Proficiency-testing issues relating to sirolimus

Background: A need exists to document laboratory proficiency to (1) compare results produced by different analytical techniques and (2) ensure consistency of results from multiple testing sites. Objectives: To enable concentration-controlled studies of sirolimus to proceed with confidence, proficiency-testing schemes were put in place at Laboratories selected to act as reference laboratories. The feasibility of establishing an ongoing proficiency-testing scheme was addressed with respect to sample stability. The scheme was then used to test proficiency for the measurement of sirolimus in 3 blinded samples each month. Methods: The method chosen for measurement of sirolimus was a prototype microparticle enzyme immunoassay. initially, 15 laboratories were asked to analyze a series of 85 blinded samples that tested their inaccuracy, repeatability, and reproducibility for the measurement and their ability to dilute over-range samples competently. Both blood samples spiked with sirolimus and pooled blood samples from patients receiving the drug were circulated to a maximum of 50 laboratories. Results: Overall, both inaccuracy and imprecision were acceptable by predefined criteria. Inaccuracy for the immunoassay (percentage difference of the measured value against the nominal value) averaged -5% (95% CI, -9% to -1%). The mean percentage difference between the immunoassay and a high-performance liquid chromatographic assay with mass-spectrometric detection for the measurement of sirolimus in pooled samples (n = 5) from patients receiving the drug was 29% (95% CI, 24% to 34%). Conclusion: The techniques documented here as part of the International Sirolimus proficiency Testing Scheme could be applied to other clinical studies requiring protocol-driven dosing adjustments based on sirolimus measurements, irrespective of analytical technique used.