What’s new and interesting here is not the substance of VerBruggen’s analysis. Whether or not you agree with Verbruggen’s particular formulation, the “paternalism” critique of proposed FDA regulation of DTC genetic testing is not new. What caught our eye is a comment from deCODE genetics’ CEO Kári Stefánsson. When questioned by VerBruggen about his company’s marketing of its DTC genetic test offering, deCODEme (see screenshot) – which includes statements such as “your genes are a road-map to better health” – here is how Stefánsson responded:

“I think that is both cheesy and somewhat incorrect. I don’t know who came up with that, but whoever it is, is going to be duly punished,” [Stefánsson] said. “I think it’s safe to say we’ll probably be removing that statement and putting up something that at least sounds better.”

After its well-publicized 2009 bankruptcy, deCODE emerged in 2010 as a privately-held company and so it is unlikely the public will know whether Stefánsson follows through with his promise to “duly punish” the source of the “road-map” statement. On the other hand, whether and how deCODE follows through with Stefánsson’s not-quite-a-promise to change deCODEme’s marketing and claims is something that will happen in full view of the public.

Why does DTC marketing matter? One of the major challenges for DTC genetic testing companies, since the industry’s inception, has been the ongoing attempt to tightrope the distinction between offering genetic tests and services that appeal to consumers (and, by extension, investors) without overly alarming state and federal regulators. The reasons for this delicate balancing act seem clear. On the one hand, a genetic test that provides a “road-map to better health” is much more likely to induce a consumer to pay several hundred dollars or more out of her own pocket than the same test promoted solely as a mere informational or educational tool. On the other hand, genetic tests intended to affect a consumer’s health or well-being, and marketed accordingly, are certain to draw far closer scrutiny from the FDA and other regulators.

We examined this issue nearly 18 months ago in “The Open Secret of DTC Medical Genetic Testing.” In many important respects the analysis has changed little since then. While the composition of the industry has changed somewhat, many of the companies still providing true DTC genetic testing products continue to attempt the seemingly impossible task of enticing consumers to purchase genetic tests by highlighting their potential clinical significance while using fine print to argue that their products’ intended uses are informational and educational.

Take, for example, leading DTC genetic testing company 23andMe. The company currently offers a single product featuring both health and ancestry components. Their “health” product page (see screenshot) offers consumers a chance to use DNA to “help you plan for the important things in life,”  “take charge of your health and wellness today” and “make better health decisions by learning your genetic risks.”

As was the case 18 months ago, however, the company’s Terms of Service continue to strike a somewhat different tune:

23andMe Services are for research, informational, and educational use only. We do not provide medical advice. The Genetic Information provided by 23andMe is for research, informational, and educational use only….23andMe does not recommend or endorse any specific course of action, resources, tests, physician or other health care providers, drugs, biologics, medical devices or other products, procedures, opinions, or other information that may be mentioned on our website. As explained on our website, 23andMe believes that (a) genetics is only part of the picture of any individual’s state of being, (b) the state of the understanding of Genetic Information is rapidly evolving and at any given time we only comprehend part of the picture of the role of genetics, and (c) only a trained physician or other health care provider can assess your current state of health or disease, taking into account many factors, including in some cases your genetics as well as your current symptoms, if any. Reliance on any information provided by 23andMe, 23andMe employees, others appearing on our website at the invitation of 23andMe, or other visitors to our website is solely at your own risk. (emphasis in original)

Most consumers, and probably the FDA as well, would be excused for taking away two fairly different messages from 23andMe’s product marketing and claims and its underlying Terms of Service.

The FDA and Intended Use. The FDA, for its part, has maintained that its regulatory interest lies with clinical DTC genetic tests (pdf), and has previously indicated and recently confirmed that the basis for determining whether a genetic test is clinical, and thus subject to FDA oversight, is the test’s “intended use” (and not its actual or potential clinical significance).

This is consistent with §201(h) of the Federal Food, Drug, and Cosmetic Act (FFDCA), which defines a medical device subject to the FDA’s authority as one “intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease…” It would also appear to logically require an FDA policy whereby DTC genetic tests clearly limited to research, educational or informational intended uses would not be subject to FDA regulation.

The claims of DTC genetic testing companies have been scrutinized before, especially last summer during the events leading up to and following the Congressional hearing and GAO report. As the FDA and other federal (e.g., FTC) and state regulators continue to ponder what’s next for these companies, it’s a safe bet that DTC marketing and product claims will come under closer scrutiny still, not just to ensure their accuracy but also to determine which products are subject to FDA regulation (and to what degree).

When it comes to DTC genetic testing, nothing is certain. Still, we think it likely that one consequence of closer regulatory oversight will be that DTC companies are forced to choose, and to much more clearly convey to their potential customers, whether they are offering a clinical service (e.g., one designed to provide clinically useful information or to otherwise affect the individual’s health or well-being) or merely an informational service (e.g., one designed to provide access to personalized genetic information, possibly in conjunction with certain interpretive tools). The former is certain to be far more tightly regulated than the latter, at least at the outset.

Again, as we wrote several times following this month’s DTC meeting, such an outcome is highly unlikely to result in meaningful limitations on the ability of motivated consumers to access their own raw genetic or genomic data. It is likely, however, to result in a greater degree of clarity and consistency with respect to the marketing and product claims of DTC genetic testing products and services (although exactly how and by whom this will be enforced remains unclear at this time). In the long run, that development should benefit DTC companies, consumers and the industry as a whole.

What should we make of this three state “groundswell?” Although not identical in scope or substance to the Massachusetts Genetic Bill of Rights (“MA GBR”), both the Vermont and California proposals appear to reflect a concern (shared by the MA GBR) that, at least when it comes to the use and misuse of genetic information, the current system of federal oversight is inadequate. Then again, as the legislative findings section of the California proposal (pdf) puts it, perhaps “the current explosion in the science of genetics” simply “compels legislative action in this area.”

Today we’ll dig into Vermont’s proposed H.368: “An act relating to privacy of genetic information” (pdf) (the “Vermont Act”). Next week, we’ll tackle California.

The Value of a Genome. In many respects the Vermont Act closely resembles the MA GBR we covered in detail last month and shares its emphasis on genetic information as a personal property right.

Nowhere is this clearer than where, matching the MA GBR word-for-word, the Vermont Act proposes the insertion of a new provision into Vermont’s existing genetic testing statute, declaring “genetic information the exclusive property of the individual from whom the information is obtained.” 18 V.S.A §9330 The Vermont Act goes on to confer upon genetic material the status of “ real¹ property subject to one’s individual control and dominion in accordance with generally held precepts of property law in Vermont.” 18 V.S.A. §9336(a)

After codifying property rights in genetic information, the Vermont Act, just like the MA GBR, goes on to require that any individual engaged in genetic research or commerce be “made aware both orally and in writing that his or her donation is a commodity and is of some material value.” And if the transaction of genetic information occurs in a for-profit context, the individual would be entitled to “compensation at fair market value.” 18 V.S.A. §9336(c) To be sure, we’re still no closer to articulating a valuation method for genetic information than when the idea was first proposed in Massachusetts earlier this year.

Ambition vs. Reality. There are also a few areas where, in its zeal to protect individual genetic rights, the Vermont Act goes a step too far and appears to conflict with federal law, with potentially problematic (or at least confusing) results.

For example, the addition of 18 V.S.A. §9336(d) would provide that:

Any report or record produced by or stored at a hospital; dispensary; laboratory; hospital-affiliated registry; physician; commercial genetic testing company, agency, or association; or insurance institution or its representative pertaining to any genetic information is the exclusive property of the individual sampled or analyzed. Such report or record shall not be considered to be a public record, and the contents thereof shall not be divulged by any person having charge of or access to the report or record without informed written consent… (emphasis added)

While there are three minor exceptions to §9336(d), none would save the provision from a nasty conflict, at least on its face, with other federal laws, including the Health Insurance Portability and Accountability Act (HIPAA).

Under HIPAA, covered entities (including healthcare providers, such as hospitals and physicians) and their business associates are not required to obtain prior consent for certain uses and disclosures (e.g., for treatment, payment and health care operations) of protected health information, including genetic information. The prior consent requirement was removed under HIPAA in certain instances due to its unintended effect of preventing “timely, quality health care to individuals in a variety of circumstances.” The Vermont Act’s supporters should take another look to ensure that §9336(d) would not produce the same unintended effect under Vermont law.

Next is §9336(e), an even broader and more confusing provision:

Information derived from the sequence of the human genome shall be part of the public domain and shall not be considered the property of any individual. Nothing in this chapter shall be construed to grant an ownership right to any individual or entity utilizing the publicly held information from the sequence of the human genome in the furtherance of the creation of a venture or enterprise, including any genetic goods, products, or services.

At first blush, this appears to be more of a statement of policy by the Vermont Act’s sponsors than a statement of law. §9336(e) refers to “the sequence of the human genome,” not a sequence of a human’s genome, and the term “genome” does not appear in the Vermont Act (or in Chapter 217 of the V.S.A.) outside of this single proposed provision.

While efforts to place genomic information in the public domain – including the work of Genomes Unzipped, the Personal Genome Project, SNPedia and The Sage Commons, to cite several such public genomics projects in which we are actively involved – are laudable, mandatory public genomics is not exactly the provenance of the Vermont state legislature.

Or perhaps this is just Representatives Pearson and Wizowaty’s way of asserting their support for the plaintiffs in the ongoing Myriad gene patent litigation by asserting, more than a decade after the fact, that none of the Human Genome Project’s fruits shall be patentable. (Although here, too, Vermont would be treading far outside the scope of its legislative authority.) Either way, this is one provision of the Vermont Act that will need to be either clarified or axed before passage.

Consumer Protection. The Vermont Act comes back to earth, and in line with the MA GBR, in proposing the addition of 18 V.S.A. §9339 and §9340, which together restrict the use of genetic information in marketing and instruct the “consumer protection unit in the office of the attorney” to “investigate and prosecute complaints relating to genetic goods, products, and services.”

As we have argued in the past, when it comes to the burgeoning field of genetic and genomic commerce, one logical and welcome form of regulation would be increased oversight from consumer protection agencies, including both state-level enforcement, as proposed by the Vermont Act, and increased national-level oversight from agencies like the Federal Trade Commission (FTC). (While the possibility of FTC oversight for genomic commerce was back in the news last week, specifically in conjunction with the FDA’s public meeting to discuss direct-to-consumer genetic testing, there are also numerous other areas of genomic commerce that might benefit from increased oversight from consumer protection agencies.)

§9339 also explicitly prohibits “genetic profiling,” which includes any effort to link an individual’s “demographic information” to her “genetic information or genetic material for marketing purposes.” However, the provision would not prohibit marketing on the basis of genetic data if those data were aggregated, did not contain identifying information and could not be used, “directly or indirectly, to obtain identifying information.” That would seem to be a fairly broad safer harbor for would-be “genetic profilers,” but given the inherent difficulty in ensuring that seemingly de-identified genetic information, even when aggregated, won’t be re-identified, this marketing safe harbor might prove to be rather limited in practice.

GINA’s Gaps, Again. As we noted in examining the MA GBR, the Genetic Information Nondiscrimination Act of 2008 (GINA) contains several gaps in its prohibition of insurance discrimination. Notably, while prohibiting healthcare insurers and employers from discriminating on the basis of genetic information, GINA does not address the use of genetic information in long-term care, life or disability insurance.

Even prior to GINA’s passage, Vermont was one of a handful of states with relatively robust statutory protections against genetic discrimination in insurance. Under current Vermont law (18 V.S.A. §9334), no insurance policy—including long-term care, life and disability insurance policies—may be “underwritten or conditioned on the basis of” a required genetic test of an individual insured or the results of a genetic test of any member of the individual’s family. §9332, however, currently permits insurers to require genetic testing in situations where doing so would not violate §9334.

The Vermont Act would revise §9332 to prevent insurers from requiring genetic testing in any setting, regardless of whether it would violate §9334. In combination with §9332(d), the Vermont Act would prevent any insurer from soliciting genetic testing without first obtaining “prior written authorization and informed consent,” including providing a warning that the results of such test might become part of the individual’s permanent medical record or materially impair the availability of insurance benefits. The Vermont Act would not, however, deny such solicitations by insurers outright.

The Vermont Act would also prohibit places of public accommodation (9 V.S.A. §4502) and financial institutions supplying credit (8 V.S.A. §10403) from discriminating on the basis of genetic information.

What does it mean? As with the MA GBR, it is crucial to emphasize that the Vermont Act is a legislative proposal and not current state law. We do not know what level of support the Vermont Act enjoys within the state legislature but, should it pass, the implications—both good and bad—would be substantially similar to those we discussed in our review of the MA GBR.

Next week we’ll examine another legislative proposal, from California, and ask whether these recent developments represent a groundswell of support for more robust genetic privacy legislation.

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¹ The text of the Vermont Act says “real property,” although this would seem to be a clear mistake as real property or real estate refers to land and not to personal or intangible property.

So just what should we expect from the next two-days? 2010 saw a flurry of DTC-related regulatory and legislative activity but, ultimately, little in the way of new oversight or concrete guidance. Both regulators (including the FDA) and industry appear to have responded in 2011 with a more measured approach, and this week’s meeting is an opportunity to thoroughly examine the state of DTC genetic testing and develop a clear, sensible strategy for future oversight of the industry.

Over at Genetic Future, Daniel MacArthur has already weighed in, adopting a tone of cautious optimism in advance of the DTC meeting. Meanwhile, with just a few hours left until the meeting kicks off, here are three key points I’ll be emphasizing in my own talk tomorrow morning (slides):

1. What does “DTC” mean? Direct-to-consumer, direct access, over-the-counter, home use…the terminology is exhausting and rarely used consistently. A key goal for the next two days will be to establish, as clearly as possible, precisely what “direct-to-consumer genetic testing” means, as well as which particular varieties of DTC genetic testing the FDA is interested in overseeing. For instance, in the Executive Summary provided in advance of the meeting (pdf), the FDA indicated that it is:

…focused specifically on issues regarding clinical genetic tests that are marketed directly to consumers (DTC clinical genetic tests), where a consumer can order tests and receive test results without the involvement of a clinician.

That’s helpful, because it identifies specific types of DTC genetic testing (e.g., clinical tests marketed to, and ordered by, consumers, without physician involvement) that concern the FDA and, by extension, other types of DTC genetic testing that, for now, appear to be in the clear (e.g., non-clinical tests). Still greater specificity is possible, however, and will be critical to developing clear guidance.

2. Planning for the DTC of tomorrow. To develop an appropriate system of oversight for DTC genetic testing, we must consider the DTC genetic testing industry not only as it exists today but also as it is nearly certain to exist tomorrow. With the rapidly declining cost of whole-genome sequencing (WGS) it is only a matter of time before we transition from SNP-based DTC genetic testing to WGS-based DTC genomic interpretation. This transition won’t happen in 2011, but it will happen, and it will happen soon enough that any DTC oversight developed today must be designed with WGS firmly in mind.

DTC’s inevitable shift from comparatively limited genotyping to whole-genome sequencing, just as it did in clinical and research genetics, will carry with it numerous important changes. First, it will obliterate the increasingly tenuous clinical/non-clinical distinction at the level of the DTC test, with DTC providers offering both clinical and non-clinical data (along with copious amounts of data of uncertain significance) as an unavoidable feature of every whole-genome sequence.

Second, it will accelerate a trend already in place today: the separation of testing (data generation) from interpretation (data analysis). Two and a half years ago, DTC spit parties graced the Fashion & Style section of The New York Times. Two and a half years from now, odds are that consumers at the forefront of DTC will have long ago mailed in their last “spit kit” and, with whole-genome sequence in (virtual) hand, will have a bevy of software-based DTC interpretative services from which to choose.

3. Coordination and Leadership. Finally, while an important part of the personal genomics landscape, clinical DTC genetic testing is still only part of that landscape. Close coordination with other federal agencies (e.g., CMS and FTC), as well as with states and international bodies, will be necessary to ensure not only meaningful oversight of clinical DTC genetic testing, but also the development of a comprehensive, coherent system of oversight for personal genomics and personalized medicine. An important part of the “path to personalized medicine” (outlined by FDA Commissioner Hamburg and NIH Director Collins last summer) will be close coordination among agencies and other forms of oversight, not mere legislative or regulatory Band-Aids.

It will also require leadership. For the second decade of human genomics to be as groundbreaking as the first, we need strong and even visionary leaders at the federal level who are focused on addressing the policy, as well as legal and social challenges that threaten to serve as barriers to scientific and medical progress. Those are not shoes the FDA will be able to fill on its own, but the FDA should be encouraged to participate fully in that process.

I will likely have more to say as the meeting progresses (you can follow along on Twitter at #FDADTC) and ultimately concludes. In the meantime, feel free to share your thoughts about what you would like to see from Washington over the next two days in the comments below.

According to Ray, SACGHS members were notified this week that Secretary Sebelius and NIH Director Francis Collins had determined that “the major topics related to genetic and genomic technologies had been successfully addressed by the committee through its comprehensive reports and recommendations over the years” and, for that reason, the decision was made “to sunset the committee’s charter.”

A Decade of Discussion. The SACGHS was first established by HHS eight years ago (pdf) to “provide a forum for expert discussion and deliberation…on the range of complex and sensitive medical, ethical, legal and social issues raised by new technological developments in human genetics” and assist policymakers at HHS and other federal agencies in addressing those issues. The committee’s charter, which was last renewed in 2008 (pdf), includes “assessing how genetic technologies are being integrated into health care,” “examining current patent policy and licensing practices” and “analyzing uses of genetic information in education, employment, insurance…and law.”

Over the past eight years, as the range of genetic technologies and information has expanded dramatically, SACGHS has tackled all of these issues, along with many others. Some of the committee’s most significant undertakings included (1) repeated efforts to encourage the passage of the Genetic Information Nondiscrimination Act (GINA) (see here, here and here), (2) a 2008 report on the U.S. System of Oversight of Genetic Testing (pdf), (3) a 2010 report on Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests (pdf) and (4) a 2010 report on Direct-to-Consumer Genetic Testing (pdf).

Although advisory in nature, the committee’s activities have had a noticeable impact on genetic law and policy in recent years. While far from GINA’s only advocate, SACGHS’s continued support helped to ensure the law’s ultimate passage in 2008. The committee’s 2008 report on the regulation of genetic testing has been widely cited by lawmakers and policymakers, particularly those seeking to reform or extend the current system of oversight. Its 2010 gene patenting and licensing recommendations, along with coverage of the ongoing Myriad gene patent litigation, continues to spur public and private debate about whether and how to redesign the biotechnology patent regime. And its most recent report, on direct-to-consumer (DTC) genetic testing, while largely obscured by other contemporaneous developments within the DTC industry, may well serve as a roadmap for future industry oversight by the Food and Drug Administraton (FDA), Federal Trade Commission (FTC) and other regulatory bodies.

A Challenge for the Next Decade. The central role that SACGHS has played in analyzing the ever-expanding range of ethical, legal and social issues presented by genetic and genomic technologies, and in formulating policy suggestions to address those issues, makes the decision by Sebelius and Collins to disband SACGHS curious, to say the least. According to Ray, Collins was scheduled to provide a more complete explanation to the committee of “why he and [Secretary Sebelius] believe that the committee has accomplished its mission…” We hope that either Collins or Sebelius will choose to share their thinking more broadly.

No matter the rationale, it is clear that even those issues SACGHS investigated in detail have not been resolved with any meaningful degree of finality. GINA, while finally law, is still being implemented by regulatory agencies, and significant enforcement has yet to occur. Regulatory agencies have only recently begun to implement new policies (e.g., the NIH’s announcement that it is developing a voluntary Genetic Testing Registry and the FDA’s proposal to commence risk-based regulation of all laboratory-developed tests (LDTs)) designed to close the gaps in genetic testing oversight identified by SACGHS more than two years ago. The issues identified in the committee’s two most recent reports – on gene patents and DTC genetic testing – have yet to be meaningfully addressed by federal agencies, and represent some of the most contentious issues in genetics law and policy today.

What’s more, the pace of technological development is not slowing and it is difficult to see how anyone could suggest that SACGHS has sufficiently investigated all or even a majority of the important issues attendant to genetic technologies. Coming advances in genomic sequencing promise to make genetic data increasingly inexpensive and available, bringing to the fore new questions about genomic privacy, reproductive genetic technologies and access and affordability, along with many others, including crucial issues we cannot predict today. Indeed, SACGHS recently formed a task force to study the implications of whole-genome sequencing, although it is unclear whether the committee will have the opportunity to pursue that investigation to its conclusion.

In the eight years since SACGHS’s inception, we have seen significant scientific advances, and these have in turn produced an impressive range of associated ethical, legal and social issues. As we head into a second decade of increasingly personal genomic science and services, there is every reason to expect that as our technological capabilities expand, so too will the number and complexity of issues we are forced to address. Our challenge is to continue to develop legal and policy strategies that are reflective and not reactionary – strategies that ensure the safety of individuals while encouraging the innovation necessary to realize the promise of personalized medicine. We hope that the announced disbanding of this experienced and distinguished committee does not signal a declining commitment on the part of Secretary Sebelius or Director Collins to this challenge.

Meggan Bushee is a student at the

This past May, Congressman Patrick Kennedy (D-RI) and Congresswoman Anna Eshoo (D-CA) re-introduced a personalized medicine bill to the U.S. House of Representatives. The bill was originally introduced in 2006 by then-Senator from Illinois Barack Obama. While HR 5440, also known as the Genomics and Personalized Medicine Act of 2010 (GPMA 2010), has retained the name of the bill originally introduced by Senator Obama, its approach to the regulation of personalized medicine has taken a new direction.

GPMA 2010 is the fourth version of the GPMA since the original bill of 2006, and includes the most ambitious initiatives of all of its predecessors. Why has the GPMA re-surfaced after three prior versions failed to make it out of committee? According to Representative Kennedy, the bill has been re-introduced in response to increased public awareness and use of genomic tests. At present, GPMA 2010 is before the House Committee on Energy and Commerce. This is the same committee that recently conducted high-profile hearings to review the current state of the direct-to-consumer (DTC) genetic testing registry.

As the tools of personalized medicine, including genetic testing, have become both less expensive and more powerful, calls for expanded oversight of the field have intensified, particularly in the area of DTC genetic testing. While there is a pressing need for appropriate regulation to protect the consumers and patients targeted by personalized medicine, there is an equally pressing need to avoid crafting a system of oversight that will be an obstacle to continued growth and innovation. The current version of the GPMA aims to strike a balance between consumer protection and flexibility to allow for innovation.

This post outlines the material provisions of GPMA 2010 and examines the transformation the bill has undergone since it was first introduced in 2006.

The GPMA Defines Itself. The stated aim of the Genomics and Personalized Medicine Act is:

To secure the promise of personalized medicine for all Americans by expanding and accelerating genomics research and initiatives to improve the accuracy of disease diagnosis, increase the safety of drugs, and identify novel treatments, and for other purposes.

Interestingly, GPMA 2010 is the first iteration of the GPMA to formally define the term “personalized medicine.” However, the bill limits its definition of “personalized medicine” to:

any clinical practice model that emphasizes the systematic use of preventive, diagnostic, and therapeutic interventions that use genome and family history information to improve health outcomes.

It’s a broad definition, but is it broad enough? Conspicuously absent from the definition is any mention of environmental information, a category that is increasingly recognized as critical to the understanding and management of complex and common traits and diseases.

Despite its narrow definition of personalized medicine, GPMA 2010 includes several expansive initiatives. GPMA 2010 would appropriate $150 million for fiscal year 2011 to accomplish these initiatives, including the creation of an Office of Personalized Healthcare and several committees to address translational challenges of personalized medicine, the standardization of the collection of human biological samples, the funding of further research and education on personalized medicine, and the creation of a national biobank.

In order for those initiatives to bear fruit, the GPMA, should it proceed, is likely to find itself in need of a similarly expansive definition of personalized medicine.

The OPH: Coordinating Personalized Medicine. GPMA 2010 would create an Office of Personalized Healthcare (OPH) within the Department of Health and Human Services (HHS). The OPH would have two main roles: (1) to oversee the implementation of GPMA 2010’s initiatives, and (2) to coordinate the activities of various federal agencies and private and public entities. To fulfill these roles GPMA 2010 would appropriate $5,000,000 for fiscal year 2011, and “such sums as may be necessary” for later years.

The OPH is a new addition to the GPMA since its previous version in 2008. Prior to GPMA 2010, the GPMA provided for the establishment of an Interagency Working Group (IWG), an initiative that was first introduced in the 2006 bill. The IWG had goals similar to those of the OPH, but had few specific responsibilities. The IWG was mainly responsible for meeting twice a year and submitting a report every two years on IWG activities. The OPH, on the other hand, would be more directly involved in directing the expansion and acceleration of research, and signifies a large departure from all prior GPMA bills.

Among other responsibilities, the OPH would be tasked with the development of a long-term plan to accelerate the research and development of personalized medicine products. Each year the OPH would issue a report discussing not only progress within personalized medicine research, but also the challenges that the OPH has identified and is currently addressing. This provides a case in point for how the narrow definition of “personalized medicine” in the bill might affect the implementation of the GPMA. To use our example, if the role of environmental factors is not included in the definition, the OPH’s long-term plan might not take adequate account of the need to utilize environmental data in developing effective personalized medicine products.

Importantly, as presently drafted, the OPH would also be responsible for recommending which personalized medicine products should be regulated, and what roles and responsibilities should be assigned to the Food and Drug Administration (FDA) as opposed to the Centers for Medicare & Medicaid Services (CMS). Presumably this would include weighing in on areas where those two agencies’ regulatory authority appears to overlap, including the regulation of laboratory developed tests. Here again, the act’s definition of “personalized medicine” makes a difference.

GPMA 2010 recognizes the need for greater cross-agency coordination and for a centralized task force to direct the implementation of GPMA initiatives. One ongoing concern is that the development of personalized medicine and its translation to clinical practice will be hampered by redundant and inconsistent oversight at the hands of multiple, overlapping regulatory bodies. The OPH would address this concern, at least in theory, by assigning regulatory authority for personalized medicine products, clarifying and simplifying existing regulations, and providing a clear delineation between the roles and responsibilities of the FDA, CMS and other regulatory agencies. The key question, however, is whether adding a new agency (OPH) to the personalized medicine mix would bring much-needed coordination and strategic vision to the field, or whether it would simply add another layer of confusion and bureaucracy.

A National Biobank. Similar to the biobank initiatives in all three previous versions of the GPMA, GPMA 2010 would create a national biobank to collect and integrate human biological specimens and biobank data. As defined by GPMA 2010, “biobank data” includes health information, demographic genotype, molecular profile data, and (despite being excluded from the definition of “personalized medicine”) environmental data.

If implemented, GPMA 2010’s national biobank would not be the first of its kind in this world. Several countries, including the United Kingdom, Japan, Sweden, Finland, and Iceland have already undertaken similar biobanking initiatives. While the United States has many smaller public (at both the state and federal level) and private biobanks, the GPMA would authorize NIH to coordinate the first truly national biobank. Depending on how swiftly the biobank was created, and whether it incorporated samples from previously existing public or private biobanks, it might quickly become one of the largest repositories of biological specimens and data in the world.

While the implementation of the biobank would be left to the Director of the NIH (currently Francis Collins), working in coordination with the Centers for Disease Control and Prevention (CDC), GPMA 2010 does provide a basic framework. The Director of NIH would be responsible for coordinating the activities of the national biobank with the other public and private biobanks and genomic databases in the United States and developing guidelines to “safeguard[] the privacy of…biobank data.” The Director would also be tasked with addressing ownership and patient access issues and investigating new models of informed consent that balance privacy, risk disclosure and the need for long-term and open-ended research, a task that has recently been shown to be particularly challenging.

One inevitable challenge in implementing a truly national biobank populated with broadly characterized specimens will be funding. To establish the national biobank and fund a related grant program, GPMA 2010 would appropriate $150,000,000 for fiscal year 2011, and “such sums as may be necessary” for later years. While the biobank’s data and specimens would be made available to both government and non-governmental entities, it is unclear whether non-governmental entities would bear some portion of the cost of the biobank.

Is $150 million and the vague promise of more to come sufficient for a biobank of such ambition? By way of comparison, while the initial appropriation, as currently drafted, would be larger than the amount used to catalyze the UK’s national biobank in 2006, which collected £62 million from a variety of funding sources, including the Wellcome Trust, the UK’s largest non-governmental source of biomedical funding. For the GPMA’s national biobank to succeed, similar private funding commitments might well be a prerequisite.

The various incarnations of the GPMA have fluctuated in their treatment of race. The 2006 GPMA had an entire section dedicated solely to “Race and Genomics,” and included several initiatives aimed at including minority populations in genomics research and in improving minority populations’ access to genetic services. The 2010 bill lacks the separate section, but does instruct the Director of the NIH to develop guidelines to “ensure the inclusion of underrepresented populations with health disparities in the activities of the national biobank.” That is itself a departure from the 2008 version of the GPMA, which did not specifically mention minority or underrepresented populations at any point. The role of minority or underrepresented populations in genomic research, and the appropriateness of personalized medicine tools and products for minority or underrepresented populations, was an issue that came up several times at last month’s Congressional hearing on DTC genetic tests, and it is one that would be likely to play a central role in any future Congressional discussion of the GPMA and a national biobank.

The GPMA and DTC Genetic Testing. GPMA 2010 directs the FDA to collaborate with the FTC to “identify and terminate…advertising campaigns that make false, misleading, deceptive, or unfair claims about the benefits or risks of products used for personalized medicine.” While similar consumer protection provisions existed in prior versions of the GPMA, the scope has been expanded in the current version of the bill to apply to advertising and marketing of any personalized medicine product (previous versions focused solely on genetic tests).

Events may have overtaken this proposal, however. Last month’s Congressional hearing and GAO report (pdf) highlighted “misleading test results” and “deceptive marketing and other questionable practices” on the part of DTC genetic testing companies. The report was forwarded to the attention of both the FDA and the FTC and, in its aftermath, it seems unlikely that it will take the passage of new legislation for those two agencies to begin working together to more aggressively police the personalized medicine marketplace.

Interestingly, a separate provision of GPMA 2010 would instruct the CDC, the FDA and the FTC to work together to “conduct an analysis of the public health impact” of “products used for personalized medicine (including genetic and genomic tests) for which consumers have direct access” and to do so “to the extent possible from available data sources.” The joint agency initiative would also “analyze the validity of claims made in [DTC] marketing” and “make recommendations…regarding necessary interventions to protect the public from potential harms” of DTC marketing and access to personalized medicine products. While such an undertaking might appear redundant with the GAO’s recently-concluded investigation, the GAO’s report was an admittedly unscientific snapshot of the field (“GAO did not conduct a scientific study but instead documented observations that could be made by any consumer.”), for which it has been frequently criticized. While a more comprehensive and data-driven analysis of the field would be welcome, recent events suggest that agencies such as the FDA are likely to proceed with additional DTC regulatory oversight on the basis of the data (or lack thereof) currently at hand.

Expanding the Role of Companion Diagnostics and Pharmacogenomics at the FDA. Another provision targeted at the FDA would permit the agency, under certain circumstances, to “require the sponsor of a drug or biological product” (emphasis added) to develop a companion diagnostic test in connection with regulatory filings for a new drug. This provision was originally included in the 2006 bill, but was removed in the 2007 and 2008 versions. Those versions merely permitted the FDA to recommend companion diagnostic development to drug and products sponsors.

The 2010 GPMA also instructs the FDA to “clarify and issue guidance” that explains when companion diagnostics will be included in labeling – including appropriate “standards of evidence…such as with respect to the analytical validity, clinical validity, clinical utility, dosing, adverse events, and drug selection…” – and when such tests will be either recommended or required.

In many respects these provisions of the GPMA seem to reflect the increasing reliance on genomic and genetic data in selecting and administering therapeutics, including the use of companion diagnostic tests.

Where Will the GPMA Go From Here? While GPMA 2010 itself represents a significant departure from the bill originally introduced by Senator Obama in 2006, it is exceedingly unlikely to become law in its current form. Among other considerations, the recent (and ongoing) developments in the areas of laboratory developed tests (LDTs) and DTC genetic testing – two important components of personalized medicine – suggest that substantial revisions would be required to reflect an ever-changing technological, commercial and regulatory environment.

At least for the moment, passage of the GPMA in any form does not appear to be imminent. Perhaps it will never become law – at least in anything like its current form – and either existing legislation or other contenders, such as Senator Hatch’s proposal to create a new regulatory category for “advanced personalized diagnostics” – will be used to fill gaps in the oversight of personalized medicine products. Then again, recall that crafting legislation to respond to the successes of modern science and technology can be a painfully slow process. For instance, the only piece of federal legislation specifically directed at genetic technologies and information, the Genetic Information Nondiscrimination Act (GINA), took thirteen years from the date it was first proposed to its signing into law in 2008. After a mere five years, the GPMA likely has a long way to go.

[Editor’s Note:

On Tuesday, Carmichael and five commentators examined what can be learned from a DTC genetic test. Yesterday, the topic was whether DTC genetic tests are trustworthy, and whether the results can be cause for concern. Today’s topic is the regulation of DTC genetic tests. In addition to several short commentaries, including a much shorter version of the piece below, Carmichael has also posted a lengthy interview with two top FDA officials on the subject of DTC genetic testing regulation.

The column below is an expanded version of what appears over at Newsweek. To see all of the commentaries in Carmichael’s series, click here.]

The recent media attention focused on direct-to-consumer (DTC) genetic tests has left companies, investors, consumers and even regulators scrambling to figure out what comes next.

As the situation stands today, companies and their investors live in a climate of unprecedented regulatory uncertainty, causing delays in the introduction of new products and rendering an already inhospitable economic climate – for both fundraising and sales – even more challenging. Commentators and regulators caution consumers that some DTC genetic tests may be unreliable or, worse, harmful, but have yet to provide clear tools and guidelines for evaluating competing tests. And regulators, including the FDA, must balance their mandate to protect the health and safety of the public with that same public’s desire for autonomy, while also recognizing that innovation is a prerequisite for a healthcare system that must continue to improve outcomes while reducing costs.

Clearly, something must change. But what will that change be? And how will the field of DTC genetic testing evolve? Will DTC be able to continue its current business while regulators and companies engage in protracted negotiations? Will oversight weed out the “snake oil salesmen” and permit legitimate companies to flourish? Will it drive all genetic testing (temporarily) out of the hands of consumers?

Or will the field change in a dramatic and completely unexpected way?

These questions, and others, caused Newsweek science editor Mary Carmichael to realize her oft-debated question – To Test or Not To Test? – might demand an answer sooner rather than later:

. . . I started to worry . . . . How much time did I even have left to decide whether I was going to take a test myself? Even before [last month’s Congressional] hearing, the FDA had announced its plans to regulate all DTC genetic tests, possibly so heavily as to keep them off the market; the hearing was just the sort of thing that could push it to move faster. What if, by the time I finally decided if I wanted one of these tests, I couldn’t buy one anymore?

Setting aside the question of whether Carmichael, or anybody else, should buy a genetic test, this column examines the history of DTC genetic testing regulation in the United States¹ and, in the final section, whether the DTC option is likely to persist in the future.

Because this post is longer than usual, here is a quick, clickable roadmap to its various sections. If you’re already familiar with the history of DTC genetic testing you may wish to jump ahead to the final section or two.

1. 2006: DTC and the First GAO Report.

2. 2007: The Beginning of Modern DTC

3. 2008: SACGHS and a Scare From the States

4. 2009: All Quiet on the DTC Front

5. 2010: DTC Goes to Washington

6. Today: Uncertainty Reigns

7. Tomorrow: Unintended Effects (and More Uncertainty)

8. Beyond: A Delicate Balancing Act

2006: DTC and the First GAO Report. Four years ago last month, the Federal Trade Commission (FTC), Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) published a consumer fact sheet entitled “At-Home Genetic Tests: A Healthy Dose of Skepticism May Be the Best Prescription.” The guidance warned consumers to be wary of claims made by DTC genetic testing companies and to involve “a doctor or trained counselor who understands the value of genetic testing for a particular situation” when ordering or interpreting any genetic test.

The joint agency guidance document was published in concert with a report from the Government Accountability Office (GAO) entitled “Nutrigenetic Testing: Tests Purchased from Four Web Sites Mislead Consumers” (pdf). The GAO report reviewed a “nonrepresentative selection” of genetic tests available to consumers at that time and concluded that those tests “mislead the consumer by making health-related predictions that are medically unproven and so ambiguous that they do not provide meaningful information to consumers.” The report was praised for “drawing attention to potentially important consumer protection issues,” even as it was criticized for “serious methodological flaws that undermine[d]” those very criticisms (pdf).

Whatever its methodological flaws, the GAO’s description of the system of regulation for DTC genetic testing, which it characterized as one of “minimal oversight [that] makes it difficult for consumers to determine whether a genetic test provides meaningful, scientifically based information,” was entirely accurate.

2007: The Beginning of Modern DTC. With the launch of DTC products from a publicly traded biopharmaceutical company (deCODE Genetics) and a Google-backed startup (23andMe) on back-to-back days in November 2007, the modern era of DTC genetic testing was born. With 23andMe, deCODE and, soon, Navigenics, consumers could now pay around $1,000 to review hundreds of thousands of SNPs. Following Knome’s launch, also late in 2007, they could pay much, much more ($350,000) for access to their entire genome.

Despite this dramatic shift in the DTC product landscape, the legal landscape remained essentially unchanged from 2006. Regulatory oversight was still incomplete, confusing and rarely invoked.

At the federal level, while most DTC genetic tests were likely covered from the outset by the Clinical Laboratory Improvement Amendments of 1988 (CLIA), it was typically difficult to determine whether DTC genetic testing companies were operating using CLIA-certified labs. (23andMe, for example, did not begin using a CLIA-certified laboratory until 2008, making the change in response to “evolving” regulatory requirements.) CLIA, which is implemented by the Centers for Medicare & Medicaid Services (CMS), requires laboratories to demonstrate the analytical validity of their tests, and covers most genetic tests regardless of whether they are provided directly to consumers or not.

In addition to CLIA, a limited number of genetic tests were also regulated by the FDA. Although the proposition was not immediately tested, it was widely assumed that DTC genetic tests constituted a new form of laboratory developed test (LDT), a large and well-established category of tests over which the FDA exercised “enforcement discretion.” While the FDA had historically declined to regulate LDTs, in 2006 and 2007 the FDA expressed its desire to regulate certain types of high-complexity LDTs (so-called IVDMIAs). As is still true today, it was unclear where, if anywhere, the newly introduced DTC genetic tests fell within the LDT conversation and FDA’s larger regulatory universe.

In addition to uncertainty at the federal level, some states possessed (and still do possess) statutes that appear to prohibit – or at least restrict – DTC genetic testing (pdf). However, it was unclear whether such statutes, which clearly predate the arrival of DTC genetic testing in its current form, were intended to prevent DTC genetic testing or whether they would be enforced by state regulators in any event. State-level regulatory restrictions contributed to at least one company withholding its service from citizens in at least 10 states at the time of its launch.

Despite all of this legal uncertainty, no federal or state regulatory agency took any formal action immediately following the introduction of DTC genetic testing to the consumer marketplace.

2008: SACGHS and A Scare from the States. During its first full year, the DTC genetic testing marketplace continued to grow as new companies arrived on the scene and existing companies refined and expanded their offerings.

Meanwhile, an influential government policy committee (SACGHS) had undertaken a review of the “U.S. System of Oversight of Genetic Testing.” When it was published in April of 2008, the 276-page report surprised almost no one when it identified major gaps in the regulation of genetic testing, including insufficient oversight of laboratory quality, clinical validity and a lack of knowledge with respect to the nature and uses of genetic tests available for purchase, whether directly by consumers or otherwise. Among the report’s several recommendations were increased FDA regulatory oversight and the creation of a mandatory, public registry for all laboratory tests.

Shortly after the publication of the SACGHS report, public health officials in New York and California sent “cease and desist” letters to a number of genetic testing companies. The states warned the companies – including 23andMe, deCODE and Navigenics, the three most prominent DTC providers at that time – that they were operating without necessary state licenses.

The SACGHS report and state regulatory letters produced widespread debate about the appropriate regulatory framework for DTC genetic testing. Companies were concerned that other states might follow the example set by New York and California and seek to regulate DTC genetic tests directly, potentially exposing DTC companies to a nightmare scenario of inconsistent, state-by-state regulation. Proponents of regulation, meanwhile, argued that the nascent field needed some regulation “lest abuses discredit the whole industry before it has a chance to thrive.”

In the following weeks, months and even years, some DTC companies received state licenses, although this came at the expense of offering tests directly to consumers in some cases. Other companies ceased selling to customers in specific jurisdictions, and still others simply went out of business. At the federal level, the SACGHS recommendations continued to generate far more discussion than action, and the regulatory landscape remained materially unchanged. Meanwhile, major DTC companies continued to press ahead, and 2008 closed with 23andMe’s DTC genetic test being named Time’s invention of the year.

2009: All Quiet on the DTC Front. In comparison to the years on either side, 2009 was a relatively quiet year for DTC genetic testing, at least from a regulatory perspective.

On the commercial side, however, 2009 saw a number of changes ripple through the DTC genetic testing marketplace. As the price of DTC genetic tests continued to fall, a new competitor, Pathway Genomics, arrived on the scene and 23andMe significantly revamped its product offerings and pricing shortly thereafter. Meanwhile, the financial crisis played a major role in causing DTC pioneer deCODE Genetics to file for bankruptcy protection, although the company quickly emerged under private control and its deCODEme test remains on the market today.

To be sure, regulators continued to ponder how to respond to the rapidly evolving genetic testing marketplace, which included but was not limited to DTC products. For example, the FDA continued to express an interest in regulating some LDTs and the California legislature considered a bill – championed by 23andMe – that would create a special regulatory framework for so-called “post-CLIA bioinformatics services,” although nothing would come of either initiative, at least in 2009. Perhaps most significantly, but unbeknownst to either the public or the major DTC genetic testing companies, Congress had instructed the GAO to begin a second investigation into the DTC genetic testing industry, the results of which would not be made public until the following year.

With regulators seemingly on the sidelines, academics and other commentators, including the Genomics Law Report, continued to stress the need for meaningful self-regulation in order to:

(1) discourag[e] consumers from purchasing products not adequately supported by scientific evidence, (2) provid[e] regulators such as the Federal Trade Commission (FTC) with a standard against which to evaluate (and sanction) false or misleading DTC tests or services, and (3) ensur[e] that inevitable governmental regulation is not overly restrictive.

Prominent scientists, including soon-to-be NIH chief Francis Collins and genomics pioneer Craig Venter, also emphasized the need for greater transparency and consistency in the way DTC companies presented genetic risk of disease to consumers. While there was widespread consensus, including on the part of DTC providers, that self-regulation and even some form of government regulation would be beneficial for the industry as a whole, by the end of 2009 no notable changes – government mandated, voluntary or otherwise – had materialized.

2010: DTC Goes to Washington. Although we are not yet two thirds of the way through the year, 2010 has already seen an explosion of activity in the oversight of DTC genetic testing.

The first major development came in March, when the NIH announced the creation of a voluntary genetic testing registry. In its 2008 report (pdf), SACGHS had recommended the creation of a “mandatory, publicly available, Web-based registry for laboratory tests” in order to “enhance the transparency of genetic testing and assist efforts in reviewing the clinical validity of laboratory tests.” The NIH adopted this recommendation with one crucial exception: the registry, at least as proposed, will be voluntary.  However, it remains to be seen, particularly in light of everything that has happened since the announcement in March, what form the NIH’s registry will ultimately take when it debuts later this year or in early 2011.

For DTC genetic testing, the excitement really began on May 11th, when Pathway Genomics announced it was partnering with Walgreens to offer its genetic testing service on the shelves of most of the drugstore giant’s 7,500 stores. The FDA responded almost immediately with an “Untitled Agency” letter to Pathway Genomics in which the agency informed Pathway that it could find no record of the necessary FDA clearance or approval for Pathway’s test. The Pathway letter – which represented the FDA’s first public foray into the oversight of DTC genetic testing – was followed by similar letters to five prominent DTC genetic testing companies in early June and letters to 14 more genetic testing companies in late July. These letters were, of course, something of a surprise to the companies. The FDA could not find evidence that it had approved the companies’ tests because, in at least some and possibly all cases, the agency had not told the companies that such approval was necessary.

In addition to taking aim at DTC genetic testing companies, the FDA also announced that it was shelving its plan to regulate a subset of LDTs (i.e., IVDMIAs) in favor of a new plan to regulate all LDTs. Late last month the FDA held a two-day “Public Meeting on Oversight of Laboratory Developed Tests” to discuss that plan. (It is important to point out that, despite devoting an entire portion of the public meeting to DTC genetic tests, on multiple occasions the FDA has indicated that it considers at least some DTC genetic tests not to constitute LDTs since the products are “not developed by and used in a single laboratory.”)

Not to be outdone, Congress quickly announced its own investigation into DTC genetic testing (one it had quietly initiated the year before) and followed that up with a public hearing on “Direct-To-Consumer Genetic Testing and the Consequences to Public Health.” The centerpiece of July’s Congressional hearing was yet another GAO report (pdf) whose conclusion was announced in the title: “Direct-To-Consumer Genetic Tests: Misleading Test Results Are Further Complicated by Deceptive Marketing and Other Questionable Practices.” The GAO also presented a striking and widely circulated YouTube video as partial support for its conclusion. (For a more detailed review of the Congressional hearing and the GAO report please see this recap.)

At the Congressional hearing, Jeffrey Shuren, the Director of the FDA’s Center for Devices and Radiological Health (CDRH), assessed the FDA’s recent activity by agreeing with Congressman Michael Burgess (R-TX) that the FDA “should have acted sooner” to regulate DTC genetic tests. Shuren was likely referring to a perceived failure on the part of the FDA to adequately safeguard the public.  Given the absence of any publicly documented harm resulting from consumer access to genetic tests , however, there are certainly those who would disagree, arguing that the FDA should still refrain from regulating DTC genetic tests.

Listening to Shuren’s remarks at the hearing, one could easily wonder whether his lament was actually directed at the agency having been caught off-guard, at least to a degree, by the debut of the GAO’s striking report, which was unveiled to the public – and the DTC companies themselves – at the hearing.  According to the report (pg. 19) the GAO officially briefed the FDA, NIH and FTC on the contents of the report in late May and early June. However, when I raised this point yesterday during an FDLI webinar on FDA’s (Emerging) Oversight of LDTs, fellow panelist Dr. Elisabeth Mansfield, Director for Personalized Medicine at CDRH, clarified that the GAO’s “briefing” consisted of a teleconference where the FDA learned only the bare fact that the GAO had conducted an inspection and had “found problems.”

Perhaps it is just a perfect storm of coincidences. But in any event, the FDA actions and the GAO report – along with other recent high-profile developments including the Pathway / Walgreens pairing and 23andMe’s “sample swap” – have created unprecedented uncertainty.

Today: Uncertainty Reigns. The GAO report, the FDA’s letters and all of the other events of the past few months have indisputably ratcheted up the level of uncertainty throughout the genetic testing industry.

However, as a purely legal matter, it does not appear that the formal regulatory framework governing DTC genetic testing has changed much if at all in recent months, or even since 2006, particularly at the federal level. Congress has passed no new legislation, and neither the FDA nor any other federal agency has promulgated new regulations or formal agency guidance.   This, of course, is not at all surprising: the rate of development in any new area of science and commerce inevitably surpasses the ability of lawmakers and regulators to keep pace. DTC genetic testing has hardly proved an exception to that rule.

Setting aside the myriad hearings, public and private meetings and statements made to the press by regulators – which, while significant, do not rise to the level of rulemaking – the only formal, public action one can point to is the FDA’s ongoing letter-writing campaign. However, as the FDA has clarified in the past, these “Untitled Letters” remain several steps removed from an FDA enforcement action:

While Warning Letters set out specific violations of law that a company must address immediately or else the agency will take an enforcement action, an Untitled Letter identifies agency concerns and gives a company the opportunity to meet with the agency and to have time to take appropriate steps to address these concerns….Based on how the companies respond to the Untitled Letters, FDA may follow up by sending Warning Letters.

Of course, an absence of documented regulatory change does not imply that the commercial DTC genetic testing landscape has remained anything close to stable.

Responses from DTC companies and investors to today’s uncertainty have varied. Some companies (including Pathway Genomics and Counsyl) have ceased offering their tests directly to consumers, at least for the moment. Others, including two original DTC genetic testing companies (23andMe and deCODE), have expressed a desire to work with regulators while continuing to make their products available to consumers. Many of the major DTC companies, whether or not they are currently offering products directly to consumers, have also criticized both the GAO and the FDA for their approach to DTC genetic testing (see these blog posts at Navigenics, 23andMe and Pathway Genomics) while simultaneously expressing their desire to work with regulators to bring greater oversight to the industry.

Meanwhile, new companies and investors must reevaluate business plans to take into account anticipated regulatory changes.  And customers, including Mary Carmichael, must weigh the possibility that today’s DTC options may disappear from tomorrow’s digital storefronts.

Since 2006, the regulation of DTC genetic testing has been consistently characterized as confusing, incomplete and inconsistently applied. That characterization remains as true today as it was four years ago. So perhaps the only meaningful difference from four years ago is one of degree: more so than at any time over the past four years, there now appears to be a consensus that something must – and will – be done to overhaul the regulation of DTC genetic tests.

Tomorrow: Unintended Effects (and More Uncertainty). But not so fast. Despite the apparent agreement among regulators, industry and most commentators that DTC genetic testing is in need of additional oversight, there is still no guarantee that change is coming soon, or even at all.

Indeed, it is not difficult to look at the events of the past few months and conclude that DTC has been down this road before:

• A GAO report decrying the evils of DTC genetic testing and subsequent Congressional hearing? 2010 and 2006.
• Threatening regulatory letters to DTC companies? 2010 and 2008.
• A controversial FDA regulatory proposal that might – or might not – encompass DTC genetic tests? 2010 and 2006.

Industry watchers who have been around since the beginning would be excused for expressing at least some skepticism that this is the time, finally, when the DTC genetic testing landscape will be fundamentally remade.

Continuing Uncertainty. There is also the possibility that a new regulatory regime for genetic tests will emerge, but that it will push DTC genetic testing to the side and in so doing cause the industry to remain mired in uncertainty.

As the FDA pushes forward with the development of agency guidance for the regulation of LDTs, there are concerns that the agency may carve out many or most DTC genetic tests from this regulatory framework. In June, the FDA expressed its belief that several prominent DTC companies (23andMe, Knome and deCode) are offering tests that do not constitute LDTs because they are “not developed by and used in a single laboratory.”

Recent signals – including the designation of a separate panel for LDTs during the FDA’s two-day public meeting and Jeffrey Shuren’s presentation of DTC genetic tests within the confines of the larger LDT regulatory conversation (pdf) at the recent Congressional hearing – suggest that the FDA may yet find a way to incorporate the regulation of DTC genetic tests into its more ambitious plan to develop a risk-based approach for all LDTs. But for the moment, the FDA appears to be intent on continuing with test-by-test review and regulation.

Unintended Effects. Among its several shortcomings, the current test-by-test approach to DTC genetic testing regulation creates the possibility that a regulatory agency such as the FDA could seek to reshape the industry using indirect methods.

When the FDA sent out its first batch of letters post-Pathway, the one unexpected recipient was array manufacturer Illumina, which, unlike the other companies receiving letters, does not appear to have ever offered its services directly to consumers without the involvement of a physician intermediary. Nor did the FDA allege that it had. Instead, the FDA’s letter to Illumina (pdf) focused on the company’s “Infinium HumanHap550 array used by deCODE Genetics and 23andMe to provide genetic information to their customers.” The FDA charged Illumina with making available an array approved for “Research Use Only” to 23andMe and deCode for use in their own DTC genetic tests.

Why does this matter? As I wrote at the time, not every company has the same set of incentives to resist the FDA’s regulatory proposals. Whereas a company such as 23andMe, which has built its business around DTC genetic testing, has a clear interest in challenging any FDA action that results in its service becoming unavailable to consumers, array manufacturers like Illumina are not similarly situated. As Illumina’s CEO, Jay Flatley, recently noted, the revenue the company “generates from sales of arrays to the DTC market is ‘immaterial.’” By targeting array suppliers such as Illumina, for whom DTC represents only a fraction of their business, the FDA may have identified a way to exert indirect but potentially much more effective regulatory pressure over the industry.

In response, Daniel MacArthur asked yesterday whether the FDA was planning to strangle the supply lines of DTC genetic testing companies by targeting array manufacturers like Illumina. As a regulatory agency charged with implementing legislation passed by Congress, the FDA is extremely unlikely to have an official “agenda” when it comes to DTC genetic testing. That does not mean, however, that the FDA could not determine that genetic testing simply cannot be paired with DTC and still satisfy its interpretation of the law.

If 23andMe or deCode (which is partially owned by Illumina) were to lose access to Illumina’s arrays, would those companies be able to contract with another manufacturer, either based in the U.S. or abroad? Would Illumina take the necessary steps to work with 23andMe and the FDA to clear its array for use in 23andMe’s product? Would this development force such a fundamental shift in the business models of these DTC companies that they would be driven out of business, or perhaps driven overseas?

Even as a hypothetical, the Illumina example illustrates the importance of considering the knock-on effects of regulation. Although the FDA may take the position that its goal is to enforce agency regulations regardless of the effects they produce on a specific business, or even an entire industry, the reality is that there are a number of viable regulatory strategies on the table, and not all of them are equal in their effects.

One of the unfortunate consequences of the test-by-test regulation currently employed by the FDA is that these effects are unlikely to be fully anticipated or explored in advance by regulators. By the same token, one obvious advantage of publicly pursuing a formal system of regulation for DTC genetic testing – e.g., through the development of agency guidance or notice and comment rulemaking – is that such regulatory effects can be explored in advance (in some instances this may even be required of the FDA), rendering them at least intended, even if they remain unwelcome to some.

Other Regulatory Routes. Finally, remember that the FDA may not be left entirely to its own devices in determining how to regulate either LDTs or DTC genetic tests. Several pieces of draft legislation, if enacted, could provide specific Congressional direction as to how the FDA or other regulatory agencies should respond to the challenges raised by these tests.

Current proposals include the Genomics and Personalized Medicine Act – originally introduced by then-Senator Obama and now in its fifth year on Capitol Hill – and the inelegantly named Better Evaluation and Treatment Through Essential Regulatory Reform for Patient Care Act.

The prudent approach – particularly for companies, investors and consumers with an interest in DTC genetic testing regulation – is to assume that some type of regulatory reform is coming to the industry. Unfortunately, important details like “what regulation” and “when will it arrive” continue to remain elusive.

Beyond: A Delicate Balancing Act. Assuming that lawmakers and regulators do decide to develop a formal DTC regulatory regime, the details will be a long time in coming. Stakeholder input will be crucial, and the rapidly changing scientific and commercial landscape will continue to pose a challenge for slower-moving lawmakers and regulators.

Despite all of this uncertainty, it is yet possible to identify (i) several key areas of relative consensus for any prospective DTC regulatory framework and (ii) some of the most pressing areas of dispute that must be resolved in order to proceed.

The First Step: Defining DTC. Before we get to areas of consensus and dispute, however, a brief word about definitions. Any formal regulatory framework will need to set out a clear definition of what, exactly, constitutes a “direct-to-consumer genetic test.” As the personal genomics industry has grown increasingly diverse, the application of the label “DTC” to all consumer-oriented genetic products has become increasingly untenable.

There are, at the moment, at least three different types of DTC genetic tests:

• tests marketed to consumers but ordered and interpreted by a healthcare provider;
• tests marketed to and ordered by consumers but received and interpreted by or only in the presence of a healthcare provider; and
• tests marketed to, ordered by and received by consumers without any requirement that a healthcare provider be involved (although this option is frequently made available to consumers).

While the focus has frequently been on the third and most consumer-oriented type of genetic test, not all so-called DTC genetic testing companies fall into this category. This is significant since the risks – whether hypothetical or actual – of “DTC genetic testing,” as well as the appropriate regulatory response, clearly depend in large part on what exactly is meant by that term.

Finding Common Ground. Although few in number, it appears that consensus is emerging in certain areas pertaining to DTC genetic testing.

Access to Raw Data. Even those who strongly support the robust regulation of DTC genetic testing, agree that individuals should have the right to directly access their raw genetic data (pdf). In public and private comments, the FDA has appeared to embrace this position as well, indicating it is medical claims or interpretations – and not genetic information per se – that concerns the agency.

We need to be careful, however, to define exactly what this outbreak of agreement covers. Although important for what it says about an individual’s right to access their own genome, it likely refers only to the most basic level of access – a large file of As, Cs, Ts and Gs – and to nothing more. This is only a first step. Meaningful “access” for the vast majority of individuals begins only with the ability to access interpreted data.

Registration and Truth in Advertising. As the recent GAO report laid plain, there is a clear need for more robust regulation of the advertising and marketing practices of existing genetic testing companies, including DTC companies, to ensure consumers are not being intentionally or even accidentally misled.

Addressing this issue requires a thorough understanding of the tests currently offered to consumers, including how they are marketed or advertised, how they are intended to be used, and how they are actually used. The FDA has acknowledged several times in public discussions, including yesterday, that the agency lacks this information and that it would be useful in developing appropriate regulations.

While there remains some disagreement over the proper agency or agencies to collect this information and to take appropriate enforcement actions where necessary (the FDA and the FTC have both demonstrated some interest, and the NIH is currently developing a genetic testing registry), there is widespread agreement that these steps should be taken, and soon.

Industry-Wide Standards. Finally, almost since the inception of DTC genetic testing in 2007, there has been a widespread recognition that the industry would benefit from a more standardized approach to interpreting and reporting genetic data.

Early efforts led by the Personalized Medicine Coalition to produce industry-developed standards have stalled, but the inconsistency demonstrated by Collins, Venter et al. and most recently the GAO report have resulted in renewed interest from industry and regulators in addressing this issue.

Here, again, it is important to acknowledge the limited scope of this consensus. There is real agreement that standards are needed. The development and application of those standards, however, raises a host of questions, some of which are discussed below, to which there are hardly consensus answers.

Resolving Disputes. Beyond the few but important areas of consensus described above, it is certain that any emerging regulatory framework will have to tackle numerous difficult questions about which there is a decided lack of agreement. While it is impossible to list all of the areas of disagreement, some of the most pressing issues are:

• whether genetic tests should ever be offered directly to consumers without the involvement of a trained intermediary such as a physician or genetic counselor (i.e., should the third type of DTC genetic testing described above disappear);
• whether to create separate standards for non-clinical genetic tests, including genetic ancestry testing, and how to appropriately define the line between clinical and non-clinical tests;
• how to regulate genetic tests or products that include a large number of interpretations and claims in light of the need to constantly update those claims to best reflect current scientific understanding;
• whether clinical utility, or lack thereof, should be included in determining whether a particular genetic test or association is made available, whether DTC or otherwise;
• how to regulate interpretative tools that do not involve any new testing, but simply offer additional interpretations of raw genetic data already in a consumer’s possession;
• how to address the role of preliminary scientific findings and research in the development of interpretive tools, including genetic tests; and
• whether to focus regulatory efforts on pre-test measures that restrict the availability of potentially harmful genetic tests or post-test initiatives designed to evaluate how consumers perceive, use and react to genetic tests.

The answers to these questions and others, as well as the role industry, consumers and healthcare providers are permitted to play in the conversation, will determine the substance of any forthcoming DTC regulatory framework.

Answering Mary’s Question: To Test or Not To Test? While tomorrow always carries the possibility of a new and clearer day for the regulation of DTC genetic testing, the reality is that, for the moment, all we can say for sure is that the conversation is continuing. What was true in 2006 is still true today: genetic tests are available for purchase directly by consumers, and the regulatory requirements imposed on the companies that offer those tests are unclear and seemingly poised to shift at a moment’s notice.

As I have written several times before, I am optimistic about the long-term prospects for personal genomics in the United States, including DTC genetic testing. As the underlying technology and science continue to improve, the price and value of individual-level genomic data will continue to move in opposite directions, generating increased demand. In time, as increasing demand leads to increasing accessibility and, ultimately, to increasing familiarity – on the part of both consumers and regulators – the development of a tailored system of oversight that permits direct access while adequately protecting consumer safety and ensuring the accuracy and validity of DTC products can be developed.

But none of this will happen overnight. For all of our own interest, DTC genetic testing remains decidedly a niche phenomenon, and the industry poses novel and difficult challenges to regulators. It will take time for these to be ironed out and, in the short-term, it is possible that DTC genetic testing will be presented with a substantially more restrictive regulatory framework than at present.

Ultimately, while I cannot advise Mary Carmichael as to whether she should or should not go through with a DTC genetic test – that’s a personal decision – I can say that if she decides to proceed there is no time like today, for there is no guarantee that the option will still be on the table tomorrow.

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¹The regulation of DTC genetic testing is far from uniform at the international level. Some countries, including Germany, appear to have effectively legislated DTC genetic testing out of existence, at least for the time being. Elsewhere, most notably the U.K., the conversation remains at the level of voluntary guidelines instead of formal – or even informal – regulation. Recent examples include the 2009 House of Lords report on genomic medicine and yesterday’s publication by the Human Genetics Commission of “A Common Framework of Principles for direct-to-consumer genetic testing services” (pdf).

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.

These developments reflect an uncertainty about the regulatory status of DTC genetic testing that is dramatic, although it is not new. In the summer of 2008, public health officials in New York and California sent warning letters to a number of DTC companies, including 23andMe and Navigenics (both targets of the current Congressional investigation). These state regulatory activities prompted concern that other states might follow suit, potentially subjecting DTC companies to the nightmare scenario of inconsistent state-by-state regulation. Nearly two years later, those particular concerns appear to be unfounded.

An Inevitable Regulatory Response. But as the DTC genetic testing industry expanded, state and federal regulators grew increasingly conspicuous by their silence. The possibility of regulatory activity has been the elephant in the DTC room for some time now (at the Genomics Law Report we have been writing about the possibility of DTC regulation since our inception) and, indeed, many DTC companies have long indicated that they would welcome more definitive federal regulation.

The specific trigger for this recent flurry of activity by the FDA and Congress is something of a puzzle—the distinction between DTC genetic tests offered on Walgreens’ shelves as opposed to online at Amazon.com is difficult to parse, and the FDA’s initial comments, delivered through the media by a variety of spokesmen, have frequently confused rather than clarified. But the simple fact is that a regulatory response to DTC genetic testing was overdue. That it happened to be Pathway’s attempt at creative product placement will prove to be, ultimately, nothing more than a footnote to a larger ongoing discussion about the proper place of DTC genetic testing in this country.

For the remainder of this post, rather than speculate about what manner of regulatory response will be forthcoming from the FDA, Congress and elsewhere, we ask (and answer) the 550,000 SNP question instead: if a regulatory response to DTC genetic testing is inevitable, what should it look like?

A Transparent Solution. More than anything else, what the DTC genetic testing industry needs right now is enhanced transparency, and not necessarily in the form of traditional direct regulation by the FDA. Rather than driving the regulation of DTC genetic tests through traditional channels, such as the FDA’s premarket review and approval regime for medical devices, regulators should focus instead on shining a bright light on DTC genetic testing, improving their own and the public’s understanding of what information is available to consumers and how that information is actually used.

As it happens, creating greater DTC transparency can be most efficiently accomplished without the application of regulations that would be onerous for early-stage DTC companies and their investors, restrictive for consumers interested in the broadest access to their genetic information and expensive and time-consuming for regulators to enforce.

Over the next 6-9 months, the DTC genetic testing industry and regulators, working together, should take three key steps to enhance transparency industry-wide, ensure that customers, regulators and healthcare professionals are better able to understand and evaluate the products offered, and encourage the DTC industry to grow responsibly without more traditional regulation.

Step 1: Make Participation in the NIH’s Genetic Testing Registry Mandatory. The most promising development for improving transparency with respect to specific DTC genetic testing companies and products is the recently announced and NIH-backed Genetic Testing Registry (GTR). The GTR is a direct outgrowth of a 2008 report prepared by the Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) on the “U.S. System of Oversight of Genetic Testing” (pdf). The SACGHS report recommended the following:

To enhance the transparency of genetic testing and assist efforts in reviewing the clinical validity of laboratory tests, HHS should appoint and fund a lead agency to develop and maintain a mandatory, publicly available, Web-base registry for laboratory tests. (emphasis added)

Although announced two months ago as voluntary initiative, many of the GTR’s supporters have long argued that such a registry should be mandatory, and its voluntary character is unquestionably the GTR’s most significant departure from the original SACGHS recommendation. At its current early stage of development, however, there is plenty of time for that feature to change.

The upside of the GTR is clear. It would provide a single, comprehensive source of information about DTC genetic tests for regulators, purchasers and other end users (including healthcare professionals), enabling side-by-side comparison of tests and allowing regulators or neutral third parties to evaluate the accuracy of their data and claims. It would also likely standardize (or at least clarify) test offerings, spur healthy competition between providers and enable consumers to make purchasing decisions on the basis of meaningful criteria (e.g., price, information content, insurance coverage, etc.) instead of marketing campaigns.

All of these benefits, however, depend on widespread participation in the GTR by DTC genetic testing companies. At the time of the GTR’s announcement, current NIH chief of staff (and long-time GTR proponent) Kathy Hudson conceded that, while she would have preferred a mandatory registry, it was unclear whether the NIH had the authority to enforce such a requirement. While that is likely the case, (arguably) the FDA and (certainly) Congress have the authority to render participation in the GTR mandatory for DTC genetic testing companies.¹ DTC companies should be eager to embrace a mandatory GTR (as at least one already has) as a relatively painless way to demonstrate to the public and to regulators their willingness to cooperate and their commitment to providing high-quality and transparent genetic testing services.

Step 2: Continue to Improve FDA Regulatory Transparency. An editorial appearing in last week’s New England Journal of Medicine by two senior FDA officials describes the agency’s recent and substantial efforts to improve transparency. The FDA’s Transparency Task Force is currently entering its third and final phase, seeking ways to improve transparency to regulated industries.

As part of this initiative, the FDA is seeking comment on 21 proposals (pdf) designed to enhance transparency at the agency. The FDA’s recommendations, particularly recommendations 10 and 11, could significantly improve public understanding of how and when the FDA evaluates regulated medical devices. The recommendations are an important step in improving transparency at an agency that has not had enough of it in recent years. Unfortunately, none of the proposed recommendations would improve the transparency of the process by which the FDA determines which products to regulate in the first place, including DTC genetic tests.

Here is where the FDA, specifically the agency’s Office of In-Vitro Diagnostic Device Evaluation and Safety (OIVD), headed by Director Alberto Gutierrez, can help appropriately regulate DTC genetic tests without actually increasing its already substantial regulatory burden. Not only should the FDA encourage transparency across the DTC genetic testing industry by supporting the NIH in its development of the GTR, and strongly encouraging or even requiring DTC genetic testing companies to participate, it should also work closely with the NIH, industry and other key stakeholders to clarify exactly what information it would like to see included in the GTR.

One of the difficulties for the DTC genetic testing industry, at least at present, is that the FDA has been less than clear in describing the elements of DTC genetic tests that most concern the agency. Is it the list of conditions or genetic variants tested? The nature of the claims (informational vs. medical) made by the company or the product? The physical locations at which a test is sold? Or is it some other consideration entirely or, more likely, a combination of all of the above?

The FDA is clearly still refining its policy with respect to DTC genetic tests, and there is plenty of time for it to continue to do so. In the meantime, it should involve DTC companies and customers, medical professionals, policymakers and other key stakeholders in determining the relevant information to collect and review with respect to DTC genetic testing. In doing so it can use the already-in-development GTR as a public tool for transparently refining its policy and collecting relevant information. This approach would go a long way toward eliminating the case-by-case review of DTC genetic testing companies and products that appears to have categorized the FDA’s approach to date.

Step 3: Involve the Federal Trade Commission. As we wrote last week, there is another regulatory agency that could play an important role in the development of DTC genetic testing: the Federal Trade Commission (FTC).

In 2006, the FTC worked with the FDA and the CDC to publish a guidance document for consumers entitled At-Home Genetic Tests: A Healthy Dose of Skepticism May Be the Best Prescription. Four years in the area of DTC genetic testing is an eternity – the FTC’s guidance was issued before any of 23andMe, Navigenics and Pathway Genomics, the three companies currently the focus of the Congressional investigation, existed – but it indicates that the agency has at least some familiarity with the industry. More importantly, the guidance reminds consumers of the FTC’s mission, which has not changed: “to work[] for the consumer to prevent fraudulent, deceptive, and unfair business practices in the marketplace and to provide information to help consumers spot, stop, and avoid them.”

By making the GTR mandatory (Step 1) and working with the FDA to carefully specify the relevant information to be included in the registry (Step 2), the FTC would be well positioned to monitor the DTC genetic testing industry for companies unwilling to subject their products or claims to the public scrutiny afforded by the GTR (Step 3). While the FDA and Congress have launched investigations into well known DTC genetic testing companies, there are a plethora of other companies (see, for example, this list at DNA Test Index or this list at AccessDNA) that appear, for the moment, to have escaped the attention of regulators. Rather than require the FDA or Congress to investigate each new DTC genetic testing company that sprouts up, why not require those companies to register with the GTR?

This would provide the FTC, along with the rest of us, with a single point of entry to collect and evaluate registered DTC genetic testing companies, while those companies that refuse to participate in the GTR will likely be quickly ferreted out and referred to the FTC by an active community of DTC genetic testing companies and consumers with a vested interest in maintaining order industry-wide.

Reports of DTC’s Death Greatly Exaggerated? Using a community- and transparency-driven approach would make it easy to separate the DTC wheat from the chaff, enabling legitimate DTC companies to continue to provide consumers with the genetic information they desire, while minimizing the risk that consumers will be presented with false or misleading genetic testing products or services.

More importantly, focusing on transparency and sustained information gathering is an appropriate, measured response to the developing DTC genetic testing industry. One that will bring companies, consumers and regulators into closer collaboration, without imposing a regulatory regime that would risk stifling the creativity and growth of the industry or depriving consumers of the ability to directly access their genetic information. While it has long been inevitable that regulatory agencies would play a significant role in shaping the future of the genetic testing industry, there is absolutely no reason why, with that day apparently upon us, that development need spell the death of DTC.
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¹ As discussed in our earlier article, there is some disagreement over whether the FDA has such authority. What is not debatable, however, is that Congress, should it desire to do so, could take action that would remove all doubt as to the authority of the FDA (or another agency of its choosing, such as CMS) to regulate DTC genetic tests.

Note, also, that a GTR that was mandatory for DTC genetic testing companies would not need to be mandatory for all providers of genetic tests. A majority of genetic tests are not provided directly to consumers, and this would be a relatively clear distinguishing characteristic upon which to evaluate whether a test was required to be included in the GTR, or simply permitted to be included at the provider’s discretion.

Introducing the FDA to Pathway, but not to genetic testing. Continuing national media coverage has focused on comments from the FDA that the agency was unaware of Pathway’s genetic test and that it has opened an investigation into its legality. Yesterday, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) Director Alberto Gutierrez told The Washington Post that he thought Pathway’s genetic test “would be an illegally marketed device” if the company proceeded with the announced Walgreens partnership. Gutierrez was also widely quoted as saying that the FDA was not aware of the test previously and that the agency was “in the process of investigating the test.”

To clarify, while this may well be the first that the FDA – or at least OIVD – has heard of Pathway Genomics and its specific DTC genetic tests, the agency is clearly familiar with DTC genetic testing and its associated policy issues and regulatory uncertainty. DTC genetic testing has been on the FDA’s radar screen for years, including as part of the ongoing discussion concerning the regulation of laboratory developed tests (LDTs). The FDA also participated in the development of the 2008 SACGHS report on the oversight of genetic testing (pdf), and FDA officials have appeared at consumer genetics conferences (pdf) to discuss the agency’s possible regulatory strategy.

It’s clear that DTC genetic tests as a category are not new to the FDA, and there is also nothing to suggest that the specific tests Pathway offers are substantively new. Although not identical to tests offered by other DTC companies, they appear to offer the same categories of information (carrier status, disease risk, drug response, etc.) and report on substantially overlapping lists of specific traits. They are also performed in a CLIA laboratory, as is true of other DTC genetic tests.

The only element of Pathway’s DTC genetic tests that appears to be new is the visibility that Pathway has achieved by partnering with Walgreens (visibility which will only increase if, as The Los Angeles Times reports, Pathway’s tests will also be available in CVS stores beginning in August). For Pathway, the primary goal of this increased visibility is likely an expanded customer base. But by turning a Walgreens-sized spotlight on itself, Pathway has also caught the eye of regulators. The FDA has responded by publicly commenting on the investigation and possible regulation of a specific DTC genetic testing company, and that is new.

All of this leaves us with a question: if the FDA investigates and ultimately decides to regulate Pathway Genomics, will the rest of the DTC genetic testing industry soon receive similar scrutiny?

Another Regulatory Route? Earlier this morning, an FDA spokeswoman told Reuters that “if a company is making claims about a product that hasn’t been reviewed or validated by FDA, we want to make sure the information to consumers is accurate and the test will do what it says it will do.”

When it comes to medical drugs and devices, the FDA plays an important role in ensuring that consumers receive accurate information. However, as we discussed yesterday, DTC genetic testing companies, including Pathway, do not necessarily agree that they are selling medical devices subject to FDA regulation. According to Reuters:

‘FDA clearance is not necessary to sell the Pathway Genomics Insight Saliva Collection Kit in retail,’ [Pathway Genomics] said.

It said the tests are not intended for use in diagnosis, treatment or for the mitigation or cure of a disease – qualities that would make it an in vitro medical device, which the FDA does regulate.

‘It does provide information that allows a person to learn about their health to make healthier lifestyle choices,’ the company said.

Without rehashing the is-this-a-medical-device-or-not debate, it should be pointed out that there is another regulatory agency that focuses specifically on consumer goods and services, including those that have nothing to do with health or medicine, that has previously taken an interest in DTC genetic testing: the Federal Trade Commission (FTC).

In 2006, well before Pathway Genomics, 23andMe and other companies offering genome-wide DTC genetic testing arrived on the marketplace, the FTC published guidance entitled At-Home Genetic Tests: A Healthy Dose of Skepticism May Be the Best Prescription. Prepared in conjunction with the FDA and the CDC, the FTC’s guidance reviews the state of DTC genetics, including a number of its limitations (circa 2006), and advises consumers to talk to their doctor before ordering, taking or making decisions based on a DTC genetic test. It also reminds consumers of the FTC’s mission: “to work[] for the consumer to prevent fraudulent, deceptive, and unfair business practices in the marketplace and to provide information to help consumers spot, stop, and avoid them.”

Let me be crystal clear: the FTC guidance was published in 2006, and does not criticize, or even discuss, any specific DTC genetic test. Indeed, most if not all of today’s most popular DTC tests were not on the market in 2006. Furthermore, this should not be read as an indication that any of the current tests, including those offered by Pathway Genomics, are themselves false or misleading.

As the Pathway/Walgreens announcement has made the rounds, many of the concerns voiced by commentators and regulators - as was the case in previous debates over the merits of DTC genetic testing - have centered on a fear that consumers may be confused or misled by the tests, or unable to interpret their results. The National Society of Genetic Counselors, for example, issued a statement yesterday (pdf) warning that “receiving genetic information directly from a manufacturer or supplier and without input from a qualified health care provider increases the chance for misunderstanding or misinterpretation of results.” If the fundamental concern here relates not to the information content of the tests themselves, but how the tests are marketed to and understood by consumers, perhaps the FTC stands as an alternative, and likely less burdensome, regulatory avenue.

1. Is DTC Getting HIPAA? The Health Insurance Portability and Accountability Act of 1996 (HIPAA), the most prominent federal regulation governing the privacy of medical records, established the Privacy Rule to provide national standards for protected medical records. HIPAA’s Privacy Rule currently applies only to “covered entities” and business associates of covered entities. A covered entity is a health plan, health care clearinghouse, or a health care provider. Since a company providing genomic sequencing services is not a health plan or a health care clearinghouse, HIPAA will apply only if such a company is determined to be a health care provider or a business associate of a covered entity.

Direct-to-consumer (DTC) genomics companies are not likely to be considered business associates of HIPAA covered entities. HIPAA defines a business associate as a person or organization that, on behalf of a covered entity, performs an activity involving the use or disclosure of individually identifiable health information, or otherwise performs services for a covered entity where the covered entity provides such health information to the business associate. The American Recovery and Reinvestment Act (ARRA) expanded the definition of business associate for purposes of the Privacy Rule and the Security Rule to include

• entities providing data transmission of protected health information to covered entities (or such entity’s business associate) and requiring access on a routine basis to such information, and
• vendors contracting with a covered entity to allow the covered entity to offer personal health records to its patients.

DTC genomics companies typically do not act on behalf of a covered entity, nor do they provide services to covered entities. Rather, as the DTC name suggests, companies such as 23andMe provide services directly to the consumer. However, this is not always the case. For example, California-based Navigenics, commonly referred to as a DTC genomics company, has announced a number of partnerships with healthcare clinics through which it offers its genotyping services to the clinic for use in developing personalized diagnostic, management and treatment strategies for patients. Just last week, Navigenics announced a partnership with Beth Israel Deaconness Medical Center in Boston to familiarize practicing physicians with its DTC offerings, among other goals. Looking at Navigenics’ list of collaborators reveals a number of relationships where Navigenics appears to be performing services (genotyping and risk prediction) and providing identifiable health information (the genotyping results) to health care providers. Whether or not a particular DTC genomics company qualifies as a business associate depends on the particulars of the services it offers, particularly those that it makes available directly to health care providers; particulars which are subject to change at a moment’s notice in this rapidly evolving field.

Moreover, it is conceivable that a DTC genomics company could be considered a health care provider itself. Although we are not aware of any regulative body that has found a DTC genomics company to be covered by HIPAA (as a health care provider or otherwise), the term “health care” is defined broadly under HIPAA regulations:

Health care means care, services, or supplies related to the health of an individual. Health care includes, but is not limited to, the following:

(1) Preventive, diagnostic, therapeutic, rehabilitative, maintenance, or palliative care, and counseling, service, assessment, or procedure with respect to the physical or mental condition, or functional status, of an individual or that affects the structure or function of the body….

If a DTC genomics company provides diagnostic or analytical information to a customer in connection with the customer’s genomic sequence, it may be considered to be offering “diagnostic care” or “counseling with respect to the physical or mental condition of an individual”—and thus, to be a health care provider subject to the HIPAA regulations. Existing DTC providers do offer substantial information that could fall into those categories, including relative risk and lifetime risk calculations for serious diseases (23andMe’s testing service, for instance, includes “carrier reports” for 32 conditions including several cancers, Parkinson’s Disease and diabetes) and the determination of carrier status for alleles with reproductive implications. In addition, other companies such as Navigenics, provide access to board-certified genetic counselors to assist customers in interpreting their results.

The provision of clinical diagnostic information and genetic counseling, even when delivered over a website rather than in a doctor’s office, may constitute the provision of health care. In recent weeks the Genomics Law Report has focused on the recurring calls for standards that would have the effect of blurring the distinction between direct-to-consumer genetic testing and the clinical practice of medicine (also see here, here, here and here). One potential effect of confusing the clinical/non-clinical divide in the DTC setting would likely be to bring DTC service providers unambiguously under the purview of HIPAA as a health care provider. As described below, however, despite the increasingly clinical nature of the services offered by DTC providers, there does not appear to be much enthusiasm for subjecting genomics companies to HIPAA or to other clinical regulations.

2. Why Does HIPAA Matter? Even if a DTC genomics company is deemed to provide a level of service sufficient to make it a covered entity under HIPAA, it may still disclose confidential protected health information (such as a customer’s genetic or genomic results) for the purpose of carrying out “health care operations.” Health care operations are broadly defined in HIPAA Section 164.501 to include business management and general administrative activities. Specifically disclosure is permitted relating to the “sale, transfer, merger or consolidation of all or a part of the covered entity with another covered entity, or an entity that following such activity will become a covered entity and due diligence related to such activity.” Among the amendments to HIPAA contained in the ARRA is a specific prohibition on the sale of protected health information, except for the sale of information in connection with the sale, transfer or consolidation of the covered entity. Therefore, even when HIPAA applies, patient or customer authorization is not required for disclosure of protected health information in the sale of the company’s assets.

HIPAA does not specifically address the bankruptcy of a covered entity; however, it seems that the sale or transfer exception would likely apply. A liquidation in bankruptcy requires the sale of the debtor’s assets. As long as the protected information is transferred to another covered entity in connection with a sale of the assets, presumably individual authorization from the DTC genomics company’s customers would not be required.

For the moment, it does not appear that HIPAA regulations are restricting much if any of the activity currently taking place in the DTC genomics space. However, as a host of factors, including both internal and external pressures, continue to drive many DTC genomics companies closer and closer to activities indistinguishable from the clinical practice of medicine, at least some DTC companies may soon find themselves subject to HIPAA’s regulations. The implications of HIPAA coverage for DTC genomics companies is the subject for another post, but in the limited case of a bankruptcy scenario, even HIPAA coverage would not appear to prohibit a DTC genomics company from transferring its customers’ genomic information.

3. DTC Escapes Stimulus Bill Unscathed? Part of the Stimulus Bill enacted this past spring directed the Department of Health and Human Services (HHS), in conjunction with the Federal Trade Commission (FTC), to conduct a study on privacy, security, and breach-notification requirements for vendors of personal health records (PHRs) and related entities that are not subject to HIPAA. In the meantime, the Act required the FTC to issue a rule requiring these entities to notify consumers if the security of their health information is breached.

The FTC issued a proposed notification rule (pdf) in April 2009, applying to PHR vendors, PHR-related entities, and third party service providers. All three categories, however, are restricted to firms that handle personal health information.

Upon publication of the proposed rule, the FTC solicited comments from the public. One of the comments was from a nonprofit health privacy watchdog group, Patient Privacy Rights, on behalf of the Coalition for Patient Privacy (a group that includes the American Civil Liberties Union and the American Association for People with Disabilities). The Patient Privacy Rights comment (pdf) objected to the limitation of the proposed rule to “the organization and sharing of personal health records,” because the definition of personal health records did not explicitly include genetic or genomic information. As the group explained:

Personal genomics companies such as 23andMe, Navigenics, Knome, and deCODE offer individual genetic testing that can provide customers with novel health services—from determining the likelihood of contracting diabetes, to identifying ancestral roots. Such companies rely on (HIPAA-compliant) labs to analyze patient DNA, which they receive directly, analyze, and store online for access by the patient.

A patient whose genetic information is leaked, stolen, or disclosed could clearly suffer harm as great as that associated with any other PHR health data, as recognized by the various state and federal laws around genetic privacy. The Commission should accordingly determine that personal genomics companies constitute [Personal Health Record] related entities insofar as they ‘access[] information in a personal health record’ or ‘offer[] or maintain[] a personal health record.’

However, when the final notification rule (pdf) was published in August of this year, the FTC had declined to modify the rule as requested by Patient Privacy Rights. The Commission’s final rule contains no mention of genetic data or genomics companies.

While we will have to wait for the completion of the joint HHS/FTC study in February 2010 to see whether it explicitly covers genomics companies in any of its privacy or security regulations, the FTC’s security breach rule suggests that it is unlikely that any such regulations will be immediately forthcoming.

Accordingly, the genomic information supplied by DTC companies is likely to be covered by the FTC’s regulations only to the extent such information constitutes personal health information (thus making a genomics company a firm that handles PHI and subject to the regulations.) This is where GINA comes in.

4. GINA and the Privacy Rule: Did Anything Really Change? The Genetic Information Nondiscrimination Act of 2008 (GINA) requires that the HHS Secretary revise the HIPAA Privacy Rule to make clear that “[g]enetic information shall be treated as health information.” Although GINA required that HHS issue implementing regulations not later than May 2009, it wasn’t until this month that HHS’ Office of Civil Rights issued its proposed rules (pdf). The background discussion of the proposed rule points out, however, that although the term “health information” would be amended “to explicitly provide that such term includes genetic information,” that does not mean that all disclosures of genetic information would necessarily be protected under HIPAA’s Privacy Rule:

We note, however, that as before, genetic information, while health information, is only covered by the Privacy Rule to the extent that it meets the definition of “protected health information.” That is, the genetic information must be individually identifiable and maintained by a HIPAA covered entity (or business associate of a covered entity) (and not otherwise fall within one of the exceptions to the definition).

Thus, although GINA amended the Privacy Rule to cover genetic information, the type of entities covered by the Privacy Rule did not change: it still only applies to HIPAA’s “covered entities.” And so we have come full circle: the key question remains whether DTC Genomics companies are considered to be covered entities, either as health care providers or as business associates of health care providers. While that question remains unsettled, the tone of the note suggests that HHS is not actively seeking ways to apply its regulations to genomics companies.

5. What Does It All Mean? As discussed above, the trend toward clinical activity on the part of many DTC genomics companies could ultimately bring them within the ambit of HIPAA and its Privacy Rule. However, at present it does not appear that there is any federal regulation—including HIPAA—that clearly restricts the transfer of customers’ information as part of a sale of assets by a troubled DTC genomics company.

As we concluded last time, the true test for the handling of individuals’ genetic and genomic information collected by DTC companies will be the first actual bankruptcy. Until then it will remain extremely difficult to predict how regulators and bankruptcy courts will address such a scenario, and the most practical advice at this time, for existing and potential customers, continues to be to understand the terms and conditions offered by each individual DTC genomics company with respect to their customers’ information—and to recognize that, in bankruptcy, genomic data may be transferred to a similar company without regard to those terms and conditions..

As for the DTC companies themselves, the possibility that they may be subjected to regulation under HIPAA and the Privacy Rule—as well as, potentially, a host of other regulations and sources of liability associated with the provision of health care—has implications far beyond the bankruptcy scenario. In the coming weeks the Genomics Law Report will begin to investigate what it might mean for DTC genomics companies if the blurry line between clinical and non-clinical activity in the DTC space finally resolves itself, with the DTC companies on the clinical side of that line.