Evaluation of analytical performance of the Revvity sFlt-1 and PlGF methods for the assessment of preeclampsia

Introduction The measurement of the angiogenic biomarkers placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) are increasingly used to support the prediction and diagnosis of preeclampsia (PE) in routine clinical practice. There are an increasing number of methods available for the analysis of these markers but data showing their analytical comparability is limited. Materials and methods The assays for PlGF and sFlt-1 from Revvity were evaluated and compared against Roche methods that are used in current clinical practice in Oxford. Imprecision and paired analytical comparisons studies were undertaken and data evaluated for numeric agreement and concordance relative to manufacturer recommended rule-in and rule-out thresholds for PE. Results Imprecision estimates for the Revvity PlGF and sFlt-1 methods calculated from quality control material analysed during the evaluation were between 3.2 and 9.0 CV%. Revvity method precision profiles derived from 581 clinical specimens analysed in duplicate had a median CV% for PlGF of 1.8%, IQR 2.3% and for sFlt-1 a median CV% of 1.1%, IQR 1.5%. Comparison against the Roche PlGF and sFlt-1 methods in 437 clinical specimens showed an overall Passing-Bablok regression relationship for PlGF of y = −23.4 + 0.73x (r = 0.983) and for sFlt-1, y = −87.7 + 0.40x (r = 0.971). However, there was statistically significant ( p < 0.0001 ) concentration dependant relative bias for both methods and the calculated ratio. Concordance of the sFlt-1:PlGF ratio relative to manufacturer specific rule-in and rule-out thresholds was 95.2%. Discussion The Revvity methods for PlGF and sFlt-1 are precise and correlate with the Roche methods. However, numeric agreement precludes result interchangeability and the use of common rule-in and rule-out thresholds. The manufacturer specific thresholds should be applied in clinical practice. Further work is required to understand how method differences impact clinical outcomes and their causes.