Introduction

1. Controversies in Screening RecommendationsGeorge 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. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. USPSTF Grades of Recommendations http://www.uspreventiveservicestaskforce.org/uspstf/grades.htm

11. What the Grades Mean: Suggestions for Practice http://www.uspreventiveservicestaskforce.org/uspstf/grades.htm

12. Analytic Framework: Screening

13. The steps: brief and generic Define questions and outcomes of interest (TF subgroup) Define, retrieve and summarize relevant evidence (EPCs) Judge quality of individual studies: good, fair, poor (EPCs) Synthesize and judge the adequacy of the evidence about benefits and harms: convincing, adequate, inadequate (TF subgroup) Determine and judge the magnitude of both benefits and harms: substantial, moderate, small, zero; if unable to determine, evidence deemed “insufficient”(TF subgroup) Determine and judge the balance of benefits and harms (net benefit) (TF subgroup) Judge the certainty of net benefit: low, moderate, high (TF) Judge the magnitude of net benefit: substantial, moderate, small, zero/negative (TF) Assign a letter grade: A, B, C, D • Sawaya GF et al Ann Intern Med. 2007;147:871-875.

14. The changes: breast cancer screening In November 2009, the US Preventive Services Task Force changed its recommendation from screening “every 1-2 years in women over age 40”, a “B” recommendation, to: - against routine screening of women aged 40-49 years. The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take into account patient context, including the patient’s values regarding specific benefits and harms. (a “C” recommendation)- biennial screening of women aged 50-74 years (a “B” recommendation)- insufficient evidence for screening women aged 75+ (an “I” statement)- insufficient evidence for clinical breast exams in addition to mammography in women 40+ (an “I” statement)- discourage teaching women self-breast examination (a “D” recommendation) http://www.ahrq.gov/clinic/USpstf/uspsbrca.htm

15. The firestorm • Headlines read: “Governmental panel: mammograms not worth it in women under 50”: confusion, fear, anger ensueExample: Contra Costa Times (2/12/10): Three years ago, [patient], then 42, rushed to a San Francisco clinic after finding a hard, rough-edged lump in her breast. A mammogram… and a subsequent biopsy confirmed… breast cancer. They caught the disease just before it spread further and, today, her cancer is in remission.When [she]… heard that a federally appointed task forcenow recommends against routine mammograms for women in their 40s, she shook her head in dismay."That's a disaster. Look at my case. They're trying to save a buck, and the first place they start is with women."

16. The firestorm continues • USPSTF comes under attack • Politicization follows: USPSTF = the Palin “death panel” • Recommendation described as a harbinger of the future of health care: rationing • USPSTF co-chairs called to testify before Congress; “message fumbled”

17. Devising Breast Cancer Screening Recommendations: The USPSTF Approach

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

19. Analytic Framework: Screening for Breast Cancer: Key questions 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? http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanupappfig1.htm

20. Analytic Framework: Screening for Breast Cancer: Key questions 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? http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanupappfig1.htm

21. 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

22. Evidence of Benefit: Mammography by Age Group http://www.uspreventiveservicestaskforce.org/uspstf09/breastcancer/brcanup.htm#tab1

23. Evidence of benefit: focus on ages 39-49 Nelson et al Ann Intern Med 2009, 151; 727

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

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

31. 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

32. 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

33. Putting it all together

34. 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

35. 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

36. 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

37. Estimation of Certainty and Magnitude of Evidence of Net Benefit of Mammography (Benefit Minus Harm) • The USPSTF emphasizes the adverse consequences for most women—who will not develop breast cancer—and 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

38. 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

39. 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

40. 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

41. Confusion continues March 3, 2010: Director of [X] University Breast Imaging… disagreed with the Task Force’s conclusion that the number of lives saved by annual mammography screening for women in their 40s was outweighed by the risks of screening for that age group.“Women need to know that [with routine mammograms] there may be false positives and a need for biopsies,” she said. “But women should make that choice for themselves, with a doctor’s help.” http://med.stanford.edu/ism/2010/march/mammogram-0322.html

42. Questions and Comments