Evaluation of uncertainty of measurement in routine clinical chemistry--applications to determination of the substance concentration of calcium and glucose in serum.

We studied the uncertainty of measurement for the calcium and glucose (amount of) substance concentrations in serum. The evaluation follows a four-step procedure, which complies with the ISO document Guide to the Expression of Uncertainty in Measurement (GUM). The applications were chosen to represent commonly used measuring systems in medical laboratories. The uncertainty components are quantified using observations of the measuring system, and information from calibration certificates, instrument specifications and literature. The evaluation focuses on the measurement step but empirical terms are used to illustrate how the pre-analytical phase and patient-related issues can be accounted for. The software GUM Workbench was used to facilitate calculations and to visualize the importance of each uncertainty component. The combined standard uncertainties (u(c)) for the measurands were < or =2% including the pre-analytical uncertainty sources. The patient-related source is discussed in relation to clinician's diagnosis and decision-making. The evaluation, as carried out here for calcium and glucose substance concentration measurements, can easily be applied to many other measurands in clinical chemistry. This work emphasizes that the internal quality control can provide much of the information needed in the uncertainty evaluation, and that external quality assessment (EQA) schemes are important in the control of the uncertainty evaluated by the individual laboratories. Due to statistical and metrological limitations routine EQA schemes should themselves not be used as a means of uncertainty evaluation.