A Comparison of Analytical Goals for Haemoglobin A_1c Assays Derived Using Different Strategies

Abstract

SUMMARY.Analytical goals for the performance characteristics of assays of haemaoglobin A,, (HbA,,) have been investigated using different assumptions for generation of estimates, these being based on strategies using data on biological variation and on the clinical use of results. The derived goals are highly dependent on the assumptions made. In general, in monitoring of patients (using results from the same laboratory), the analytical imprecision is the most demanding, whereas bias (inaccuracy) is the most important characteristic when strategies for several centres (laboratories) to achieve similar results are invoked. Goals for analytical quality should be given in a form in which both analytical imprecision and bias (or systematic error) are specified. When several goals are to be considered (for different relevant assumptions), the most demanding should be used.

Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference

“…Using this approach that includes summing of mutual exclusive terms, an overestimation of the permissible TE was demonstrated [30]. An alternative model, in which the maximum permissible bias and imprecision are interrelated and described in a curve and the permissible TE calculated from each point of the graph, has therefore to be considered to give a more realistic description of the permissible TE [31].…”

The use of error and uncertainty methods in the medical laboratory

“…With the transferability of reference intervals as starting point, the permissible bias and imprecision are calculated based on the premise that the reference interval limits will remain valid. Because of the inclusion of the biological variation in the model, the resulting relationship between maximum permissible bias and imprecision is curved (see Figure 2) where the related model of Larsen et al [32] is used.…”

“…It should be noted, however, that in the conventional model, this bias term is applied in the case of monitoring although this expression had been derived from a reference range model and only applies to diagnosis. As an alternative, a model based on a reference change value model was developed that is only based on CV I and not on CV G [32]. 3.…”

“…Biological variation, although not relevant when monitoring variation in control samples, is certainly relevant when dealing with patient samples [10]. Biological variation can be taken into account by including biological variation in the model transforming the relationship between imprecision and bias into a curve (see Figure 2 Larsen et al [32]). The consequence is that the value of pTAE is not a constant in this model for any combination of bias and imprecision (Figure 2).…”

Proposal for the modification of the conventional model for establishing performance specifications

“…A modified model for the calculation of quality specifications is presented. The validity of reference limits and reference change values are central to this model that is a modification of existing models (further called the "modified model") [8][9][10].…”