Functional Reference Limits: Describing Physiological Relationships and Determination of Physiological Limits for Enhanced Interpretation of Laboratory Results
Issued Date
2023-09-01
Resource Type
eISSN
22343814
Scopus ID
2-s2.0-85153434642
Pubmed ID
37080741
Journal Title
Annals of laboratory medicine
Volume
43
Issue
5
Start Page
408
End Page
417
Rights Holder(s)
SCOPUS
Bibliographic Citation
Annals of laboratory medicine Vol.43 No.5 (2023) , 408-417
Suggested Citation
Chuah T.Y., Lim C.Y., Tan R.Z., Pratumvinit B., Loh T.P., Vasikaran S., Markus C. Functional Reference Limits: Describing Physiological Relationships and Determination of Physiological Limits for Enhanced Interpretation of Laboratory Results. Annals of laboratory medicine Vol.43 No.5 (2023) , 408-417. 417. doi:10.3343/alm.2023.43.5.408 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/81589
Title
Functional Reference Limits: Describing Physiological Relationships and Determination of Physiological Limits for Enhanced Interpretation of Laboratory Results
Other Contributor(s)
Abstract
Functional reference limits describe key changes in the physiological relationship between a pair of physiologically related components. Statistically, this can be represented by a significant change in the curvature of a mathematical function or curve (e.g., an observed plateau). The point at which the statistical relationship changes significantly is the point of curvature inflection and can be mathematically modeled from the relationship between the interrelated biomarkers. Conceptually, they reside between reference intervals, which describe the statistical boundaries of a single biomarker within the reference population, and clinical decision limits that are often linked to the risk of morbidity or mortality and set as thresholds. Functional reference limits provide important physiological and pathophysiological insights that can aid laboratory result interpretation. Laboratory professionals are in a unique position to harness data from laboratory information systems to derive clinically relevant values. Increasing research on and reporting of functional reference limits in the literature will enhance their contribution to laboratory medicine and widen the evidence base used in clinical decision limits, which are currently almost exclusively contributed to by clinical trials. Their inclusion in laboratory reports will enhance the intellectual value of laboratory professionals in clinical care beyond the statistical boundaries of a healthy reference population and pave the way to them being considered in shaping clinical decision limits. This review provides an overview of the concepts related to functional reference limits, clinical examples of their use, and the impetus to include them in laboratory reports.