Last November, FDA ordered 23andMe (Mountain View, CA) to discontinue offering its direct-to-consumer DNA testing service, which provided individuals with assessments of their genetic risk for nearly 200 diseases. Many had praised 23andMe’s Personal Genome Service (PGS) as a medical revolution. However, when the company failed to provide FDA with evidence of the PGS test’s validity, the agency shut down the operation to protect consumers from receiving invalid test results that could lead them to either seek unnecessary or not seek necessary medical treatment.
AACC’s Clinical Chemistry recently published an opinion article that examines whether FDA’s move is a violation of the First Amendment or a necessary step to protect consumers. In this article, Linnea M. Baudhuin, PhD, of the Mayo Clinic (Rochester, MN) takes a closer look at the 23andMe test’s shortcomings and why the information it provided might be more aptly considered misinformation. One of the author’s main criticisms of the test is that it is not a comprehensive genetic analysis, a limitation that many consumers are not aware of.
I asked some IVD industry analysts for their thoughts on this article and the 23andMe situation in general. One analyst, Bradley M. Thompson, JD, an attorney at Epstein Becker Green (Washington, DC), agreed with the opinion piece’s author and said the argument that people somehow have some inalienable rights to their genetic information makes no sense.
“The threshold question is whether the manufacturer of the test is making medical type claims about the test,” said Thompson. “By medical type claim, I’m referring to the type of claim that gets regulated because it pulls the test within the definition of a medical device. So the proper question is whether the manufacturer of the test is promoting it for use in the diagnosis, as that word is loosely understood, of diseases or other conditions. There is a long history of interpreting the word diagnose as broader than the very technical meaning of determining whether someone in fact has a disease or condition. Instead, diagnose has been interpreted to include such things as a screening test or a monitoring test, neither one of which involves supporting a formal diagnosis.”
Thompson stated that these medical type claims stand in contrast to, for example, claims about helping someone understand their heritage. He added that if the promotional claims around the test being sold meet that definition, FDA can regulate it. When FDA regulates a test, the agency is operating at a few different levels by regulating: the performance to make sure that the test works; the claims about that performance to make sure that they are based on data; and the manner in which people have access to the test, whether by prescription or over-the-counter.
“People who make broad assertions that consumers have inherent rights to their genetic information completely bypass the question of whether a given test actually produces accurate information,” said Thompson. “Why on earth would someone have the right to see information that isn’t even accurate with regard to their genetic makeup? Further, we have decades of applying prescription status to certain articles where, by definition, adequate directions for use cannot be written. That’s the whole foundation of prescription status. The company, if it has the data, can overcome prescription status by proving that ordinary patients and consumers can understand and appropriately use the test. So if someone really thinks this belongs over-the-counter, there’s no legal prohibition, just a standard to be met. They need to prove that people without a medical education can appropriately interpret the data.”
Another analyst, Fred Lasky, PhD, principal consultant at Lasky Consulting (Arlington, MA) said that he is a skeptic with regard to the benefit that 23andMe would have provided to an individual’s health and that the author of the Clinical Chemistry article covered most of his relevant concerns.
“FDA is chartered with assuring that medical devices are shown to be safe and effective before they are permitted on the market, not prohibiting devices that have been shown to be unsafe or ineffective,” said Lasky. “The risk to public health is obvious. If the reverse were true, any device could be distributed until it was shown to be unsafe or ineffective. The impact on public health and welfare is obvious.”
Lasky stated that in working with genetic testing companies, he became aware of many issues. First, the medical literature is generally weak in presenting data and information that is useful for the care of patients. Many publications are also weak in patient selection and statistical analysis. Specifically, pre-selection bias is too frequently identified in many studies by follow-up publications that could not reproduce the original findings.
“There is often value in such observational studies, because it could lead to bigger, better-controlled investigations that can provide benefits to the public health,” said Lasky. “Interestingly, despite lay publication editorializing, the more conclusive studies are very often conducted by the drug and device manufacturers in an effort to convince FDA that their product is indeed safe and effective. The costs in time, money, and operational difficulties (e.g., patient recruitment) have been reported in the clinical and lay literature.”
Second, Lasky added that physicians and consumers have great difficulty in synthesizing the meaning of such terms as risk ratio, penetration (for mutations), likelihood ratio, etc.
“For example, if a patient is told that his genetic makeup predicts that he is twice as likely to develop a disease as the general population, what does that mean?” said Lasky. “If the disease is common, say 1 in 50, and serious without treatment, the patient will probably think about reviewing his will. If the disease is rare, say 1 in 10,000, regardless of the seriousness, will it or should it really change the patient’s lifestyle? My experience is that physicians generally lack the training to present this information in a way that is coherent and understood by patients.”
Third, Lasky stated that specifically when it comes to genetic test results, the validity of mutations and their association with disease is varied.
“Multiple sclerosis is a good example in which over a hundred mutations are associated with disease, but fewer than half the mutations have strong evidence that there is a cause and effect relationship,” said Lasky. “How do a physician and the lay public make sense of such information? Has anyone looked at how all the mutation reporting has affected pre- and post-natal responses?”
According to a press release from 23andMe, the company “will comply immediately with the U.S. Food and Drug Administration’s directive to discontinue consumer access to its health-related genetic tests during the ongoing regulatory review process. The company will continue to provide consumers both ancestry-related information and raw genetic data without interpretation. In addition, the company will continue to conduct research using its database of genetic and phenotypic data, and also will continue its educational efforts.”
