Overselling without proper education leads to abuse of patients
With our understanding of how our genes are working having made truly remarkable progress over the last two decades (see also a related article on “epigenetics” in this month’s newsletter), and with diagnostic testing capabilities often leapfrogging even that advanced understanding, we have been witnessing a rapidly growing genetic testing industry that, increasingly, appears out of control. We do not use the term “out of control” lightly, but with genetic diagnoses assuming increasing importance as part of personalized and/or precision medicine in so many different specialty areas, the same or similar complaints are heard all over and can be best summarized as diagnostic tests being brought to market before being properly validated. Tests, therefore, are often over-interpreted in clinical relevance. In a rush to bring these tests to market, corners are cut, and clinical activities are set into motion, which not always serve the best interest of the public.
Another highly complex aspect of the genetic testing industry is that very consequential genetic tests are marketed directly to the public without adequate consideration for potential unintended consequences. One story that recently attracted considerable media attention was the individual who for a lifetime assumed to have no siblings but, after waiving anonymity with one of these direct-to-consumer genetic testing companies, discovered (by last count) over a dozen half-siblings, all sharing the same sperm donor.
Problems with genetic testing are not only restricted to direct marketing to the public. Tests offered through the medical community are also often inadequately explained to physicians, who then are not adequately educated to pass the message on to patients. They are frequently unable to accurately judge the accuracy of representations made by the commercial genetic laboratory industry. Especially in reference to preimplantation genetic screening (PGS), now renamed preimplantation genetic testing for aneuploidy (PGT-A), the VOICE has on prior occasions in depth addressed this issue in a number of articles. Here, many reproductive endocrinologists offering the PGS/PGT-A routinely with every IVF cycle still do not know how to correctly interpret the received lab-reports.
Non-invasive prenatal screening (NIPS) as a troubling example
Reproductive medicine is also greatly affected by overaggressive marketing drives of the genetic laboratory industry in other areas. For example, Linda Carroll in a Reuters dispatch recently reported that “no U.S. lab follows guidelines for cell-free prenatal testing” for chromosomal abnormalities in offspring during early pregnancy, quite a remarkable observation, considering that these recommendations were published by the American College of Medical Genetics.
The behavior of the genetics industry here in many ways mimics what has been happening with PGS/PGT-A: So-called non-invasive prenatal screening (NIPS), a simple blood test, is not meant to be a final diagnostic test in determining whether an early pregnancy is chromosomally normal or not but as a preliminary screening test in women considered to be at increased risk for chromosomal abnormal pregnancies. The idea behind the test was that such women, if demonstrating a negative NIPS, would be saved from having to undergo an invasive prenatal test such as chorionic villous biopsy (CVS) or amniocentesis.
The predictability of NIPS is based on a number generated by the blood test in combination with the mother’s age, which allows calculation of the percentage of women with the same results that ended up having a pregnancy with, for example, Down’s syndrome. Instead of reporting this “probability,” many labs, however, simply report out the test as “positive” or “negative.” The positive range is quite wide and neither parents nor treating physician can make an appropriate judgment call without knowing what the probability is (i.e., where their result falls in that range).
This is the same unacceptable way of reporting results that PGS/PGT-A was exposed to for years, when embryos were declared either euploid (chromosomally normal) or aneuploid (chromosomally abnormal). In July of 2016, the industry, finally, added a third diagnostic category, the so-called mosaicism, to the reporting scheme, but till today, has not validated this reporting system. Linda Carroll also pointed out that many labs also ignored the recommendation to provide adequate education about how the test should be interpreted. Here again, the analogy with what has been going on with PGS/PGT-A is quite remarkable; till today, not only patients have largely gone uninformed but physicians ordering the test are often also unaware what a given result really means.
Rapid increase in the use of expanded carrier screening
Another product the genetic industry has been heavily promoting to fertility centers and general Ob/Gyn practices is expanded carrier screening for recessively inherited diseases. If an individual is a carrier (i.e., inherited a single mutation causing a given disease) of a recessive disease, she/he is not affected by the disease. If the carrier, however, produces a child with another carrier, the couple has a 1 in 4 (25%) chance of giving birth to a child who is affected by the disease.
Testing for recessive diseases, therefore, makes sense, especially if they have a significant prevalence within a given ethnic community. For the longest time, CHR and most other fertility centers performed such selective ethnicity-based testing only on the female, because if one partner was negative, the other no longer had to be tested. This practice resulted in relatively little testing since most women were, of course, negative in their restrictive ethnicity-based testing and their partners required no further testing.
That, however, has changed because the genetic testing industry, using new and more economic techniques, is now offering expanded carrier screening, including close to 300 tests for different diseases for basically the same costs as only a handful of diseases required with ethnicity-based restricted testing. When women are tested for ca. 300 diseases, however, almost everybody will test positive for one disease or the other, resulting in the automatic need to also test the partner. As a consequence, much more partner testing is now done and the genetic testing industry, of course, financially profits from more testing.
The industry is arguing that this is good medical practice because how can one not test when it, potentially, prevents the birth of affected children. In many ways, this is a valid argument; however, on the other side stands an equally good argument against such testing because, when testing for almost 300 recessive diseases, most of which have very low prevalence in the population, the associated risk for each of these extremely rare condition to be present in carrier state in both partners is extremely remote. Expanded carrier testing, therefore, increases overall testing costs even though costs per test have significantly declined. What is also usually overlooked are the additional administrative and clinical staffing costs required to manage such an expanded testing program. The only real winner in all of this, therefore, is, once again, the genetic testing industry.
Problems with genetic testing do not only exist within reproductive medicine. Similar issues as pointed out here also exist in other areas of medicine, no more so than in oncology (cancer medicine). Though dramatic and important progress has been made in this field because of genetic research and subsequent changes in therapies arising from newly obtained knowledge, over-interpretation of genetic results in this sphere of research and clinical practice appears only too common. That genetic testing has become big business is not necessarily a bad thing as long as such testing serves patients’ well-being. When genetic testing, however, becomes abusive by providing unnecessary and/or even incorrect information simply because of financial business incentives, one must call attention to such abuse. Much of what is going on in the genetic testing industry today does, indeed, border on abuse.