Establishment of Critical Difference for Diagnostic Immunoassays

Abstract

Background: Critical difference (CD) is a significant difference between sequential laboratory results in a patient and is a major parameter for comparative evaluation of quantitative clinical laboratory tests, and how significant the difference is should be set by the laboratory itself. In this study, we established the criteria for CD that can be referenced in each laboratory for diagnostic immunoassays. Methods: We targeted 17 major diagnostic immunoassays as follows: alphafetoprotein (AFP), cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), prostatespecific antigen (PSA), free PSA, tri-iodothyronine (T3), thyroxine (T4), free T4, thyroglobulin, thyroid-stimulating hormone (TSH), estradiol (E2), folliclestimulating hormone (FSH), luteinizing hormone (LH), testosterone, and prolactin. According to Clinical and Laboratory Standards Institute EP31, we investigated acceptance criteria for CD based on clinical outcomes, clinician's questionnaire, biological variation, published professional recommendations, goals set by accrediting agencies, and general capability in the Korean Association of External Quality Assessment Service. Results: We selected the acceptance criteria for CD as follows: 6.0% for total PSA and TSH based on well-designed clinical study's outcomes; 20.0% for AFP, CA19-9, CEA, and free PSA, 10.0% for T3, 14.3% for T4, 12.5% for free T4, 16.9% for thyroglobulin, 22.2% for E2, 22.9% for FSH, 20.0% for LH, 10.0% for testosterone, and 25.0% for prolactin based on clinician's questionnaire; 8.4% for CA125 and 10.2% for CA15-3 based on general capability. Conclusions: Applying the acceptance criteria for CD from this study may help assess the comparability of the quantitative tests in routine laboratory practice.