1. Dr Andrew Rose MCRN Deputy Assistant Director Driving Research Collaboration through NIHR Clinical Research Network: Focus on NIHR Medicines for Children Research Network

2. NIHR Research Infrastructure > £0.5 billion p.a. investment in relevant infrastructure to support clinical research at all points in the development pipeline Ravi Chana/Oliver Rausch (NOCRI) Late-phase clinical research NIHR Biomedical Research Centres Early-phase clinical research Early-phase clinical research InventionEvaluationAdoption NIHR Biomedical Research Units NIHR Clinical Research Facilities Experimental Cancer Medicine Centres NIHR Clinical Research Network NIHR Health Technology Cooperatives NIHR Diagnostic Evidence Cooperatives NIHR CLAHRCs

3. EU Regulation “Better medicines for children” Became law in across EU on 26 January 2007 Incentives and requirements for industry to undertake paediatric studies Paediatric Committee – Based in European Medicines Agency Paediatric Investigation Plan (PIP) – Development agreed with Paediatric Committee Coordinated European Paediatric Trials Network 3

4. To improve children’s health and alleviate suffering through the provision of better and safer medicines MCRN’s Vision AIMS The best infrastructure in the world to support studies which address the safety and efficacy of medicines for children. An excellent base for clinical research for children which is an attractive resource for the global pharmaceutical industry. To ensure that world-leading research addresses the needs of children.

5. NIHR Medicines for Children Research Network Large network supporting randomized and other studies of medicines for children in NHS sites Work closely with Clinical Research Facilities (CRFs) etc Supporting: – All phases – All therapy areas (except oncology) Studies supported by MCRN – Industry-sponsored/funded – Publicly-sponsored, including Investigator-initiated (industry supported) Research (IIR) – Publicly-funded industry and academic/NHS consortia 5

6. Clinical Studies Groups (CSGs) 1. Allergy, Infection and Immunity (BPAIIG)Prof Saul Faust 2. Anaesthesia, Intensive Care and CardiologyDr Mark Peters 3. Cleft and Craniofacial AnomaliesMs Rona Slater (Craniofacial Society of GB & I/The Healing Foundation) 4. Diabetes and Endocrinology (BSPED)Prof Timothy Barrett 5. Gastroenterology, Hepatology & Nutrition (BSPGHAN)Prof Stephen Allen 6. General Paediatrics (including Dermatology) (BAGP)Dr Alastair Sutcliffe 7. Inherited Metabolic Disorders Dr Chris Hendriksz (UK LSD Patient Collaborative Group) 8. Methodology Prof Ruth Gilbert 9. Neonatal (Action Medical Research) Dr Mark Turner 10. Nephrology (BAPN)Dr Richard Coward 11. Neurosciences Prof Helen Cross 12. Pain and Palliative Care (Louis Dundas Dev’ Fund)Dr Richard Howard 13. Pharmacy and PharmacologyProf James McElnay 14. Respiratory and Cystic FibrosisDr Paul Seddon 15. Rheumatology (Arthritis Research UK) Prof Michael Beresford 6

7. LRN/Area staff support the conduct of paediatric research in the NHS and work in accordance with Good Clinical Practice (GCP) Director Manager Research Nurses Pharmacists Data entry staff Administration Local Research Networks (LRNs) and Areas 7

8. Growth of Portfolio 8

9. Recruitment to studies 9 Number of participants recruited

10. Recruitment to target (2012/13) 10

11. Support for industry- sponsored and funded studies Dedicated MCRN Industry Staff Facilitate close working with companies and contract research organisations (CROs) – Interacted with close to 200 companies interested in children’s research Detailed knowledge of/access to expertise – EU Paediatric Regulation (PIPs) – Study and programme design (inc pharmacy) – Implementation (feasibility, set-up, delivery) – Consumer matters (patient information etc) industry@mcrn.org.uk 11

12. NIHR CRN Feasibility Services 1.Early Feedback – A rapid assessment of feasibility (10 days) by clinical specialists: Current UK practice, prevalence of the relevant patient population Network knowledge of competing studies etc. 2.Site Intelligence – Sites selected - process ensures that proposed recruitment targets are realistic (15 days) Complements existing feasibility data In parallel with other processes (study added to portfolio) 3.Site Identification – Identification of new sites (15 days) supportmystudy@nihr.ac.uk 12

13. Growth of Industry Portfolio 13 update

14. Industry-sponsored and funded case study 1 Systemic Juvenile Idiopathic Arthritis – Sponsored by F. Hoffmann-La Roche Ltd (Roche) Tocilizumab in children aged 2 to 17 Interactions between Rheumatology CSG and company Despite significant challenges, the MCRN recruited on time and to target Product now – Licensed for use in this setting and – Approved by National Institute for Health and Clinical Excellence (NICE) Programme of related research with tocilizumab 14

15. Industry-sponsored and funded case study 2 Study to evaluate an antibody for the treatment of neonatal sepsis (Biosynexus) 93 international sites (8 UK) MCRN staff/resources supported: – Site identification (CRO found challenging) – Ethics approval – Site setup (costing/approvals/logistics) – Recruitment Success in this and other neonatal studies have helped to attract other studies 15

16. Licensed Products Prevenar 13 vaccine/Pneumococcal disease Cozaar/Proteinuria Tocilizumab/systemic juvenile idiopathic arthritis (sJIA) Xalatan (Latanoprost)/Glaucoma Menveo vaccine/Meningococcal disease Kalydeco (Ivacaftor)/Cystic fibrosis (G551D) More in the pipeline... Others no paediatric indication, but info added to SPC 16

17. Investigator-initiated (industry supported) Research (IIR) Publicly (NHS/Uni)-sponsored and led, with industry support: – Academic investigator develops protocol and approaches industry for: – Funding, drug, placebo, device and/or other support – Uni/NHS act as sponsor Industry benefits – To support “research that advances medical and scientific knowledge about our products and that generates promising medical interventions” Pfizer.com – Retain product IP Academic benefits – Access to products, funding etc to conduct research for the benefit of patients 17

18. Investigator Studies Operations Group (ISOG) UK Pharma Industry Group (with NIHR representation) Discusses challenges with investigator-initiated studies Working to standardise IIR contracts Meets several times per year Investigator Initiated-Sponsored Research Association (IISRA) 18

19. IIR case study SYCAMORE RCT of Adalimumab in combination with Methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis – Clinical effectiveness, safety and cost effectiveness CI - Dr Athimalaipet Ramanan Sponsor - University Hospitals Bristol NHS Foundation Trust Funders – NIHR Health Technology Assessment – Arthritis Research UK Active and placebo provided by Abbvie (Abbott) 19

20. Industry and academic/NHS consortia studies Publicly funded: – EU FP7, MRC, NIHR Invention for Innovation (i4i) etc – Industry or public (NHS/University) sponsorship Collaborative development of protocols/programmes Industry benefits – Obtain funding, develop academic links, develop company expertise, IP and products, commercialisation opportunities Academic/NHS benefits – Obtain funding, develop industry links, develop Uni/NHS team expertise, helps get products to patients, financial benefits (royalties/IP) 20

21. Industry and academic consortia case study Stratified medicine – Duchenne muscular dystrophy (DMD) – Collaboration including experts from London, Newcastle and Serepta Therapeutics (formerly AVI) Study team (with support of NIHR infrastructure) designed and validated antisense oligonucleotides (“molecular patches”) for DMD gene MCRN/CRF and other NIHR resources supported clinical study Sponsor - AVI BioPharma Funders - MRC and AVI BioPharma Encouraging early results 21

22. Children’s Research Industry Group (CRIG) Direct MCRN links with industry previously not formalised Established CRIG, for MCRN/wider NIHR to: – Improve collaboration with industry – Improve the support that we offer industry – Obtain support and advice on industry matters – Provide a forum for the discussion of children’s research issues of relevance to industry Membership – Pharma – CRO – Med tech Meetings 10 May 2013 and 23 September 2013 Next early 2014 22

23. industry@mcrn.org.uk www.mcrn.org.uk 23