hRI Working Group Publications

Nov 2023
What progress has been made towards harmonizing reference intervals in Canada? Academy of Diagnostics & Laboratory Medicine – Scientific Short
Higgins V.
https://myadlm.org/science-and-research/scientific-shorts/2023/what-progress-has-been-made-towards-harmonizing-reference-intervals-in-canada
Harmonizing the total testing process in laboratory medicine is crucial for consistent patient care, yet reference intervals in the post-analytical phase remain highly variable across Canadian laboratories. A 2017 survey by the CSCC Reference Interval Harmonization Working Group (hRI-WG) found significant differences in reference intervals, even among labs using the same instruments, despite comparable test results. This variation is likely due to the inconsistent adoption of reference intervals from different sources rather than true analytical differences. To address this, the CSCC hRI-WG has taken an evidence-based, big data approach to establish harmonized reference intervals in Canada, similar to international initiatives like NORIP and AHRIP. In Phase I, the group assessed 16 analytes, recommending harmonized reference intervals for most, while acknowledging limitations for some. Local verification is advised before adoption, and the CSCC hRI-WG urges all Canadian labs to implement these standardized intervals to improve test result interpretation and patient care.
 
Sep 2023
Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals across Populations and Testing Platforms
Bohn MK, Bailey D, Balion C, Cembrowski G, Collier C, De Guire V, Higgins V, Jung B, Ali ZM, Seccombe D, Taher J, Tsui AKY, Venner A, Adeli K. 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. PMID: 37478022.
https://pubmed.ncbi.nlm.nih.gov/37478022/
This article is the first by the hRI working group to publish harmonized reference intervals for 16 analytes which were calculated from Canadian population data obtained from community laboratories across the country on multiple instrument platforms. The study established a novel comprehensive approach which included the statistical evaluation of age, sex, and analytical differences, the derivation of hRIs using the refine method and the direct verification of the proposed hRIs across 9 laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults.
 
Dec 2018
CSCC Working Group on Reference Interval Harmonization. Pediatric and adult reference interval harmonization in Canada: an update
Parker ML, Adeli K; CSCC Working Group on Reference Interval Harmonization. Pediatric and adult reference interval harmonization in Canada: an update. Clin Chem Lab Med. 2018 Dec 19;57(1):57-60. doi: 10.1515/cclm-2017-0965. PMID: 29303773.
https://pubmed.ncbi.nlm.nih.gov/29303773/
This short report identified 24 common biochemical markers in five test groups for the first round of harmonization in Canada: (1) Electrolytes: sodium, potassium, chloride, total carbon dioxide, magnesium; (2) Renal function markers: creatinine, calcium, phosphate; (3) Hepatic markers: ALT, ALP, albumin, total protein, total bilirubin, lactate dehydrogenase (LDH); (4) Endocrine markers: glucose, hemoglobin A1c (HbA1c), FT4, free triiodothyronine (FT3), thyroid stimulating hormone (TSH); and (5) Lipids: cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides, low density lipoprotein cholesterol (LDL-C, calculated), non-HDL-C (calculated). As well, the proposed Canadian approach to developing nation-wide harmonized intervals is described which includes both consensus and statistical analyses of community population data.
 
Nov 2017
CSCC Reference Interval Harmonization (hRI) Working Group. National Survey of Adult and Pediatric Reference Intervals in Clinical Laboratories across Canada: A Report of the CSCC Working Group on Reference Interval Harmonization
Adeli K, Higgins V, Seccombe D, Collier CP, Balion CM, Cembrowski G, Venner AA, Shaw J; CSCC Reference Interval Harmonization (hRI) Working Group. National Survey of Adult and Pediatric Reference Intervals in Clinical Laboratories across Canada: A Report of the CSCC Working Group on Reference Interval Harmonization. Clin Biochem. 2017 Nov;50(16-17):925-935. doi: 10.1016/j.clinbiochem.2017.06.006. Epub 2017 Jun 21. PMID: 28647526.
https://pubmed.ncbi.nlm.nih.gov/28647526/
This study presented data from a national survey conducted across 37 laboratories by the Reference Interval Harmonization (hRI) Working Group to evaluate the variation in adult and pediatric reference intervals used in clinical laboratories in Canada. Of the seven analytes included in the survey for the assessment of reference interval consistencies, ALT, ALP, and creatinine reference intervals showed the highest degree of variation. As well, a baseline assessment involving the direct measurement of six analytes in a reference sample across 40 clinical laboratories showed that observed variation in reference intervals across instruments cannot be explained by the bias between the results obtained on instruments by different manufacturers. Together, these findings showed a clear lack of reference interval harmonization across laboratories; wherein 92% of survey respondents across Canada either agreed or strongly agreed that there is a need for harmonized RIs and decision limits in clinical laboratories.
 
Nov 2017
What is the current state of reference intervals in Canada? A need for harmonization. Academy of Diagnostics & Laboratory Medicine – Scientific Short
Higgins V. What is the current state of reference intervals in Canada? A need for harmonization. Academy of Diagnostics & Laboratory Medicine – Scientific Short.
https://myadlm.org/science-and-research/scientific-shorts/2017/current-state-of-reference-intervals-in-canada
The Canadian Society of Clinical Chemists (CSCC) formed the Reference Interval Harmonization (hRI) Working Group in 2016 to standardize pediatric and adult reference intervals across Canada. A national survey revealed significant variation in reference intervals among laboratories, even those using the same instruments, with pediatric intervals showing greater discrepancies than adult ones. Analysis of commutable reference samples found that reference interval variation far exceeded analytical test result variation, suggesting that the inconsistencies were not due to true analytical differences. Similar issues have been observed internationally, likely due to outdated or improperly sourced reference intervals. To improve consistency in test result interpretation, various countries, including Canada, are working on harmonized reference intervals. The CSCC hRI Working Group aims to establish evidence-based reference intervals, enhancing laboratory practices and patient care.
 
Feb 2016
Opinion Paper: Deriving Harmonised Reference Intervals – Global Activities
Tate JR, Koerbin G, Adeli K. Opinion Paper: Deriving Harmonised Reference Intervals – Global Activities. EJIFCC. 2016 Feb 9;27(1):48-65. PMID: 27683506; PMCID: PMC4975217.
https://pubmed.ncbi.nlm.nih.gov/27683506/
This opinion paper argues for the adoption of common reference intervals specifically for general chemistry analytes. It describes the requirements and framework for the process of deriving harmonized reference intervals. Global reference interval studies including harmonization initiatives such as the CALIPER study and the Canadian Health Measures Survey (CHMS) were reviewed. A key table in this article shows adult reference intervals for chemistry analytes determined by direct RI studies or by consensus from over seven different countries and across multiple instrument platforms.