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

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

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. Medical Research Council

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. The MRC mission:

~£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 MRC funding for research

Scientific Decision Making - Research Boards and Panels College of Experts (CoE) SPOG MCMBHSPHRBPSCSBIIBNMHB Competition Panels COUNCIL

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%)

Board engagement remains vital Boards are pivotal in helping shaping the MRCs 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)

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

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.

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

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 Culyers review, hospital trusts had to justify amount based on research activity

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 National enquiries into R & D base

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 New organisation for health research

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

What is the UK Clinical Research Network? 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.

UKCRN Coordinating Centres Professor Gary Ford Director, Stroke Research Network Professor Des Johnston Director, Diabetes Research Network Professor David Cameron Director, National Cancer Research Network Professor Til Wykes Director, Mental Health Research Network Professor Ros Smyth Director, Medicines for Children Research Network Professor Martin Rossor Director, Dementias and Neurodegenerative Diseases Research Network Professors Janet Darbyshire & Peter Selby UKCRN and PCRN

What is a Comprehensive Local Research Network (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

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)

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.

A Review of UK Health Research Funding Sir David Cooksey December 2006

Research Spend versus Disease Burden

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

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

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

MRC – NIHR: The joint initiative

MRC CSR 2007 allocation Baseline TotalEnd CSR07 Increase £543m£605m£658m£707m£1971m30.1% 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

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

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

Targeted calls and initiatives Patient-based cohorts (November 14 th ) 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

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

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 new MRC/Charity Clinical Training Fellowships Priorities for Clinical Trials Asthma, COPD, Pulmonary Fibrosis, Lung Cancer Collaborative link with Cancer Research UK for increased research in lung cancer New links with industry for joint initiatives

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

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