Proof of concept of a new scale for the harmonization and the standardization of the ETP‐based APC resistance

Abstract

BackgroundThe evaluation of the activated protein C resistance (APCr) based on the endogenous thrombin potential (ETP) is recommended during the development of steroid contraceptives. Results are usually expressed as “normalized APC sensitivity ratio” (nAPCsr) using a reference plasma that should achieve an ETP ratio of 0.1 in presence of exogenous APC. Because of the interassay variability, achieving exactly an ETP ratio of 0.1 in each run is almost impossible, which significantly affects the theoretical 0‐10 scale of nAPCsr. ObjectivesTo compare the nAPCsr to the nAPCsr10, a newly proposed method to express the degree of APC resistance. MethodsIndividual plasma samples (n = 854) were analyzed to compare nAPCsr and nAPCsr10. These values were obtained using the validated ETP‐based APCr assay. ResultsThe Spearman correlation between nAPCsr and nAPCsr10 had a coefficient of 0.99. Linear regression showed the following equation y = 0.9315*x + 0.03942 (r2 = .97). When differences (nAPCsr10 – nAPCsr) were plotted against nAPCsr10, the mean difference equaled 0.16% or 4.95%. The correction obtained with the use of the nAPCsr10 showed that the results of the nAPCsr were statistically different (P < .0001). ConclusionsThis new scale provides a harmonization and normalization of the nAPCsr. Results show a better reproducibility with the nAPCsr10. It avoids the additional variability and the unharmonized scale introduced by the use of a reference plasma. This adapted method for the calculation of the APC resistance could provide the regulatory and scientific bodies with more reproducible and harmonized evaluations.