WoHIT, Barcelona March 2010

Early Adoption of VPH

TechnologyTowards Realising more Personalised,

Predictive and Integrative Medicine

Marco Viceconti

VPH Network of Excellence

Outreach program

WoHIT, Barcelona March 2010

Synopsis

• What is the VPH?

• Examples of early adoption

© 2007 STEP Consortium

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

Paradigmatic Shift in

Biomedical Research

Complement

Reductionism

With

Integrationism

© 2007 STEP Consortium

Integration across ….

Across organ systems

© 2007 STEP Consortium

Environment

Population

Integration across ….

Across

dimensional scales

Across

Temporal scalesOrganism

Organ System

Organ

Tissue

Cell

Molecule

Atom

C C

H H

H H

© 2007 STEP Consortium

Integration across ….

Across DisciplinesMedicine

BioEngineering

Biology

© 2007 STEP Consortium

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

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

VPH Research Road Map

http://www.europhysiome.org/roadmap

The VPH constellation

Networking

NoE

Osteoporosis

IP

Alzheimer's/ BM &

diagnosis STREP

Heart /CV

disease STREP

Cancer

STREP

Liver surgery

STREP

Heart/ LVD surgery

STREP

Oral cancer/ BM

D&T STREP

CV/ Atheroschlerosis

IP

Breast cancer/

diagnosis STREP

Vascular/ AVF &

haemodialysis STREP

Liver cancer/RFA

therapy STREP

Security and

Privacy in VPH CA

Grid access CA

Heart /CV

disease STREP

Industry

ClinicsInternational

Related Research

WBM - neurovascular

12IMAG Futures meeting

Bethesda, December 2009http://www.aneurist.org/

Clinical Parameters: -weight- opportunistic infections and tumors-survival

Molecular DynamicsBinding Affinity

ProteinStructure& Binding Affinity

VIROLABDRUG RANKING

DECISION SUPPORT

Text Mining Drugranking 1st order logic

Complex Networks Epidemics

Agent-Based Entry

Simulation

CXCR4

CCR5

CD4+ Target Cell

HIV

Phenotype

CA Based Immune Response

Protease and RTmutations

Peter Sloot: Computational Science, University of Amsterdam, The Netherlands.

http://www.virolab.org/

Philips Research Europe - Aachen

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:

- Cardiac Resynchronization Therapy

- Radiofrequency Ablation

- Heart Failure

- Coronary Artery Diseases

- Valves and Aorta

Project coordination: Philips Research

Scientific coordination: The University of Oxford

17 partners (6 companies, 6 universities, 5 clinics)

Budget ~19M€ (~14M€ EU funding)

USFD, DKFZ

INRIA

UOXF

Philips Research

http://www.euheart.eu/

Kostas Marias – ICS FORTH

Modellingat the molecularlevel

Simulating tissuebiomechanics

Tumour imageanalysisand visualization

Modelling cancerat the cellularlevel N

SG

1

G

2

M G

0

A

time

Multi-level Modelling In Silico Optimal therapy planning

Simulating Therapy A

Simulating Therapy B

Multi-level data Multi-level modelling

Clinically Oriented Translational Cancer Multilevel Modelling

• ContraCancrum will integrate

molecular, cellular, tissue and

higher level modelling concepts

into a single technological entity

that will simulate therapy

outcome based on the individual

patient information.

• This could serve as a powerful

weapon to better understand and

fight cancer. The most important

IT challenge is to integrate

across different scales into an

integrated cancer

therapy/growth simulator.

• The primary clinical challenge is

to gather histopathology,

microarrays and multi-modal

imaging exams (e.g. DT-MRI,

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/

WoHIT, Barcelona March 2010

PreDiCT: Computational

Prediction of Drug Cardiac Toxicity

Drug/Ion Channel model

17.4 17.7 18 18.3 18.6-100

-80

-60

-40

-20

0

20

40

60

V (

mV

)

time (s)

Cellular model

Torsades de Pointes – ElectrocardiogramWhole-ventricular model

Action Potential

Aim: to identify new biomarkers of drug-induced cardiotoxicity using

computational modelling and simulation techniques

Partners

AstraZeneca

Aureus

CRS4 in Sardinia

Fujitsu

GlaxoSmithKline

Novartis

Pfizer

Roche

University of Oxford

University of Szeged

Universidad Politecnica

de Valencia

http://www.vph-predict.eu

Copyright © 2008-2012 VPHOP Consortium - All right reserved 17

Organ-level Model

Cell-levelModel

Constituent-levelModel

Tissue-levelModel

Body-level Model

Boundary Conditions

Bone

Rem

odellin

g

FailureCriterion

ConstitutiveEquation

VPHOP Technology to fight osteoporosisOsteoporotic Virtual Physiological Human

http://www.vphop.eu/

Models in clinical use

18IMAG Futures meeting

Bethesda, December 2009

1 month 7 months 13 months 29 months 36 months 44 months Pre-op

Copyright © 2008-2012 VPHOP Consortium - All right reserved 19

CBA of model-based diagnosis

• Preliminary CBA according to VHOP Technology assessment protocol largely favourable (21% cost reduction)

• Improving effectiveness of 1.3% is enough to break even

Cost of exam 100 patients

(€)

Cost 1 hip fracture

(€)

Effectiveness (% fractures prevented)

Total cost

x 100 patients

(€)

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

WoHIT, Barcelona March 2010

Thank You!!• Useful URLs:

– http://www.biomedtown.org

– http://www.vph-noe.eu

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