Evaluating feasibility of ferritin assay harmonisation with commutable proof-of-concept reference materials and EQA-based monitoring.

OBJECTIVES: Clinical interpretation of ferritin is hindered by between-assay differences, persisting despite the introduction of different generations of WHO standard. To aid harmonisation efforts, this study investigates the commutability of External Quality Assessment (EQA) materials, proof-of-concept reference materials (cRMs), and the newest generation of WHO standard (19/118). METHODS: Four multi-level serum-based cRMs, 50 clinical samples, four EQA materials, and WHO 19/118 were measured with Abbott Alinity, Beckman Coulter Access DxI, Roche Cobas and Siemens Atellica. Commutability was analysed using the prediction interval approach for EQA materials and the difference in bias and calibration effectiveness approaches for cRMs and WHO standard. RESULTS: Differences in assay selectivity did not allow for formal commutability assessment of EQA materials. Nevertheless, all four investigated EQA materials fell within the 95 % prediction interval around clinical samples in all six method comparisons, indicating their suitability for monitoring harmonisation status. Calibration effectiveness demonstrated commutability for cRM1 and cRM3, in contrast to poor commutability for cRM2, cRM4 and WHO 19/118. Recalibration with cRM1 decreased inter-assay CV four-fold from 34 % to 8.2 %. CONCLUSIONS: Improving harmonisation among current ferritin assays is possible, and success of such efforts can be monitored with EQA materials. Although limited by differences in selectivity, the harmonisation potential of the current assays is substantial, and therefore we encourage harmonisation based on a ISO15194-proof material produced like our cRM1 or cRM3. True standardisation will need much more time, requiring prior measurand characterisation, identification of a clinically relevant ferritin measurand, and subsequent assay redesign to eliminate differences in selectivity.