Evidence-based marginal analysis:
Cost-effectiveness of MRI for breast cancer
screening in BRCA1/2 mutation carriers
Reka Pataky
Priorities 2010, Boston
Advancing Health Economics, Services, Policy and Ethics
Outline
• The BC Cancer Agency
• Evidence-based marginal analysis
• MRI screening study
– Background
– Model construction
– Results
• Discussion and Conclusions
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About the BC Cancer Agency
• Provides a province-wide, publicly-funded, population-based
cancer control program for British Columbia, Canada
• Prevention
– Education and outreach in smoking cessation, sun protection
• Screening and early diagnosis
– Cervical cancer screening, screening mammography program
• Treatment and supportive care
– Sole provider of radiation therapy and drugs for systemic therapy
• Research
– Basic science to cancer control
– Registry and administrative data available
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Evidence-Based Marginal Analysis
PBMA
Define aim and
scope
Determine current
program budget
Form Steering
Committee
Objective:
to pilot innovations in the program budgeting and marginal
analysis (PBMA) process, by generating program-specific
empirical evidence and incorporating that evidence into
decision-making for resource reallocation (EBMA).
EBMA
For each area identified:
Establish decisionmaking criteria
Identify areas
for new
resource use
Identify areas
for resource
release
Form Advisory
Panel
Collect local
costs/outcomes
Make allocation
recommendations
Build Markov
model
Validity check and
final decisions
Calculate costeffectiveness
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5 areas identified:
• Adjuvant trastuzumab in
breast cancer
• Bevacizumab in metastatic
colorectal cancer
• Mammography for women
with dense breast tissue
• PET for lung cancer staging
• MRI for breast cancer
screening
Current Practice at the Agency
• Hereditary Cancer Program and MRI screening
– Offers genetic counseling and mutation testing to referred
patients
– Confirmed BRCA1/2 mutation carriers (& family) are
offered annual MRI screening and mammography
• 55% risk of breast cancer by age 70
• MRI begins at age 25, or 5 years before earliest cancer in family;
mammography begins at age 30
• Continues until age 65 or first cancer
– Annual mammography for others at high hereditary risk
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MRI for Breast Cancer Screening
• Objective:
– Examine the cost effectiveness of MRI and mammography
for breast cancer screening in high-risk women
• What is the cost-effectiveness of current practice?
• What would be the cost-effectiveness of expanding the program?
• How does preventive surgery fit within screening program?
• Rationale:
– MRI screening for breast cancer is more sensitive than
mammography, but less specific and more expensive
• Advisory Panel:
– Genetic counselors from HCP; radiologist and oncologists
from Breast Tumour Group; VP of Population Oncology
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Markov Model Design
false positives
MRI screen
Mammography
MRI screen
(2)
false negatives
Diagnostic
work-up
(screen-detected)
Mammography
(2)
true positives
Diagnostic
work-up
(non-detected)
In Situ
Well
Local
Regional
Distant
Metastatic
relapse
Dead
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1. Screening and
Diagnostics
2. Treatment
3. Outcomes
Local BRCA1/2 Population
871 women with BRCA1/2
test results in 2002-2007
668 mutation negative
or uninformative
203 confirmed BRCA1/2
mutation positive
98 with no cancer
105 BRCA1/2 positive
breast cancer cases
18 with prior cancer or
missing stage information
87 patients with first
breast cancer
19 patients diagnosed
before 1995
68 patients with
complete records
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Screen Effectiveness
Sensitivity
Specificity
% (95% CI)
% (95% CI)
MRI
77 (70-84)
86.3 (80.9-91.7)
Mammography
39 (37-41)
94.7 (93.0-96.5)
Combined
94 (90-97)
77.2 (74.7-79.7)
Warner, 2008 (Ann Intern Med. 148: 671-679)
• Used pooled sensitivity to calculate conditional probabilities – sensitivity
of either screen given false negative from the other
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Stage Distribution
Method of detection
MRI
Mammography
Not screen-detec.
(%, 95% CI)
(%, 95% CI)
(%, 95% CI)
In Situ
16 (10-22)
27 (17-38)
5 (3-6)
Local
68 (62-72)
49 (38-58)
48 (46-50)
Regional
16 (10-22)
22 (12-31)
40 (37-42)
Distant
1 (0-4)
2 (0-11)
8 (6-9)
Kuhl, 2005 (J Clin Oncol. 23:8469-8476); Warner, 2004 (JAMA. 292:1317-1325); Leach, 2005
(Lancet. 365:1769-1788); Hagen, 2007 (Breast. 16:367-374); Lee, 2008 (Radiology. 246:763-771)
• Pooled MRI- and mammography-detected cancers from 4 MRI screening
studies
• Distribution of non-screen-detected cancers from US SEER data in prescreening era
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Screen Costs
• MRI scan: $277
– Average of estimates from BCCA and 2 regional health authorities
– Includes radiologist cost, other staff costs (technologist and clerical),
supplies and support costs
• Bilateral Mammogram: $95
• Average diagnostic work-up: $175
– Mix of diagnostic mammograms, ultrasound, biopsies and consults
– Used individual-level data from screening mammography program,
and provincial insurance fee schedule
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Cost-Effectiveness of MRI
Mammography
Only (%)
MRI &
Mammography (%)
Incidence
45.4
45.4
Program sensitivity
71.0
92.7
Average specificity
92.4
86.7
In Situ
20.9
18.2
Local
48.8
61.0
Regional
26.8
19.1
Distant
3.6
1.7
Survival
83.7
85.1
Increment
Cost ($)
3,787
7,749
3,962
Effectiveness (QALY)
17.230
17.288
0.058
220
448
68,498
Stage Distribution
Cost-Effectiveness ($/QALY)
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One-way Sensitivity Analysis
Variable
Range
ICER range
MRI sensitivity
0.85-0.70
56,414-84,972
MRI specificity
0.95-0.80
58,257-77,809
In Situ
0.20-0.10
60,491-82,411
Local
0.75-0.60
59,571-80,874
Regional
0.10-0.20
52,388-88,017
Distant
0.005-0.02
63,839-80,986
Cost of MRI
200-700
48,790-176,420
Discount rate
0-0.05
32,569-68,498
$30,000
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$90,000
$150,000
ICER ($/QALY)
Probabilistic Sensitivity Analysis
Probability Cost-Effective
Acceptability Curve
1
0.8
0.6
MRI & Mammography
0.4
Mammography alone
0.2
0
$0
$50,000
Willingness to Pay
$100,000
25%
Median
75%
Incremental cost ($)
3,453
3,931
4,451
Incr. effectiveness (QALY)
0.047
0.064
0.082
ICER ($/QALY)
43,381
59,313
83,461
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Conclusions – MRI Model
• Annual screening of BRCA1/2 mutation carriers with MRI and
mammography, compared to mammography alone, is costeffective, given the low cost of MRI
– ICER of $68,500 is within Agency’s generally accepted range
– For current program size (approx. 200 women), incremental cost of
MRI screening is $800,000, for 12 QALYs gained
• Limitations:
– Assumes full participation starting at age 25, with no movement
into/out of screening program
– Variability in current practice due to geography, wait times, etc.
– Data: used BRCA1/2-specific local data where possible, but it was
often not possible
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Conclusions – MRI Model
• Comparable to findings from studies in US and UK:
– $55,500/QALY for BRCA1 and $130,500/QALY for BRCA2 (Plevritis,
2006)
• around $86,000 for population mix seen at BC Cancer Agency
– £13,500/QALY (Norman, 2007)
• screening for 10-year intervals (30-39, 40-49 yrs) only
– $180,000/QALY (Moore, 2009)
• sensitive to cost of MRI; decreased to <$50,000/QALY when cost
of MRI $315
– $69,000/QALY for BRCA1 carriers (Lee, 2010)
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Conclusions – EBMA Process
• Engagement of MRI Advisory Panel been good throughout
– Interested in development of model; provided valuable direction and
feedback at each stage
– Challenge to communicate between disciplines
• Interest in further modeling
– Recommended ages for MRI screening
– Expanding to lower risk groups: BRCA1/2 mutation negative or
unconfirmed
– Incorporation of preventive mastectomy and/or oophorectomy
• Cost-effectiveness evidence being used in evaluation of
screening program
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Conclusions – EBMA Process
• Steering Committee and BC Cancer Agency Executive also
committed to process
– Combination of top-down and bottom-up engagement is necessary
• Participant interviews and qualitative analysis
– Variety of perspectives on priority-setting
• Future direction for EMBA project
– Levels of evidence required to support decision-making
– When to build new models and when to use existing evidence
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Acknowledgements
• Stuart Peacock, Lindsay Hedden and Elena Papadakis
• Advisory Panel members: Linlea Armstrong, Stephen Chia,
Andrew Coldman, Barbara McGillivray, Charmaine KimSing, Jenna Scott and Christine Wilson
• BC Cancer Agency Provincial Systemic Therapy Program
• Canadian Institutes for Health Research
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