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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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A growing number of media stories claim medical lab companies that develop genetic screening assays oversell the accuracy of such tests and fail to educate parents and doctors about the risks of false positives and false negatives

In response to growing concerns by consumers about the accuracy of some proprietary genetic screening assays, several media outlets have begun reporting on this sector of the clinical laboratory industry.

What gives these news stories emotional punch is the fact that patients use these proprietary medical laboratory tests to make decisions that can be life-changing. In its story about these tests, the Boston Sunday Globe used the headline “Oversold prenatal tests spur some to choose abortions.”

Accuracy of Marketing Claims Concerning Prenatal Lab Tests

The reporter raised questions about the accuracy of the marketing claims some clinical laboratories performing these prenatal tests make to physicians. The story also addressed the lack of understanding physicians and patients have about scientific sensitivity and specificity of genetic screening tests.

Some patients were relying on the results of genetic screening tests exclusively and were not getting follow-up clinical lab testing to verify the genetic screening test results, wrote Beth Daley, an investigative reporter for the New England Center for Investigative Journalism. The article was published in the Globe and on the center’s website. The center published the article under the headline, “Have New Prenatal Tests Been Dangerously Oversold?”.

Physicians Do Not Get Enough Information on Reliability of Genetic Tests

“[Lab testing] companies selling the most popular of these screens do not make it clear enough to patients and doctors that the results of their [genetic] tests are not reliable enough to make a diagnosis,” Daley wrote. The difference between a screening test that can detect the possibility of a chromosomal abnormality and a medical laboratory test that a physician can use to diagnose a life-threatening condition is significant, she explained.

Daley’s story was published just over two months into the 120-day period that the federal Food and Drug Administration has set for pathologists, clinical laboratory directors, and other interested parties to submit comments on its proposal to regulate LDTs (laboratory-developed tests) as medical devices (see The Dark Report, November 3 and November. 24, 2014). Citing the FDA’s proposal to regulate LDTs, Daley reported that agency officials said the new prenatal tests may be among the first tests to be regulated.

In recent months, newspapers, such as The Boston Globe, and media outlets have published stories about the growing use of genetic screening tests and the fact that these tests have rates of false positives and false negatives that are not well understood by the physicians who order and use these genetic tests.

Richard S. Cooper

Consequently, because physicians and patients are unaware of this information, the decisions they make often result in needless treatments. This problem is a particular concern in prenatal settings where this information vacuum can cause unnecessary abortions. This situation is among the reasons that the FDA wants to regulate laboratory-developed tests (LDTs), according to Richard S. Cooper (pictured above at Executive War College for Lab Leaders), attorney at McDonald Hopkins. (Photo by Duane Stork and copyright The Dark Report.)

In an article for The Dark Report, November 24, “Attorneys Outline Issues in FDA’s LDT Guidance,” Rick Cooper, an attorney with the national law firm of McDonald Hopkins, said the FDA has proposed to regulate LDTs because:

  • Current regulations under the Clinical Laboratory Improvement Amendments of 1988 do not require post-marketing safety monitoring or data gathering on adverse events;
  • Because some labs may be marketing unnecessary tests to clinicians and selling these tests directly to consumers; and,
  • Because labs need test-specific processes to verify that each LDT is safe, accurate, or efficacious.

Many Genetic Screening Assays Offered Under the LDT Exemption

While the genetic screening assays are unregulated under the LDT exemption, Daley pointed out that some clinical lab companies offering such assays claim they have near-perfect accuracy to detect the risk that a fetus may have chromosomal abnormalities, such as those for Down or Edwards syndromes. In addition, she reported that when physicians want to detect the presence of abnormalities, genetic screening tests often outperform ultrasound and traditional blood tests.

Daley cited two recent studies by clinical laboratory companies that raise questions about the reliability of such tests. The studies revealed that, when the results of a genetic screening test show that a fetus is at high risk for a chromosomal abnormality, this finding could be a false alarm in about half of all cases. In addition, Daly wrote that, when chromosomal abnormalities are extremely rare, the rate of false alarms rises.

Another Story About Questionable Accuracy of Some Gene Tests

Pathologists and clinical laboratory administrators will find another story about the questionable accuracy of prenatal testing labs to be quite unsettling. This study was also published by the New England Center for Investigative Journalism. Under the title, “Unusual Experiment Raises Concerns About Prenatal Testing Labs,” Shan Wang reported on the work of two obstetricians, Tamara C. Takoudes, M.D., and Benjamin Hamar, M.D., who specialize in high-risk pregnancies at Boston Maternal Fetal Medicine.

Taking blood samples from two women who were not pregnant, Takoudes and Hamar submitted test requests to five medical laboratory companies that perform genetic screening tests. When submitting specimens to the different labs, the two physicians claimed the blood samples were from women who were 12 weeks pregnant.

Three Medical Lab Companies Returned Inaccurate Results

Of the five medical lab companies receiving these specimens, three lab companies returned results that showed the presence of a normal female fetus, Wang wrote. The two obstetricians concluded that this result demonstrated the need for more oversight of genetic screening tests. Takoudes and Hamar published their results in a letter to the editor, “Performance of non-invasive prenatal testing when fetal cell-free DNA is absent,” in Ultrasound in Obstetrics & Gynecology.

“Quality controls are zero,” Takoudes said of the genetic screening tests, according to Wang. “As physicians we have to be more leery about the products we are using.”

NBC News also covered the story in an article, “Prenatal Tests Have High Failure Rate, Triggering Abortions,” by Susan Donaldson James. “Hundreds of thousands of pregnant women have used these noninvasive prenatal tests since they appeared on the market in 2011, with little reason to doubt their effectiveness. And indeed, studies have found the tests to be more accurate than standard screening,” she wrote.

Concern is That Test Results Cause Patients to Opt for Needless Abortions

But positive results can be incorrect in about half of these tests, added James. It could be that hundreds of women have aborted fetuses as a result of using genetic screening assays without getting a confirming diagnosis, she reported.

“One [lab test] company reported a 6.2 percent abortion rate based on screening results alone—and without further testing, there is no way to know how many of those may have been due to a false positive,” James wrote.

To confirm a diagnosis, a pregnant woman should be advised to undergo more testing, such as amniocentesis, which can be used to determine if a fetus has a chromosomal deformity that could cause Down syndrome or spina bifida, or chorionic villus sampling, which can be used to show whether a baby has cystic fibrosis, James reported.

It was not difficult for Dark Daily to find the variety of news stories and published articles quoted above that directly address the various problems with some proprietary gene screening assays. What is notable is the absence of similar stories in peer-reviewed laboratory medicine journals.

Does this mean that local pathologists—who provide routine testing to the same physicians who order these proprietary gene screening assays for some of their patients—have not yet noticed the opportunity to help their local physicians understand the true clinical implications of the advertised sensitivity and specificity of these proprietary gene sequencing tests? It this is the case, then the opportunity exists for local pathologists to be more proactive in helping physicians in their communities to understand the ramifications of the published sensitivity and specificity of these types of genetic screening assays. Doing so could lead to more informed diagnoses by physicians and improved patient outcomes.

—Joseph Burns

Related Information:

Oversold Prenatal Tests Spur Some to Choose Abortions

Oversold and Misunderstood: Prenatal Screening Tests Prompt Abortions

Unusual Experiment Raises Concerns About Prenatal Testing Labs

Prenatal Tests Have High Failure Rate, Triggering Abortions