METHODS: Five fresh-pooled blood samples were sent to participating laboratories twice each year. The results were evaluated against target values assigned by the National Glycohemoglobin Standardization Program network laboratories; a passing criterion of +/-7% of the target value was used. Measurement uncertainty at Hb A(1c) concentrations of 7.0% and 8.0% were determined.
RESULTS: A total of 276 laboratories from 11 countries took part in the Hb A(1c) survey. At the Hb A(1c) concentrations tested method-specific interlaboratory imprecision (CVs) were 1.1%-13.9% in 2005, 1.3%-10.1% in 2006, 1.2%-8.2% in 2007, and 1.1%-6.1% in 2008. Differences between target values and median values from the commonly used methods ranged from -0.24% to 0.22% Hb A(1c) in 2008. In 2005 83% of laboratories passed the survey, and in 2008 93% passed. At 7.0% Hb A(1c), measurement uncertainty was on average 0.49% Hb A(1c).
CONCLUSIONS: The use of accuracy-based proficiency testing with stringent quality criteria has improved the performance of Hb A(1c) testing in the Asian and Pacific laboratories during the 4 years of assessment.
METHODS: Published population pharmacokinetic models and the Australasian Neonatal Medicines Formulary were used to simulate antimicrobial concentration-time profiles in a virtual neonate population. Laboratory quality assurance data were used to quantify analytical variation in antimicrobial measurement methods used in clinical practice. Guideline-informed dosing recommendations based on drug concentrations were applied to compare the impact of analytical variation and nonanalytical factors on antimicrobial dosing.
RESULTS: Analytical variation caused differences in subsequent guideline-informed dosing recommendations in 9.3-12.1% (amikacin), 16.2-19.0% (tobramycin), 12.2-45.8% (gentamicin), and 9.6-19.5% (vancomycin) of neonates. For vancomycin, inaccuracies in drug administration time (45.6%), use of non-trough concentrations (44.7%), within-subject biological variation (38.2%), and dosing errors (27.5%) were predicted to result in more dosing discrepancies than analytical variation (12.5%). Using current analytical performance specifications, tolerated dosing discrepancies would be up to 14.8% (aminoglycosides) and 23.7% (vancomycin).
CONCLUSIONS: Although analytical variation can influence neonatal antimicrobial dosing recommendations, nonanalytical factors are more influential. These result in substantial variation in subsequent dosing of antimicrobials, risking inadvertent under- or overexposure. Harmonization of measurement methods and improved patient management systems may reduce the impact of analytical and nonanalytical factors on neonatal antimicrobial dosing.