CLSI-based transference of CALIPER pediatric reference intervals to Beckman Coulter AU biochemical assays
Introduction
Reference intervals serve as health-associated benchmarks with which a patient’s individual test results are compared and are essential for accurate interpretation of laboratory test results. The levels of many biomarkers may vary with age, sex, and ethnicity; thus, age- and sex-specific reference values are critical for the appropriate interpretation of test results. This is particularly important for the pediatric population, where the high rates of growth and development can alter the otherwise predicted levels of many analytes [1], [2], [3], [4], [5]. The use of adult reference intervals for the interpretation of pediatric test results, a common practice in many healthcare centers worldwide, is inappropriate, and represents a major source of post-analytical error that can lead to patient misdiagnoses and inappropriate treatment decisions [6], [7], [8], [9].
The lack of pediatric-specific reference intervals has remained a major problem in the pediatric setting due to the difficulty in collecting samples from healthy community children, particularly from young children and infants, where only a small blood volume can be obtained. In an effort to address this important evidence gap, the CALIPER (Canadian Laboratory Initiative on Pediatric Reference Intervals) project was established as a collaborative initiative between several pediatric centers across Canada [10], [11]. In 2006, the CALIPER project released the first pilot data describing pediatric reference intervals for several basic chemistry analytes [12]. Since then, CALIPER has produced a comprehensive database of pediatric reference intervals for many specialty immunoassay and chemistry analytes [1], [11], [13], [14], [15], [16], [17], [18], [19], [20], [21], and has effectively filled many of the previous gaps in pediatric reference intervals [10], [11]. A major caveat was that CALIPER reference intervals were established using the Abbott ARCHITECT assays, which limits the application of these reference intervals to pediatric centers that use Abbott analytical platforms.
Establishing new reference intervals is a complex, costly, and daunting task, involving recruitment and sample collection from a large number of healthy individuals. As a result, the Clinical and Laboratory Standards Institute (CLSI) has issued guidelines on transferring reference intervals established in one laboratory (the “donor” laboratory) to other (“receiving”) laboratories [22]. This process involves transference and verification steps to ensure validity of the transferred reference intervals. First, transference of reference intervals can only occur if (1) there is a good correlation between methods used in “donor” and “receiving” laboratories and (2) the results produced by both methods are normally distributed [23]. If these criteria are met, a mathematical equation that governs the relationship between the results produced by both platforms is determined, and this equation is used to convert the original reference intervals into transferred reference intervals that can be applied to the platform in the receiving laboratory [22]. Next, the receiving laboratory must verify the transferred reference intervals using specimens from a small number of reference individuals recruited from a healthy population.
We have previously adopted this approach to transfer reference intervals from the Abbott ARCHITECT analyzer to a multitude of assays on four other commonly used clinical chemistry analyzers [24]. There is, however, still a need to transfer reference intervals to additional systems that are commonly used in major pediatric hospitals across Canada, and worldwide. Here, in order to broaden the utility of the CALIPER reference interval database [1], we report transference of pediatric reference intervals to the widely used Beckman Coulter AU assays, which will further enhance the global utility of the CALIPER database.
Section snippets
Method comparison
The present study was approved by the Institutional Review Board (IRB) at the Hospital for Sick Children (Toronto, Canada) and the review boards of collaborating hospitals. Approximately 200 pediatric pooled patient serum specimens (The Hospital for Sick Children, Toronto, Ontario) were analyzed on the Abbott ARCHITECT c8000 (at Eastern Health Authority, St. John's, Newfoundland) and the Beckman Coulter AU Systems (at Beckman Coulter, Brea, California). Samples represented a wide range of
Results
First, correlation between assays on the two platforms was carefully assessed using 200 pediatric serum samples. The results from 32 Abbott ARCHITECT assays were correlated with 60 corresponding assays on the Beckman Coulter AU system, where Beckman Coulter offered more than one assay for the majority of the tested analytes, with the exception of apolipoprotein B (APOB), anti-streptolysin O (ASO), complement C3 (C3), complement C4 (C4), C-reactive protein-high sensitivity (CRPHS), haptoglobin
Discussion
Establishing new reference intervals is particularly challenging for pediatric populations where sample collection is technically difficult and the need to obtain parental consent poses additional obstacles. The CALIPER program has recruited a large population of healthy children and adolescents and established a new database of pediatric reference intervals for laboratory biomarkers using Abbott ARCHITECT assays. To broaden the application of CALIPER reference standards, we have initiated a
Acknowledgements
This study was supported by an operating grant from the CIHR (Canadian Institutes of Health Research) and Beckman Coulter, Inc. We thank all of the CALIPER participants and their families; this study would not have been possible without their participation. We also thank the CALIPER coordinators, and all of the CALIPER volunteers for their hard work in participant recruitment and sample collection. Lastly, we acknowledge Abbott and Beckman Coulter, for providing reagents, and Dr. Jack Zakowski
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