Sources of variability: a College of American Pathologists Therapeutic Drug Monitoring study.
OBJECTIVE
To determine the magnitudes and sources of analytic variation in testing for therapeutic drugs. Specifically, among laboratories using the same analytic method, to compare the within-laboratory variation (including both short- and long-term variation) with the between-laboratory variation.


METHODS
Four identical challenges were prepared from a lyophilized pool of spiked sera and were sent in pairs 4 months apart to laboratories participating in a nationwide proficiency-testing program. For each of 25 drugs, the variability in reported results from laboratories using the same method was investigated using nested analysis of variance.


METHODS
The first 2 mailings of the College of American Pathologists Therapeutic Drug Monitoring Survey, 1996, sets Z and ZM.


METHODS
For each drug, total variance was partitioned into within- and between-laboratory components for common methods. The within-laboratory component was further partitioned into short- and long-term components.


METHODS
The approximately 5000 laboratories enrolled in the survey.


RESULTS
For the 25 drugs, the average percentages of the total variance due to short-term, within-laboratory variance; long-term, within-laboratory variance; between-laboratory variance; and total laboratory variance were 25.0% (range, 8.8--50.6%), 57.8% (35.3--73.7%), 17.3% (5.0--35.4%), and 82.7% (64.6--95.0%), respectively.


CONCLUSIONS
For all drugs tested, the within-laboratory component of variance was greater than the between-laboratory component of variance. Within laboratories, the magnitude of the long-term component was generally greater than the magnitude of the short-term component. This information will be helpful in determining the clinical utility of various drug assays and in evaluating the appropriateness of regulations involving therapeutic drug testing.
Steele
B W
BW
Department of Pathology, School of Medicine, University of Miami, FL, USA. bsteele@med.miami.edu
Wang
E
E
Palomaki
G
G
Klee
G G
GG
Elin
R J
RJ
Witte
D L
DL
D000704:Analysis of Variance; D002623:Chemistry Techniques, Analytical / Q000379:methods; D016903:Drug Monitoring / Q000706:statistics & numerical data*; D006801:Humans; D007753:Laboratories / Q000706:statistics & numerical data*; D010336:Pathology; D004364:Pharmaceutical Preparations / Q000097:blood; D011786:Quality Control; D012680:Sensitivity and Specificity
D004364:Pharmaceutical Preparations