Advancing Health Economics, Services, Policy and Ethics
Evidence-based marginal analysis: Cost-effectiveness of MRI for breast cancer
screening in BRCA1/2 mutation carriers
Reka PatakyPriorities 2010, Boston
• The BC Cancer Agency• Evidence-based marginal analysis• MRI screening study
– Background– Model construction– Results
• Discussion and Conclusions
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Outline
• 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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About the BC Cancer Agency
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Evidence-Based Marginal Analysis
Define aim and scope
Form Steering Committee
Determine current program budget
Establish decision-making criteria
Identify areas for resource
release
Identify areas for new
resource use
Make allocation recommendations
Validity check and final decisions
For each area identified:
Form Advisory Panel
Collect local costs/outcomes
Build Markov model
Calculate cost-effectiveness
EBMA
PBMA
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).
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
• 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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Current Practice at the Agency
• 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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MRI for Breast Cancer Screening
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Markov Model Design
Mammography
Diagnostic work-up
(screen-detected)
Metastatic relapse
Diagnostic work-up
(non-detected)
MRI screen
Well Dead
false negatives
false positives
Mammography (2)
MRI screen (2)
true positives1. Screening and
Diagnostics
2. Treatment
3. Outcomes
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Local BRCA1/2 Population
98 with no cancer
68 patients with complete records
871 women with BRCA1/2 test results in 2002-2007
203 confirmed BRCA1/2 mutation positive
105 BRCA1/2 positive breast cancer cases
87 patients with first breast cancer
668 mutation negative or uninformative
18 with prior cancer or missing stage information
19 patients diagnosed before 1995
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)
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Screen Effectiveness
• Used pooled sensitivity to calculate conditional probabilities – sensitivity of either screen given false negative from the other
Warner, 2008 (Ann Intern Med. 148: 671-679)
• Pooled MRI- and mammography-detected cancers from 4 MRI screening studies
• Distribution of non-screen-detected cancers from US SEER data in pre-screening era
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Stage DistributionMethod 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)
• 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: $175
– Mix of diagnostic mammograms, ultrasound, biopsies and consults– Used individual-level data from screening mammography program,
and provincial insurance fee schedule
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Screen Costs
Mammography Only (%)
MRI & Mammography (%)
Incidence 45.4 45.4
Program sensitivity 71.0 92.7
Average specificity 92.4 86.7
Stage Distribution
In Situ 20.9 18.2
Local 48.8 61.0
Regional 26.8 19.1
Distant 3.6 1.7
Survival 83.7 85.1 Increment
Cost ($) 3,787 7,749 3,962
Effectiveness (QALY) 17.230 17.288 0.058
Cost-Effectiveness ($/QALY) 220 448 68,498
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Cost-Effectiveness of MRI
Variable Range ICER range
MRI sensitivity 0.85-0.70 56,414-84,972
MRI specificity 0.95-0.80 58,257-77,809
In Situ 0.20-0.10 60,491-82,411
Local 0.75-0.60 59,571-80,874
Regional 0.10-0.20 52,388-88,017
Distant 0.005-0.02 63,839-80,986
Cost of MRI 200-700 48,790-176,420
Discount rate 0-0.05 32,569-68,498
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One-way Sensitivity Analysis
25% Median 75%
Incremental cost ($) 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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Probabilistic Sensitivity Analysis
• Annual screening of BRCA1/2 mutation carriers with MRI and mammography, compared to mammography alone, is cost-effective, 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)
Conclusions – MRI Model
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• 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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Conclusions – EBMA Process
Acknowledgements
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• Stuart Peacock, Lindsay Hedden and Elena Papadakis• Advisory Panel members: Linlea Armstrong, Stephen Chia,
Andrew Coldman, Barbara McGillivray, Charmaine Kim-Sing, Jenna Scott and Christine Wilson
• BC Cancer Agency Provincial Systemic Therapy Program• Canadian Institutes for Health Research