Principles of Screening

A successful screening test should be inexpensive, safe, easy to perform, well accepted by consumers and providers, sensitive (identify persons with the disease in question), and specific (exclude persons lacking disease).

Screening for colorectal cancer and precancerous polyps must be carried out with knowledge of the costs, benefits, risks, and limitations. For those who would actually order or perform any of the available tests, a basic understanding of technique is helpful as well.

Several epidemiologic principles should be borne in mind in considering the performance characteristics of commonly employed screening tests. Fecal occult blood testing (FOBT), the test most commonly used, provides a good framework for a brief discussion of factors that affect such important variables as sensitivity, specificity, and positive and negative predictive value.

Sensitivity is the ratio of persons with the disease having positive test results to all subjects with disease. The category of "all with disease" includes both those with positive test results and those with negative test results. The formula for sensitivity then is TP/(TP + FN), where TP = true positive and FN = false negative. From this it can be seen that the most critical factor in determining sensitivity is the rate of false negatives—that is, those persons with the disease in question whose disease is missed by the test. Conversely, specificity is the ratio of healthy (disease-free) subjects with a negative test result to the total persons without disease [TN/(TN + FP)], where TN = true negative and FP = false positive. Here, the factor adversely affecting specificity is the proportion of false positives. Other important performance characteristics of a test are positive predictive value [TP/(TP + FP)] and negative predictive value [TN/(TN + FN)]. Using FOBT to illustrate these, consider the effect of rehydrating FOBT slides. It has been shown that by increasing the positivity rate for FOBT from a range of 2% to 4% up to 6% to 10%, rehydration increases the rate of detection of colorectal cancers. Hence, rehydration improves the sensitivity of the test. However, because colonoscopy performed to follow up such positive test results often yields negative findings, a substantial rate of false posi-tivity is shown to exist for rehydrated slides, representing a compromise in positive predictive value. A trade-off thus exists, and the practitioner or policy-maker must decide, on the basis of other considerations, whether the rate of negative follow-up colonoscopies is an acceptable trade-off in relation to the improved test sensitivity. In fact, those who take into account all the costs and benefits generally conclude that rehydration is not worthwhile.

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