Performance specifications for sodium should not be based on biological variation

Oosterhuis W. P., COSKUN A., Sandberg S., Theodorsson E.

Clinica chimica acta; international journal of clinical chemistry, vol.540, pp.117221, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 540
  • Publication Date: 2023
  • Doi Number: 10.1016/j.cca.2023.117221
  • Journal Name: Clinica chimica acta; international journal of clinical chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.117221
  • Keywords: Analytical performance specification, Biological variation, Number of distinct categories, Sigma metric, Six Sigma, Total error
  • Istanbul University Affiliated: No


When increasing the quality in clinical laboratories by decreasing measurement uncertainty, reliable methods are needed not only to quantify the performance of measuring systems, but also to set goals for the performance. Sigma metrics used in medical laboratories for documenting and expressing levels of performance, are evidently totally dependent on the "total permissible error" used in the formulas. Although the conventional biological variation (BV) based model for calculation of the permissible (or allowable) total error is commonly used, it has been shown to be flawed. Alternative methods are proposed, mainly also based on the within-subject BV. Measurement uncertainty models might offer an alternative to total error models. Defining the limits for analytical quality still poses a challenge in both models. The aim of the present paper is to critically discuss current methods for establishing performance specifications by using the measurement of sodium concentrations in plasma or serum. Sodium can be measured with high accuracy but fails by far to meet conventional performance specifications based on BV. Since the use of sodium concentrations is well established for supporting clinical care, we question the concept that quality criteria for sodium and similar analytes that are under strict homeostatic control are best set by biology.