The round robin study for cardiac troponin – progress report

Background. Currently, the various cardiac troponin I (cTnI) assays produce results that are non comparable and, consequently, need different clinical cut-off values for biomarker interpretation. To improve this situation, suitable commutable reference materials that are assigned cTnI concentrations by a higher-order measurement procedure are required. They can be used by industry to assign values to working and product calibrators through a value-transfer process. Using routine procedures with these validated calibrators to measure patient samples, clinical laboratories will obtain standardised and traceable values. The IFCC Working Group on Standardization of cTnI (WG-TNI) has recently undertaken a project to address the establishment of a secondary reference immunoassay measurement procedure for cTnI of a higher metrological order than current commercial immunoassay methods, and the development of a serum-based commutable reference material for cTnI to which companies can reference their calibration process. A pilot study has been planned to compare the candidate immunoassay reference measurement procedure for cTnI (cRMP) with commercial assays and to investigate the feasibility of preparing a commutable and stable secondary reference material for cTnI by use of serum pools. Methods. The cTnI pools are prepared in three different ways, namely: 1) by the addition of individual cTnI-positive native patient samples; 2) by dilution of a high cTnI concentration pool with low and medium concentration pools; and 3) by dilution of a high and medium pool with a normal pool. The commutability of these pools is tested between routine assays and cRMP utilising sets of individual patient samples at different cTnI concentrations. At the same time, the short term stability of cTnI in the pool materials will be evaluated by assay before and after the addition of a cocktail of protease and phosphatase inhibitors. A preliminary phase preceding the study is planned to enable participant companies to actively familiarise themselves with the protocol. Sample handling and preparation of frozen materials prior to the duplicate assay of patient specimens, pools and quality control materials during the study are designed to ensure standardised procedures. Results. The pilot study has started early in 2011 and involves the National Institute of Standards and Technology (US), the National Physical Laboratory (UK), the Institute for Reference Materials and Measurements (EU), the Department of Pathology, University of Maryland School of Medicine (US), and nine diagnostic companies. Method comparability, commutability and stability results from the evaluation of individual patient samples and pools by 23 commercial assays and by cRMP are planned. Conclusions. The IFCC WG-TNI is presently investigating the feasibility of preparing a commutable reference material and its value assignment using a higher-order cRMP (1). Although this is a research project and there is no guarantee of success, we think that such experimental work is needed if there is to be progress in the standardisation of cTnI.