Quality Control Levels

Vol. 24 • Issue 5 • Page 34

Quality Control

Almost every laboratorian struggles with setting appropriate levels of quality control (QC) to analyze in clinical diagnostic testing. Those looking to learn what “the right QC” is for any given assay must consider not only regulation and guideline requirements, but also performance characteristics specific to the assays themselves. Identifying “the right QC” can be a daunting task for most laboratories; however, the process of implementing the Center for Medicare & Medicaid Services’ (CMS) Individualized Quality Control Plan (IQCP) may present a viable solution to this challenge. Part of CMS’ process includes the assessment of what the right QC strategy is for a lab and another is to evaluate which types of quality controls to employ ( i.e., liquid versus lyophilized product, electronic QC, proper utilization of patient averages, delta checks, proficiency material, etc.). This article focuses specifically on how to determine the right QC levels needed when running liquid and/or lyophilized QC products.

5 Considerations

1. Be cognizant of manufacturer recommendations. QC design strategy usually occurs during the assay validation process; however, it is important to review any future changes communicated by the manufacturer, as changes could contradict with the original QC design decisions.

2. Lab professionals must follow all requirements set in place by respective accrediting organizations, including those from local and/or state regulatory agencies. Failure to comply with regulatory standards, regardless of intention or QC conclusions, may lead to citations during inspection. Each agency has its own requirements. Careful and regular review is the responsibility of the laboratory.

3. Laboratorians must review the assay’s reference range and determine the key medically relevant decision levels that clinicians require when treating a patient. This action minimizes potential inaccurate patient results and ultimately leads to improved patient outcomes.

4. Lab professionals must review the manufacturer’s assay package insert to be aware of any potential interference or instability issues.

5. Lastly, one must assess an assay’s calibration type (linear vs. nonlinear) before choosing how many levels to run. An inadequate choice of QC levels could lead to undetected failures along target sections of the calibration curve.

QC at Medically Relevant Levels

QC results should recover at key diagnostic relevant ranges to ensure accuracy of patient results. If a test has three distinct medical decision levels, it is critical to run three levels of control. Doctors may rely on specific ranges to decide what the best course of action is for treating their patient. A patient who is compliant with a prescribed therapeutic drug, for example, should fall within the therapeutic (normal) range. If, however, the physician is concerned whether the patient has taken too much or too little of the prescribed medication, the lab must assure results get monitored at each of these areas of the reportable range. Otherwise, when an assay calibration curve drifts out of specification, potential errors could go unnoticed, allowing erroneous results to be reported. Labs that only monitor QC at two levels, as in this example, would run the risk of reporting such erroneous results.

Beware of Interferences

Setting improper levels of QC could lead to assay interferences going undetected. The FDA released a notice to laboratorians and doctors in March 2013 after determining that assay interferences led to elevated Troponins I and T results, therefore leading physicians to misdiagnose patients with myocardial infarction. These interfering substances resulted in a falsely high Troponin I or T result. In the notice, the FDA stated that “. at least one control should be run at the cutoff level. If the risk stratification and acute myocardial infarction cutoff are different, separate controls should be considered at those levels.”

By using three levels of QC to monitor Troponin I and T results, laboratories increase confidence in final patient results while minimizing risk.

The Role of a Calibration Curve

A test’s calibration curve shape must also be considered. The laboratorian should ask the following questions:

• How many calibrators are used to determine and set the assay curve?

• Does the calibration curve stability meet the minimum requirement instructed by the manufacturer?

Many feel that running two levels of control (one normal and one abnormal) for every assay is an acceptable laboratory practice. Though it may be in some cases, the laboratorian should consider an additional level of control when validating nonlinear tests, as explained by R. Neill Carey, PhD, clinical chemist, Peninsula Regional Medical Center, Salisbury, MD:

“Historically, immunoassay tests were generally done with three levels of control because immunoassay dose-response curves are nonlinear and require multiple calibrators. Since medical decisions are made at several concentrations for many analytes, the usual ‘normal and abnormal’ controls often do not provide a high enough comfort level. Many analytes have multiple decision levels. There are three for TSH: below reference range (boarder line hypothyroid), normal and elevated (hyperthyroid).”

The additional level of QC in Dr. Carey’s example increases the probability that accurate patient results get reported within each portion of the clinically relevant range. The laboratory may risk releasing patient results that are not accurate if the calibration curve drifts at concentrations where a bi-level control is not analyzed (Fig. 1).

Archive Image

Click to view larger graphic.

If the lab runs a linear assay (Fig. 1, chart A), the high QC level would detect the systematic error, prompting most laboratories to hold new patient results and troubleshoot the test system. However, with the nonlinear assay (Fig. 1, chart B), the laboratory would only detect the error if the lab were running a tri-level control product at key ðconcentrations. If the laboratorian chose to use two levels of controls (a low and a high concentration), patients’ results in the level two (or middle of calibration curve) could be inaccurately reported or go undetected. Depending on the test, doctors may rely on this second level, which in this case, could have been reported erroneously.

Budget vs. Risk

Lab managers must not only report accurate and reliable results, but need to do so within the constraints of increasingly tight budgets. While doing more with less has become a key objective for laboratory administrators, it is vital that steps are taken to prevent risk from occurring due to budget decreases. ðLowering QC frequency or the number of levels to monitor may provide easy solutions to budget issues, but more importantly, such actions could negatively impact lab reputation or, ultimately, cause harm to patients.

Terri Wolek, MT(ASCP), is senior sales product manager, Quality Control, and Adalto Nascimento is the associate sales product manager, Quality Control, Bio-Rad.


1. http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/TipsandArticlesonDeviceSafety/ucm109362.htm

2. Carey RN, PhD, Clinical Chemist, Peninsula Regional Medical Center, Salisbury, MD. http://www.westgard.com/guest4.htm#qcfor

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