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Measurement uncertainty as a tool for evaluating the ‘grey zone’ to reduce the false negatives in immunochemical screening of blood donors for infectious diseases

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Abstract

The risk of misclassifying infected individuals as healthy constitutes a crucial challenge when screening blood donors by means of immunoassays. This risk is especially challenging when the numerical results are close to the clinical decision level, i.e. in the ‘grey zone’. The concept of using measurement uncertainty for evaluating the ‘grey zone’ has previously not been systematically applied in this context. This article explains methods, models and empirical (top-down) approaches for the calculation of measurement uncertainty using results from a blood bank according to the internationally accepted GUM principles, focusing on uncertainty sources in the analytical phase. Of the different approaches available, the intralaboratory empirical approaches are emphasised since modelling (bottom-up) approaches are impracticable due to the lack of reliable model equations for immunoassays. Different methods are applied to estimate the measurement uncertainty for the Abbott Prism® HCV immunoassay. The expanded uncertainty obtained at the clinical decision level from the intralaboratory empirical approach was 36 %. The estimated uncertainty was used to set acceptance and rejection zones following the procedure set in the Eurachem guideline, emphasising the need to minimise the occurrence of false negatives.

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References

  1. White G (1998) Risk management in blood transfusion services. Vox Sang 74:105–109

    Article  Google Scholar 

  2. Soldan K, Barbara J, Ramsay M, Hall AJ (2003) Estimation of the risk of hepatitis B virus, hepatitis C virus and human immunodeficiency virus infectious donations entering the blood supply in England, 1993–2001. Vox Sang 84:274–286

    Article  CAS  Google Scholar 

  3. Pereira P, Westgard J, Encarnação P, Seghatchian G, Gracinda De Sousa (2015) Quality management in the European screening laboratories in blood establishments: a view on current approaches and trends. Transfus Apher Sci 52:245–251

    Article  Google Scholar 

  4. Pereira P, Westgard J, Encarnação P, Seghatchian G, Gracinda De Sousa (2015) The role of uncertainty in results of screening immunoassays in blood establishments. Transfus Apher Sci 52:252–255

    Article  Google Scholar 

  5. Williams E, Jarreau P, Zitzmann M, Pitocco C (2012) Transfusion-transmitted diseased. In: Harmening D (ed) Modern blood banking & transfusion practices, 6th edn. F.A. Davis, Philadelphia

    Google Scholar 

  6. Abbott Diagnostics Division (2008) Abbott Prism HCV, code: 84-5342/R9. Abbott Laboratories, Wiesbaden

    Google Scholar 

  7. Coste J, Jourdain P, Pouchot J (2006) A gray zone assigned to inconclusive results of quantitative diagnostic tests: application to the use of brain natriuretic peptide for diagnosis of heart failure in acute dyspneic patients. Clin Chem 52:2229–2235

    Article  CAS  Google Scholar 

  8. Kisner HJ (1998) The gray zone. Clin Lab Manage Rev 12:277–280

    CAS  Google Scholar 

  9. Ellison SLR, Williams A (2007) Use of uncertainty information in compliance assessment. 1st edn. Eurachem/CITAC

  10. Joint Committee for Guides in Metrology (2008) Evaluation of measurement data—guide to the expression of uncertainty in measurement. JCGM 100:2008, GUM 1995 with minor corrections. JCGM. http://www.bipm.org/utils/common/documents/jcgm/JCGM_100_2008_E.pdf. Accessed 24 May 2015

  11. Commission Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components. Official Journal of the European Union L33/30-40

  12. Commission Directive 2004/33/EC Implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components. Official Journal of the European Union L91/25-39

  13. Commission Directive 2005/61/EC Implementing Directive 2002/98/EC of the European Parliament and of the Council as regards traceability requirements and notification of serious adverse reactions and events. Official Journal of the European Union L256/32-40

  14. Commission Directive 2005/62/EC Implementing Directive 2002/98/EC of the European Parliament and of the Council as regards Community standards and specifications relating to a quality system for blood establishments. Official Journal of the European Union L256/41-48

  15. American Association of Blood Banks (2014) Standards for blood banks and transfusion services, 29th edn. AABB, Bethesda

    Google Scholar 

  16. Commission Directive 98/79/EC of the European Parliament and of the Council on in vitro diagnostic medical devices. Official Journal of the European Union L331/1-3712

  17. Clinical Laboratory Improvement Amendments (2015) CLIA law & regulations. http://wwwn.cdc.gov/clia/Regulatory/default.aspx. Accessed 24 May 2015

  18. ISO 15189 (2012) Medical laboratories—requirements for quality and competence, 2nd edn. International Organization for Standardization, Geneva

    Google Scholar 

  19. ISO/IEC 17025 (2005) General requirements for the competence of testing and calibration laboratories, 2nd edn. International Organization for Standardization, Geneva

    Google Scholar 

  20. EUROLAB (2007) Technical report no. 1/2007 measurement uncertainty revisited: alternative approaches to uncertainty evaluation. www.eurolab.org. Accessed 6 Sept 2015

  21. Khalil OS, Zurek TF, Tryba J, Hanna CF, Hollar R et al (1991) Abbott prism: a multichannel heterogeneous chemiluminescence immunoassay analyzer. Clin Chem 37:1540–1547

    CAS  Google Scholar 

  22. SYKE (2014) MUkit—measurement uncertainty kit. Finnish Environmental Institute. http://www.syke.fi/en-us/Services/Calibration_services_and_contract_laboratory/MUkit__Measurement_Uncertainty_Kit. Accessed 6 Sept 2015

  23. Magnusson B, Näykki T, Hovind H, Krysell M (2011) NordTest NT TR 537 handbook for calculation of measurement uncertainty in environmental laboratories, 3.1st edn. Nordic Innovation, Oslo

    Google Scholar 

  24. Justice T (1997) What is guard band? Solid State Technol 40:85–86

    Google Scholar 

  25. Abbott Diagnostics Division (2005) Abbott Prism positive run control kit HCV, code: 34-3827/R7. Abbott Laboratories, Wiesbaden

    Google Scholar 

  26. Hovind H, Magnusson B, Krysell M, Lund U, Mäkinen I (2011) NordTest NT TR 569 internal quality control—handbook for chemical laboratories (Trollboken—Troll book), 4th edn. Nordic Innovation, Oslo

    Google Scholar 

  27. Theodorsson E, Magnusson B, Leito I (2014) Bias in clinical chemistry. Bioanalysis 6:2855–2875

    Article  CAS  Google Scholar 

  28. Magnusson B, Ellison SLR (2008) Treatment of uncorrected measurement bias in uncertainty estimation for chemical measurements. Anal Bioanal Chem 390:201–213

    Article  CAS  Google Scholar 

  29. Ellison SLR, Williams A (2012) Quantifying uncertainty in analytical measurement, 3rd edn. Eurachem/CITAC

  30. ISO 11352 (2012) Water quality—estimation of measurement uncertainty based on validation and quality control data. International Organization for Standardization, Geneva

  31. ISO 5725–2 (1994) Accuracy (trueness and precision) of measurement methods and results—part 2: basic method for the determination of repeatability and reproducibility of a standard measurement method. International Organization for Standardization, Geneva

    Google Scholar 

  32. ISO 21748 (2010) Guidance for the use of repeatability, reproducibility and trueness estimates in measurement uncertainty estimation. International Organization for Standardization, Geneva

    Google Scholar 

  33. Thompson M, Ellison SLR (2011) Dark uncertainty. Accred Qual Assur 16:483–487

    Article  Google Scholar 

  34. Clinical and Laboratory Standards Institute (2014) EP15-A3 user verification of precision and estimation of bias: approved guideline, 3rd edn. CLSI, Wayne (PA)

    Google Scholar 

  35. Walker S, Dimech W, Kiely P, Smeh K, Francis B et al (2009) An international quality control programme for PRISM chemiluminescent immunoassays in blood service and blood product laboratories. Vox Sang 97:309–316

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Quality Assurance, Portuguese Institute of Blood and Transplantation, Avenida Miguel Bombarda 6, 1000-208, Lisbon, Portugal

    Paulo Pereira

  2. SP Technical Research Institute of Sweden, Borås, Sweden

    Bertil Magnusson

  3. Department of Clinical Chemistry and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

    Elvar Theodorsson

  4. Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, WI, USA

    James O. Westgard

  5. Católica Lisbon School of Business and Economics Research Unit, Catholic University of Portugal, Lisbon, Portugal

    Pedro Encarnação

Authors
  1. Paulo Pereira
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  2. Bertil Magnusson
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  3. Elvar Theodorsson
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  4. James O. Westgard
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  5. Pedro Encarnação
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Correspondence to Paulo Pereira.

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Pereira, P., Magnusson, B., Theodorsson, E. et al. Measurement uncertainty as a tool for evaluating the ‘grey zone’ to reduce the false negatives in immunochemical screening of blood donors for infectious diseases. Accred Qual Assur 21, 25–32 (2016). https://doi.org/10.1007/s00769-015-1180-x

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  • DOI: https://doi.org/10.1007/s00769-015-1180-x

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