Audit of sweat chloride testing reveals analytical errors

Area of Science:

• Clinical Chemistry
• Diagnostic Accuracy
• Biomarker Validation

Background:

• Sweat chloride testing (SCT) is crucial for diagnosing cystic fibrosis (CF) and evaluating CFTR-modifying drugs.
• External quality assessments indicate significant analytical variance (CVA) in routine SCT practice.
• Minimizing CVA is essential for the reliability and validity of SCT as a diagnostic tool.

Purpose of the Study:

• To identify and quantify technical errors in SCT through proficiency testing and simulations.
• To assess the impact of a counseling session on reducing imprecision and bias in SCT.
• To improve the accuracy and consistency of SCT in clinical settings.

Main Methods:

• Chloride concentrations were measured in blinded samples across 9 CF centers using chloridometers.
• Technical errors were simulated and quantified.
• Coefficients of variation (CV), tolerance limits, and inter-rater variability were compared before and after a counseling intervention.

Main Results:

• Pipetting errors were the primary source of error, causing deviations up to 41%.
• Following counseling, overall CVA decreased from 7.6% to 5.2%, and the pass rate improved from 67% to 92%.
• Inter-rater variability was reduced, though significant center-specific deviations persisted.

Conclusions:

• Preventing technical errors in SCT directly reduces imprecision and bias.
• Implementing comprehensive quality assurance programs, including staff training and proficiency testing, is vital for all CF centers.
• Standardized procedures and ongoing quality control are necessary to ensure reliable SCT results for CF diagnosis and treatment monitoring.