Drugdu.com expert's response:

The selection of threshold values for reference intervals of in vitro diagnostic reagent products is a crucial step, directly impacting the accuracy and reliability of diagnostic results. Here is a reference guide for selection methods based on the following responses:

Ⅰ. Basic Principles for Selecting Threshold Values of Reference Intervals

Depending on the clinical significance, in vitro diagnostic reagents typically use either bilateral or unilateral threshold values to determine reference intervals. Bilateral threshold values usually select the population distribution range of 2.5% to 97.5%, meaning that 95% of the normal population's test values will fall within this range. For unilateral threshold values, 95% or 5% can be chosen, depending on the clinical needs and significance of the test item.

Ⅱ. Specific Methods for Selecting Threshold Values of Reference Intervals

Determining the Clinical Significance of the Test Item: Firstly, it is necessary to clarify the clinical significance of the test item, i.e., what disease or physiological state the test is used to diagnose, monitor, or predict. Based on this clinical significance, decide whether bilateral or unilateral threshold values are required.

Selecting the Reference Population: The reference population should be representative, reflecting the characteristics of the target population. Additionally, the number of individuals in the reference population should be sufficiently large to ensure the stability and reliability of statistical results.

Collecting and Analyzing Data: Collect test result data from the reference population and perform statistical analysis on the data to determine the threshold values of the reference intervals. Common statistical methods include normal distribution testing, percentile calculations, etc.

Verifying and Adjusting Reference Intervals: After initially determining the reference intervals, verification and adjustment are necessary. Verification can be conducted by comparing with other established reference intervals or through clinical applications. Based on the verification results, make necessary adjustments to the reference intervals.

III. Precautions

Considering Individual Differences: There may be differences among individuals, such as age, gender, physiological status, etc. When determining reference intervals, these individual differences' impact on test results should be fully considered.

Complying with Relevant Regulations and Standards: When determining reference intervals, it is necessary to comply with national regulations and standards. For example, documents such as the "Measures for the Registration and Filing of In Vitro Diagnostic Reagents" have specific provisions for determining reference intervals.

Continuously Updating and Optimizing: As technological advancements and clinical needs change, reference intervals may require continuous updating and optimization. Regularly assess the applicability and accuracy of the reference intervals and adjust them as needed.

In summary, the selection of threshold values for reference intervals of in vitro diagnostic reagent products is a complex and crucial process, requiring comprehensive consideration of clinical significance, reference populations, data collection and analysis, and other aspects. By using scientific methods and a rigorous approach to determine the threshold values of reference intervals, the accuracy and reliability of diagnostic results can be ensured.