## To the Editor:

The concept of measurement uncertainty (*u*), as laid down in the *Guide to the Expression of Uncertainty in Measurement* (GUM) (1), is gaining more and more importance in the field of laboratory medicine. This concept does not include bias in the calculation of *u*, but instead requires it to be reported separately. Many are dissatisfied with that approach and try to “fix” GUM by treating bias as a variance and propagating it as such(2). I contend that the calculation of *u* should adhere to the original GUM document. Assume that an analytical procedure with a CV_{A} of 10% and a bias of +10% is used for the measurement of a serum component, *x*, in a group of healthy individuals with a CV_{G} of 20% (CV_{G}, group biological variation, consisting of within- and between-individual biological variation). These values yield a distribution with a total CV (CV_{T}) of 22.4% [CV_{T} = √(CV_{G}^{2} + CV_{A}^{2})]. The test results are used to detect “hypo-*x*” and “hyper-*x*” values at particular clinical-decision limits. For simplification, let us assume that these limits are set at ±3 CV_{G}, which is equal to the mean of *x* ± 60%. Fig. 1⇓ shows the distributions of component *x* for the unbiased (solid line) and biased situations. The biased situation is presented as actually observed values (dashed line) and those predicted by the treatment of bias as variance [*u* = √(CV_{A}^{2} + bias^{2}) = 14.1%] (dotted line). When bias is treated as a variance, CV_{A} increases from 10% to 14.1%, and the distribution of values for component *x* becomes slightly broader [CV_{T} = √(CV_{G}^{2} + CV_{A}^{2} + bias^{2}) = 24.5%]. This choice slightly increases the number of hypo-*x and* hyper-*x* cases. In reality, however, the population is moved by the bias to the hyper-*x* side. Consequently, the number of hypo-*x* and hyper-*x* cases significantly decreases and increases, respectively. This example shows that the treatment of bias as variance leads to an erroneous prediction of the influence of test performance in clinical practice. Therefore, bias should not be included as a variance component in calculations of measurement uncertainty but should be reported separately.

## Acknowledgments

**Grant/Funding Support:** None declared.

**Financial Disclosures:** None declared.

- © 2008 The American Association for Clinical Chemistry