Wang, Edward

Abstract Context. —The College of American Pathologists (CAP) provides proficiency testing (PT) surveys to laboratories around the world. Objectives. —To compare diagnostic assay methods for serum/plasma cortisol and immunoglobulin (Ig) E in terms of their bias and precision, to determine how well CAP PT specimens simulate human serum, and to reassess proficiency test grading criteria in light of these findings. Design. —A participant-blinded, prospective trial. One vial of pooled fresh frozen serum (FFS) and 4 different admixtures of PT material (PTM) were sent to laboratories participating in PT surveys. Participants. —Laboratories providing cortisol (>1000) or IgE (>230) results among the subscribers to the CAP surveys, Ligand (General) 2003, set K/KN-A and Chemistry 2003, set C-C. Main Outcome Measures. —The main outcome measures were (1) bias among laboratories using the same method (peer groups), defined relative to the median of method means (MedMM); (2) imprecision as measured by the SD and coefficient of variation (CV) about each method mean; and (3) total error across laboratories for the FFS cortisol results, defined as |Bias Relative to Reference Method| + 2 SD. Results. —Cortisol method biases, relative to MedMM, ranged from −22% to 9% for the FFS challenge and from −24% to 36% for comparable PTM challenges. The method biases, relative to the reference method, ranged from −3% to 19% for the FFS challenge. The cortisol method CVs ranged from 4.2% to 13.6% for the FFS challenge and from 4.7% to 12.7% for comparable PTM challenges. Total error across laboratories ranged from 1.4 to 6.9 μg/dL (39 to 190 nmol/L) for the FFS challenge. Immunoglobulin E method biases, relative to MedMM, ranged from −8% to 9% for the FFS challenge and from −7% to 5% for comparable PTM challenges. The IgE method CVs ranged from 3.6% to 6.7% for the FFS challenge and from 3.4% to 9.8% for comparable PTM challenges. Conclusions. —The bias for cortisol results was less with FFS than with PTM, but imprecision was comparable. The FFS MedMM was 8.5% higher than the reference value. Fresh frozen serum and PTM bias and imprecision for IgE methods were each less than 10%. Because some of the methods demonstrated greater bias when analyzing PTM than FFS, peer group grading of both these analytes is appropriate.

Abstract Objective.—To identify the sources of analytical variation for cyclosporine and tacrolimus in a 3-year longitudinal study. Design.—Two pools of whole blood were spiked with cyclosporine and tacrolimus, respectively. One aliquot of cyclosporine and 2 of the tacrolimus pool were distributed in the first and last mailing for years 1999 to 2001. For both drugs, the total variance for each method was partitioned into within- and between-laboratory components. Setting.—The A and C mailings of the 1999, 2000, and 2001 AACC/CAP [American Association for Clinical Chemistry/College of American Pathologists] Immunosuppressive Drugs (CS) Monitoring Survey. Main Outcome Measures.—For each drug, total variance was partitioned into specimen, mailing, year, and interlaboratory effects for each analytical method. Participants.—The 292 laboratories for cyclosporine and 177 laboratories for tacrolimus enrolled in the survey from 1999 to 2001. Results.—For both cyclosporine and tacrolimus, the major source of imprecision came from within-laboratory factors, which accounted for nearly 85% (range, 77% to 90%) of the total variance. For cyclosporine, the major component of within-laboratory variance was between-mailing, within-year effect, whereas for tacrolimus it was the between-year, within-laboratory variation. Conclusion.—The major source of long-term survey imprecision for cyclosporine and tacrolimus is within-laboratory factors. The finding that 85% of the total variance was due to within-laboratory variation is similar to other therapeutic drugs.