting the centres. As part of the Quality Control, we had to delete all clinics for a country, because they were not expert enough. This questionnaire can also allow us to quality control expert centre already registered, and validate "old" data.

Validation of data: In last year meeting, it was decided that generally speaking it should be a coordinator or scientific committee decision.

Most important criteria: Multidisciplinary approach, Publications or collaboration in expert Networks, Participation in clinical trials

Question: Example of a Metabolic clinic specialising in some specific diseases: what link should be used?

Answer: always better to have a specific and defined group of disease than a too large one. Cases met in Quality meetings help the coordinating team to answer and help Partners.

http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert

https://www.orpha.net/plator/


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Question: About labels in the Orphanet website, there are differences between "head of" and "Coordinators", secretaries are not always so, but also nurses, could labels be "flagged" to adjust national situations?

Answer: Agreement that in Locs we could change "Secretary Email" to "Contact email".

Question: In Major, could we have a "Comment" window to give information that could be read in QC meetings?

Answer: A dialog box is already planned in Collector, our tool in development to collect and update information in Orphanet.

Diagnostic tests

Question: In Major, the window for diagnostic tests labels is not large enough to write the whole label of the test with necessary details.

Answer: expansion of the list of types of diagnostics is already planned. Three lines should be enough for the title. The detailed description (additional information) should be put in a Word file, copied by "SSH transfer" on the server, and accessed by a link created in the "Protocol" window.

2. DATA COLLECTION OF R&D (minutes taker: Ana Vera Ruiz de Castaneda )

The aim is to have a comprehensive directory of expert resources for rare diseases in a given country.

In decreasing order of priorities:

Directory of expert resources

The points 4 to 7 above were analysed and explained in details according to the presentation

(available here).

Before collecting information

- Importance of the identification of sources and data selection.

1 • Expert centres / Centres of expertise

2 • Diagnostic tests

3 • Patient organisations

4 • Clinical trials

5 • Patient registries

6 • Mutation registries / Biobanks

7 • Research projects



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Data collection of expert resources

Clinical trials

- Definition - Concept of national clinical trials and multinational clinical trials (network of clinical

trials) - How to collect information on clinical trials?

• Registration on Orphanet of anonymous clinical trial • Data collection of non anonymous dataset of clinical trial (principal investigator at

National level) - Important sources for clinical trials:

• Europe: website: https://www.clinicaltrialsregister.eu/ • US website: http://clinicaltrials.gov/

- Dataset to be collected • Core Dataset important to keep in mind EUDRACT Number, NCT Number (URL) • National dataset

- How to collect information on clinical trials in the future? • The acquisition of a core dataset on clinical trials will be automated soon.

Patient registries

- Definition - Important sources: European Networks (Treat-NMD), patient organisations… Biobanks

- Definition Research projects

- Definition - network of research projects is a collaborative research project funded by the

Framework Program of DG Research or E-Rare, clinical networks funded by DG Sanco, a multinational non-therapeutic clinical research study, a network of experts (such as Treat-NMD, ECORN-CF, PRINTO), or a network of clinical investigation centers.

- Important sources for research projects: Websites of funding bodies - Partnerships with national funding agencies - Mandatory dataset:

• Informative label • Name of investigator • Funding body

- Protocols or abstract are very important to highlight the goal of the project and to allow

quality control.

- Research Networks

• Completed research projects: flagged as “completed” No more visible on

• Orphanet

• Completed networks : unlike “completed” activities are kept in Orphanet

https://www.clinicaltrialsregister.eu/

http://clinicaltrials.gov/


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Things to keep in mind

• Avoid duplication between Registry and Research

• Avoid misregistration between Clinical trials and Research • Avoid duplication between diagnostic clinically performed and research projects

aiming to develop diagnostic tests • A diagnostic test with clinical setting has to be registered only in the diagnostic test

section and should be removed from the research project section

Questions & Answers (minutes taker: Konstantina Merou)

Question: What if we have two registries in the same disorder? What can I do?

Answer: Two registries are ok. Both are recorded separately

3. VALIDATION PROCESS AND QUALITY ASSURANCE (minutes taker: Maria Elena Mateo)

All the information included in Orphanet database must be accurate: complete, validated, consistent, uniform and unique. In order to achieve this condition, a validation process has to be performed, but until now this validation was done only after publication, so there is information published which is not correct.

How validation process is currently working

At the moment, validation process is done after publication by the coordination team who organizes data cleansing to ensure accurateness in data between countries and activities, over time and per medical domain.

The “Quality Assurance Review” includes new and updates procedures, a monthly quality control, and specific projects to be implemented.

In the near future, this process will be continued but adapted to better fit the teams’ needs

- Participants requested for shorter and more frequent reports, with more time to answer in order to contact professionals when extra information is needed. It was also requested a summarized conclusion of general recommendations or common mistakes detected.

New validation process before publication

New tools are being developed in order to carry out the validation before the launch of the new entries, and also for old entries already published.


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First of all, at country level must be decided who will be in charge of the validation.

• Validation after release: mini-directories

In May-June 2012, mini-directories will be available for each country by medical domain and type of data. With the tool Exor, the directories will be produced in XML format and offered in html and doc formats, in order to be validated.

- It was commented that people in charge of validation could be too much specialized in some diseases, so they wouldn’t be qualified to evaluate a whole medical area. It was suggested that in those cases, scientific or learned societies could be helpful.

• Quality control after release: Exor

Exor will allow the creation of the mini-directories mentioned, but also other directories in response to particular requests to the database, without SQL knowledge.

Workflow for new entries and their validation

All data must remain unpublished until they are validated at national level: “standby” option in Major.

In order to perform the collection of new data and its validation, a new tool is being developed: Collector. This tool will allow professional and the national Orphanet team to update information on a secure web-based platform.

Information scientists will be in charge of appointing the person who will validate each specific activity and they will be able to monitor the update process.

It was commented that perhaps this online validation process wouldn’t be well received by evaluators or would slow down the process. With a printed version of data, as it is made in the after publication evaluation, the information scientists can manage the validation process and insist with evaluators for the revision.


4. NEW PROCEDURES ON QUALITY ASSURANCE OF MEDICAL LABORATORIES

(minutes taker: Bénédicte Belloir) Because lab results have to be trusted, there is a real need for quality assurance for laboratory results. Quality assurance data This is assessed by 2 main features which are accreditation and EQA. These assessments should be visible on the Orphanet website to show that the laboratory is following the right procedure for its diagnostic tests.



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Then, quality has to be defined; you can have several quality definitions, but one ISO definition corresponds to one standard. Quality standards and accreditation ISO9001 confirms that a laboratory follows correctly its designed procedure, but not that the procedure is correct for a specific test. This can be used in certification of labs: such certifications are not reported in Orphanet. ISO15189 applies to medical labs. It is delivered by one and only one accreditation body per country and applies to the laboratory as a whole entity (including all procedures, internal quality control and participation to EQA). Other country specific standards for accreditation are also available. Other types of quality assurance exist like licensing which is mainly in France and Belgium. They are not reported in Orphanet. Quality management systems EQA is specific for a disease or a technique. It has to be renewed each year to be always up to date with new discoveries (mutations, techniques etc). Only participation and not result is registered, as EQA participation proves that the lab participates and learns. As an example over the past years, labs with mistakes for CF network went down from 33% to 5% One has to be careful with central labs, dispatching the analyses according to the requests: all final labs should be quality checked. The new procedure for validation of quality data is now approved by Eurogentest and available on Orphanetwork (here). Els Dequeker is in contact with all countries accreditation bodies and is willing to help if contact is needed with them to check data.




www.orpha.net

Orphanet

Information Scientists’training

26 April 2012

www.orpha.net

Morning session Agenda

Feedback on the annual update

Feedback on Eqa validated/not validated; off/on line

Post-release validation and mini directories planning

Feedback on Quality assurance procedures

Feedback on IT projects

Feedback on QA review

Any other questions

www.orpha.net

Afternoon session agenda

Orphanet tools

Standard Operating procedures

Data collection

Disease and gene linking

Data validation

Ongoing projects

Any other question

MINUTES OF THE CONFERENCE CALL TRAINING

FOR MAJOR USERS

26 April 2012

MINUTES OF THE CONFERENCE CALL TRAINING FOR MAJOR USERS

2


List of participants

Martin Arles (ES)

Judith Carlier De Leeuw Van Weenen (NL)

Loredana D’Amato Sizonenko (CH)

Béatrice Geissbuhler (CH)

Tiziana Lauretti (IT)

Sylvie Maiella (FR)

Maria Elena Mateo (ES)

Petra van Overveld (NL)

Ana Rath (FR)

Ana Ruiz de Castaneda (CH)

Roberta Ruotolo (IT)

Agenda


Feedback on EQa validated/not validated; online/offline

Feedback on pre-release validation and the EUCERD questionnaire

Post release validation and mini directories planning

Feedback on quality assurance procedures “R”



Any other question about any topic related to Orphanet


The 2011 annual update was launched in November 2011 by contacting by email each professional

registered in Orphanet inviting him/her to verify the up to date status of the activities registered for

him/her in the database through a link. Indication to click on the right panel ‘additional information’ was

given.

The procedure proposed for this update (foreseen by contract) was not ideal but it was the best one for the

current situation (no definitive tool availability yet and no resources to be dedicated for the development

of an intermediary tool which would have delayed the delivery of the other developments). The next

update will be luckily carried out through the definitive tool (COLLECTOR) and therefore the process shall

be optimized and easier.


3

The coordinating team is currently still in the process of updating all the information received by the

professionals who answered the update. The deadline to fill in the tracking table by the 13 May is flexible.

Switzerland team decided to carry out the annual update by contacting all the professionals by alphabetical

order. Globally more than an update of the data what is requested from professionals is to add new data. It

is an ongoing process, which requires more manpower than currently available in the team.

Spain team estimated that approximately 20% of the professional contacted answered. Most of the

updates regard the telephone numbers; probably the professional did not take the time to verify also the

information present in the ‘additional information’ panel. Currently they are not carrying up a follow up on

the professionals who did not answer.

Netherlands team estimated that approximately 24% of the professional contacted answered, however the

emails received did not contained all the information necessary for the update and required a re-contact of

the professional for clarification.

Feedback on EQa validated/not validated; online/offline

The developments regarding this implementation are done and they are currently being tested. This

information will be available online by the 2nd May 2012.

Feedback on pre-release validation and the EUCERD addendum questionnaire

For those countries where there is no official designation of expert centers, an addendum questionnaire

(here) was established according to the EUCERD criteria and it has been made available to the national

teams. This questionnaire is a tool to help the national teams to evaluate the expertise and the relevance of

the expert centre to be registered in Orphanet. The addendum questionnaire shall be validated by the

national coordinator/the scientific committee in charge of pre-release validation (guidelines to assess the

questionnaire are available here). Major using teams upload this document in the dedicated MAJOR screen.

The other teams shall send them to the coordinating team. No quality control is performed without those

questionnaires for non-officially designated centres of expertise. Data will not be published online if not

approved by the designated staff at country level. Country coordinators and/or NAB should decide which

items are the more relevant to define a centre of expertise according to the National landscape.

This questionnaire is not to be filled in by genetic counseling clinics.

The Switzerland team is currently using electronic online registration forms; the EUCERD questionnaire has

been integrated in these forms.

It was suggested that this questionnaire is freely available online for Orphanet users, as some Swiss

professionals asked for. But there may be legal issues in some countries. This issue will be submitted to the

Management Board in Brussels.

Post release validation and mini directories planning

EXOR is a tool that allows creating any kind of request to query the Database for specific purposes. This tool

is being used for the production of mini directories and it will also be used for the transversal quality

control. It is currently being tested by the coordinating team. Technical procedures and user guide will be

made available for the partners in due time.




4

Mini directories are intended for post release validation. The ALTOVA licensing (allowing to produce word

or PDF format from the native XML format) is still pending. Upon availability of this software the mini

directories shall become available and edited for all the countries.

The validation of these mini directories shall be organized at national level and communicated to the

coordinating team.

Currently the mini directories are edited for a given activity and by medical domain. For expert centers the

resulting mini directories for big countries is reasonable however in the case of genetic counseling the

resulting mini directory is not easily manageable (hundreds of pages) and geographical sorting has been

suggested for these directories. The same goes for diagnostics labs data, the national team shall decide

how these date are to be validated and how these data are to be presented in the mini directory ( by

institution, by region, by pages?...) to ease the validation by experts.

However because of the important amount of time needed for the editing of these mini directories it is

kindly asked to the national team to decide before-hand the planning of the production of different mini

directories per activity for the last six months of the year. This will allow a controlled planning of the mini

directories availability and the on-time release by the coordinating team. (For instance, Switzerland wants

to start post-release validation by September)

In addition guidelines for validators and reviewers as well as national teams to manage this process will be

made available by the summer 2012.

It was reminded that mini-directories could also be edited for communication purpose.

Data management process

Standby status of data will be available to allow publication of data only after the validation and quality

control steps. The data could be (by checking the appropriate box in the MAJOR screen) either-not yet

validated at national level either validated at national level.

Quality control will be carried out only on the data that teams have pre-release validated and transmitted.

Pro and cons: Less entries, process could seem slowed down BUT this will result in an improvement in the

quality of data available. In the end there will be less information but more reliable.

This process will be shortly in place within the tool MAJOR (addition of dedicated screens) to ease the

transition to COLLECTOR where this data management process will be implemented also.

It was suggested that in the new MAJOR screens a comment box should be made available for the teams to

ask questions and for the coordinating team to explain the reasons of the QC amendments regarding the

corresponding data.

In COLLECTOR each step will have a comment field, and the coordinating team will ask the IT team to know

if in MAJOR a comment field could be implemented also.

Feedback on quality assurance procedures “R”

The national teams feel that this process is too long, too hard and often late. The problems are due to the

understaffed situation and also to the non-availability of tools. Hopefully the process will be easier and


5

smoother with the new COLLECTOR tool, but also with the implementation of a comment box in MAJOR (if

possible).


The migration of the servers to the new hosting structure (the CINES of Montpellier) will occur in May.

First the development servers and then the production servers: THERE WILL BE NO SERVERS

INTERRUPTION DURING THE MIGRATION. However, as the VPN currently in use (Caribou) is DSI-

dependent (the structure we are migrating from) a new VPN access will be used, all the partners will be

informed on time and detailed procedure will be sent to make the transition the smoother possible.

The IT team will be pretty busy with this migration; therefore the development of the other ongoing IT

projects will be slowed down in May and June.

Currently the way activities are displayed is being modified in CONSOR. As to now it was a geographical

sort (country-region-town), what is being tested is the sort by activities relevance (according to the

level of linking of the activity to the classification). For example for Marfan syndrome all the specific

centres for Marfan syndrome will appear first and then the less specialised centres where Marfan

syndrome can also be treated.

Warning: the information given will be more relevant but if there are linking errors these will be

highlighted.

A warning message like “no specific centre for your disease is present in the DataBase yet “ will appear on

the page if no specific centres are registered. Then the list of more general centres (that is, linked to

entities one or more levels up/down in the classification) will be displayed.

This implementation is currently being tested, partners will also be asked to test it when in pre-production.

COLLECTOR is the name of the tool which main objective is to give more independence to the national

teams in the data collection, validation and update process. This project has been divided into smaller

phases to be more manageable.

Phase 1: defining the data management process (validation steps at national level and quality control)

Phase 2: defining the datasets activity by activity

Phase 3: back office (for national teams and collaborators to manage their data in compliance with

Orphanet quality standards)

Phase 4: Front office (the professional will be able to access and modify their data)


The national teams agreed that more feedback on the amendments and on the decisions taken during

Quality control at the coordinating level shall be communicated by the coordinating team (as previously

discussed, this issue could be addressed by the implementation of a comment box in the MAJOR screen. A

comment box will be definitively present in the future tool COLLECTOR).

Feedback on national IS comments is given in the final “R” report when it is definitely published in

OrphaNetWork website. Pending issues and ongoing discussions are summarised at the end of each “R”

report.


6

Any other question about any topic related to Orphanet

Patient organisation alliances are not very visible on CONSOR as they are under the ‘network’ tab. A

request shall be made to the IT team so that CONSOR can manage heterogeneous lists of activities (Ass and

Net).

A question was raised about how to link exome sequencing with a disease. Genetic testing techniques are

evolving so fast that these changes will warrant changes in the model of genetic tests in Orphanet in the

near future. It is an evolution we will need to address.

Conference call report – 8th October 2012

CONFERENCE CALL REPORT

(JOINT ACTION N°2012 22 06)

8th October 2012


2

CONFERENCE CALL REPORT

Agenda

Post release Quality Control Validation

Mailing to the Expert centres registered in Orphanet and EUCERD criteria questionnaire

Other topics to be addressed by the teams

Participants

Orphanet Austria: Sandro

Orphanet Canada/Québec: Mayss and Nancy

Orphanet Germany: Kathrin and Elisabeth

Orphanet Netherlands: Petra

Orphanet Portugal : Sandra

Orphanet Spain: Maria Elena and Martin

Orphanet Switzerland: Béatrice

Orphanet UK : Idoia

Orphanet Coordinating team: Ana, Charlotte, Sylvie and Virginie

Post Release Quality Control Validation

Mini-directories have been created at coordinating level thanks to new extraction tool EXOR for the

Post release quality control (PRQC) of data available in Orphanet regarding expert resources in every

country. Mini-directories on expert resources for the countries in which a restrained amount of data

is available were sent in June while for the countries for which bigger amount of data are available

mini-directories on expert centres by medical domain were sent in September.

These mini-directories should be submitted to validators together with methodology guidelines

produced to assist them in the validation process (Methodology guidelines are produced per expert

resource and stored in Orphanetwork website in the Post-release quality control section


3

https://network.orpha.net/network/cgi-bin/articles.php?lng=en&pg=163).

A deadline should be decided, according to the amount of data to be checked (it could be one

month-time).

In order to help information scientists and country coordinators to manage the PRQC process, a

technical procedure is also available

https://network.orpha.net/network/cgi-bin/articles.php?lng=en&pg=163).

It is possible to modify the format of the word file to make it the more user-friendly possible for the

validators (i.e. translation of the English terms in your national language..)

A round table was made to know the feedback on the mini-directories received and to know

if reception one expert resource per month is manageable:

Netherlands: the mini-directories were sent to the Scientific Advisory Board members, they already

received 6/7 positive responses sowing that an effort is being made.

The team agrees to receive one expert resource mini-directories per month.

Portugal: being a small country it was possible to send to PT all the mini-directories of the different

expert resources in June. They have been sent to the Medical Genetic commission of the Health

minister for validation, while research projects mini-directories have been sent to the National

Funding agencies of Portugal. The deadline given for validation was July, however they are still

waiting for the feedbacks because of the summer holiday period.

UK: They have not sent the mini-directories yet, they need to “cleanup” the data and add a few in

the database before sending it away. They are also adding members to the Scientific advisory board

who will receive the data to validate.

Switzerland: same problem of necessity of cleaning up the data before sending it for validation.

Because of the difficulties in establishing a Scientific Advisory Board they are still trying to identify

the right professionals to validate the data

Spain: They are currently modifying the mini-directories to make it more user-friendly possible for

the validators and then they will send them to the Scientific Advisory Board.

Austria: Sandro was not updated on the mini-directories situation in Austria as he joined the team

the previous week.

Canada: is the youngest team of the consortium and they have been entering data for too short a

period to send it to validation.

Ana Rath underlined that it is a difficult and time consuming work here at coordinating level

to produce the mini-directories. Therefore from now on customization will not be possible

and the format of mini-directories will be standardized. She then reminded that EXOR the

tool allowing querying of the database could be available for the partners also, but being a

difficult tool to use training must be given before. Nevertheless, a specific program (ALTOVA)

is needed to produce Word format mini-directories from EXOR, so it is difficult that partners




4

could produce their own mini-directories by themselves (precision added after consulting the

IT team).

She then addressed the questions made by the teams and gave some precisions

It is possible for the teams having received the mini-directories and having realized that the

data presented are incomplete or inaccurate to re-enter or add the data in the database, a

new extraction of the mini-directories will be made upon their request

Everyone agreed that no extraction will be carried out in October and the next batch of mini-

directories will be sent in November

The Canadian team has just started entering data, therefore it is preferable to concentrate

on pre-release quality control and then next year perform the post-release quality control of

data.

Mailing to the all Orphanet registered expert centers and EUCERD criteria

questionnaire

At the EUCERD meeting held on 20-21 June 2012, the representatives of the Member States expressed their wish to access the list of centres of expertise for RD in their country published by Orphanet. They wish to know which of these centres match the EUCERD criteria, in order to prepare their plan/strategy for designating these centres officially in the context of the EU Directive on Cross-border Healthcare to be implemented at national level by 2013. By no way this mapping exercise will be used for designating officially the centres at national level. The process for designation is a national matter. The Orphanet data will be useful to anticipate the process and design the lists produced will serve as a basis to conceive the national strategy regarding the designation of these centres in the context of the national plan/strategy. Ségolène Aymé proposed to systematically send a questionnaire to all registered centres of expertise, asking them to complete the questionnaire, and explaining the purpose of the exercise (text here). The final deadline for answering after two reminders is the 15th October. The answers are being collected at the coordinating level and will be transmitted to the national teams together with the results of the preliminary analysis and the list of non-responders. It will be asked to the country coordinators to validate/amend the preliminary analysis, and to make decisions on keeping/deleting expert centres on the database. After a conference call to address all the different questions (date to be fixed), final results are going to be transmitted to the EUCERD Scientific secretariat that will write a report intended to the Member States. Ideally the lists should be ready by the end of the year 2012. The EUCERD-based questionnaire mailing will allow making quality control on the relevance of expert centres currently in the database. In this sense, this action is complementary with Post-release quality control (mini-directories). We expect that there will be three different scenarios:

centres that are fully compliant with the EUCERD criteria but are not officially designated:

they will be identified by a new pictogram

centres that fulfill some but of not all of them.

centres that do not fulfill the EUCERD criteria

The input of country coordinators on which ones of the EUCERD criteria are major ones in their

country is of paramount importance doing this exercise. It will in turn result in decision-making

keeping (or not) some expert centres currently listed in Orphanet. In this sense, this action

contributes to quality control.

https://network.orpha.net/network/cgi-bin/file/Mailing%20to%20expert%20centres%20to%20ask%20them%20to%20complete%20the%20questionnaire%20based%20on%20EUCERD%20criteria.pdf


5

The information scientists informed the coordinating team that several professionals are confused by

the questionnaire (i.e. the Netherlands and UK).

They wished to know the number of questionnaire received, however the estimation given are gross

numbers as questionnaires are being received every day as the deadline given is 15th October. The

global response rate is currently of approx. 10%.

Other topics

Information scientist expressed their wish to have standard reply to give to patient who contact

them requesting information on a rare disease.

The coordinating team would like to remind that a document with standard answers exists in ONW

(standard answer sub-section of the data collection on expert resources section):

https://network.orpha.net/network/cgi-bin/file/Registration_forms/standard-emails.pdf

It was updated in January 2012 and on page 4 there is the standard text used for answering patients

requesting information on their RD:

Dear Ms/Mr....,

Thank you for contacting Orphanet.

Orphanet cannot respond to individual queries: We collect information on patient groups rather than

patients themselves.

For personal queries, you can contact the dedicated helpline for [Name of your country] :

[Contact details for the helpline]

Best wishes,

https://network.orpha.net/network/cgi-bin/file/Registration_forms/standard-emails.pdf


(N°2010 22 06)

TRAINING REPORT

Paris, 5 & 6 June 2013

TABLE OF CONTENT

Agenda .................................................................................................................................................... 2 Participants ............................................................................................................................................. 3 SESSION I ............................................................................................................................................. 4

Orphanet portal .................................................................................................................................. 4 The Orphanet coordinating team roles and description ................................................................... 5 Information scientist’s key roles ........................................................................................................ 5 Publication of quality ensured data & Collector tool ........................................................................ 6 Directory of expert resources: criteria for data collection, dataset, quality control and feedback. 8 International Rare Disease Research Consortium ........................................................................... 12

SESSION II .......................................................................................................................................... 13

Orphanetwork website ..................................................................................................................... 13 MAJOR workshop ............................................................................................................................. 13 Description of the Professor tool ..................................................................................................... 13 Annual update .................................................................................................................................. 15 Post release quality control .............................................................................................................. 16

Agenda

Wednesday 5 June 2013

Room: Primevère (ground floor)

9h30-11h Orphanet Information scientists’ key roles

11h-11h30 Coffee break

11h30-13h Patient care services (Inclusion criteria; datasets; Quality control & teams’feedback)

13h-14h Lunch (room Pétunia)

14h-16h30 Patient care services (Inclusion criteria; datasets; Quality control & teams’ feedback)

16h30-17h Coffee break

17h-18h30 R&D (Inclusion criteria; datasets; Quality control & teams’ feedback)

19h Dinner: Restaurant "Au Moulin Vert", 33 rue du Moulin Vert, 75014 PARIS

Thursday 6 June 2013

Room Primevère (ground floor)

9h-9h30 OrphaNetWork

9h45-12h30 “MAJOR” Workshop

12h30-13h30 Lunch (room Pétunia)

13h30-15h ProfessOR tool description

15h-15h45 Post Release Quality Control

15h45-16h30 Coffee & feedback session/ general discussion (partners’survey, past and future distant trainings….)

Participants

Sandro Coelzer (AT)

Paz Urbina (BE)

Annelies Mallezie (BE)

Nancy Anoja (CA-QC)

Susan Rogers (CA-QC)


Ana Vera Ruiz de Castaneda (CH)

Marek Turnovec (CZ)

Elisabeth Nyoungui (DE)

Mareike Derks (DE)

Martin Arles Soler (ES)

Leena Toivanen (FI)

Konstantina Merou (GR)

Marta GARAMI (HU)

Serena Ciampa (IT)

Roberta Ruotolo (IT)

Mai Tanabe (JP)

Birute Burnyte (LT)

Santa Rozite (LV)

Imane Cherkaoui-Jaouad (MA)

Judith Carlier (NL)


Patricia Arinto (PT)

Rula Zain (SE)

Mina Mansoor (SI)

Ales Maver (SI)

Gabriela Nagyova (SK)

Idoia Gomez-Paramio (UK)

Observers

Gail Ouellette (CA-QC)

Loredana D’Amato-Sizonenko (CH)

Petra van Overveld (NL)

Speakers

Ana Rath

Charlotte Gueydan

Virginie Hivert

Sylvie Maiella

Claude Barrère

Marie-Pierre Becas-Garro

Bénédicte Belloir

Sandra Peixoto

Orphanet Europe Joint Action Training report – 5-6 June 2013 - Paris

4

SESSION I

JUNE 5TH, 2013


Orphanet During this session a brief presentation of Orphanet was given by Virginie Hivert. She stressed that Orphanet is a registered brand name owned by INSERM. She also reminded everyone that it is an international website that is freely accessible and that has national entry points from all countries in which a team is appointed. The site is dedicated to a broad range of end-users from patients to healthcare professionals, regulators, and pharmaceutical companies. It is also a communication tool used to share and spread expertise via the Orphanews newsletter. Behind the website there is a very complex relational database which also represents a pre-competitive tool highly-valuable to R&D in the field of rare diseases (data available for download at www.orphadata.org). Moreover, new services and collaborations are developed regularly to resolve the issue of information dispersion and to address the specific needs of the different stakeholders. The ongoing international partnerships were described (refer to the 2012 Activity report for more details here). The number of partnerships developed grows every year because of the international influence that Orphanet has, notably: Orphanet is highlighted as the reference resource for rare diseases (RD) in the documents of the European commission on RD, it is involved in the WHO’s ICD 11 revision as well as SNOMED CT nomenclature revision, with IRDIRC (see page 13), we also collaborate with European Medecine Agency in establishing consistent RD prevalence figures, and with ECRIN (Rare diseases hub for European clinical research infrastructures network) and with EBI and it is part of Elixir’s French node. The scientific content of Orphanet was also presented. Literature is surveyed daily by a dedicated professional, which facilitates the collection of information on newly or further described RD, RD epidemiology & genes involved in RD. It also allows the revision and updating of the in house produced RD inventory and classifications. There is also a massive in house encyclopaedia production (of summary abstracts on RD but also emergency guidelines, general public texts) which is very appreciated by the end users (as shown by the users’ survey). RD are indexed with ICD-10, OMIM, and cross-referenced with MeSH descriptors, UMLS, MedDRa and SNOMED CT. Genes are cross-referenced with HGNC, UniprotKB, Genatlas, OMIM, ensemble, Reactome and IUPHAR. One of the added-values that Orphanet features is that all the information produced in-house is expert validated.

This topic was followed by a short description of the Orphanet Directory of resources (expert centres, medical laboratories, patient organisations, research projects, patient registries, mutation registries, biobanks, clinical trials and networks), stressing that the establishment of the directory of resources can only be achieved thanks to the work of the national teams in the different countries of the consortium. A brief overview of the organisational chart was then given.


http://www.orpha.net/orphacom/cahiers/docs/GB/ActivityReport2012.pdf


5

The Orphanet coordinating team roles and description A reminder of how the international coordinating team works was given. The team is supervised by the chief medical officer and Orphanet deputy director Ana Rath. The quality manager, Charlotte Gueydan, is in charge of the technical supervision of the national teams. Virginie Hivert, the expert resources and pharmaceutical affairs team manager is in charge of the scientific support. Valérie Lanneau, the Client Project Manager, is in charge of IT development follow-up while Sylvie Maiella is the International coordinator in charge of following the ongoing contracts, the user rights, the translation workflow and the administration of the internal website, OrphaNetWork. More generally, the coordination comprises: coordination of data collection at a global level, training and supervision of national teams, supervising overall quality of the database (between types of data, countries...) and also collection of information concerning transnational data. It was also reminded that communication between teams is equally ensured by the collaborative tools that have been established or improved. OrphaNetWork consists of a website plus an internal newsletter (intended to communicate and share information; all the documents needed at a national level are uploaded onto the site). The Quality Assurance Review (QAR) is intended to assist and to guide the information scientists (IS) in data collection and a translation report is issued regularly, containing the necessary information to carry out translation activities. Deeper insight on how the expert resources team works at the coordinating level was given: Virginie supervises the team. Data collection and registration is provided by Claude Barrère (expert centres & patient organisations), Bénédicte Belloir (diagnostic tests & labs quality), Marie-Pierre Becas-Garro (drugs & clinical trials), Sandra Peixoto (research projects, registries and biobanks) and Marie Villemeur, who assists them with their tasks.

Information scientist’s key roles The principal topic of the first session was then addressed and the key roles of the information scientists (ISs) were described: they are in charge of identifying the sources of information in the country and of collecting the information about expert centers, laboratories with diagnostic tests, patient organisations, clinical trials, patient registries, mutation registries, biobanks, research projects and platforms (according to the technical SOPs here). They also have to follow the process of validation of the collected data according to the workflow established by the Country Coordinator, ensure the publication of the validated data on Orphanet (using the registration tool Major, that since June 2013 is available for all Information scientists after the appropriate training) and update the data once a year. Other roles are communication with the coordinating team, regular reporting to the country coordinator, reading of the Orphanetwork internal newsletter and the Orphanet Quality assurance review (and the translation report when applicable) and carrying out the action points posted in them, contributing to the OrphaNetWork internal newsletter by sending short reports on activities performed by the national team and, for some, to manage the country website and find specific sources of information on rare diseases at the national level. The information scientist’s tasks and national team roles are detailed in the SOPs available here.




6

Publication of quality ensured data & Collector tool It was reminded that in order to publish data which are relevant and accurate, a process to ensure quality assured data has been established. The general process and the different actors involved were then described as it is detailed in the SOPs. It was stressed that the priority list of data collection suggested in the SOPs should be adapted to the national situation in terms of resources & policy and that it is also dependent on the objectives of data collection (ex: if a national research agency transmits a list of research projects in the frame of the IRDiRC, it should be entered in the database in priority). Then it was reminded that the country coordinator is responsible for the data quality management of expert resources in the country, and he/she should check the relevance of the national data prior to its release online. It is of paramount importance that the country coordinator validates the data collected by the information scientist prior to its online release, because currently the quality control is performed on data which are already available online. This implies that if the entered information is not relevant it will still be displayed until QC is carried out at the coordinating level. A pre-release validation can reduce the risk of publishing non relevant data. With the availability of the new registration tool COLLECTOR (see below), all the steps of data validation, including QC, will be performed before online publication. Finally it was reminded that for the post-release quality control, mini directories are issued through a tool called Exor which allows for the production of data directories that can be submitted to the scientific advisory board or the person in charge of PRQC. (Guidelines to assist the persons in charge of PRQC are available here ). It was also stressed that it is of paramount importance that sources of information and selection criteria be advertised on the national website as decided by the Orphanet management board. A detailed description of the Collector tool was given by Ana Rath. It was explained that it is an integrated tool for data management and quality assurance. It was decided to develop it in order to face several challenges that go along with the development of the consortium such as: to make the national team autonomous, to simplify the dataset collected (some data are too difficult to obtain while some of the collected data are never used) and to adopt the UTF8 standard (for the website and the database). This tool has also been developed to follow the evolution in RD health & research policies such as the definition of shared quality standards used to collect expert resources, data normalisation to ease data exchange with other databases, quality improvement of the expert resources database (in order to achieve coherence and to make the database exploitable for analysis by a third party and for decision support). Currently the data collection integrates different job expertise and the management of this integration is hard and time-consuming, often resulting in loss of information in the decision cycle. Therefore several needs have been identified, such as the integration of different jobs in a single data-management tool, the possibility of tracking decisions and sources, the implementation of quality rules BEFORE publication and to facilitate quality control AFTER publication. In parallel, because of the increase in scientific information available on RD, the scientific projects also need to have a structured literature survey and a tracking of decisions and sources. In addition, to address the increasing demands to produce high-quality, structured,



7

up-to-date data, it was necessary to improve data structure in terms of concepts and relationships for disorders, genes, drugs and phenotypes. It was also necessary to produce new data on epidemiology, analytes and cross-referencing. The needs identified were exactly the same as those associated with the data collection of expert resources. This is the reason « CollectOR » became an umbrella term, but the tool has two inter-connected sides with one more related to the expert resources/international coordination and the other to the scientific resources. The integration of data and workflows in the same tool requires some changes, such as evolution of the Orphanet database as a whole, moving to UTF8 , creation of new tools and the update of the existing tools and, of course, mobilisation of all Orphanet staff.

From a technical point of view, this ambitious project has been divided into several smaller projects to be more manageable. The different 6 sub-projects were presented and described, in particular:

The sub project 1 includes development of Professor (internal name not to be used for external communication purposes), a tool allowing annual and continuous updates for professionals (it will be explained in full length during D2).

The sub-project 2 includes creation of a new database (including revision of the dataset) and update of the international site and of the extraction tool. This will allow the presentation of new data (epidemiology, diseases, analytes, techniques and purpose of diagnostic tests…), the production of automatic definitions for certain disorders (moved-to, etiological sub-types, groups…), and the improvement of the presentation of expert resources and networks of expert resources (clinical trials, networks of expertise …). It will also allow for improved searching via the website (advanced search for tests & labs…) A first version of the definitive tool (Collector light) will be available. It is a web based interface replacing MAJOR. At this time, an updated version of Professor (V2) will be connected to the new website

The sub project 5 includes the final version of Collector. This platform allows for: management of the professional’s demands, publication of validated data (after national validation and QC) and it keep tracks of the decisions made and the data life cycle. It will also manage exchanges between teams and it will present the role and responsibilities of each position.

An overview of the general process was given: The professional must log in to update or register new data (please refer to the Professor tool description in the second section of this report). Selection of the country in which he/she is will define the attribution to a Country workspace. The entered data then undergoes the above mentioned steps of validation. It has to be noted that according to the kind of modification (major or minor) and according to the sensitivity of the data, different actors may be concerned for validation (IS, country coordinator and QC coordinating team). For example, IS can modify and validate Persons (Prs), Hosting institutions (Adr) and Departments/laboratories (Loc), whilehile officially designated status, person functions, network coordinating role for an expert resource and funding data may need further validation.


8

Questions (Q) & answer (A)

Q: How long will it take between the collection of new data and its online publication when the new tool is in use? A: Currently QC is slowed down because it is looking at massive datasets and because of the difficulty in integrating the different jobs participating in the workflow with the different teams

involved. Moreover, currently the QC team is also checking for relevance of the data when this should be the national coordinator’s job. With the new tool the procedure will change: all the demands will be treated one by one and weekly meetings will be held where entries are looked over. Probably the slower step will be the national validation carried out by the coordinator who is in charge of checking the relevance of the data. Q: What is the point in training for the use of Major with the arrival of the new tool? A: To manage the 2013 update and because Collector will be similar but more user-friendly; what has been learned for Major will be applicable to Collector as it is about entering data in the database.

A. Directory of expert resources: criteria for data collection, dataset, quality control and feedback.

It was reminded that the aim of data collection is to have a comprehensive directory of expert resources for rare diseases in a given country. Criteria used for the data collection of each resource were explained (please refer to the technical Standard Operating Procedures (SOPs) https://network.orpha.net/network/cgi-bin/articles.php?lng=en&pg=68 for more information). It was stressed that these criteria will also be explained in the Terms & Conditions page which has to be signed by the professional upon registration when using the new tool.

General recommendations on Data registration

All information should be checked by you and the country coordinator (relevance).

Specify if it is an update of existing information or a new data submission.

Remember to check if a person is already registered because many duplicates currently exist.

Mapping with diseases and genes is crucial – take some time to check the classification in Arbor 2! It is of paramount importance that the disease link is correct, as activities displayed on the website are now sorted by specificity of the disease link you select, therefore mistakes in the link will result in the display of wrong information and this could result in consequences for patient referral.

Validate the complete list of diseases you have chosen with the professional, whenever the initial submitted list was too vague or too specific. You can export an ARBOR classification and submit it to him/her.

If a disease or a gene is missing, contact the coordinating team and explain why you asked for a creation, and add corresponding references in the literature. The demand will be treated at the monthly disease meeting and, if relevant, the disease/gene missing will be added in the database.




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The current database structure was described in comparison with the next version of the database. In particular, the dataset has been reviewed to evolve towards the new database, each dataset will move from the current infrastructure to the new one. It was reminded that some resources have funny looking names because they are a shortened version of the French name (Ass for “associations” which is patient organizations in French…). Regarding the contemplated changes in the datasets:

Address will be kept but renamed ”Hosting institution” with Town, Region (if relevant), Country

Location will be kept but renamed « Department/Laboratory », it is an additional piece of information always associated with a hosting institution and linked to an expert resource.

‘Person’ will be split in two tabs: Person & Legal entity (Person is a professional or a stakeholder in the field of rare diseases). It will be linked to an expert resource or an abstract and is defined by a function in the database.

Questions (Q) & answer (A) Q. The editorial teams often create duplicates of expert addresses. A. This problem has been addressed. A big clean up of the addresses associated with the experts involved in the editorial process has been performed and great attention is now given on not creating duplicate addresses. Q. The problem with the registration of the same patient organisation in countries with multiple languages. A. It will be possible for a patient organisation to have their name in several languages. Q. Why are telephone number, email and precise address are not collected anymore for locations? A. IS lose too much time collecting this info that is too heavy to update. Since our role is to give visibility of the expertise, a link to the website of the hospital is all that is needed (as on their site the information will always be updated). Q. It is often a request of the professional to have the precise address of the centre listed as often the hospitals are located in very different buildings or not even in the same area. A. It will be specified in the terms and conditions of activity registration and the team can always explain the reason why this choice has been made. Q. The postal code and region field are not mandatory A. It is possible for the region, however either the postal code or the suffix should be entered. Q. Is it possible to combine titles for example Prof & MD, as in some countries this is very important? A. No it is not possible.


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Q. What happens in case of homonymy of persons when they register? A. This case has been investigated, there are very few homonyms in the database, and the difference will be made thanks to the email address. Q. What happens to patient organisations that are also charities? A. In this case they could be registered as both a patient organisation AND a legal entity. It will be the only duplicate allowed. Q. What is the utility of having funding bodies? A. They have a utility for the users using OR to support health policy decisions. They can be attached to the different resources and at national level they allow for statistical questions on health policy matters to be answered (for example which disease is more funded). Q. Is the Involvement of funding bodies possible for the PRQC? A. Yes it is possible, for example for research projects.

For each resource the definition and selection criteria were given as stated in the technical SOPs available here. In addition some specific points were further discussed: Expert centres Particular attention was given on the selection of expert centres, this argument will

be further addressed during the 2013 management board to reach a definitive consensus. Check the meeting report here.

Guidelines on how to assess the questionnaire will be produced according to the discussion held at this year’s meeting. Check the meeting report here.

It was stressed that validation of the relevance of a selected centre by the country coordinator is of paramount importance.

Selection criteria, in particular if an official designation exists in the country, has to be decided jointly with the health authorities and explicitly stated in the national country website.

Some important improvements with the new database will be the possibility of flagging a centre as both Genetic counseling and Medical management. Also, if the center is a coordinator of a network, it is possible to link 0 to n expert centre(s) to i .

Diagnostic tests Diagnostic tests for chromosome number anomalies and ring chromosomes done by

FISH (e.g. Trisomy 11) are not registered in Orphanet, as their detection does not require a specific expertise in molecular cytogenetics.

Research projects: When research projects are completed, they should be flagged as « completed ». The consequence is that they would not be visible on Orphanet anymore and they

will be removed from the database: except for those funded by a member of IRDiRC from 2010 on.





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Tips To avoid duplication between Registry and Research

o Research projects may concern the construction of a registry as long as the registry is not yet established

o Research project may concern an already-established registry as long as it implies an actual research project conducted with the participation of patients of the registry

o Collection of data corresponding to the expressed goal of a registry should not be entered as an additional research project.

To avoid duplication between diagnostic tests performed in a clinical setting and research projects aimed at developing a diagnostic test

A diagnostic test with clinical setting has to be registered only in the diagnostic test section and should be removed from the research project section.

To avoid misregistration between Clinical trials and Research o Clinical research projects have to be registered as research projects not as

clinical trials. o Clinical trials are mostly interventional studies, with a phase and a registration

number from a national or international drug agency. o Clinical research projects are mostly observational and are performed with

ethical committee authorisation but are not registered by a national or international drug agency (but they are sometimes listed in clinicaltrials.gov).

Quality control of the data entered Quality control of all entered data is carried out monthly by the coordinating team. Charlotte Gueydan presented the type of modifications or mistakes occurring frequently and their evolution over time for each resource. (This information is provided monthly to the Information scientists in the QA review; analysis per country has also been carried out and is available upon request). It must be kept in mind that currently errors are classified into 5 categories: Relevance: when an entry does not meet the Orphanet inclusion criteria (e.g. expert

center for a non rare disease) QC-failed: when assessment of the entry could not be performed as the associated

information was not sufficient (e.g. research project without a description of the research aim or medical management expert centre with no addendum questionnaire)

Mapping: when there is a discrepancy between the actual mapping with the Orphanet nomenclature of diseases and a more relevant one (i.e. wrong diseases and gene links)

Other amendments: when items other than the disease mapping should be corrected (e.g. flags, types of tests or research projects, labels…)

Classification: when modifications in the Orphanet nomenclature of rare diseases, genes, or classification should be performed to meet the needs of the current state-of-the-art in rare diseases, as suggested by the corresponding expert resource.

It was stressed that most of the corrections suggested are related to mapping problems. This is particularly unfortunate as wrong mapping results in an erroneous sort by specificity,


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therefore irrelevant information will be displayed on the website. This could also result in a further diagnosis delay and misreferrals. QC often failed on expert centres because no sufficient info is available, notably, it is often that the addendum questionnaire is missing or it is not validated by the country coordinator.

International Rare Disease Research Consortium

It is an initiative between the European Commission & the American NIH. Members are funding bodies spending a minimum of 10 millions USD over 5 years in research contributing towards IRDiRC objectives (200 new therapies by 2020).

Orphanet is the reference portal for R&D information for IRDIRC.

Implications for Orphanet’s workflow and database:

The scientific secretariat of IRDiRC is located in Paris, in Orphanet’s office. One of our roles is to analyse the RD research landscape by analysing the research projects funded by IRDiRC members.

The IRDiRC team keeps record of everything to be able to perform analysis Every Orphanet partner team takes care of its Research data Sandra takes care of FR, US and EC-funded projects Quality Control is performed by the coordination team of Orphanet


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SESSION II

JUNE 6TH, 2013

The power point presentations of this session are available here.

Orphanetwork website

It was reminded that ORPHANETWORK is a site dedicated to Orphanet's national teams. It houses a wide range of tools and informative documents, as well as all the technical standard operating procedures regarding the information scientists’ tasks. It is accessible with a login and a password (one login/team).

https://network.orpha.net/network/cgi-bin/index.php?lng=en

In order to improve the website, partners were surveyed for suggestions on what could be done to make it more useful for them. Many suggestions were received (refer to the 2011 & 2012 Partners’survey here) and all the improvements that were possible using the current administration tool were implemented. It was stressed that there are some limitations in the implementations suggested because this site is administrated thanks to a free tool due to there being no dedicated funding for this activity. However, it was decided that it is important to implement a better search tool allowing searches within PDFs documents, therefore some resources will be dedicated for this.

MAJOR workshop

All the participants from countries where access to the current registration tool was not granted were trained to use it. This approach will make national teams autonomous regarding the management of updates. A survey to collect feedback on the workshop and suggestions for the next distant training and for the annual training was launched.

Description of the Professor tool

Professor is the new tool that allows professionals to register or update expert resources. Please note that this is an internal name that should not be used for external communication purposes. The interface for professionals will be available by clicking on the tab «Register your activity" found on the international website. The link to this interface can also be sent by email whenever an update campaign is launched or it can be bookmarked in the browser of professionals. An important feature is that this interface can be available in all the languages, the professional will be able to choose from a drop down menu. All 7 Orphanet languages will be





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made available progressively, plus all the other languages for which the teams are willing to carry out the translation. According to the discussion held at the 2013 training and also at the 2013 meeting it was decided that: Upon accessing the interface the professional will have to: verify he/she is not already registered in Orphanet then he/she will access the login screen

o a button for if you have forgotten your username or your password will be available

o a “contact us” button will also be available If the professional is not registered He/she has to create an account. The system offers two basic request choices:

o Declare a new expert resource o Declare being involved in an expert resource already referenced

If the professional is already registered Either he/she is linked to at least one expert resource, in which case the system

offers him four object requests: o Update my personal record o Declare a new expert resource o Declare being involved in expert resource already referenced o Update my expert resources

Either he/she is not linked to any expert resource, but it is linked to at least one abstract (so it has the function "expert reviewer in Orphanet "), in which case the system offers him three object requests:

o Update my personal record o Declare a new expert resource o Declare involvement in an expert resource already referenced

In the forms, the professional will have to select, from a scroll down menu, the disease to which the resource he/she is registering should be linked to (the list corresponds of course to the Orphanet rare disease inventory). If the disease is not present in the list there is a comment box that allows for the addition of this information. The ISs will have access to these forms through their back office/workspace for pre-release validation of the data. The professional is the only one able to submit the demand by clicking the “submit” button. The ISs should regularly check his/her workspace in order to follow up any new form submitted by the professionals and then proceed to the pre-release quality control of the data and registration in the database before online availability. In Collector, when the form is submitted by the professional, the information scientist receives a notification in his/her workspace.


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Please note that: If the professional is registering an expert centre it will also have to fill in questions

that are presently collected through the addendum questionnaire. If the professional has indicated a disease not available in the scroll down menu the

IS has to check for relevance of the disease and then when applicable, submit it for creation of a new disease in the inventory of RD.

The forms in Professor have three possible states: o Saved : the form is not yet ready to be submitted, but it is stored in the

professional’s workspace o Submitted: the professional has validated the information entered by

him/her o Treated: the demand has undergone pre-release validation by the national

team

An important feature of this tool is the traceability of the exchanges.

Additional feedback from the IS: in the field “are you an officially designated expert centre” it should be specified “for

RD” to avoid confusion as in some countries all the hospitals are officially designated but not necessarily for RD.

add a comment box at the end of the registration form for translation by the national teams it was suggested to send screen shots to help

the translator contextualize having automatic emails sent to the professional is a possibility. However it could be

better to have template emails available in the workspace that can be customised by the information scientists (for example in the case where a professional has updated 20 tests at the same time, if it is an automatic generated email, the professional will receive 20 times the same email for each test modified, clearly in this case the IS can send just one email recapping the 20 tests). In both cases a validation by the IS will be required before sending the email to the professionals.

Annual update It was reminded that we are obliged by contract to have annual updates. This year’s update of data will be launched through PROFESSOR. All registered professionals in the database will receive an email containing a link to the new interface asking them to create an account and to check their data. The ISs will access these forms through their backoffice space. The modifications shall be entered in the database trough the MAJOR tool by the IS. A button will be created in the backoffice “treated”.

The update has to be launched before the migration of the datasets to the new version of the database.


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Post release quality control

It was reminded that published data on expert resources should be quality controlled in each country in order to be sure that:

all the relevant expert resources are there (completeness for a country at a given time)

no superfluous resource is present, which means, all the expert resources collected comply with the inclusion criteria according to the Orphanet standards (relevance)

information given is exact (to the best of the validator’s knowledge) (accuracy)

Performing PRQC is also necessary to have good-quality mini-directories for communication purposes thus it is an unavoidable step before disseminating the expert resources information in each country. It should be organized at the National level. Mini-directories intended for quality control of the database content were generated by country and by expert resources, before the evolutions in the data model take place. These mini-directories are available for you to download at the following address: https://backoffice.orpha.net/fichor/cgi-bin/views/

Guidelines describing how to perform PRQC have been produced to help validators in their task, they are available here. They should be sent together with the mini-directories to all validators.

https://backoffice.orpha.net/fichor/cgi-bin/views/



(N°2010 22 06)

TRAINING REPORT

Paris, 15,16,17 October 2014

TABLE OF CONTENT

SESSION I ............................................................................................................................................. 4

Upgrade of the scientific content of the database ............................................................................ 4

Session II .............................................................................................................................................. 4

Practical workshops ............................................................................................................................ 4

Session III ............................................................................................................................................. 5

Future evolutions of the database ..................................................................................................... 5

Translation procedures ....................................................................................................................... 5

Agenda

Wednesday 15 October 2014

Room 119, Atrium building, University Pierre et Marie Curie, 10 rue Cuvier 75005 Paris

13h Welcome coffee

13h30-15h30 New data in the database: ORPH 4.1.3


16h-18h30 Expert resources: Inclusion criteria and Online registration tool presentation (PROFESSOR)

Thursday 16 October 2014

Room 119, Atrium building, University Pierre et Marie Curie, 10 rue Cuvier 75005 Paris

9h30h-11h Making Backdor evolve to Collector 1

11h-11h30 Coffee break

11h30-13h “COLLECTOR1-MAJOR” Workshop

13h-14h Lunch (L’ardoise brasserie, on campus)

14h-15h30 “COLLECTOR1-MAJOR” Workshop


16h-18h R&D “COLLECTOR1-MAJOR” Workshop

19h Dinner

Friday 17 October 2014

Salle Primevère ( ground floor), Plateforme Maladies Rares, 96 rue Didot, 75014 Paris

9h00h-10h30 Future evolutions of the database: Orph 4.2


11h-11h30 Translation procedures

11h30-11h45 Overview of the ONW website

11h45-13h30 Questions

Participants

Patricia Arinto (PT)

Gustavo Barros Sabino (FR)

Birute Burnyte (LT)

Imane Cherkaoui-Jaouad (MA)

Serena Ciampa (IT)

Mareike Derks (DE)

Martina DiGiacinto (IT)

Reviva Einy (IL)


Dorra H’Mida-Ben Brahim (TN)

Kristine Hovhannesyan (AM)


Tihana Kreso (HR)

Debby Lambert (IE)

Luca Lovrecic (SI)

Annelies Mallezie (BE)

María Elena Mateo (ES)

Brenda McInnes (CA)

Marina Moraitou (GR)

Gabriela Nagyova (SK)

Elisabeth Nyoungui (DE)

Urbina Paz (BE)

Paulius Raugalas (LT)

Kathrin Rommel (DE)

Maja Stojiljkovic (RS)

Rita Teek (EE)

Leena Toivanen (FI)

Marek Turnovec (CZ)

Ursula Unterberger (AT)

Rula Zain (SE)

Training team

Ana Rath

Martin Arles

Claude Barrère

Marie-Pierre Bécas Garro

Bénédicte Belloir

Valérie Lanneau

Sylvie Maiella

Annie Olry

Sandra Peixoto

Marie Villemeur


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SESSION I

OCTOBER 15TH, 2014


The 3rd and last Annual Training of the current Orphanet Europe Joint Action contract took place in

Paris. 30 information scientists from 25 different countries gathered to learn and discuss the last

developments on the project.

As a novelty this year, the first two days were held in an informatics room at the Paris6 University.

Upgrade of the scientific content of the database

The first session was focused on the upgrade of the scientific content of the database (these new

modifications, already explained in the QAR of last august (here), affects the type of disorders, the

flag of disorders, the new relation between disorders, the automatic texts, the external references,

the information on genes and the epidemiological data), and the inclusion/exclusion criteria for the

different resource collected in the database.

Session II

OCTOBER 16TH,2014

Practical workshops

The second day consisted mainly in a practical workshop on how to handle the main Orphanet tools,

with a special focus on Collector1, the upgrade of the backoffice tool to treat the professional’s

demands. The ISs were divided in 10 teams, and based in example situations specially prepared by

the coordinating team for this training, the teams were able to practice Collector’s workflow, since

the submission by the professional up until Major’s registration.


https://network.orpha.net/network/cgi-bin/file/QAR-August2014.pdf


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Session III

OCTOBER 17TH,2014


Future evolutions of the database

In this section the new Orphanet database called Orph4.2 was presented. As it was explained, the current version of the database will progress step by step through the implementation of a series of “small” upgrades. The new model for each expert resource was presented, with a close look into their new dataset, mandatory fields and unicity criteria.

Translation procedures

Increasing the language availability of the Orphanet website and related documents is one of the top priorities of the Orphanet Europe Joint action. Currently the only mandatory translation is the Orphanet National website in the national language, however if a National funding is identified, Orphanet National teams can also have the possibility to work on 5 different translation packages:

- Orphanet International website, including the website layout, list of diseases and thesaurus clinical signs and symptoms

- Encyclopaedia for professionals - Emergency guidelines - General public encyclopaedia - Disabilities factsheets - OrphaNews Europe.

It was also reminded that according to partners’feedback the translation procedure were smoothened and if an adaptation of the translated text was validated or/and requested by a learned society in the country it was possible to publish the document online in a given template containing an appropriate disclaimer (please refer to the section here: https://network.orpha.net/network/cgi-bin/articles.php?lng=en&pg=97 for procedures and layouts)

Overview of the Orphanetwork Website.

It was reminded that ORPHANETWORK is a site dedicated to Orphanet's national teams. It

houses a wide range of tools and informative documents, as well as all the technical

standard operating procedures regarding the information scientists’ tasks. It is accessible

with a login and a password (one login/team).




Documents

AGENDA - Europa · 2016-09-26 · automation) - Improve user-friendliness (e.g. providing autonomy to national teams, increasing online interactivity with Orphanet users) - Be sustainable