How Should the U.S. Regulate Genetic Testing?

Stanford Law School’s Center for Law and the Biosciences held a conference Monday to tackle the increasingly important question, ‘How Should the U.S. Regulate Genetic Testing?’

I attended the conference along with some hundred others to hear experts address the question from various perspectives: government, professional, payor, industry, and academic. Notably, social and ethical perspectives were not explicitly included, and only inched in at the peripheries.

Nonetheless, the conference was fascinating and incredibly informative. The biggest take-away of the day was that better regulation of genetic testing is certainly needed, but that it is a hugely complicated problem, from every perspective.

Center Director Hank Greely asserted that population-wide, next-generation sequencing will be the future and asked how we can maximize the benefits of this coming sea change while minimizing the harms. This may be obvious, but it’s actually critical, since in some cases people are receiving life-changing information of relevance to the whole family from these tests.

The timing of the conference couldn’t have been better, since the FDA just released its draft guidance on laboratory developed tests (LDTs) for comment last week, and will be holding a webinar October 23 to address questions. While not all genetic tests are LDTs, an awful lot are, and the FDA has good reason to cast light on this opaque world:

The FDA has identified problems with several high-risk LDTs including: claims that are not adequately supported with evidence; lack of appropriate controls yielding erroneous results; and falsification of data. The FDA is concerned that people could initiate unnecessary treatment or delay or forego treatment altogether for a health condition, which could result in illness or death.

Concerns about genetic tests are often described as three-fold: do they provide analytical validity, clinical validity, and clinical utility (or patient validity, as Greely put it)? In other words, do genetic tests accurately report the sequences they say they’re analyzing? Do they actually correspond to a given health condition? Is there any clinical benefit of knowing this information? And what should we do with the information we get? The current lack of over-arching regulation, oversight, or independent review of genetic tests makes it nearly impossible for anyone to answer even the first of these questions, let alone the others.

There was broad agreement among the speakers that the interests of patients (or “patients/consumers” in the case of 23andMe) need to come first. Multiple people noted inadequacies or irregularities among CLIA certified labs and tests and welcomed more comprehensive regulation. For example, Megan Grove, a genetic counselor at Stanford, pointed out that genetic counseling does not scale up to genomic counseling and insisted that counselors need more guidance on how to communicate an onslaught of (quickly changing) information to their patients.

Kathy Hudson from the NIH argued that we need a “nimble and risk-based regulatory system.” She pointed to President Obama’s recent remark that “we’re going to have to change how we regulate some of this stuff,” and advised us to “watch this space.” Pamela Bradley from the FDA echoed this sentiment, insisting that we need a framework of oversight in the interest of public health in order to realize the promise of personalized medicine. She stressed the FDA’s desire to hear from the public on the agency’s new guidance, as well as its desire to improve what can be a dangerous marketplace, while continuing to encourage innovation.

A couple speakers from the “professional perspective” were vocal in their disagreement. They strongly rejected “dual regulation” by the FDA and CMS (Centers for Medicare & Medicaid Services, which administer CLIA), asserting that if the agencies don’t communicate well enough with each other they will end up caught in the middle, with increased burdens and costs for their labs.

However, John Richardson of the National Society for Genetic Counselors pointed out that he is seeing 30% of tests being ordered inappropriately and that too often there are pressures coming from heavy marketing to primary care physicians, at the expense of the best interests of patients.

The sole voice from the “payor perspective,” Wade Aubry, formerly of the Philip R. Lee Institute for Health Policy Studies, said he believes payors will be happy with the FDA’s efforts because they want to see more evidence of validity so they know they're only paying for tests that are clinically useful.

The “industry perspective” was remarkably diverse. Mya Thomae of Illumina was happy with the FDA’s willingness to be flexible with her company in allowing their sequencer to gain fast approval, and felt that CLIA regulations aren’t “cutting it” because not all labs are compliant. Ethan Knowlden of Complete Genomics (recently acquired by BGI) had a very BGI-esque dream of the “ultimate genetic test,” which could be compared to a vast whole-genome sequencing database. Jill Hagenkord of 23andMe smiled a lot and insisted multiple times that 23andMe is “working with the FDA to move forward.” Regarding the new FDA regulations, she said she agreed with the agency’s concerns, but wanted to see them balanced against the costs to innovation, access, and cost.

Ken Song of Ariosa was impressively honest, stating that his new company has not done everything right and that oversight is definitely needed, though he was concerned about whether it could keep pace with the evolution of testing processes. Importantly, he pushed back against the notion that more is always better, pointing out that without a high degree of accuracy and complex counseling, this notion can be dangerous in the realm of genetic testing. John West of Personalis, whose whole business model is based upon providing accurate genomic medical information, went so far as to suggest further regulations from the FDA to monitor the quality of tests instead of merely whether they do what they say they will.

From the “academic perspective,” Stanford Law’s Jacob Sherkow argued that patents are yet another kind of regulatory tool. He shared his concern that they will increase costs and decrease competition, noting that there are countless patents right now blocking ways of looking at and manipulating genetic data, and turning valuable information into “trade secrets.” Bob Cook-Deegan of Duke University also talked about gene patent problems, particularly of the Myriad variety, which have really impeded information flow at the expense of researchers and patients. He suggested three possible solutions to this problem: That payors insist they’ll only pay for tests that have independently reviewable data, that consumers demand access to their own data, or, that we build a system that enables this flow of information from the outset. Cook-Deegan made a strong case for moving away from the language of ownership of genetic data so that we can work towards improved access, transparent analysis, and collaborative science.

After a healthfully heated concluding discussion among all speakers about the appropriate degree and kind of regulation, Greely joked that he wasn’t sure whether the conference had managed to really get a handle on its central question, but that he felt gratified to see everyone wanting to “do the right thing.” I’m not sure I would be quite as generous, since notions of the “good” or “ethical” played such a supporting role to the “practical” and "innovative" throughout the day. But I wholeheartedly agree that there is a real need here, and found it heartening and invigorating to see so many intelligent people, from so many perspectives, working to address it.