Screening for haemochromatosis: Influence of analytical imprecision, diagnostic limit and prevalence on test validity

P. Wiggers*, J. Dalhøj, P. Hyltoft Petersen, O. Blaabjerg, M. Hørder

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Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
BogserieScandinavian Journal of Clinical and Laboratory Investigation
Vol/bind51
Udgave nummer2
Sider (fra-til)143-148
Antal sider6
ISSN0036-5513
DOI
StatusUdgivet - 1. jan. 1991

Fingeraftryk

Hemochromatosis
Serum
Population
Iron

Citer dette

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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.",
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Screening for haemochromatosis : Influence of analytical imprecision, diagnostic limit and prevalence on test validity. / Wiggers, P.; Dalhøj, J.; Petersen, P. Hyltoft; Blaabjerg, O.; Hørder, M.

I: Scandinavian Journal of Clinical and Laboratory Investigation, Bind 51, Nr. 2, 01.01.1991, s. 143-148.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Screening for haemochromatosis

T2 - Influence of analytical imprecision, diagnostic limit and prevalence on test validity

AU - Wiggers, P.

AU - Dalhøj, J.

AU - Petersen, P. Hyltoft

AU - Blaabjerg, O.

AU - Hørder, M.

PY - 1991/1/1

Y1 - 1991/1/1

N2 - 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.

AB - 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.

KW - Diagnostic test

KW - Serum ferritin

KW - TIBC-sat

KW - Transferrin saturation

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JO - Scandinavian Journal of Clinical and Laboratory Investigation. Supplement

JF - Scandinavian Journal of Clinical and Laboratory Investigation. Supplement

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