Collaboration between Pharmacy and Laboratory: Defining Total Allowable Error Limits for Therapeutically Monitored Drugs

The objective of this study was to evaluate the analytical performance of the Abbott ARCHITECT Tacrolimus immunoassay. Proficiency panels and specimens from a population of organ transplant recipients were analyzed in 6 clinical laboratories in Europe and the United States, and the results were compared with other methods. The ARCHITECT assay requires a whole blood specimen pretreatment step with methanol/zinc sulfate to precipitate protein and extract the drug, followed by a 30-minute immunoassay using anti-tacrolimus antibody-coated paramagnetic microparticles and an acridinium-tacrolimus tracer. The assay was free from hematocrit interference in the range 25%-55% and from interference by extremes of cholesterol, triglycerides, bilirubin, total protein, and uric acid. The total percent of coefficient of variations of the assay were 4.9%-7.6% at 3 ng/mL, 2.9%-4.6% at 8.6 ng/mL, and 3.1%-8.2% at 15.5 ng/mL. Limit of detection was < or =0.5 ng/mL and limit of quantification (LOQ) ranged from 0.69 to 1.07 ng/mL across the 6 sites (based on the upper 95% confidence interval concentrations). The 2007 European Consensus Conference on Tacrolimus Optimization recommended the use of assay methods with an LOQ around 1 ng/mL, based upon the need to measure trough tacrolimus blood concentrations precisely down to 3 ng/mL during low-dose tacrolimus regimens. Tacrolimus International Proficiency Testing Scheme samples were measured by the ARCHITECT immunoassay at 5 sites and showed an average bias of -0.28 to +0.85 ng/mL versus IMx Tacrolimus II immunoassay historical values and -0.21 to +0.68 ng/mL versus liquid chromatography/tandem mass spectrometry (LC-MSMS) Tacrolimus historical values. Method comparison studies were performed with the ARCHITECT Tacrolimus immunoassay on patient specimens with the following results: ARCHITECT Tacrolimus assay versus the Abbott IMx Tacrolimus II immunoassay (4 sites) yielded average biases between -0.94 and +0.26 ng/mL; ARCHITECT assay versus the Dade Dimension Tacrolimus immunoassay (2 sites) yielded average biases of -0.46 and +0.11 ng/mL; and ARCHITECT assay versus LC-MSMS methods at 2 sites yielded average biases of +0.51 and +1.63 ng/mL. Spearman correlation coefficients were >/=0.90 on all method comparisons. The ARCHITECT Tacrolimus assay is a semiautomated, robust, and highly sensitive immunoassay, representing an alternative approach for laboratories not equipped with LC-MSMS, and meets the 1 ng/mL recommendation of LOQ by the European Consensus Conference on Tacrolimus Optimization.

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“…Total error (TE) was calculated at the AU and US sites using the imprecision data in Table 3 for each control and the Table 4 as follows 10 :…”

Section: Total Errormentioning

confidence: 99%

Multi-site Analytical Evaluation of the Abbott ARCHITECT Tacrolimus Assay

Wallemacq

Goffinet²,

O'Morchoe³

et al. 2009

Therapeutic Drug Monitoring

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“…Traditional TDM requires close collaboration between the clinical laboratory and the pharmacist to ensure appropriate sample collection and timely interpretation of results. 1 The benefits of pharmacist-directed TDM through a Clinical Pharmacokinetics service have been well-documented and include decreased adverse effects which translate into decreased length of treatment, length of hospital stay, and reduced costs. 2–4 …”

mentioning

confidence: 99%

Development and implementation of a pharmacist-managed clinical pharmacogenetics service

Crews

Cross

McCormick

et al. 2011

American Journal of Health-System Pharmacy

137

130

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Purpose The development and implementation of a pharmacist-managed Clinical Pharmacogenetics service is described. Summary Therapeutic drug monitoring (TDM) is a well-accepted role of the pharmacist. Pharmacogenetics, the study of genetic factors that influence the variability in drug response among patients, is a rapidly evolving discipline that integrates knowledge of pharmacokinetics and pharmacodynamics with modern advances in genetic testing. There is growing evidence for the clinical utility of pharmacogenetics, and pharmacists can play an essential role in the thoughtful application of pharmacogenetics to patient care. A pharmacist-managed Clinical Pharmacogenetics service was designed and implemented. The goal of the service is to provide clinical pharmacogenetic testing for gene products important to the pharmacodynamics of medications used in our patients. The service is modeled after and integrated with an already established Clinical Pharmacokinetics service. All clinical pharmacogenetic test results are first reported to one of the pharmacists, who reviews the result and provides a written consult. The consult includes an interpretation of the result and recommendations for any indicated changes to therapy. In 2009, 136 clinical pharmacogenetic tests were performed, consisting of 66 TPMT tests, 65 CYP2D6 tests, and 5 UGT1A1 tests. Our service has been met with positive clinician feedback. Conclusion Our experience demonstrates the feasibility of the design and function of a pharmacist-managed Clinical Pharmacogenetics service at an academic specialty hospital. The successful implementation of this service highlights the leadership role that pharmacists can take in moving pharmacogenetics from research to patient care, thereby potentially improving patient outcomes.

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