Presentation at ABPI -- NIHRT R&D Conference, 360 Degrees of Health Data – Harnessing Big Data for Better Health, London, 21 November 2013

1. Stratified Medicine: International Examples
What can be learned from other countries about
clinical implementation of stratified medicine?
Professor Adrian Towse
360° of Health Data: Harnessing Big Data for Better Health
ABPI and National Institute for Health Research Conference
London • 21 November 2013

2. Agenda
•
Phases of translation – getting to clinical implementation
•
Translation into clinical practice: The INCa approach in France
•
•
US evidence: physicians do not feel equipped to translate tests
results into actionable prescribing decisions
•
•
Regional provision of subsidised testing
Use of evidence-based clinical pharmacogenetic guidelines offer a way
forward to overcome this barrier
Generating the evidence, linking it to value, getting it used:
•
Need institutional processes and a framework for value assessment of
new diagnostics
•
Need innovative approaches to evidence collection
•
Generate evidence into practice guidelines
•
Tackle the “silo budget” problems
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3. Phases of translation: trastuzumab
and HER2 testing as example
Based on the framework proposed by Khoury et al (2007)
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4. France (INCa) – An approach to
clinical implementation
•
28 regional platforms
•
Partnerships between several laboratories located in University hospitals and cancer
centres
•
Cooperation between pathologists and biologists
•
Compensation of local pathologists for sample shipment
•
Free of charge to patients and hospitals
•
Public-private partnerships for molecular testing
•
Early phase network of 16 early phase clinical trial centers (CLIP2)
Source: Buzyn (2013)
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5. France – estimates of economic
impact of molecular testing
PFS = progression free survival Source: Calvo (2011)
•
Focus on cost-offset arising from not treating nonresponder subgroups of patients identified through
testing
•
May explain willingness to fund the INCa initiative
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6. US evidence on physician barriers
to implementation
•
US Survey: 97.6% of responding physicians agreed that genetic
variations may influence drug response, but only 10.3% felt adequately
informed about pharmacogenomic testing. Physicians who feel well
informed and have had pharmacogenetic instruction as part of their
education are more often early adopters. Source: Stanek et al (2012)
•
Approaches to fill the current knowledge gap
•
Inclusion of information about genomic biomarkers in drug
labels
•
Examples of a coordinated multidisciplinary team approach with
appropriate informatics infrastructure are being researched
(e.g. the 1200 patients project – ClinicalTrials.gov no.
NCT01280825 [O’Donnell et al, 2012])
•
Clinical guidelines from professional organizations (e.g., Clinical
Pharmacogenetics Implementation Consortium)
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7. US Clinical Pharmacogenetics
Implementation Consortium (CPIC)
Originated late 2009. Members worldwide. Shared effort of
Pharmacogenomics Research Network (PGRN) and The
Pharmacogenomics Knowledge Base (PharmGKB) – originally US
projects
•
Provides guidelines that enable the translation of genetic results into
actionable prescribing decisions
•
Designed to help clinicians understand HOW available genotype results
should be used to optimize drug therapy, not WHETHER tests should be
ordered. 62 guidelines available on PharmGKB’s website, 14 available
as peer-reviewed publications, e.g.:
Drug
Gene
Publication date
Abacavir
HLA‐B
Feb 2012
Clopidogrel
CYP2C19
Jun 2011, 2013
5‐FU, Capecitabine
DPYD
Source:
http://www.pharmgkb.org/
page/cpic
Sep 2013
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8. Institutional processes for the value
assessment of new diagnostics
Source: Garau et al (2013)
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9. Proposed framework for assessing
value of co-dependent technologies
Source: Garau et al (2013)
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10. Molecular diagnostic tests: the
evidence hurdle
Marker
Main study design
Study size (patient
numbers)
Sponsor
KRAS mutations (Anti‐EGFR
monoclonal antibodies in
CRC)
Retrospective cohort
analysis of an RCT
1198
Drug developer & public
research body
(a) Oncotype DX® &
(b) MammaPrint®
(Prognostic/predictive in
BrCa)
Retrospective RCT cohorts
(a) 688, 651, 895
(b) Prognostic:
117, 295, 307, 123
Predictive: 241
Diagnostic manufacturer
RCTs
(a)
(b)
Public research bodies
Retrospective RCT cohort+
Healthy volunteers
1477, 162
Public research body
Prospective cohort study
4471 (Terminated early)
Payer
Proof‐of concept RCT
187
Diagnostic manufacturer
CYP2C19
(Clopidogrel in ACS)
11248
6600
Public research body
Source: Towse et al (2013)
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11. Innovative approaches: examples of
performance-based arrangements
•
Oncotype DX breast cancer essay in U.S.
•
•
UnitedHealthcare agreed to reimburse OncotypeDx test for 18
months; change in price based on appropriate use
CYP2C9 and VKORC1 Genetic testing in U.S.
•
Pharmacogenomic testing of CYP2C9 or VKORC1 alleles to predict
warfarin responsiveness is covered only for patients enrolled in a
prospective RCT meeting specific standards
• Gefitinib in the UK
•
Supplied at a single fixed cost of £12,200 per patient irrespective
of the duration of treatment. NHS is not charged until third month
of treatment is supplied
• Oncology risk / cost sharing in Italy
Source: Carlson (2013)
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12. Conclusions and next steps
International evidence suggests
•
Subsidising testing can promote uptake – but a flawed value assumption?
•
Evidence-based guidelines can support clinicians
•
Innovative approaches to evidence generation may be necessary
•
Both separate and combined HTA processes for assessing value are
required
May also be important to address “silo budgeting” with test budgets and drug
budgets held and managed separately
“Big Data” has a key role to play:
•
Use of data to generate evidence for clinical practice guidelines
•
Ability to monitor and feed back outcomes for patients and actual costs to
later validate (or not) assumptions made at time of launch
•
Support guideline implementation and provide feedback to clinicians
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13. Sources
Buzyn, A. (2013) How is INCa supporting the development of personalised medicine? Presentation. Worldwide innovative networking in
personalised cancer medicine. Paris. 10-12 July. Available at: http://www.winsymposium.org/wp-content/uploads/2013/07/WIN2013_AgnesBuzyn-REVISED.190713.pdf.
Calvo, F. (2011) Personalised medicine: A nationwide initiative for an equal access to cancer treatment in France. Paris: National Cancer
Institute. Available at: http://ec.europa.eu/research/health/pdf/event06/13052011/fabien-calvo_en.pdf
Carlson, J. (2013) Performance-based risk sharing arrangements. Pesentation at the Second Annual Health Economics and Personalized
Medicine Symposium.
Garau, M. et al (2013) Can and should value-based pricing be applied to molecular diagnostics? Personalized Medicine.
Khoury, M.J. et al. (2007) The continuum of translation research in genomic medicine: How can we accelerate the appropriate integration of
human genome discoveries into health care and disease prevention? Genetics in Medicine.
O'Donnell, P.H. et al (2012) The 1200 patients project: creating a new medical model system for clinical implementation of pharmacogenomics.
Clinical Pharmacology & Therapeutics.
PharmGKB website. Clinical Pharmacogenetics Implementation Consortium (CPIC) page. Available at: http://www.pharmgkb.org/page/cpic
Stanek, E.J. et al (2012). Adoption of pharmacogenomic testing by US physicians: results of a nationwide survey. Clinical Pharmacology &
Therapeutics.
Towse, A. and Garrison, L. (2013) Economic incentives for evidence generation: Promoting an efficient path to personalized medicine. Value in
Health.
Towse, A. et al (2013) Understanding the economic value of molecular diagnostic tests: Case studies and lessons learned. Journal of
Personalized Medicine.
Vijverberg, S.J.H. et al (2010) Ethical and social issues in pharmacogenomics testing. Current pharmaceutical design.
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