Background: Glycated haemoglobin (HbA1c) is an important outcome measure in diabetes clinical trials. For\nmulticentre designs, HbA1c can be measured locally at participating centres or by sending blood samples to a\ncentral laboratory. This study analyses the agreement between local and central measurements, using 1-year follow-up\ndata collected in a multicentre randomised controlled trial (RCT) of newly diagnosed children with type I diabetes.\nMethods: HbA1c measurements were routinely analysed both locally and centrally at baseline and then at 3, 6, 9 and\n12 months and the data reported in mmol/mol. Agreement was assessed by calculating the bias and 95 % limits of\nagreement, using the Bland-Altman analysis method. A predetermined benchmark for clinically acceptable margin of\nerror between measurements was subjectively set as Ã?±10 % for HbA1c. The percentage of pairs of measurements that\nwere classified as clinically acceptable was calculated. Descriptive statistics were used to examine the agreement within\ncentres. Treatment group was not considered.\nResults: Five hundred and ninety pairs of measurement, representing 255 children and 15 trial centres across four\nfollow-up time points, were compared. There was no significant bias: local measurements were an average of 0.\n16 mmol/mol (SD = 4.5, 95 % CI âË?â??0.2 to 0.5) higher than central. The 95 % limits of agreement were âË?â??8.6 to 9.\n0 mmol/mol (local minus central). Eighty percent of local measurements were within Ã?±10 % of corresponding\ncentral measurements. Some trial centres were more varied in the differences observed between local and\ncentral measurements: IQRs ranging from 3 to 9 mmol/mol; none indicated systematic bias.\nConclusions: Variation in agreement between HbA1c measurements was greater than had been expected\nalthough no overall bias was detected and standard deviations were similar. Discrepancies were present across all\nparticipating centres. These findings have implications for the comparison of standards of clinical care between\ncentres, the design of future multicentre RCTs and existing quality assurance processes for HbA1c measurements.\nWe recommend that centralised HbA1c measurement is preferable in the multicentre clinical trial setting.
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