Trueness assessment of HbA1c routine assays: are processed EQA materials up to the job?

Background: With the worldwide increase of diabetes mellitus prevalence, ensuring that HbA(1c) assays are accurate is essential. External quality assessment (EQA) programs enable laboratories to verify that analytical methods perform according to the manufacturers' specifications. However, assessing trueness requires commutable materials, a property that is rarely characterized for EQA materials. Methods: The difference in bias approach was used to assess commutability of 26 processed quality control materials for 17 of the most frequently used HbA(1c) assays. Involved assays included immuno-assays, enzymatic assays, affinity, ion-exchange HPLC boronate affinity HPLC and capillary electrophoresis. The measurements were performed at manufacturers or expert laboratories. Assay trueness was additionally assessed against the IFCC reference measurement procedure using fresh clinical specimens that were distributed to 450 medical laboratories. Results: Commutability of processed EQA materials was highly heterogeneous and globally insufficient to rigorously assess the trueness of HbA(1c) assays. Using fresh clinical specimens, mean bias was -0.13 mmol/mol for low HbA(1c) (34 mmol/mol), between +1.0 and +1.3 mmol/mol for intermediate HbA(1c) (49 and 58 mmol/mol) and +1.2 mmol/mol for elevated HbA(1c) (90 mmol/mol). Conclusions: This study demonstrates that due to insufficient commutability, most processed EQA materials are unsuitable to assess trueness of HbA(1c) assays and agreement between the different assays. These materials can only provide information on comparability of individual laboratory results with its peers and on assay precision. Using fresh whole blood samples, this study additionally shows that most HbA(1c) assays are fairly accurate and meet the total allowable error quality target of 5 mmol/mol.