Equivalence limits of reference intervals for partitioning of population data. Relevant differences of reference limits

Reference limits need to be compared with each other for two main purposes: to evaluate the clinical relevance of a possible difference, if limits are obtained from the same population but at different time periods, or to check if limits derived from two different subpopulations can be considered as identical. The comparison of reference limits required for the periodic reviewing of applied reference limits and for checking the transferability of reference limits adopted from external sources according to international standards is an example for the first case. In the second case, a decision is intended whether the full population has to be partitioned (stratified) into the subpopulations under consideration (e.g. males and females). In both situations, differences may be due either to analytical errors, to biological differences or to both effects. The difference between reference limits may be acceptable if it is within permissible limits. For establishing permissible limits, the concept of equivalence limits was adopted to assess the relevance of differences between two reference limits. The concept bases on the permissible uncertainty at a particular reference limit. The permissible uncertainty is quantified by the permissible analytical standard deviation derived from the empirical biological variation as recently proposed. It is defined separately for lower and upper reference limits. The concept proposed can be condensed to simple equations.