Unit 15: Screening

1. Unit 15: Screening

2. Unit 15 Learning Objectives: • Understand the role of screening in the secondary prevention of disease. • Recognize the characteristics of diseases appropriate for screening. • Understand the impact of implementing screening on prevalence and incidence of disease. • Calculate and interpret measures of the validity of a screening test: • --- Sensitivity • --- Specificity

3. Unit 15 Learning Objectives (cont.): • Understand the relationship between sensitivity and specificity. • Calculate and interpret measures of the performance (yield) of a screening test: • --- Predictive value positive (PV+) • --- Predictive value negative (PV-) • Understand factors that influence PV+ and PV- • Recognize issues and sources of bias in evaluating screening programs.

4. Epidemiology in Disease Control: Screening

5. Screening for Disease Control • Screening: The application of a disease-detection test to people who are as yet asymptomatic. • Purpose: To classify individuals with respect to their likelihood of having a particular disease. • Screening procedure itself does NOT formally diagnose illness.

6. Screening for Disease Control • Examination of asymptomatic people likely • Classification as unlikely ….. to have a disease

7. Screening for Disease Control • “Unlikely” referred to next screening cycle • “Likely” further testing for diagnosis yes no referred to next treatment screening cycle

8. Screening for Disease Control • Screening Objective: To lower morbidity and mortality of the disease in a population (control, rather than elimination of disease). • Screening provides access to the medical care system which is not an actual goal of screening, but is a benefit.

9. Screening for Disease Control • Screening is important because: • 1) Diagnostic and therapeutic advances are often slow, but screening may be a “direct solution” to modify history of a disease in a population. • 2) It provides a model for studying disease mechanisms and the natural history of a disease.

10. Screening for Disease Control Primary requirements for screening: 1) Early detection of disease leads to a more favorable prognosis due to early treatment, as compared to delayed treatment. 2) Pre-clinical disease left untreated typically progresses to clinically-evident disease (e.g. no spontaneous regression).

11. Screening for Disease Control Primary requirements for screening: 3) The disease should be serious (relates to cost effectiveness, ethics, and prognosis). 4) Prevalence of pre-clinical disease should be relatively high among those screened.

12. Diseases for which screening has been recommended • Cervical cancer • Breast cancer • Prostate cancer • Colon cancer • Diabetes • Hypertension

13. Screening for Disease Control “PRICES” OF SCREENING: 1) Financial - may be very costly if screening is spread out over an entire population. 2) Anxiety - Individuals may have to be screened more often. 3) Some morbidity occurs - both in terms of the initial screening procedure, and subsequent procedures. 4) Creation of “lead time” morbidity.

14. Natural History of Disease Age of Individual 20 30 40 45 50 55 60 Birth Exposure Cells Screened Symptom Death Neoplasia Exfoliate Diagnosis Diagnosis

15. Natural History of Disease Age of Individual 20 30 40 45 50 55 60 Birth Exposure Cells Screened Symptom Death Neoplasia Exfoliate Diagnosis Diagnosis Total Pre-Clinical Phase (TPCP) TPCP: Begins at the initiation of disease; ends when the disease is clinically manifested (25 years in this example)

16. Natural History of Disease Age of Individual 20 30 40 45 50 55 60 Birth Exposure Cells Screened Symptom Death Neoplasia Exfoliate Diagnosis Diagnosis Detectable Pre-Clinical Phase (DPCP) DPCP: Begins when screening test is able to detect disease; Ends when disease is clinically evident (10 years)

17. Impact of Screening on Epi Measures Prevalence of clinical disease (found by either symptoms or screening) Steady state Screening Time

18. Impact of Screening on Epi Measures Incidence of clinical disease Note incidence rises, and then drops sharply because the “pool at risk” is temporarily depleted Steady state Screening Time

19. Evaluating Screening Tests Characteristics of a screening test: • Validity – the extent to which the test distinguishes between persons with and without the disease: High validity requires: • High Sensitivity • High Specificity • Reliability (High) • Low cost, invasiveness, and discomfort • Performance (Yield)

20. Validity of Screening Tests True Disease Status Results of Screening Test - + a b + - c d a = true positive b = false positive c = false negative d = true negative

21. Validity of Screening Tests How good is the screening test compared with the confirmatory diagnostic test? • The test will actually classify a diseased person as likely to have the condition (“sensitivity”). • The test will actually classify a non-diseased person as unlikely to have the condition (“specificity”).

22. Validity of Screening Tests True Disease Status Results of Screening Test - + a b + - c d Sensitivity: The probability of testing positive if the disease is truly present Sensitivity = a / (a + c)

23. Validity of Screening Tests True Disease Status Results of Screening Test - + a b + - c d Specificity: The probability of screening negative if the disease is truly absent Specificity = d / (b + d)

24. Validity of Screening Tests Breast Cancer - + Physical Exam and Mammo- graphy 132 983 + - 63650 45 Sensitivity:a / (a + c) Sensitivity = Specificity: d / (b + d) Specificity =

25. Validity of Screening Tests Breast Cancer - + Physical Exam and Mammo- graphy 132 983 + - 63650 45 Sensitivity:a / (a + c) Sensitivity = 132 / (132 + 45) = 74.6% Specificity: d / (b + d) Specificity = 63650 / (983 + 63650) = 98.5%

26. Validity of Screening Tests Sensitivity:a / (a + c) Sensitivity = 132 / (132 + 45) = 74.6% Specificity: d / (b + d) Specificity = 63650 / (983 + 63650) = 98.5% Sensitivity: Screening by physical exam and mammography will identify 75% of all true breast cancer cases. Specificity: Screening by physical exam and mammography will correctly classify 98.5% of all non-breast cancer patients as being disease free.

27. Validity of Screening Tests SETTING THE CRITERION FOR POSITIVITY Bi-modal distribution Population Blood Sugar Question: What is the best cutpoint? (Depends on the price for a negative outcome)

28. Validity of Screening Tests RELATIONSHIP BETWEEN SENSITIVITY & SPECIFICITY: 1. Lowering the criterion of positivity results in increased sensitivity, but at the expense of decreased specificity. 2. Making the criterion of positivity more stringent increases the specificity, but at the expense of decreased sensitivity.

29. Validity of Screening Tests RELATIONSHIP BETWEEN SENSITIVITY & SPECIFICITY: 3. The goal is to have both high sensitivity and high specificity, but this is often not possible or feasible. 4. The decision for the cutpoint involves weighing the consequences of leaving cases undetected (false negatives) against erroneously classifying healthy persons as diseased (false positives).

30. Validity of Screening Tests RELATIONSHIP BETWEEN SENSITIVITY & SPECIFICITY: 5. In general, specificity must be at least 98%to be effective --- because misclassifying 2% of the population will create as many false positives as the sensitivity of the test will actually detect.

31. Validity of Screening Tests RELATIONSHIP BETWEEN SENSITIVITY & SPECIFICITY: 6. Sensitivity should be increased when the penalty associated with missing a case is high (e.g. minimize false negatives) --- when the disease can be spread --- when subsequent diagnostic evaluations are are associated with minimal cost and risk

32. Validity of Screening Tests RELATIONSHIP BETWEEN SENSITIVITY & SPECIFICITY: 7. Specificity should be increased when the costs or risks associated with further diagnostic techniques are substantial (minimize false positives – e.g. positive screen requires that a biopsy be performed).