1. Screening of diseases Dr Zhian S Ramzi Screening 1 Dr. Zhian S Ramzi

2. Screening 2 Screening Definition: Presumptive identification of an unrecognized disease or defect by the application of tests, examinations, or other procedures. Classifies asymptomatic people as likely or unlikely to have a disease or defect. Usually not diagnostic. Dr. Zhian S Ramzi

3. Screening 3

4. Screening 4 Screening Purpose: Delay onset of symptomatic or clinical disease. Improve survival. Dr. Zhian S Ramzi

5. Screening 5 Screening Seems simple but is complex. There are hidden costs and risks. Screening can create morbidity and anxiety. Must be aware of biases. Dr. Zhian S Ramzi

6. Screening 6 Screening For screening to be successful you need a: –Suitable disease –Suitable test –Suitable screening program Dr. Zhian S Ramzi

7. Screening 7 Suitable Disease Has serious consequences Is progressive Disease treatment must be effective at an earlier stage Prevalence of the detectable pre-clinical phase must be high Examples of suitable diseases: breast cancer, cervical cancer, hypertension Dr. Zhian S Ramzi

8. Screening 8 Suitable Test Ideally, it's inexpensive, easy to administer, has minimal discomfort has high level of validity and reliability Valid Test: Does what it's supposed to do, that is, correctly classify people with pre-clinical disease as positive and people without pre- clinical disease as negative Dr. Zhian S Ramzi

9. Screening 9 Suitable Test Reliable Test: Gives you same results on repetition Validity is more important than reliability Dr. Zhian S Ramzi

10. Screening 10 Suitable Test Disease Status (Truth) Screening Test Result

11. Screening 11 Suitable Test Measures of test validity Sensitivity - enables you to pick up the cases of disease Sensitivity = a / a + c = those that test positive / all with disease Dr. Zhian S Ramzi

12. Screening 12 Suitable Test Specificity - enables you to pick out the no diseased people Specificity = d / b + d = those that test positive / all with disease Valid test has high sensitivity and specificity Dr. Zhian S Ramzi

13. Screening 13

14. Screening 14 Suitable Test Breast Cancer Screening Program - Heath Insurance Plan HIP) Women assigned to screening or usual care. Screening consisted of yearly mammogram and physical exam. Five years of follow ‑ up produced these results: Breast Cancer Screening Test Result

15. Screening 15 Suitable Test Sensitivity = 132/177 = 74.6% Specificity = 63,650/64,633 = 98.5% Interpretation: The screening was very good at picking out the women who did not have cancer (see specificity) but it missed 25% of the women who did have cancer (see sensitivity). Dr. Zhian S Ramzi

16. Screening 16 Suitable Test To measure sensitivity and specificity you can wait for disease to develop (as in this example) or you can measure the results of the screening test against the outcome of another screening or diagnostic test (the Gold Standard). Dr. Zhian S Ramzi

17. Screening 17 Suitable Test Criterion of Positivity ‑ test value at which the screening test outcome is considered positive Test Result Clearly Negative Grey Zone Clearly Positive -------------------------??????????????????--------------------- A B C Criterion of positivity affects sensitivity and specificity. Must trade off between the two. Dr. Zhian S Ramzi

18. True Disease Status Screening Test PositiveNegativeTotal Positive True Positives (TP) False Positives (FP) TP+FP Negative False Negatives (FN) True Negatives (TN) FN+TN Total TP+FNFP+TNTP+FP+FN+TN Outcomes of a Screening Test 18 Dr. Zhian S Ramzi

19. Screening 19 Suitable Test What are the sensitivity and specificity if A (or B or C) is used as the cutoff for a positive result? If criterion is low (Point A) then sensitivity is good but specificity suffers. If criterion is high (Point C) then specificity is good but sensitivity suffers. Decisions about criterion of positivity involves weighing the cost of false positives against the cost of false negatives. Dr. Zhian S Ramzi

20. Consider: -The impact of high number of false positives: anxiety, cost of further testing -Importance of not missing a case: seriousness of disease, likelihood of re-screening Where do we set the cut-off for a screening test? Screening 20

21. Screening 21 Suitable Screening Program Definition of a screening program: Application of a specific test in a specific population for a specific disease You want to determine if screening program is successful. Does it reduce morbidity and mortality? How to evaluate? –Feasibility Measures –Effectiveness Measures Dr. Zhian S Ramzi

22. Evaluation of Screening Program Feasibility Measures Acceptability, cost, predictive value of a positive test (PV+), predictive value of a negative test (PV-) Screening 22

23. Screening 23 Evaluation of Screening Program Dr. Zhian S Ramzi

24. Evaluation of Screening Program Breast Cancer Screening Program of HIP Breast Cancer Screening Test PV+ = 132/1115 = 11.8% PV- = 63,650/63,695 = 99.9% Screening 24

25. Screening 25 Evaluation of Screening Program PV will increase when sensitivity, specificity, and disease prevalence increases. For example, PV+ will increase if you perform breast cancer screening on higher risk population (i.e. women with a family history of breast cancer) Dr. Zhian S Ramzi

26. Screening 26 Demonstration of how prevalence effects PV Use screening test with 99.9% sensitivity and 99.9% specificity in two populations: Population A: 1,000 people with low prevalence of disease (1/1,000) Two positive results. One will be true positive. One will be a test error. PV+ is 50% Dr. Zhian S Ramzi

27. Screening 27 Demonstration of how prevalence effects PV Use screening test with 99.9% sensitivity and 99.9% specificity in two populations: Population B: 1,000 people with high prevalence of disease (10/1,000) Eleven positive test results. 10 will be true positives. One will be a test error. PV+ is 10/11 or 90.9% Dr. Zhian S Ramzi

28. Screening 28 Evaluation of Screening Program Efficacy measures of evaluation Want to reduce morbidity and mortality For chronic diseases you can assess effectiveness by examining severity of disease at diagnosis, cause-specific mortality rate among people picked up by screening versus people picked up by routine care. Dr. Zhian S Ramzi

29. Screening 29 Summary of Screening Screening is the presumptive identification of unrecognized disease by the application of tests, exams, etc. Suitable disease must be serious with important consequences and progressive Dr. Zhian S Ramzi

30. Screening 30 Summary of Screening (cont’d) Suitable test must have low cost, be acceptable, and have a high degree of validity Validity is measured by sensitivity and specificity Dr. Zhian S Ramzi

31. Screening 31 Summary of Screening (cont’d) Screening programs administer screening tests in particular populations Programs are evaluated mainly by examining predictive value and outcome measures such as stage distribution and cause-specific mortality Evaluation must consider lead-time bias, length-biased sampling, and volunteer bias. Dr. Zhian S Ramzi

32. Screening 32 Dr. Zhian S Ramzi

33. Screening 33

34. Screening 34 Natural History of Disease Dr. Zhian S Ramzi

35. Screening 35 Natural History of Disease Total pre-clinical phase = A to C (Age 30 to Age 60) = 30 years Detectable pre-clinical phase (DPCP) = B to C (Age 45 to Age 60) = 15 years Dr. Zhian S Ramzi

36. Screening 36 Natural History of Disease DPCP varies with the test, the disease, and the individual Lead Time: Duration of time by which the diagnosis is advanced as a result of screening. B to C (Age 45 to Age 60) = 15 years Dr. Zhian S Ramzi