Sources of variability - A college of American pathologists therapeutic drug monitoring survey 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 . Design.-Four identical challenges were prepared from a lyophilized pool of spiked sera and were sent in pairs 4 months apart to laboratories participa ting in a nationwide proficiency-testing program. For each of 25 drugs, the variability in reported results from laboratories using the same method wa s investigated using nested analysis of variance. Setting.-The first 2 mailings of the College of American Pathologists Thera peutic Drug Monitoring Survey, 1996, sets Z and ZM. Main Outcome Measures.-For each drug, total variance was partitioned into w ithin- and between-laboratory components for common methods. The within-lab oratory component was further partitioned into short- and long-term compone nts. Participants.-The approximately 5000 laboratories enrolled in the survey. Results.-For the 25 drugs, the average percentages of the total variance du e to short-term, within-laboratory variance; long-term, within-laboratory v ariance; 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% (6 4.6-95.0%), respectively. Conclusion.-For all drugs tested, the within-laboratory component of varian ce was greater than the between-laboratory component of variance. Within la boratories, the magnitude of the long-term component was generally greater than the magnitude of the short-term component. This information will be he lpful in determining the clinical utility of various drug assays and in eva luating the appropriateness of regulations involving therapeutic drug testi ng.