Successful measurement uncertainty training on haemoglobin test for calibration laboratories

EMN TraceLabMed member provides measurement uncertainty training for calibration laboratories and External Quality Assessment providers

EMN TraceLabMed

The European Metrology Network (EMN) for Traceability in Laboratory Medicine brings together European National Metrology Institutes, Designated Institutes and partners from medicine and industry to support the application of metrology, the science of measurement, to in vitro diagnostics tests.

Health care affects the lives of almost every European citizen. A significant number of medical decisions depends upon in vitro diagnostics tests. With numerous applications, from detecting diseases, conditions and infections, these tests can be performed in laboratories, hospitals or even in the home.

Calibration labs play a crucial role in disseminating traceability, and offer their services to European and international stakeholders.

Background

According to the International Diabetes Federation, about 32.3 million adults were diagnosed with diabetes in the European Union in 2019 and an additional estimated 24.2 million more people had diabetes but hadn't been diagnosed. These numbers underscore the growing concern of diabetes as a significant public health issue in the European Union, with both diagnosed and undiagnosed cases contributing to the overall burden of the disease. Effective awareness, prevention, and management strategies are crucial in addressing this health challenge.

Measuring the blood concentration of glycated haemoglobin (HbA1c) became a standard method for assessing long-term glycaemic control in individuals with diabetes and is used for screening and diagnosis of type 2 diabetes mellitus. In comparison with other methods of diabetes mellitus diagnosis, HbA1c measurement does not require fasting before measurement, is not affected by stressful situations or the acute phase of the disease, and has simpler sampling and analysis requirements (due to the stability of HbA1c compared with plasma glucose levels).

The routine use of HbA1c measurements in the diagnosis, management, and monitoring of type 2 diabetes today have been enabled by establishing a full traceability chain in a standardisation campaign led by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Establishing traceability involves the provision of suitable calibrators with values assigned by the reference measurement procedure to manufacturers – this is done by calibration laboratories.

The necessity for precision arises from the presence of clinical decision thresholds influencing treatment approaches. Given the high number of patients affected, the accuracy of measurements becomes even more crucial. Even slight biases or increased imprecision could lead to incorrect treatment choices or misclassification of many individuals. Physicians commonly consider a 5 mmol/mol alteration in HbA1c as clinically meaningful. Consequently, it's crucial to ascertain that changes in concentration are clinically significant rather than resulting from measurement variability.

In the field of metrology, which is the science of measurement, uncertainty of measurements (often denoted as "U" or "uncertainty") is a fundamental concept used to quantify the range within which the true value of a measurement is likely to lie. It reflects the limitations and variability associated with any measurement process, therefore its use is essential in understanding if a measurement is fit for its intended purpose. Several guidelines exist for calculating measurement uncertainty. However, in the context of HbA1c, there is no universally accepted procedure.

Measurement uncertainty training

PTB –the German National Metrology Institute and a member of the EMN TraceLabMed – therefore provided training for the calibration laboratories and external quality assessment providers from RfB, and INSTAND on the specific example of HbA1c. The training was tailored to their specific needs and questions that arose from a real data set provided by the participants.

Dr. Caroline Stobe from RfB, who attended the course, said:

‘HbA1c is one of the most important bio markers in diabetes diagnosis and management. In order to ensure a high level of patient safety, the German Medical Association included HbA1c into its guidelines for quality assurance of medical laboratory analyses (Rili-BÄK). Consequently, it is mandatory for German medical laboratories to participate in external quality assessment (EQA) for this analyte.

Furthermore, the guidelines require these EQA schemes to be accuracy-based, applying target values assigned by the IFCC reference measurement procedure (RMP). RfB is one of the few EQA providers appointed by the German Medical Association for this purpose. Being a member of the IFCC Network for Standardisation of HbA1c, our calibration laboratories have been assessing RfB’s EQA samples since 2019. However, the acceptance limits set by the Rili-BÄK have gradually been tightened from ± 18% to ± 8%. We consider it our responsibility to continuously monitor our RMP and its MU to be fit-for-purpose to meet the requirements for these accuracy-based EQA schemes.

This is why we decided to join forces with our colleagues from INSTAND, MHH and PTB to discuss and examine the method regarding all possible contributions to its MU. We consider this kind of collaboration essential and especially fruitful to both establishing and maintaining reference measurement systems in clinical chemistry: Calibration laboratories contribute with their long-time experience of applying RMPs on a daily basis to many kinds of samples. NMIs like PTB offer a unique, critical and sophisticated view on traceability to the highest metrological order and in the calculation of MU for complex RMPs. The excellent workshop offered by PTB for HbA1c is only one showcase for this important collaboration. I’d like to thank all participants for their contribution – especially Dr. Olaf Rienitz who did an impressive and excellent job elaborating and leading the workshop.’

Dr Christine Brauckmann, from PTB’s Department of Biochemistry, organiser of the workshop added:

‘The close collaboration between PTB and the German calibration laboratories, INSTAND, RfB and MHH, allows us to have a much greater insight into the needs and challenges of supporting metrological traceability in clinical laboratory medicine. To identify and discuss those needs, representatives of PTB and the calibration laboratories meet regularly. This enables us to discuss topics from different points of view, obtain a comprehensive impression of the situation and understand how PTB can best contribute with its metrology expertise. The uncertainty workshop resulted from one such meeting and was planned and designed specifically to meet the requirements identified by the calibration laboratories.

In planning the workshop, it was crucial to understand the most suitable measurand and the measurement procedure in calibration labs. Dr. Olaf Rienitz used this info and RfB data to estimate uncertainty in HbA1c measurement results. This approach was presented and discussed at the workshop, fostering global comparability of patient measurements through collaboration with calibration labs.’

Dr. Vincent Delatour, Chair of the EMN TraceLabMed, comments:

‘The EMN TraceLabMed is fostering collaboration and promotes leveraging the expertise of metrology institutes, calibration laboratories, and EQA providers. This is essential for establishing fit for purpose measurements in laboratory medicine.

Training and knowledge transfer are integral to the aims of the EMN. This workshop is an excellent illustration of a training course designed to meet a specific stakeholder’s requirements. The result enables the implementation of accurate uncertainty calculations for calibration and their use in EQA programs with target values defined by reference methods. In response to survey feedback from External Quality Assessment providers and Calibration Laboratories, the EMN is partnering with the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM) to explore the possibility of expanding tailored training activities. This initiative underscores EMN's dedication to addressing educational needs, promoting knowledge exchange, and enhancing skills in laboratory medicine traceability.’

EMN TraceLabMed is supported by the joint network project 18NET02. EMPIR projects are co-funded by the European Union's Horizon 2020 research and innovation programme and the EMPIR Participating States.

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Successful measurement uncertainty training on haemoglobin test for calibration laboratories