Internal Quality Control in Medical Laboratories: Westgard and the Others

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear author,

I have read your work. I find it very practical and useful as an overview article on an area that is not easy to interpret. The concept of quality control is widespread and diverse in the world. I'll start with two approaches and possible interpretations. The Westgard approach is quite practical and easy to apply. It is practically the basis for further considerations. The newer approach, which is broader and includes measurement uncertainty and traceability, is not as simple for end users. In addition, when patient samples are used. The inaccuracy can be checked quite easily using commercial controls. For the use of patient samples, although much more reliable under real conditions, laboratory personnel need to master the basics of statistics, which is sometimes not possible in practice. This paper shows what the Italian society has defined and applies at the national level and following the ISO standards for the field of quality in laboratory medicine.

For all these reasons, I believe that the work can be published in its current form and that there is no need for corrections.

Author Response

Thank you for the appreciations. I hope to contribute to the growth of knowledge on the subject by medical laboratories.

Reviewer 2 Report

Comments and Suggestions for Authors

The present manuscript provides a comprehensive examination of current requirements and emerging alternatives related to internal quality control (IQC) within medical laboratories, with a specific focus on the recent ISO 15189:2022 standard and the Italian Society of Clinical Pathology and Laboratory Medicine (SIPMeL) Recommendations Q19.

This paper begins by contextualizing the evolution of ISO 15189:2022, highlighting its extensive revision process and its focus on both monitoring examination results and estimating measurement uncertainty.

A substantial segment of the review delineates a comparison between two overarching methodologies in Internal Quality Control (IQC): the “metrological” (tracealogic) methodology, which prioritizes traceability and calibration through the utilization of certified reference materials, and the “statistical” methodology, which centers on the surveillance of system variability employing third-party control materials. The author provides a critique of the tracealogic methodology, positing that although traceability is essential for calibration, the application of reference materials for routine IQC is fundamentally flawed due to economic considerations, impracticality for continuous monitoring, and infringement upon established quality control principles.

Subsequently, the paper examines alternative IQC strategies that align with ISO 15189 and SIPMeL Q19, such as the Moving Average (MA) of Patient Results, Repeated Patient Examinations (RPT-QC), and the Bayesian Approach.

The paper thoroughly covers the latest ISO 15189:2022 requirements and SIPMeL Q19 recommendations, offering a balanced critique of both metrological and statistical approaches. By discussing alternatives such as the moving average, repeated patient examinations, and Bayesian approaches, the paper encourages laboratories to adopt more robust and adaptive IQC strategies, thereby moving beyond traditional control chart methods.

I have some minor comments to improve the overall quality of the manuscript:

• The review is significantly reliant on existing literature and recommendations; however, it offers limited original data or case studies that illustrate the real-world impact or efficacy of the IQC methods discussed. Please consider incorporating some practical examples.
• Although the paper acknowledges the computational and optimization requirements associated with methods such as moving averages, it fails to comprehensively investigate the practical obstacles hindering adoption (e.g., software availability, staff training) or offer detailed guidance for implementation. I suggest including a brief paragraph addressing this issue.

Author Response

Comment 1: it offers limited original data or case studies Please consider incorporating some practical examples.

The review examines proposals that have recently appeared in the literature or in promotional events (courses, webinars, and the like) for IQC, which induce laboratory operators to change their procedures or purchase ad hoc products or services. The objective of the article (derived from an oral presentation) is to point out the compatibility or non-compatibility of the proposals with ISO 15189 requirements. Providing practical examples for all alternatives drawn from the real world, moreover easily found in the sources cited, would be beyond the scope of the article.

However, we supplement the R1 text with a note and two very recent articles for moving averages:

"Practical examples from the real world can be found in the literature contributions cited, such as in the recent example of hematology examinations [Rossum2025], [Cembrowski2025]. While this article merely judges the compatibility of alternatives with ISO 15189 requirements.

• van Rossum, H.H., Giannoli, J.-M. and Badrick, T. (2025), Patient Moving Average for Continuous Real-Time QC; Real-World Application Illustrated. Int J Lab Hematol, 47: 570-573. https://doi.org/10.1111/ijlh.14462

• Cembrowski, G. (2025), Whither Hematology Moving Averages?. Int J Lab Hematol, 47: 555-556. https://doi.org/10.1111/ijlh.14432"

 

Comment 2: investigate the practical obstacles hindering adoption (e.g., software availability, staff training)

The issue of availability of IT resources is very important. The reviewer is right in noting that some considerations would be needed in this regard. Let us add a small paragraph to R1 for this purpose.

"The principle of averaging over patient results has been known for many years and used in many computer systems [Rossum2016][7]. General-purpose spreadsheets or programs such as Matlab, as well as patented systems, have also proved useful for analyzing data. Despite this, it is little used in laboratories, for various reasons studied by researchers. But the subject has undergone many evolutions. There are those who offer free computer programs [Çubukçu2024][23]. Mention of commercially offered tools is present in many articles, but the relative responsibility remains with their Authors; it is not appropriate for it to be also charged in this review."

Reviewer 3 Report

Comments and Suggestions for Authors

This review compares some requirements for internal quality control from ISO and SIPMeL.  The manuscript reads like a legal document or technical manual and is challenging for a general laboratorian to understand.  That makes the review of interest and use for a fairly narrow audience of laboratory professionals interested in developing laboratory standards.  Basically it describes how some recommendations for IQC from ISO and SIPMET differ.

There is little discussion about the merits of different proposals for IQC, and it is all on a theoretical level without any examples of how the recommendations would be applied to any specific test.  There probably should be some discussion at the advantages and disadvantages of different proposed IQC measures.

Moving averages have problems if there is wide variation in the patient population.  Perhaps batches of specimens from a dialysis clinic or pediatric ward would deviate from values from other populations for many tests.  A moving average probably works better for tests with a narrow distribution such as sodium and not so well for enzyme values where a few extreme high values might affect a mean.  Perhaps a median would often be a more robust measure of bias, and percentages of low or high values might detect problems at assay extremes not detected by measures near the median.  Batchwise molecular testing often examines positivity rates of batches to assess changes that may indicate a problem of contamination, for example. 

Use of traceable QC materials usually poses a significant additional expense, and there may a more limited selection of materials., and usually with a matrix slightly different than patient specimens.

The scope of the discussion is narrow.  Maybe that is related to the scope of the documents discussed.  There would be quite a few other approaches that can be taken to assure the quality of testing.

Many QC materials have programs for peer comparison that may help improve harmonization.

There is the potential for many internal QC measures that apply to the detection of problems with an individual analysis, some that are implemented in automated instruments to assess specimens such as serum indices, pressure sensors to detect clots or bubbles, signal processing or multiple measurements that may be applied to electrode measurements or kinetic analyses.  Some of these measures assess specimen integrity and the performance of an instrument for each analysis.   Delta checks serve as another common IQC procedure although depending on availability of prior test results for an individual patient.

Evaluating ratios such as urea/creatinine and calculations such as anion gaps can serve as IQC measures.  When there is a trend in anion gaps, our technologies know that it is time to clean or replace the electrode sensors, for example.  In the future, AI is likely to be able to identify more complex patterns of results that are suggestive of an assay problem.

 

 

 

 

 

 

 

 

 

Author Response

Comment 1: discussion about the merits of different proposals for IQC … advantages and disadvantages of different proposed IQC measures.

The objective of the review is to highlight the compatibility of different solutions with ISO 15189 requirements, not to build a ranking of merits and demerits, which would require a different kind of study. When a laboratory seeks accreditation, there is no obligation to adopt one or another solution. The one adopted by the laboratory, however, must be adequate for the ISO standard. Advantages and disadvantages depend greatly on the conditions of the individual laboratory.

This note is added to the R1 text in final messages paragraph.

 

Comment 2: Perhaps a median would often be a more robust measure of bias, and percentages of low or high values might detect problems at assay extremes not detected by measures near the median. Batchwise molecular testing often examines positivity rates of batches to assess changes that may indicate a problem of contamination, for example. … There would be quite a few other approaches that can be taken to assure the quality of testing. ... serum indices, pressure sensors to detect clots or bubbles, signal processing … Delta checks … ratios such as urea/creatinine and calculations such as anion gaps … AI is likely to be able to identify more complex patterns

The reviewer's comments are all correct and very helpful. However, the IQC chapter is very large; this review is not intended to exhaust all its points, but rather to highlight proposals that have recently appeared in the literature or in promotional or educational events (courses, webinars, and the such like) for IQC, which cause laboratory operators to modify their traditional procedures or purchase ad hoc products or services. The limitations of this review are succinctly stated in the conclusions or final messages of R1, without overextending the text of the article.

“This concise review does not exhaust all alternatives for IQC, but points out only those more recently brought to the attention of laboratories in the literature or in promotional or educational events (courses, webinars, and the like). It does not consider the possibility of using estimators such as median or percentage of high or low results, neither peer comparison, nor the use of individual sample data, such as serum indices, clot detection, bubbles, kinetics analysis, or electronic signals. As well as individual delta check or calculations on results such as urea/creatinine ratio or anion gap. About the so-called “artificial intelligence”, one waits to see the possibilities in this field.”