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Background: Reference intervals are essential to interpret diagnostic tests,but their determination has become controversial. Methods: In this paperparametric, non-parametric and robust reference intervals with Tukey and blockelimination are calculated from a dataset of over 32,000 serum immunoglobulin A(IgA) measurements. Results: The outlier elimination method was significantlymore determinative of the reference intervals than the calculation method. TheTukey elimination procedure consistently eliminated significantly more valuesthan the block method of Dixon and Reed across all age ranges. If Tukeyelimination was applied, variation between reference intervals produced by thedifferent calculation methods was minimal. Block elimination rarely eliminatedvalues. The non-parametric reference intervals were more sensitive to outliers,which in the IgA context, led to higher and wider reference intervals for theolder age groups. There were only minimal differences between robust andparametric reference intervals. Conclusions: This suggests that Tukeyelimination should be preferred over the block D/R method for datasets similarto the one used in this study. These are predominantly new observations, asprevious literature has focused on the calculation technique and not discussedoutlier elimination. This suggests the robust method is not advantageous overthe parametric method and therefore due to its complexity is not particularlyuseful, contrary to CLSI Guidelines.

An Investigation into Outlier Elimination and Calculation Methods in the  Determination of Reference Intervals using Serum Immunoglobulin A as a Model  Data Collection