Revolutionizing Translational Medicine in Ireland: A Case Study

1. Developing translational medicine in Ireland Bill Powderly MD FRCPI Dean of Medicine, UCD School of Medicine Chief Academic Officer, Dublin Academic Medical Centre

2. Ireland – small island in global world

3. Irish medical landscape 2000 • 5 Medical Schools • ~700 students pa • Small faculty • Limited research. • University rankings low • Loosely affiliated teaching hospitals • High quality clinical staff • 95% trained in USA, UK or Australia • Beginning of significant Irish government and philantropic investment in science infrastructure

4. Infrastructural Investment • Commencing in 1998, Irish Government launched Programme for Research in Third-Level Institutions (PRTLI) • €1.22 billion (exchequer and private matching funds) to strengthening national research capabilities via investment in human and physical infrastructure. • Over 5 cycles, PRTLI provided integrated financial support for institutional strategies, programmes and infrastructure

5. Molecular Medicine Ireland – a case study • 1999-2001 • UCD Conway Institute and TCD Institute for Molecular Medicine funded as separate Institutes • 2002 • UCD and TCD collaborated to create Dublin Molecular Medicine Centre (DMMC) • 2005 • RCSI joined DMMC • 2008 • DMMC evolved into Molecular Medicine Ireland (MMI) with UCC and NUIG joining as full partners

6. UCD Conway Institute • 11,500M2 biomedical science complex opened in 2003 housing 550 research, technical & administrative staff • 94 Conway Fellows & their teams with 255 graduate students • Research Focus : Translational Sciences & Systems Biology • Diabetes & vascular biology; infection, immunity & repair; neuroscience • Core technologies • Bioinformatics, genomics, proteomics, transcriptomics, transgenics • Funding • €92 million Capital • >€150 million Research Grants • Innovation Culture • Wyeth Research Labs • Discovery antibody technologies Conway Institute for Biomedical & Biomolecular Research

7. TCD Core facilities Centre for Biomedical Sciences 70,000 sq m facility, dedicated to the integration of the research efforts of Medicine, Biochemistry and Immunology, Chemistry and Pharmacy with a strong focus on translational technologies involved in drug discovery such as structural biology and medicinal chemistry Institute of Molecular Medicine With core facilities in bio-banking, immunology, high level genomics, functional genomic, proteomic and high content screening capacity Trinity Centre for Bioengineering With a biomechanical testing laboratory, tissue preparation laboratory, biomaterials laboratory, tissue engineering laboratory and the impact biomechanics laboratory

8. Molecular Medicine Ireland – a case study • 1999-2001 • UCD Conway Institute and TCD Institute for Molecular Medicine funded as separate Institutes • 2002 • UCD and TCD collaborated to create Dublin Molecular Medicine Centre (DMMC) • 2005 • RCSI joined DMMC • 2008 • DMMC evolved into Molecular Medicine Ireland (MMI) with UCC and NUIG joining as full partners

9. Collaboration • UCD and TCD created the Dublin Molecular Medicine Centre (DMMC) to provide critical mass in Irish biomedical research. • promote collaborative translational research and cross-institution post-graduate education and training curriculum. • Enabled construction of infrastructure for molecular medicine in Dublin providing core facilities in genomics, proteomics, cell biology and ‘cellomics’ within an integrated architecture with citywide access, • Commenced process of integrating clinical research.

10. Molecular Medicine Ireland – a case study • 1999-2001 • UCD Conway Institute and TCD Institute for Molecular Medicine funded as separate Institutes • 2002 • UCD and TCD collaborated to create Dublin Molecular Medicine Centre (DMMC) • 2005 • RCSI joined DMMC • 2008 • DMMC evolved into Molecular Medicine Ireland (MMI) with UCC and NUIG joining as full partners

12. Dublin Centre for Clinical Research DMMC partners developed a joint application (led by Dermot Kelleher at TCD) to Wellcome Trust to create Dublin Center for Clinical Research PRTLI funded CRCs at UCD and RCSI Wellcome Trust funding new CRC and HRB funding network activities Building on research strengths in infection & immunity, neuropsychiatry, molecular therapeutics, cancer. Funding commenced in 2008 – over 2,000 patients recruited to network studies

13. Dublin Centre for Clinical ResearchWellcome Trust – HRB Clinical Research Centre at St. James’s Hospital 3 Tesla MRI Neurophysiology Suite (EEG) Exercise Physiology Lab Six Bed Day Unit Four Isolation Rooms Gene Therapy Pharmacy

14. Molecular Medicine Ireland – a case study • 1999-2001 • UCD Conway Institute and TCD Institute for Molecular Medicine funded as separate Institutes • 2002 • UCD and TCD collaborated to create Dublin Molecular Medicine Centre (DMMC) • 2005 • RCSI joined DMMC • 2008 • DMMC evolved into Molecular Medicine Ireland (MMI) with UCC and NUIG joining as full partners

15. Vision - improved healthcare through the development of diagnostics and therapies from concept to realisation The mission of MMI is to mobilise the strengths of the five partner institutionsand their associated hospitals to build a sustainable national system to coordinate, support and promotetranslational and clinical research

16. MMI Education & Training Widely Available Short Courses & Workshops in Clinical and Translational Research • Designed for a cross-institutional audience: 2942 attendances (2003-2009). • Application and provision of course materials via MMI website. Attendances Breakdown 2003-2009

17. MMI PhD Training Programmes in Clinical & Translational Research • From 2008, 22 medical graduates are undertaking PhD studies in five academic institutions as MMI Clinician Scientist Fellows with shared national structured training (funded through PRTLI Cycle 4). • The structured training curriculum will form a sustained resource, available via the MMI website, for all medical graduates undertaking PhD studies in the future. Over sixty graduate education modules have been assembled to date from MMI partner institutions. • From 2011, 20 basic science graduates will undertake PhD studies in clinical and translational research as MMI Scholars with industry involvement in courses and placements (funded through PRTLI Cycle 5). For more information visit www.molecularmedicineireland.ie

18. Information Technology Infrastructure Professional IT Manager IT function has a cross institutional mandate IT Priority: IT that supports multisite clinical research activities: Study Management eCRF Sample tracking Research Ethics

19. DCCR’s Clinical Research Networks • Diabetes Group – John Nolan • GUIDANCE Study (EASD) – completed with 946+ patients recruited by 17 Consultants • Respiratory Medicine Group – Michael Keane • IPF/Sarcoidosis – Bio – repository - 215+ patients recruited to date • Device for Asthma Patients – Going through ethics for six hospital sites • Gastroenterology Group – Ross McManus • Coeliac Disease DNA collection – ongoing – 200 + samples collected in 9 months • Barrett’s Oesophagus – Invited to participate in WT Case Control Consortium • Inflammatory Skin Disease – Alan Irvine • WT and Children’s Research Foundation funding for international collection of 4000 samples from Children with Eczema to start in 2010 • Neuropsychiatry – Michael Gill • Extension of Wellcome Trust Case Control Consortium Study of patients with psychosis • Prostate Cancer Research Consortium – Mark Lawler • 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 (studies in planning) • Neurodegeneration – Orla Hardiman • Registry for Young Onset Neurodegeneration • Ophthalmology – David Keegan • Registry of Patients with Severe Retinal Dystrophy

20. DCCR - Excellence in Research Coeliac Disease Genetics and Immunology Nature Genetics 2010, BMC Medical Genetics 2010 Neuropsychiatric Genetics Nature Genetics 2009, NEJM 2008 Platelets & Coronary Artery Disease J of Thrombosis and Haemostasis, 2008 Novel Bioactive Peptides Nature Chem. Biol. 2007 Lung Cancer Diagnostics Nature Medicine 2007 Cystic Fibrosis Pathogenesis J Biol. Chem. 2007, 2008 Prostate CancerProstate 2010, British Journal of Urology, 2010

21. DCCR - New Therapeutics Discovery - fuelling the pipeline Vaccine for Helicobacter Pylori Novartis Phase II Clinical Trial OPN-501 New Drug for IBD Opsona Clinical Development Opsovax Cancer Vaccine Opsona Clinical Development RNAi Therapeutics Genable GT015 Dissociated APC Pure anti-inflammatory properties Clinical Research activity undertaken Funded by? Resulting Publications?

22. Ireland a country of choice for scientifically relevant multi-centre clinical studies and trials in specialist fields where partners are strong.

23. Objectives Network MMI partner CRCs and research teams into a national infrastructure Develop and deliver clinical research education/training programmes PIs, Research nurses, clinical research staff Facilitate academic and industry clinical investigators to conduct multi-centre clinical studies/trials Drive harmonisation of clinical research procedures Research Governance, Informed Consent, Ethical Review, Data Monitoring and Safety Reporting Research Readiness Programme As the Irish scientific partner, contribute to building the European Clinical Research Infrastructure Network Irish Clinical Research Infrastructure Network- ICRIN 23

24. ICRIN Research Readiness Research Governance, Sponsorship Quality Oversight Advisory and Consulting Quality Management (SOPs, Training) Training/Education Trial Management and Oversight ICRIN Hub CRC/CTU Regulatory and Ethics Administration and Logistics Communication and Promotion Trial Design and Statistical Methodology Regulatory/Best Practice Horizon Scanning IT solutions and Data Management National and EU Interface Clinical/Hospital Governance 24 Process Management

25. Irish public policy Centres of excellence in Health Care Delivery Centres of world significance in translational health research Clear and transparent governance structures between teaching hospitals and their associated university Critical need to reduce expenditures and staff numbers Leveraging Health for job creation • Children’s Health First (2006), • Strategy for Cancer Control (2006), • Report of the National Task Force on Medical Staffing (2003) • Strategy for Science, Technology & Innovation 2006-2013 • Towards better health: achieving a step change in Health Research in Ireland, 2006 • Fottrell report on Medical Education, 2005 • Report of the Special Group on Public Service Numbers and Expenditure Programmes (2009); • OECD Public Management Review – Ireland: Towards an Integrated Public Service 2009; • Building Ireland's Smart Economy: A Framework for Sustainable Economic Renewal, 2008

26. Investment - UCD Significant public investment UCD Conway Institute UCD Charles Institute (Dermatology) UCD Geary Institute (economics) Systems Biology Ireland (SFI -CSET) TRIL (Ageing, Intel) NIBRT UCD Clinical Research Centres at MMUH and SVUH

27. Hospital relationship • Two major teaching hospitals • Combined annual budget 600 m euro state funded but independently managed • majority of clinical staff no deep loyalty to the University • Even University-appointed clinical staff have divided loyalties.

28. Why an AMC - UCD issues UCD identified translational medicine as a key strategic goal ‘UCD Conway Institute will be a global leader in biomedical research and through partnership will translate this knowledge to benefit patients’ For university to be successful, need a cadre of clinical investigators need to be able to have a major input into their appointment and into the allocation of their time. Need to establish research and education as key missions and values in hospital

29. Dublin Academic Medical Centre Ireland’s first patient-focused academic medical centre incorporating Mater Misericordiae University Hospital, St. Vincent’s Healthcare Group, and University College Dublin

30. DAMC at a glance Merger creates largest hospital group in Ireland Improved financial and operational performance Patients, population and staff Currently > 400,000 patient contacts a year Serving a local population of 750,000 5000 staff including 350 consultants National and regional specialty services maintain and improve of excellent patient care with a culture of research driven quality Can expand to other hospitals

31. How it works Single integrated leadership and management throughout C hief Academic Officer key position Integrated strategic, operational and capital planning Development of site specific clinical services Joint appointments and programmes Clinical services, research, innovation and education purposefully linked Patient Care Education Research and Innovation

32. Core Activities • Patient care • Integrated clinical care strategy • Evidence-based • Technology-enabled • Digital health – UCD School of Computer Science and Informatics* • Effectively and efficiently managed • Education • Undergraduate • Medicine • Other professions - Nursing, Physio, DI • Postgraduate • Healthcare management - UCD Business School* • CPD

33. Core Activities • Research • Rigorous review and single research strategy • Major categories • Translational bench-to-bedside research • UCD Conway Institute • Clinical trials and clinical investigation • Clinical Research Centre, Molecular Medicine Ireland • Health systems, outcomes and economics • UCD Geary Institute • Niche areas • Biomedical engineering* • Dermatology (Charles) • Technology Research for Independent Living (Intel)* • Site-specific differentiation • Education/research magnet for recruitment tool

34. Core Activities • Innovation and Enterprise • NovaUCD • DAMC as technology test bed • Thought leadership • DAMC-Geary Institute Partnership • Children/poverty/health/human development • Ageing/elder abuse/social change • Evidence-based health policy • Wider public engagement

35. Current challenge • Just as we get the infrastructure in place to potentially become internationally competitive, bottom falls out of Irish economy • Core University funding cut by 20% and likely to fall further • Health care spending to be cut 20% in next 3 years • Patient services will take priority over research and education • Research funding dropped dramatically – 75%

36. UCD/TCD Innovation Alliance • National recovery initiative built around the development of the Smart Economy • UCD/TCD Joint Venture in Enterprise Development • UCD/TCD Innovation Academy • Closer collaboration between Medical Schools • Dublin Centre for Rheumatologic Research • Joint Centre for Vision Sciences • Joint Dept of Paediatrics at new CHOI

37. Experience is what we call our mistakes. Oscar Wilde

38. Ireland – small island in global world • Collaboration essential • Internal and external • Identify strengths (and weaknesses) • Coherent strategic vision – government and organization • Fortitude to execute the vision • Funding models • Core • Research • People