False positives of screening in large-scale population with low infection rate of an infectious diseasea： a modeling analysis

Abstract

ObjectiveTo explore the positive predictive value （PPV） and false positive （FP） number of screening test in mass testing when the prevalence of infection is low.MethodsAssuming a population of 20 million with the prevalence of disease infection ranging from 0.1% to 5.0%， PPV， true positive （TP） and FP numbers were calculated under different scenarios of combination of sensitivity （99.0%， 99.5%， and 100.0%） with specificity （97.0%， 97.5%， 98.0%， 98.5%， 99.0%， 99.5%， and 99.9%）.ResultsFor low infection prevalence （≤5.0%）， specificity has a greater impact on PPV than sensitivity； with the decrease of infection prevalence， the increase in PPV elevates when the specificity increases. When the infection prevalence is >1.0%， the closer the specificity is to 99.9%， the closer the PPV is to 100.0%. However， when the infection prevalence is <1.0%， the maximum PPV is only about 90.0%. When the infection rate is 0.1%， a screening test with more than 99.0% sensitivity could detect about 20 thousand TP cases in a population of 20 million. Additionally， the FP and PPV are estimated to be 599 thousand and 3.2% if the specificity is 97.0%， and 20 thousand and 50.0% if the specificity is 99.9%. When the infection rate is 1.0%， a screening test with ≥99.0% sensitivity and ≥97.0% specificity could detect about 0.198‒0.200 million TP cases； and the number of FP decreases from 594 thousand to 20 thousand when the specificity increases from 97.0% to 99.9%. When the infection rate is 5.0%， a screening test with ≥99.0% sensitivity and ≥97.0% specificity could detect about 0.99‒1.00 million TP cases； and the number of FP decreases from 570 thousand to 19 thousand when the specificity increases from 97.0% to 99.9%. When the infection prevalence is ≤5.0% in a total population of 20 million， there are about 20，000 FP cases even if the sensitivity and specificity reach the maximum values of 100.0% and 99.9%， respectively.ConclusionWhen the population is large and the infection prevalence is low， in addition to improving the specificity of the screening test in mass testing， the problem of a large number of false positives cannot be ignored.

Keywords

• screening test
• false positive
• positive predictive value
• sensitivity
• specificity
• infection prevalence