title: Sources of variability: a College of American Pathologists Therapeutic Drug Monitoring study.
abstract: 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.
authors.affiliation: Department of Pathology, School of Medicine, University of Miami, FL, USA. bsteele@med.miami.edu
authors.forename: B W
authors.initials: BW
authors.lastname: Steele
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Palomaki
authors.forename: G G
authors.initials: GG
authors.lastname: Klee
authors.forename: R J
authors.initials: RJ
authors.lastname: Elin
authors.forename: D L
authors.initials: DL
authors.lastname: Witte
mesh_terms: 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
chemical_list: D004364:Pharmaceutical Preparations