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.


METHODS
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.


METHODS
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.


METHODS
For each drug, total variance was partitioned into specimen, mailing, year, and interlaboratory effects for each analytical method.


METHODS
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.


CONCLUSIONS
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.
Steele
Bernard W
BW
Department of Pathology, University of Miami School of Medicine, Miami, FL, USA. bsteele;camed.miami.edu
Wang
Edward
E
Soldin
Steven J
SJ
Klee
George
G
Elin
Ronald J
RJ
Witte
David L
DL
D000704:Analysis of Variance; D002983:Clinical Competence / Q000592:standards; D019411:Clinical Laboratory Techniques / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D016572:Cyclosporine / Q000097:blood; D016903:Drug Monitoring / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D008137:Longitudinal Studies; D011786:Quality Control; D012016:Reference Values; D012680:Sensitivity and Specificity; D016559:Tacrolimus / Q000097:blood; D014481:United States
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus