ahrq’s effective health care program: applying existing evidence to breast cancer prevention and...
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AHRQ’s Effective Health Care Program: AHRQ’s Effective Health Care Program: Applying Existing Evidence to Breast Applying Existing Evidence to Breast
Cancer Prevention and DiagnosisCancer Prevention and Diagnosis
Friday, December 3, 2010Friday, December 3, 2010
CALL-IN TELEPHONE NUMBER:CALL-IN TELEPHONE NUMBER:
(888) 632-5065(888) 632-5065
ACCESS CODE: ACCESS CODE:
27294007#27294007#
Questions Questions
To submit a question: To submit a question: – Press the “Ask Question” button located Press the “Ask Question” button located
at the bottom of the screen. at the bottom of the screen.
– When you click on the button, a box will When you click on the button, a box will appear at the bottom of your screen appear at the bottom of your screen requesting that you enter your question. requesting that you enter your question.
– Once completed, press the “Submit” Once completed, press the “Submit” button.button.
22CALL-IN NUMBER: CALL-IN NUMBER: (888)-632-5065(888)-632-5065 ACCESS CODE: ACCESS CODE: 27294007#27294007#
AgendaAgenda
Brief Overview of Patient-Centered Outcomes Brief Overview of Patient-Centered Outcomes Research and AHRQ’s Effective Health Care Research and AHRQ’s Effective Health Care Program-Program- Deborah L. Rogal, Moderator Deborah L. Rogal, Moderator
Comparative Effectiveness of Medications to Comparative Effectiveness of Medications to Reduce Risk of Primary Breast Cancer in Women-Reduce Risk of Primary Breast Cancer in Women- Heidi Nelson, M.D., M.P.H., FACPHeidi Nelson, M.D., M.P.H., FACP
Comparative Effectiveness of Core Needle and Comparative Effectiveness of Core Needle and Open Surgical Biopsy for the Diagnosis of Breast Open Surgical Biopsy for the Diagnosis of Breast Lesions- Lesions- Karen Schoelles, M.D., S.M., FACPKaren Schoelles, M.D., S.M., FACP
Q&A from Audience Q&A from Audience
33CALL-IN NUMBER: CALL-IN NUMBER: (888)-632-5065(888)-632-5065 ACCESS CODE: ACCESS CODE: 27294007#27294007#
Patient-Centered Outcomes Patient-Centered Outcomes Research and AHRQ’s Effective Research and AHRQ’s Effective
Health Care ProgramHealth Care Program
Deborah L. Rogal, M.P.P. Deborah L. Rogal, M.P.P.
AHRQ’s Office of Communications and AHRQ’s Office of Communications and Knowledge TransferKnowledge Transfer
44
Patient-Centered Patient-Centered Outcomes ResearchOutcomes Research
Benefits
Harms
Also known as comparative effectiveness researchAlso known as comparative effectiveness research
Unbiased and practical, evidence-based Unbiased and practical, evidence-based information information
Compares drugs, devices, tests and surgeries, and Compares drugs, devices, tests and surgeries, and approaches to health care approaches to health care – Benefits and harms Benefits and harms – What is known and what isn’tWhat is known and what isn’t
Descriptive, not prescriptiveDescriptive, not prescriptive 55
Horizon Horizon ScanningScanning
EvidenceEvidence NeedNeed
IdentificationIdentification
Evidence Evidence SynthesisSynthesis
EvidenceEvidence GenerationGeneration
StrategiesStrategiesInterventionsInterventionsConditionsConditionsPopulationsPopulations
DisseminationDisseminationTranslationTranslation
ImprovementsImprovements inin
Health CareHealth Care
Research PlatformResearch PlatformInfrastructure – Methods Development – Training Infrastructure – Methods Development – Training
A Framework for A Framework for Patient-Centered Outcomes Patient-Centered Outcomes
ResearchResearch
66
Research Focus: Research Focus: 14 Priority Conditions14 Priority Conditions
Arthritis and nontraumatic joint Arthritis and nontraumatic joint disordersdisorders
CancerCancer
Cardiovascular disease, Cardiovascular disease, including stroke and including stroke and hypertensionhypertension
Dementia, including Dementia, including Alzheimer’s diseaseAlzheimer’s disease
Depression and other mental Depression and other mental health disordershealth disorders
Developmental delays, ADHD Developmental delays, ADHD and autismand autism
Diabetes mellitusDiabetes mellitus
Functional limitations and Functional limitations and disabilitydisability
Infectious disease Infectious disease including HIV/AIDSincluding HIV/AIDS
ObesityObesity
Peptic ulcer disease and Peptic ulcer disease and dyspepsiadyspepsia
Pregnancy including Pregnancy including preterm birthpreterm birth
Pulmonary disease/asthmaPulmonary disease/asthma
Substance abuseSubstance abuse
77
Research Focus: Research Focus: Priority PopulationsPriority Populations
Low-income groupsLow-income groups
Minority groups Minority groups
Women Women
Children Children
The elderly The elderly
Individuals with special health-care needs, such as Individuals with special health-care needs, such as those with disabilities, those who need chronic care or those with disabilities, those who need chronic care or end-of-life care, or those who live in inner-city and rural end-of-life care, or those who live in inner-city and rural areas. areas. 88
Effective Health Care Program Effective Health Care Program Translation ProductsTranslation Products
99
Executive Summary
Web Site
ClinicianGuide
ConsumerGuide Policymaker
Summary
Interactive Case Study
CE Modules
Faculty Slides
Patient Decision Aid(available soon)
Systematic Review Report
Breast Cancer ResourcesBreast Cancer Resources
1010
Public InvolvementPublic Involvement
Topic Topic GenerationGeneration
Topic Topic DevelopmentDevelopment
Topic Topic RefinementRefinement
Research Research ReviewReview
Research Research Needs Needs
DevelopmentDevelopment
Report Report Translation & Translation & DisseminationDissemination
During the Research ProcessDuring the Research Process
Web Web linkslinks
Newsletter Newsletter blurbsblurbs
Articles Articles or or
commentariescommentaries
Web Web conferencesconferences
Continuing Continuing educationeducation
Disseminating the FindingsDisseminating the Findings
• Nominate topics using the online Nominate topics using the online formform• Participate in key question Participate in key question refinementrefinement• Comment via the Web on draft key Comment via the Web on draft key questions and reportsquestions and reports
1111
Heidi D. Nelson, M.D., M.P.H., FACPHeidi D. Nelson, M.D., M.P.H., FACPResearch ProfessorResearch Professor
Departments of Medical Informatics & Clinical Departments of Medical Informatics & Clinical Epidemiology and MedicineEpidemiology and Medicine
Oregon Evidence-Based Practice CenterOregon Evidence-Based Practice CenterOregon Health & Science UniversityOregon Health & Science University
Comparative Effectiveness of Comparative Effectiveness of Medications to Reduce Risk of Medications to Reduce Risk of
Primary Breast Cancer in WomenPrimary Breast Cancer in Women
1212
Prevention strategies for breast cancer currently focus on Prevention strategies for breast cancer currently focus on early detection with screening mammography.early detection with screening mammography.
Newer approaches target risk reduction:Newer approaches target risk reduction:– Identification of Identification of BRCABRCA mutation carriers mutation carriers – Prophylactic mastectomy/oophorectomy for high-risk Prophylactic mastectomy/oophorectomy for high-risk
womenwomen– MedicationsMedications
Despite availability of medications that reduce risk of Despite availability of medications that reduce risk of primary breast cancer: primary breast cancer: – Not commonly used in the U.S.Not commonly used in the U.S.– Unclear how to apply results of recently published trials Unclear how to apply results of recently published trials
in clinical practicein clinical practice1313
BackgroundBackground
Comparative effectiveness review was commissioned by Comparative effectiveness review was commissioned by AHRQ for new USPSTF recommendations.AHRQ for new USPSTF recommendations.
Previous recommendations in 2002 include:Previous recommendations in 2002 include:
B Recommendation for High Risk B Recommendation for High Risk
Clinicians should discuss chemoprevention with women at Clinicians should discuss chemoprevention with women at high risk for breast cancer and at low risk for adverse high risk for breast cancer and at low risk for adverse effects of chemoprevention.effects of chemoprevention.
D Recommendation for Low RiskD Recommendation for Low Risk
The USPSTF recommends against routine use of The USPSTF recommends against routine use of tamoxifen or raloxifene for the primary prevention of breast tamoxifen or raloxifene for the primary prevention of breast cancer in women at low or average risk for breast cancer.cancer in women at low or average risk for breast cancer.
1414
BackgroundBackground
Develop & prioritize topicDevelop & prioritize topic Develop key questionsDevelop key questions Collect abstracts and papers by searching for published Collect abstracts and papers by searching for published
and unpublished studies and registries; and soliciting and unpublished studies and registries; and soliciting information from drug companies (to January 2009) information from drug companies (to January 2009)
Select studies based on predetermined eligibility criteria:Select studies based on predetermined eligibility criteria:
– Efficacy: Efficacy: RCTs RCTs
– Harms: Harms: RCTs, observational studiesRCTs, observational studies
– Risk Models: Risk Models: discriminatory and diagnostic accuracy discriminatory and diagnostic accuracy studiesstudies
1515
Comparative Effectiveness ReviewComparative Effectiveness ReviewSummary of Available Scientific EvidenceSummary of Available Scientific Evidence
Abstract data from studies meeting eligibility criteriaAbstract data from studies meeting eligibility criteria Evaluate studies for quality and applicability using Evaluate studies for quality and applicability using
predefined criteriapredefined criteria Statistically combine results of trials in meta-analyses for Statistically combine results of trials in meta-analyses for
major health outcomesmajor health outcomes Evaluate strength of evidence for each comparator and Evaluate strength of evidence for each comparator and
outcome using GRADE criteriaoutcome using GRADE criteria Interpret results in the context of strengths and limits of Interpret results in the context of strengths and limits of
evidenceevidence Identify future research needsIdentify future research needs
1616
Comparative Effectiveness ReviewComparative Effectiveness ReviewSummary of Available Scientific EvidenceSummary of Available Scientific Evidence
DisseminationDissemination
1717
1: In adult women without pre-existing breast cancer, what 1: In adult women without pre-existing breast cancer, what is the comparative effectiveness of selective estrogen is the comparative effectiveness of selective estrogen receptor modulators (SERMs) tamoxifen citrate and receptor modulators (SERMs) tamoxifen citrate and raloxifene, and the selective tissue estrogenic activity raloxifene, and the selective tissue estrogenic activity regulator (STEAR) tibolone, when used to reduce risk regulator (STEAR) tibolone, when used to reduce risk for primary breast cancer on improving short-term and for primary breast cancer on improving short-term and long-term outcomes including:long-term outcomes including:– Invasive Breast CancerInvasive Breast Cancer
– Noninvasive Breast Cancer including Ductal Carcinoma in situ Noninvasive Breast Cancer including Ductal Carcinoma in situ (DCIS)(DCIS)
– Breast Cancer MortalityBreast Cancer Mortality
– All-Cause MortalityAll-Cause Mortality
– Osteoporotic FracturesOsteoporotic Fractures
1818
Key QuestionsKey Questions
Thromboembolic EventsThromboembolic Events Cardiovascular EventsCardiovascular Events Metabolic DisordersMetabolic Disorders Musculoskeletal Musculoskeletal
SymptomsSymptoms Genitourinary OutcomesGenitourinary Outcomes Breast OutcomesBreast Outcomes
Other MalignanciesOther Malignancies Ophthalmologic DisordersOphthalmologic Disorders Gastrointestinal/ Gastrointestinal/
Hepatobiliary DisordersHepatobiliary Disorders Others Impacting Quality Others Impacting Quality
of Lifeof Life
1919
2: What is the evidence for harms? 2: What is the evidence for harms?
Key QuestionsKey Questions
3: How do outcomes vary by heterogeneity in subpopulations?3: How do outcomes vary by heterogeneity in subpopulations?
4: What methods, such as clinical risk assessment models, 4: What methods, such as clinical risk assessment models, have been used to identify women who could benefit from have been used to identify women who could benefit from medications to reduce risk of primary breast cancer?medications to reduce risk of primary breast cancer?
2020
Key QuestionsKey Questions
AgeAge Menopausal StatusMenopausal Status Use of Exogenous EstrogenUse of Exogenous Estrogen Risk of Breast CancerRisk of Breast Cancer Ethnicity and RaceEthnicity and Race
21
Drugs to Reduce Drugs to Reduce Breast Cancer RiskBreast Cancer Risk
Tamoxifen Tamoxifen citratecitrate
SERMSERM NolvadexNolvadexSoltamoxSoltamox
Reduce breast cancer risk in Reduce breast cancer risk in high-risk women.high-risk women.
Breast cancer treatment. Breast cancer treatment.
RaloxifeneRaloxifene SERMSERM EvistaEvista Reduce breast cancer risk in Reduce breast cancer risk in high-risk postmenopausal high-risk postmenopausal women.women.
Treatment and prevention of Treatment and prevention of postmenopausal osteoporosis.postmenopausal osteoporosis.
TiboloneTiboloneNot FDA Not FDA approvedapproved
STEARSTEAR LivialLivial Prevention of postmenopausal Prevention of postmenopausal osteoporosis.osteoporosis.
Treatment of vasomotor Treatment of vasomotor menopausal symptoms.menopausal symptoms.
LasofoxifeneLasofoxifeneNot FDA Not FDA approvedapproved
SERMSERM FablynFablyn Under developmentUnder development Reduces bone loss.Reduces bone loss. Reduces LDL cholesterol.Reduces LDL cholesterol.
2121
ComparatorsComparators 9 Primary Prevention Trials9 Primary Prevention TrialsN (Drug vs N (Drug vs Placebo)Placebo)
Tamoxifen vs. Tamoxifen vs. RaloxifeneRaloxifene Study of Tamoxifen & Raloxifene (STAR) Study of Tamoxifen & Raloxifene (STAR) 9872 vs 98759872 vs 9875
Tamoxifen Tamoxifen vs.vs.
PlaceboPlacebo
International Breast Cancer Intervention International Breast Cancer Intervention Study (IBIS-1)Study (IBIS-1) 3579 vs 35753579 vs 3575
National Surgical Adjuvant Breast and National Surgical Adjuvant Breast and Bowel Project P-1 (NSABP-1)Bowel Project P-1 (NSABP-1) 6681 vs 67076681 vs 6707
Royal Marsden Hospital TrialRoyal Marsden Hospital Trial 1238 vs 12331238 vs 1233
Italian TrialItalian Trial 2700 vs 27082700 vs 2708
RaloxifeneRaloxifenevs. vs.
PlaceboPlacebo
Multiple Outcomes of Raloxifene Multiple Outcomes of Raloxifene (MORE/CORE)(MORE/CORE) 5129 vs 25765129 vs 2576
Raloxifene Use for the Heart (RUTH)Raloxifene Use for the Heart (RUTH) 5044 vs 50575044 vs 5057
Tibolone vs. Tibolone vs. PlaceboPlacebo
Long-term Intervention on Fractures with Long-term Intervention on Fractures with Tibolone (LIFT)Tibolone (LIFT) 2249 vs 22572249 vs 2257
Lasofoxifene Lasofoxifene vs. Placebovs. Placebo
Postmenopausal Evaluation and Risk Postmenopausal Evaluation and Risk Reduction with Lasofoxifene (PEARL)Reduction with Lasofoxifene (PEARL) 2852 vs 28522852 vs 2852
Meta-Analysis of Meta-Analysis of Placebo-Controlled TrialsPlacebo-Controlled Trials
Invasive Breast CancerInvasive Breast Cancer
FavorsDrug
FavorsPlacebo
0.125 0.25 1 2
Study (yr)Study (yr)Risk Ratio Risk Ratio
(95% CI)(95% CI)
TamoxifenTamoxifen NSABP P-1 (2005)NSABP P-1 (2005) 0.57 (0.46-0.70)0.57 (0.46-0.70)
IBIS (2007)IBIS (2007) 0.74 (0.58-0.94)0.74 (0.58-0.94)
Marsden (2007)Marsden (2007) 0.78 (0.58-1.04)0.78 (0.58-1.04)
Italian (2007)Italian (2007) 0.80 (0.56-1.15)0.80 (0.56-1.15)
Tamoxifen combinedTamoxifen combined 0.70 (0.59-0.82)0.70 (0.59-0.82)
RaloxifeneRaloxifene MORE (2004)MORE (2004) 0.34 (0.22-0.50)0.34 (0.22-0.50)
RUTH (2006)RUTH (2006) 0.56 (0.38-0.83)0.56 (0.38-0.83)
Raloxifene combinedRaloxifene combined 0.44 (0.27-0.71)0.44 (0.27-0.71)
TiboloneTibolone LIFT (2008)LIFT (2008) 0.32 (0.13-0.80)0.32 (0.13-0.80)
LasofoxLasofox PEARL (2010)PEARL (2010) 0.15 (0.04-0.50)0.15 (0.04-0.50)
0.5 2323
2424
Summary of BenefitsSummary of BenefitsEvents Prevented in Placebo-Controlled TrialsEvents Prevented in Placebo-Controlled Trials
Major Clinical Major Clinical
OutcomeOutcomeTamoxifenTamoxifen
(5 trials)(5 trials)RaloxifeneRaloxifene
(2 trials)(2 trials)TiboloneTibolone
(1 trial) (1 trial) Lasofoxi-Lasofoxi-
fene* (1)fene* (1)
Invasive Breast Invasive Breast
CancerCancer8/1,000*8/1,000* 9/1,0009/1,000 10/1,00010/1,000 7/1,0007/1,000
Estrogen Receptor + Estrogen Receptor + 8/1,0008/1,000 8/1,0008/1,000 NANA 7/1,0007/1,000
Estrogen Receptor -Estrogen Receptor - xx xx NANA xx
Noninvasive CancerNoninvasive Cancer xx xx NANA xx
All-Cause DeathAll-Cause Death xx xx NANA xx
Vertebral FractureVertebral Fracture xx 7/1,0007/1,000 44/1,00044/1,000 47/1,00047/1,000
Nonvertebral FractureNonvertebral Fracture 3/1,0003/1,000 xx 34/1,00034/1,000 29/1,00029/1,000
**Per 1000 women-years assuming 5 years of treatment.
2525
Summary of BenefitsSummary of BenefitsEvents Prevented in STAR Head-to-Head TrialEvents Prevented in STAR Head-to-Head Trial
Major Clinical OutcomeMajor Clinical OutcomeRaloxifene vs Raloxifene vs
Tamoxifen 2010Tamoxifen 2010
Invasive Breast CancerInvasive Breast Cancer More with RaloxifeneMore with Raloxifene
Estrogen Receptor + Estrogen Receptor +
Estrogen Receptor -Estrogen Receptor -
Noninvasive CancerNoninvasive Cancer No DifferenceNo Difference
All-Cause DeathAll-Cause Death No DifferenceNo Difference
Vertebral FractureVertebral Fracture
Nonvertebral FractureNonvertebral Fracture
Outcomes in SubgroupsOutcomes in Subgroups
TamoxifenTamoxifen Reduces breast cancer:Reduces breast cancer:
– Age (≤50/>50)Age (≤50/>50)– Pre/post menopausalPre/post menopausal– Estrogen use (yes/no)Estrogen use (yes/no)– Family history of breast Family history of breast
cancer (with/without)cancer (with/without)– LCIS or atypical LCIS or atypical
hyperplasiahyperplasia In National Surgical Adjuvant In National Surgical Adjuvant
Breast and Bowel Project Breast and Bowel Project (NSABP)(NSABP) P-1, cancer rates P-1, cancer rates were highest and risk reduction were highest and risk reduction greatest:greatest:– Prior atypical hyperplasiaPrior atypical hyperplasia– Highest modified Gail Highest modified Gail
model risk category (>5%)model risk category (>5%)
RaloxifeneRaloxifene Reduces breast cancer:Reduces breast cancer:
– Age (≤60/>60 or ≤65/>65) Age (≤60/>60 or ≤65/>65) – Age at menarcheAge at menarche– ParityParity– Age at first live birthAge at first live birth– Body mass index (≤25/>25)Body mass index (≤25/>25)
2626
2727
Summary of HarmsSummary of HarmsEvents Caused in Placebo-Controlled TrialsEvents Caused in Placebo-Controlled Trials
Major Clinical Major Clinical
OutcomeOutcomeTamoxifenTamoxifen
(5 trials)(5 trials)RaloxifeneRaloxifene
(2 trials)(2 trials)TiboloneTibolone
(1 trial) (1 trial) Lasofoxi-Lasofoxi-
fene (1)fene (1)
Thromboembolic Thromboembolic
eventsevents4/1,000*4/1,000* 7/1,0007/1,000 xx 8/1,0008/1,000
Coronary heart Coronary heart
disease disease xx xx xx
12/1,000 12/1,000
lessless
StrokeStroke xx xx 11/1,00011/1,0007/1,000 7/1,000
lessless
Endometrial Endometrial
cancercancer4/1,0004/1,000 xx NANA NANA
CataractsCataracts 3/1,000**3/1,000** xx NANA NANA
*Per 1000 women-years assuming 5 years of treatment.**Results from NSABP P-1 trial.
2828
Summary of HarmsSummary of HarmsEvents Caused in STAR Head-to-Head TrialEvents Caused in STAR Head-to-Head Trial
Major Clinical Major Clinical
OutcomeOutcomeRaloxifene vs Tamoxifen Raloxifene vs Tamoxifen
20102010
Thromboembolic eventsThromboembolic events More with TamoxifenMore with Tamoxifen
Coronary heart disease Coronary heart disease
StrokeStroke
Endometrial cancerEndometrial cancer More with TamoxifenMore with Tamoxifen
CataractsCataracts More with TamoxifenMore with Tamoxifen
Common Side EffectsCommon Side Effects
TamoxifenTamoxifen Hot FlashesHot Flashes Vaginal Symptoms Vaginal Symptoms
(discharge, dryness)(discharge, dryness) Leg CrampsLeg Cramps Bladder Control Bladder Control
ProblemsProblems
RaloxifeneRaloxifene Hot FlashesHot Flashes Leg CrampsLeg Cramps
MusculoskeletalMusculoskeletal ProblemsProblems Weight GainWeight Gain
LasofoxifeneLasofoxifene Leg CrampsLeg Cramps Hot FlashesHot Flashes Vaginal CandidiasisVaginal Candidiasis
2929
TiboloneTibolone Vaginal BleedingVaginal Bleeding Reduces Hot Reduces Hot
FlashesFlashes
AgeAge Age at MenarcheAge at Menarche Age at First BirthAge at First Birth Family History of Breast Cancer in First Degree Family History of Breast Cancer in First Degree
RelativeRelative History of Atypical HyperplasiaHistory of Atypical Hyperplasia Prior Breast BiopsiesPrior Breast Biopsies
cancer.gov/bcrisktool/cancer.gov/bcrisktool/
Selecting Candidates for TherapySelecting Candidates for TherapyRisk Based on Gail Model (≥1.67% 5-year RiskRisk Based on Gail Model (≥1.67% 5-year Risk))
3030
False Positive Rate (1-Specificity)
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Tru
e P
osi
tive
Rat
e (S
ensi
tivi
ty)
0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1.0
ExcellentGoodWorthless
0.55-0.66
Summary of Risk Model ResultsSummary of Risk Model ResultsDiscriminatory Accuracy (16 studies of 9 models)Discriminatory Accuracy (16 studies of 9 models)
3131
Questions Questions
To submit a question: To submit a question: – Press the “Ask Question” button located Press the “Ask Question” button located
at the bottom of the screen. at the bottom of the screen.
– When you click on the button, a box will When you click on the button, a box will appear at the bottom of your screen appear at the bottom of your screen requesting that you enter your question. requesting that you enter your question.
– Once completed, press the “Submit” Once completed, press the “Submit” button.button.
3232
Comparative Effectiveness of Core Comparative Effectiveness of Core Needle and Open Surgical Biopsy for the Needle and Open Surgical Biopsy for the
Diagnosis of Breast LesionsDiagnosis of Breast Lesions
Karen Schoelles M.D., S.M., FACPKaren Schoelles M.D., S.M., FACP
Director, ECRI Institute Evidence-based Practice Director, ECRI Institute Evidence-based Practice CenterCenter
3333
ObjectivesObjectives
To describe the process of developing To describe the process of developing this comparative effectiveness reviewthis comparative effectiveness review
To describe the findings of the reviewTo describe the findings of the review To describe the implications of the To describe the implications of the
reviewreview
3434
Women referred for biopsy after detection of a
breast abnormality
Adverse events related
to biopsy procedure
Diagnosis/ classification of
breast abnormality
1
2
Core-needle or open biopsy?
3
Treat or followup or return to
routine screening?
Change in clinical decisions
Adverse events related to treatment or followup tests
Results of additional testing
Clear surgical margins
Response to treatment
Cosmetic results
Patient population
Intervention and Comparator of interest
Diagnostic thinking and Therapeutic decision making
Patient outcome efficacy
Diagnostic Accuracy
Survival
Recurrence
Quality of life
Total number of surgical procedures
required
P C O
Intermediate Outcomes
Patient-oriented Outcomes
I
Analytic FrameworkAnalytic Framework
3535
PopulationPopulation
Asymptomatic women with an abnormality Asymptomatic women with an abnormality identified on self-exam or by clinician examidentified on self-exam or by clinician exam
Asymptomatic women with an abnormality Asymptomatic women with an abnormality identified by screening imagingidentified by screening imaging Ultrasound – solid or mixedUltrasound – solid or mixed Mammography – typically BI-RADS® 4Mammography – typically BI-RADS® 4
3636
ACR Breast Imaging Reporting ACR Breast Imaging Reporting and Data System (BI-RADS®)and Data System (BI-RADS®)
0: Need additional imaging evaluation and/or prior 0: Need additional imaging evaluation and/or prior mammograms for comparisonmammograms for comparison
1: Negative1: Negative 2: Benign finding2: Benign finding 3: Probably benign; initial short-interval follow-up 3: Probably benign; initial short-interval follow-up
suggestedsuggested 4: Suspicious abnormality. Biopsy should be considered4: Suspicious abnormality. Biopsy should be considered 5: Highly suggestive of malignancy. Appropriate action 5: Highly suggestive of malignancy. Appropriate action
should be takenshould be taken 6: Known biopsy-proven malignancy6: Known biopsy-proven malignancy
3737
Intervention: Core Needle Intervention: Core Needle Biopsy (CNB)Biopsy (CNB)
Hollow core needle inserted percutaneouslyHollow core needle inserted percutaneously Usually 11-, 14-, or 16-gauge needlesUsually 11-, 14-, or 16-gauge needles Lesion located by palpation or imaging Lesion located by palpation or imaging
(stereotactic mammography, ultrasound, or MRI) (stereotactic mammography, ultrasound, or MRI) during the procedureduring the procedure
May be inserted multiple times or only once if May be inserted multiple times or only once if using vacuum assistanceusing vacuum assistance
3838
Comparator: Open Surgical Comparator: Open Surgical BiopsyBiopsy
Excisional: Attempted complete removal of Excisional: Attempted complete removal of abnormalityabnormality
Incisional: Sample of the abnormalityIncisional: Sample of the abnormality
Nonpalpable lesions: May first use imaging to Nonpalpable lesions: May first use imaging to place marking wire, carbon particles, dye, etc. place marking wire, carbon particles, dye, etc. which is then used by the surgeon to identify which is then used by the surgeon to identify the lesion in the operating roomthe lesion in the operating room
3939
Comparator: Clinical Comparator: Clinical Follow-UpFollow-Up
Clinical and imaging followup for at least Clinical and imaging followup for at least 6 months6 months
4040
MethodsMethods
4141
Searches: biopsy, breast biopsy, breast diseases, breast cancer, breast tumor, excision, incisional, large core, Mammotome (Ethicon Endosurgery, Cincinnati, OH), needle biopsy, percutaneous biopsy, stereotactic breast biopsy, surgery, etc. (September 2009)
Articles identified: 1224
Articles retrieved: 589
Studies included: 107
Abstracts screened for potential relevance
Full articles screened against inclusion criteria
635 excluded at abstract level
482 excluded articles
Evaluation of the Risk of Bias Evaluation of the Risk of Bias in Individual Studiesin Individual Studies
Based on the QUADAS tool: BMC Med Res Based on the QUADAS tool: BMC Med Res Methodol 2003 Nov 10;3(1):25. PMID: 14606960Methodol 2003 Nov 10;3(1):25. PMID: 14606960 4242
Test CharacteristicsTest Characteristics
Sensitivity, specificity – commonly understoodSensitivity, specificity – commonly understood Sensitivity = TP/(TP+FN)Sensitivity = TP/(TP+FN) Specificity = TN/(FP+TN)Specificity = TN/(FP+TN)
Predictive values – incorporates prevalencePredictive values – incorporates prevalence Positive predictive value = TP/(TP+FP)Positive predictive value = TP/(TP+FP) Negative predictive value = TN/(FN+TN)Negative predictive value = TN/(FN+TN)
Likelihood ratios – independent of prevalence, but clinical use requires assessment of Likelihood ratios – independent of prevalence, but clinical use requires assessment of pre-test probability pre-test probability
Disease Present Absent Test Results Positive True positives (TP) False positives (FP)
Negative False negatives (FN) True negatives (TN)
4343
Test CharacteristicsTest Characteristics
Likelihood ratio – useful for comparing testsLikelihood ratio – useful for comparing tests Positive likelihood ratio =Positive likelihood ratio = (TP/(TP+FN))/(FP/(FP+TN))(TP/(TP+FN))/(FP/(FP+TN)) Negative likelihood ratio =Negative likelihood ratio = (FN/(TP+FN))/(TN/(FP+TN)) (FN/(TP+FN))/(TN/(FP+TN))
For this evaluation, not missing a cancer was For this evaluation, not missing a cancer was considered the most important outcome, reflected by: considered the most important outcome, reflected by: Sensitivity, Negative Predictive Value and Negative Sensitivity, Negative Predictive Value and Negative
Likelihood RatioLikelihood Ratio
Disease Present Absent Test Results Positive True positives (TP) False positives (FP)
Negative False negatives (FN) True negatives (TN)
4444
0.0010.0020.0050.010.020.050.10.20.51251020501002005001000
Likelihood Ratio
0.1
0.20.30.50.71
235710
20304050607080
9093959798
9999.399.599.799.8
99.9
Po
st-t
est P
roba
bili
ty (
%)
0.1
0.20.30.50.7
1
2357
10
20304050607080
9093959798
9999.399.599.799.8
99.9
Pre
-te
st P
rob
abili
ty (
%)
Prior Prob (%) = 30
LR_Positive = 54Post_Prob_Pos (%) = 96
LR_Negative = 0.04Post_Prob_Neg (%) = 2
Fagan's Nomogram
0.0010.0020.0050.010.020.050.10.20.51251020501002005001000
Likelihood Ratio
0.1
0.20.30.50.71
235710
20304050607080
9093959798
9999.399.599.799.8
99.9
Po
st-t
est P
roba
bili
ty (
%)
0.1
0.20.30.50.7
1
2357
10
20304050607080
9093959798
9999.399.599.799.8
99.9
Pre
-te
st P
rob
abili
ty (
%)
Prior Prob (%) = 30
LR_Positive = 54Post_Prob_Pos (%) = 96
LR_Negative = 0.04Post_Prob_Neg (%) = 2
Fagan's NomogramFagan TJFagan TJLetter: Nomogram for Bayes Letter: Nomogram for Bayes theorem. N Engl J Med 1975; theorem. N Engl J Med 1975; 293:257.293:257.
http://www.cebm.net/http://www.cebm.net/index.aspx?o=1161index.aspx?o=1161
Interactive version:Interactive version:
Fagan’s NomogramFagan’s Nomogram
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0 0.05 0.1 0.15 0.2 0.25 0.3
Negative likelihood ratios
Freehand automated gun
US vacuum-assisted
US automated gun
Stereotactic automated gun
Stereotactic vacuum-assisted
Open surgical
4747
0 10 20 30 40 50
DCIS underestimation percentage
US automated gun
Stereotactic automated gun
Stereotactic vacuum-assisted
Open surgical
DCIS: Ductal carcinoma in situDCIS: Ductal carcinoma in situ4848
0 10 20 30 40 50 60
ADH underestimation percentage
US automated gun
Stereotactic automated gun
Stereotactic vacuum-assisted
Open surgical
ADH: Atypical ductal hyperplasiaADH: Atypical ductal hyperplasia4949
Overall Strength of Evidence for Overall Strength of Evidence for Each Question-Outcome PairEach Question-Outcome Pair
Risk of bias in the studies included to answer the Risk of bias in the studies included to answer the questionquestion
Quantity of evidence (number of studies and patients)Quantity of evidence (number of studies and patients) Consistency of the findings across and within studiesConsistency of the findings across and within studies Robustness of the results (sensitivity analyses)Robustness of the results (sensitivity analyses) Possible grades: high, moderate, low, or insufficientPossible grades: high, moderate, low, or insufficient
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Summary of Key Accuracy Summary of Key Accuracy FindingsFindings
Type of biopsy
Number of missed cancers expected for every 1,000 biopsies
Risk of malignancy following a “benign” test result
Number of malignancies expected per 1,000 biopsy diagnoses of “high risk” lesion
Number of invasive cancers expected per 1,000 biopsy diagnoses of DCIS
Strength of evidence supporting the conclusion
Open surgical
3 to 6 0 to 1% 0 0 Not rated
Freehand automated gun
24 to 73 3.4 to 10%
Insufficient data to estimate
Low
US guidance automated gun
6 to 9 1 to 2% 234 to 359 271 to 450
Low
Stereotactic guidance automated gun
3 to 13 0.5 to 2% 357 to 517 180 to 321
Low
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Summary of Key Accuracy Summary of Key Accuracy FindingsFindings
Type of biopsy
Number of missed cancers expected for every 1,000 biopsies
Risk of malignancy following a “benign” test result
Number of malignancies expected per 1,000 biopsy diagnoses of “high risk” lesion
Number of invasive cancers expected per 1,000 biopsy diagnoses of DCIS
Strength of evidence supporting the conclusion
Open surgical4
3 to 6 0 to 1% 0 0 Not rated
MRI guidance automated gun
Insufficient data to estimate Insufficient
US guidance vacuum-assisted
2 to 56 0.3 to 8% Insufficient data to estimate Low
Stereotactic guidance vacuum-assisted
1 to 6 0.1 to 1% 177 to 264 111 to 151 Low
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Type of biopsyAnalysis results
If analysis overestimated sensitivity by 1%(e.g., sensitivity 97% rather than 98%)
If analysis overestimated sensitivity by 5%(e.g., sensitivity 93% rather than 98%)
If analysis overestimated sensitivity by 10%(e.g., sensitivity 88% rather than 98%)
Freehand automated gun
6% 6% 8% 9%
Ultrasound guidance automated gun
1% 1% 3% 5%
Stereotactic guidance automated gun
1% 1% 3% 5%
Ultrasound guidance vacuum-assisted
2% 2% 3% 6%
Stereotactic guidance vacuum‑assisted
0.4% 0.8% 3% 5%
Post-Biopsy Probability of Having Post-Biopsy Probability of Having Cancer After A Negative Core-Needle Cancer After A Negative Core-Needle
Biopsy ResultBiopsy Result
5353
For Additional InformationFor Additional Information
Clinician Guide:Clinician Guide:
http://www.effectivehealthcare.ahrq.gov/index.cfm/http://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=406pageaction=displayproduct&productID=406
Full Report:Full Report:
http://www.effectivehealthcare.ahrq.gov/index.cfm/http://www.effectivehealthcare.ahrq.gov/index.cfm/search-for-guides-reviews-and-reports/?search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=370pageaction=displayproduct&productID=370
Manuscript:Manuscript:Bruening W, Fontanarosa J, Tipton K, Treadwell JR, Launders J, Bruening W, Fontanarosa J, Tipton K, Treadwell JR, Launders J, Schoelles K. Systematic review: comparative effectiveness of core-Schoelles K. Systematic review: comparative effectiveness of core-needle and open surgical biopsy to diagnose breast lesions. Ann needle and open surgical biopsy to diagnose breast lesions. Ann Intern Med. 2010 Feb 16;152(4):238-46. Epub 2009 Dec 14. PMID: Intern Med. 2010 Feb 16;152(4):238-46. Epub 2009 Dec 14. PMID: 2000874220008742
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Questions Questions
To submit a question: To submit a question: – Press the “Ask Question” button located Press the “Ask Question” button located
at the bottom of the screen. at the bottom of the screen.
– When you click on the button, a box will When you click on the button, a box will appear at the bottom of your screen appear at the bottom of your screen requesting that you enter your question. requesting that you enter your question.
– Once completed, press the “Submit” Once completed, press the “Submit” button.button.
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For more information about…For more information about…
AHRQ’s Effective Health Care Program: AHRQ’s Effective Health Care Program: www.effectivehealthcare.ahrq.gov.www.effectivehealthcare.ahrq.gov.
Accessing these FREE resources through Accessing these FREE resources through AHRQ’s Publications Clearinghouse: AHRQ’s Publications Clearinghouse: (800) 358-9295.(800) 358-9295.
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If you have a question about utilizing AHRQ If you have a question about utilizing AHRQ resources please e-mail us at: resources please e-mail us at: EHC_Clinicians@ahrq.hhs.gov.EHC_Clinicians@ahrq.hhs.gov.
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Upcoming Web ConferencesUpcoming Web Conferences
Monday, December 6 at 2 p.m. ET. Monday, December 6 at 2 p.m. ET.
Applying Existing Evidence to Cardiac CareApplying Existing Evidence to Cardiac Care
Monday, December 13 at 11 a.m. ET. Monday, December 13 at 11 a.m. ET.
Evidence-Based Medicine for Pharmacists Evidence-Based Medicine for Pharmacists in the Patient-Centered Medical Homein the Patient-Centered Medical Home
Tuesday, December 14 at 12 p.m. ET. Tuesday, December 14 at 12 p.m. ET.
Applying Existing Evidence to Diabetes CareApplying Existing Evidence to Diabetes Care
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Thank you!Thank you!
Thank you for joining us today! Thank you for joining us today! Please take a moment to provide us Please take a moment to provide us
feedback at the end of this event. feedback at the end of this event. A recording and transcript for today’s A recording and transcript for today’s
event will be available on the AHRQ event will be available on the AHRQ Web site. Web site.
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