ESPE Abstracts (2016) 86 RFC5.2

Limits of Agreement between HbA1c Levels Measured in Different Laboratories Following the Introduction of the International Federation of Clinical Chemistry and Laboratory Medicine Standardised Values

Barbara Archa, Andrew McKaya, Paul Newlandb, Joanne Blairb, John Gregoryc, Matthew Peakb, Mohammed Didib, Keith Thornboroughb & Carrol Gamblea

aUniversity of Liverpool, Liverpool, UK; bAlder Hey Children’s NHS Foundation Trust, Liverpool, UK; cCardiff University, Cardiff, UK

Background: Between 2011 and 2015, 294 children from 15 UK centres were randomised to the SCIPI study (SubCutaneous Insulin: Pumps or Injections?), which compares insulin delivery by pump to multiple daily injections, during the first year following diagnosis of type I diabetes. HbA1c is measured every 3 months, locally by (1) a ‘point of care’ device or a local laboratory and (2) a central laboratory. Since 2009 HbA1c assays have been calibrated against the International Federation of Clinical Chemistry and Laboratory Medicine standardised values. This should remove the need for centralised measurement of HbA1c for clinical or research purposes.

Objectives: To determine the limits of agreement between local and central measurements of HbA1c.

Methods: Bias and 95% limits of agreement were determined using the Bland and Altman method.

Results: About 590 pairs of measurement, representing 255 children and 15 trial-centres across 4 time-points, were compared. There was no significant bias: local measurements were an average of 0.16 mmol/mol (SD=4.5, 95% CI: −0.2 to 0.5) higher than central. The 95% limits of agreement were −8.6 to 9.0 mmol/mol (local minus central). 93% of local measurements were within 10% of corresponding central measurements. Some trial centres were more varied in the differences observed between local and central measurements; none indicated systematic bias.

Conclusion: Variation in agreement between HbA1c measurements was greater than had been expected although no overall bias was detected. 5% of measures differed by > 9 mmol/mol, and 7% of pairs showed >10% difference between central and local measurements. Discrepancies were present across all participating centres. These findings have implications for the comparison of standards of clinical care between centres, the design of future multi centre RCTs and existing quality assurance processes for HbA1c measurements. We recommend that centralised HbA1c measurement is preferable in the multi-centre clinical trial setting.