Collaboration between pharmacy and laboratory: defining total allowable error limits for therapeutically monitored drugs

OBJECTIVE: To define the total allowable variability that is clinically tolerated for certain drug assays performed by the therapeutic drug monitoring (TDM) laboratory at our institution. METHODS: The monthly coefficient of variation (CV) for 13 of the most commonly performed drug assays was recorded for two concentrations: the upper and lower limits of the therapeutic range for each drug. A dosing simulation was performed for each drug by using population parameters to estimate the doses that would yield the two target concentrations in an adult patient. The smallest practical dosage adjustment that could be implemented in clinical practice was determined and the serum concentration resulting from this dosage change was estimated. Each change was equated to two standard deviations from the original drug concentration, and the corresponding CV or total allowable error (TEa) was calculated and compared with the laboratory's CV value. RESULTS: The laboratory CV was greater than the clinically defined TEa for amikacin at both trough and peak ranges, and for gentamicin and tobramycin at the trough range. Simulations for a patient with compromised renal function produced TEa values less than the reported CV for amikacin at both trough and peak ranges. Simulations for an obese patient produced TEa values less than the reported CV for amikacin, gentamicin, and tobramycin at both trough and peak ranges. The assay variability for these aminoglycosides is greater than the expected change in serum drug concentrations produced by the dosage changes used in the simulations. The TEa for all other drugs exceeded the laboratory CV, demonstrating assay variability within the clinically tolerated range. CONCLUSIONS: Knowledge of how the variability of a drug assay compares with its TEa allows clinicians to assess the usefulness of a serum drug concentration as a clinical tool.