Gene-Expression Profiling
Microarray Testing in
Breast Cancer Treatment
Constructive Technology Assessment in
Early Stage Clinical Implementation
Willem H. van Harten, Jolien M. Bueno de Mesquita,
Marjan Hummel, Kim Karsenberg, Valesca P. Retèl
Sauter, G. et. al. N Engl J Med 2002;347:1995-1996
70-Gene Microarray testing in
Node Negative Breast Cancer
• Based on validated retrospective series
(van ’t Veer, Nature 2002, van de Vijver,
NEJM 2002)
• Confirmed by independent retrospective
validation series (Buyse, 2006)
• Dutch Health Care Insurance Board
sponsored controlled introduction study
Constructive Technology Assessment
• Based on Technology dynamics & Public
policy
• Combination of assessment and influence
• Broad evaluation
– IOM aspects of quality
– Ethical & juridical aspects
– Scenario drafting and revision
Constructive Technology Assessment
• Mutual influence of technology & environment
(especially early stage)
• Lack of impact many HTA-studies
• -Delay study draft and implementation of
results.
• - Scientific and practice developments
interfering
• -Cost-effectiveness focus
CTA 70-Gene Microarray
• 16 Dutch hospitals
• 812 Breast cancer patients enrolled
• 427 70-Gene tested
• Clinical;Logistic;Patient;Scenario’s.
• Int Journal HTA 2007 Douma et.al.
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CTA 70-Gene Microarray
Clinical Results
N = 427
70-gene signature risk profile
Low risk profile
High risk
profile
CTA 70-Gene Microarray
Clinical Results
Total
Clinical (CBO)
profile
Low risk
167
(39%)
76
(18%)
243
(57%)
Clinical (CBO)
profile
High risk
52
(12%)
132
(31%)
184
(43%)
219
(51%)
208
(49%)
427
(100%)
Total
CTA 70-Gene Microarray
Logistic Analysis
• Change of work routine for ORtissue handling and Pathologist
• Mean duration of implementation of
logistics 2,2 months (0,2 – 9,4)
after Review Board approval!
CTA 70-Gene Microarray
Patient Centeredness
• 14% (partly) contradictory information
• 10% dissatisfied with test
communication (discordant!)
• -54% informed treatment decision
• -20% not informed.
• -26% don’t know.
In 19% of patients the adjuvant systemic
treatment advice was changed based on
the 70-gene signature profile:
– in 5% the treating physician refrained from
adjuvant systemic treatment
– in 14% adjuvant systemic treatment was
added
CTA 70-Gene Microarray
Patient Centeredness
• Questionnaires (n = 49) based on taped pilot
Patient Interviews.
• -44% not clear about influence on treatment.
• -32% aware of >50% chance of metastasis in
high risk test result.
• Impact of events scale; HSCL scale ;
psychosocial well-being scale non conclusive
CTA 70-Gene Microarray
Two round scenario
• Method: Shell based approach: TINA &
“what-if”-deviations; Rogers phases.
• Round One and Two: written draft with one
round of professional comments….
• What if…. Debate on validity and alternative
tests..
• What if…. Different reactions of insurance
agencies projected.
• Round Three: formally structured meeting
with various professionals.
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CTA 70-Gene Microarray
Conclusions:
CTA 70-Gene Microarray
Future Implications
• -Prolonged implementation due to
logistic adaptations + complex
technology.
• -30% discordant results (NL majority
low >high vs USA maj. high > low??)
• -Risk communication/Informed decision
making important issues, espec. in
discordant cases.
• Input for a large EU-trial (MINDACT)
• Third Round Scenario Draft
• Cost effectiveness: Modelling (scenario
input)
CTA 70-Gene Microarray
Future Implications
CTA 70-Gene Microarray
• Controlled Introduction is feasible
• CTA is a promising assessment
method for technologies that are
unstable or introduced in an early
stage
• Defensive behavior?
• Juridical Ethical Issues (Patient Rights!)
• Psychological impact
Thanks to:
Marc van de Vijver, Sabine Linn,
Harm van Tinteren, Frits van Dam,
Kirsten Douma, Laura van ‘t Veer
Prof. dr. W.H van Harten
Orlando, June 5, 2007
Microarray Testing in
Breast Cancer Treatment
Constructive Technology Assessment in
Early Stage Clinical Implementation
Willem H. van Harten, Jolien B.M. Bueno de Mesquita,
Marjan Hummel, Kim Karsenberg, Valesca P. Retèl
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