“Academic Clinical Research Facilities in Ireland”

1. “Academic Clinical Research Facilities in Ireland” Patrick Murray, MD, FASN, FRCPI, FJFICMI Professor, University College Dublin, Mater Misericordiae University Hospital, Dublin, Ireland patrick.murray@ucd.ie Dublin Academic Medical Centre IMDA/ICRIN Symposium, September 13th, 2012

2. Outline • Profiles of Academic CRCs/CRFs in the Republic of Ireland • Irish CRF Networks: • Dublin Centre for Clinical Research (DCCR) • Development of a National Clinical Research Framework (NCRF)

3. HRB Clinical Research Facility at University College Cork (CRF-C) • Co-funded by HRB and UCC • Comprises • Adult Research Unit in Mercy University Hospital • Paediatric ‘Discovery’ Unit on CUH campus • Separate adult research rooms throughout CUH • Goal • Promote excellence in the design, conduct and analysis of patient focused research • To protect the welfare of research participants • To mitigate all elements of risk associated with the conduct of research in human subjects • Facilitate UCC in undertaking role of Clinical Trial Sponsor • Develop Interface between UCC and its affiliated Hospitals • Staff: • Clinical Director, Business Manager, 7 research nurses, Biostatistician, Data Manager, Research Pharmacist, Quality Manager, Research Methodologist • Services: • Provision of experienced research staff, dedicated space and validated research equipment • Assistance in protocol development, ethics and regulatory submission, grant submissions • Supporting study monitoring and risk mitigation activities in UCC sponsored trials • Supporting clinicians in conduct of Industry funded Trials

4. CRF-CCurrent Activities • Observational studies: 18 • Pharmaceutical Trials • 10 Phase 3A/3B clinical trials • 2 UCC sponsored clinical trials • UCC Investigators with Medical Devices under development: • Declan Soden (Cork Cancer Research Centre): • Endoscopic electroporation device • Padraig Cantillon-Murphy (UCC School of Engineering) • Small bowel retractor • 3D navigation platform for endoscopic lung biopsy • Geraldine Boylan (UCC Neonatal Brain Research Group) • Neonatal seizures analysis • Finbar Allan (UCC School of Dentistry) • Bioactive Dental Implant Material • George Shorten: UCC School of Medicine • ASSERT (Application of Science to Simulation Education, Research and Training) Centre

5. HRB Clinical Research Facility, Galway (CRFG)www.crfg.ie CRFG is a HRB-funded joint venture between Galway University Hospitals (GUH) and National University of Ireland, Galway (NUIG) and has been in operation since March 2008.

6. CRFG Core Research Staff (n=34) by Category

7. CRFG Study Types (Sep 2012)

8. CRFG Studies (Sep 2012): Research Area

9. CRFG Current Services to Medical Device Companies • Clinical investigation plan development • Study budget preparation • Ethical and regulatory submissions • Biostatistical support for study design • Clinical investigation study management • Research nursing • Database development/Data management/eCRF development • Monitoring • Statistical analysis reporting • Medical writing

10. UCD Clinical Research Centre Enabling High Quality Research UCD CRC MMUH Campus SVUH Campus Core Infrastructure / Enabling Resources

11. UCD CRC • Single operational CRC • MMUH Site- opened 2006 • SVUH Site- opened 2007 • Approx. 80 Investigators • Over 250 Users • Direct Leveraged Funding over 18M • Over 22,000 Patient Contacts • Activity across all clin/trans domains

12. UCD CRC Activity- Patient Contacts by Study Type

13. UCD CRC Activity – Leveraging Funding

14. UCD CRC - Abbott Partnership • 5 year Umbrella agreement with Abbott Diagnostics • Covers - • Development of core biomarker validation lab • Supply of Architect immunoassay and clinical chemistry analyser • Supply of all reagents and test kits • Exhibit 1 • Core lab for Akinesis Clinical trial • Analysis of urinary NGAL, Cr and Alb • + other plasma analytes

15. Core Lab Activity to Apr 2012

16. AKINESIS Enrolling and Participating Centers UCSD KUMC St. Vincent, Univ. H UHB , Switzerland Stanford Henry Ford Health Mater Misericordiae UMC Groningen VAMC, CA NY Methodist Lariboisiere Hospital Charite’, Germany ALERE Medical VCU Abbott Diagnostic San FilippoNeri Sponsors Core Lab Center Enrolling Center Data Analysis Center

17. Immunohistochemical Localisation: The Human Kidney GST in Proximal Tubules GST in Distal Tubules www.argutusmed.com Collagen IV in Glom HCD (green) in Collecting Duct 17

18. RCSI Clinical Research Centre 1784 2000

19. RCSI Clinical Research Centre • 1st Academic Clinical Research Centre in Ireland, opened in September 2000 • To date 16,299 Patient to the CRC • 1st Phase I trial in an academic CRC in Ireland, 2012 • 1st Clinical Research Nursing Course 2009 • INCA Study • National Screening Programme for Alpha 1 AntiTrypsin Deficiency, 2004 • Strategic partner with Biomedical Diagnostics Institute (BDI) at Dublin City University, and testing site for BDI prototypes

20. INCA Device: Portable Acoustic MonitorTo provide adherence information Cheap & low power consumption Acoustic monitoring device Sampling rate: 8000Hz Microphone Easily attaches to side of Diskus DPI Bit depth: 8 bits/sample

21. Wellcome Trust – HRB Clinical Research Facility at St. James’s Hospital

22. Wellcome Trust – HRB Clinical Research Centre CAMI 3T MRI Neurophysiology Suite (EEG) Exercise Physiology Lab Six Bed Unit Four Isolation Rooms Gene Therapy Pharmacy

23. Wellcome Trust – HRB Clinical Research Centre

24. Clinical Research Service Cluster

25. About the Dublin Centre for Clinical Research (DCCR) • In 2006, three Dublin Medical Schools (TCD, RCSI and UCD) responded to a Wellcome Trust call to fund clinical research infrastructure. • Dublin application scored second and this resulted in €23M in funding from the Wellcome Trust and Health Research Board: • ~€10m the development of a Clinical Research Centre (CRC) at St. James’s Hospital • Five years operational funding (~€13m) for DCCR Network and St. James’s Hospital Clinical Research Facility

26. Dublin Centre for Clinical Research – Network of CRCs in Dublin:RCSI CRC, BeaumontUCD CRC, MaterWellcome Trust HRB CRF at St. James’s HospitalUCD CRC at St. Vincent’s

27. DCCR Organisational Structure Aligned With Function Institute of Biopharm. Sciences (RCSI) DCCR Consortium Board DCCR Network Management TeamP. Murray, UCD (Chair)D. Kenny, RCSI (Ass. Dir.)M. Gill, (PI)P. Doran, UCDG. Cunnane, TCD/SJHR. Barrington, MMI J. Towns, DCCRP. Barry, DCCR DCCR Thematic Research Groups Conway Institute (UCD) DIRECTION Diabetes & Metabolism Respiratory Disease Stroke IMM (TCD) Chronic Kidney Disease Neuropsychiatry Ophthalmology Prostate Cancer DCCR Operations Team J. Towns, ChairP. Barry, DCCRM. Burke, UCD/MMUHD.. Hyland, RCSIV. Trimble, SJHM. McGrath, UCD/SVUHJ. McCourt (Informatics) Neurodegeneration Infectious Disease & HIV Gastroenterology IBTS SUPPORT Institute of Preventative Medicine (AMNCH ) SJHCRC SVUH CRC MMUH CRC RCSI CRC Others to be identified CAMI (SJH)

28. DCCR’s Research Network Infrastructure Research Nursing Development: • Recruitment of Network Research Nurses – 12 Network Nurses Now in Place • Common GCP Training – 4 courses per annum • Certificate Course in Research Nursing: • 12 candidates 2009 • 10 candidates 2010 • 9 candidates 2011 • Revival of Irish Research Nurses Network • Further post graduate education for nurses and other clinical researchers

29. Professional IT Manager (John McCourt) started in April 2009 IT function has a cross-institutional mandate IT Priority: IT that supports multisite clinical research activities: Study Management eCRF/study databases Sample tracking Research Ethics Network Information Technology Infrastructure

30. DCCR Disease Groups DCCR’s Clinical Research Networks • Diabetes Group – Ronan Canavan/Louise Healey • GUIDANCE Study (EASD) – completed with 950+ patients recruited by 30+ Consultants/GPs • Respiratory Medicine Group – Michael Keane • IPF/Sarcoidosis – Biorepository - 277+ patients recruited to date • Device for Asthma Patients – INCA; at Beaumont, SVUH and SJH • Gastroenterology Group – Ross McManus • Coeliac Disease DNA collection – ongoing – 300 + samples collected • Barrett’s Oesophagus – WT (Eagle) Consortium - 250+ samples collected from Mater and SJH • Inflammatory Skin Disease – Alan Irvine • WT funding for international collection of 4000 samples from Children with Eczema • Neuropsychiatry – Michael Gill • Extension of Wellcome Trust Case Control Consortium Study of patients with psychosis • Prostate Cancer Research Consortium – Bill Watson • Continued investigation of potential biomarkers • Infectious Diseases (HIV/TB) – Paddy Mallon/Colm Bergin • Latent TB Incidence, HIV and TB and TB immunity and Vitamin D • Neurodegeneration – Orla Hardiman • Registry for Young Onset Neurodegeneration • Ophthalmology – David Keegan • Registry of Patients with Severe Retinal Dystrophy • Stroke – Peter Kelly • Stroke Biomarkers • Cardiology - IHF • Aspirin compliance study

31. Potential for a National Clinical Research Framework (NCRF): expert cores and coordination hub