Received on January 16, 2008
Accepted on April 22, 2008

Informatics and Statistics

Statistical Methods for Monitoring the Relationship between the IFCC Reference Measurement Procedure for Hemoglobin A1c and the Designated Comparison Methods in the United States, Japan, and Sweden

¹ Roche Diagnostics GmbH, Department of Biostatistics, Penzberg, Germany
² Institute of Biopathological Medicine, Kanagawa, Japan
³ Malmoe University Hospital, Malmoe, Sweden
⁴ University of Missouri School of Medicine, Columbia, MO
⁵ Queen Beatrix Hospital, Winterswijk, The Netherlands
⁶ Roche Diagnostics GmbH, Department of Biostatistics, Penzberg, Germany, and Institute of Biopathological Medicine, Kanagawa, Japan, and Malmoe University Hospital, Malmoe, Sweden, and University of Missouri School of Medicine, Columbia, MO, and Queen Beatrix Hospital, Winterswijk, The Netherlands

^* To whom correspondence should be addressed. E-mail: andrea.geistanger{at}roche.com.

BACKGROUND: The American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD)/International Diabetes Federation (IDF)/IFCC Consensus Statement on the worldwide standardization of HbA1c states that "HbA1c results are to be reported world-wide in IFCC units and derived NGSP units, using the IFCC-NGSP master equation."

METHODS: We describe statistical methods to evaluate and monitor the relationships as expressed in master equations (MEs) between the IFCC Reference Measurement procedure (IFCC-RM) and designated comparison methods (DCMs) [US National Glycohemoglobin Standardization Program (NGSP), Japanese Diabetes Society/Japanese Society for Clinical Chemistry (JDS/JSCC), and Mono-S in Sweden]. We applied these statistics, including uncertainty calculations, to 12 studies in which networks of reference laboratories participated, operating the IFCC-RM and DCMs.

RESULTS: For NGSP and Mono-S, slope, intercept, and derived percentage HbA1c at the therapeutic target show compliance with the respective MEs in all 12 studies. For JDS/JSCC, a slight deviation is seen in slope and derived percentage HbA1c in 2 of the 12 studies. Using the MEs, the uncertainty in an assigned value increases from 0.42 mmol/mol HbA1c (IFCC-RM) to 0.47 (NGSP), 0.49 (JDS/JSCC), and 0.51 (Mono-S).

CONCLUSIONS: We describe sound statistical methods for the investigation of relations between networks of reference laboratories. Application of these statistical methods to the relationship between the IFCC-RM and DCMs in the US, Japan, and Sweden shows that they are suitable for the purpose, and the results support the applicability of the ADA/EASD/IDF/IFCC Consensus Statement on HbA1c measurement.