Early Adoption of VPH Technology – Towards Realising more Personalised, Predictive and Integrative Medicine. Viceconti M. eHealth week 2010 (Barcelona: CCIB Convention Centre; 2010)

1. Early Adoption of VPH
Technology
Towards Realising more Personalised,
Predictive and Integrative Medicine
Marco Viceconti
VPH Network of Excellence
Outreach program
WoHIT, Barcelona March 2010

2. Synopsis
• What is the VPH?
• Examples of early adoption
WoHIT, Barcelona March 2010

3. The human Puzzle
• The human body is currently investigated as
if it is a jigsaw puzzle made of a trillion pieces
• We are trying to understand the whole picture
by looking at a single piece, or at a few
closely interconnected pieces
• We do need a frame, within which we can
finally start to place the pieces all together,
and the glue that connect them
• The frame is not the whole picture, but is the
only way we might hope to see it one day
© 2007 STEP Consortium

4. Paradigmatic Shift in
Biomedical Research
Complement
Reductionism
With
Integrationism
© 2007 STEP Consortium

5. Integration across ….
Across organ systems
© 2007 STEP Consortium

6. Integration across ….
Environment
Population Across
Organism Temporal scales
Organ System
Organ
Tissue
Cell
Across Molecule
dimensional scales Atom
H H
C C
H H
© 2007 STEP Consortium

7. Integration across ….
Medicine
Across Disciplines
BioEngineering
Biology
© 2007 STEP Consortium

8. Integrative Research
• The Integrative Research approach
requires a radical transformation on the
way biomedical research is conducted
• It is necessary to create a framework
made of technology and methods
• We call this framework
Virtual Physiological Human
© 2007 STEP Consortium

9. Virtual Physiological Human
• The Virtual Physiological Human is a
methodological and technological framework
that once established will enable the
investigation of the human body as a single
complex system
• This framework should be:
– Descriptive
– Integrative
– Predictive
© 2007 STEP Consortium

10. VPH Research Road Map
http://www.europhysiome.org/roadmap
© 2007 STEP Consortium

11. The VPH constellation
Industry Related Research
Grid access CA
CV/ Atheroschlerosis Liver surgery
IP STREP
Breast cancer/
Heart/ LVD surgery diagnosis STREP
STREP
Osteoporosis
Oral cancer/ BM IP
D&T STREP
Cancer
Networking STREP
Heart /CV NoE
disease STREP
Vascular/ AVF & Liver cancer/RFA
haemodialysis STREP therapy STREP
Heart /CV
disease STREP
Alzheimer's/ BM &
diagnosis STREP
International Security and Clinics
Privacy in VPH CA

12. WBM - neurovascular
http://www.aneurist.org/ IMAG Futures meeting
Bethesda, December 2009 12

13. HIV
CCR5
CXCR4
CD4+ Target Cell CA Based Immune
Complex Networks
Response
Epidemics
Agent-Based
Entry Phenotype
Simulation
VIROLAB
Protein DRUG RANKING
Structure
& Binding
DECISION SUPPORT
Affinity
Molecular Dynamics http://www.virolab.org/ Clinical Parameters:
-weight
Binding Affinity
Protease and RT - opportunistic
mutations infections
and tumors
-survival
Text Mining  Drugranking
 1st order logic
Peter Sloot: Computational Science, University of Amsterdam, The Netherlands.

14. euHeart – Integrated Cardiac Care Using
Patient-specific Cardiovascular Modeling
euHeart is about the development, personalization
and validation of computational models of the
heart to improve:
- Diagnosis,
- Treatment planning,
- Interventions and
- Design of implantable devices
5 clinical focus areas: Philips Research
- Cardiac Resynchronization Therapy
- Radiofrequency Ablation
- Heart Failure UOXF
- Coronary Artery Diseases
- Valves and Aorta
Project coordination: Philips Research
Scientific coordination: The University of Oxford
INRIA
17 partners (6 companies, 6 universities, 5 clinics)
Budget ~19M€ (~14M€ EU funding)
http://www.euheart.eu/ Philips Research Europe - Aachen
USFD, DKFZ

15. Clinically Oriented Translational
• ContraCancrum will integrate
Cancer Multilevel Modelling
molecular, cellular, tissue and
higher level modelling concepts Multi-level data Multi-level modelling
into a single technological entity
Modelling cancer Simulating Simulating
that will simulate therapy at the cellular
G
1
S G
2
M G
0
Therapy A Therapy B
outcome based on the individual level N A
patient information.
Modelling
• This could serve as a powerful at the molecular
level
weapon to better understand and
fight cancer. The most important
IT challenge is to integrate Simulating tissue
across different scales into an biomechanics
integrated cancer
therapy/growth simulator.
Tumour image
• The primary clinical challenge is analysis
to gather histopathology, and visualization time
microarrays and multi-modal
imaging exams (e.g. DT-MRI, Multi-level Modelling In Silico Optimal therapy planning
CT, etc) of the same patient.
• A significant validation on lung and brain cancer cases will demonstrate the added value of
modelling assisted cancer therapy design and will pave the way for its future clinical use.
http://www.contracancrum.eu/ Kostas Marias – ICS FORTH

16. PreDiCT: Computational
Prediction of Drug Cardiac Toxicity
Aim: to identify new biomarkers of drug-induced cardiotoxicity using
computational modelling and simulation techniques
Drug/Ion Channel model
Partners
AstraZeneca
Cellular model 60 Action Potential Aureus
40 CRS4 in Sardinia
20
0 Fujitsu
V (mV)
-20
-40
GlaxoSmithKline
-60 Novartis
-80
-100
Pfizer
17.4 17.7 18 18.3 18.6
time (s) Roche
University of Oxford
Whole-ventricular model Torsades de Pointes – Electrocardiogram University of Szeged
Universidad Politecnica
de Valencia
http://www.vph-predict.eu WoHIT, Barcelona March 2010

17. VPHOP Technology to fight osteoporosis
Osteoporotic
Virtual Physiological Human
Constitutive Boundary
Equation Conditions
Tissue-level
Model Organ-level
Model
Remodelling
Bone
Body-level
Model
Failure
Criterion
Cell-level Constituent-level
Model Model
Copyright © 2008-2012 VPHOP Consortium - All right reserved http://www.vphop.eu/ 17

18. Models in clinical use
Pre-op 1 month 7 months 13 months 29 months 36 months 44 months
IMAG Futures meeting
Bethesda, December 2009 18

19. CBA of model-based diagnosis
Cost of exam Cost 1 hip Effectiveness Total cost
100 patients fracture (% fractures x 100 patients
(€) (€) prevented) (€)
DXA € 30,000.00 € 70,000 82.5% € 1,255,000
CT + Model € 116,200.00* € 70,000 87.5%** € 991,203
Cost saving € 2,637 x patient
* Based on research tools
** Estimated from preclinical tests
• Preliminary CBA according to VHOP Technology assessment
protocol largely favourable (21% cost reduction)
• Improving effectiveness of 1.3% is enough to break even
Copyright © 2008-2012 VPHOP Consortium - All right reserved 19

20. Thank You!!
• Useful URLs:
– http://www.biomedtown.org
– http://www.vph-noe.eu
WoHIT, Barcelona March 2010
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