Using the likelihood ratio to evaluate allowable total error – an example with glycated hemoglobin (HbA1c)
-
Arne Åsberg
,
Sven Magnus Carlsen
Abstract
Background: Allowable total error is derived in many ways, often from data on biological variation in normal individuals. We present a new principle for evaluating allowable total error: What are the diagnostic consequences of allowable total errors in terms of errors in likelihood ratio (LR)? Glycated hemoglobin A1c in blood (HbA1c) in diagnosing diabetes mellitus is used as an example. Allowable total error for HbA1c is 3.0% derived from data on biological variation compared to 6.0% as defined by National Glycohemoglobin Standardization Program (NGSP).
Methods: We estimated a function for LR of HbA1c in diagnosing diabetes mellitus using logistic regression with a clinical database (n=572) where diabetes status was defined by WHO criteria. Then we estimated errors in LR that correspond to errors in the measurement of HbA1c.
Results: Measuring HbA1c 3% too low at HbA1c of 6.5 percentage points (the suggested diagnostic limit) gives a LR of 0.36 times the correct LR, while measuring HbA1c 3% too high gives a LR of 2.77 times the correct LR. The corresponding errors in LR for allowable total error of 6% are 0.13 and 7.69 times the correct LR, respectively.
Conclusions: These principles of evaluating allowable total error can be applied to any diagnostically used analyte where the distribution of the analyte’s concentration is known in patients with and without the disease in a clinically relevant population. In the example used, the allowable total error of 6% leads to very erroneous LRs, suggesting that the NGSP limits of ±6% are too liberal.
Acknowledgments
We thank Frode Width Gran for valuable assistance with data extraction.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Financial support: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2015 by De Gruyter
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Articles in the same Issue
- Frontmatter
- Editorial
- New trends in the long and puzzling history of HbA1c
- Review
- Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges
- Opinion Paper
- Possible role of fructosamine 3-kinase genotyping for the management of diabetic patients
- EFLM Original Article
- Compliance of blood sampling procedures with the CLSI H3-A6 guidelines: An observational study by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PRE)
- Genetics and Molecular Diagnostics
- Quantitative-fluorescent-PCR versus full karyotyping in prenatal diagnosis of common chromosome aneuploidies in southern Spain
- HIF1A and MIF as potential predictive mRNA biomarkers of pre-eclampsia: a longitudinal prospective study in high risk population
- General Clinical Chemistry and Laboratory Medicine
- Evidence of Crohn’s disease-related anti-glycoprotein 2 antibodies in patients with celiac disease
- Myocardial interleukin-6 in the setting of left ventricular mechanical assistance: relation with outcome and C-reactive protein
- Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing
- Automated immunoassays for the autoantibodies to carbamylated or citrullinated telopeptides of type I and II collagens
- Relevance of correction for drift and day-to-day variation in cystatin C measurement: a post-hoc analysis of the PREVEND cohort, with independent replication in the ESTHER cohort
- Laboratory utilization improvement through a computer-aided algorithm developed with general practitioners
- Quantitation of 1α,25-dihydroxyvitamin D by LC-MS/MS using solid-phase extraction and fixed-charge derivitization in comparison to immunoextraction
- Reference Values and Biological Variations
- Establishment of trimester-specific thyroid stimulating hormone and free thyroxine reference interval in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600
- Cancer Diagnostics
- Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas
- Influence of ABO type on global coagulation assay results: effect of coagulation factor VIII
- Diabetes
- Benchmarking by HbA1c in a national diabetes quality register – does measurement bias matter?
- Comparing HbA1c, fasting and 2-h plasma glucose for screening for abnormal glucose regulation in patients undergoing coronary angiography
- Erroneous HbA1c measurements in the presence of β-thalassemia and common Chinese hemoglobin variants
- Using the likelihood ratio to evaluate allowable total error – an example with glycated hemoglobin (HbA1c)
- Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography
- Analytical performances of the D-100TM hemoglobin testing system (Bio-Rad) for HbA1c assay
- Letters to the Editors
- Glycation rate of haemoglobins S, C, D, E, J and G, and analytical interference on the measurement of HbA1c with affinity chromatography and capillary electrophoresis
- Hemoglobin Valme HBB:c.124T>G: a new hemoglobin variant with diminished oxygen affinity causes interference in hemoglobin A1c measurement in an automated ion-exchange HPLC method
- Hemoglobin A1c reported in units and diagnostic cut-offs in relation to the international recommendations
- Hemoglobin measurements in samples containing hemoglobin-based oxygen carriers
- Serologic false-positive reactions for syphilis in children of allergic purpura
- Exploration of the pre-analytical stability of β-lactam antibiotics in plasma and blood – implications for therapeutic drug monitoring and pharmacokinetic studies
- Fungal contamination of hyaluronidase solution mimicking fungal joint infection: a preanalytical pitfall in synovial fluid analysis
- Stroke and inherited thrombophilia in a Tunisian girl with sickle cell anemia
- Faecal haemoglobin concentrations do vary across geography as well as with age and sex: ramifications for colorectal cancer screening
