Reply.

Abstract

Potential conflict of interest: Nothing to report. Many thanks to Mauro Pantheghini and Ferruccio Ceriotti for raising important analytical issues regarding the standardization of laboratory tests. Measurements of serum enzymes are among the 20 most frequently ordered tests in clinical laboratories.1 Current participation reports for external quality assessment schemes (EQAS) show that the assays (Roche Diagnostics) used for our study2 are used widely in Germany and account for approximately 50% of EQAS participants for aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma‐glutamyltransferase (GGT). For our study, these assays were implemented on only one platform (cobas analyzer; Roche Diagnostics, Risch‐Rotkreuz, Switzerland), and no other assays or manufacturers were used. AST and ALT assays included the addition of pyridoxal‐5‐phosphate, as required for standardization by the International Federation of Clinical Chemistry and Laboratory Medicine. Analytical performance of all assays was evaluated in accordance with the current “Guidelines of the German Medical Association on Quality Assurance in Medical Laboratory Examinations” (Rili‐BÄK), which define the minimum requirements for internal and external quality assessment of quantitative measurements.3 The maximum allowable EQAS deviation is provided by Rili‐BÄK, and EQAS target values for ALT, AST, and GGT are reference method values.3 EQAS limits according to Rili‐BÄK were never violated during the entire study period. The root mean square of measurement deviations (RMSMDs, indicating imprecision and bias) always fulfilled the Rili‐BÄK requirements for internal quality assessment. Exemplary data (high/low control) from the middle of the study period, representative for the entire study period, showed interassay coefficients of variation (indicating imprecision) of 1.9%/2.2% (ALT), 1.7%/3.0% (AST) and 1.1%/2.3% (GGT), and RMSMDs of 2.7%/2.4% (ALT), 3.2%/4.6% (AST) and 2.6%/3.1% (GGT), respectively. Hence, we agree that measurements of enzyme concentrations should not ignore the type of method used, but we insist that our study fulfills the necessary standardization and quality assessment requirements. Furthermore, the focus of our work was not methodology, but to clarify the effects of sex, age, body mass index, and puberty on ALT, AST, and GGT enzyme levels.2 We completely agree that legislation shortcomings, manufacturing limitations, and lack of a proactive role of laboratory professionals to abandon nonstandardized assays are the most significant issues.1 Additionally, if laboratory professionals manage to sensitize clinicians to the clinical relevance of laboratory test standardization, clinicians themselves might become keener to ask for standardized assays as an inevitable requirement for optimal patient care and clinical guidelines.