Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals across Populations and Testing Platforms

Mary Kathryn Bohn; Dana Bailey; Cynthia Balion; George Cembrowski; Christine Collier; Vincent De Guire; Victoria Higgins; Benjamin Jung; Zahraa Mohammed Ali; David Seccombe; Jennifer Taher; Albert K Y Tsui; Allison Venner; Khosrow Adeli

doi:10.1093/clinchem/hvad099

Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals across Populations and Testing Platforms

Clin Chem. 2023 Sep 1;69(9):991-1008. doi: 10.1093/clinchem/hvad099.

Authors

Mary Kathryn Bohn^{1

2}, Dana Bailey³, Cynthia Balion⁴, George Cembrowski⁵, Christine Collier⁶, Vincent De Guire⁷, Victoria Higgins⁸, Benjamin Jung^{1

2}, Zahraa Mohammed Ali⁹, David Seccombe¹⁰, Jennifer Taher^{2

11}, Albert K Y Tsui^{5

12}, Allison Venner^{12

13}, Khosrow Adeli^{1

2}

Affiliations

¹ Department of Clinical Biochemistry, Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
² Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
³ Dynacare, Brampton, ON, Canada.
⁴ Department of Pathology & Molecular Medicine, McMaster University, Hamilton, ON, Canada.
⁵ Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
⁶ Department of Laboratory Medicine, Fraser Health Authority, New Westminster, BC, Canada.
⁷ Department of Clinical Biochemistry, Hospital Maisonneuve-Rosemont, Montreal, QC, Canada.
⁸ DynaLIFE Medical Labs, Edmonton, AB, Canada.
⁹ Department of Laboratory Medicine, Scaraborough Health Network, Toronto, ON, Canada.
¹⁰ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
¹¹ Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.
¹² Alberta Precision Laboratories, Calgary, AB, Canada.
¹³ Department of Pathology & Laboratory Medicine, University of Calgary, Calgary, AB, Canada.

PMID: 37478022
DOI: 10.1093/clinchem/hvad099

Abstract

Background: Harmonization in laboratory medicine is essential for consistent and accurate clinical decision-making. There is significant and unwarranted variation in reference intervals (RIs) used by laboratories for assays with established analytical traceability. The Canadian Society of Clinical Chemists (CSCC) Working Group on Reference Interval Harmonization (hRI-WG) aims to establish harmonized RIs (hRIs) for laboratory tests and support implementation.

Methods: Harnessing the power of big data, laboratory results were collected across populations and testing platforms to derive common adult RIs for 16 biochemical markers. A novel comprehensive approach was established, including: (a) analysis of big data from community laboratories across Canada; (b) statistical evaluation of age, sex, and analytical differences; (c) derivation of hRIs using the refineR method; and (d) verification of proposed hRIs across 9 laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults.

Results: Harmonized RIs were calculated for all assays using the refineR method, except free thyroxine. Derived hRIs met proposed verification criterion across 9 laboratories and 5 manufacturers for alkaline phosphatase, albumin (bromocresol green), chloride, lactate dehydrogenase, magnesium, phosphate, potassium (serum), and total protein (serum). Further investigation is needed for some analytes due to failure to meet verification criteria in one or more laboratories (albumin [bromocresol purple], calcium, total carbon dioxide, total bilirubin, and sodium) or concern regarding excessively wide hRIs (alanine aminotransferase, creatinine, and thyroid stimulating hormone).

Conclusions: We report a novel data-driven approach for RI harmonization. Findings support feasibility of RI harmonization for several analytes; however, some presented challenges, highlighting limitations that need to be considered in harmonization and big data analytics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Albumins
Canada
Data Science*
Humans
Laboratories*
Reference Values

Substances

Albumins