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

Scand J Clin Lab Invest. 1991 Apr;51(2):143-8. doi: 10.1080/00365519109091100.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • False Positive Reactions
  • Ferritins / blood
  • Hemochromatosis / diagnosis
  • Hemochromatosis / epidemiology
  • Hemochromatosis / prevention & control*
  • Homozygote
  • Humans
  • Iron / blood
  • Male
  • Mass Screening / standards*
  • Transferrin / metabolism

Substances

  • Transferrin
  • Ferritins
  • Iron