Download Bell BHF TRanslational med

Orchestrating a National
Translational Research
Strategy
John Bell
O.S.C.H.R.
UK Health Research Analysis
• Published May 2006
• First ever comprehensive national
analysis of health research funding
• 11 largest Government and charity
funders of health related research in
the UK
• Collected peer-reviewed research
funded 2004/2005 – £950m/9500 awards
• All types of research activity and all
areas of health and disease
O.S.C.H.R.
UK Health Research Analysis
O.S.C.H.R.
UK Health Research Analysis
O.S.C.H.R.
Drivers for Change
O.S.C.H.R.
O.S.C.H.R.
Key Findings
UK Health research system has many strengths
But:

Risk of failing to meet full economic, health and
social benefits of UK public investment;

No overarching health research strategy;

Key gaps in the translation of health research;

Funding of health research from concept to
practice could be more coherent;

Cultural, institutional and financial barriers to
translating research.
O.S.C.H.R.
O.S.C.H.R.
A Single Health Research
Strategy

A new, sustainable, strategic framework for health
research and cultural change

Continued investment in basic biomedical science

A ‘Health Research Ring-fence’

Commitment and engagement across all four UK
Administrations

New investment targeted in key strategic areas
Government Investment in
Health Research
1600
1400
Millions GBP
1200
1000
800
600
400
200
0
2000
2004
2006
2009
OSCHR Partners developing a single UK
Health Research Vision
UK Health
Research Vision
Office for Strategic Coordination of Health Research
OSCHR
Translational
Medicine Board
E-Health Records
Research Board
Human Capital
Infrastructure
Office for Strategic Coordination of Health Research
Public Health
Board
O.S.C.H.R.
UK Health Research Priorities
Survey of unmet
medical need
Evaluation of
Scientific Opportunity
Health economic
impact
England – Forecast Increase in Diabetes Prevalence by
Local Authority District, 2001-2020
The Burden of Disease and Illness in the UK: S. Green, R Miles. April 2007
Source: Yorkshire & Humber Public Health Observatory 2007
The Burden of Disease and Illness in the UK: S. Green, R Miles. April 2007
England and Wales – Age-standardised rates for three
major causes of death (per million population), 1971-2005
The Burden of Disease and Illness in the UK: S. Green, R Miles. April 2007
Source: Office for National Statistics 2007
England and Wales – Cancer Mortality Trends – Agestandardised Mortality rates per Million Population,
1991-2005
The Burden of Disease and Illness in the UK: S. Green, R Miles. April 2007
Source: Office for National Statistics 2007
Health Research Opportunities 2
•
•
•
•
•
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•
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•
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Stratification of phenotype
Regeneration and replacement
Tracking response to intervention
Measure, understand and modify environmental and
inherited influences on health
Exploitation of world leading position in hypothesisgenerating science to deliver improved health
Early detection of the opportunity for effective
intervention
Primary prevention
Behaviour modification
Understanding the burden of illness
Development of new interventions
Office for Strategic Coordination of Health Research
O.S.C.H.R.
Rebuilding Basic Science
Infrastructure
National
Institutes
MedicalBiology,
Research,
Mill Hill
MRC
Laboratory
for for
Molecular
Cambridge
Translational Pipeline
O.S.C.H.R.
Translational Medicine
• Experimental Medicine and Exploratory Development,
including imaging, biomarkers: MRC
• Methodology for large and small clinical trials: MRC
• Large trials and evaluations of therapeutics, devices,
diagnostics, and other interventions (overlapping with
public health): NIHR
• Clinical training: NIHR
Charities
The complex environment of
translational medicine
High throughput
screening
MRC
NIHR, WORD,
Scotland DA
Training
HTA
BRCs
Biomarkers
BRUs
Trial
Methodology
AHSCs
Molecular
pathology
Cohorts
Imaging
Cyclotrons
Preclinical
models
Biologics
CRFs
Stratification
Regulation
Enabling
technology
Biobank
RNAi
GMP facilities
Genetics
Technology
transfer
Stem cells
Large trials
Chemistry
Translational Medicine: Enabling
Technology
•
•
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•
•
Imaging
Biomarkers
Drug Safety
Experimental Medicine
Genotype:Phenotype
O.S.C.H.R.
Developmental Pathway funding Scheme
(MRC)
Large Scale
Evaluation
Discovery
Target identification
L.I.

L.O.
Preclinical
models
Biologics
P.o.C.
Regulatory Support
Safety and Toxicology
Manufacturing and Formulation
Phase II and III Trials
Phase I
HTS
O.S.C.H.R.
Biomedical Research Centres
(NIHR)
• 5 Centres selected in competition
• £100 million p.a. support for infrastructure
and personnel
• Increase capacity in experimental
medicine and exploratory development
O.S.C.H.R.
Well-characterised Small
Cohorts (MRC & NIHR)
• Common disease cohorts (e.g. COPD,
osteoarthritis, heart failure, stroke,
hepatitis C, HIV, Alzheimer’s disease)
• Phenotyping using imaging, physiology,
genetics and genomics
• Disease progression monitoring
• Maintained for experimental medicine and
exploratory development
Molecular Diagnostics:
The new genetics in clinical practice
Translational Genetics
Bridging the Gap
Translational Funding
Research Labs
Basic
Science
Diagnostic Labs
Proof of
Concept
Clinical
Trials
Clinical
Practice
Next Generation Sequencing
454 Life Sciences
SOLEXA / ILLUMINA
Oxford Nanopore
Sequencing Projects
PROJECTS
• Sudden Cardiac Death
• Retinal Degeneration
• Mental Retardation
• Pathogens
• HNPCC cancer
• CHD
• Type 2 diabetes
• Renal cancer
• Melanoma
POTENTIAL TLN OUTCOMES
• Improved test for 5-10 genes
• New UK /European test
• New UK /European test
• Infection surveillance in hospitals
• Improved test & novel application
• New UK /European test
• Identification common variants
• Pharmacogenetics tests
• Signal transduction pathways,
Stratified medicine
Sudden Cardiac Death
Syndromes
•Hypertrophic and dilated cardiomyopathies, long QT syndrome
•Heterogeneous single gene conditions - autosomal dominant
•Incidence 1:500-1:1000
•Condition treatable once diagnosed – lifestyle, beta blockers, defribillators
•Oxford GKP programme
•Up to 5 genes currently tested for HCM, DCM or LQT
•Potential to increase referrals (cardiologists, coroners) & expand genes tested (10)
•Technology upgrades required to support this
•Once validated can be applied to other established NHS genetic tests (eg BRCA1/2)
Retinal Degeneration
•Inherited eye conditions
•Defects in photoreceptors and retina leading to progressive visual loss
•Genes known, but currently lack of comprehensive testing
•25-30 genes known for autosomal recessive retinitis pigmentosa
•200-300 genes for ARRP, ADRP, XLRP and other relevant eye disorders
Pathogen Surveillance
Clinical applications: Novo virus, MRSA, C difficile, TB
At national level: identify new epidemic strains
At local level:
identify endemic outbreaks
Individually:
identify pathogen to inform clinical intervention
Array CGH-NHS Potential
• Develop as first line test for chromosomal anomalies
• Multi-sample formats and high density
• Cost implications and commissioning (>50% cost efficiency)
• Extend Applications
• Speech and language / autism
• Congenital heart disease
• Leukaemia
• Pre-implantation genetic diagnosis
• Cancer
• Diagnosis, prognosis, treatment selection
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Large Scale Evaluation
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Therapeutics
Diagnostics
Devices
Other interventions
O.S.C.H.R.
E-Health
• Contribute to developing Connecting for
Health for research purposes (Research
Capability Program)
• Pilot studies with databases in UK (GPRD),
Scotland and Wales
• Federate databases across UK
Benefits - Research
• Epidemiology scale follow up
of patient cohorts.
• Content rich databases
allowing integration of data
• Evaluation of efficacy and
toxicity of therapeutics in real
populations
• Rapid ascertainment for
clinical trials
• Novel cohort methodology for
evaluations of all forms of
interventions
Integration of patient data
Laboratory
data
Genomic
data
E-Health Record
Imaging
GP record
Hospital
admission
E-Health
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Effective systems of record linkage in Scotland, Wales
and parts of England (North west and Birmingham) but
international competition is growing
Research capability program is delivering tools for
research purposes that will work in most systems
CfH is unlikely to be the platform in its current form but
multiple exisiting record systems will work together
Governance of data could be limiting factor
We have lost the international lead
Why have we lacked in Public Health
Research?

Multiple disciplines (epidemiology, infectious
disease, modelling, behavioural psychology)
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Much is outside the health system and
Department (education, transport, workplace
environment)

Multiple disease areas (cardiovascular, cancer,
infectious disease, mental health, diabetes)
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Inconsistent and sparse funding
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No career track for professionals
Public Health
Chronic Disease
Infectious
Disease
Discovery
Infectious
Infectious
Disease
DISEASE
Discovery
Surveillance
Evaluation
Evaluation
Going Global with Public Health
Can we do better in Public Health?
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Multi-agency/multi-departmental funding
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Leadership in a few major areas (addictions and
mental health, infections, obesity, ageing)

Obtain national experiments from others
(transport, education)

Work with industry
The Economy….
Maintaining a Competitive Commercial
Health Sciences Sector
• Pharma pipelines are poor and late stage failures
are frequent
• Efficacy is low in unstratified populations
• Marketing exceeds innovation
• Clinical Trials are too slow and expensive
• Biotech business model is broken. Gestation is too
long and Venture Capital is scarce
• Not enough partnerships
Patient Recruitment HPS-Thrive
7000
6000
• Too slow
• One size fits all
• Too many sites
5000
4000
Costs:
3000
2000
US
1.0
UK
0.6
China
0.3
1000
0
Jan-07
Feb-07
Mar-07
UK
Apr-07
May-07
Scandanavia
Jun-07
China
Jul-07
Aug-07
Stratification Imperatives
Rheumatoid Arthritis (Mkt $16 billion)
Biologics
Target
Infliximab
TNF
30-40% non response
Remicade
TNF
30-40% non response
Humira
TNF
30-40% non response
Kineret
IL-1
Limited efficacy
Rituxan
CD20
Orencia
CTLA-4
Actemra
IL6-R
Limited efficacy
10% super responders
Current development path
PV & RM
I
II
IIIa
Review
HTA
Access
IIIb
FIM
PoC
Ph III entry
Key characteristics of current model
• Linear processes
• Expensive-increasing data demands
• Segmented input & decision making
• Delayed access
IV
Submission
P&R
Launch
External activities
Sponsor activities
www.abpi.org.uk
Potential flexible blueprint
Safety and PV
Explore : R & D
Review &
design
Confirmatory trials
Confirm
broad approval
Access (& revenue)
Effectiveness/ comparative studies
Key characteristics of new model:
Potential for flexibility, based on patient need
•Multi-stakeholder input, and partnership, at an
earlier stage, esp at ‘review and design stage’
above
•More parallel processes
•More measured , less binary, assessment of
risk/benefit , potentially managed on a rolling
basis
•Early (conditional) access, when justified
•Supports incr. productivity and decr. costs
Timing of ‘blocks’ is movable,
dependant on need
Company activity
Regulator/HTA activity
Both
www.abpi.org.uk
Contribution of changes to blueprint
Safety and PV
Explore : R & D
Review &
design
Confirmatory trials
Confirm
Broad approval
Access (& revenue)
Collaboration of Stakeholders,
for example:
-enabling technology
(eg biomarkers)
-cooperation on confirmatory trials
between companies
- partnering with healthcare provider
Reduction in CT costs &
time
-challenge accumulation of
new demands
-move away from one size
fits all
-simplify/ rationalise GCP
-increased targeted
medicines
Joint design , with
innovator +regulators
+regional HTA
Effectiveness and potentially comparative studies
Better b enefit/risk
assessments - to include
patient views, and be more
internationally consistent
More flexible options for design and
analysis in confirmatory trials
- eg adaptive study design and
Bayesian methods
Early access schemes , on
condition of subsequent data
collection
Flexible pricing and
reimbursement , to a)
support multiple
indications and b)
reflect evolving
evidence base
O.S.C.H.R.
Benefits for Industry: Translational Medicine
• Creating new insights into pathways relevant to disease, providing
new targets for industry for therapeutic intervention.
• Validating targets and pathways using both small molecules and
antibodies
• Development of new and preclinical models that more appropriately
mimic disease pathogenesis
• Managing programmes that are surplus to requirements but
informative to industry through exploratory development
• Development of new diagnostics, therapeutics or devices up to and
including exploratory development that could be further exploited
by industry
• Development of better tools for the evaluation of preclinical and
clinical safety
• Exploratory development programmes
• Content-rich large-scale trials
• Methodology innovation for trials
OSCHR Future Challenges and
Opportunites
• Effective communication of the role of
OSCHR and the entire UK funding
landscape
• Commercial Interactions
• Public Health Research
• E-Health Records Research
• Capacity Building
• The Economy!
Office for Strategic Coordination of Health Research