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European Trial Assesses HbA1c Testing in 2,200 Labs in 17 Countries

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NEW YORK (360DX) – The quality of hemoglobin A1c diabetes testing varies not just from laboratory to laboratory, but from country to country and test manufacturer to test manufacturer, according to findings of a massive multicountry trial conducted by the International Federation of Clinical Chemistry and Laboratory Medicine.

The trial involved HbA1c proficiency testing in 2,166 laboratories across 17 countries and 24 testing manufacturers. One in 20 laboratories tested did not meet IFCC HbA1c testing criterion, according to the study, which was published in the June issue of Clinical Chemistry.

The trial represents a latest step in a multiyear effort by IFCC HbA1c focus groups to standardize HbA1c diabetes testing in laboratories, according to Cas Weykamp, a clinical chemist with Queen Beatrix Hospital in the Netherlands, and the network coordinator for the IFCC HbA1c laboratory network. Those efforts included the development of a reference system for HbA1c testing in 2008, followed by the establishment of quality targets three years ago, he said.

"We had created a reference system; we had created a model for quality targets; and now we wanted to see how well laboratories perform in daily life in the field. That can be best tested by sending out the same sample to as many laboratories as possible to see how well they work," Weykamp said.

The study looks at lab performance by manufacturer, lab performance by country, and manufacturer performance by country. Half of the labs were evaluated using fresh whole blood and the other half were tested using lyophilized hemolysates, depending on the preference of the external quality assessment organizations participating in the study. Seventeen external quality assessment organizations, which are the equivalent of US proficiency testing organizations, participated in the trial.

For many manufacturers, trial data indicated that their tests performed similarly across different countries. There were occasional exceptions, however. A Roche test performed very well in Sweden, the Netherland, and the United Kingdom, but performed poorly in Switzerland and Turkey, according to the report. The specific Roche test was not identified.

"That can trigger Roche to investigate. They see it can be done well, but why doesn't it work in Switzerland and Turkey?" Weykamp said.

Although the trial is intended to evaluate lab quality, publication of these types of trials can often prompt corrective actions within the industry, Weykamp noted.

"In general with trials like these, and also with [the College of American Pathologists] in the US, manufacturers that have a poor performance are triggered to improve their products," Weykamp said. "Also, customers of laboratories that can see they are using a test kit that in general has a poor performance will either contact the manufacturer and ask to improve, or will simply choose the best test kit of a competitor."

Among countries as well as among manufacturers, the major contribution to total error derived from between-laboratory variation, meaning the mean calibration of laboratories appeared to be fine, but the differences between laboratories were substantial and should be the focus of further improvement, according to Weykamp.

At the country level, with fresh whole-blood testing, six countries met the IFCC criterion, while two did not, and two were borderline. With lyophilized hemolysates, five countries met the criterion, two did not, and three were borderline. In whole blood testing, Ireland had the best performance testing, while Turkey and Switzerland did not meet the IFCC criterion. In lyophilized hemolysates testing, Italy performed best while Greece and Austria were outside the criterion.

While the study did not examine reasons for disparities in performance, it is possible that different countries might have different quality standards, such as narrower acceptance limits for external quality assessment, Weykamp speculated. Some countries might also use better quality testing equipment than others, he noted.

Among manufacturers, using fresh whole blood, 13 manufacturers met the criterion, eight did not and three were borderline. Using lyophilized hemolysates, seven manufacturers met the criterion, six did not, and three were borderline. With fresh whole blood, Abbott's Architect Enzymatic test performed best. With lyophilized hemolysates testing, Bio-Rad Laboratories' D100 system was the top performer.

The trial is scheduled to be repeated annually, according to Weykamp. The second study has already been completed, and proficiency testing for the third study is scheduled to begin in October. The study is growing both in the number of labs participating and in the number of countries represented, Weykamp noted, adding the third study will include labs in Africa and Latin America.

"The number of labs, especially from Africa, will be low, but it's important to make a start," he said. "There are many diabetics in the western world, but many, many more in developing countries. HbA1c will be used more and more in those countries, and being aware of quality and trying to achieve good quality and monitor quality is important there as well."