An evaluation of analytic goals for assays of drugs: a College of American Pathologists Therapeutic Drug Monitoring Survey Study.
OBJECTIVE
To determine if the levels of imprecision of the commonly used analytic methods for drug measurements are suitable for long-term therapeutic drug monitoring.


METHODS
In 1996, 4 identical lyophilized samples (2 in the first mailing and 2 in the second mailing 4 months later) were sent to laboratories participating in a nationwide proficiency testing program. Similarly, in 1999, replicates from a liquid pool of spiked sera were mailed 3 times, 4 months apart, to participating laboratories. For each of 11 drugs regulated under the Clinical Laboratory Improvement Amendments of 1988 and 1 metabolite, the total variance for each method was partitioned into within- and between-laboratory components. The total within-laboratory and the total survey coefficients of variation (CVs) for each method were then compared with the "acceptable" precision criteria of Glick, Burnett, and Fraser for each drug.


METHODS
The first 2 mailings of the College of American Pathologists Therapeutic Drug Monitoring surveys for 1996, sets Z and ZM, and the 3 mailings of 1999, sets ZM, Z, and Z2.


METHODS
For each drug studied, the CV of each method was compared with the various imprecision criteria, and if greater than any of the criteria, the method was then tabulated as not meeting that specific criterion.Participants.-The approximately 5000 participants of the survey.


RESULTS
The number of methods deemed as not having acceptable total long-term within-laboratory precision by the various criteria ranged from 35% to 88% in 1996 and from 22% to 77% in 1999.


CONCLUSIONS
The number of failures possibly indicates that many of the reagent assays being utilized are not precise enough for long-term therapeutic drug monitoring of chronically administered drugs or that the published criteria used to evaluate the data in this study are too stringent.
Steele
B W
BW
Department of Pathology, University of Miami School of Medicine, Miami, FL, USA. bsteele@med.miami.edu
Wang
E
E
Palomaki
G E
GE
Klee
G G
GG
Elin
R J
RJ
Soldin
S J
SJ
Witte
D L
DL
D003625:Data Collection; D016903:Drug Monitoring / Q000592:standards / Q000706:statistics & numerical data; D006801:Humans; D007753:Laboratories / Q000592:standards; D010336:Pathology; D004364:Pharmaceutical Preparations / Q000032:analysis*; D011786:Quality Control; D012955:Societies, Medical; D014481:United States
D004364:Pharmaceutical Preparations