A Black Swan in clinical laboratory practice: the analytical error due to interferences in immunoassay methods.

It is well known that the results of immunoassay methods can be affected by specific or non-specific interferences, ranging from 0.4% to 4.0%. The presence of interference may greatly compromise the accuracy of immunoassay analyses causing an error in the measurement, producing false-positive or false-negative results. From a clinical point of view, these analytical errors may have serious implications for patient care because they can cause misdiagnosis or inappropriate treatment. Unfortunately, it is a very difficult task to identify the irregular analytical errors related to immunoassay methods because they are not detectable by normal laboratory quality control procedures, are reproducible within the test system, may be clinically plausible and are relatively rare. The first line of defense against erroneous results is to use in laboratory practice only immunoassay systems with the highest level of robustness against interference. The second line of defense is always taking into account the possibility of interference in immunoassay results. A correct approach should be addressed on identification of samples at high risk of interference. The attainment of this goal requires a critical review of the test result in relation to patient's clinical conditions and literature data, taking into account the analytical characteristics of the immunoassay system. The experts in immunoassay systems should make every effort to find some specific and reliable quality indicators for irregular analytical errors in order to better detect and monitor erroneous immunoassay results due to specific or non-specific interferences.

Health-care cost reduction resulting from primary-care allergy testing in children in Italy.

BACKGROUND: Allergy places a considerable cost burden on society. Specific immunoglobulin E (spIgE) testing may improve the management of allergy patients. There is therefore a reason to quantify the economic consequences of the use of spIgE testing in the diagnosis of allergic conditions. METHODS: The expected costs of spIgE testing versus no-testing were calculated using a clinical decision model based on a prospective clinical trial performed in primary care. RESULTS: The expected costs per patient over 2 years decreased from 802 euros in the "no-test strategy" to 560 euros in the spIgE "test strategy". Cost savings persisted even after assumptions about the prevalence of allergy and the prices of medications were changed. The "test strategy" increased the percentage of patients correctly diagnosed from 54 to 87%. CONCLUSIONS: spIgE testing of children with respiratory and/or skin problems in primary care in Italy reduces overall costs to society. These cost savings mostly result from a reduction in the use of medications, particularly corticosteroids. The study indicates that spIgE testing of all children with respiratory and/or skin symptoms would be a cost-effective strategy.

20-25% lower concentrations of total and free prostate-specific antigen (PSA) after calibration of PSA assays to the WHO reference materials--analysis of 1098 patients in four centers.

AIM: To examine the potential clinical implications of the recalibration of total prostate-specific antigen (PSA) and free PSA (fPSA) assays to the World Health Organization (WHO) standard materials. MATERIAL AND METHODS: Data from 1098 patients with or without clinically detected prostate cancer (PCa) from four independent cohort studies were compared using commercial assays calibrated to the traditional Hybritech PSA (PSA-Hyb) and fPSA (fPSA-Hyb) standards and to the WHO 96/670 (PSA-WHO) and 96/668 (fPSA-WHO) standards. The Access Immunoassay System (Beckman Coulter, Inc.) was used in all studies. RESULTS: All studies showed 20% to 25% lower PSA and fPSA test results with the WHO-standardized assays. No significant change in %fPSA (fPSA/PSA x 100) was observed. Continuing to use the traditional clinical PSA cutoffs obtained with the Hybritech standard after changing to the PSA-WHO standard could result in up to one-third of prostate cancer cases being missed. CONCLUSIONS: Manufacturers should fully inform laboratories about a calibration change and its clinical impact. Laboratory reports for PSA measurements should indicate the assay's manufacturer and which calibration standard was used to avoid misleading information concerning PCa risk.

Different biological matrices (serum and plasma) utilization in consolidation processes: evaluation of seven Access immunoassays.

BACKGROUND: The compatibility of immunoassay tests in different sample matrices is extremely important during the assay validation process. In this study, we investigated the interchangeability of some Access (and therefore all the UniCel Family platforms) assays between serum and plasma. METHODS: We tested approximately 200 samples in parallel between serum and lithium heparin plasma for seven analytes: alpha-fetoprotein (AFP), carcino-embryonic antigen (CEA), total prostate specific antigen (tPSA), free prostate specific antigen (fPSA), digoxin, progesterone and unconjugated estriol (uE3). We used the Access2 Immunoassay System (Beckman Coulter), a fully automated random access system with a chemiluminescent signal. We performed statistical comparative analysis using two commercially available programs, Analyze-it from Microsoft Excel and MedCalc Software, and a dedicated statistical program. RESULTS: Firstly, we showed the results of the statistical tests performed on each population to verify their distribution. Analysis by several statistical tests (Passing and Bablok regression, Youden and Bland and Altman diagrams, the Mountain plot and multivariate analysis) showed that all the assays studied were valid in both serum and lithium heparin plasma matrices. CONCLUSIONS: As all Access and UniCel Family instruments use the same reagent packs, these results are transferable to all Beckman Coulter immunochemistry platforms, without a commutability problem between serum and plasma and without a need for establishment of a plasma reference interval.