Harmonization of contemporary-sensitive troponin I immunoassays: calibration may only be a part of the problem

Background. Standardization of cardiac troponin I (cTnI) immunoassays remains an unmet target and comparability of current commercial methods is modest. We hence planned a study to investigate whether realignment of cTnI data by means of reference samples may improve comparability among different cTnI methods. Methods. Seventy six routine serum samples were collected in one center, centrifuged, aliquoted and shipped to participant centers, along with four additional reference serum samples with defined cTnI concentrations. The centers performed blind measurement of thawed aliquots and reference samples using four widespread contemporary-sensitive immunoassays (Ortho-Clinical Diagnostics Vitros cTnI ES, Beckman Coulter DXI 800 AccuTnI, Siemens Healthcare Diagnostics Dimension Vista cTnI and Abbott Diagnostics Architect STAT cTnI). Test results were analyzed as provided by the centers, and also after data alignment by means of polynomial regression parameters obtained on reference sera. Results. In five out of six circumstances the Deming fit improved after harmonization. The median inter-assay variability increased from 22% to 53% after alignment with polynomial regression parameters. A reduction of bias was observed in half of the circumstances, whereas in the remaining the bias increased. After harmonization, the agreement at diagnostic thresholds decreased in 4 out of 6 circumstances. Conclusions. These results show that calibration may only be a minor contributor of inter-assay variability of commercial cTnI immunoassays. Harmonization by means of reference sera was also counterproductive for improving methods agreement around a diagnostic threshold.