What is Screening? Basic Public Health Concepts Sheila West, Ph.D. El Maghraby Professor of Ophthalmology Wilmer Eye Institute Johns Hopkins University

SCREENING: DEFINITION “The PRESUMPTIVE identification of UNRECOGNIZED disease or defect by the application of tests, exams or other procedures which can be applied RAPIDLY to sort out apparently well persons who PROBABLY have a disease from those who PROBABLY do not”* Key Elements: disease/disorder/defect screening test population Screening tests are not intended to be diagnostic. It is a public health approach to disease control by identification at an early stage of those affected *Commission on Chronic Illness, 1957

Disease Issues in Screening -Disease/disorder should be an important public health problem High prevalence Serious outcome -Early Detection in asymptomatic (pre-clinical) individuals is possible -Early detection and treatment can affect the course of disease (or affect the public health problem?) Example of arguemnts around screening for early HIV in persons, , settled on screening in blood.

Screening Test Concerned with a Functional Definition of Normality versus Abnormality Screening Test What is a normal value on a lab test, how do healthy persons or those not at risk of disease of interest score on the test? Identification of normal” values is not straightforward. Sometimes lab values are not normally distributed, so statistical approach is not correct; simple classification of normal and abnormal may oversimplify a complex situation. Abnormal Normal

Criteria for Evaluating a Screening Test Validity: provide a good indication of who does and does not have disease -Sensitivity of the test -Specificity of the test Reliability: (precision): gives consistent results when given to same person under the same conditions Yield: Amount of disease detected in the population, relative to the effort -Prevalence of disease/predictive value

Validity of Screening Test (Accuracy) - Sensitivity: Is the test detecting true cases of disease? (Ideal is 100%: 100% of cases are detected) -Specificity: Is the test excluding those without disease? (Ideal is 100%: 100% of non-cases are negative)

(Talk about sensitivity, specificity, false positives, false negatives) No question that IOP is a RISK FACTOR for glaucoma, but its use as a screening tool is terrible-a level of 22 mg misses 50% of glaucoma cases, and incorrectly labels a high percentage of persons in population as having glaucoma.

Sensitivity = 50% (50/100) False Negative=50% Screening for Glaucoma using IOP True Cases of Glaucoma Yes No IOP > 22: Yes 50 100 No 50 1900 (total) 100 2000 Sensitivity = 50% (50/100) False Negative=50% Specificity = 95% (1900/2000) False Positive=5%

Where do we set the cut-off for a screening test? 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 Extent that distributions overlap between normals and abnormals, minimizing error will be hard. For complex disorders with multiple causes, one test alone for just one cause may be woefully insufficient.

Inter-Observer Agreement in Grading Severity of Cataract Reliability (reproducibility) Agreement within and between examiners ________________________________________________ Inter-Observer Agreement in Grading Severity of Cataract Examiner 1: Grade Examiner <1 1-<2 2-<3 3-<4 4 2 <1 10 2 1 0 0 1-<2 1 20 2 0 0 2-<3 0 1 20 1 0 3-<4 0 0 1 10 2 4 0 0 0 2 5 % Agreement = 81.3% Kappa = 0.76

Validity versus Reliability of Screening Test Examiner 1 Examiner 2 Examiner 3 Good Reliability Low Validity True cases

Yield from a Screening Test for Disease X Predictive Value Screening Test X X X X X X Positives Negatives

Yield from the Screening Test: Predictive Value Relationship between Sensitivity, Specificity, and Prevalence of Disease Prevalence is low, even a highly specific test will give large numbers of False Positives Predictive Value of a Positive Test (PPV): Likelihood that a person with a positive test has the disease Predictive Value of a Negative Test (NPV): Likelihood that a person with a negative test does not have the disease

Specificity = 95% (1900/2000) False Positive=5% Screening for Glaucoma using IOP True Cases of Glaucoma Yes No IOP > 22: Yes 50 100 No 50 1900 (total) 100 2000 Specificity = 95% (1900/2000) False Positive=5% Positive Predictive Value =33%

How Good does a Screening Test have to be? IT DEPENDS -Seriousness of disease, consequences of high false positivity rate: -Rapid HIV test should have >90% sensitivity, 99.9% specificity -Screen for nearsighted children proposes 80% sensitivity, >95% specificity -Pre-natal genetic questionnaire could be 99% sensitive, 80% specific

Principles for Screening Programs Condition should be an important health problem There should be a recognizable early or latent stage There should be an accepted treatment for persons with condition The screening test is valid, reliable, with acceptable yield The test should be acceptable to the population to be screened The cost of screening and case finding should be economically balanced in relation to medical care as a whole