This document provides an agenda and overview from a conference on generating evidence and assessing the value of stratified medicines and diagnostic tests. The summary includes: 1. The conference discussed elements of value for diagnostic tests, including reducing adverse drug effects and uncertainty about treatment value. 2. Institutional arrangements for assessing diagnostic value were examined, including joint drug-diagnostic assessments and diagnostic-specific processes. 3. Generating evidence to link diagnostics to patient value and incentivizing uptake were areas of focus, with examples provided.

1. Setting the Scene:
A Health Economics Perspective
Adrian Towse
Generating a NICE Assessment for Stratified Medicines
Event Sponsored by BIVDA1 and ABPI2
London • 20 January 2014
1British
In Vitro Diagnostics Association
2Association
of the British Pharmaceutical Industry

2. Agenda
•
What are the elements of value in a diagnostic test?
•
•
What institutional arrangements are needed for the
assessment of value?
•
•
A summary of nine case studies
Options for appraising stratified medicines and diagnostics
Generating the evidence, linking it to value, getting the
technologies used
•
Where does the evidence come from?
•
The need to align incentives
•
Flexible pricing and coverage with evidence development
•
Challenge of diagnostic uptake
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3. Framework to assess value of diagnostic test
technologies in the context of treatment
1. Reducing
drug
adverse
effects
5.Reducing
uncertainty
about value
Value
4. Enabling Tx
effective in a
small fraction
to be made
available
2. Reducing
time delays
in selecting
optimal Tx
3.Increasing
adherence
or
willingness
to start Tx
Source: Garau et al. (2013)
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4. Pathways for value of molecular diagnostics and key
examples
Source: Garau et al. (2013)
4

5. Agenda
•
What are the elements of value in a diagnostic test?
•
•
What institutional arrangements are needed for the
assessment of value?
•
•
A summary of nine case studies
Options for appraising stratified medicines and diagnostics
Generating the evidence, linking it to value, getting the
technologies used
•
Where does the evidence come from?
•
The need to align incentives
•
Flexible pricing and coverage with evidence development
5

6. Institutional processes for the value
assessment of new diagnostics
Dx-Tx pair launched
simultaneously
New Dx
Dx not linked to a Tx
Single Dx launched
separately
Dx assessed via
Diagnostic-dedicated
process
Multiple Dx with same
clinical use
Dx linked to a Tx
(companion Dx,
personalised medicine)
Dx-Tx joint assessment
via Drug process
Dx assessed via
Diagnostic-dedicated
process
Dx assessed via
Diagnostic-dedicated
process
Source: Garau et al. (2013)
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7. Agenda
•
What are the elements of value in a diagnostic test?
•
•
What institutional arrangements are needed for the
assessment of value?
•
•
A summary of nine case studies
Options for appraising stratified medicines and diagnostics
Generating the evidence, linking it to value, getting
the technologies used
•
Where does the evidence come from?
•
The need to align incentives
•
Flexible pricing and coverage with evidence development
•
Challenge of diagnostic uptake
7

8. 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: Adapted from Towse et al. (2013)
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9. Aligning incentives
• Greater willingness on the part of payers to accept prices that reflect
value
• Will involve a need for price flexibility for drugs as evidence of their
value for different groups of patients emerges over time
• Consideration of some form of intellectual property protection (e.g.
data exclusivity) for diagnostics to cover evidence of clinical utility
• Realistic expectations about standards for evidence. This involves the
use of CED and real-world evidence collection for both drugs and
diagnostics
• Public investment to complement the efforts of payers and
manufacturers, recognising the limitations on the incentives for both
to invest in evidence collection on all the questions that matter.
Source: Towse and Garrison (2013)
9

10. Need for flexible pricing and more
outcomes-based PAS
Garrison et al (2013)
Academy of Medical Sciences (2013)
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11. 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
•
Compensate 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)
11

12. France – estimates of economic
impact of molecular testing
PFS = progression free survival
•
Focus on cost-offset arising from not treating nonresponder patient subgroups identified through testing.
•
May explain willingness to fund the INCa initiative
Source: Calvo (2011)
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13. Sources
Academy of Medical Sciences. (2013) Realising the potential of stratified medicines. London: Academy of
Medical Sciences.
Buzyn, A. (2013) How INCa is supporting the development of personalized medicine. Presentation at the
2013 WIN symposium. Paris. 10-11 July 2013. Available at: http://www.winsymposium.org/wpcontent/uploads/2013/07/WIN2013_Agnes-Buzyn-REVISED.190713.pdf
Calvo, F. (2011) Personalized medicine: A nationwide initiative for an equal access to cancer treatment
in France. 20 May. Available at: http://ec.europa.eu/research/health/pdf/event06/13052011/fabiencalvo_en.pdf
Garau, M., Towse, A., Garrison, L., Housman, L. and Ossa, D. (2013) Can and should value-based
pricing be applied to molecular diagnostics? Personalized Medicine. 10(1), 61-72.
Garrison, L.P., Towse, A.T., Briggs, A., de Pouvourville, G., Grueger, J., Mohr, P.E., Severens, J.L.,
Siviero, P. and Sleeper, M. (2013) Performance-based risk-sharing--Good practices for design,
implementation, and evaluation: Report of the ISPOR Good Practices for Performance-based Risksharing Task Force. Value in Health. 16(5), 703-719.
Towse, A., Ossa, D., Veenstra, D., Carlson, J. and Garrison, L. (2013) Understanding the economic value
of molecular diagnostic tests: Case studies and lessons learned. Journal of Personalized Medicine. 3(4),
288-305. doi: 10.339/jpm3040288.
Towse, A. and Garrison, L.P. (2013) Economic incentives for evidence generation: promoting an efficient
path to personalized medicine. Value in Health. 16(6Suppl), S39-S43. doi: 10.1016/j.jval.2013.06.003.
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