Screening and Early Detection

1. Screening and Early Detection Epidemiological Basis for Disease Control – Fall 2001 Joel L. Weissfeld, M.D. M.P.H.

2. Objectives • Theoretical justification for disease control through early detection of disease. • Concepts and quantitative methods used to evaluate a screening test.

3. Definitions • Screening program -- comprehensive disease control activity based on the identification and treatment of persons with either unrecognized disease or unrecognized risk factors for disease. • Screening test -- specific technology (survey questionnaire, physical observation or measurement, laboratory test, radiological procedure, etc.) used to help identify persons with unrecognized disease or unrecognized risk factors for disease.

4. Definitions • Primary prevention -- disease control approach based on the elimination or reduction of risk factors for disease. Primary prevention aims to prevent the occurrence of disease. Primary prevention may use screening tests to identify persons with risk factors.

5. Definitions • Secondary prevention -- disease control approach based on the active identification and treatment of persons with unrecognized disease. Secondary prevention aims to prevent the occurrence of adverse outcomes from disease (such as fatal outcomes), without necessarily reducing the occurrence of disease. Secondary prevention must screen to identify persons with unrecognized disease.

6. Generalities • Screening often implies a public health related activity involving asymptomatic or healthy subjects coming from the general population. • Case-finding refers to special clinical efforts to recognize disease among persons who consult a health professional.

7. Two essential attributes of successful secondary prevention • Screening must accomplish early detection of disease. The screening program must detect disease in asymptomatic persons or in sympto-matic persons not recognized to have disease. Relative to background conditions, screening must identify affected persons at an earlier time point in the natural history of disease. • The act of early detection increases the effectiveness of treatments for the disease.

8. Evaluation framework used by US Preventive Services Task Force • Assess burden of suffering. • Assess properties of the screening test. • Determine the efficacy, effectiveness, and cost-effectiveness of early detection.

9. Important properties of a screening test • Screening is simple, inexpensive, and easily diffused through the population. • The act of screening is safe and acceptable. • The screening test is reliable. • The screening test is accurate.

10. Reliability • Kappa -- an appropriate reliability measure (or measure of agreement) for a screening test which gives a categor-ical result. • Intraclass correlation coefficient -- an appropriate reliability measure for a screening test, which gives a quantitative result.

11. Cohen’s Kappa Po = a + d = proportion observed agreement Pe = P1∙P2 + Q1∙Q2 = proportion expected agreement kappa = (Po - Pe)/(1 - Pe)

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13. Origin of the term • Screening implies a simple process, which classifies persons into one of two groups. • Members of the group with a positive (or abnormal) screening test result have disease with a probability high enough to justify diagnostic testing (for confirmation of disease presence) and/or medical therapies (for prevention of adverse outcomes from disease). • Members of the group with a negative (or normal) screening test result have disease with a probability too low to justify diagnostic testing (for confirmation of disease presence) and/or medical therapies (for prevention of adverse outcomes from disease).

14. Comparison of screening test results against gold standard • A screening test may produce only a categorical (positive or negative) result. Important concepts include disease prevalence, test sensitivity, test specificity, positive predictive value, negative predictive value, proportion test positive, proportion test negative, and disease yield.

15. Classification of screening test results against gold standard

16. Classification of screening test results against gold standard

17. Comparison of screening test results against gold standard • Sensitivity and specificity are said to be properties of the screening test. That is, sensitivity and specificity of a screening test may be relatively independent of the population being screened.

18. Comparison of screening test results against gold standard • For rare conditions, specificity has a major impact on positive prediction (Bayes Theorem). Despite a direct effect on yield, sensitivity has quantitatively less impact on positive prediction.

19. Deriving Bayes theorem Step 1: Specify the prevalence (P) of disease

20. Deriving Bayes theorem Step 2: Use sensitivity (Se) to distribute test results among the diseased

21. Deriving Bayes theorem Step 3: Use specificity (Sp) to distribute test results among the non-diseased

22. Deriving Bayes theorem Step 4: Determine the proportion testing positive and the proportion testing negative

23. Deriving Bayes theorem Step 5: Equate PPV and NPV with appro-priate expressions from Step 5

24. Comparison of screening test results against gold standard • A screening test may produce quantitative values. However, for decision-making purposes, a screening program must convert quantitative test results into two (or more) discrete categories. The screening program has a choice of different cutpoint(s), which may be used to categorize test results. In general, the choice of cutpoint(s) will affect values for sensitivity and specificity. Analysis of receiver operating characteristic (ROC) curves provides a graphical method for studying the effects of different cutpoints on the performance (sensitivity and specificity) of a screening test. ROC curve analysis also provides a method for comparing competing screening tests.

25. Net effects from screening • True negatives are exposed to the costs, inconvenience, and hazards of screening. True negatives may be reassured by knowledge of a negative screening test result. • False positives are exposed to the costs, inconvenience, and hazards of screening and follow-up diagnostic evaluations. The falsely positive screening test result may cause psychological and emotional distress.

26. Net effects from screening • False negatives are exposed to the costs, inconvenience, and hazards of screening. False negatives may be falsely reassured by knowledge of a negative screening test result. False negatives represent lost opportunities to prevent adverse outcomes from disease. • True positives are exposed to the costs, inconvenience, and hazards of screening, follow-up diagnostic evaluations, and therapeutic interventions. Only true positives have an opportunity to benefit from medical therapy.

28. Generalities • Specificity is often the major determinant of the costs and feasibility of a screening program. • Sensitivity establishes the maximum extent (upper bound) to which a screening program is capable of producing health benefit.