This will, I believe, mark direct-to-consumer (DTC) genetic testing’s formal debut at ASCO. It should also serve as another reminder that, despite its relatively small numbers (both in terms of dollars and customers), DTC genetic testing continues to exert an outsized influence when it comes to conversations about the future of genomic medicine. This is particularly true when the discussion turns to appropriate policy and regulatory oversight.

In advance of ASCO, here are several items of interest from the past few weeks in DTC genetic testing.

“Trial by Press Release.” That’s exactly what Daniel MacArthur of Genetic Future termed this week’s press release from the European Society of Human Genetics (ESHG) highlighting two presentations on DTC genetic testing at the recent ESHG annual meeting.

The studies themselves have yet to be published, but preliminary findings were meant to provide new evidence that (a) the risk prediction models employed by personal genomics companies are neither perfect nor consistent and (b) clinical geneticists are skeptical of the value of DTC genetic tests.

Neither finding is surprising, although, as MacArthur points out, the first study – from Rachel Kalf of Erasmus University – will need to be published in full before its claims, including the claim that one DTC company (deCODEme) utilizes fundamentally flawed risk prediction models, can be fully vetted.

The desire to encourage greater transparency and consistency among the risk prediction models employed by DTC genetic testing companies has been expressed numerous times in the past (higher-profile examples include current NIH Director Francis Collins, genomic pioneer Craig Venter and colleagues and last summer’s GAO report) and repeatedly embraced by DTC companies themselves (see, e.g., here and here).

When it comes to debating the future of the DTC genetic testing industry there are plenty of areas of legitimate disagreement. For example, should different types of DTC tests (e.g., carrier screening vs. pharmacogenomic testing vs. genetic ancestry testing) which make different types of claims be regulated differently? And how, if at all, should the concept of utility, whether clinical or personal, be incorporated into a genetic test evaluation?

But the need to improve transparency and consistency in DTC risk prediction models already appears to be shared nearly universally among DTC stakeholders.

The second study included in the ESHG release, conducted by Heidi Howard of the University of Leuven, Belgium, includes the finding that 63% of a “representative sample of clinical geneticists” from across Europe “wanted to proscribe whole genome scans carried out by DTC companies.”

That statistic has bounced around the internet echo chamber the past few days, but, again, is it offering us anything we did not already know (or at least strongly suspect)? As MacArthur points out, asking the current cohort of genetic testing gatekeepers how they feel about being sidestepped by genetic testing companies seeking to engage directly with individuals feels slightly rhetorical:

While it is important that personal genomics companies consult with medical professionals in devising their risk prediction algorithms and interfaces, regulation of genetic testing should not be based on the views of the traditional gatekeepers of genetic information.

As both MacArthur and Razib Khan of Gene Expression note, the appropriate question to ask is not whether clinicians believe genetic tests are harmful in the hands of consumers, but whether genetic tests are actually harmful in the hands of consumers.

Thankfully, a growing list of researchers is asking that very question, including Bloss et al. (see also a recent back-and-forth in the NEJM), Kauffman et al. and the recently launched Impact of Personal Genomic Services (IPeG) study (some details here), about which my co-presenter Stacy Gray will be providing more details during today’s panel.

As the Food and Drug Administration (FDA) and others continue to wrestle with the difficult job of shaping DTC regulatory policy, the data generated by these and other studies will be critical in ensuring that any policy which eventually emerges responds to the demonstrated challenges of DTC genetic testing, and not merely to hypothesized harms.

The FDA Sends Three More DTC Letters. Speaking of the FDA, nearly a year to the day after it sent its first letter of concern to a DTC genetic testing company (Pathway Genomics), the agency sent out its latest batch of DTC letters. The recipients this time: Lumigenix, American International Biotechnology Services and Precision Quality DNA.

Much has transpired since that first FDA letter – including many more DTC letters, a Congressional hearing last summer and a closely watched advisory panel meeting earlier this spring – but for now, at least in public, the FDA is continuing to employ the same case-by-case approach to DTC genetic testing oversight it has utilized from the outset.

Not everyone is happy with the FDA’s current approach. One of the most recent companies to receive a letter, Precision Quality DNA, has devoted a section of its company website to the FDA’s handling of DTC regulation, and has published its strongly worded reply to the agency’s most recent letter.

While it would be inaccurate to characterize Precision Quality DNA’s response as representative of the views held throughout the DTC industry, several of the points the company raises – including the need for greater transparency surrounding the FDA’s review and oversight of DTC genetic testing products – seem likely to resonate with other companies, whether they are currently in dialogue with the FDA or anxiously awaiting their own letter from the agency. (A good bet for a future FDA letter: companies offering direct-to-consumer telomere measurement tests, several of which drew criticism in recent weeks for over-inflating the ability of telomere length to predict individual longevity.)

The Latest in DTC Offerings. American International Biotechnology Services (AIBioTech), another company to receive a recent DTC letter from the FDA, found itself under the FDA’s microscope thanks to its Sports X Factor Genetic Athletic Assessment Test. The test purports to “reveal a person’s genetic athletic performance indicators as well as the potential for several risk factors,” including the risk of “negative results after an injury to an individual, such as a concussion,” or the possibility of an “undiagnosed heart condition.”

AIBioTech is not the first company to attempt to combine genetic testing and athletics – we dissected offerings from Athleticode and Atlas Sports Genetics back in 2009 – but the company’s test has received additional scrutiny due to its inclusion of markers for the apolipoprotein E (APOE) gene. The APOE gene, which comes in at least three different versions or alleles (ε2, ε3 and ε4), has been shown to affect an individual’s risk of coronary heart disease, as well as for developing late-onset Alzheimer’s disease.

Providing APOE results directly to consumers raises a host of delicate ethical and legal issues, as we discussed last month when DTC veteran 23andMe unveiled APOE reporting as part of its standard service. AIBioTech has drawn criticism for largely ignoring these issues in offering its athletics-focused test. (This in addition to criticism of the scientific validity of the claims offered up by AIBioTech and other athletic genetic testing companies.)

The inclusion of APOE in the AIBioTech test also highlights one of the frequently discussed challenges of trying to regulate any genetic test – whether DTC or otherwise – on the basis of its claims or intended use. As the proliferation of genomic data continues and our collective genomic understanding grows, the number of genetic markers which exert influence upon multiple traits of varying significance is likely to rise.

APOE’s implication in both heart disease and Alzheimer’s is a classic illustration of the phenomenon of pleiotropy – the ability of a single gene to influence multiple phenotypic traits – although it is hardly the only pleiotropic gene (genes responsible for sickle-cell disease, PKU and albinism, among others, also exert pleiotropic effects). As additional pleiotropic biomarkers are identified, the notion that genetic tests should be evaluated based on their intended use is likely to come under increasing pressure. How, for instance, will regulators address a genetic ancestry test when one or more of the biomarkers employed by the test could be used to predict an individual’s genetic risk for a serious disease? While this dilemma is not a conceptually new one, as the regulatory framework for genetic testing evolves, the nonlinearity of gene-trait relationships seems likely to pose a significant challenge for regulators, clinicians and companies who would prefer the ability to provide precisely targeted genetic test results to individuals.

Regardless, the issue seems likely to be mooted in large part at the point in the not-too-distant future where individuals have routine and early access to complete whole-genome sequences. Then the issue will no longer be whether or how to provide data with the potential to help predict multiple phenotypic effects, but how to exert any control whatsoever on the interpretative tools available (including, perhaps, IBM’s Dr. Watson, which is now reportedly “as good as the smartest second year med student”) to individuals who have access to complete and portable personal genomic data.

Are You Ready for RUO? Finally, one very recent development of potential significance to the DTC industry is the applicability of the just-released FDA draft guidance for research-use-only (RUO) and investigational-use-only (IUO) in vitro diagnostic products.

Published earlier this week, the RUO/IUO guidance clarifies the rules for marketing and commercializing diagnostic products under the widely used RUO and IUO exemptions, which allow device manufacturers to avoid submitting their products under the FDA’s rigorous medical device approval pathway. (For more see this article in Pharmacogenomics Reporter.)

The draft guidance, which is open for public comment for the next 90 days, is a significant event for manufacturers of laboratory developed tests (LDTs), many of which are thought to incorporate RUO/IUO components despite being offered for clinical or diagnostic purposes. Expect LDT manufacturers and industry groups, such as the Association of Molecular Pathology and American Clinical Laboratory Association, to have plenty to say on the RUO/IUO draft guidance before the comment period expires at the end of the summer.

Less clear is what impact the RUO/IUO guidance might have on the DTC industry. As with LDTs, it is not known exactly how many DTC genetic test providers utilize RUO/IUO components in their products. However, the pairing of an RUO or IUO device with a DTC product certainly occurs. For instance, 23andMe utilizes the Illumina OmniExpress Plus in its popular DTC service. The OmniExpress is part of a family of popular DNA microarray products offered by Illumina and labeled for research use only (pdf).

This exact issue appeared last summer when the FDA included Illumina in its first batch of DTC letters following the Pathway/Walgreens dust-up. From our coverage last June:

Of all the companies receiving letters, Illumina is the only one not to offer at least one product directly to consumers (the company does offer a commercial whole-genome sequencing service, although that product requires the participation of a healthcare professional). Illumina’s letter notes that the company has “received FDA clearance or approval for several of its devices,” but not for the HumanHap550 array. “Yet Illumina is knowingly providing the HumanHap550 array to 23andMe and deCODE Genetics for clinical diagnostic use without FDA clearance or approval” despite its being labeled “For Research Use Only.” As Gutierrez notes, “…Illumina has to follow the law, and they are aware that the chips are not being used for research only.”

Although the specific product has changed over the past year, the fundamental issue has not. The new RUO/IUO guidance, if approved in its current form, places a heavier burden on providers of RUO/IUO devices to “not sell such products to laboratories they know use the product for clinical diagnostic use.”

Which brings us back to one of the fundamental tensions concerning DTC genetic testing services: whether such services are intended, at least in the eyes of the FDA, for clinical diagnostic use. While the FDA and DTC genetic testing companies may not agree on the reasonably intended uses of these services, the FDA’s draft RUO/IUO guidance threatens to insert another key player – platform technology providers, like Illumina – squarely into the middle of the DTC debate.

If the FDA continues to maintain that the genetic testing services offered by 23andMe, Lumigenix and other DTC providers are intended for use in clinical and/or diagnostic testing, the Illuminas of the world will find themselves with a difficult choice to make. They will likely be forced to (a) defy the FDA’s RUO/IUO guidance, (b) stop selling their RUO/IUO devices to DTC companies or (c) attempt to shepherd their RUO/IUO devices through the FDA’s resource-intensive medical device approval process.

Or as the FDA puts it:

FDA is aware that laboratories sometimes use IVD products labeled RUO in clinical diagnosis and that many manufacturers, importers, and distributors of IVD products labeled RUO are also aware of such use. Manufacturers who label their IVD products: “For Research Use Only. Not for use in diagnostic procedures,” should not sell such products to laboratories that they know use the product for clinical diagnostic use. If a manufacturer learns that a laboratory to which it sells its RUO-labeled IVD product is using it in clinical diagnosis, it should halt such sales or comply with FDA requirements for IVD products, including premarket review requirements, if applicable.

If it were only DTC companies utilizing RUO/IUO devices, manufacturers like Illumina might simply stop selling those devices in light of the small (current) size of the DTC industry. But because those same devices also appear to be used by a number of LDT manufacturers, who represent a much larger market, there is a strong possibility that RUO/IUO device suppliers like Illumina will seek to obtain FDA approval for those devices, hopefully while working with the FDA to keep those devices on the market in the interim to avoid interruptions to patient care (or, in the case of their DTC customers, consumer product supply).

Regardless, the next few months will bear close watching to see whether the FDA’s attempt to more strictly enforce RUO/IUO labeling results in any significant shift in the relationships between DTC genetic testing companies and their technology suppliers.

What’s Next for DTC? Remember that it was roughly this time last year when Pathway Genomics’ failed partnership with Walgreens kicked off a busy summer of DTC (and related) activities at the FDA and on Capitol Hill. Up until this week, Washington had been relatively quiet since the end of last summer, at least in public. While the RUO/IUO situation bears watching, there are some who expect this summer to bring further fireworks on a par with last year.

While several important initiatives continue to loom as possibilities – including the FDA’s long-anticipated LDT guidance and new diagnostic-focused legislation from Congress – with 2011 nearly halfway gone I continue to think that the prospects for industry-wide regulation of DTC genetic testing in 2011 remain dim.

(1) presymptomatic and (2) mildly symptomatic but pre-dementia, along with (3) dementia caused by Alzheimer’s. This reflects current thinking that Alzheimer’s begins creating distinct and measurable changes in the brains of affected people years, perhaps decades, before memory and thinking symptoms are noticeable.

At least for the moment, the new guidelines are intended to be used only with patients enrolled in clinical trials, making them more of a work in progress and not a standardized method of determining disease onset in Alzheimer’s patients.

Federal Alzheimer’s Activity. The revisions to the diagnostic guidelines – the first in nearly three decades – indicate how far scientists have come in understanding the disease and are reflected in new legislation introduced in both the Senate (S.738) and the House (H.R.1386) that would expand Medicare coverage of Alzheimer’s to cover “comprehensive Alzheimer’s disease diagnosis and services,” including for individuals who fall under stage (1) or (2) of the new guidelines.

More significantly, the new guidelines and proposed legislation follow closely on the heels of the passage, earlier this year, of the National Alzheimer’s Project Act (NAPA). NAPA (pdf) charges the Secretary of Health and Human Services with developing “an integrated national plan to overcome Alzheimer’s,” including by accelerating the development of treatments, improving patient diagnosis and care and coordinating efforts across all Federal agencies. Although NAPA did not include any Federal appropriations, its supporters believe it represents a significant commitment to fighting the disease and will lead to an increase in funding, as well as in awareness.

DTC APOE Testing. As Alzheimer’s researchers continue to refine how to define and diagnose the disease – and, of course, seek treatments as well – and the Federal government attempts to coordinate and strengthen its attack on the disease, a few companies are offering consumers the ability to take diagnostic testing for Alzheimer’s disease into their own hands.

Recently, direct-to-consumer (DTC) genetic testing company 23andMe introduced an optional Alzheimer’s health report for its customers (of European ancestry). 23andMe customers who have been genotyped on the company’s latest platform – or who are willing to upgrade – can choose to learn which variants of the apolipoprotein E (APOE) gene they carry. The APOE gene, which comes in at least three different versions or alleles (ε2, ε3 and ε4), has been shown to affect an individual’s risk of developing late-onset Alzheimer’s, although the full physiological and genetic complexity of the disease is likely far from understood.

While 23andMe’s customers must separately choose to learn their APOE status, and are presented with a detailed report (pdf) outlining the gene’s predictive limitations in the face of other important factors, at least one prominent Alzheimer’s researcher has already criticized 23andMe for providing APOE results DTC. Allen Roses, a researcher at Duke University who helped to identify the link between APOE and late-onset Alzheimer’s disease, “believes that 23andMe should not report APOE status through DTC channels,” according to Pharmacogenomics Reporter. (In addition to 23andMe, other DTC genetic testing services, including the Decode Genetics service deCODEme, also offer customers the opportunity to examine their APOE status.)

At the center of the debate is whether individuals will benefit or be harmed, on balance, from learning whether they are at increased risk of developing a genetically influenced – but not determined – condition such as Alzheimer’s Disease for which there is no known cure.

This is exactly the issue that researchers at Boston University have sought to examine through the REVEAL (Risk Evaluation and Education for Alzheimer’s Disease) Study. While the REVEAL study is ongoing, proponents of DTC genetic testing in general, and of APOE testing in particular, point to preliminary findings which indicated that reporting APOE status to individuals “did not result in significant short-term psychological risks.” (pdf) Study researchers also recently published additional findings, concluding that one year after the initial disclosure of APOE status “test recipients still consider the pros to strongly outweigh the cons.”

Opponents of DTC testing, on the other hand, note that (1) the preliminary REVEAL findings measure only short-term outcomes, (2) individuals who tested negative for the APOE genotype associated with higher risk did experience reduced test-related distress, and (3) the initial REVEAL data involved subjects with significant exposure to Alzheimer’s disease who received direct access to genetic counseling, neither of which may apply to many DTC customers. (For more, see the final section of this Pharmacogenomics Reporter piece.)

A Matter of Utility. Then there is the issue of “clinical utility.” While there is no universally accepted definition of “clinical utility,” it is generally used to refer to the usefulness of a test or other procedure to alter (hopefully for the better) medical care. For example, the Centers for Disease Control and Prevention (CDC), in describing its ACCE model process for evaluating genetic tests, defines clinical utility as “how likely the test is to significantly improve patient outcomes.”

At least for the moment, there is no established cure or prevention strategy for Alzheimer’s disease, meaning that a genetic test designed to indicated predisposition to the disease fails to satisfy many traditional definitions of “clinical utility.” This lack of clinical utility, particularly for pre-symptomatic individuals, is frequently cited as a reason why such information should not be returned. For example, Muin Khoury, director of the CDC’s Office of Public Health Genomics, told Pharmacogenomics Reporter he believes tests that lack a sufficient level of demonstrated clinical utility, including, presumably, APOE testing, “should be offered in a medical setting, with counseling,” and should not be made available DTC. Similarly, last fall the European Society of Human Genetics issued genetic testing guidelines (pdf) in which it opposed “the premature DTC commercialization of various genetic tests,” including tests for which clinical utility is unproven.

Proponents of DTC genetic testing, including 23andMe, have adopted a very different perspective, arguing that APOE information – as with other genetic information – should be available to any individual who desires it. The “utility” noted by DTC proponents is slightly different, with a focus on “personal” as opposed to “clinical” utility. Even if it is unable to alter a course of treatment or improve a patient’s likely outcome, genetic information may still possess significant personal utility for some individuals.

For example, to return to APOE testing, the REVEAL study has demonstrated that even though there are no proven effective treatments for Alzheimer’s Disease, providing participants with genetic information regarding their genetic risk of Alzheimer’s has been found “to be useful by allowing [individuals] to prepare their families and arrange personal affairs including long-term care.” (The quoted language is supplied by Khoury et al. and is the byproduct of a 2009 joint NIH/CDC workshop investigating, among other topics, the utility of personal genomic tests. A summary is also available here.)

What’s Next? For patients and family suffering through Alzheimer’s at any stage of the disease, the hope is that increased Federal funding and continued scientific awareness will continue to improve the ability to diagnose the disease early and accurately but, soon, begin to supply effective treatments or even preventative measures.

As for DTC genetic testing for Alzheimer’s disease, 23andMe now offers what is likely the most widely available and least expensive DTC test (although there are other avenues for consumer-ordered APOE genetic testing, including DTC competitor deCODEme) and has pushed the door wide open for individuals to directly assess (a portion of) their genetic risk for Alzheimer’s disease. At least so far, despite objections from scientists and policymakers like Roses, Khoury and others, regulators have not expressed any public concern with 23andMe’s decision to offer APOE testing and Alzheimer’s risk analysis as part of its service.

Looking ahead, however, there are at least two potential barriers to the continued availability of DTC APOE genetic testing. With the FDA continuing to evaluate the appropriate regulatory approach to DTC genetic testing (the latest opportunity for public comment closed earlier this month), there is no guarantee that DTC genetic testing services such as the one offered by 23andMe will remain available indefinitely in its current form.

And more specifically to DTC APOE genetic testing, Turna Ray of Pharmacogenomics Reporter recently noted that Duke University is considering whether DTC companies, including 23andMe, are infringing APOE patents developed by Duke and exclusively licensed to Athena Diagnostics. As discussed in Ray’s article, a variety of factors, including the uncertain status of Duke’s APOE patents (which claim an association between APOE variants and Alzheimer’s risk) in light of the ongoing Myriad gene patent litigation, suggest that both Duke and Athena may elect to be cautious in considering whether to challenge 23andMe’s DTC APOE testing.

For the moment, anyway, new and recent customers of 23andMe (those genotyped on the company’s current v3 platform) have the option to explore their APOE status if they so choose. Earlier customers (those genotyped on the v2 platform) are left with a choice: upgrade to 23andMe’s latest offering, wait until a later date for APOE genotyping or, as my colleagues at Genomes Unzipped will discuss soon, make an educated guess on the basis of their v2 results.

Social Media as a Research Tool. Last month, PatientsLikeMe, an online patient community, made headlines with a study published in Nature Biotechnology in which the company analyzed self-reported data from nearly 600 patients to demonstrate that the use of lithium had no effect on the progression of amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease).

The study’s findings are valuable for ALS patients, who frequently experiment with unproven treatments in an attempt to slow progression of the degenerative disease for which there is not yet an effective therapy. But the long-term impact of the study’s methodological approach, which suggests “that data reported by patients over the internet may be useful for accelerating clinical discovery and evaluating the effectiveness of drugs already in use,” should be felt far beyond the ALS community.

PatientsLikeMe was formed after the brother of two of the company’s co-founders was diagnosed with ALS. The company, which initially sought effective treatments for ALS, has broadened its focus in recent years. PatientsLikeMe now seeks to help patients representing a range of diseases manage those conditions and to help medical researchers and companies improve the way they develop treatments, including by involving both patients and social media.

The Nature Biotechnology publication is a validation of the company’s efforts and, while not a substitute for traditional clinical trials, the PatientsLikeMe approach does demonstrate that social media tools, including networks of like-minded individuals (in this case ALS patients) “can provide supplementary data to support effective decision-making in medicine and discovery.”

Or, as PatientsLikeMe Chairman and Co-Founder Jamie Heywood told Health Business Blog, the study affirms that “there is tremendous value in reconnecting researchers to the patients they are working hard to serve by changing the norm from doing research ON patients to doing research WITH patients.”

Joining the Revolution in Progress. The PatientsLikeMe study, while impressive, is just the latest development in an ongoing and increasingly widespread effort to change how personalized medicine is pursued.

Consider, for example, Hugh Rienhoff, who launched a search to find the cause of his daughter’s mysterious genetic condition and, along the way, created a non-profit company to help others tackle similar problems. Or Genomera, a Bay Area start-up which aims to provide tools to help individuals design and carry out their own, personalized research projects.

Or 23andMe, the most prominent direct-to-consumer (DTC) genetic testing company in the market today, which has already demonstrated its ability to use social media and customer-driven data to identify novel genetic associations. While those particular associations are of admittedly limited utility, 23andMe is employing the same approach to identify the causes of – and potentially a cure for – Parkinson’s disease, a disease for which Sergey Brin, the Google co-founder and the husband of 23andMe co-founder Anne Wojcicki, carries a genetic predisposition.

23andMe also recently opened recruitment for a new study, in conjunction with researchers at Stanford University, to examine how social networking impacts health behavior and research.

And there are plenty of other projects seeking to expand the role individuals and social media play in scientific and medical research, including the Personal Genome Project, Sage Bionetworks, CollabRx, Genetic Alliance and DIYgenomics, to name just a few.

A Revolution Hiding in Plain Sight. While companies like PatientsLikeMe and 23andMe have successfully leveraged social media tools to demonstrate alternative pathways for personalized medicine research, social networking alone would be insufficient to produce a true revolution in personalized medicine. Another key factor has been the dramatic increase in availability of personalized health data, particularly genomic data.

Over the past year, a spate of articles has appeared in mainstream media publications describing the alleged failure of the Human Genome Project (HGP) to live up to the lofty expectations it set for itself a decade earlier. Last fall, for example, The New York Times’ Nicholas Wade lamented that “ten years after President Bill Clinton announced that the first draft of the human genome was complete, medicine has yet to see any large part of the promised benefits.” Francis Collins, then one of the leaders of the HGP and now the head of the NIH, opined in the journal Nature that “while the promise of a revolution in human health remains quite real…it is fair to say that the [HGP] has not yet directly affected the health care of most individuals.” And Matt Ridley criticized the HGP and its successors in the pages of The Wall Street Journal for “underdelivering useful medical knowledge and overdelivering other stuff.”

Yet by focusing solely on more easily quantifiable scientific and medical advances, and dismissing all of the “other stuff,” Wade, Collins, Ridley and others have largely overlooked a crucial legacy of the HGP: the rapid and continued democratization of genomics. Over the past ten years, technological advances have made it possible for increasingly large numbers of researchers, clinicians, patients and consumers to access personal genomic data. What was once a decade-long, multi-billion dollar, public-private collaboration to obtain a single human genome now requires nothing more than a credit card, a saliva sample and a few weeks.

While there can be no doubt that the ultimate goal is an improved understanding of the mechanisms of human disease and, as a result, an improved ability to effectively and efficiently treat those diseases, we should not lose sight of the tremendous progress we have made over the past decade in democratizing genomics and changing how personalized medicine is pursued.

Last fall, in “The Failed Promise of Genomics,” Matt Ridley wrote that “…personalized genomics will struggle to say anything at all, for the simple reason that it will be too personal.” That argument never made much sense to me in large part due to one simple fact, which was beautifully articulated by Joe Pickrell of Genomes Unzipped in a post explaining why DTC genetic testing is good for research. Wrote Pickrell, “all research is driven by curiosity, and the people most curious about a disease or trait are those who have it.”

The dramatically increased personalization of many aspects of health and medicine, especially genomics, is one promise the HGP has delivered in spades. As for Ridley, after initially worrying that personalized genomics was somehow too personal, he finally decided to see for himself. Apparently prompted by the threat of FDA regulation of DTC genetic tests, Ridley recently opted in to the personalized genomics movement and appears to have come away a changed man.

Last month, writing again in The Wall Street Journal, Ridley argued that the promised genomic revolution may indeed be realized, but only if it is embraced by the masses. “Genetic knowledge, whether the high priests like it or not, is going to be a crowd-sourced phenomenon,” Ridley wrote.

Of course, as the work of PatientsLikeMe, 23andMe and others continues to demonstrate, the revolution has been ongoing for some time now. Ridley is right that it will take many more doctors, researchers, consumers, patients, policymakers and, yes, even pundits before the active involvement of individuals in personalized medicine research becomes commonplace. And he is right that the revolution will occur whether or not personalized medicine’s “high priests” – including groups like the American Medical Association – are ready for it. What Matt Ridley failed to grasp is that the revolution is already here, and now he is a part of it.

Welcome to the Revolution, Matt.

The Continuing Threat of Decreased Science Funding. At least for the moment, the two houses of Congress appear, finally, to be edging toward a budget compromise that would bridge the $51 billion gap between the House bill (which passed at the beginning of March) and the most recent Senate proposal. That’s a good thing, given that the current continuing resolution is set to expire on April 8.

Nevertheless, it seems increasingly clear that federal science funding is unlikely to increase from its fiscal year 2010 levels, and funding almost certainly will not meet the targets President Obama set in his FY 2012 budget proposal.

The current budgets and proposed funding changes, as set forth in a recent AAAS report on federal R&D (see pages 40 and 42), are as follows:

While overall science funding looks to be in for a rough year, other innovation-boosting legislation appears to be gaining support, at least in the Senate. The Small Business Innovation Research (SBIR) program requires 11 federal agencies with large outside research budgets to award at least 2.5% of this spending to small businesses. The Senate’s bi-partisan SBIR/STTR Reauthorization Act would extend the set-to-expire SBIR program through 2019 and increase the percentage devoted to the program by federal agencies to 3.5% by 2023. This bill would also open the program to small-businesses that are majority-owned by venture capital firms, which were previously excluded because they aren’t independently owned.

This would particularly benefit small biotechnology companies, as many more biotech start-ups rely on venture capital funding than software start-ups (pdf). The Senate bill would allow the NIH and the NSF to award 25% of their SBIR funds to venture-owned small businesses. Not surprisingly, the Biotechnology Industry Organization supports the proposal.

However, even if the Senate is able to pass the SBIR reauthorization bill, there is no guarantee that the House will follow, particularly when it comes to opening up SBIR grants to VC-owned small businesses.

DTC Developments. Despite considerable commercial and regulatory uncertainty, the direct-to-consumer (DTC) genetic testing continues to attract new businesses, at least abroad. Australian-based Lumigenix, which launched its first DTC product earlier this year, was profiled this past week by GenomeWeb. Daniel MacArthur and Michael Müller also drew attention to a new (and pricey) DTC offering from Indian company Avesthagen. In Germany, meanwhile, there is at least one new and satisfied 23andMe customer despite recent German legislation that, at least on its face, appears to ban DTC genetic testing entirely. This is a helpful reminder that legislation—even proscription—is only as effective as its enforcement.

Finally, back in the United States, the debate over how to properly regulate DTC genetic tests is set to continue with the FDA announcing this week that it is reopening the docket from last month’s DTC meeting for additional public comment. With that discussion certain to continue for the foreseeable future it was encouraging, therefore, to see the NHGRI highlight regulation of genetic testing, including DTC genetic testing, as one of its new ELSI (Ethical, Legal and Social Implications) research priorities, even if the NHGRI may find it difficult to supply adequate funding for that research (see above).

Medical Technology Caucus. In a new development that could increase the lobbying power of medical device developers and other personalized medicine companies, Senator Scott Brown (R-MA) has joined forces with Senator Amy Klobuchar (D-MN) to form the bipartisan Senate Medical Technology Caucus.

Both Massachusetts and Minnesota have large medical technology industries and the move has been applauded by industry representatives, including the Medical Device Manufacturers Association. The corresponding House Caucus was formed in 1993 and is chaired by Eric Paulsen (R-MN) and Anna Eshoo (D-CA).

Roundup of tweets from the intersection of genomics, personalized medicine and the law:

• GLR Post: The FDA and DTC: Time to Set the Record Straight: http://bit.ly/fWJBg4 #FDADTC
• #FDADTC docket reopens tomorrow, until 5/2: http://bit.ly/i80OKs Chance to set the record straight: http://bit.ly/f9lWgq
• RT @drjonboyg: Newborn screening programs need better consent rules, experts say http://j.mp/eGfdZm
• The impact of human gene patents on genetic testing in the United Kingdom: http://bit.ly/hBHxui from GiM, HT @eurogene
• RT @pgx_reporter: Q&A: Cancer Commons’ Tenenbaum on Building a Patient-Centric System for Personalized Oncology: http://bit.ly/hvqz8K
• Germany’s strict genetic testing law (http://bit.ly/gXMgkg) didn’t stop this @23andMe customer: http://bit.ly/f0zqdE
• More on SBIR/STTR reauthorization progress in Senate, from @gw_dailyscan: http://bit.ly/fawftu
• RT @bachinsky: DARPA Puts Out Call for a DNA-Embedded Genetic Surveillance Machine http://t.co/C6gijo1
• Interesting profile/update by @Xconomy of patent aggregator/licensor Intellectual Ventures: http://bit.ly/erJBLo
• Taming the dragon: genomic biomarkers to individualize the treatment of cancer http://bit.ly/fNDPzE in Nature Med HT @FierceBiotech
• Good to see NHGRI articulate detailed ELSI research priorities/targets: http://1.usa.gov/fYuiGL Better had it come w/ news of add’l $$$
• Petition: “Congress: Don’t Cut Life-saving Funding for the National Institutes of Health”: http://bit.ly/gw30ST >14K signatures so far.
• MT @JohnCFierce: FDA insider allegedly made $119K on Somaxon insomnia drug approval. At least somebody made $$ on it. http://reut.rs/g6OMHN
• Avesthagen DTC product apparently 1.8M SNPs for 45K Rupees (=~$1K). PR focuses soley on disease. No PGx, carrier screening or ancestry incl?
• RT @dgmacarthur: Personal genomics hits India, via local biotech Avesthagen: http://bit.ly/gzeRgK (via @nutrigenomics) More on this soon…
• FDA chemist charged by SEC with insider trading: http://on.wsj.com/h16lBY via WSJ
• RT @GENbio: Legal Challenges to Healthcare Reform Threaten Biopharmaceutical Legislation http://bit.ly/fT16bt
• MT @daphnezohar: Startupamerica @ MIT FDA session takeaways: reduce duplication of failure by cos (use FDA knowledge), increase transparency
• RT @dgmacarthur: Christine Patch and Barbara Prainsack have their considered take on the #FDADTC meeting at BioNews: http://bit.ly/hggIVk
• RT @ldtimmerman: Cambridge, MA’s Epizyme, riding high on 2 pharma deals, zeroes in on personalized cancer therapy. http://bit.ly/g4Vy6H
• GLR Post: Frustrated by NIH Inaction, Fabry Patients Attempt End Run Around Bayh-Dole: http://bit.ly/hUmGwe
• RT @GenCounsNews: Advanced degree options for genetic counselors being explored by @NSGC_Org taskforce http://bit.ly/efjdAV
• RT @JCainHart: Interesting & timely given some recent similar situations in RTP. “Academic bias & biotech failures” | http://bit.ly/esYQ1D
• RT @matthewherper: Why are there so few biotech billionaires? http://ow.ly/4nW55
• RT @wilbanks: When you share data, you make it more valuable. Here comes the science. http://hdl.handle.net/2027.42/78307
• Update on SBIR reauthorization: http://bit.ly/gyubGx VC’s pushing for access. Another house/senate stalemate looming? cc @JCainHart
• Interesting reading: Humana’s coverage policies for genetic testing (http://bit.ly/iav6X1). No surprise: DTC, WGS generally excluded.
• Been on market since at least Jan. RT @GenomeWeb_News: Australia’s Lumigenix Launches DTC Genomics Offering: http://bit.ly/hQyO4p
• (For those actually using twitter, if you have suggestions for how to improve the GLR’s Twitter Roundup please let me know)
• Twitter Roundup: #FDADTC Edition (& a new format): http://bit.ly/dXQ592 Incl. @genomesunzipped/CC0, patent reform & more
• Friday already? RT @genomesunzipped: ‘Disguised’ heritability, mktg personal genomics, deciphering dev. disorders http://bit.ly/eRHTTl
• RT @InheritedHealth: Genzyme hit with more Fabrazyme drug woes http://ow.ly/4lUVx
• Interesting paper in GiM re: “medical & graduate students’ attitudes towards personal genomics” http://bit.ly/gVuHqp
• Thought RNAi litigation was done after last week’s settlement (http://bit.ly/dRjafg)? Think again: http://bit.ly/gvM5m9
• RT @S_O_NYC Signups for #sonyc are near room limit—if you’re coming, sign up now so we can book a larger room. http://bit.ly/hsNU6q
• RT @daphnezohar: .@ldtimmerman asks VCs: “Are you toast?” and reports that Canaan is still doing ok http://bit.ly/fH7nqi
• RT @GenomeWeb_News: Celera Sued Over Plans to Sell to Quest: http://bit.ly/gg11Bb
• RT @GenomeWeb_News: Bill Seeks to Restore Minnesota Genomics Partnership Funding: http://bit.ly/fWaKHS
• Watch @anderson_carl of @genomesunzipped niftily double my UC risk (but reassure me not to lose any sleep over it): http://bit.ly/dYfwnw

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.

A New Padilla Proposal. The California proposal comes from state Senator Alex Padilla. If Padilla’s name sounds familiar, it is likely because he is the same Senator Padilla who introduced a widely discussed “bioinformatics bill” to the California legislature two years ago. That bill (S.B. 482) was drafted with the close participation of direct-to-consumer (DTC) genetic testing company 23andMe, and 23andMe and Senator Padilla later co-sponsored a policy forum in San Francisco on “genomics and the consumer” (at which I presented).

Unlike Padilla’s earlier effort, which would have significantly altered the regulatory environment for so-called “post-CLIA bioinformatics services” (basically, genetic interpretation performed after the generation of genetic genotype or sequence data in a CLIA environment), 2011’s effort (S.B. 559 (pdf)) will almost certainly be viewed as a much less controversial proposal.

Genetic Information and Civil Rights. The primary purpose of S.B. 559 is to “expand the bases upon which discrimination is prohibited” under California law to include genetic information.

The act opens with numerous legislative findings detailing both the promise of genetic testing and related technologies, including genomic sequencing, as well as California’s “shameful” history of involuntary sterilization and race-based genetic discrimination. As a result, according to S.B. 559, California has a “compelling public interest in” both “realizing the medical promise of genetics” and “relieving the fear of discrimination and in prohibiting its actual practice.”

In light of the act’s purpose, the substantive provisions of S.B. 559 will come as no surprise. The two major changes are to the Unruh Civil Rights Act (California Civil Code §51 et seq.) and the Fair Employment and Housing Act (California Government Code §12900 et seq.). Both would be amended to include “genetic information” as an impermissible basis of discrimination, alongside sex, race, color, religion and a number of other specified bases. Appropriately, the definition of “genetic information” to be used closely tracks the language found in §201 of the Genetic Information Nondiscrimination Act of 2008 (GINA).

While Senator Padilla’s announcement declares that S.B. 559 would expand the protection of genetic information under California law beyond GINA’s provisions, to prohibit discrimination based on genetic information “in the areas of housing, employment, education, public accommodations, health insurance coverage, life insurance coverage, mortgage lending and elections,” the reality is that use of genetic information in several of these areas is already prohibited or substantially restricted. (See, for example, §10140 et seq. of the California Insurance Code for disability and life insurance).

Unlike Vermont’s proposed H.368 and Massachusetts’ Genetic Bill of Rights, which represent more significant departures from the status quo when it comes to the regulation of genetic information, California’s S.B. 559 would not break any new conceptual legislative ground. Rather, it would continue the ongoing and important process, begun by many states (including California) and advanced significantly by GINA, of placing genetic information on a par with other prohibited bases of discrimination.

Looking Beyond “Genetic Legislation.” Having looked at the recent proposals in Massachusetts, Vermont and California, is it fair to say, as both the Council for Responsible Genetics and Forum on Genetic Equity have, that there is a “groundswell for genetic privacy building in states”?

Before we answer that question, a few key points of clarification. First, these are legislative proposals, not enacted state law. As we saw with GINA, which took 13 years of Congressional debate before it was finally passed, shepherding a legislative proposal through the political process and turning into the law of the land is rarely as simple or quick as its sponsors might hope.

Second, and more importantly, not every piece of “genetic legislation” shares the same aims or would produce the same effects. While not identical, it is true that the legislative proposals in Vermont and Massachusetts appear to reflect a shared vision of granting individuals clear property rights in their genetic information and bolstering privacy protections for that information.

The California proposal, on the other hand, actually shares fairly little in common with Vermont and Massachusetts; at least once you look beyond the fact that it is a proposal for “genetic legislation.” S.B. 559 declares its purpose to be “relieving the fear of genetic discrimination and….prohibiting its actual practice.” That’s clearly an important goal, but it is just as clearly substantively distinct from articulating new genetic property rights or seeking out greater privacy protections for genetic information. (However, as reported by Pharmacogenomics Reporter, sponsors of the California proposal are considering expanding its scope to potentially address issues such as genetic property rights.)

So is a “groundswell” building at the state level? Perhaps, although when it comes to the specific issue of genetic privacy, we’re not sure that a pair of state legislative proposals (Massachusetts and Vermont) qualifies as a groundswell. We’ll need to see more state proposals – and at least some legislative adoption – before declaring that a meaningful change in the genetic privacy landscape is taking place. After all, as both the National Conference of State Legislatures and the Council for Responsible Genetics have demonstrated, most states have at least some laws on the books pertaining to genetic privacy. The extent of these laws, including the degree to which they are enforced, varies considerably, but it is not as if the issue of genetic privacy has never before been considered by the states.

What is clear is that, at both the federal and state level, legislators and regulators are continuing to grapple with how to handle the proliferation of personal genetic information. It remains to be seen whether these most recent legislative proposals – in Massachusetts and Vermont, and to a lesser extent California – represent the arrival of a new legislative approach grounded in privacy protection and individual rights to genetic information or whether they are only the latest word in a much broader conversation that has only just begun.

Numerous private and public conversations following the meeting indicate that there is considerable confusion about what actually happened at the meeting, including what the MCGP “recommended” to the FDA and what the FDA is likely to do with those recommendations. With that in mind, I followed up today with Dr. Alberto Gutierrez and Dr. Elizabeth Mansfield of the FDA’s Office of In Vitro Diagnostic Evaluation and Safety (OIVD) to seek clarification.

The MCGP’s “Recommendations.” Perhaps the single greatest source of confusion, and concern, centers on the MCGP’s “recommendations” to the FDA. A likely cause of this confusion is the original Federal Register notice (pdf), published last month, which indicated that at this week’s meeting the MCGP would “discuss and make recommendations on scientific issues concerning direct to consumer (DTC) genetic tests that make medical claims,” including the risks and benefits of offering such DTC genetic tests without clinician involvement. It was not immediately clear, even after the first day of the meeting, what form, if any, those recommendations would take.

As it turns out, “recommendations” is simply the wrong word to describe what the MCGP actually provided to the FDA.

The MCGP was formed three years ago (pdf) to advise the FDA on scientific issues relating to molecular and clinical genetics. Gutierrez and Mansfield confirmed that the panel was not formed, nor was its membership adjusted, in contemplation of the DTC meeting. While the panelists are certainly experts in their respective fields, a majority of the panelists did not appear to be well versed in the technologies, products (including specific tests) and business models employed by DTC genetic testing companies.

At the meeting, the MCGP heard presentations from the FDA, invited speakers (my own slides) and other parties who requested an opportunity to speak to the panel, including representatives from several DTC companies. With these presentations providing context, the MCGP then spent several sessions spread over two days commenting on the three primary questions, and numerous subquestions (pdf), on which the FDA sought the panel’s input.

Although a number of panelists consistently offered their opinion that the vast majority of genetic tests should be “routed through a physician,” for many questions there was no clear consensus from the MCGP. Furthermore, the panel’s deliberations were largely unstructured and, for most of the questions asked by the FDA, there was time for only a minority of the 21 panelists to offer their input.

Here, then, are a few important points of clarification about the MCGP’s activities at this week’s meeting and its influence on the FDA:

• The MCGP did offer its input in response to a number of specific questions (pdf) presented by the FDA;
• The MCGP did not vote or otherwise establish formal consensus with respect to any of those questions;
• The MCGP will not issue written recommendations following the meeting to the FDA with respect to any of those questions; and
• The FDA is not bound by the input it received from the MCGP in determining how to regulate DTC genetic tests moving forward.

With those clarifications in mind, did the MCGP actually accomplish anything of substance during the two day meeting? As I wrote earlier in the week, probably not:

…we should be careful not to inflate the importance of the MCGP’s recommendations. While they will be the most recent, and certainly the most public (by statute, MCGP meetings are open to the public absent a specific reason for closure) DTC recommendations, they will remain but one set of non-binding recommendations among many sets of recommendations, solicited and unsolicited, received by the FDA.

Furthermore, the MCGP’s composition (the panel’s 21 members feature 18 clinicians and academics, one consumer representative, one patient representative and one industry representative) and fairly obvious inexperience with DTC genetic testing technologies, products, companies and issues should diminish the weight the FDA lends to its recommendations. Whatever you may think of the FDA’s DTC policies to date, or lack thereof, the agency has been considering how to regulate DTC genetic tests for years, and is clearly more knowledgeable on this topic than its own advisory panel.

Ultimately, while it’s hard to find fault with the FDA for holding a public meeting on a topic of such public interest, it has been even harder to locate any indication that this meeting, or the MCGP’s recommendations, will significantly alter the agency’s thinking on the topic of clinical DTC genetic testing.

Nothing from day two of the meeting, or subsequent conversations with FDA officials, has suggested any reason to change this analysis. The MCGP’s input will surely be considered by the FDA, but I can find no credible evidence or argument to suggest that its “recommendations,” such as they were, will have a material impact on the manner in which FDA decides to proceed with the regulation of DTC genetic tests.

What’s Next for DTC Genetic Testing Regulation? For nearly a year, the FDA has publicly stated that it considers many genetic tests currently offered directly to consumers to represent medical devices subject to regulation under Section 201 of the Federal Food, Drug and Cosmetic Act (FDCA). Each of the published “it has come to our attention” letters sent by the FDA to DTC companies in 2010 (first to Pathway Genomics, next to five more companies, including 23andMe, and finally to 14 more companies) clearly made this point. Both Gutierrez and Mansfield reiterated this point at this week’s meeting.

The issue, for quite some time now, has not been whether the FDA intends to regulate DTC genetic tests. Instead, it has been (i) what form that regulation will take and (ii) when and how it will be implemented. Thus, the purpose of this past week’s meeting was not to solicit input on whether to regulate DTC genetic tests – at least for the FDA, that ship appears to have sailed and, as I argued at the meeting, most people agree that some additional oversight of the DTC genetic testing industry would be beneficial - but to discuss how such tests should be regulated, including “the risks and benefits of making clinical genetic tests available for direct access by a consumer without the involvement of a clinician” (pdf).

Again, despite suggestions from many panelists that a clinician should be involved in the ordering and interpretation of the vast majority of genetic tests, there was no formal or binding recommendation to that effect from the MCGP. Nor will one be forthcoming. There is also no good reason to suspect that genetic tests which are currently available DTC without clinician involvement, some of which have remained available for nearly a year since the FDA first publicly announced its intention to regulate these tests as medical devices, are going to be yanked from the market by the FDA tomorrow. If you’re considering purchasing a DTC genetic test, there are plenty of factors to consider in determining whether to take the plunge. A concern that you might not have the option next week should probably not be one of them.

When will the FDA decide to act more aggressively, if at all? That remains unclear. For the moment, the FDA is waiting for formal company submissions to review, while numerous companies, for their part, seek clearer guidance from the FDA regarding what types of products the agency might approve, and what data might need to be collected in order to win an approval. As for the continued availability of DTC genetic tests, some companies (e.g., Pathway Genomics) responded to the FDA’s letters by voluntarily removing their products while they seek to come into compliance. Others (e.g., 23andMe) have continued to offer their products directly to consumers while they negotiate with the FDA. Both companies, as Turna Ray of Pharmacogenetic Reporter writes, are prepared to comply with FDA regulations but ultimately committed to maintaining direct consumer access to DTC genetic tests. While it’s possible that the FDA will move aggressively against currently available DTC genetic tests at some point this year, I have noted, repeatedly, the low probability of this type of significant industry-wide regulation in 2011, and I continue to stand by that prediction.

Doctor’s Orders? So just what is the FDA likely to do, and when is it likely to do it? As discussed by FDA officials at the meeting, the FDA plans to continue to work with companies to develop appropriate regulatory submissions (which will be published once reviewed), with formal, public FDA regulatory guidance for DTC genetic tests following only after the agency has been through the clearance process, start-to-finish, with one or more products. While nothing is set in stone, and Congressional action could always upend everything, this is the most likely path forward for DTC genetic testing regulation.

As for what shape the FDA’s regulation will take, should it succeed (and remember, not all attempted FDA regulations ultimately succeed), there are a number of important questions to consider. For example:

• Should the agency require proof of analytical validity, clinical validity and/or clinical utility prior to approving a particular test and, if so, what standards of proof should be required?
• Should the agency regulate tests SNP-by-SNP, claim-by-claim or test-by-test, and what should be done to prepare for the inevitable arrival of tests based on whole-genome sequence data?
• Should the agency oversee the labeling and advertising claims offered by companies in association with such tests?
• Should the agency require companies to collect and submit data regarding the post-test benefits and harms and the actual (as compared to intended) uses of their tests?
• Should the agency impose requirements on companies to prevent unauthorized testing, protect data privacy and limit companies’ ability to share genetic information without their customers’ consent?

While these questions, and countless more, will be critical to the development of sensible genetic testing regulation, one question clearly generates more and more emotional responses than any other:

• Should regulators require some or all genetic tests to be routed through a clinician, or should tests be made available directly to consumers who desire them?

And so we come full circle. It was on exactly this question that the FDA solicited input from the MCGP, as well as other stakeholders, at this past week’s meeting. It was in answering this question that the MCGP developed the clearest consensus. And it is in reaction to this question, and to the comments from MCGP members at the meeting, that many proponents of DTC genetic testing feel most strongly that the FDA is in danger of going badly awry. Many individuals are seriously concerned that the FDA either does not understand or is simply not interested in how the actual and potential purchasers of these tests feel.

Many people believe, as do I, that “people have a right to access their own genetic information.” However, as I have also written and argued on multiple occasions, I do not believe the FDA is seeking to ban individuals’ access to their raw genetic or genomic data. Nothing that has happened this past week has convinced me otherwise. In the unlikely event that I am wrong, and the FDA in due course attempts to broadly restrict individual access to genetic information, there are a variety of factors (including the increasing clinical importance and availability of genetic data, the move to personally controlled medical records, the declining cost of generating genetic data and the globalization of the personal genomics marketplace, to name just a few) that seem certain to frustrate such an effort. Therefore, whatever the short-term consequences of any FDA action in this area, I fully expect that in the not-too-distant-future all individuals who desire it will have ready and inexpensive access to their complete genomic data, whether or not the FDA (or a panel of clinicians or anybody else) thinks that it is a good idea.

Setting the Record Straight. But that doesn’t mean that what the FDA does today does not matter, and it doesn’t mean that those who are concerned with how the FDA is seeking to regulate DTC genetic tests should not speak up. While the FDA has been atypically forthcoming in public discussions with details of its plans to regulate DTC genetic testing, the availability of genetic information, and the area of personal genomics more broadly, is one of atypical interest to many members of the public. Clearly, for many, the FDA has not listened closely enough to the public’s point of view.

If you are confused or concerned by the FDA’s actions in this area, speak up. Although the FDA does not regulate by majority vote, that happens to be exactly how Congressmen are elected, and one good option is to follow Jennifer Wagner’s lead and write a letter to your representatives in Washington.

For those who would prefer to express their views directly to the FDA, while the public DTC meeting has concluded, there will be several additional opportunities to be heard. First, the agency has agreed to reopen the public docket from this past week’s meeting to permit the submission of additional public comments into the official record for consideration by the FDA. You can find the docket at regulations.gov, docket number “FDA-2011-N-0066”. In addition, after holding three public “Town Hall” meetings in 2010, CDRH is holding another three meetings this year. The first was held this week, in Irving, Texas, with CDRH Director Jeffrey Shuren and other FDA officials. The next two will be in Orlando and in San Francisco, and the FDA should be announcing dates and other pertinent details soon.

Particularly in the context of DTC genetic testing, where so many of the reasons offered for stronger regulation revolve around how people actually react, or might react, to the results of genetic tests, personal experiences and views can be influential in shaping the FDA’s policy. Thankfully, there are still plenty of opportunities for the public to set the record straight on how it feels about the FDA’s plans to regulate DTC genetic tests.

1. Will the $1,000 genome live up to the hype?

2. Will personal genomics stay DTC?

3. How will the ongoing gene patent debate affect the progress of personalized medicine?

4. When and where will the next regulatory shoe fall?

5. Who will control the data?

A year later the question that comes first to mind is, has anything really changed?

The short answer is no, not fundamentally, although that is not meant to imply that nothing of note happened in 2010. Far from it, as significant legal, regulatory, policy and technological developments continued to reshape the personal genomics landscape.

With that in mind, we welcome 2011 with a look back at the year that was, and a look ahead at what to expect from 2011 and beyond.

The $1,000 Genome. With the draft human genome sequence turning 10 this past year, numerous media outlets reflected on the contributions of genomics and personalized medicine over the past decade. A frequent focal point – and measure of success – was the march toward what Keith Robison has termed the “arbimagical goal” of the $1,000 genome. Companies and investors continue to be enamored of low-cost, high-throughput genome sequencing, as evidenced in part by the IPOs of Complete Genomics and Pacific Biosciences this past fall.

At the same time, as we’ve written previously, the goal is not inexpensive genomics, but personal genomics. What matters is not how much it costs to generate a genome sequence (i.e., raw data), but what you can do with that genome once you have it. Thus, genomics is only personal once both the data and the interpretation are individually tailored.

2011 seems likely to be the year in which we finally crack the $1,000 barrier for a data-only genome, driven in large part by continued advances in sequencing technology, including Ion Torrent’s new Personal Genome Machine. But interpreting the data is another story. Already the dominant meme of 2011 is: “$1,000 genome; $100,000 analysis?”

If you’re waiting for a $1,000 genome delivered by your doctor, complete with advice about how to use the data to improve your health, Matthew Herper of Forbes advises you not to hold your breath. Likewise, analyst Amanda Murphy of the investment firm William Blair, believes that “the wide-scale incorporation of whole genome sequencing into the clinical realm is 10 or more years away.” Herper, Murphy and others think interpreted, clinical-grade genomes are going to remain elusive and expensive, particularly in the short-term and certainly for 2011. At Genetic Future, Daniel MacArthur largely agrees, but notes that for consumers willing to take more of a do-it-yourself approach, a $1,000 genome is a distinct and near-term possibility.

By 2012, motivated do-it-yourself (DIY) genomics pioneers like MacArthur will be able to locate cheap data and free or nearly-free tools to help make sense of that data for around $1,000 (not counting their own labor costs). And patients with an acute clinical need, particularly sufferers of cancer and certain rare diseases, will find that genomics plays an increasingly important role in their care, with insurers or even researchers or healthcare providers bearing the brunt of the cost.

However, the majority of us – non-scientists and generally healthy – are likely to find that full-genome sequences continue to remain just out of reach. With the combined cost of obtaining both complete genomic data and a layperson-accessible, reasonably accurate and personalized interpretation of that data remaining well north of $1,000 through 2011 and beyond, the number of consumers who choose to plunge into their full genomes will remain comparatively small. Most individuals will opt to dip their toe in the gene pool, paying several hundred dollars for a more modestly-sized chunk of personalized genomic data (e.g., the 1,000,000+ SNPs genotyped and analyzed by the likes of 23andMe) while they wait for either a clinical (and reimbursable) need to sequence or the cost of an interpreted personal genome to fall further.

As Yogi might say, the $1,000 genome may arrive this year, but it will still cost more than a grand, at least for most of us.

DTC Personal Genomics. For many, “personal genomics” is synonymous with “direct-to-consumer (DTC) genomics.” But despite the continued decline in the cost of genomic data, we begin 2011 with fewer significant providers of DTC genomic services than at the start of 2010.

The major developments have been covered extensively here at the Genomics Law Report. From the Pathway/Walgreens kerfuffle (and the FDA’s response) to the Congressional hearing and critical GAO report (and the FDA’s response), 2010 was certainly a tough year in Washington for DTC companies. (For a complete recap see: The Past, Present and Future of DTC Genetic Testing Regulation.)

While some erstwhile DTC providers (in particular Navigenics and Pathway Genomics) have, at least for the time being, shelved the consumer-facing side of their business, others continue to push forward. 23andMe remains the DTC front-runner, recently raising funds from both venture capitalists and the National Institutes of Health, but a handful of other DTC providers (including deCODE genetics) continue to offer products while a new generation of DIY genomics companies and researchers strive to put genetic data directly into the hands of increasingly large numbers of individuals.

For all of the apparent interest in DTC genomics from Congress and the FDA, the reality is that neither has yet articulated a clear plan to regulate that industry and, at the same time, both lawmakers and the regulators have bigger fish to fry in 2011. DTC personal genomics providers and their tests represent a mere fraction of the laboratory developed tests (LDTs) the FDA has vowed to regulate more aggressively and expansively than ever before (more on this below).

More importantly, the market for DTC personal genomics pales in comparison (at least in terms of market size and clinical importance, although perhaps not necessarily media coverage) to a host of other pressing issues facing Congress, the FDA and other regulatory agencies in 2011. These include, in no special order, the development, regulation and reimbursement of companion and other advanced diagnostics, follow-on biologics, how to deal with a rise in genomic data in regulatory submissions and what to do about whole-genome sequencing in particular and, of course, the fate of the healthcare reform legislation.

Remember, too, that following the recent mid-term election there will be personnel turnover in Washington as well. To cite two examples: the FDA’s No. 2 official, Joshua Sharfstein, has already resigned and one of the most vocal critics of DTC genetic testing during last summer’s House hearing, Congressman Parker Griffith – who compared providing genetic information to consumers with throwing live snakes into a crowded hearing room: useful only to incite panic – failed to win reelection.

Stepping back to view the prospect of DTC genetic testing regulation through this broader lens helps explain why, despite continuing uncertainty and ominous regulatory overtures, the DTC industry is likely to survive 2011 intact. Just as it did in 2010.

That is not to say that industry will not face increased scrutiny in 2011; or that this would be a bad thing.

There continues to be a clear need for more industry transparency, as well as heightened regulation of the advertising and marketing practices of existing genetic testing companies. The arrival of the NIH’s genetic testing registry (GTR), although not without its own critics, remains slated to arrive this spring. The GTR, along with increased enforcement of existing regulations from agencies like the FDA and the FTC, could do much to put a halt to true consumer abuses in the DTC personal genomics market.

There is also a widespread recognition that the DTC industry would benefit from greater standardization. A primary need is for greater definitional clarity. Terms like “DTC genomics” and “DIY genomics” frequently receive user-defined and inconsistent definitions, and no regulation – whether government- or self-imposed – will be practical until this terminological confusion is resolved. More substantively, there is a clear need to develop data standards, including both a standard format for returning genomic data as well as for interpreting and reporting those data. While DTC companies have frequently expressed interest in pursuing the latter, including in cooperation with federal agencies, considerable progress in all of these areas still needs to be made.

Of course, while unlikely, it remains a possibility that regulators or lawmakers will succeed in directly regulating DTC personal genomics in 2011. This could happen as part of the broader LDT regulatory movement or, more likely, take the form of narrower and more targeted regulatory requirements, such as interposing a physician or genetic counselor between the company and consumer at the ordering and/or data delivery stage. Or the FDA could always come up with some other out-of-the-box approach to DTC regulation.

Nevertheless, as we enter 2011 it remains legal throughout most of the United States to provide healthy individuals with direct access to their personal genomic data. While that is not the case worldwide, technological innovation and the proliferation of genomic data and of DIY genomic tools will drive continued growth and diversification of the DTC personal genomics landscape in the United States in 2011 and beyond.

Gene Patents. Without question, last year’s biggest story was – and continues to be – the ongoing Myriad gene patent litigation. Judge Robert Sweet’s jaw-dropping district court decision invalidated Myriad’s challenged patents across the board, for the moment, and thrust the debate further into the public and political spotlight than ever before.

While we entered 2010 anticipating a decision in Myriad, as well as in other important litigation (notably Prometheus and Bilski), we wrote that “there is little reason to believe that 2010 will be the year that the gene patent question will be finally resolved.” And we’re fully prepared to say the exact same thing in 2011 (and possibly in 2012, as well).

Those who first caught wind of the gene patent issue in March of 2010 (when Sweet’s opinion issued) may find it inconceivable that by the end of 2011 – a full 21 months later – there could be no resolution. But courts move slowly, and with the Supreme Court choosing once again to ignore biotechnology patents (the Supremes issued a heavily hyped Bilski opinion that proved to be just hype, and little more), the Federal Circuit rehearing Prometheus and saying exactly what it said in 2009 and the Myriad litigation in all likelihood multiple appeals from reaching its conclusion, a definitive answer does not appear imminent. Those waiting on the courts to resolve the patentability of genes or the increasingly important diagnostic methods at issue in Myriad, as well as Prometheus and Classen, are going to be forced to keep waiting.

Still, just as in 2010, 2011 will see its share of high-profile gene patent opinions issuing from courts. The most eagerly anticipated is the Federal Circuit’s Myriad opinion, which is expected in late spring or early summer. But the likelihood that Myriad or any other legal opinion will bring substantial and lasting clarity to the patentability of genes and related diagnostic methods in 2011 is slim.

However, not all parties are likely to be content to sit idly by and wait for the courts to decide (or not) the issue of gene patents. 2010 saw the publication of the highly publicized and equally controversial SACGHS report on gene patents and licensing. The report sparked plenty of conversation in biotechnology industry and policy circles and, though the SACGHS was disbanded later in 2010, those conversations have not quieted (as evidenced, in part, by the Justice Department’s unexpected amicus brief in Myriad). As genomic sequencing and diagnostic tools play an increasingly prominent role in clinical care, the role of patents – as either facilitators or inhibitors of personalized medicine innovation – will come under increasing scrutiny.

Persistent patent uncertainty continues to be a challenge for biotechnology companies and their investors. In large part for that reason, many are actively seeking out alternative pathways through the increasingly thorny gene patent thicket. Thus, don’t be surprised if 2011’s most noteworthy gene patent developments happen outside of the courtroom.

Legislation and Regulation. There was a lot of talk about regulating genetic testing in 2010, but the most significant regulatory action occurred late in the year with the EEOC’s publication of final regulations for Title II of the Genetic Information Nondiscrimination Act (GINA), which finally took effect this past week. With the increasing proliferation of genetic information, expect to see GINA – now in its third full year as law – in the headlines with more frequency in 2011.

As for genetic testing regulation, yes, 2011 could be the year that the FDA implements sweeping regulatory changes for laboratory developed tests (LDTs), including most genetic tests. But after announcing its intent to do just that back in June, the second half of 2010 came and went without significant follow-up activity from the FDA. After watching the FDA attempt to regulate a subset of LDTs (in vitro diagnostic multivariate index assays, or IVDMIAs) for four years before sending IVDMIA regulation to the regulatory trash heap for good late in 2010, there is good reason to be skeptical.

There’s a reasonable likelihood that the FDA will offer at least one concrete proposal for an LDT regulatory framework in 2011. But don’t expect that proposal – whatever its particulars – to be embraced by regulated entities, and we certainly wouldn’t bet on the FDA being able to finalize such an initiative and produce final guidance (or regulations, depending on which way it chooses, or is forced, to proceed) in the same year.

Other possibilities include two oft-discussed pieces of personalized medicine legislation, the Genomics and Personalized Medicine Act (GPMA) and the yet-to-be-introduced bill from Senator Hatch on advanced personalized diagnostics. But as we sit here today, the most likely scenario is that 2011 will bring no significant new final legislation or regulation affecting genomics and personalized medicine.

Such a rapidly-moving field poses substantial challenges for overburdened lawmakers and regulators even in the best of political environments and 2011, with its newly divided Congress and promise of contentious battles over healthcare reform and other key issues, hardly qualifies as an ideal political environment. Never say never, but those who would bring legislative and regulatory change to personal genomics are likely to spend 2011 primarily laying the groundwork for 2012 and beyond.

Access and Control. Our final question last year continues as perhaps the most important of 2011: who will control the data?

All of the issues above – from how much a genome will cost to who will be able to purchase one and whether a company can patent parts of it – reflect concern with access to and control of genomic data. Laws like GINA protect the use of genetic information in certain contexts, but at present there is no federal genetic privacy law and little consensus on whether an individual owns her own genetic material and data once it leaves her body.

As courts and legislatures continue to wrestle with these issues across an increasingly broad range of factual backgrounds – from state-mandated testing of newborns for genetic disease to the use of forensic DNA to monitor an increasingly broad subset of the country’s criminal (and frequently non-criminal) population – the pressure to clarify the rights individuals have in their genomes will intensify. Will we (along with courts and legislatures) conceptualize genomic data primarily as personal, with the individual the locus of control, or as medical, routing access and interpretation through the healthcare system?

Other challenges of no less importance will continue to demand attention in 2011 and beyond. We have already discussed, above, the issue of access to personal genomic data, and, indeed, no less an authority than NIH Director Francis Collins has written that “free and open access to genome data has had a profoundly positive effect on progress.”

But even as we strive to maintain broad and individualized access to genomic data, we will simultaneously need to ensure that those without the means (financial or otherwise) or desire to pursue their own genomic data are still able to benefit from personalized genomics. Among many, many challenges, this will require continuing the uphill battle to retrofit a healthcare system populated with institutions and individuals largely unprepared to handle the increasing size and complexity of incoming genomic data.

We Will Finish Where We Started. Again. These are big challenges, and they will not be met in full in 2011. We are confident that, when 2012 rolls around, most (and perhaps all) of the same issues will present themselves yet again to the field of personal genomics.

The $1,000 genome will continue to remain more hype than reality for most individuals. DTC personal genomics will continue to spark concern from legislators and regulators, tantalizing unscrupulous businesspeople even as it is embraced by an increasingly broad segment of the population. Gene patents will remain an unsettled area of law, even as public and private efforts to resolve the issue progress. The specter of FDA regulation will continue to loom large—and advance slowly. And, most importantly, while more people than ever before will have affordable and largely unfettered access to their genomic data, that access will be uneven, with many who could benefit most from personal genomics denied that opportunity.

Still, even as personal genomics’ challenges remain largely the same today as they were in 2010, and likely will be again in 2012, progress is apparent. After all that happened in 2010, perhaps all that really changed in the last year is that personal genomics is now a year older, a year wiser and continuing to advance. And perhaps that is enough. At least for 2011.

This November, just before Thanskgiving, 23andMe announced it was undoing most of last November’s changes, eliminating the separate ancestry and health editions and offering, once again, a single product. Not reversed: the price increase.

A Rationale for Raising Prices. The combined product remains priced at $499, although it now requires a 1 year subscription to 23andMe’s (previously optional) Personal Genome Service (PGS). The PGS, which debuted in September, provides customers with access to regular scientific updates and product features for $5 per month. The changes make the effective list price for 23andMe’s service $559, although the company has run frequent $99 sales, and there are rumors that another one is imminent.

23andMe has not yet publicly discussed the reason behind the price increase, although several individuals, including CeCe Moore of Your Genetic Genealogist, have reported that the company recently upgraded its genotyping platform (and that there will be an $89 upgrade option for existing customers). [Update: 23andMe has confirmed the upgrade, and Daniel MacArthur of Genetic Future discusses the pros and cons (mostly pros) of the company's new Illumina chip.]

23andMe’s new hardware, and the resources involved in analyzing a growing number of genetic variations and associated traits, may well explain the minor price increase. Keep in mind that, despite the rush for the $1,000 genome, cheaper genetic data does not necessarily mean cheaper genetic analyses. More available data means there is also more data to interpret, so even as the cost of obtaining personalized genetic data falls, the cost of making sense of those data may not immediately follow suit.

A Temporary Combination? But what about the company’s decision to recombine its products? Last year, when 23andMe split its health and ancestry products—a move which mimicked the strategy of its DTC competitor Pathway Genomics—I applauded the decision. At the time, the regulatory environment for DTC genetic testing was highly uncertain. While some form of regulation at some point seemed likely, it was unclear where regulation would come from or what shape it would take. (See “The Past, Present and Future of DTC Genetic Testing Regulation” for more detail.)

As I wrote at the time, employing separate commercial products to distinguish “educational or recreational uses of genetic data (such as genealogy) from clinical or medical uses (such as disease, pharmacogenetics or carrier testing)” seemed like a good way to provide commercial flexibility should future regulations discriminate between DTC products and services based on their intended use or likely risk.

Fast forward to today. In the past seven months alone, Pathway Genomics attempted to expand into Walgreens, only to draw the FDA’s immediate ire; the FDA sent letters to a host of DTC genetic testing companies, including 23andMe, warning that the companies were failing to comply with federal regulations; Congress held a public hearing to review a GAO-produced report on DTC genetic testing that cast the industry in an unfavorable light; and the FDA announced its intent to regulate all laboratory developed tests (LDTs), including DTC genetic tests, far more broadly and aggressively than ever before.

One important thing that hasn’t changed in the past year: the regulatory environment for DTC genetic testing remains as uncertain as ever. Still, as companies like 23andMe await the next move from the FDA, and perhaps from Congress as well, all indications are that a “risk-based application of oversight” is the most likely regulatory approach. Nobody yet knows what, exactly, that will entail, but products deemed by regulators to be lower risk are almost certain to receive less oversight both immediately and longer-term. Since 23andMe’s service involves examining genetic variants that are quite clearly low-risk (such as those used to identify genetic ancestry) and others that pose a higher potential risk (such as variants associated with drug metabolism or disease risk), recombining the health and ancestry products is a curious move.

At least from a regulatory perspective. But there is little reason to expect that clear or final regulations will be forthcoming from the FDA in the immediate future. With that in mind, 23andMe—which recently announced a new $22M round of venture funding led by Johnson & Johnson Development Corporation (and including existing investors New Enterprise Associates and Google Ventures)—may have simply decided not to allow regulatory prognostications to drive its commercial strategy.

Whatever 23andMe’s decision ultimately means from a regulatory perspective—and I would not be surprised to see separate products reemerge at some point in the company’s future—the real question is how its customers will take the news. While the price increase may be understandable to some, at $500+, the cost of a consumer genome scan would appear to be moving in the wrong direction for most consumers as the holiday shopping season approaches.

[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).