The Importance of Establishing Reference Intervals - is it still a Current Problem for Laboratory and Doctors?

Diagnostics utility of the obtained laboratory test results strictly depends on their possible interpretation in the context of distinguishing of both the health and disease state as well as the desired effects of therapeutic interventions. For this purpose, it is necessary to compare the obtained results to the reference intervals. Current recommendations obligate each laboratory to determine its own reference intervals for each of examined parameters. Many laboratories are unable to define and implement their own reference intervals because it is an expensive and time-consuming procedure when using a best known - direct method. This problem is particularly evident in hard-to-access populations, such as pediatric and geriatric. An alternative solution designed to determine reference intervals is using indirect methods, which are based on the results of studies performed for diagnostic purposes in outpatients and inpatients and archived in digital medical databases, which may be subjected to statistical analysis.

The search for peer-reviewed articles was conducted in PubMed and Scopus databases. Variations of terms: Biological Variation, Reference Interval, Clinical Decision Limits, Laboratory Information System, Medical Laboratory, Direct Method, Indirect Method were used with different combinations of logical operators to ensure exhaustive search results. The original and review publications and recommendations best suited to the presented topic were selected from among the results of searches based on the previous list of terms from the period 2001 - 2019.

This work presents and critically analyses the currently existing guidelines related to determining and applying reference intervals in medical diagnostic laboratories, as well as to identify both the associated problems and difficulties and perspectives concerning the ways of their establishment and implementation.

It is crucial to remember that interpretation of a laboratory test result is a process of comparison and it usefulness depends mainly on the adopted reference system or decision limits. The process of establishing reference intervals and decision limits is complex and the choice of appropriate method depends of the many biological and technical factors connected with populations and laboratory equipment differences. The knowledge of advantages and limitations of the reference interval and decision limits allows for significant enhancement of the accuracy in daily clinical practice.