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 SPOGSPOGSPOGSPOG

MCMB HSPHRBPSCSB IIB NMHBCompetition

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 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)

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-genome Health of the Public

Individual

Understandinghealth & 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 Culyer’s 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

TraineesInvestigatorsSenior

Investigators

UniversitiesInfrastructure

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

ResearchEthics

Information Systems

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.

UKCRN Coordinating Centres

Professor Gary FordDirector, Stroke Research Network

Professor Des JohnstonDirector, Diabetes Research Network

☺

Professor David Cameron

Director, National Cancer Research Network

Professor Til WykesDirector, Mental Health Research

Network

Professor Ros SmythDirector, Medicines for Children

Research Network

Professor Martin RossorDirector, Dementias and

Neurodegenerative Diseases Research Network

Professors Janet Darbyshire & Peter Selby

UKCRN and PCRN

www.ukcrn.org.uk

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

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 CookseyDecember 2006

Research Spend versus Disease Burden

Proportion of combined total UK spend by research activity as %

of total spend(UKCRC Research Analysis 2005)

• Un

der

pin

nin

g

• Ae

tiolo

gy

• Pre

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tion

• De

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& D

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atm

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atm

en

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• Dis

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se M

an

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• He

alth

Se

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e %

20 1

0 0 10

20

UKCRC: Research by Type

Translational Research

Health

service

Treatm

ent developm

ent

Aetiology

Pathway for translation of health research into healthcare improvement

Basicresearch

PrototypeDiscovery &

Design

Preclinical development

EarlyClinical

trials

LateClinical

trials

HealthTechnology assessment

Health serviceresearch

Knowledgemanagement

Healthcaredelivery

MRC and Medical Charities

NIHR

NH

S

2n

d Gap

in tran

slation

1st Gap in translation

NICEMHRA

MRC – NIHR: The joint initiative

MRC CSR 2007 allocation

2007-08Baseline

2008-09 2009-10 2010-2011 Total End CSR07Increase

£543m £605m £658m £707m £1971m 30.1%

•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 lead NIHR 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 PeopleStatistics

Microbiology

Informatics

Public health modelling

Pharmacology

Experimental medicineIn-vivo

Systems biomedicine Clinical research skills

Methodology

Multidisciplinary approaches

•ExperimentalMedicine (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 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

UK Respiratory ResearchStrategy Committee

UK Respiratory ResearchCollaborative

Medical PractitionersOccupational physiciansBasic ScientistsLung function scientistsNursesPhysiotherapistsPharmacistsLung-related charitiesNCRINational Library

Observers:MRCUKCRC

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

3 new MRC/Charity Clinical Training

Fellowships

Priorit

ies

for C

linica

l Tria

ls Ast

hma,

CO

PD,

Pul

mon

ary

Fibr

osis,

Lun

g Can

cer

Colla

bora

tive

link

with C

ance

r Res

earc

h UK

for i

ncre

ased

rese

arch

in lu

ng c

ance

r

New links with industry for joint initiatives

Lung Research Moves Forward:The UK Respiratory Research Strategy Committee

Prioritisation Organisation

Coming

TogetherRebuild

Capacity

Engage StrengthenTo prevent lung disease and improve patient care