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Future of Personalised Medicine and its role in making healthcare sustainable
Exeter College symposium Professor Richard Barker
Director, CASMI 1
Key points
Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation
gap The four ‘gaps in translation’ and how to
bridge them Personalised medicine as a major contributor
to sustainable healthcare
2
Key points
Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation
gap The four ‘gaps in translation’ and how to
bridge them Personalised medicine as a major contributor
to sustainable healthcare
3
5.0
7.0
9.0
11.0
13.0
15.0
17.0
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
USA
Belgium
Denmark
France
Germany
Greece
Ireland
Italy
Netherlands
Norway
Portugal
Spain
Sweden
Switzerland
UK
Japan
>2% increase
1.5% increase
Health expenditure as a percentage of GDP
Source: OECD
2010 2010 2030 2030
Healthcare costs
Supply forces Demand forces
Aging populations
Higher expectations
Lifestyle-driven disease
New infectious diseases
Several powerful demand drivers
Not this …. But this …. And even this ….
Great expectations …
Self-inflicted disease … obesity …
Deaths, Men 45-64
Other Europe Scotland
England & Wales
Alcoholism ….
Unpredictable pandemics add predictable costs
Historical growth rate
Aging population
Greater expect-ations
Negative lifestyle changes
New technologies
2.5 – 5.0%
1%
1-2%
1%
1-2% 6 – 9%
Demand and supply drivers combine to create unsustainable real terms growth
Socialised systems: unacceptable tax burden
Private insurance: Unaffordable premiums
Both: reduced coverage and/or greater co-payments
Key points
Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation
gap The four ‘gaps in translation’ and how to
bridge them Personalised medicine as a major contributor
to sustainable healthcare
12
2010 2010 2030 2030
Healthcare costs
Supply forces Demand forces
Biotherapeutics
Gene and cell therapies
Molecular diagnostics
Imaging
Implantable devices
Major information projects
Supply of new technologies also adds to healthcare costs
Key points
Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation
gap The four ‘gaps in translation’ and how to
bridge them Personalised medicine as a major contributor
to sustainable healthcare
14
Disruptive technologies and ideas
Tools & technologies Next generation sequencing Biomarkers for stratified
medicine In vitro toxicology Pathway and organ e-
simulation Electronic clinical trial
monitoring EMRs and real world data
analysis (‘Big Data’) Mobile health apps
Ideas Open innovation Crowd-sourcing solutions Patient group initiatives &
leadership Bayesian analysis Adaptive licensing Flexible regulatory routes Patient need/concern
profiling Patient-reported outcomes
15
Research
Clinical Development
Real World Application
Genetic links to disease -
Genetic links to disease -
Diseases and Traits with Published GWA Studies • Macular Degeneration • Exfoliation Glaucoma • Lung Cancer • Prostate Cancer • Breast Cancer • Colorectal Cancer • Bladder Cancer • Neuroblastoma • Melanoma • TP53 Cancer Predispos’n • Chr. Lymph. Leukemia • Inflamm. Bowel Disease • Celiac Disease • Gallstones • Irritable Bowel Syndrome • QT Prolongation • Coronary Disease • Coronary Spasm • Atrial Fibrillation/Flutter • Stroke • Subarachnoid Hemorrhage • Intracranial Aneurysm • Hypertension • Hypt. Diuretic Response • Peripheral Artery Disease
• Syst. Lupus Erythematosus • Sarcoidosis • Pulmonary Fibrosis • Psoriasis • HIV Viral Setpoint • Childhood Asthma • Type 1 Diabetes • Type 2 Diabetes • Diabetic Nephropathy • End-St. Renal Disease • Obesity, BMI, Waist, IR • Height • Osteoporosis • Osteoarthritis • Male Pattern Baldness • F-Cell Distribution • Fetal Hgb Levels • C-Reactive Protein • ICAM-1 • Total IgE Levels • Uric Acid Levels, Gout • Protein Levels • Vitamin B12 Levels • Recombination Rate • Pigmentation
• Lipids and Lipoproteins • Warfarin Dosing • Ximelegatran Adv. Resp. • Parkinson Disease • Amyotrophic Lat. Sclerosis • Multiple Sclerosis • MS Interferon-β Response • Prog. Supranuclear Palsy • Alzheimer’s Disease in ε4+ • Cognitive Ability • Memory • Hearing • Restless Legs Syndrome • Nicotine Dependence • Methamphetamine Depend. • Neuroticism • Schizophrenia • Sz. Iloperidone Response • Bipolar Disorder • Family Chaos • Narcolepsy • Attention Deficit Hyperactivity • Personality Traits • Rheumatoid Arthritis • RA Anti-TNF Response
Diabetes
HLA Type I Monogenic diabetes (rare variants)
MODY
GCK
HNF1A HNF4A HNF1B IPF1 NeuroD1
INS CEL MODY X
Type II (Common variants)
Neonatal
6q ZAC KCNJ11 ABCC8 INS GCK
HLA
Predicting personal risk …
Disease
Personal disease prevention
Seven markers in blood
And full sequencing is dramatically falling in cost and time…
Source: Forbes
Epigenetics imprints our health history on our genes …. And our childrens’ genes
2025 drug targets
Gene – disease associations Protein structures determined
Advanced genomics and proteomics are yielding many drug targets
The Innovation Gap
time
progress Bioscience – understanding human biology and disease = potential patient benefit
Actual patient benefit
The Innovation Gap
Pharmaceutical R&D Productivity
The danger of doing nothing
progress Bioscience – understanding human biology and disease = potential patient benefit
Actual patient benefit
time
- First ever industry reduction in R&D spend - $4bn drop in overall US spending in 2011
Key points
Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation
gap The four ‘gaps in translation’ and how to
bridge them Personalised medicine as a major contributor
to sustainable healthcare
28
• Basic bioscience
Translation to clinical candidates
• Innovations in clinical trial
Regulatory & reimbursement
approval • Approved products
Uptake by health systems
• Innovations used by patients
Patient Benefit
Addressing the the four “gaps in translation”
Translating research into candidate products: New ‘open innovation’ models; IP law; governance; business economics; public policy
Improving productivity of clinical development: Adaptive licensing approaches: statistics; ethics; trial design; regulatory science; health economics
Ensuring effective diffusion and adherence: Behavioural health; psychology; sociology
Feeding back from clinical outcomes to R&D: Big Data analysis, statistics, epidem-iology
Gap 2
Gap 1 Gap 3
Gap 4
Current development path
I II IIIa Review HTA
IIIb IV
PoC Ph III entry Launch
Key characteristics of current model • Inflexible processes and methods • Expensive, increasing data demands • Lack of early alignment between key parties: • Segmented input & decision making • Access Needs- not designed in • Patient perspective - not fully addressed
FIM P&R
Access
PV & RM
External activities
Sponsor activities
Submission NDA
Potential new flexible blueprint
Exploratory R & D Review & design Confirmatory trials
Effectiveness/comparative studies
Submit & Confirm approval
Initial Access
Key Features:
-Basic division between exploratory and confirmatory trials rather than Phases I-IV
-Collaborative design step before the most expensive confirmatory trials are commissioned
-Ability/need to customise the model for different benefit/risk/uncertainty profiles
-Early, controlled patient access if justified by interim findings of confirmatory trials
-Subject to requirements for pharmacovigilance and pharmacoeconomic analysis before full ‘green light’ for wide access and longer term reimbursement policy
Key points
Why healthcare is unsustainable Medical innovation: problem or solution? New biomedical science and the innovation
gap The four ‘gaps in translation’ and how to
bridge them Personalised medicine as a major contributor
to sustainable healthcare
32
33
Personalised treatment for cystic fibrosis
Disease segmentation has great benefit
Lilly Jaffe
Cameron Lundfelt
35
= Centre for the Advancement of Sustainable Medical Innovation
=
www.casmi.org.uk