Managing biological variation data: modern approaches for study design and clinical application

Abstract

For more than one half-century, variability observed in clinical test result measurements has been ascribed to three major independent factors: (i) pre-analytical variation, occurring at sample collection and processing steps; (ii) analytical variation of the test method for which measurements are taken, and; (iii) biological variation (BV). Appreciation of this last source of variability is the major goal of this review article. Several recent advances have been made to generate, collate, and utilize BV data of biomarker tests within the clinical laboratory setting. Consideration of both prospective and retrospective study designs will be addressed. The prospective/direct study design will be described in accordance with recent recommendations discussed in the framework of a newly-developed system of checklist items. Potential value of retrospective/indirect study design, modeled on data mining from cohort studies or pathology laboratory information systems (LIS), offers an alternative approach to obtain BV estimates for clinical biomarkers. Moreover, updates to BV databases have made these data more current and widely accessible. Principal aims of this review are to provide the clinical laboratory scientist with a historical framework of BV concepts, to highlight useful applications of BV data within the clinical laboratory environment, and to discuss key terms and concepts related to statistical treatment of BV data.

Keywords:

• Biological variation
• checklist
• study design
• proficiency testing
• reference change value

Disclosure statement

No potential conflict of interest was reported by the author(s). The findings and conclusions in this paper have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy. Use of trade names and commercial sources is for identification only and does not constitute endorsement by the U.S. Department of Health and Human Services or the U.S. Centers for Disease Control and Prevention.