Standardisation in clinical laboratory medicine: an ethical reflection

Many efforts have been undertaken to standardise diagnostic tests. For example, the introduction of CRM-470, an international reference preparation for proteins in human serum1 has reduced the among-laboratory variance of protein quantification. (The examples provided are from the field of Clinical Laboratory Immunology and Protein Chemistry.) The Dutch Red Cross Institute together with the World Health Organization (WHO) prepared an international standard for quantification of antibodies to double-stranded DNA. The International Union of Immunological Societies (IUIS), together with the American Arthritis Foundation and the Centers of Disease Control (CDC), made available reference sera selected by the International Committee on Autoantibody Testing in Rheumatic Diseases and Related Disorders for detecting anti-nuclear antibodies. These initiatives improved worldwide harmonisation of laboratory test results. However, despite efforts to harmonise laboratory tests, reference reagents are still lacking for many tests. For example, standardisation is unsatisfactory for IgG subclass determination. A number of promising new laboratory tests have recently become available, such as the determination of antibodies to (a) tissue transglutaminase, (b) Saccharomyces cerevisiae and (c) (cyclic) citrullinated peptides (CCP) and proteins (anti-citrullinated protein antibodies (ACPA)). These tests have been introduced without standardisation. Results obtained in different laboratories or in different clinical studies are not interchangeable, which impairs evidence-based medicine. In spite of this, there are encouraging initiatives, as more reference reagents are being prepared at this moment. A new reference reagent for anti-CCP antibody quantification is being prepared by the IUIS Autoantibody Standardization Committee. If the material is appropriate, it will become available as a standard through CDC. New reagents for standardisation of proteinase 3 anti-neutrophil cytoplasmic autoantibodies (ANCA) and myeloperoxidase ANCA have recently been made ready for use through CDC.