Determining and verifying reference intervals in clinical laboratories

Based on the original recommendation of the Expert Panel on the Theory of Reference Values of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC-LM), updated guidelines were recently published under the auspices of the IFCC-LM and the Clinical and Laboratory Standards Institute (CLSI). This article summarises these new proposals: (1) defining more precisely the terminology, which is often confusing, noticeably concerning the terms of reference limits and decision limits; (2) showing the different steps for determining reference limits according to the original procedure and the conditions which should be respected and (3) proposing a simple methodology allowing to the Clinical Laboratories to satisfy the needs of the Regulation and Standards. The updated document proposes to verify if published reference limits are applicable to the Laboratory involved. Finally the strengths and limits of the revised recommendations (noticeably the selection of the reference population, the maintenance of the analytical quality, the choice of the statistical methodology, etc.) will be briefly discussed.