Preventive Health Care Screening

1. Preventive Health Care Screening Miriam Rabkin, MD

2. Preventive Health Care Screening • Screening basics:clinical epidemiology • Screening guidelines • Cancer screening: some examples

3. Screening Basics • What does “screening” mean? • What do we screen for? • risk factors for disease • presence of disease • What makes a disease or risk factor an appropriate target for screening? • What makes a test a good screening test?

4. Screening Basics does more screening = better health care?

5. Characteristics of Disease • Serious • Treatable • Pre-clinical detectable period • Early treatment is better than late • Prevalent

6. Characteristics of Disease • Why do we screen for serious disease? • why don’t we screen for varicose veins? • Why do we screen for treatable disease? • why don’t we screen for pancreatic cancer?

7. Characteristics of Disease • Why do we screen for diseases with a pre-clinical detectable period? • Ex: HIV vs. Legionella • Why do we screen for diseases where early treatment is better than late? • Ex: lung cancer

8. Characteristics of Disease • Why do we screen for prevalent disease? • More bang for the buck • Prevalence affects predictive value • predictive value depends not only on sensitivity and specificity but on prevalence • PPV = the chance of having the disease in the presence of a positive test • NPV = the chance of not having the disease in the presence of a negative test

9. Characteristics of Disease • The more prevalent a condition, the fewer false positive tests there will be • The less prevalent a condition, the fewer false negative tests there will be • No matter how good the test is!

10. Why do we test for prevalent diseases? Although the combination ELISA/Western Blot test for HIV has extremely high sensitivity and specificity, predictive value is dependent on prevalence. High risk population: prevalence = 40% PPV = 0.985 NPV = 0.993 Low risk population: prevalence = 0.01% PPV = 0.0098 NPV = 0.999

11. Characteristics of Test • sensitive/specific • low-risk • “tolerable” • low-expense

12. Screening Basics • Volunteer bias • Lead-time bias • Length bias

13. Volunteer Bias • Volunteers are different (“the volunteer effect”) • more health conscious? • more preventive health care? • more risk factors? • Volunteers tend to be healthier and to have lower rates of morbidity and mortality, no matter what the hypothesis under study is

14. Length Bias • Diseases are heterogeneous • A screening test finds prevalent cases, not incident cases • Prevalence = incidence x duration • Cases with longer duration are, therefore, more likely to be detected by a screening test

15. Length Bias Screening maneuver:

16. Length Bias Length bias is the preferential detection of slowly progressive disease

17. Lead Time Bias • Identifying a disease in its preclinical detectable period can artificially create the impression that screened populations do better than unscreened • can “phase-shift” the disease

18. Lead Time Bias screen-detectable clinically evident death 5 years clinically evident death 2 years

19. Lead Time Bias • Because of lead-time bias, it is necessary to look at disease-specific and age-specific death rates in screened and unscreened groups when assessing a screening intervention. • Time from diagnosis to death does not tell you if a screening test is effective

20. Preventive Health Care Screening • Screening basics:clinical epidemiology • Screening guidelines • Cancer screening: some examples

21. Screening Guidelines • Whose guidelines? • Based on what sort of data? • How strict are the criteria? • What are the goals?

22. Screening Guidelines • Who publishes guidelines? • The US Preventive Services Task Force • The American Medical Association, the American Cancer Society, the National Cancer Institute • Subspecialty organizations (AGA, AAFP etc.) • Health maintenance organizations • Patient advocacy organizations

23. Hierarchy of Evidence • Randomized controlled trials • Nonrandomized controlled trials • Cohort studies • Case control studies • Comparisons between times and places • Uncontrolled experiments • Descriptive studies • Expert opinion

24. Strength of Recommendations A: good evidence to support the recommendation that the condition be considered in a periodic health exam B: fair evidence to support the recommendation C: insufficient evidence to recommend for or against D: fair evidence to recommend exclusion E: good evidence to recommend exclusion

25. Preventive Health Care Screening • Screening basics:clinical epidemiology • Screening guidelines • Cancer screening: some examples

26. Screening for Cervical Cancer • Prevalent • Serious • Preclinical detectable period • Treatable • Early treatment is better than late

27. Papanicolaou testing • Papanicolaou testing is not sensitive but quite specific • There are no randomized trials of cervical cancer screening • Estimates are that triennial screening in women ages 20-64 reduces the cumulative incidence of cervical cancer by 91% and yields 96 cases for every 100,000 tests

28. Screening for Cervical Cancer A: routine Pap smears for all women who have ever been sexually active and who have a cervix B: frequency - at least every three years There is little evidence that more frequent screening is beneficial (except in HIV-infected patients). May be effective in HPV-infected patients. C: discontinue Pap smears at age 65 if patient has had regular normal Paps in past C: HPV infection screening

29. Screening for Colorectal Cancer • Prevalent • Serious • Preclinical detectable period • Treatable • Early treatment is better than late

30. Screening for Colorectal Cancer Case for screening with annual DRE (digital rectal exam): None. There is no evidence to support this screening strategy.

31. Screening for Colorectal Cancer Case for screening with FOBT (fecal occult blood testing): • Mandel et al. 1993 randomized 46,551 patients from 50-80 to FOBT screening every year, every two years, or control. Patients with positive FOBT underwent colonoscopy • After 13 years of follow-up, the age-adjusted mortality rate from colon cancer was 33% lower than in the annual testing group

32. Screening for Colorectal Cancer • Subsequent randomized trials have duplicated this result and this screening maneuver (FOBT) is universally recommended • Annual FOBT is better than biennial screening • Byers et al. 1997: 33% reduction in mortality with annual FOBT, no reduction with biennial • Hardcastle et al. 1998: only 18% reduction with biennial FOBT

33. Screening for Colorectal Cancer Case for screening with sigmoidoscopy: > No randomized trials ! > Selby et al. 1992: case-control study of rigid sigmoidoscopy screening. Odds ratio for dying of distal colorectal cancer was 0.41 (0.25-0.69) for those screened. No protective effect on dying of proximal colorectal cancer.

34. Screening for Colorectal Cancer • Muller and Sonnenberg 1995: Case-control study of 32,702 veterans showed that endoscopic procedures of the large bowel (colonoscopy or sigmoidoscopy) reduced the risk of developing colorectal cancer by 50%

35. Screening for Colorectal Cancer • Case for screening with colonoscopy: NB: There are no studies evaluating whether screening colonoscopy alone reduces the incidence or mortality of CRC in patients at average risk.

36. Screening for Colorectal Cancer • Case for screening with colonoscopy: • colonoscopy was an integral part of RCTs of fecal occult blood testing • sensitivity of sigmoidoscopy (compared to colonoscopy as gold standard) was 44% in a 1991 study • “polyp science” • “expert opinion”

37. Screening for Colorectal Cancer • Rex et al. 1997: Two consecutive same-day colonoscopies were performed in 183 patients showing miss rates of: • 6% for adenomas > 1 cm • 13% for adenomas 6-9 mm • 27% for adenomas < 5mm • Complication rates (and cost) of colonoscopy are significantly higher than those of sigmoidoscopy

38. Screening for Colorectal Cancer B: For all normal risk persons age > 50 1) annual FOBT (with colonoscopy if + ) 2) flexible sigmoidoscopy every 3-5 years C: DRE, BE, routine colonoscopy

39. Screening for Ovarian Cancer • Prevalent • Serious Preclinical detectable period? • Treatable • Early treatment is better than late

40. Screening for Ovarian Cancer • transvaginal ultrasound has low yield • 5,678 volunteers age > 45 with a prior history of breast or gyn malignancy screened with TVUS • 2 stage I ovarian cancers were were found • screening 100,000 women would produce • 40 ovarian cancers • 5,398 false positives • 160 complications of laparoscopy

41. Screening for Ovarian Cancer • Serum tumor markers (CA-125, NB/70K, TAG 72.3, CA 15-3) have limited specificity • screening studies have not yet been done in asymptomatic women

42. Screening for Ovarian Cancer D: routine screening with ultrasound or serum tumor markers is not recommended C: there is insufficient evidence to recommend for or against screening women at increased risk

43. Screening for Breast Cancer • Prevalent • Serious • Preclinical detectable period • Treatable • Early treatment is better than late

44. Screening for Breast Cancer • Self breast exam (SBE) • Clinical breast exam (CBE) • Mammography

45. Screening for Breast Cancer • Self breast exam • widely taught • has benefits other than screening (education, empowerment) • evidence to support its use is weak • poor sensitivity and specificity • interim results from a very large RCT in China (267,040 women) show no difference in number, stage or size of breast cancers diagnosed or in mortality (after 5 years of follow-up)

46. Screening for Breast Cancer • Clinical breast exam • higher sensitivity than SBE (87% detection rate for masses > 1 cm using a standardized model) • in randomized studies of breast cancer screening, a small percentage of cancers not seen by mammography are detected by CBE • mammography provides a substantial advantage over CBE alone

47. Screening for Breast Cancer • Mammography • multiple trials in women aged 50-74 demonstrate a significant reduction in age-adjusted mortality with periodic mammography and all public health organizations support this strategy • data suggest but do not prove a benefit to more frequent mammography (every 12-18 months vs. every 24 months)

48. Screening for Breast Cancer • Mammography - when to start? • 1993 NCI “there is insufficient evidence to make an informed decision regarding efficacy of screening as measured by reduction in breast cancer mortality in women aged 40-49 years.” • 1/97 NIH Consensus Development Conference “the data currently available do not warrant a universal recommendation for mammography for all women in their forties…”

49. Screening for Breast Cancer • There have been 8 randomized controlled trials of screening mammography • none were designed to answer this question • meta-analyses show no reduction in mortality in women 40-49 after 7-9 years of follow-up • would there be a mortality benefit after 10-15 years of follow-up? (remember, then the women would be in their 50s and 60s and would be screened anyway)

50. Screening for Breast Cancer • Kerlikowske et al. JAMA 1995 meta-analysis of 13 studies (the 8 RCTs and 5 case-control studies) RR for breast cancer mortality women 50-74 0.74 (0.66 - 0.83) women 40-49 0.93 (0.76 - 1.13) 7-9 years of follow-up 1.02 (0.82 - 1.27) 10-12 years 0.83 (0.65 - 1.06)