1. Controversies in Screening Recommendations George F. Sawaya, MD Professor of Obstetrics, Gynecology and Reproductive Sciences and Epidemiology and Biostatistics, University of California, San Francisco. Member of the US Preventive Services Task Force from 2004-2008

2. Case A 40-year-old woman presents to your clinic for a periodic health examination. She is healthy and has no risk factors for any particular diseases. She does not smoke, is sexually active and is not pregnant. You note that the US Preventive Services Task Force recommends screening for the following diseases: cervical cancer, hypertension, alcohol misuse and obesity. Routine mammography is not recommended. She has read about the mammography controversy and wants to know more about the benefits and harms.

3. Introduction Recommendations for prevention strive to maximize benefits and minimize harms. Competing factors: US population highly enthusiastic about frequent cancer screening; medico-legal environment rewards vigilance from clinicians Sawaya GF N Engl J Med 2009 361;26 2503-2505

4. Introduction Controversies common in determining: when to begin, when to end, screening frequency and use of newer screening technologies USPSTF: widely recognized as setting the standard for evidence-based recommendations related to prevention Sawaya GF N Engl J Med 2009 361;26 2503-2505

5. Introduction Devising recommendations for prevention can be complicated at all steps. Determining the appropriate balance between benefits and harms is challenging. Sawaya GF N Engl J Med 2009 361;26 2503-2505

6. What is the US Preventive Services Task Force? Congressionally mandated independent panel of non- Federal experts in prevention and evidence-based medicine 16 primary care providers (e.g., internists, pediatricians, family physicians, gynecologists/obstetricians, nurses and health behavior specialists) http://www.uspreventiveservicestaskforce.org/about.htm

7. What is the US Preventive Services Task Force Mission? to evaluate the benefits of individual services based on age, gender, and risk factors for disease; make recommendations about which preventive services should be incorporated routinely into primary medical care and for which populations; and identify a research agenda for clinical preventive care. http://www.uspreventiveservicestaskforce.org/about.htm

8. Who Supports the US Preventive Services Task Force? Administrative, research, technical and dissemination support provided by the Agency for Healthcare Research and Quality (AHRQ) Scientific support from Evidence-Based Practice Centers (EPCs) 14 centers in the US and Canada conduct systematic evidence reviews on topics in clinical prevention that serve as the scientific basis for USPSTF recommendations products: evidence reports and technology assessments http://www.uspreventiveservicestaskforce.org/about.htm

9. What are US Preventive Services Task Force activities? develops recommendations for primary care clinicians and health systems on a broad range of clinical preventive health care services (e.g., screening, counseling, and preventive medications) does not consider costs, medical-legal issues or insurance coverage in deliberations http://www.uspreventiveservicestaskforce.org/about.htm

10. What are US Preventive Services Task Force activities? recommendations published in the form of recommendation statements; opportunity for public comment provided Affordable Care Act (July 2010) singles out positive recommendations by the USPSTF (those deemed an A or B) for coverage recommendations graded to convey two major elements: certainty and magnitude of net benefit of the service http://www.uspreventiveservicestaskforce.org/about.htm

11. USPSTF Grades of Recommendations Certainty of Net Benefit Magnitude of Net Benefit SubstantialModerateSmallZero/negative HighABCD ModerateBBCD LowInsufficient http://www.uspreventiveservicestaskforce.org/uspstf/grades.htm

12. What the Grades Mean: Suggestions for Practice http://www.uspreventiveservicestaskforce.org/uspstf/grades.htm GradeSuggestions for practice AOffer or provide this service. B COffer or provide this service only if other considerations support the offering or providing the service in an individual patient. DDiscourage the use of this service. I statementRead the clinical considerations section of USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms.

13. Case A 40-year-old woman presents to your clinic for a periodic health examination. She is healthy and has no risk factors for any particular diseases. She does not smoke, is sexually active and is not pregnant. Routine mammography is not recommended by the USPSTF. She has read about the mammography controversy and wants to know more about the benefits and harms.

14. Devising Breast Cancer Screening Recommendations: The USPSTF Approach

15. Analytic Framework: Screening for Breast Cancer http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanupappfig1.htm 2 major key questions (see next slide)

16. Analytic Framework: Screening for Breast Cancer: Key questions http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanupappfig1.htm 1a. Does screening with mammography (film and digital) or MRI decrease breast cancer mortality among women age 40–49 years and 70 years? 1b. Does clinical breast examination screening decrease breast cancer mortality? Alone or with mammography? 1c. Does breast self-examination practice decrease breast cancer mortality?

17. Analytic Framework: Screening for Breast Cancer: Key questions http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanupappfig1.htm 2a. What are the harms associated with screening with mammography (film and digital) and MRI? 2b. What are the harms associated with clinical breast examination ? 2c. What are the harms associated with breast self- examination?

18. Breast Cancer Screening: Benefits Decreased breast cancer mortality and total mortality Decreased morbidity from breast cancer (reduction of late-stage breast cancer) http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanup.htm

19. Breast Cancer Screening: Harms Radiation exposure Pain during procedures Anxiety, distress, and other psychological responses False-positive and false-negative mammography results, additional imaging, and biopsies http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanup.htm

20. Evidence of Benefit: Mammography by Age Group http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanup.htm#tab1 AgeTrials included, n RR for Breast Cancer Mortality (95% CrI) NNI to Prevent 1 Breast Cancer Death (95% CrI) 39-49 y80.85 (0.75-0.96)1904 (929-6378) 50-59 y60.86 (0.75-0.99)1339 (322-7455) 60-69 y20.68 (0.54-0.87)377 (230-1050) 70-74 y11.12 (073-1.72)Not available

21. Evidence of Harms: Other Evidence Related to Mammography Data about harms often obtained from a variety of sources. For breast cancer screening, data from 600,830 women aged 40+ years undergoing routine mammography screening at Breast Cancer Surveillance Consortium (BCSC) sites obtained BCSC data intended to represent the experience of a cohort of regularly screened women http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanup.htm

22. Evidence of Harms: False Positive Testing with Mammography Estimated risk of false positive testing after 10 mammograms (all ages): 21-49% Estimated risk of false positive testing after 10 mammograms in women aged 40-49: 56% http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanup.htm

23. Judging Evidence of Benefit of Mammography There is convincing evidence that screening with film mammography reduces breast cancer mortality, with a greater absolute reduction for women aged 50 to 74 years than for women aged 40 to 49 years. The strongest evidence for the greatest benefit is among women aged 60 to 69 years. http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

24. Judging Evidence of Harm of Mammography Adequate evidence that the overall harms associated with mammography are moderate for every age group considered… False-positive results are more common for women aged 40 to 49 years, whereas overdiagnosis is a greater concern for women in the older age groups. http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

25. Putting It All Together: Balancing Benefits and Harms of Mammography Decision analysis: a method by which the balance of benefits and harms can be judged. USPSTF commissioned a decision analysis to assist in the determination of net benefit (benefit minus harms). http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

26. Decision Analysis Estimates the outcomes of different clinical decisions Breaks down problem into components: treatment options, outcome probabilities with each option (both benefits and harms) Uses systematic reviews and meta-analyses Applies to large, theoretic cohorts of individuals going forward in time (effectiveness) Estimates both benefits and harms

27. Putting It All Together: Balancing Benefits and Harms of Mammography Benefits: Percentage of mortality reduction Cancer deaths averted per 1000 women Life years gained life-year: a measure of the quantity of life lived may be expressed as life years expected per 1000 people for an intervention strategy http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanart.htm

28. Putting It All Together: Balancing Benefits and Harms of Mammography Harms: False-positive results per 1000 women Unnecessary biopsies per 1000 women http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanart.htm

29. Putting It All Together: Balancing Benefits and Harms of Mammography Conclusions (all ages): biennial screening produced 70% to 99% of the benefit of annual screening, with a significant reduction in the number of mammograms required and therefore a decreased risk for harms. http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

30. Putting It All Together: Balancing Benefits and Harms of Mammography Screening between the ages of 50 and 69 years produced a projected 17% (range, 15% to 23%) reduction in mortality (compared with no screening) Extending the age range produced only minor improvements (additional 3% reduction from starting at age 40 years and 7% from extending to age 79). http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

31. Estimation of Certainty and Magnitude of Evidence of Net Benefit of Mammography (Benefit Minus Harm) For biennial screening mammography in women aged 40 to 49 years, there is moderate certainty that the net benefit is small. http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

32. Estimation of Certainty and Magnitude of Evidence of Net Benefit of Mammography (Benefit Minus Harm) The USPSTF emphasizes the adverse consequences for most womenwho will not develop breast cancerand therefore use the number needed to screen to save 1 life as its metric. By this metric, the USPSTF concludes that there is moderate evidence that the net benefit is small for women aged 40 to 49 years. For biennial screening mammography in women aged 50 to 74 years, there is moderate certainty that the net benefit is moderate. http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

33. Further the additional benefit gained by starting screening at age 40 years rather than at age 50 years is small, and that moderate harms from screening remain at any age. This leads to the C recommendation. a C grade is a recommendation against routine screening of women aged 40 to 49 years. The Task Force encourages individualized, informed decision making about when to start… http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

34. Back to the Case: Talking to Patients About Mammography The precise age at which the benefits from screening mammography justify the potential harms is a subjective judgment and should take into account patient preferences. Clinicians should inform women about the potential benefits (reduced chance of dying from breast cancer), potential harms (for example, false-positive results, unnecessary biopsies), and limitations of the test that apply to women their age. http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanrs.htm

35. Summary Devising recommendations for prevention can be complicated at all steps. While screening benefits are often cited and widely promulgated, the USPSTF gives equal attention to screening harms. Determining the appropriate balance between benefits and harms is challenging. http://www.uspreventiveservicestaskforce.org/uspstf07/methods/benefit.htm

36. Summary Different groups may evaluate the same evidence and arrive at different conclusions. The USPSTF method of devising recommendations involves judgment at all steps but strives for transparency. http://www.uspreventiveservicestaskforce.org/uspstf07/methods/benefit.htm

37. Questions and Comments