SCREENING OF DISEASES

INTRODUCTION
DEFINITION : The search for unrecognized disease or defect by means of rapidly applied tests, examinations or other procedures in apparently healthy individuals. The active search for disease among apparently healthy people fundamental concept.

Screening and diagnostic tests

1. Done on apparently healthy. 2. Applied to groups. 3. Results are arbitrary and final. Done on those with indication or sick. Applied to single patient. Diagnosis not final, but sum of all evidence.

4. Based on one Evaluation of criterion or cut symptoms, signs off point. and lab findings. 5. Less accurate and less expensive More accurate and more expensive.

6. Not a basis for Basis of treatment. treatment. 7. Initiative comes Initiative comes from from a patient. investigator

AIMS AND OBJECTIVES

To sort out from a large group of apparently healthy persons those likely to have the disease or at increased risk of the disease under study, to bring who are apparently abnormal under medical supervision and treatment.

USES OF SCREENING
Case detection presumptive identification unrecognized disease, which does arise from patients request. E.g. neonatal screening, bacteriuria in pregnancy, diabetes mellitus.

Control of disease people screened for benefit of others. E.g. screening of immigrants from infectious disease. Research purpose. Educational opportunities.

TYPES OF SCREENING
Mass screening. High risk or selective screening. Multiphasic screening.

CRITERIA FOR SCREENING DISEASE

Important health problem. Recognizable latent or early asymptomatic stage. Natural history of the condition should be known. Presence of a test that can detect the disease prior to onset of signs and symptoms.

Facilities should be available for confirmation of the diagnosis. Effective treatment. Agreed on policy concerning whom to treat as patients. Good evidence that early detection and treatment reduces morbidity and mortality. Benefits exceeds risks and costs.

CRITERIA FOR SCREENING TEST

Acceptability. Repeatability/ Reliability/ Precision/ Reproducibility. Validity (accuracy) Yield Simplicity, safety, rapidity, easy and cost.

Repeatability
Test must give consistent results when repeated more than once on same individual or material, under same conditions. Sometimes , called reliability, precision or reproducibility.

Depends on:
Observer variation : a) Intra observer variation. b) Inter observer variation. Biological (subject) variation : a) Changes in parameter observed. b) Variations in the way patients perceive their symptoms and answers.

Errors relating to technical methods. Yield : amount of previously unrecognized disease that is diagnosed as a result of screening effort. Depends on : sensitivity, specificity, prevalence and participation of individuals. calculated by : prevalence of disease / positive predictive value

Validity (accuracy)
To what extent the test accurately measures which it purports to measure. Expresses ability of test to separate or distinguish those who have the disease from who do not. Closeness with which measured values agree with true values.

Components of validity
Sensitivity : ability of test to identify correctly all those who have the disease i.e. true positive. Rest of the diseased wrongly classified as non diseased are said to be false negative.

 Specificity : ability of a test to identify correctly those who do not have the disease, i.e. true negatives. Rest of the non diseased people wrongly classified as diseased called false positive.

Predictive accuracy
Reflects diagnostic power of test. Depends upon sensitivity, specificity and disease prevalence. Predictive value of a positive test (PPV): probability that a patient with positive test has in fact, the disease in question. Predictive value of a negative test (NPV)

Screening test result Positive

Diagnosis Positive D+ Negative DTrue positive False (TP) (a) positive (FP) (b) False True negative negative (FN) (c) (TN) (d)

Negative

 Sensitivity : TP(a) x 100 TP(a) + FN(c) Specificity : TN(d) x 100 TN(d) +FP(b) PPV : TP(a) x 100 TP(a) + FP(b)

Prevalence 5% D+ T+ T25 (TP) (a) 25 (FN) (c) D95 (FP) (b) 855 (TN) (d) TOTAL 120 880

TOTAL 50

950

1000

 Sensitivity : 50% (25 / 25 + 25) x 100 Specificity : 90% (855 /855 + 95) x 100 PPV : 21% (25/ 25 + 95) x 100

Prevalence 15% D+ T+ T75 (TP) (a) 75 (FN) (c) D85 (FP) (b) 765 (TN) (d) 850 TOTAL 160

840

TOTAL 150

1000

 With constant sensitivity of 50% and specificity of 90% and prevalence 15% PPV : 47% Similarly, if prevalence increase to 25%, PPV will be 63%.

The problem of borderline

Sensitivity and specificity versus criterion value

ROC CURVES
Receiver operating characteristic curves. In a ROC curve the true positive rate (Sensitivity) is plotted in function of the false positive rate (1-Specificity) for different cut-off points.

 The dotted diagonal line corresponds to a test that is positive or negative just by chance. A test with perfect discrimination (no overlap in the two distributions) has a ROC plot that passes through the upper left corner (100% sensitivity, 100% specificity). Therefore the closer the ROC plot is to the upper left corner, the higher the overall accuracy of the test

Uses of ROC curves

For comparing two or more diagnostic tests. For selecting cut-off levels for a test.

Basis for cut off in screening

Disease prevalence highly prevalent - sensitivity The disease lethal sensitivity prevalent disease for which treatment does not markedly alter outcome eg diabetes specificity. PPV is useful index in making this decision.

Combining screening tests in series and parallel

Parallel testing two screening tests whether identical or different, are said to be applied in parallel if a positive result on either test is sufficient to prompt a diagnostic work up. For e.g. breast cancer screening frequently employs a combination of mammography and breast physical examination applied in parallel. If either is positive, further investigation is required.

 Series testing Two screening tests are said to be applied in series if both tests must be positive in order to prompt action. E.g. HIV screening generally employs a combination of ELISA and western blot test applied in series. If ELISA is repeatedly positive (i.e. in series) then a western blot test is done (i.e. series testing of ELISA and western blot) before making a decision that HIV antibody is present.

 The overall sensitivity called net sensitivity and overall specificity (net specificity) for the two tests can be calculated using probability concept.

(1)A correct, B incorrect.

(2) Both incorrect

(3) Both A and B correct

(4) A incorrect, B correct

 Combined sensitivity for A and B in series = sensitivity of A X sensitivity of B. Combined sensitivity for A and B in parallel = A correct (1+3) + B correct (3+4) both A and B correct (3). sensitivity of A + sensitivity of B (sensitivity of A X sensitivity of B).

 Hence, series testing decreases sensitivity and parallel testing increases sensitivity. For e.g. sensitivity of A = 90% sensitivity of B = 80% A and B combined in series = 72% A and B combined in parallel = 98%

 Combining specificities For A and B in parallel :-Specificity of A X specificity of B For A and B in series :specificity of A + specificity of B (specificity of A and specificity of B) So, series testing decreases specificity and parallel testing increases specificity.

Bias in screening tests

Arise when screen detected cases are compared with cases detected by signs and symptoms. Lead time bias : overestimation of survival duration among screen detected cases when survival is measured from diagnosis.

 Lenth time bias : Overestimation of survival duration among screendetected cases due to the relative excess of slowly progressing cases. These are disproportionally identified by screening because the probability of detection is directly proportional to the length of time during which they are detectable.

 Over diagnosis bias : Overestimation

of survival duration among screendetected cases due to the inclusion of pseudodisease - subclinical disease that would not become overt before the patient dies of other causes.

Evaluation of screening program

Randomized control trials. Uncontrolled trials. Other methods.

REFERENCES
Parks textbook of preventive and social medicine. Wikipedia.org.