An evaluation of analytic coals 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 therapeut ic drug monitoring. Design - In 1996, 4 identical lyophilized samples (2 in the first mailing a nd 2 in the second mailing 4 months later) were sent to laboratories partic ipating in a nationwide proficiency testing program. Similarly, in 1999, re plicates from a liquid pool of spiked sera were mailed 3 times, 4 months ap art, to participating laboratories. For each of 11 drugs regulated under th e Clinical Laboratory Improvement Amendments of 1988 and 1 metabolite, the total variance for each method was partitioned into within- and between-lab oratory components. The total within-laboratory and the total survey coeffi cients of variation (CVs) for each method were then compared with the "acce ptable" precision criteria of Click, Burnett, and Fraser for each drug. Setting - The first 2 mailings of the College of American Pathologists Ther apeutic Drug Monitoring surveys for 1996, sets Z and ZM, and the 3 mailings of 1999, sets ZM, Z, and Z2. Main Outcome Measures - For each drug studied, the CV of each method was co mpared with the various imprecision criteria, and if greater than any of th e criteria, the method was then tabulated as not meeting that specific crit erion. 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. Conclusion - The number of failures possibly indicates that many of the rea gent assays being utilized are not precise enough for long-term therapeutic drug monitoring of chronically administered drugs or that the published cr iteria used to evaluate the data in this study are too stringent.