Assessment of analytical bias in ferritin assays and impact on functional reference limits

Choy, Kay Weng; Sezgin, Gorkem; Wijeratne, Nilika; Calleja, John; Liwayan, Rachelle; Rathnayake, Geetha; McFarlane, Robert M.; McNeil, Alan; Doery, James C.G.; Lu, Zhong X.; Markus, C.; Loh, Tze Ping

doi:10.1016/j.pathol.2021.06.123

Cited by 9 publications

(14 citation statements)

References 18 publications

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“…The bias between the two assays is also as high as 49%. This is consistent with findings from other similar studies comparing other ferritin assays although the degree of bias may be different [ 6 , 26 ]. This high level of bias provides a significant challenge for people interpreting results using the different assays.…”

Section: Discussionsupporting

confidence: 92%

“…assessed the analytical bias in ferritin assays and impact on functional reference limits among five widely used commercial ferritin assays in Australia [ 26 ]. They concluded that there remained significant biases among some of the commonly used commercial ferritin assays in Australia and that more studies were needed to assess if functional reference limits are a way to overcome method commutability issues [ 26 ]. They did not have patients with CKD in their sample, but their results aligned with our findings.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of two ferritin assay platforms to assess their level of agreement in measuring serum and plasma ferritin levels in patients with chronic kidney disease

et al. 2023

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Background Ferritin levels are used to make decisions on therapy of iron deficiency in patients with chronic kidney disease (CKD). Hyperferritinaemia, common among patients with CKD from the Northern Territory (NT) of Australia, makes use of ferritin levels as per clinical guidelines challenging. No gold standard assay exists for measuring ferritin levels. Significant variability between results from different assays creates challenges for clinical decision-making regarding iron therapy. In the NT, different laboratories use different methods. In 2018, Territory Pathology changed the assay from Abbott ARCHITECT i1000 (AA) to Ortho-Clinical Diagnostics Vitros 7600 (OCD). This was during the planning of the INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on haemodialysis (INFERR) clinical trial. The trial design was based on AA assay ferritin levels. We compared the two assays’ level of agreement in measuring ferritin levels in CKD patients. Methods Samples from INFERR clinical trial participants were analysed. Other samples from patients whose testing were completed the same day on OCD analyzers and run within 24 h on AA analyzers were added to ensure wide range of ferritin levels, adding statistical strength to the comparison. Ferritin levels from both assays were compared using Pearson’s correlation, Bland–Altman, Deming and Passing-Bablok regression analyses. Differences between sample types, plasma and serum were assessed. Results Sixty-eight and 111 (179) samples from different patients from Central Australia and Top End of Australia, respectively, were analyzed separately and in combination. The ferritin levels ranged from 3.1 µg/L to 3354 µg/L and 3 µg/L to 2170 µg/L for AA and OCD assays respectively. Using Bland–Altman, Deming and Passing-Bablok regression methods for comparison, ferritin results were consistently 36% to 44% higher with AA than OCD assays. The bias was up to 49%. AA ferritin results were the same in serum and plasma. However, OCD ferritin results were 5% higher in serum than plasma. Conclusions When making clinical decisions, using ferritin results from the same assay in patients with CKD is critical. If the assay is changed, it is essential to assess agreement between results from the new and old assays. Further studies to harmonize ferritin assays are required.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Comparison of two ferritin assay platforms to assess their level of agreement in measuring serum and plasma ferritin levels in patients with chronic kidney disease

et al. 2023

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“…When the authors examined the RIs quoted by the manufacturer, they found that many of them were taken from published literature. Another study examined ferritin assays from 5 different manufacturers (Beckman Coulter, Roche, Ortho, Siemens, and Abbott) and found significant method bias even though traceable standards had been implemented in an attempt to standardise methods [ 42 ]. Comparison of Beckman and Roche methods showed differences in results ranging from 31% to 57% at clinical decision points.…”

Section: Limitations Of the Standard Reference Intervalmentioning

confidence: 99%

The Role and Limitations of the Reference Interval Within Clinical Chemistry and Its Reliability for Disease Detection

Timbrell

2024

Br J Biomed Sci

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Reference intervals (RIs) are a range of values that are supplied alongside laboratory measurements for comparison to allow interpretation of this data. Historically, RIs were referred to as the normal range. However, the perception of what is normal can lead to confusion in clinicians and unnecessary emotional distress in patients. RIs can be acquired using several methods. Laboratories may quote published studies or derive their own using established direct or indirect methods. Alternatively, laboratories may verify RIs provided by assay manufacturers using in-house studies. RIs have several limitations that clinicians should be aware of. The statistical methodology associated with establishment of RIs means that approximately 5% of “disease free” individuals will fall outside the RI. Additionally, the higher the number of tests requested, the higher the probability that one will be abnormal, and repeat results in an individual may show regression to the mean. Completion of studies for establishment of RIs can be expensive, difficult, and time consuming. Method bias and differences in populations can greatly influence RIs and prevent them from being transferable between some laboratories. Differences in individual characteristics such as age, ethnicity, and sex can result in large variation in some analytes. Some patients, such as those whose gender differs from that which was presumed for them at birth, may require their own RIs. Alternatively, a decision will need to be made about which to use. Overall, the issue common to these factors lies within interpretation. As such, RIs can be improved with better training in their use, combined with a better understanding of influences that affect them, and more transparent communication from laboratories in how RIs were derived.

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“…Foy, et al [22] reported a 5% reduction in erythrocyte indices at serum ferritin concentrations of 10-25 μg/L based on data from 58,451 hospitalized adult patients, whereas Sezgin, et al [20] found a hematological plateau (where the erythrocyte value difference between subsequent correlated ferritin values becomes < 1) at a serum ferritin concentration of 10 μg/L. Choy, et al [38] found that analytical bias in ferritin measurement procedures between the Abbott and Siemens platforms did not significantly influence the functional reference limits. While more studies are required to confirm this result, the analytical bias in ferritin measurement found in this study significantly affects the application of clinical decision limits [38].…”

Section: Serum Ferritin and Hb Parameters In Iron-deficiency Anemiamentioning

confidence: 99%

“…Choy, et al . [ 38 ] found that analytical bias in ferritin measurement procedures between the Abbott and Siemens platforms did not significantly influence the functional reference limits. While more studies are required to confirm this result, the analytical bias in ferritin measurement found in this study significantly affects the application of clinical decision limits [ 38 ].…”

Section: Serum Ferritin and Hb Parameters In Iron-deficiency Anemiamentioning

confidence: 99%

Functional Reference Limits: Describing Physiological Relationships and Determination of Physiological Limits for Enhanced Interpretation of Laboratory Results

Chuah¹,

Lim

Tan

et al. 2023

Ann Lab Med

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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.

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Assessment of analytical bias in ferritin assays and impact on functional reference limits

Cited by 9 publications

References 18 publications

Comparison of two ferritin assay platforms to assess their level of agreement in measuring serum and plasma ferritin levels in patients with chronic kidney disease

Comparison of two ferritin assay platforms to assess their level of agreement in measuring serum and plasma ferritin levels in patients with chronic kidney disease

The Role and Limitations of the Reference Interval Within Clinical Chemistry and Its Reliability for Disease Detection

Functional Reference Limits: Describing Physiological Relationships and Determination of Physiological Limits for Enhanced Interpretation of Laboratory Results

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