|QC Practices for Molecular Testing|
Historically, the first publication of the “Westgard Rules” was shown with an example from
QC Practices for Molecular Testing
Joan Gordon, BS, MT (ASCP), Clark Rundell, PhD, Jeanne Carr, PhD, BCLD, MT(ASCP), and Todd W. Kelley MD
The laboratorians’ experience and knowledge, availability of QC materials, capabilities of test systems, test costs, and regulatory requirements have an impact on current QC practices. The earliest molecular tests were done manually and the results were determined by interpreting the presence or absence of bands on a gel. Such testing was often performed by researchers with minimal experiencein traditional QC techniques, and the QC materials consisted of previously tested patient samples. Monitoring for systematic errors was deemed to be unnecessary because test failure was easilydetected. Furthermore, since the QC materials were variable, labs did not know if a change in band intensity meant an enzyme was degrading or the selected patient control samples did not containenough DNA. Once failure occurred, the labs had to trouble-shoot and retest all of the patient samples as required by regulations. Even though the cost of doing so was a day’s work, the reagents were inexpensive, physicians did not expect a fast turn-around time, and the system was relatively easy to trouble-shoot. However, molecular test systems are now more complex and expensive, and physicians expect quicker results. Since samples for genetic molecular tests can cost at least $40 each and workloads have increased, retesting is a significant problem. The traditional QC practice of using homogeneous (consistent lot to lot) QC materials could be useful for molecular diagnostics in identifying degrading or defective system components before an actual test failure. Faced with the limited commercial availability of QC materials, some labs pool patient samples to create a reproducible source of such materials. Furthermore, new molecular systems have quantitative outputs, such as fluorescence (signal strength) or allelic ratio, which can be tracked to monitor test system performance. Statistical analysis of the QC results over time can establish expected variations. Such results can then be serially plotted on Levey-Jennings charts to monitor the test system for shifts or trends in performance. “Westgard Rules” can be applied to determine when corrective action should be taken to prevent test failure.
These traditional QC practices satisfy best practice and CLIA regulations. Particularly pertinent to QC practices but often not stringently followed by molecular labs are CLIA Sections §493.1201:
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