Definitions and major prerequisites of direct and indirect approaches for estimating reference limits.

Reference intervals are established either by direct or indirect approaches. Whereas the definition of direct is well established, the definition of indirect is still a matter of debate. In this paper, a general definition that covers all indirect models presently in use is proposed.

Problems with estimating reference change values (critical differences).

The concept of reference change values (RCVs) for diagnosis and monitoring of diseases has become well established. Several models habe been developed, e. g.

The importance of correct stratifications when comparing directly and indirectly estimated reference intervals.

Objectives: There are generally two major reasons for the comparison of reference intervals (RIs): when externally determined RIs (from the literature or provided by a manufacturer) are compared with presently used intra-laboratory RIs and when indirectly estimated RIs are compared with directly established RIs. Discrepancies within these comparisons may occur for two reasons: 1. the pre-analytical and/or analytical conditions do not agree and/or 2.

A new indirect estimation of reference intervals: truncated minimum chi-square (TMC) approach.

All known direct and indirect approaches for the estimation of reference intervals (RIs) have difficulties in processing very skewed data with a high percentage of values at or below the detection limit. A new model for the indirect estimation of RIs is proposed, which can be applied even to extremely skewed data distributions with a relatively high percentage of data at or below the detection limit. Furthermore, it fits better to some simulated data files than other indirect methods.

Next-generation reference intervals for pediatric hematology.

Background Interpreting hematology analytes in children is challenging due to the extensive changes in hematopoiesis that accompany physiological development and lead to pronounced sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, and limitations in current approaches to laboratory test result displays restrict their use when guiding clinical decisions.