In the clinical laboratory, quality control (QC) refers to the process of detecting analytical errors to ensure both the reliability and accuracy of patient test results. It is critical that laboratories have a robust method of detecting assay drifts and any other changes in test system performance that could impact patient reporting. Poor performance can result in misdiagnosis, delayed/inappropriate treatment, increased costs, and may even be potentially life threatening for the patient. Independent, or as they are more commonly known, third-party controls offer a superior solution for better error detection and accurate test system performance.
Control materials explained
Dependent / First-party control material has been produced by the instrument or reagent manufacturer for use on a specific test system. Such controls are often manufactured from the same raw materials as the calibrator, making them less sensitive to subtle changes in performance. As dependent controls are generally optimized for use with the manufacturer’s test system, these controls can mask weaknesses, and therefore, are increasingly considered less effective than independent controls.
Semi-dependent control material, although produced independently of the instrument or reagent, is often supplied or recommended by the instrument/reagent manufacturer. It is this manufacturing relationship between the two that requires close scrutiny when considering if these controls are fit-for-purpose. Although the control material is not directly produced by the instrument manufacturer, they are often produced according to their exact specifications and therefore, optimized to work with a specific test system.
Independent or third-party quality control material has not been designed or optimized for use with any instrument, kit, or method. This complete independence enables the quality control material to closely mirror the performance of patient samples, and in doing so, provides an unbiased, independent assessment of analytical performance across multiple test systems.
Benefits of using third-party controls
Third-party controls have been designed to deliver an independent, unbiased assessment of performance with any instrument or method and can even help to maintain or gain laboratory accreditation. Below are some of the key benefits of third-party controls:
- Detection of analytical test system errors and/or reagent issues.
- Sensitive monitoring of any shifts in test system performance.
- Analytical performance assessment throughout the patient reportable range especially at clinical decision levels.
- QC target values are often assigned using a large number of independent laboratories ensuring statistically valid targets to compare to.
- Highly consolidated, multi-analyte controls allow for space, time, and ultimately, cost savings.
- Designed to be used with many different laboratory analyzers and methods helping to further reduce the number of controls required.
- Boosted shelf life ensures long term QC monitoring, continuity of lot supply, fewer lot crossovers and reduced costs.
- Reduced preparation time and increased efficiency by removing the need for multiple instrument controls.
Third-party controls are growing in popularity across the globe. And more and more laboratories are beginning to use third-party controls as part of their daily QC strategy. The benefits of such controls are also recognized by the International Organization for Standardization:
“Use of independent third-party control materials should beconsidered, either instead of, or in addition to, any control materials supplied by the reagent or instrument manufacturer.”
ISO 15189:2012 Section 5.6.2.2
ISO 15189:2012 Medical Laboratories – Requirements for Quality and Competence
Case studies
The benefit of running third-party controls in your laboratory cannot be underestimated. The following case studies highlight their many benefits and how they have helped laboratories across the world to provide more accurate and reliable test results.
Case study one
Identifying lot-to-lot variability with third-party controls: A laboratory in the United Kingdom contacted its third-party control supplier reporting higher than expected QC results for thyroglobulin. When using a third-party control, the results were four times higher on their main analyzer compared to other systems. However, when they ran the instrument’s manufacturer control alongside the third-party control, it failed to show the issue. After an exhaustive review of procedures and processes, the customer contacted the instrument manufacturer, who advised of a positive bias with several batches of reagent, including the batch the laboratory was using.
Conclusion: By using a third-party control, the laboratory was able to detect a shift in results after changing the reagent batch that the manufacturer’s control did not.
Case study two
Overcoming instrument errors with third-party controls: A laboratory using a third-party control observed a consistent, negative bias for a alanine aminotransferase (ALT) test that was not replicated by the instrument’s manufacturer control. The laboratory contacted its instrument manufacturer who advised that the problem was with the control and not the reagent or instrument. The third-party control supplier was also contacted; they investigated the problem and were able to demonstrate that patient results were also wrongly reported low. This later led the instrument manufacturer to recommend a wash stage to eliminate any interference.
Conclusion: The use of a third-party control in this instance enabled the identification of a procedural error with the instrument that the recommended control did not identify.
Case study three
In Vitro diagnostic company recall: A study in Biochemia Medica1 reported on an in vitro diagnostic (IVD) field safety notice relating to an intact parathyroid hormone (PTH) assay. The IVD company explained the reasons for the recall as follows:
- Performance shifts seen with their intact PTH assay had the potential to generate falsely elevated patient results.
- Results generated from impacted reagent lots demonstrated a positive shift compared to those generated with previous reagent and/or calibrator lots.
- The magnitude of the shift averaged approximately 13% to 45%.
- The instrument’s manufacturer controls did not detect the shift
Conclusion: In this example, the instrument’s manufacturer controls did not detect the performance shift. The paper concluded that PTH result variability could have been prevented by third-party control materials independent from the calibrator materials — either instead of or in addition to any control materials supplied by the analyser manufacturer. The recall could have resulted in up to 40,000 inaccurate laboratory tests in 19 labs in the Lombardy region of Italy.
References
- Lima-Oliveira G, Lippi G, Salvagno GL, Brocco G, Guidi GC. In vitro diagnostic company recalls and medical laboratory practices: an Italian case. Biochem Med (Zagreb). 2015;25(2):273-278. doi:10.11613/BM.2015.028.
