Scientific Secretariat Report IRDiRC Executive Committee Meeting November 6, 2014 Shenzhen, China

Topics to be covered Analysis of the activities from the secretariat perspective Communication Assistance to SC and WG Assistance to Executive Committee Proposal for changes Change in scope Change in organisation

Analysis of Current Communication channels

Number of visitors of the IRDiRC public website Increasing 933 2916 29860 visitors in total

Number of page view of the IRDiRC public website Increasing 2183 6632 70297 page view in total

IRDiRC website visitors by country (from July 2013 to October 2014) + 1. France 16. Sweden 2. USA 17. Austria 3. UK 18. Ireland 4. Spain 19. Greece 5. Italy 20. South Korea 6. Germany 21. Israel 7. Canada 22. Hungary 8. Belgium 23. Denmark 9. China 24. Finland 10. Netherlands 25. Czech Republic 11. Australia 26. Norway 12. Switzerland 27. Poland 13. India 28. Hong Kong 14. Japan 29. Turkey 15. Portugal 30. Romania … -

% of page view of the IRDiRC public website from July 2013 to October 2014 25% + Homepage Research highlights Lists of projects funded by IRDiRC members Goals , Members About RD, Upcoming Activities Current results of research Governance Structure, IRDiRC Policy & Guidelines, IRDiRC Related Calls, Reports & guidelines Background history, Become a member, Conferences, Contact us, Exec Com meetings, Related RD initiatives, Research in RD, SC meetings, WG Activities … 9% 8% 6% 4% 3% 2% 1% -

Most accessed articles from July 2013 to October 2014 + Horizon 2020 call for proposals in the field of RD research DECIPHER – a valuable database for researchers and clinicians: Q&A with Dr. Helen Firth First IRDiRC conference on April 16-17 2013 in Dublin, Ireland FORGE: A successful Canadian project to identify genes causing rare pediatric disorders Petition requesting amendments to the draft on Data Protection Regulation Save the date for the second IRDiRC conference in Shenzhen, China Pharmacological chaperones to cure genetic diseases – Q&A with G. Andreotti and M.V. Cubellis Open Info Day – Horizon 2020 ‘Health, demographic change and wellbeing’ – first funding round China celebrates the founding of the Chinese Rare Disease Research Consortium SpainRDR aims to build the National Rare Diseases Registry in Spain – Q&A with Dr Manuel Posada FDA clarifies aspects of the Orphan Drug Act in the Final Rule document RD-Connect: An integrated platform connecting databases, registries, biobanks and bioinformatics for rare disease research China imposes restrictive regulation of genetic testing Registration opens for joint EMA/FDA/MHLW-PMDA orphan medicinal product workshop The International Rare Diseases Research Consortium announces its second conference with renowned speakers The much awaited ontology of rare diseases has just been released … -

Most accessed lists of projects funded by IRDiRC members from July 2013 to October 2014 + European Commission (EU) E-RARE (EU) Telethon Foundation (Italy) Canadian Institutes for Health Research (Canada) National Cancer Institute, NIH (USA) French Muscular Dystrophy Association, AFM (France) National Institute of Neurological Disorders and Stroke, NIH (USA) Orphan Products Grants Program, FDA (USA) Federal Ministry of Education and Research (Germany) National Institute of Health Carlos III (Spain) … -

Number of page view of the IRDiRC private website Increasing 108 235 1140 page view in total

Number of visitors of the IRDiRC private website Stable 15 19 134 visitors in total

% of page view of the IRDiRC private website from February 2014 to October 2014 + 27% Homepage Executive Committee TSC DSC, Scientific Secretariat, WG Biomarkers, WG Model Systems, WG Repurposing WG Biotechnology, WG Genome/Phenome, WG Ontologies, WG Regulatory ISC, WG Biobanks, WG Data Sharing, WG Ethics, WG Registries, WG Sequencing WG Population Controls on Variant Datasets 19% 5% 4% 3% 2% 0,5% -

IRDiRC Newsletter Launched in July 2013 252 internal subscribers 54% of subscribers do not open the newsletter 30% of subscribers open the newsletter 16% of subscribers open and click on the links of the newsletter 6 unsubscriptions since July 2013

Conclusion Importance of writing research highlight articles Better promotion of policy and guidelines documents Suggestions from YOU ?

Report on research projects funded by IRDiRC members

Analysis of SC and WG activity

Meetings and Teleconference (TC) 2012 DSC meeting ISC meeting ISC meeting TSC meeting TSC meeting May June July August September October November December

Meetings and Teleconference (TC) 1st semester 2013 Invitation DSC WG DSC meeting ISC meeting Meeting WG Biobanks Meeting WG Data sharing Invitation ISC WG Meeting WG Ethics Meeting WG Registries TSC meeting January February March April May June

Meetings and Teleconference (TC) 2nd semester 2013 WG Genome DSC TC DSC meeting TC WG Genome TC WG Model System TC WG Sequencing TC WG Genome TC WG Ontologies TC WG Sequencing TC WG Model System TC WG Biobanks ISC meeting TC WG Data sharing TC WG Ethics TC WG Registries TC WG Registries TC WG Biomarkers TSC TC TC WG Biotech Invitation TSC WG TC WG Regulatory July August September October November December

Meetings and Teleconference (TC) 1st Semester 2014 WG Ontologies TC WG Model System TC WG Model System ISC TC ISC TC ISC meeting TSC TC TSC meeting TC WG Biomarkers TC WG Regulatory TC WG Biomarkers TC WG Biotech TC WG Repurposing TC WG Repurposing January February March April May June

Meetings and Teleconference (TC) 2nd Semester 2014 DSC TC DSC TC TC WG Model System TC WG Genome DSC TC TC WG Ontologies TC WG Pop Controls TC WG Pop Controls TC WG Sequencing TC WG Sequencing TC WG Biobanks TC WG Registries TC WG Biobanks TC WG Data sharing TC WG Ethics TSC TC TC WG Repurposing TC WG Biomarkers July August September October November December

Participation to meetings (m) and teleconferences (tc) 3rd 4th 5th 6th 7th Diagnostics SC 8/9 (m) 6/9 8/10 (tc) 6/12 5/11 6/11 WG Genome 7/9 7/10 6/10 WG Model System 7/8 5/8 6/8 WG Ontologies 9/10 5/10 11/18 WG Sequencing 3/10 4/10 WG Pop Controls Interdisciplinary SC 10/10 9/11 9/12 WG Biobanks 3/9 5/40 WG Data sharing 8/14 7/14 10/14 WG Ethics 3/12 8/12 7/12 WG Registries 12/15 10/15 11/17 11/19 Number of participants/ number of members >70 % 50 -69 % < 50 %

Participation to meetings (m) and teleconferences (tc) 3rd 4th 5th 6th 7th Therapies SC 12/12 (m/tc) ? (tc) 7/12 (m) 10/16 11/16 9/18 11/18 WG Biomarkers 4/7 5/7 3/6 WG Biotech 6/10 WG Repurposing WG Regulatory 4/11 9/11 Number of participants/ number of members >70 % 50 -69 % < 50 %

Conclusions Intense brain storming during more than 2 years with an exhaustment of the topics to discuss by most groups Very heavy workload for the secretariat, not proportionate to the outcome relevance

Proposal for a change in scope

More focus on fewer topics Topics specific to RD With International scope Actionable with our human means Not yet covered by another International initiative Identified by Exec, SC, WG or secretariat

Specific proposals by the Secretariat Already decided: Development of the Clearinghouse of Data Standards Development of the Generic Consent Form New proposals (in addition to proposals from SC): Coordination of initiatives to identify in silico new drugs and/or new indication Coordination of initiatives to develop patient-centered outcome measures for RD Coordination of initiatives on small population trials

Data Standards Clearinghouse Progress report Data Standards Clearinghouse

Scope of Clearinghouse project Developed by the WG on Data Sharing and Bioinformatics. Promote adoption of data standards and common data elements across rare disease research communities Provide a dynamic data standards inventory for research on rare diseases, in the fields of: Genomics Phenomics Data Elements Ontologies Patient Outcome Measures Publicly available. Researchers invited to contribute and update data.

Progress of Clearinghouse project Compilation of standards Sources: Peer-reviewed literature Recognized (institutional) initiatives Criteria: Sustainability Endorsement by high profile institutions or expert groups Standards organized based on: Categories A peer-review process An agreed upon proposal

Next Steps and Requirements Establish a methodology to develop, deploy and manage the Clearinghouse: Adopt clear definitions of standards and data elements Construct a clear architecture based on categories Define the peer-review process Identify funding to develop a dynamic Clearinghouse Jeffrey Krischer

Specific proposals by the Secretariat Already decided: Development of the Clearinghouse of Data Standards Development of the Generic Consent Form New proposals (in addition to proposals from SC): Coordination of initiatives to identify in silico new drugs and/or new indication Coordination of initiatives to develop patient-centered outcome measures for RD Coordination of initiatives on small population trials

1-Graph Theory Enables Drug Repurposing Gramatica et Al 1-Graph Theory Enables Drug Repurposing Gramatica et Al.: PLOS one, Vol 1 e84912, 2014 23 Million articles from PubMed Possible to link the gathered information on drugs, physiological pathways and resulting biological activities with the pathophysiological signs & symptoms of diseases Possible to rank the matches in order to identify the most promising leads

Graph Theory Enables Drug Repurposing Gramatica et Al Graph Theory Enables Drug Repurposing Gramatica et Al.: PLOS one, Vol 1 e84912, 2014

Graph Theory Enables Drug Repurposing Gramatica et Al Graph Theory Enables Drug Repurposing Gramatica et Al.: PLOS one, Vol 1 e84912, 2014

In silico research for drug positionning/repurposing THERAMetrics.com have developed a system to generate scientific rationales for unmet medical needs Plataforma Drug Discovery (Barcelona) GSK and Sanofi discovery platform EBI NIH Drug repurposing initiative others………..to be identified

Specific proposals by the Secretariat Already decided: Development of the Clearinghouse of Data Standards Development of the Generic Consent Form New proposals (in addition to proposals from SC): Coordination of initiatives to identify in silico new drugs and/or new indication Coordination of initiatives to develop patient-centered outcome measures for RD Coordination of initiatives on small population trials

2- Patient-centered outcome measures COMET: Core Outcome Measures in Effectiveness Trials: EC funded project for the development and application of agreed standardized sets of outcomes PCORI: Patient-Centered outcome Research Institute: US NGO established in 2010 to improve the quality and relevance of evidence ICHOM: International Consortium for Health Outcomes Measurement: define health outcomes ISPOR: International Society for Pharmacoeconomics and Outcomes Research has a Patient Reported Outcomes (PRO) Content Validity Good Research Practices Task Force MAPI is the leading Patient-Centered Research company

Specific proposals by the Secretariat Already decided: Development of the Clearinghouse of Data Standards Development of the Generic Consent Form New proposals (in addition to proposals from SC): Coordination of initiatives to identify in silico new drugs and/or new indication Coordination of initiatives to develop patient-centered outcome measures for RD Coordination of initiatives on small population trials

3- Small Population Trials Three projects in Europe Integrated DEsign and AnaLysis of small population group trials (IDEAL) Innovative methodology for small populations research (INSPIRE) Advances in Small Trials dEsign for Regulatory Innovation and eXcellence (ASTERIX) Other similar projects in other regions ?

Proposal for a change in organisation

Change in organisation Stop the activity of the 12 existing WG to re-establish ad hoc WG in relation with topics selected for action Proposal to have now only 2 SC ,for each of the goals: Diagnostics and Therapy, to facilitate communication Secretariat workforce dedicated to preparing documents to be discussed at workshops + reports from workshops and follow-up of further actions identified + publications in journals + communication in meetings

Secretariat proposed Scope of Activity Secretariat of Executive Committee Communication on projects funded by IRDiRC members + publications Website and internal newsletter Secretariat of 5 or 6 WG maximum composed of the key stakeholders of a given topic with a defined action plan Management of The clearinghouse of data standards The « IRDiRC recommended » process The Core terminology of phenome terminologies

Secretariat Team Coordination: Ségolène Aymé Management: Lilian Lau (will replace Barbara Cagniard) Communication: Antonia Mills for scientific documents and Sophie Höhn for website, PWP and internal newsletter Research projects: Sandra Peixoto Administration: Mariane Bellanger

Thank you for your attention and Suggestions