It has been a busy week in Washington for direct-to-consumer (DTC) genetic testing companies. Following public FDA meetings and a new round of FDA device notification letters earlier in the week, representatives from three major DTC genetic testing companies (23andMe, Navigenics and Pathway Genomics) were hauled in front of Congress today to defend their companies, their industry and the practice of DTC genetic testing.
The hearing on “Direct-To-Consumer Genetic Testing and the Consequences to Public Health” was conducted by the House Committee on Energy and Commerce Subcommittee on Oversight and Investigations. The meeting was chaired by Representative Bart Stupak of Michigan. Materials from the hearing, including a briefing memorandum, opening statements from Stupak and Representative Henry Waxman of California and witness testimony are available on the Committee’s website. Also available are materials from the Government Accountability Office (GAO) investigation into DTC genetic tests. These materials include the report the GAO submitted to Congress – “Direct-to-Consumer Genetic Tests: Misleading Test Results Are Further Complicated by Deceptive Marketing and Other Questionable Practices” (pdf) – as well as a YouTube video featuring excerpts from undercover phone calls made by the GAO to DTC companies as part of their investigation (both of which are discussed in detail below).
Opening Remarks. The hearings began with opening remarks from members of the House Committee. Chairman Stupak (MI) began (pdf) by reading from a statement in which he identified a familiar set of concerns pertaining to DTC genetic testing:
…how accurate are the companies’ analyses of direct-to-consumer genetic tests? By sending the customer the results of genetic tests without counseling or medical advice may cause more harm than good for some consumers? How accurate is the health information? How do companies explain differences in their analyses? Is there sufficient government oversight of the practices of direct-to-consumer genetic testing manufacturers?
Representative Stupak was followed in succession by Representatives Burgess (TX), Waxman (CA), Griffith (AL), DeGette (CO), Latta (OH), Christensen (VI) and Gingrey (GA). As expected, there was considerable overlap in the opening statements. Nearly every Representative expressed his or her desire to ensure that the American public was presented with information that was accurate, safe and effective. They differed, however, in how they thought this might best be done.
Burgess and Waxman, for instance, were consistent in their hearing-long concern that the benefits of personalized medicine not be derailed either by unscrupulous DTC testing companies or by overly intrusive government regulation, and generally urged the use of a “deft touch” in regulating the industry. Others, including Representative Parker Griffith, struck a more alarmist tone, comparing the information supplied by DTC genetic testing companies to his throwing a snake into the middle of the Congressional hearing. According to Griffith, when presented with genetic risk information for serious diseases such as Alzheimer’s or cancer, consumers are likely to panic first and ask questions only later, if at all. Representative Phil Gingrey (GA) was on the same page, expressing his concern that DTC genetic testing might lead patients to jump to the wrong conclusions “or, indeed, jump off of a building” without appropriate guidance.
Other Representatives had specific issues they wished to explore. Representative Diana DeGette (CO) focused throughout the day on the privacy of genetic information collected and maintained by DTC companies. She acknowledged, quite correctly, that current laws (including GINA) provide incomplete protection against the misuse of genetic information. Representative Donna Christensen (VI) devoted her opening – and the majority of her subsequent questions – to the treatment of ethnic and racial minorities by DTC companies. Particularly worrying to Christensen were instances (documented by the GAO’s investigation) in which DTC companies failed to adequately notify minority consumers that their test results were incomplete or inaccurate. This typically occurred with respect to traits where the underlying genetic research was conducted in Caucasian populations and not yet verified in applicable minority populations.
Reports from the Regulators. Following the opening statements, the first witnesses called to testify were Gregory Kutz, Managing Director of Forensic Audits and Special Investigations for the GAO and Dr. Jeffrey Shuren, Director of the FDA’s Center for Devices and Radiological Health (CDRH). Kutz began by presenting findings from the GAO’s investigative report into DTC genetic testing products and marketing (pdf).
For those seeing the report for the first time (a group that included all of the DTC companies present at the hearings), Kutz’s testimony and the GAO’s report certainly raised some eyebrows. Although, by the GAO’s own admission, it “did not conduct a scientific study but instead documented observations that could be made by any consumer,” its conclusions to Congress were crystal clear: DTC genetic testing companies provide “results that are misleading and of little or no practical use.” The GAO reached this conclusion following a year-long, two-part investigation into the tests and marketing practices of DTC companies.
Part I: The Tests. During the first phase of the investigation, the GAO purchased 10 tests each from four companies (23andMe, Navigenics, Pathway Genomics and Decode Genetics). For each company the GAO selected five donors and submitted two samples – one containing factual information and one “using fictitious information, such as incorrect age and race or ethnicity.” In findings representative of those published in Nature by Ng et al. last year, the GAO found that the four DTC companies did not provide consistent risk estimates for all customers across the full range of conditions tested. Although the GAO report doesn’t do the math, Kutz testified before Congress that 58% of the time donors received different predictions for the same disease.
The issue of consistent genetic interpretation and risk reporting is an issue that DTC companies have widely acknowledged, both during the course of the GAO investigation and elsewhere. Previous efforts include a collaboration led by the Personalized Medicine Coalition to develop guidelines for scientific validity and 23andMe’s recent letter to the heads of NIH and FDA requesting assistance in developing transparent standards for reporting the positive and negative predictive values of genetic tests. There was widespread agreement among the companies, regulators and Congressmen that this is an area where DTC must improve in order to help avoid consumer confusion and there can be little doubt after today’s hearing that this will be a top priority for DTC companies and regulators alike.
The GAO also investigated how risk predictions matched against factual illnesses and family medical histories, with the GAO and several Representatives emphasizing the example of one donor with an implanted pacemaker for an irregular heartbeat who “was told that he was at decreased risk for developing such a condition.” While this particular example was widely discussed at the hearing, as Steven Pinker eloquently explained last year upon learning that he was at a high risk for baldness despite possessing a flowing mane, prediction is not the same as diagnosis. The fact that the two do not always align is far from damning evidence against DTC genetic testing, or indeed genetic testing in general. Unfortunately, this distinction was largely overlooked in the GAO report and in the Congressional hearing.
The GAO also criticized the four DTC companies for their poor performance in handling samples from (fictitious) African American and Asian customers and the companies’ failures to provide follow-up interpretation and consultation support as advertised. Here is the GAO’s summary of its findings from part one of the investigation:
Comparing results for 15 diseases, we made the following observations: (1) each donor’s factual profile received disease risk predictions that varied across all four companies, indicating that identical DNA can yield contradictory results depending solely on the company it was sent to for analysis; (2) these risk predictions often conflicted with the donors’ factual illnesses and family medical histories; (3) none of the companies could provide the donors who submitted fictitious African American and Asian profiles with complete test results for their ethnicity but did not explicitly disclose this limitation prior to purchase; (4) one company provided donors with reports that showed conflicting predictions for the same DNA and profile, but did not explain how to interpret these different results; and (5) follow-up consultations offered by three of the companies provided only general information and not the expert advice the companies promised to provide.
Part II: The Follow-Up. After receiving and comparing the test results supplied by the companies, the GAO followed up by conducting the second phase of its investigation: “undercover calls to the companies seeking health advice.” The GAO presented excerpts from those calls in the form of a dramatic YouTube video shown at the hearing.
A number of the encounters presented in the video are unquestionably troubling. The first, for instance, is a conversation between a GAO investigator and a company (identified by Kutz at the hearing as Navigenics) representative discussing the woman’s breast cancer results:
Fictitious Customer: So if I’m high risk, does that mean I’ll definitely get breast cancer?
Company Representative: You…you’d be in the high risk of, you know, pretty much getting it.
The GAO reports that “experts” considered “this statement ‘disconcerting’ and ‘horrifying’ because it erroneously implies that the test can diagnose breast cancer and could needlessly alarm consumers.” (Note also that this is a good example of the prediction/diagnosis confusion, discussed above.)
Other DTC encounters that received particular scrutiny included:
- a representative from a DTC company (identified at the hearing as Pathway Genomics) encouraging a fictitious consumer to collect and send in a saliva sample from her fiancé, without his consent, in order to surprise him with the results. Testing without consent - so-called “surreptitious testing” - is illegal in some form in more than 20 states, according to a recent report from the Genetics and Public Policy Center (pdf).
- a representative from a separate DTC company (identified by Representative Stupak as GeneWize Life Sciences) appearing to endorse the use of supplements as an alternative to or replacement for blood pressure and cholesterol medication. Such supplements, whatever their value, have not been approved by the FDA to treat, prevent or cure disease.
The GAO reported that 10 of the 15 companies it investigated engaged in what it termed “deceptive marketing, misinformation, and questionable practices.” There is really little room to disagree with the GAO’s findings. At best the examples highlighted by the GAO report reflect poorly informed company representatives; at worst they represent irresponsible marketing and even outright “fraud,” a term Kutz used in his testimony to Congress.
Where the report is lacking, however, is in its failure to identify which companies were guilty of which practices, and whether such practices are representative of the DTC genetic testing industry as a whole. It was initially confusing – to Congressmen, witnesses and the audience alike – whether the companies selected for follow-up interviews were the same as those selected for initial testing. (They were not; the pool for the second phase of the investigation was expanded by an additional 11 companies.) In testimony to Congress at the hearing, it was frequently unclear whether Kutz’s comments and conclusions (which often referenced various sections of the GAO report, jumping between the two sections) pertained to the DTC companies currently before Congress, to some or all of the 15 companies reviewed as part of the full GAO investigation or to the entire DTC genetic testing industry.
One result of this confusion was a tendency for Congressmen and even other witnesses to default to the lowest common denominator in describing the DTC genetic testing industry. Despite a clear range in testing and business practices (recall that for 1/3 of the companies investigated, the GAO uncovered no questionable marketing behavior) the term “snake oil” was repeatedly invoked to describe all DTC genetic tests. For example, during one stretch of Q&A, Representative Stupak paused the conversation to remind the audience that “in the last 48 hours this committee went from Gulf Oil to Snake Oil; we are on top of our game.” Representative Griffith took it a step further, accusing DTC companies of being in the business not of selling genetic tests but of marketing, using the tests as a lure to encourage consumers to part with genetic and other information and adding them to marketing lists for vitamins, drugs and supplements (note: the prior link incorrectly identifies Representative Latta).
To reiterate, there is no question that the GAO uncovered disturbing and even “horrifying” instances of misleading and even fraudulent practices employed by certain DTC genetic testing companies. Steps must be quickly taken to halt such practices. But it remains unclear whether the examples cited by the GAO are representative of the entire DTC genetic testing industry and, for that reason and others, what the proper regulatory response to such practices should be.
In its section on Corrective Action Briefings, the GAO report notes that it briefed the FDA, NIH and FTC on its findings in May and June of this year. There can be little doubt that one or more of those agencies will soon take steps aimed at eliminating certain of the practices identified by the GAO. What those steps might be – and whether they will target specific companies or the industry as a whole – remains to be seen.
The FDA’s Plan. While details of what new regulatory oversight might be in store for DTC genetic testing were expectedly sparse, some modest insight came from the testimony of Dr. Shuren of the FDA (written testimony). Shuren’s oral and written comments emphasize that the FDA subjects a genetic test to regulatory oversight only if it qualifies as a medical device; “that is, if it is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease.” Shuren specifically mentioned genetic tests for ancestry or curly hair as tests that would not be subject to FDA regulation (and, it would appear, are likely to be permitted to remain on the market provided they are marketed and sold appropriately). Shuren’s comments lent weight to the argument that the FDA, at least for the moment, considers “intended use” to be a key factor in determining whether and how to regulate a genetic test.
Shuren also made it clear that the FDA did not consider many of the genetic tests provided by DTC companies to be LDTs because they were purchased from another company and not developed in-house. Shuren singled out Pathway Genomics (which operates its own CLIA-certified lab) as an example of a non-LDT DTC genetic test. Shuren did not clarify whether the FDA intended to apply this same rigorous assessment of what is and what is not an LDT to any of the estimated 2,500 – 5,000 (Shuren’s own “conservative estimate”) non-DTC genetic tests currently offered for sale as LDTs without FDA clearance or approval under the Agency’s policy of “enforcement discretion.”
With respect to DTC genetic tests, Shuren’s written comments – briefly echoed in his testimony – reflect the FDA’s previously reported concern with the changing nature and scope of genetic testing. “For example, one company provided test reports for 17 diseases, conditions, or traits in 2008 but provided over 100 types of results in 2010.” Shuren’s testimony cites “escalation in risk and aggressive” marketing as the reasons that ultimately convinced the FDA to send Pathway Genomics a letter on May 10th informing the company that its product was a medical device subject to regulation. Under questioning from Representative Burgess, Shuren admitted that he thought the FDA “should have acted sooner” to address DTC genetic tests.
So what is the FDA’s plan now that the public meeting and Congressional hearing have come and gone? Will the Agency continue to send informational letters to DTC companies and start to take even more aggressive actions? That will likely be part of the strategy – perhaps even a significant part – but Shuren also outlined the barest details of a plan to help allow DTC genetic tests to remain (or at least re-enter) the market. Shuren indicated the FDA was looking into the possibility of working with the NIH, scientific experts and community representatives to review the scientific literature and identify viable genetic association claims and appropriate standards of interpretation. Shuren also mentioned that the FDA is looking at ways to allow the Agency to approve general tests or testing platforms through a scheme that would allow additional data to be added to tests, and claims or interpretations presented to recipients, without having to seek additional FDA approval or clearance. Details of the plan were minimal, and given the context seem likely to apply both to DTC genetic tests and LDTs more broadly, but we will need to wait for the FDA to publicly elaborate on its plans (Shuren’s written comments do not address either of these topics).
None of the above should be taken to suggest that the FDA intends to let DTC genetic testing companies off of the hook when it comes to FDA clearance or approval. In response to questions from Representatives Waxman and Burgess, Shuren indicated that he thought most DTC tests would be classified as Class III or Class II devices (not Class I or Class II, as Burgess had suggested) and that, while companies that come to the FDA with data and low-risk tests in hand might be permitted to remain on the market for an interim period pending FDA review, “if they aren’t ready with the data or there are concerns about patient safety, then we would not allow them to market” their tests.
As usual, precise details and timing remain “to be determined,” or at least “to be publicly announced.”
Over the Horizon. Representatives Burgess and Waxman also pressed Shuren to discuss whether he felt the FDA was prepared to address the challenges of personalized medicine, including technologies (presumably including whole-genome sequencing) that are “just over the horizon.” Waxman, in particular, while expressing his desire to ensure that companies not mislead the public, worried about setbacks that might result from branding the entire industry as a group of charlatans and responding by pulling all of the products from the market. Shuren, for his part, held fast to his line that the FDA’s primary concern was that information presented to patients was truthful, accurate and understandable.
Similarly, Burgess worried whether the FDA possessed the tools (read: resources) to deal with what lies ahead, including the potential regulatory responsibility for entirely new areas of personalized medicine such as DTC genetic testing and LDTs. Shuren responded that the FDA has authority to adapt its current regulations and resources to new technologies, and was considering “down-regulating” less risky devices to make resources available for DTC/LDT regulation.
Finally, Shuren was asked by Waxman whether he thought DTC genetic testing companies were helping to advance the state of scientific knowledge, thereby bringing the ideal of personalized medicine closer to reality. Shuren responded that he believed DTC companies were interpreting and synthesizing scientific research, but not directly contributing. (23andMe general counsel Ashley Gould later offered her own perspective, citing recently published research derived from customer data as evidence to the contrary.)
DTC Takes the Stage. After the regulators stepped down, representatives from 23andMe, Navigenics and Pathway Genomics were invited to testify, along with Dr. James Evans of the University of North Carolina-Chapel Hill. In addition to his many titles and responsibilities, Dr. Evans was the “primary consultant” to the GAO during the course of its investigation.
Evans’ prepared remarks (pdf) largely reflect his opening statement to the Committee, which focused on the need to balance the ample benefits of genetic testing with the critical importance of ensuring that patients and consumers receive high quality and accurate information, that their privacy is protected and that the claims made on behalf of genetic testing “comport with reality.” Throughout his comments Evans was adamant that while more regulation was needed, particularly over DTC genetic tests, individuals should continue to be permitted direct access to their genomic information:
I believe that the public deserves access to the information contained in their own genomes. But they also deserve an honest accounting of what such information means and the assurance that it is derived in a manner that ensures quality, reliability and confidentiality.
The opening statements that followed from Ashley Gould of 23andMe (written testimony), Vance Vanier of Navigenics (written testimony) and David Becker of Pathway Genomics (written statement) were comparatively brief.
Gould talked about 23andMe’s achievements in advancing genomic access and research and, while acknowledging the necessity of a sensible regulatory framework that ensures consumers receive scientifically valid, accurate and understandable information, emphasized the need for more data about the risks and uses of DTC genetic testing prior to regulation. Vance Vanier followed by describing DTC genetic testing as a tool that could help fight preventable disease and emphasized that not all DTC genetic testing companies operate using the same business model or hold themselves to the same standards. Vanier highlighted Navigenics’ focus on clinical genetic testing and its commitment not to sell or share any customer data with third parties (both distinctions from other DTC genetic testing companies). In wrapping up the introductory comments, David Becker of Pathway Genomics largely echoed Vanier and Gould while reminding the Committee that, while he believed a reasonable regulatory framework could be developed to permit DTC genetic testing, Pathway had already voluntarily suspended DTC sales of its products while working with the FDA to address its concerns.
After that the questions – and attacks – resumed. As the only witnesses not provided with access to the GAO report prior to the hearing, the DTC representatives were at a distinct informational disadvantage from the outset. Members of Congress peppered the companies with questions about whether they agreed that the “triumvirate” of companies:
- needed more consistent standards for genetic risk prediction (all three agreed they did);
- needed some form of additional regulatory oversight (all three agreed they did);
- must be willing to implement strong consumer privacy protection measures (all three agreed they did); and
- were providing medical advice and interpretations (23andMe and Pathway largely held to the company line that their tests are for “informational or educational” purposes, while Navigenics embraced the clinical aspects of its service).
As the panel wound down, Representative Stupak pressed the DTC companies to consider withdrawing their products from the marketplace pending development of an adequate system of regulatory oversight. Gould declined to take the bait, focusing on the rights of consumers to access their genetic information. Vanier attempted to argue that such a drastic move would harm not only Navigenics but other small businesses as well, and render the entire industry hostile to investment and invention. Vanier was quickly redirected by Stupak into conceding that the company was pre-profitable and “losing money every year.” Becker again pointed out that Pathway had already ceased offering its tests for sale directly to consumers and saw no need to withdraw completely from the marketplace.
The final line of questioning from Representative Burgess concerned international efforts to review or regulate DTC genetic testing, with all three companies conceding that, to their knowledge, the FDA was taking the lead in pursuing regulatory oversight of the industry. While neither the Congressmen nor the companies seemed overly familiar with international efforts to review and regulate DTC genetic testing, they clearly exist. In the U.K., for instance, the House of Lords reviewed the DTC genetic testing landscape in its 2009 report on genomic medicine and the Human Genetics Commission is currently developing a “Common Framework of Principles” for DTC genetic testing. Other countries have been even more proactive, with Germany enacting legislation that effectively banned all DTC genetic testing just last year. It will be interesting to see whether the heightened scrutiny of DTC genetic testing by U.S. regulators prompts regulatory or legislative bodies in other countries to take a closer look at adjusting or enforcing laws and regulations pertaining to DTC or other forms of genetic testing.
The Future of DTC? Four and a half months ago, in “Why the State of Personal Genomics is Not as Dire as You Think,” I wrote the following:
Over time, the diversification of personal genomics will be a good thing, aiding in the identification of viable business models and separating legitimate businesses from snake-oil salesmen. But it will require time, investment (not all of which will be recouped) and quite probably additional legislative or policy interventions, particularly in the areas of intellectual property and regulatory review that apply to personal genomic services…
Looking ahead, I am confident that [Linda] Avey is correct when she writes that personal genomics will become “such an every day concept that future generations will be amused that we even questioned its viability.” And judging from the abundance of activity and advancement in the field as a whole, as well as the dozens of entrepreneurs and investors that have contacted me in recent months to discuss their plans for starting or growing personal genomics businesses, I think it will hardly take a generation before personal genomics moves mainstream.
In the months since, the field of personal genomics has been shaken by a string of regulatory developments, each seemingly more dire than the last. From the failed Pathway Genomics/Walgreens partnership to the FDA’s letter-writing campaign to today’s events, especially the GAO’s conclusion that DTC genetic tests mislead consumers and are of no practical use, it is clear that “additional legislative or policy interventions” are no longer probable. They are inevitable, and they are likely to be substantial.
In spite of these developments - and no matter how many times the term “snake oil” is thrown around – I continue to believe that it is premature to declare the death of DTC genetic testing, or its close cousin personal genomics. There remains a broad spectrum of possible responses available to Congress and the various regulatory agencies now scrutinizing the field of genetic testing and, while today’s events did not paint DTC genetic testing in the most favorable light, the industry and many of its companies have received considerable (and deserved) praise on other days.
Obviously, much depends on where the regulatory and legal landscape moves from here. Certain possibilities, such as enhanced genetic test transparency and FTC oversight to separate legitimate tests from fraudulent ones, would strengthen the DTC industry over the short- and long-term. Others, including applying the traditional medical device regulation framework to all or most DTC genetic tests, have the potential to deal a considerable setback to DTC companies, consumers and investors. With nearly limitless possibilities, everything hinges on the precise details and timing of the new regulatory framework, whatever it may be.
No matter what comes next, over the long term I continue to believe – based on my day-to-day interactions with investors, companies, consumers and researchers – that there is considerable demand for direct consumer access to personalized genetic information. And this demand is only going to increase with time. The personal genomics landscape is certain to change, possibly drastically, in the coming weeks and months. But I am extremely doubtful that it will be wiped clean. As long as demand persists, I have confidence that companies, consumers and regulators will find a way to work together to continue to provide individuals with direct access to and control over their genomic data.