title: Screening for haemochromatosis: influence of analytical imprecision, diagnostic limit and prevalence on test validity.
abstract: Serum ferritin (S-ferritin) and the saturation of transferrin iron-binding capacity (TIBC-sat) were evaluated as screening procedures for idiopathic haemochromatosis in a non-diseased population. Special attention was paid to the influence of the analytical quality, but the effects of prevalence and discrimination limits were also considered. Changes in the analytical quality for S-ferritin and TIBC-sat used as single tests highly influenced the number of false test-positives. Increasing the coefficient of variation from 0.0 to 0.2 resulted in nearly a doubling of the number of false test-positives to be further investigated. Using even a high, yet achievable analytic quality with a low coefficient of variation of 0.056 and 0.059 for S-ferritin and TIBC-sat respectively, screening procedures had unacceptably high fractions of false test-positives and false test-negatives associated with any discrimination limit. If the prevalence of haemochromatosis is 0.003, the predictive value of a positive test result did not exceed 0.05, accepting a fraction of false test-negatives of 0.025. This was found to be too low for a screening test to be used in the general population. The combined use of S-ferritin and TIBC-sat resulted in higher performance with a sensitivity of 0.90, a specificity of 0.99 and a predictive value of a positive test result of 0.29 if a fraction of misclassification of 0.01 is accepted for each.
authors.affiliation: Department of Clinical Chemistry, Odense University Hospital, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Wiggers
authors.forename: J
authors.initials: J
authors.lastname: Dalhøj
authors.forename: P
authors.initials: P
authors.lastname: Hyltoft Petersen
authors.forename: O
authors.initials: O
authors.lastname: Blaabjerg
authors.forename: M
authors.initials: M
authors.lastname: Hørder
mesh_terms: D005189:False Positive Reactions; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008403:Mass Screening / Q000592:standards*; D014168:Transferrin / Q000378:metabolism
chemical_list: D014168:Transferrin; D005293:Ferritins; D007501:Iron