1. Safe and Effective Medicine for Children Daring to be Rare, BIOTECanada Panel 2015 CADTH Symposium Saskatoon, April 12-14

2. MICYRN Federal non-profit society (2011) Joins 20 maternal – child health research institutions and disease networks Collaboration on research infrastructure (ethics review, data management…) to reduce duplication of effort and harmonize processes Prime focus to reduce barriers to multi-jurisdictional research (national, international) Focus on rare diseases

3. Why a focus on Rare Diseases? Affect < 1/2000 individuals, 1/12 = 2.7 M Canadians Around 7,000 disorders 80% genetic origin 75% present in childhood

4. Global Objectives 2020:  diagnosis of most rare diseases  200 new therapies New therapies

5. MICYRN & Rare Diseases 1.Diagnosis: - Advisory to Orpha-net - Rare Diseases Models & Mechanisms Network - Patient Registries/Harmonization 2.Therapies: - National plan for pediatric clinical trials research infrastructure (KIDSCAN) - Collaboration in Industry-instigated PCTRI and EU Research Infrastructure 2020 Roadmap initiatives

6. www.orpha.net *

7. RD Models and Mechanisms Network GeneX $25K $2.3 M Catalyst Grant

8. RDMM

9. Understanding Pathogenesis: Patient Registries Health Canada Industry Investigator trials MOH-HTA Patients Foundations Care providers Numbers: incidence, prevalence Natural history Patient outcome measures Surrogate measures pre-debility Stratification of disease Post authorization monitoring beyond safety Adaptive authorization MICYRN Clinical Research Informatics platform supports Registries; International harmonization projects between rare disease registries

10. Clinical trials: methodological Challenges - Small populations, original methods - Rare disease, recruitment at multiple sites - Identifying age –appropriate clinical outcomes - Age –appropriate measurements - QOL questionnaires and validation - Age –appropriate interventions - Doses, routes….. - Blood draws in pediatric patients/ invasive tests - When “2 table spoons” are already too much - “Will it hurt?” - Inclusion in multiple trials - Complex regulation, multiple REB, contracts,..

11. Children take medications, many of which have not been proven safe and effective for their use. Children respond to medications differently from adults; thus, medicines must be studied in children and formulated for children. Studying medicines in children is always possible and in their best interests. In the United States and the European Union, pediatric medicines research is encouraged, required and monitored in ways that offer lessons for Canada. Pediatric medicines research is a Canadian strength, but it requires reinforcement and sustained capacity and infrastructure to realize its full potential. Council of Canadian Academies report, Sept 2014

13. KIDSCAN: a Proposal to develop a Canadian Coordinating and Advisory Network and Infrastructure to Ensure Best Therapies for Children

14. A national infrastructure coordinating and enabling pediatric clinical trials. New clinical trial methodologies, developed with patients and other stakeholders, will provide regulators and reimbursors with the best evidence to determine drug authorization and access. Coordinated development of registries of patient populations with sharing of harmonized phenotype and genotype data both nationally and internationally, will capture the natural history of disorders, establish markers of disease and disability, and determine the impact of interventions.