Utilization of assay performance characteristics to estimate hemoglobin A1c result reliability

Area of Science:

• Clinical Chemistry
• Laboratory Medicine
• Diabetes Diagnostics

Background:

• Hemoglobin A1c (HbA1c) testing accuracy is vital for diabetes management.
• Allowable total error (TE(a)) goals necessitate minimal assay imprecision and bias.
• Effective quality control (QC) programs are essential for reliable HbA1c results.

Purpose of the Study:

• To compare the influence of TE(a) goals, QC practices, and assay performance on reporting unreliable HbA1c results.
• To evaluate six different HbA1c instruments across four academic medical centers.
• To determine the risk of unreliable results based on analytical performance.

Main Methods:

• Applied CLSI protocols EP-5 and EP-9 to assess imprecision and bias.
• Investigated six HbA1c platforms: Bio-Rad (Variant II Turbo, Variant II), Tosoh (G8), Sebia (Capillarys 2 Flex Piercing), Roche (COBAS Integra 800), and Siemens (DCA Vantage).
• Calculated patient-weighted sigma (σ) values and risk of unreliable results at 5%, 6%, and 7% TE(a) specifications.

Main Results:

• Observed a wide range of patient-weighted σ values, spanning 0.5 orders of magnitude at a 6% TE(a).
• While imprecision was consistently low (<3%), assay bias significantly affected σ values.
• Analytical performance alone resulted in nearly a 500-fold variation in estimates for reporting unreliable results.

Conclusions:

• Significant differences exist in the probability of reporting unreliable HbA1c results among NGSP-certified platforms.
• At a 6% TE(a), most platforms require maximum QC implementation, except for the Capillarys 2 Flex Piercing.
• Laboratory-specific risk assessments can guide QC strategies to mitigate unreliable HbA1c results.