Impact of ISO/TS 20914-based measurement uncertainty on HbA1c diagnostic classification: A real-world comparison of two analytical systems.

Objectives

HbA1c is interpreted using fixed clinical decision limits, but measurement uncertainty (MU) may affect analytical interpretation of results near these thresholds. This study estimated ISO/TS 20914-based MU for two HbA1c analytical systems and evaluated the patient-level impact of including calibration- and traceability-related uncertainty.

Methods

In this retrospective two-center study, 30,791 routine HbA1c results from independent patient cohorts were obtained using Roche cobas c501 and Adams HA-8180 V systems. MU was estimated from within-laboratory reproducibility uncertainty (uRw), calibration- and traceability-related standard uncertainty (ucal), and uncertainty associated with the IFCC-to-NGSP master equation (uME). Decision-limit-specific coverage intervals were calculated at 5.7% and 6.5% HbA1c using a calibration-included MU model (uRw, ucal, and uME) and a calibration-excluded sensitivity analysis (uRw and uME). Patient-level reclassification was evaluated using McNemar's test with Holm adjustment.

Results

Roche showed higher uRw than Adams, whereas ucal was higher for Roche (2.35% vs 1.75%). Calibration-included standard MU was 3.77% and 3.76% for Roche at 5.7% and 6.5%, respectively, and 2.47% and 2.45% for Adams. Inclusion of ucal increased the proportion of results within MU coverage intervals from 38.81% to 48.05% for Roche at 5.7%, from 15.45% to 20.76% at 6.5%, and from 10.69% to 15.90% for Adams at 6.5% (all Holm-adjusted P < 0.001). No reclassification occurred for Adams at 5.7%.

Conclusions

Inclusion of calibration- and traceability-related uncertainty materially affected analytical interpretation around clinical decision limits in three of four system-threshold analyses. Patient-level impact depended on both MU budget composition and the distribution of results around the relevant threshold.