Earlier this week the Food and Drug Administration sent a warning letter to the direct-to-consumer gene testing company 23andMe ordering the company to stop marketing its $99 genotype screening test. The agency does, in fact, have broad authority to regulate any medical "device" ranging from bedpans to pacemakers that is used to treat or diagnose people. So if tongue depressors fall under the FDA's jurisdiction, it's pretty clear that 23andMe's saliva collection kits do too. The letter gives the company 15 days in which to respond. If the agency doesn't hear back or like what the company has to say, it advises that it might initiate regulatory actions that could "include, but are not limited to, seizure, injunction, and civil money penalties."
23andMe has been selling its Personal Genome Service since 2006, so why did the FDA act now? It made its move, at least in part, because the company apparently has been ignoring the agency's bureaucrats for too long. The warning letter notes that the FDA "has not received any communication from 23andMe since May." Yet, the company rolled out a big new marketing campaign for its personal genome service this fall. Frankly, it is not very smart for a company to snub the regulators who have the power to shut it down at their whim. 23andMe's belated response to the FDA acknowledges, "We recognize that we have not met the FDA's expectations regarding timeline and communication regarding our submission." The company diffidently adds, "Our relationship with the FDA is extremely important to us and we are committed to fully engaging with them to address their concerns."
So what are the FDA's bureaucrats so worried about? Basically that purchasers of 23andMe's personal genome services will do something dangerously stupid in reaction to the information that the tests provide. But will they? As an instance, the FDA letter puts forth a hypothetical in which 23andMe customers could be misled by the results of the company's BRCA breast cancer gene tests. "If the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist," argues the agency.
Researchers around the world use the same biochip, the Illumina OmniExpress Plus, that 23andMe uses and find that it provides highly accurate results. Nevertheless, all diagnostic tests produce false positives (false alarms) and false negatives (false all-clears). It bears noting that Myriad Genetics claims that the overall error rate for its more comprehensive BRCA test is less than one percent.
So let's consider more deeply the likely reactions of 23andMe customers to the results of its BRCA test. First, 23andMe flatly states that it tests for only three of the more prevalent BRCA breast and ovarian cancer mutations found generally among Ashkenazi Jewish women. At the very top of its BRCA webpage the company emphasizes that there are hundreds mutations in the BRCA1 and BRCA2 genes for which it does not test that can cause cancer.
Now let's assume that a 23andMe customer tests positive for one of the BRCA mutations, what are they likely to do next? On the strength of their letter, FDA bureaucrats seem to believe that women with a positive test will immediately go look for surgeons to remove their breasts; start gobbling down tamoxifen pills to ward off cancer; or get more mammograms. Of course, these scenarios are ridiculous. What a customer would do is consult with her physician and most likely get another more comprehensive genetic test. That is exactly what Huffington Post blogger Jill Steinberg did when her 23andMe results came back showing that she carried one of the BRCA mutations. Her subsequent test confirmed the 23andMe finding and she eventually decided to have a double mastectomy.
What if the 23andMe BRCA test missed one of the three mutations in a customer who actually has one of them? In this case, a customer might wrongly assume that she is not at an especially high risk of breast cancer. Let's put the seriousness of such an error in a bit of context. Consider, for example, that the FDA has approved the OraQuick at-home HIV test that produces "about one false negative result out of every 12 tests performed in HIV infected individuals." In this case, a person who wrongly relies on the negative HIV result, like the person with an incorrect BRCA negative result, may be harmed by not seeking appropriate medical care.
To be sure, the FDA does warn users of the HIV test that it is "important never to use a negative test result to decide on whether to engage in behavior that puts you at risk for HIV infection." In a similar manner, 23andMe carefully explains to its customers, "No matter what your ethnicity or ancestry, it is important to understand that the absence of these mutations does not rule out the possibility that a person may have another genetic variation that increases the risk of these diseases."
The good news is that a 2013 peer-reviewed study by 23andMe researchers of how customers reacted to their BRCA results found that those who tested negative "did not report inappropriate actions, such as foregoing cancer screening." The study also noted that "all but one of the 32 mutation-positive participants appreciated learning their BRCA mutation status." In addition, the researchers who conducted a 2009 Genetics in Medicine study that analyzed how patients responded to the results of a suite of eight genetic risk susceptibility tests reported, "We found no evidence that those who considered or sought testing were inclined to overestimate the contributions of genetics to common health conditions or to underestimate behavioral risk factors."
The FDA also sketches out a scenario in which 23andMe customers would use their warfarin sensitivity results to "self-manage their treatments through dose changes" producing dangerous blood clots or bleeding incidents. As it happens, my 23andMe results indicate that I have increased sensitivity to the blood-thinning drug. Fortunately, I don't have to use it right now, but I certainly would let my physician know these results in the event that I needed such a treatment.
23andMe tests for the same variants relevant to warfarin sensitivity that the test approved by the FDA does. By the way, stand-alone warfarin sensitivity tests cost between $200 to $400. In any event, I seriously doubt that 23andMe customers who aren't using warfarin will all of a sudden start anti-coagulant therapy for the fun of it. Nor will those currently on warfarin stop listening to their doctors and begin to self-treat by swallowing d-CON pellets. Furthermore, 23andMe advises at the top of the webpage reporting my warfarin results, "Only a medical professional can determine whether warfarin is the right medication for a particular patient. The information contained in this report should not be used to independently establish a warfarin regimen, or abolish or adjust an existing course of treatment."
So far, nearly 500,000 people have purchased 23andMe's Personal Genome Service. Interestingly, the FDA's warning letter does not mention that the agency has received any substantial customer complaints about the service. Anecdotally, I have recommended 23andMe to many friends and colleagues and have not heard any serious complaints about what they purchased or the information they received.
I have explained elsewhere that the development of all new technologies involve a societal learning process in which some early adopters try it out, explain to others how it works, and find out its flaws—which newer innovators then fix. The way the genetic testing industry will evolve is that the companies that tease out and explain useful information about disease risks and pharmaceutical interactions will be the ones to succeed. Despite the FDA's parade of horrible hypotheticals, the bigger risk is that increased federal regulation will slow down the progress of beneficial genetic testing and treatment innovations.
Finally, New York University law professor Richard Epstein is right when he argues, "The FDA should have to show by clear and convincing evidence that 23andMe leads to the dangerous results that the FDA claims by surveying customers of the firm." Until then, the agency should leave 23andMe and its customers alone.