Reference Manual - IARC Screening Group

Screening Test Qualities and Their Interpretation• An independent assessment of the accuracy of the reference or goldstandard should be included as part of quality diagnostic test studies.• Statistical techniques can also be applied to assess the effect of usinga particular reference standard in a diagnostic test study.VERIFICATION OR WORKUP BIAS• This occurs when the results of the test being evaluated influence thedecision to perform the reference or gold standard test. When thishappens, the sampling fraction for subjects undergoing the referencetest to verify the presence or absence of disease is much greater fortest-positive than test-negative cases.• Valid test quality measures assume 100% of all subjects havereceived both the test under evaluation and the reference test. Whenonly a fraction of test-negative cases in fact receive the reference test,statistical extrapolation is possible but this also can yield biasedresults (especially if the selection of test-negative cases to receivesubsequent testing is anything but random).• Even with random selection of a sample of negatives to receivefurther testing, if the proportion of test-negatives is less than 50%,bias may still be introduced when statistically adjusting the data.• Significant bias of this sort usually results in overestimatedsensitivity and underestimated specificity rates.Spectrum ofDisease/ResearchSetting• This refers to the distribution of disease categories in the researchpopulation.• Sensitivity and specificity may differ across research studies if thespectrum of disease is substantially different. This is because the testmay function better at picking up more severe disease or vice versa.• For this reason, the accuracy of a test, as measured by all of the testqualities mentioned above, is likely to vary according to whether it isbeing used for screening or followup purposes (and whether followupis immediate as with adjunctive testing or whether followup is part ofroutine care).• The best design for establishing the accuracy of a new test is crosssectional(i.e., across a range of disease) with a population previouslyunscreened for the disease.• Test results are most valuable when the test is studied underconditions that most closely resemble clinical practice (i.e., theclinical conditions under which the test is most likely to be applied).Cervical Cancer Prevention Guidelines for Low-Resource Settings B-3