A longitudinal replicate study of immunosuppressive drugs: A College of American Pathologists Study

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 inter-laboratory 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.