Laboratory reference intervals - history and modern approaches for improved utility.

Area of Science:

• Clinical Chemistry
• Laboratory Medicine
• Biomarker Analysis

Background:

• Current laboratory diagnostics predominantly rely on reference intervals for biomarker interpretation.
• This statistical decision theoretical approach dichotomizes results into 'normal' or 'abnormal'.
• This method overlooks critical factors influencing diagnostic accuracy and clinical utility.

Purpose of the Study:

• To critically evaluate the limitations of traditional reference intervals in laboratory diagnostics.
• To discuss the history, properties, advantages, and disadvantages of reference intervals.
• To explore and present alternative diagnostic strategies for biomarker interpretation.

Main Methods:

• Review of the historical development and statistical underpinnings of reference intervals.
• Analysis of the shortcomings of dichotomizing laboratory results.
• Examination of alternative statistical approaches for biomarker interpretation.

Main Results:

• Reference intervals fail to account for measurement uncertainty, biomarker concentration extremes, disease prevalence, and cost-benefit analyses of diagnostic errors.
• The dichotomous nature of reference limits can lead to misinterpretation and suboptimal clinical decisions.
• Alternative methods like standard scores, percentiles, and likelihood ratios offer more nuanced interpretations.

Conclusions:

• Traditional reference intervals are an oversimplified approach to laboratory diagnostics.
• Rethinking diagnostic strategies is crucial for improving the accuracy and utility of laboratory results.
• Adoption of advanced statistical methods can enhance biomarker interpretation and patient care.