How to realize accurate testing? Diagreat has the answer.

How to realize accurate testing? Diagreat has the answer.

How to realize accurate testing? Diagreat has the answer.

IVD products all want to ensure that clinical test results are accurate and reliable, so that doctors' diagnostic results are accurate and consistent, and the test results of different testing systems, different hospitals, different periods, and different operators are comparable, which ultimately promotes the development of clinical testing and benefits patients. The essence of clinical test results is in fact the calibration product traceability and transmission of the results, so the realization of accurate calibration product traceability and transmission of the value of the test results of in vitro diagnostic reagents is critical to the accuracy of the test results, only to pay attention to the study of the traceability of the value of in vitro diagnostic reagents, to ensure that the traceability of the accuracy of the consistency of the value to ensure that the clinical value of the measurement of the value of the accuracy and reliability.

Then how to realize accurate traceability and transmission of quantitative value?

First of all, we have to first understand what is the traceability and transmission of quantitative value.

Measurement traceability is a bottom-up process by means of an unbroken chain of comparisons with a defined uncertainty that enables the measurement result or the value of the measurement standard to be related to a defined reference standard (Figure 1). In contrast, the transfer of measurements is the transfer of its own measurements from a higher level of measurement and calibration department to a department with a lower accuracy level than its own. The main difference between traceability and transfer is that traceability is a bottom-up activity with initiative, while transfer of measurements is a top-down activity with compulsion. Therefore, IVD manufacturers should establish a calibration traceability program for each batch of calibrators produced, and take the initiative to trace quantitative values higher than their own accuracy level to determine their own accuracy.

How to realize accurate testing? Diagreat has the answer.


How to realize the traceability and transmission of quantitative values?

There are two things to realize in simple terms:

The first step is to establish our own traceability standards, i.e. where we trace back to;

Next, a traceability chain is established and strictly enforced to ensure that traceability does not deviate (Figure 2).

How to realize accurate testing? Diagreat has the answer.

Figure 2

Then in order to realize accurate traceability and transmission of quantitative value, it is necessary to start from the above two points, establish scientific and reasonable traceability standards, find reliable reference substances and reference measurement procedures, and strictly control the traceability process to ensure the consistency of traceability.


Selection of reference substances and reference measurement procedure

Measurement results are metrologically traceable to the SI of the measured object

There are available primary reference measurement programs and one or more (certified) primary reference substances (as calibrators). There are about 25-30 types of quantities at such levels with well-defined components, e.g. some electrolytes, metabolites, steroid hormones and some thyroid hormones.

Measurement results cannot be metrologically traced back to the SI measured

1)There is an available internationally agreed reference measurement procedure (which cannot be referred to as a primary reference measurement procedure) and one or more internationally agreed calibration substances, such as glycated haemoglobin, which are calibrated with this reference test measurement.

2)There are available internationally agreed reference measurement procedures, but no internationally agreed calibration substances. The quantities of about 30 types of components that meet these conditions, e.g., such as certain coagulation factors, blood cells (ICSH reference method), HDL cholesterol, etc., are available

3)One or more internationally agreed calibration substances (used as calibrators) and assignment schemes are available, but there is no internationally agreed reference procedure. There are about 300 quantities that meet these conditions, e.g., quantities using World Health Organization (WHO) international standards (protein hormones, certain antibodies and tumor markers, etc.).

4)Neither a reference measurement program nor a calibrated reference substance is available. Manufacturers establish their own "in-house" source measurement programs and source calibrators to value product calibrators. These qualify for the quantities of approximately 300 components, such as certain tumor markers and antibodies.

Depending on the item to be tested we can choose the reference substance and the reference measurement procedure of the highest current level of measurement. It should be noted in particular that for items without an international reference substance, nor a national reference substance, nor an agreed reference method, it is preferable to use a pure substance to prepare an alternative reference substance and to establish an internal measurement procedure, and the manufacturer should examine the scientific and rigorous nature of the procedure, which is generally based on the use of a recovery method for confirming and correcting the quantitative value of a customized source reference substance.


Strict control of the traceability process

 Equipment Confirmation

The equipment used in the traceability process must be measured by qualified laboratories and within the validity period. Even if there is a measurement certificate, the qualification certificate of the measurement unit should be examined to see whether the proper position can be found on the traceability chart and whether the deviation level meets the requirements; whether the equipment is in normal condition when it is in use, so as to avoid deviation caused by equipment problems.

Confirmation of detection methods

1)Direct Assignment Method.

This is a method of transferring quantitative values by directly assigning values to the manufacturer's calibration products using a higher-level reference substance or reference measurement system.

2)Comparison method. 

Regression adjustment of the fixed value of the manufacturer's calibration product with the detection results of the selected reference detection system. When the slope is close to 1 and the intercept is close to 0, it means that the vendor's detection system can be traced back to the reference measurement system, and this method of traceability means that the value is transferred through the calibration product.


Uncertainty assessment

Different levels and concentrations of calibration products in the process of value transfer due to its own stability, homogeneity, the assignment process will introduce uncertainty, the uncertainty of the calibration products will also be transferred to the patient's test results, the uncertainty of the calibration products is a measure of the reliability of the value assigned to the calibration products of the quantitative indexes, so according to the source of the uncertainty, as far as possible, to reduce or eliminate the influencing factors caused by the uncertainty is the relationship between the patient's test results is one of the key factors of the accuracy of one of the key elements of the test results.

In the process of establishing the traceability system, the sources of uncertainty of in vitro diagnostic reagent calibrators mainly contain 3 aspects:

  • First, the calibration process, including the precision of the instrument and reagent, the uncertainty of the previous calibration, and the reconstitution or correction of the calibration. Second, the calibration product uniformity, including the uniformity between bottles and the uniformity within bottles.

  • Second, the uniformity of the calibration product, including inter-bottle uniformity and intra-bottle uniformity.

  • Third, calibration product stability.

The uncertainty is reduced by standardizing the calibration process, strictly controlling the precision of instruments and reagents, improving the stability of calibrators, reducing the number of calibrations, etc., so as to control the uncertainty within the target uncertainty. It should be noted that, in the process of value transfer, in order to ensure that the target uncertainty of the measurement can be achieved, it is necessary to specify the target uncertainty of each grade of calibration products, and the target uncertainty of the measurement needs to meet the clinical needs of the end customer.


[1] ISO. In vitro diagnostic medical devices — Requirements for establishing metrological traceability of values assigned to calibrators,trueness control materials and human samples[S]. ISO 17511:2020

[2] Wang Ning. On quantity value traceability and quantity value transmission [J]. Measurement and Testing Technology, 2016, 43 (1): 54-55.

[3] Xie Jing, Zhang Ying. Method for transmitting quantitative values of in vitro diagnostic reagent product calibrators [J]. Shanghai Medicine, 2019, 40 (13): 43-64.

[4] Liang Chunying, Li Xiaojiang, Chen Hongzhen. Analysis on the current status of traceability of in vitro diagnostic reagent calibrators [J]. Journal of Clinical Laboratory Science, 2020, 9 (1): 247-249.

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