New opportunities in translational research

1. New opportunities in translational research Professor Stephen Holgate Chairman MRC Physiological Systems and Clinical Sciences Board University of Southampton

2. Principles and Practise of Medicine: 1892 Medicine became a science by combining clinical observation with pathology and function and through the application of chemical, biological and physical sciences

4. Medical Research Council • Established in 1913 as the Medical Research Committee by Christopher Addison (Prof of Surgery in Sheffield) to tackle TB and illness related to poor housing and other socioeconomic inequalities. • Supporting medical research across the full spectrum of biological sciences. • 25 Nobel prizes and major medical advances – penicillin, DNA, MRI imaging, link between smoking and cancer, benefits of cholesterol lowering drugs. • Largest non-commercial funder of clinical trails in UK. Major contributions to clinical practice and public health.

5. The MRC mission: Discovery Science for Health • Encourage and support high quality research with the aim of maintaining and improving human health. • Produce skilled researchers. • Advance and disseminate knowledge and technology to improve the quality of life and economic competitiveness in the UK. • Promote dialogue with the public about medical research.

6. MRC funding for research ~£500m • ~50% of funding is directly to MRC research establishments - 3 Institutes, 29 Units • ~50% of funding is in response mode - 9 Centres, research grants, training awards and fellowships • ~£50m pa on training and career development People • Employs over 3300 staff in UK and overseas • Supports ~3000 staff on research grants • 350 research fellows and ~ 1400 students

7. SPOG SPOG SPOG SPOG SPOG Scientific Decision Making - Research Boards and Panels COUNCIL MCMB PSCSB IIB NMHB HSPHRB CompetitionPanels College of Experts (CoE)

8. MRC gross spend by scientific area in 2004/05 • Health Services and Public Health Research £61.9m (13%) • Molecular and Cellular Medicine £180.8m (39%) • Neurosciences and Mental Health £82.1m (17%) • Infections and Immunity £77.3m (16%) • Physiological Systems and Clinical Sciences £72.6m (15%)

9. Board engagement remains vital Boards are pivotal in helping shaping the MRC’s Strategy and Delivery Plan Examples where PSCSB has led strategic priority setting: • Integrative mammalian biology (£12m total – MRC £2m, 2005) • Mouse models of disease (mutagenesis £4m, 2006) • Experimental Medicine (I and II - £30m, 2006/08) • Biomarkers ‘qualification’ (£17m total – MRC £8m, 2007)

10. Board engagement remains vital Interim Strategy Portfolio Group and Council: Delivery Plan and Board budget discussions. Boards have delegated authority to award grant funds. Current PSCSB priorities: • Musculoskeletal, respiratory, obesity, drug safety, • Integrative Physiology, ageing Future opportunities: • Environment and health, nutrition – strategic review • Lifelong health and wellbeing

11. Research is changing • Evidence-based medicine – need for trials. • Need to harness molecular revolution. • Move from taking things apart to understanding complexity. • Funding arrangements: Research Assessment have separated NHS and academic research. • Training in research methods now more professional. • Involvement of patients. • Research ethics and governance complex.

12. Biomedical Research Post-genome Health of the Public ‘continuum’ Challenges ahead Individual • Forging Partnerships • Training and retaining • researchers • Research infrastructure • Development gap funding • Engaging the public • Meeting expectations Understanding Animal Families health & disease · prevention Organ · diagnosis Population · treatment Cell Genome Environment

13. DH Research and Development • R & D Directorate established in 1990 following a HOLSC enquiry into medical research. • Led by Sir Michael Peckham, a series of Regional R & D Centres were established. Held local budgets. • National Centres established Reviews & Dissemination, Health Technology Assessment, Primary Care, Information Technology, Cochrane Centre. • Funded largely by top-slicing Regional finance and some central resource. • Intrinsic budget supported cost of research in teaching hospitals (previously SIFTR) and under Sir Anthony Culyer’s review, hospital trusts had to justify amount based on research activity

14. National enquiries into R & D base • Major concerns about the state of clinical research in the UK • Pharmaceuticals Industries Competitiveness Task Force (PICTF) 2001 • Biosciences Innovations & Growth Team (BIGT) 2003 • Academy of Medical Sciences (AMS) 2003 • Sir David Cooksey Report 2006 • Establishment of Research for Patients Benefit Working Party

15. New organisation for health research • From a base of £540DHm p.a., announcement March 2004 (Dr Sally Davies) : extra £100m p.a. by 2008 for research (in England) building on successful model for cancer research. • Targeted research funding • Medicines for Children • Diabetes • Dementias and Neurodegenerative Disease (DeNDRoN) • Stroke • Cancer • Mental Health • Clinical Research Network model (UKCRN). • UK Clinical Research Collaboration (UKCRC). • NHS R&D Strategy: “Best Research for Best Health” – Sally Davies, DH National Institute for Health Research

16. Faculty Senior Investigators Investigators Trainees Programmes Infrastructure Research Projects Research Networks Research Programmes Experimental Medicine Facilities Research Units Technology Platforms National Schools for Research Research Centres Governance Network Information Systems Advice Service ResearchEthics Systems National Institute for Health Research (NIHR) Universities NHS Trusts Networks Patients&Public

17. What is the UK Clinical ResearchNetwork? • UKCRN consist of a managed set of Clinical Research Networks to facilitate the conduct of randomised trials and other well designed studies. • Research projects funded by both commercial and non-commercial organisations will be incorporated. • 6 initial priority areas – Cancer (NCRN), Mental Health (MHRN), Medicines for Children (MCRN), Diabetes (DRN), Stroke (SRN) and Dementias and Neurodegenerative Disease (DeNDRoN). Each has a small Coordinating Centre. • UKCRN is being extended to cover full spectrum of disease and clinical need through Comprehensive Clinical Research Network. • Links with developments in Scotland, Wales and Northern Ireland. • Aim: to provide a world-class health service infrastructure to support clinical research.

18. UKCRN Coordinating Centres Professors Janet Darbyshire & Peter SelbyUKCRN and PCRN Professor Gary FordDirector, Stroke Research Network Professor David Cameron Director, National Cancer Research Network Professor Ros SmythDirector, Medicines for Children Research Network Professor Til WykesDirector, Mental Health Research Network Professor Martin RossorDirector, Dementias and Neurodegenerative Diseases Research Network Professor Des JohnstonDirector, Diabetes Research Network ☺ www.ukcrn.org.uk

19. What is a Comprehensive Local ResearchNetwork (CLRN)? • Primary vehicle for providing infrastructure to support study delivery (set-up, recruitment, follow-up, data collection, publicity) • Primary, secondary and tertiary care (and social care) • All appoint Clinical Lead (p/t) and Network Manager (f/t) • A typical LRN will include: • Appropriate NHS staff costs – research nurses, data managers, secretarial support • Appropriate infrastructure in the primary care setting – practice nurse time, receptionist time, manager time • Appropriate diagnostic test or clinical services costs – pharmacy, pathology, radiology • Essential running costs • Must be embedded into clinical care provision www.ukcrn.org.uk

20. Local Elements of CLRNs • Coverage across England • Covers all areas of healthcare • Within SHA boundaries - 25 CLRNs • Natural catchments – primary, secondary and tertiary • One to four per SHA – minimum essential • Local capacity and expertise important • Flexible per capita funding UK Clinical Research Network (UKCRN)

21. How do clinical research studies become UKCRN studies? • Studies funded by a UKCRC partner who awards funds in open national competition • Exceptionally, studies not funded by a UKCRC partner are adopted • Commercial trials and studies after adoption.

22. A Review of UK Health Research FundingSir David CookseyDecember 2006

23. Research Spend versus Disease Burden

24. Proportion of combined total UK spend by research activity as % of total spend(UKCRC Research Analysis 2005) • Detection & Diagnosis • Disease Management • Treatment Development • Treatment Evaluation • Health Service • Underpinning • Prevention • Aetiology % 20 10 0 10 20

25. UKCRC: Research by Type Health service Treatment development Aetiology Translational Research

26. MHRA NICE 1st Gap in translation Early Clinical trials Late Clinical trials Health Technology assessment Prototype Discovery & Design Preclinical development Basic research MRC and Medical Charities 2nd Gap in translation Health service research NIHR Knowledge management NHS Healthcare delivery Pathway for translation of health research into healthcare improvement

27. MRC – NIHR: The joint initiative

28. MRC CSR 2007 allocation • Average increase of other Research Councils: 17% • Values include 80% FEC • Funding includes specific allocation of • £25m/£44m/£63m for OSHRC related strategy – • translational and public health research • £30m for collaboration with TSB

29. Informatics OSCHR Delivery Plan MRC OSCHR MRC lead NIHR lead • Genetics/genomics • Structural biology • Imaging • Systems medicine • Global health • Ageing: lifecourse • Stem cells • Infections • Population science • Experimental • Medicine • (therapies, • diagnostics, • devices) • Methodology • Pharmacogenomics • Animal/human models • Regenerative medicine • HTA Trials • Public health • E-health Multidisciplinary approaches MRC activities in Developing People Statistics In-vivo Microbiology Experimental medicine Public health modelling Systems biomedicine Clinical research skills Methodology Pharmacology

30. New Funding Schemes • Exploratory Development Programme (new) • Efficacy and Mechanisms Evaluations (EME) Programme • – science driven (new) • Health Technology Assessment Programme • -use driven • Global Health Programme

31. Targeted calls and initiatives Patient-based cohorts (November 14th) • Well-characterised patient cohorts for patient stratification studies • Tissue banks • Population-based cohorts (e.g. birth cohorts) to provide control data Models (Mid December) • Pathways of disease – to identify potential ‘treatable’ targets • Animal and human models of disease • In silico modelling, including predictive toxicology Biomarkers (Mid January) • Activity/mechanism • Surrogate end points • Toxicology Methodology Research • Increased support for investigator-led and commissioned research

32. UK Respiratory Research Collaborative UK Respiratory Research Strategy Committee Medical Practitioners Occupational physicians Basic Scientists Lung function scientists Nurses Physiotherapists Pharmacists Lung-related charities NCRI National Library Observers: MRC UKCRC

33. UK Respiratory Research Collaborative • Using a joint funding model increase capacity for lung research in all areas – PhD Studentships, Postdoctoral and Clinical Training Fellowships. • Establish a support group for new research trainees. • Seek support and establish clinical trial networks. • Coordinate the bringing together of birth and other cohorts for biobanks. • Explore ways of engaging industry and DH as members of UKRRC. 21 new PhD Capacity Building Studentships for 2007- 8 Collaborative link with Cancer Research UK for increased research in lung cancer Priorities for Clinical Trials Asthma, COPD, Pulmonary Fibrosis, Lung Cancer New links with industry for joint initiatives 3 new MRC/Charity Clinical Training Fellowships

34. Lung Research Moves Forward: The UK Respiratory Research Strategy Committee Organisation Prioritisation

35. Capacity Coming To prevent lung disease and improve patient care Engage Strengthen Together Rebuild