A study of cell free DNA testing laboratories adherence to medical guidelines made the following finding: all met some of the guidelines, none met all of the guidelines.
In 2016, the American College of Medical Genetics issued updated medical guidelines on cell free DNA screening. The guidelines included recommendations for what information should be shared with a test result.
While the marketing materials of cell free DNA screening laboratories highlight the testing’s accuracy, the ACMG guidelines recommended information be shared with patients so that they understand how relatively accurate their test results are.
As has been covered at length on this blog, testing laboratories have touted reporting “positive” or “negative” results, even though their test results remain probability assessments and are neither truly positive nor negative. The numerous comments on this blog from expectant couples receiving a “positive” result and asking what their test results actually means testify to the confusion caused by the imprecise lab reports.
Seeking to address this confusion, over two years ago, the ACMG recommended that testing laboratories report the “positive predictive value” or “PPV” for each test result. While the test’s ability to detect conditions like Down syndrome may be as high as 99%, when the chance the result is a false positive is taken into account, that arrives at the test’s PPV. This is why a 25 year old mom may receive a “positive” test result with 99% accuracy, but her true chances of her result being positive, her PPV, is 51%.
As can be seen in the image at the beginning of this post, only one of the ten commercial labs surveyed are reporting PPV with its test results. If all labs adhered to these years-old guidelines, I expect patients would understand the relative accuracy of their screen results and quite likely fewer would leave comments here expressing anxiety, fear, and confusion.
Similarly, professional guidelines have recommended since 2008 that patients be provided accurate information about the tested-for condition, be referred to a genetic counselor, and recognize that national and local parent support organizations can be very helpful. The ACMG in its initial statement on cell free DNA testing in 2013 and again in its updated statement in 2016 listed specific resources that patients should be provided when they receive a test result.
The testing laboratories entered the market highlighting their ability to provide information about conditions like Down syndrome sooner than ever and with greater accuracy. So, let’s see how they’re doing in providing information about Down syndrome and the other conditions they test for:
Again, Q’Natal is the exception that proves the rule: while Q’Natal reports PPV and provides patient resources as recommended by the ACMG guidelines, NONE of the other nine laboratories satisfied the guideline. Only three others partially satisfied the recommendation. And, included in the remaining six laboratories is Sequenom: the lab first to market in 2011, who launched relying on a study that stated educational materials would be needed for patients and physicians alike!
As the headline reads, all of the labs met some of the guidelines. The report recognizes when guidelines are satisfied by giving those labs a “green” passing rating. For example, the ACMG guidelines recommended that all reports should include a clearly visible fetal fraction. Here is how the labs scored:
All but one got green ratings. So, it has been shown that the laboratories can meet the ACMG guidelines. As Dr. Brian Skotko, the lead author of the study commented in a Reuters report on the study,
“We want this big table to be replaced by one with all green dots,”
The full table has helpfully been published at the Prenatal Information Research Consortium. The article appears in the April 2019 edition of Genetics in Medicine.
I was fortunate enough to be included as a co-author for this study. My fellow co-authors deserve commendation for the hours and months of work this study required of assembling test report data, analyzing information provided by the laboratories, and then the multiple rounds of scoring to arrive at a consensus amongst professionals of varied disciplines.
Like Dr. Skotko said, it is my hope as well that the laboratories are motivated by this public scoring of their adherence to the ACMG guidelines to bring all of their ratings to the green level. By doing so, they will be delivering test results marketed as being accurate, as truly being accurate for what the test results mean, both in terms of probability and what a life with the tested-for condition can be like.
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