Principles of Epidemiology E Screening Principles of Epidemiology E

Principles Underlying Screening Programs Validity – the ability to predict who has the disease and who does not Sensitivity – the ability of a test to correctly identify those who have the disease A test with high sensitivity will have few false negatives Specificity – the ability of a test to correctly identify those who do not have the disease A test that has high specificity will have few false positives

Principles Underlying Screening Programs (cont.) An ideal screening test would be 100% sensitive and 100% specific – that is there would be no false positives and no false negatives In practice these are usually inversely related It is possible to vary the sensitivity and specificity by varying the level at which the test is considered positive

Calculating Measures of Validity True Diagnosis Test Result Disease No Disease Total a b a+b Positive Negative Sensitivity = a/(a+c); the probability of having a positive test if you are positive Specificity = d/(b+d); the probability of having a negative test if you are negative Positive Predictive Value = a/(a+b); the probability of having the disease if you test positive Negative Predictive Value = d/(c+d); the probability of not having the disease if you test negative Prevalence = (a+c)/(a+b+c+d) Accuracy (efficiency of test) = (a+d)/(a+b+c+d) c d c+d Total a+c b+d a+b+c+d

Note the Following Screening Relationships Specificity + false positive rate = 1 d/(b+d) + b/(b+d) = 1 If the specificity is increased, the false positive rate is decreased If the specificity is decreased, the false positive rate is increased Sensitivity + false negative rate = 1 a/(a+c) + c/(a+c) = 1 If the sensitivity is increased, the false negative rate is decreased If the sensitivity is decreased, the false negative rate is increased

Interrelationship Between Sensitivity and Specificity

Sensitivity and Specificity of a Blood Glucose Level Sensitivity and Specificity of a Blood Glucose Level of 110 mg/100 ml for Presumptive Determination of Diabetes Status Blood Glucose Level (mg/100 ml) Diabetics (Percent) Nondiabetics (Percent) All those with level over 110 mg/100 ml are classified as diabetics 92.9 (true positives) 51.6 (false positives) All those with level under 110 mg/100 ml are classified as nondiabetics 7.1 (false negatives) 48.4 (true negatives) 100.0 100.0

Adjusting Sensitivity and Specificity by Adjusting Cut Points

Which is Preferred: High Sensitivity or High Specificity? If you have a fatal disease with no treatment (such as for early cases of AIDS), optimize specificity If you are screening to prevent transmission of a preventable disease (such as screening for HIV in blood donors), optimize sensitivity

Remember…. Sensitivity and specificity are functions of the screening test If you use a given screening test on a low prevalence population, you will have a low positive predictive value and potentially many false positives

Principles Underlying Screening Programs Reliability – the ability of a test to give consistent results when performed more than once on the same individual under the same conditions Variation in the method due to variability of test chemicals or fluctuation in the item measured (e.g., diurnal variation in body temperature or in relation to meals) Standardize fluctuating variables Use standards in laboratory tests, run multiple samples whenever possible Observer variation Train observers Use more than one observer and have them check each other

Principles Underlying Screening Programs Yield – the amount of previously unrecognized disease that is diagnosed and brought to treatment as a result of the screening program Sensitivity You must detect a sufficient population of disease to be useful Prevalence of unrecognized disease Screen high risk populations Frequency of screening Screening on a one time basis does not allow for the natural history of the disease, differences in individual risk, or differences in onset Diseases have lead time Participation and follow-up Tests unacceptable to those targeted for screening will not be utilized

Conditions for Establishing Screening Programs The condition should be an important health problem There should be an accepted treatment for patients with recognized disease If there is no treatment, it is premature to institute screening Facilities for diagnosis and treatment should be available It is unethical to screen without providing possibilities for follow-up There should be a recognizable latent or early symptomatic stage If early detection does not improve survival, there is no benefit from screening

Conditions for Establishing Screening Programs (cont.) There should be a suitable test for examination, with sufficient sensitivity and specificity to be of use in identifying new cases The test should be acceptable to the population The natural history of the condition, including development from latent to declared disease, should be adequately understood There should be an agreed-upon policy concerning whom to treat as patients

Conditions for Establishing Screening Programs (cont.) The cost of case-finding should be economically balanced in relation to possible expenditure on medical care as a whole Case-finding should be in a continuing process and not a one-time project

Biases in Screening Referral Bias (volunteer bias) Length Bias Screening selectively identifies those with a long preclinical and clinical phase (i.e., those who would have a better prognosis regardless of the screening program)

Biases in Screening (cont.) Lead Time Bias The apparently better survival that is observed for those screened is not because these patients are actually living longer, but instead because diagnosis is being made at an earlier point in the natural history of the disease

Biases in Screening (cont.) Overdiagnosis Bias (a misclassification bias) Enthusiasm for a new screening program may result in a higher rate of false positives and give false impression of increased rates of diagnosis and detection Also, false positives would result in unrealistically favorable outcomes in persons thought to have the disease

Dis - Dis + Prv 5% Sn70% Sp80% 2250 1900 35o Test+ 7750 7600 150 Test - 10000 9500 500 Test 1 Dis - Dis + Prv 5% Sn90% Sp90% 505 190 315 Test+ 1745 1710 35 Test - 2250 1900 350 Test 2

Dis - Dis + Prv 20% Sn80% Sp60% 480 320 160 Test+ 520 40 Test - 1000 800 200 Test 1 Dis - Dis + Prv 20% Sn90% Sp90% 260 80 180 Test+ 740 720 20 Test - 1000 800 200 Test 2