A plea for intra-laboratory reference limits. Part 1. General considerations and concepts for determination

Area of Science:

• Clinical Laboratory Science
• Medical Diagnostics
• Quality Management Systems

Background:

• Accurate laboratory results depend on reliable reference limits for interpretation.
• Current quality management emphasizes the need for laboratories to verify and identify appropriate reference limits.
• Many laboratories neglect internal limit determination, relying on external sources with transference issues.

Purpose of the Study:

• To review methods for determining laboratory reference limits.
• To evaluate the diagnostic efficiency of different reference limit concepts.
• To discuss the challenges and future directions in establishing reliable reference limits.

Main Methods:

• Review of prospective and retrospective methods for reference limit determination.
• Evaluation of unimodal and polymodal concepts, with and without disease prevalence.
• Assessment of statistical approaches and their diagnostic sensitivity, specificity, and efficiency.

Main Results:

• The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) unimodal prospective approach is the current gold standard for harmonization.
• Harmonization is limited to analytes with achievable SI units and traceability.
• Newer retrospective concepts using laboratory information system data show promise for internal limit derivation.

Conclusions:

• Trueness-based standardization with IFCC reference limits offers the best basis for decision-making but faces traceability challenges.
• Significant research is needed for most laboratory medicine measurands.
• Retrospective methods using large datasets are a promising avenue for developing efficient, internal, population-based reference limits.