A comparison of human chorionic gonadotropin-related components in fresh frozen serum with the proficiency testing material used by the College of American Pathologists

Context. - As part of a College of American Pathologists (CAP) proficiency testing survey, a comparison is made between human chorionic gonadotropin (hCG) results from an actual patient pool and a similarly targeted artificial sample. The goal is to gain insight into the possible source(s) of bias attributable to the proficiency testing material (PTM) with a view toward creating more appropriate survey materials. Objective. - To compare hCG and related variants in a pool of fresh frozen sera (FFS) with that found in PTM. Design. - The 2003 CAP K/KN-A Survey included a FFS specimen along with admixtures of PTM. The FFS (K-02) and 1 PTM admixture (K-01) had similar mean hCG values. Five hCG-related analytes were measured on these 2 samples by a reference laboratory. Participants. - Approximately 1800 clinical laboratories and diagnostic test kit manufacturers participated in the K/ KN-A Survey. Main Outcome Measures. - Method imprecision (coefficient of variation) and method bias (relative difference between peer group mean and all-method median) were computed for the 2 samples. Differences were evaluated with respect to hCG-related analytes levels. Results. - All-method hCG results were 12.9 mIU/mL (12.9 IU/L) for the PTM material and 21.6 mIU/ml (21.6 IU/L) for the FFS material. Method biases for 14 manufacturers were greater for PTM than for FFS (-40% to +35% and -16% to +23%). Twelve of 14 methods had higher coefficients of variation on PTM. Total hCG and free β hCC measurements by the reference laboratory were 14.1 mIU/ mL (14.1 IU/L) for the PTM material and 18.5 mIU/mL (18.5 U/L) for the FFS material (FFS), and 2.4 (PTM) and 0.7 (FFS) mIU/mL (2.4 and 0.7 IU/L), respectively. On a molar basis, free β represented 17% and 4% of the total hCG, respectively. Levels of hyperglycosylated hCG, nicked hCG, and β core fragment were not measurable in either sample. Conclusions. - It is unlikely that the hCC added to the PTM is the source of the increased bias and variability. The main difference is a 3-fold increase in free β found in the PTM, but methods previously found to strongly react with free β were not systematically elevated. The biases between manufacturers found for the FFS specimen are likely attributable to calibration differences.