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Not all biases are created equal: how to deal with bias on laboratory measurements

  • Mauro Panteghini ORCID logo EMAIL logo
Published/Copyright: November 26, 2024
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 5

Abstract

Although the concept of bias appears consolidated in laboratory science, some important changes in its definition and management have occurred since the introduction of metrological traceability theory in laboratory medicine. In the traceability era, medical laboratories should rely on manufacturers who must ensure traceability of their in vitro diagnostic medical devices (IVD-MD) to the highest available references, providing bias correction during the trueness transfer process to calibrators before they are marketed. However, sometimes some bias can be observed arising from an insufficient correction during the traceability implementation. This source of bias can be discovered by the IVD-MD surveillance by traceability-based external quality assessment and confirmed by ad-hoc validation experiments. The assessment of significance should be based on its impact on measurement uncertainty (MU) of results. The IVD manufacturer, appropriately warned, is responsible to take an immediate investigation and eventually fix the problem with a corrective action. Even if IVD-MD is correctly aligned in the validation steps and bias components are eliminated, during ordinary use the system may undergo systematic variations such as those caused by recalibrations and lot changes. These sources of randomly occurring bias are incorporated in the estimate of intermediate reproducibility of IVD-MD through internal quality control and can be tolerated until the estimated MU on clinical samples fulfils the predefined specifications. A readjustment of the IVD-MD by the end-user must be undertaken to try to correct the bias becoming significant. If the bias remains, the IVD manufacturer should be requested to rectify the problem.

Keywords: bias; measurement uncertainty; metrological traceability; analytical performance specifications; variance component analysis
Corresponding author: Mauro Panteghini, Department of Laboratory Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 9 Sklodowskiej-Curie Street, 85-094 Bydgoszcz, Torun, Poland, E-mail:

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: The author has accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The author states no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

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Received: 2024-10-16
Accepted: 2024-11-18
Published Online: 2024-11-26
Published in Print: 2025-04-28

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Are the benefits of External Quality Assessment (EQA) recognized beyond the echo chamber?
  4. Reviews
  5. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part I – EQA in general and EQA programs in particular
  6. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part II – EQA cycles
  7. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part III – EQA samples
  8. Behind the scenes of EQA–characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part IV – Benefits for participant laboratories
  9. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part V – Benefits for stakeholders other than participants
  10. Opinion Papers
  11. Not all biases are created equal: how to deal with bias on laboratory measurements
  12. Krebs von den Lungen-6 (KL-6) as a diagnostic and prognostic biomarker for non-neoplastic lung diseases
  13. General Clinical Chemistry and Laboratory Medicine
  14. Evaluation of performance in preanalytical phase EQA: can laboratories mitigate common pitfalls?
  15. Point-of-care testing improves care timeliness in the emergency department. A multicenter randomized clinical trial (study POCTUR)
  16. The different serum albumin assays influence calcium status in haemodialysis patients: a comparative study against free calcium as a reference method
  17. Measurement of 1,25-dihydroxyvitamin D in serum by LC-MS/MS compared to immunoassay reveals inconsistent agreement in paediatric samples
  18. Knowledge among clinical personnel on the impact of hemolysis using blood gas analyzers
  19. Quality indicators for urine sample contamination: can squamous epithelial cells and bacteria count be used to identify properly collected samples?
  20. Reference Values and Biological Variations
  21. Biological variation of cardiac biomarkers in athletes during an entire sport season
  22. Increased specificity of the “GFAP/UCH-L1” mTBI rule-out test by age dependent cut-offs
  23. Cancer Diagnostics
  24. An untargeted metabolomics approach to evaluate enzymatically deconjugated steroids and intact steroid conjugates in urine as diagnostic biomarkers for adrenal tumors
  25. Cardiovascular Diseases
  26. Comparative evaluation of peptide vs. protein-based calibration for quantification of cardiac troponin I using ID-LC-MS/MS
  27. Infectious Diseases
  28. The potential role of leukocytes cell population data (CPD) for diagnosing sepsis in adult patients admitted to the intensive care unit
  29. Letters to the Editor
  30. Concentrations and agreement over 10 years with different assay versions and analyzers for troponin T and N-terminal pro-B-type natriuretic peptide
  31. Does blood tube filling influence the Athlete Biological Passport variables?
  32. Influence of data visualisations on laboratorians’ acceptance of method comparison studies
  33. An appeal for biological variation estimates in deep immunophenotyping
  34. Serum free light chains reference intervals for the Lebanese population
  35. Applying the likelihood ratio concept in external quality assessment for ANCA
  36. A promising new direct immunoassay for urinary free cortisol determination
https://doi.org/10.1515/cclm-2024-1208
Keywords for this article
bias; measurement uncertainty; metrological traceability; analytical performance specifications; variance component analysis

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Are the benefits of External Quality Assessment (EQA) recognized beyond the echo chamber?
  4. Reviews
  5. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part I – EQA in general and EQA programs in particular
  6. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part II – EQA cycles
  7. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part III – EQA samples
  8. Behind the scenes of EQA–characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part IV – Benefits for participant laboratories
  9. Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part V – Benefits for stakeholders other than participants
  10. Opinion Papers
  11. Not all biases are created equal: how to deal with bias on laboratory measurements
  12. Krebs von den Lungen-6 (KL-6) as a diagnostic and prognostic biomarker for non-neoplastic lung diseases
  13. General Clinical Chemistry and Laboratory Medicine
  14. Evaluation of performance in preanalytical phase EQA: can laboratories mitigate common pitfalls?
  15. Point-of-care testing improves care timeliness in the emergency department. A multicenter randomized clinical trial (study POCTUR)
  16. The different serum albumin assays influence calcium status in haemodialysis patients: a comparative study against free calcium as a reference method
  17. Measurement of 1,25-dihydroxyvitamin D in serum by LC-MS/MS compared to immunoassay reveals inconsistent agreement in paediatric samples
  18. Knowledge among clinical personnel on the impact of hemolysis using blood gas analyzers
  19. Quality indicators for urine sample contamination: can squamous epithelial cells and bacteria count be used to identify properly collected samples?
  20. Reference Values and Biological Variations
  21. Biological variation of cardiac biomarkers in athletes during an entire sport season
  22. Increased specificity of the “GFAP/UCH-L1” mTBI rule-out test by age dependent cut-offs
  23. Cancer Diagnostics
  24. An untargeted metabolomics approach to evaluate enzymatically deconjugated steroids and intact steroid conjugates in urine as diagnostic biomarkers for adrenal tumors
  25. Cardiovascular Diseases
  26. Comparative evaluation of peptide vs. protein-based calibration for quantification of cardiac troponin I using ID-LC-MS/MS
  27. Infectious Diseases
  28. The potential role of leukocytes cell population data (CPD) for diagnosing sepsis in adult patients admitted to the intensive care unit
  29. Letters to the Editor
  30. Concentrations and agreement over 10 years with different assay versions and analyzers for troponin T and N-terminal pro-B-type natriuretic peptide
  31. Does blood tube filling influence the Athlete Biological Passport variables?
  32. Influence of data visualisations on laboratorians’ acceptance of method comparison studies
  33. An appeal for biological variation estimates in deep immunophenotyping
  34. Serum free light chains reference intervals for the Lebanese population
  35. Applying the likelihood ratio concept in external quality assessment for ANCA
  36. A promising new direct immunoassay for urinary free cortisol determination
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