Procalcitonin assay variation in an Australasian external quality assurance program

Sepsis accounts for approximately 20% of global deaths, and early diagnosis is a critical factor in intervention. In 2017, the FDA approved procalcitonin (PCT) to guide antibiotic use for patients with suspected sepsis, and there are recognized intervals for clinical interpretation. Therapeutic algorithms incorporating PCT measurement have implications for antibiotic stewardship in the age of antibiotic resistance. A 2021 review of external quality assurance programs for PCT, including the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) PCT program, highlighted variable performance between assays. We reviewed the RCPAQAP's PCT program results from 2019 to 2021 to analyse any variation in reported results. The RCPAQAP's PCT program is conducted annually and consists of a lyophilized human/bovine serum albumin base with added recombinant PCT sent to participating laboratories. Results received for the 2019, 2020 and 2021 PCT programs were analysed using two-way ANOVA with Tukey's multiple comparison test and a Student's t-test to investigate variation in assay performance. We found significant variation between the different assay manufacturers at all PCT concentrations analysed. Additionally, bimodal reporting was observed, where bioMerieux/Beckman Coulter/Siemens methods had significantly higher results when compared to Roche/Abbott methods. There was also a significant increase in the average coefficient of variation between 2019 and 2020/2021, coinciding with reported method changes. Finally, variable performance of the semi-quantitative PCT method at both low and high PCT concentrations was detected. These findings suggest that clinical decision cut-offs must be validated for each assay. However, the commutability of the program material has yet to be determined.