Gepersonaliseerde gezondheidszorgVan utopie tot realiteit
Personalised HealthcareHype or reality?
Rob Geraerdts
Personalised Healthcare (PHC)Is it more than a media reality – hype – or will it truly develop ?
Personalised medicine may be our future approach
Targeted drugs: The race is on
Targeted cancer drugs gain backers
Personalised drugs draw biotech dollars
Personalised approach to cancer
Personalised medicine: New approach to staying well
‘Targeted‘ drugs prove powerful against forms of cancer
FDA acts to foster ‘personalised drugs`
The Challenge of Personalised Healthcare
What the public came to expect of PHC are truly individualised therapies – something science and industry may not be able to deliver for some time
Source: JAMA. 2006;296:1453-1454.
Same symptomsSame findingsSame disease
Same Drug...
...different effects
Variability of diseaseDrug metabolismDrug-drug interactionsNon-compliance
Why a new approach to staying well is required ? What's the challenge and promise of Personalised Healthcare?
Development towards A More Personalised Healthcare
Using clinical differentiators to achieve optimal pharmaceutical efficacy and safety for the purpose of creating sustainable clinical benefits
Still today, almost all patients are treated in a few similar ways
Increasingly, treatment will be tailored to patient groups defined by their genetic disease pattern
Therapeutic stratification
Personalised HealthcareNot a totally new concept but an evolution
Today
Diagnosis and treatment expanded with rapidly growing insights into molecular processes and variations in our genes
For more than 10, 000 years
Diagnosis and treatment based on what could be seen, smelled, tasted, palpated or intuited
The last 100 years
Diagnosis and treatment expanded with knowledge about biochemistry and cellular processes
Challenges for the Healthcare system
Technological development and evolution in Diagnostics
Potential future role for the General Practioner
Costcontrol
Quality
of Life
Best medical
practice
Health Economic Value of Medical DevicesThe outside world is changing
Cost pressure
Medical innovation
Aging population Borderless world
IT revolution
Empowered people withincreased health consciousnessand demands to the system
Involvement of all players in the creation of health networks that form strong health care brands.
Payers controlling providers and redistributing costs to people Providers forced by people and payers to change the way they perform medical practice
Payers
Peo
ple
Provid
ers
Challenges for the Healthcare system
Technological development and evolution in Diagnostics
Potential future role for the General Practioner
Personalised Healthcare: hype or reality?Evolution in literature of definitions for In Vitro Diagnostics
In Vitro Diagnostics are Medical Devices which enable analysis of bodily fluids and tissues for determining disease conditions
In Vitro Diagnostics are enabling technologies to structure tomorrow's health care processes based on medical evidence
In Vitro diagnostics are a valuable tool for preventing illness, for early diagnosis and for
optimising therapy through patient monitoring and/or stratification
Personalised Healthcare: hype or reality?The need for health information as basis for medical decisions
Today:
Tomorrow:
• Tests with blood, liquid and tissue
• Health information
- „the right information in the right place at the right time“
- individual patient treatment (i.e. test result, risk profile, treatment recommendation)
- transition of today's IVD products into specific biomarkers
Result Standardisation
Novel Content
ImprovedInformation
Reagents
Systems
Laboratroy Organisation
Total IVD infrastructure( Lab Network / IT )
Re-engineeringMedical Processes with IVD
Pro
du
cti
vit
y
investments
- Reagent harmonization- Robustness improvement- Result standardisation
- System portfolio- Professional System Service
- IT solutions-Hospital solution
- DRG’s- Indication management- Personalised Health Care
- Increase laboratory productivity
Personalised Healthcare: hype or reality? How did technological development in IVD testing contribute to creating value in the laboratory ?
Therapymonitoring
toring
Therapydecision
DiagnosisPreventivemeasures
Tools
CO
NT
EN
T
Predispositionscreening
Targetedmonitoring
Personalised Healthcare: hype or reality?Populating the laboratory health value chain with tools and content to create personalised healthcare
TO
OLS
TO
OLS
InstrumentsInstrumentsand Reagentsand Reagents
DecisionAlgorithmsRisk Stratification
Algorithms Databases
Data Management Systems
DecisionAlgorithms
InstrumentsInstrumentsand Reagentsand Reagents
InstrumentsInstrumentsand Reagentsand Reagents
PortableSensor Platform
Risk profile analysis
Risk alertsDecision
Algorithms
Personalised Health Information
Current OfferingCurrent Offering
Supporting and Integrative Services
+
Personalised Healthcare: hype or reality?More fundamental knowledge of the "system biology" increases our understanding for underlying causes for diseases
DNA (gene)
mRNA (transcript
)
protein
genome transcriptome
proteome
genomics transcriptomics proteomics
Bioinformatics
Personalised Healthcare: hype or reality?To unveil the secrets of the "system biology" novel technologies are to be developed – used for diagnostic purposes
Ascher Shmulewitz et al, Nature Biotechnology – March 2006
Personalised Healthcare: hype or reality?To understand "system biology", convergence of novel technologies will provide the full potential to understanding disease patterns
Personalised Healthcare: hype or reality?"Systems biology" transparency in disease processes
Confirmatory Phase
Dx launch/ Post-launch assessment
Biomarker development
Creating PHC from an industrial perspectiveDiagnostics input is key - from discovery to market of pharmaceuticals
Target Selectio
n
Exploratory PhaseDiscove
ryPhase
Research
Companion diagnosticfeasibility & attractiveness
Tailored prescribing & monitoring
Target identification
Patient selection
Research assay Technically validated assayClinically validated IVD assay
Develop CommercialiseLead
Generation/
Optimisation
Phase 0 Phase I Phase II Phase III FilingMarket
Phase IV
PoC
Personalised healthcare: hype or reality?Understanding of disease "genetic" pattern will drive usage of new technologies in Diagnostics
Examples
* under development
Parameters (eg, Genes, Mutations)
1 10 100 1000
Genotyping Examples:
Expression Examples:
PCR Linear Arrays Microarrays
Point Mutations; Simple Gene Analysis
Complex Gene Analysis Resequencing
Single parameter “Expression”:
Complex Expression:
•CYP450 2C9
•Factor II/V
•CF Linear Array (US)
•AmpliChip CYP450Test (CE-IVD)
•AmpliChip p53*
•Taqman HIV Monitor•Taqman HCV Monitor
•Leukemia*•Breast Cancer•Cardiovascular Disease
Personalised Healthcare in the market todayCurrent examples in oncology
• Implementing biomarker strategy for all pipeline drugs
• Distribution of K-RAS and EGFR Cancer Mutation Tests– Tests identify genetic mutations that can affect patient response to certain cancer drugs
• Identifying patients who have an improved response to launched drugs
– e.g. Tarceva in 1st line maintenance NSCLC / SATURN trial
• Assessing opportunities for companion diagnostics– Pertuzumab/HER dimerization inhibitors: Expression of HER
2– MDM2: Active only in p53 wild-type patients– PLX4032: Presence of BRAF V600E gene mutation
• Detecting Hepatitis C virus subtype and monitoring viral load/ Pegasys response
– Determine length of treatment by strain of virus
– Monitor viral load to determine likelihood of response and aid in compliance
Personalised Healthcare today in the marketCurrent examples in virology
• Determining genotype 16 and 18 of Human Papilloma Virus
– Reduce risk of cervical cancer by closer monitoring
– Support Roche Pharma studies on therapeutic vaccines
Personalised Healthcare in the market todayIAT-Beispielliste
1. Invirase; 2. Crixivan
Oncology
TamoxifenTamoxifenTamoxifenTamoxifenChemotherapyArimidexHerceptinXeloda 6-MercaptopurineGleevec (CML)Gleevec (GIST)DasatinibIressaTarcevaIrinotecanErbituxRetinoic acidMabTheraTykerb
ER/PR StatusBRCA1BRCA2CYP2D6Oncotype DxER/PR statusHER2 assayEnzyme activityTPMTBCR-ABLC-KitBCR-ABLEGFR StatusEGFR/HER1UGT1A1 EGFR statusPML/RAR geneCD20EGFR status
CNSPhenytoinVenlafaxineModafinilResperidoneAtomoxetineThioridazineLevodopaTasmarAripiprazole
CYP2C9CYP2D6CYP2D6CYP2D6CYP2D6CYP2D6COMTCOMTCYP2D6
RespiratoryProlastinTheophylline
PiZZ, PiZ PiCYP2D6
Virology/Infectious Diseases
HCV GenotypingViral LoadViral LoadViral GenotypingViral GenotypingNAT Influenza A/B testHCV EVLHCV EVL
Pegasys/CopegusHIV Prot. Inh. (1st to mkt)1
HIV Prot. Inh. (2nd to mkt)2
HIV Prot. Inh. (1st to mkt)1
HIV Prot. Inh. (2nd to mkt)2
IsoniazidTamifluPegintronARoferon
CellceptAzathioprineNeoral (Cyclosporine)Prograf (Tacrolimus)Rapamune (Sirolimus)Mabthera
IATPMTIA’s for CsAIAIARA profiles
Autoimmune and Transplant
OmeprazoleProton pump inh. and Antibiotics
CYP2C19H Pylori
GIT
Cardiovascular
BiDiLHydralazineProcainamideGPIIb/IIIaStreptokinase
EthnicityNATNATTroponinTroponin
Succinylcholine Pseudochol-Inesterase levels
Anaesthesia
Metabolic and Vascular DiseaseFosamaxSomatropinInsulinSimvastatin
P1NPChr 15 HbA1cLipid profiles
WarfarinWarfarinHeparinEPO
CYP2C9VKORC1APTTCBC
Haematology
Challenges for the Healthcare system
Technological development and evolution in Diagnostics
Potential future role for the General Practioner
Personalised Healthcare: hype or realityThe proven promise of personalised health care is to further improve effectiveness of treatmentEffectiveness of treatment can be improved…
• 20-75% of patients do not receive effective treatment1
• >100.000 deaths/yr from adverse drug reactions in US2
…by tailoring treatments to selected patient groups defined by biomarkers1 Spears et al., Trends Mol Med, 2001
2 Lazarou et al., JAMA, 1998
Genom
ic
s
Prot
eom
i
cs
Patient StatusLik
elih
ood
of
treatm
en
t su
ccess
for
the in
div
idu
al p
ati
en
t
Today
Future
Cost
Effec
tiven
ess
lower
higher
asymptomatic symptomatic
higher
lower
Today diagnostics often addresses end stages of diseases. Here (e.g. late cancer phase) treatment is expensive and may not cure the patient.
New markers for the disease onset change this picture dramatically. Health care cost go down and treatment success improves.
This is were marker identification programs like proteomics and genomics come in.
New testing algorithms – A new paradigm shift in "how to treat" patientsEarlier, better diagnosis allowing for better and cost effective treatment – Early patient stratification
Risk Assessme
nt
Personalised healthcare: hype or reality Role of the treating physician across the healthcare value chain
Predisposition for
developing disease
Therapy adaptation
Patient Stratification / Therapy Selection
Screening/ Diagnosis Prognostic Predictive
Monitoring
Early detection
Predict probable disease course
Predict likely
response to a drug
Monitor efficacy/
recurrence
Healthy Asymptomatic disease
Chronic disease CuredSymptomatic disease
Personalised Healthcare: hype or reality? Benefits for patients and healthcare system
Physicians & Providers
Maximum benefit,minimum toxicity
Regulators & Policy Makers
Increased efficacy & safetyReduced healthcare costs
Payers & Reimbursers
Efficient use of healthcarebudgets
Patients
Best treatment