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