College of American Pathologists
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Conflicting data on genetic testing quality

July 2001
Anne Paxton

Are there quality problems in the nation’s genetic testing laboratories? The question has been subject to debate. In a much-cited article in the Journal of the American Medical Association (1999;281: 835-840), Margaret McGovern, MD, PhD, and colleagues surveyed molecular genetic testing laboratory directors and assigned quality assurance scores based on the responses to process items. They found evidence that some laboratories have not made the grade, but interpretations of the survey's findings vary.

The researchers assessed the QA practices of the laboratories using standards defined by the American College of Medical Genetics Laboratory Practice Committee. For each of the common methods used in clinical molecular genetic testing—Southern blot analysis, analytical gels, polymerase chain reaction, and fluorescent in situ hybridization (FISH)—a QA score was assigned according to whether the standards were met. Seven standards were considered for Southern blot, four for analytical gels, seven for PCR, and five for FISH.

For example, to meet the PCR containment standard, a laboratory had to have in place a minimum of three of the following procedures to minimize contamination: dedicated pipettes, dedicated reagents and solutions, pipette tips that contain a filter, positive displacement pipettes, separation of preamplification and postamplification work areas, setup under a hood, and use of gloves.

The mean total QA score for all laboratories was 90 percent, with a range of 54 percent to 100 percent. Several factors were associated with higher QA scores: a test menu of more than four tests, performance of more than 30 analyses annually, directors with board certification, and hospital settings versus research settings. Surveyed laboratories had a mean QA score of 92.4 percent for PCR, 90.9 percent for analytical gels, 89.3 percent for Southern blot analysis, and 74.1 percent for FISH. A relatively high percentage of laboratories conducting FISH (16.9 percent) failed to meet standards regarding the number of cells analyzed.

"A number of laboratories had QA scores that may reflect suboptimal laboratory practices," the study authors concluded, noting that 36 laboratories in the survey (15 percent) had QA scores below 70 percent, "suggestive of substandard laboratory practice and with the potential for adverse clinical outcomes due to incorrect diagnoses."

Some molecular pathologists believe, however, that the study can give support to both sides of the quality debate.

"The JAMA article has been quoted a lot. But another way of looking at the article is that it shows most laboratories have made the grade," says Dr. Walter Noll of Dartmouth-Hitchcock Medical Center.

Moreover, another study reported in the American Journal of Clinical Pathology (1999;112:14-21), often quoted in rebuttal to the McGovern study, surveyed laboratories on their actual errors. "To me that article carried more weight," says Dr. Wayne Grody of UCLA Medical Center. "There were a few minor errors, but the number of serious ones was only .03 percent, which is probably better than most areas of the clinical laboratory."

There probably are some problems with quality, says Dr. Steven Gutman of the Food and Drug Administration. "What we don’t know is what is the scope of these. I really can’t answer that." There are certainly a number of ways to improve quality, he adds. "But one thing I feel quite certain of: There is a real and recurrent concern about these issues, and it doesn’t seem over the last 10 years to have gone away."