Immunoassay Standardization: Is It Possible, Who Is Responsible, Who Is Capable?(Opinion) (Clinical Report‪)‬

Standardization in clinical chemistry aims at improving trueness, i.e., lack of bias, but it does not directly affect assay imprecision. Standardization is important because it facilitates clinical interpretation and comparison of results from various studies (1, 2). This is especially important with analytes used for screening, and this was one reason that cholesterol assays have been standardized in the US (3). Standardization of assays for prostate-specific antigen (PSA) is important for the same reason, and also because these assays are important for monitoring of disease progression in prostate cancer. Large differences in assay calibration lead to misinterpretations of the clinical course when different assays are used (4). Variation in assays for chorionic gonadotropin (CG) (5) cause similar problems when women with pregnancy-related disorders are monitored by determination of CG in serum (6). It is a testimony of the clinical importance of standardization that the preparation of standards for PSA was initiated and carried out by a urologist, Thomas Stamey from Stanford (7). Standardization is a fairly new concept in clinical chemistry. The notion of "comprehensive measurement systems" and various levels of reference methods evolved in the 1970s (1, 2) and was formulated by Tietz in 1979 (8). Pure standards, reference methods, and standard reference materials (SRMs) are now available for many of the most important analytes determined by conventional chemical methods, but immunoassay standardization is less well developed. Immunoassay standardization was extensively discussed at two meetings organized in 1990 and 1992 by the IFCC. At these, two standardization projects were initiated: the one for cortisol was intended to serve as a model for hapten immunoassays, the other project, for standardization of assays for CG, was intended to serve as a pilot study for protein immunoassays.