Editor’s Note: This was first published at Genomes Unzipped and was co-authored by Daniel MacArthur and Luke Jostins. Genomes Unzipped received 12 free kits from Lumigenix for review purposes, and Dan Vorhaus has provided legal advice to the company. Genomes Unzipped plans to release a full review of the Lumigenix service in early July.

Last month three direct-to-consumer (DTC) genetic testing companies opened their mailboxes to find a slightly ominous but entirely expected letter from the FDA. The three recipients (Lumigenix, American International Biotechnology Services and Precision Quality DNA) received substantively equivalent letters, with the FDA warning each company that its genetic testing service “appears to meet the definition of a device as that term is defined in section 201(h) of the Federal Food Drug and Cosmetic Act,” and that the agency would like to meet with company representatives “to discuss whether the service [they] are promoting requires review by FDA and what information [they] would need to submit in order for [their] product to be legally marketed.”

Translated from bureaucratese, that means that the FDA views these services as ones that may need to be formally reviewed by the agency and either approved or cleared before they can be legally sold. The FDA letter asks each company to describe its service and to explain either (1) why it does not require FDA approval or (2) how the company plans to pursue such approval.

This is a strategy that the FDA has pursued with a growing cadre of DTC service providers. These letters (currently 23 and counting¹) represent the only public and company-specific actions the agency has taken to date with respect to DTC genetic testing. While many DTC letter recipients are engaged in dialogue with the FDA, those conversations have occurred beyond the public’s view. Until now.

Ending the regulation guessing game? For more than a year, the FDA has dealt with DTC genetic testing providers by mailing (and publishing) an initial letter followed by the initiation of a private dialogue and a company-specific regulatory determination. The agency has yet to publish, or even to propose, anything resembling industry-wide regulatory guidance for current or prospective personal genomics companies.

For their part, personal genomics companies have been reluctant to publicly disclose the nature of their conversations with the FDA. Recently, however, a new approach appears to be emerging, at least on the company side.

Last month, a recent DTC letter recipient (Precision Quality DNA) published a strongly worded response to the FDA on its website. Another letter recipient, Lumigenix, soon followed suit, launching a new corporate blog with the publication of its own more measured response to the agency. Each company undoubtedly has its own reasons for bucking the prevailing trend and choosing to take its conversation with the FDA into the public square. There should be little doubt, however, that the FDA’s current company-by-company approach to personal genomics regulation, which has left the industry with a considerable measure of uncertainty, was a major contributing factor in each decision. As Dan and his colleague Allain Andry noted last summer, the effects of that regulatory uncertainty can be substantial.

They include:

• Reduced access to capital. Genetic testing companies may find that investors are more cautious about making new and add-on investments.
• Fewer new products. Companies may delay plans to introduce new products both because of lack of funds and concern about the regulatory response to innovative products or business models.
• Fewer entrants. Numerous investors, and companies in related industries, have been preparing to enter into the genetic testing field. Many of those plans may be put on hold.
• Litigation risks. The well-publicized GAO report and Congressional hearings, which highlighted apparent operational deficiencies of some DTC companies, could lead to tort (e.g., negligence, emotional distress, malpractice), securities or other lawsuits from plaintiffs’ lawyers and litigious customers. Although the GAO report and Congressional investigation focused on DTC genetic tests, the broad and negative public attention focused on genetic testing could spur similar litigation against more traditional genetic testing developers and providers.
• Reduced access to technology. Companies dependent on third-party providers for some portion of their own test or business might find their options limited if regulatory uncertainty or changes discourage such collaborations.
• Encouraging overseas development. Increased regulation – or even the possibility of increased regulation – may encourage companies and investors to focus on developing new products and businesses overseas in advance of, or instead of in, the United States, with potentially detrimental consequences for patients and consumers in this country.

Current and prospective DTC genetic testing providers alike are no doubt burdened by some or all of these challenges. Lumigenix, in particular, appears hopeful that a more public DTC discussion might help to lessen the effects of regulatory uncertainty, noting at several points in its response to the FDA the company’s desire to work with the agency to develop “a clear and reasonable system of oversight for the emerging field of personal genomics.”

The challenge of “clinical” DTC claims. Perhaps the greatest area of current DTC regulatory uncertainty concerns the ability of companies to provide interpretations of personal genomic data with potential clinical or medical significance. The FDA has consistently maintained that its regulatory interest lies first and foremost with clinical genetic tests, with a test’s intended use determining whether it qualifies as clinical.

The FDA’s emphasis on clinical genetic testing has presented personal genomics companies with a dilemma: offer medically relevant personal genomic results in response to consumer demand and thereby risk stricter scrutiny from regulators, or attempt to cater to regulators (but risk losing customers) by removing or deemphasizing results that could be construed as clinical.

Personal genomics companies have deployed a variety of solutions in response to this dilemma. 23andMe, for instance, has simply braved regulatory ire by continuing to offer tests for the BRCA breast cancer risk variants, pharmacogenomic response and other serious disease mutations. Pathway Genomics responded to its own FDA letter by promptly eliminating the ability of consumers to purchase its product without physician involvement. Carrier testing company Counsyl avoided a letter entirely by dropping DTC marketing as soon as the FDA began to make serious regulatory overtures.

Lumigenix, for its part, has thus far taken an intermediate approach, steering clear of reporting on variants with unambiguous clinical relevance while maintaining DTC access to its service. In its response to the FDA, Lumigenix emphasizes that the company “strongly believes that individuals should have the right to access their own genetic information,” but explains that Lumigenix has opted to exclude certain information from its current service to avoid any clinical confusion:

In order to ensure there is no doubt about the educational purpose of our service, Lumigenix’s current service intentionally excludes certain categories of genetic tests. For that reason, Lumigenix’s does not currently include in its customers’ genomic reports results from genotype data known to be associated with or to indicate:

• carrier status for a recessive disease (e.g., Cystic Fibrosis or Tay-Sachs disease);
• pharmacogenomic status related to an individual’s likely response to certain medications (e.g., Warfarin or Clopidogrel); or
• a serious or untreatable illnesses with a large genetic component (e.g., breast cancer, Huntington’s disease or Alzheimer’s disease).

We understand that some individuals desire such results for their informational value. But we also acknowledge that the risks associated with personal genomics, including the risk that an individual will make an important medical or other decision without first consulting a healthcare professional, are not equal across all categories of genetic tests.

For that reason, Lumigenix has decided to focus its current service on providing personalized genetic information pertaining to genetic ancestry, non-medical traits and conditions, and certain relatively common medical- or health-related conditions that tend to be influenced by many genes and include a substantial environmental component.

It’s worth noting that Lumigenix is still early in its conversation with the FDA and has not yet had the same length of time to respond (e.g., in the form of modifications to its service or business model) as earlier DTC letter recipients, including 23andMe and Pathway Genomics. Lumigenix’s response does, however, hint that changes may be in store: the company applies the adjective “current” in describing its service eight separate times in its response to the FDA.

The range of approaches taken by personal genomics companies on this issue alone reflects a much broader uncertainty about the industry’s regulatory future in the hands of the FDA. The agency’s reluctance to publicly pursue a comprehensive personal genomics regulatory framework is understandable, particularly in light of the rapid pace of scientific and technological innovation and the paucity of data about DTC genetic tests and their affect on consumer behavior. Still, for so long as the FDA continues with its current private, company-by-company regulatory approach, personal genomics innovation and investment are likely to remain hampered by uncertainty.

A glimpse into the regulatory future. Interestingly, despite Lumigenix’s focus on non-medical data as part of the formal interpretations it provides to its customers, the raw data generated by the company’s genome-wide test contains plenty of medically relevant genetic variants. For example, there are at least 196 sites on the chip that match the position and sequence of known Mendelian disease mutations, including 12 in the BRCA1/2 genes and 6 in the cystic fibrosis gene CFTR². Lumigenix simply does not report on or interpret these variants, although customers can choose to explore those variants on their own, including through the use of free software such as SNPedia’s Promethease.

This approach to medically relevant personal genomic data, at first blush needlessly confusing and inefficient, is unsurprising in light of the FDA’s insistence that their regulatory target is not genomic data but the claims – particularly clinical or medical claims – made on the basis of those data. Last August, for example, reporter Mary Carmichael and Dr. Elizabeth Mansfield, Director of Personalized Medicine for the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD), had the following exchange:

[MC]: I want to move on to whether the issue with direct-to-consumer is actually providing data to people, or is it the interpretation algorithms these companies are using? So, would a company need to be approved just to provide a raw SNP list to people?
EM: They would if they made medical claims about that data. If they don’t make any medical claims about that data, then they’re free to provide information as far as we’re concerned.

Over the past year, nothing has happened that would suggest that the FDA has revised its policy on this point. This bodes well for both DTC companies and their customers because, barring a striking reversal by the FDA, high-quality personal genomic data appears likely to remain readily available, including via direct-to-consumer channels. Whatever else the FDA may have in store for the personal genomics industry, the availability of raw genomic data should enable DTC companies to remain on the market in some form.

Still, the increasing availability of raw personal genomic data will itself soon pose a challenge for the FDA. Already widely accessible and inexpensive, personal genomic data will soon transition from SNP chips to whole-genome sequences. As data proliferates alongside increasingly numerous and sophisticated publicly available software tools (like Promethease, SNPTips and Interpretome, the topic of a recent post) used to mine those data, the FDA will find that focusing on all-inclusive providers of DTC personal genomics services is insufficient. As the separation of testing (genomic data generation) from interpretation (genomic data analysis) accelerates, the FDA will be faced with a growing array of personal genomics service providers, many of whom are likely to provide software-only tools and will see no pressing need to operate from within the United States (and within easy reach of the FDA).

How the agency responds to the inevitable expansion and diversification of the personal genomics industry – e.g., with an expanded letter-writing campaign or a concerted effort to develop flexible and forward-looking industry guidance – remains to be seen.

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1. The count: Pathway Genomics (May 2010); 23andMe, Navigenics, Knome, deCODE Genetics, Illumina (June 2010); Graceful Earth, SeqWright DNA Technology Services, Interleukin Genetics, DNATraits, CyGene Direct, Consumer Genetics, Matrix Genomics, The Genetic Testing Laboratories, Sequenom, EnteroLab Reference Laboratory, BioMarker Pharmaceuticals, DNA Dimensions, HealthCheckUSA, easy DNA (July 2010); Lumigenix, Precision Quality DNA, American International Biotechnology Services (May 2011).

2. Analysis by DM: I looked at the overlap between the SNPs included in my raw data from Lumigenix (available for download here) and the disease mutations in the full version of the Human Gene Mutation Database (available only via an academic collaboration or a license fee, unfortunately). I counted positions where both the position and both alleles matched. Note that this approach won’t detect disease-causing insertions and deletions, only SNPs.

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

In response, the FDA agreed to reopen the public docket in order to receive additional public input on scientific issues concerning DTC genetic tests. The docket will reopen tomorrow and will remain open through May 2nd (pdf).

For those with an interest in the FDA’s oversight of DTC genetic testing, this is the first of several opportunities to be heard. In addition to the newly reopened public docket, the FDA has also announced its next “town hall discussion” with top officials from the Center for Devices and Radiological Health (CDRH), the FDA center responsible for the regulation of medical devices, including genetic tests. Both CDRH director Jeffrey Shuren and OIVD Director Alberto Gutierrez are scheduled to participate in a public question-and-answer session on May 5th in Orlando, FL.  An additional town hall discussion is slated for San Francisco, CA later in the year. The Genomics Law Report will post additional details for that meeting as they are made available.

This is also a good time to introduce Genomics Law Report readers to Sharon Goswami, the Genomics Law Report’s new intern. Sharon is a 2L at New York University’s School of Law and and holds a degree in chemical engineering from Princeton University. At NYU, she is technology co-chair of the student intellectual property organization IPELS and an active student member of the William C. Conner IP Inn of Court.

This edition of the Twitter Roundup is divided into two sections.

The FDA Meets DTC. Again. Since this is the first Twitter Roundup since the FDA’s two-day public panel meeting on direct-to-consumer (DTC) genetic testing two weeks ago, we have collected all of the recent tweets on that topic in a separate section. We covered this topic in extensive detail (see posts here, here and here), but there have been plenty of others sharing their thoughts and opinions on the meeting, the FDA’s actions and the future direction of DTC genetic testing. You can find links to many of those below, as well as Dan’s live-tweeting of the meeting itself. You can also find additional coverage on Twitter under the hashtag #FDADTC and you can find all of the GLR’s DTC coverage here.

Also in the News: Public Genomics and Patent Reform. All other Tweets are collected below as usual. In addition, here are a few recent highlights our readers may have missed.

Genetic Data in the Public Domain: Genomes Unzipped Implements CC0. Raw genetic data from the Genomes Unzipped (GNZ) contributors (including Dan) are now officially available under the Creative Commons CC0 public domain option. By placing data under CC0 the GNZ contributors have waived their copyright to their genetic information, permitting the use of those data without restriction or attribution. GNZ joins other efforts – including the Personal Genome Project (which also utilizes CC0), SNPedia and Sage Bionetworks – in seeking to broaden the availability of public genomic data.

GNZ data can be browsed using the group’s Genome Browser in a manner similar to the tools available through the International HapMap Project website – looking at particular sets of data that correspond to RefSeq materials. However, unlike the HapMap data, GNZ data comes from identified individuals who have chosen to share their genomic data with the public freely and without restriction.

Update on Patent Reform Legislation. Earlier this month, the Senate passed by a 95-5 vote the America Invents Act (S.23) or, as it is more commonly known, the Patent Reform Act of 2011 (pdf). Its passage, after six years of ongoing legislative debate, was hailed by many. President Barack Obama called it “the most significant patent reform in over half a century” and David Kappos, Director of the United States Patent and Trademark Office (PTO), declared it “a win for all American innovators, of all sizes and industries.”

Among the legislation’s numerous reform proposals, the most controversial is a proposed change to a first-to-file system (from a first-to-invent system), which would award priority in most cases to the first inventor to file with the PTO. Supporters of the switch to first-to-file, including the Biotechnology Industry Organization (BIO), argue that the change would bring the United States in line with international patent practice and that, on the whole, the reform would improve the U.S. patent system, spur innovation and create jobs.

Detractors, on the other hand, argue that the current first-to-invent system protects small inventors who lack the patent prosecution of large corporations. For example, the National Venture Capital Association (NVCA), the nation’s largest trade group for early-stage investors, argued this week that the current version of the Patent Reform Act substantially disadvantages small start-up companies and could harm innovation and investment.

Over the past few weeks, as politicians, lobbyists and industry groups have lined up on both sides of the Patent Reform Act, the bill’s odds of becoming law have become far less clear than they initially appeared. With the reform act currently stalled in the House (another hearing is set for next week) it remains to be seen whether 2011 will be the year that patent reform legislation is finally passed and, if so, what portions of the Senate version will survive the legislative process intact.

Now, on to the Tweets:

Tweets from or about the FDA’s public meeting on clinical DTC genetic testing:

• HT to @razibkhan & his post on “Genetic Paternalism & the FDA” http://bit.ly/hkJak9 for pointing me to Kari/deCODE quote #FDADTC
• GLR Post: Closer Scrutiny Ahead for DTC Genetic Testing Claims: http://bit.ly/gxnpEn #FDADTC
• Last wk’s House jobs forum reminder some in DC see #FDADTC regulation as inhibiting job creation: http://bit.ly/fjLXwJ cc @PathwayGenomics
• FDA promises reg guidance for mHealth apps this yr. @mobilehealth says it’s been happening for yrs: http://bit.ly/hiB9O2 sounds like #FDADTC
• RT @shwu: FDA’s summary of the #FDADTC panel meeting: http://1.usa.gov/hy6MPx
• Want to share your #FDADTC thoughts? CDRH Town Hall-Orlando-on 5/5: http://1.usa.gov/i2oGgp Shuren to discuss FDA strategic priorities
• RT @dgmacarthur: A more optimistic take on the #FDADTC meeting from @PathwayGenomics: http://cot.ag/gqGm1Z
• More excellent coverage from #FDADTC by Turna Ray of @pgx_reporter: http://bit.ly/fhiZ1U (sub)
• GLR Post: The FDA and DTC Genetic Testing: Setting the Record Straight: http://bit.ly/f9lWgq #FDADTC
• Have been told House DTC investigation “bipartisan,” not over simply due to Republican control of comm. Will E&C revisit GAO report? @shwu
• RT @shwu: Source docs for GAO restructuring: http://1.usa.gov/hPIzbt
• RT @dgmacarthur: Official who led GAO report into DTC genomics shown to have fudged schools report: http://bit.ly/eYyqZj (via @shwu)
• Expanded, revised #FDADTC slides for AM talk @DukeIGSP. Have posted for those interested: http://bit.ly/gRZ8mQ
• Different take on #FDADTC: RT @GW_The_Sample: Clinical Labs Should Rejoice Over FDA Panel’s DTC Genetic-Test Ruling: http://bit.ly/hewnDH
• DNA Dilemma: Denoument (or what @mary_carmichael would have liked to say to the #FDADTC panel): http://bit.ly/h6ckBe
• RT @genomesunzipped People have a fundamental right to access their own genetic information – a consensus statement: http://bit.ly/eQw8ai
• +1 RT @matthewmarkus: I enjoy analyzing lats & lons more than SNPs because my results don’t have to be routed through a geographer. #FDADTC
• RT @mary_carmichael: “PPl should be free to make own choices. Harm from [DTC] tests ltd, as is benefit.” Altshuler: http://bo.st/ffebu1
• RT @dgmacarthur: At @genomesunzipped, Joe Pickrell points out the benefits to research of DTC genetic testing: http://bit.ly/iecbZt #FDADTC
• Frustration with #FDADTC spilling from twitter to blogs (#2): @razibkhan prepares to defend his genomic rights: http://bit.ly/fIc7gl
• Frustration with #FDADTC spilling from twitter to blogs (#1): @DNAlawyer challenges FDA’s authority: http://bit.ly/fCinuI
• Detailed coverage from Day 1 of #FDADTC from @pgx_reporter: http://bit.ly/gyJimX (subscription)
• Need to think beyond spit kits, too. Where will WGS analysis occur? RT @MishaAngrist: Suspect lot of saliva will be headed offshore. #FDADTC
• Speakers? Probably. Panel itself? No. RT @RDGene: Gutierrez: assures panel that provided speakers that were balanced #FDADTC
• Add’l VC funding since. RT @RDGene: Rose Romeo @23andMe: layoffs referred to yesterday due to recruitment of experienced personnel #FDADTC
• That begs a good q: is DTC test must be routed through clinician, must post-test follow-up-eg surveys-go through clinician as well? #FDADTC
• RT @RDGene: Pathway: move to HP only model has made collection of lifestyle data used in risk calcs more difficult #FDADTC
• Panel composition not well balanced. RT @shwu: All this concern for consumers-has anyone thought to ask consumers themselves? #FDADTC
• Assume from audience, not from panel/FDA. RT @RDGene: (Round of applause when Pendergrast finished her talk #FDADTC)
• RT @aliciaault: Pendergast said MDs on panel could not keep info from consumers, nor compel them to see MDs after test results. #FDADTC
• RT @aliciaault: Wow, former FDA official Mary Pendergast just chewed out the panel for being paternalistic, controlling doctors. #FDADTC
• Breaking for lunch at #FDADTC. That’s going to be it for me as off to @DukeIGSP: http://bit.ly/bkroGw. Will follow rest of mtg from afar.
• Mansfield: we have used direct-to-consumer for simplification. Tests also called “direct access,” various other terms. #FDADTC
• Mahowald: key idea is people are buying these tests. (Not sure I see consumer/customer distinction Mahowald is trying to make) #FDADTC
• Mahowald: wants to make a strong pitch to change from “consumer” to “customer”; wants panel to vote on it #FDADTC (What’s the difference?)
• Ng: need a pre-test/post-test risk calculator? Know in advance extent genetic info will modify your risk after consid other factors #FDADTC
• House: why can’t we tell individuals that the test has limitations (not all factors incl), but allow them to manage that information #FDADTC
• House: assume we have approved genetic test mtg FDA reg requirements. If that test is not the only factor, why not make avail #FDADTC
• Hersch: issue imp for labeling; clarify medical risk uncertain, true risk of disease must be considered in context of other factors #FDADTC
• D’Agostino: tests should be developed in light of existing knowledge, incl. all relevant clinical parameters (not just genetic) #FDADTC
• Netto: inability of DTC companies to provide other types of data collection, interpretation is what will keep most tests from DTC #FDADTC
• Netto: this is the issue that is going to bring most DTC back to prescription testing; to do this properly will need a clinician #FDADTC
• Ransohoff: patient is not really interested in “what’s my test result”? Interested in “what’s my risk for X”? (Do consumers agree?) #FDADTC
• D’Agostino: absolutely. Ransohoff: a great q b/c it shows distinction b/w HIV test and a genetic test – latter has add’l complexity #FDADTC
• Q from FDA to panel: should test reports for future risks incl. warnings/info about add’l risk factors (eg env, health history) #FDADTC
• Lipkin and others generally agree that absolute risk is easiest for consumers to understand; can have relative risk as well #FDADTC
• Lee: descriptive categories easiest to understand (for consumers), but need to be tied to number (absolute risk) #FDADTC
• Q from FDA to panel: what are best ways to present risk to consumers in genetic testing context? Relative, absolute, high/low risk #FDADTC
• Lipkin: need to make avail genetic “counseling” by a qualified individual; whether that’s a GC or somebody else TBD #FDADTC
• Tsongalis: are we confusing genetic counseling w/ clinical counseling? GC’s and MD’s have different roles #FDADTC
• Ransohoff: making GC available may not be enough. Disingenuous to leave too much in hands of consumer. #FDADTC
• (NB: panel discussion at this point is all hypothetical; background assumption is their rec to FDA that most/all tests not DTC #FDADTC)
• Wyne: if we let tests go DTC w/out “routing through clinician,” should at least make a GC available #FDADTC
• Wyne: should rec involvement of GC; the fact #s are insufficient today is not a surprise; field is growing, more GCs will be trained #FDADTC
• Ransohoff: if a test is so complicated that a genetic counselor is required, then perhaps that is a sign the test shouldn’t be DTC #FDADTC
• Shamburek: sub-specialists are nice for specific traits (HD), but won’t work for whole-exome, WGS; need broader genetics expertise #FDADTC
• FDA: looking for recommendation from panel: should GCs be required, should they be available? How should they be involved? #FDADTC
• Gallagher: agrees, but notes not enough qualified genetic counselors; also be wary of conflict of interest (GCs employed by co) #FDADTC
• Mahowald: important that the clinician involved in genetic testing counseling be “qualified”; cos obligated to ensure this. #FDADTC
• Panel now asked to consider appropriate role of genetic counselors in clinical DTC genetic testing #FDADTC HT @GenCounsNews @alliejanson
• Gutierrez: but given panel is clear that most (maybe all?) tests should not be DTC, ok to move on #FDADTC
• Gutierrez: when we put panel together, had to consider possibility of panel going either pro or con on DTC. So qs thus designed #FDADTC
• (Panel clarifying that high-risk tests should not be available DTC; but panel reminded – by other panelists – that only making recs #FDADTC)
• Wyne: how do you decide what is medically actionable w/ 100,000 genes on chip? Screen every one? #FDADTC
• Gutierrez: consider whether particular disease/ symptom requires clinical intervention – requirement of going through MD #FDADTC
• Wyne: can we allow as DTC anything that is not “medically actionable”? #FDADTC
• Panel: will we be asked about privacy issues related to (DTC) genetic testing? Mansfield: not the place for that discussion either #FDADTC
• Hirschhorn: how will FDA integrate regulation w/ state laws? Gutierrez: not the place for this discussion. #FDADTC
• Shamburek: much of practice of medicine is “routed through physician”; genetic testing can follow same pathway for certain tests #FDADTC
• Netto: needs to be sure consumers are told that a test, delivered to clinician, will wind up in medical record #FDADTC
• Panel now discussing whether people test DTC b/c they are trying to avoid putting information in medical record #FDADTC
• (Interesting panel so reluctant to limit access of test to targeted pop’n-want wide access-but not concerned w/ limiting in toto #FDADTC)
• Panel seems to agree: can regulate test, marketing claims – but once test out there should be available to everyone #FDADTC
• Panel: going to be hard to define which pop’n is target? how would FDA be able to control/limit avail of testing? #FDADTC
• Q from FDA: Should test for rare conditions/marker be offered only to pop’n with higher prevalence of condition/marker? #FDADTC
• Shambuurek: suggests NIH genetic testing registry as place to provide info for confirmatory testing, follow up info for patients/MDs #FDADTC
• Panel qs: will consumer have option to order competitor’s test to confirm? How will this happen? Will result in unnecessary testing? #FDADTC
• Ransohoff: in general, confirmatory testing imp. But FDA needs to tie to the clinical significance, risk of the test-case-by-case #FDADTC
• Panelists: confirmatory testing very important; responsibility should be on cos to provide confirmatory testing #FDADTC
• (Prediction: panel will favor confirmatory testing #FDADTC)
• Q from FDA to panel: how to address false positive rate in rare disease pop’n? Should there be confirmatory testing in this situ? #FDADTC
• Question from FDA to panel: “what are essential risk mitigation tools to providing DTC genetic tests?” #FDADTC
• (The panel keeps coming back to “how do we know these tests actually work?” FDA keeps saying – we’re going to regulate like devices #FDADTC)
• Gutierrez: accuracy/validity of test will be regulated by FDA. For high-risk (Class I) will be on cos to prove safety, efficacy #FDADTC
• (Unfortunate that panel didn’t take up House’s suggestion to use consumer-demonstrated education as a form of mitigation #FDADTC)
• Gutierrez: clarifies re: labeling. For FDA “labeling” means everything, including advertising #FDADTC
• Ransohoff: will FDA judge the genetic test “package” or each individual test w/in that package/test panel #FDADTC
• Ransohoff: heard good exs of mitigation from Benson’s (FDA) talk this AM. But FDA needs to consider every single SNP/claim on panel #FDADTC
• (House w/ a really interesting suggestion. Similar to what PGP requires in the form of an entrance exam http://bit.ly/i8NOV3 #FDADTC)
• House: can FDA req patient to pass some type of screening/educational exam prior to ordering a test DTC to address info concerns? #FDADTC
• Hejazi: what about Humanitarian Device Exemption route for DTC? Gutierrez: doesn’t think cos limiting to small enough pop’n #FDADTC
• Waterson/Mansfield: here we’re talking about hypothetical. If FDA *does* permit some tests DTC, what mitigation measures req? #FDADTC
• D’Agostino: clarifying that yesterday we recommended most tests should *not* be DTC. Did this change? #FDADTC
• Shamburek: addition to pre-test info, labeling, will need to be confirmatory testing in many cases. That risk/cost must be shared #FDADTC
• Boughman: will depend heavily on FDA to evaluate proprietary algorithms. Davis: labeling needs to be appropriately simple #FDADTC
• Q to panel: when might info to consumers about risks/benefits be sufficient to allow for DTC genetic testing? #FDADTC
• Panel in general agreement re: need for truth in labeling/advertising for genetic tests – necessary but not sufficient for DTC path #FDADTC
• For #FDADTC, clarified during break: FDA appears to be leaning toward DTC as home use kit (for DNA collection) + med device (for claims)
• Shamburek: if truth in labeling, consumers can understand some tests / FDA can work w/ FTC to ensure this #FDADTC
• Panel now considering second of charged questions: http://bit.ly/hvOR9Z Basically: what mitigations avail for DTC tests #FDADTC
• Netto: another issue: DTC means results don’t necessarily wind up in medical record. (True but may be a reason some desire DTC) #FDADTC
• (Very difficult to see how that model doesn’t bankrupt both FDA & any test sponsor. However, know FDA is looking at alternatives #FDADTC)
• (Heard FDA – I think Philip – confirm that each new variant, claim needs to be submitted, validated, approved separately. #FDADTC)
• (This followed by minimal discussion of how to deal w/ adding new variants, claims to massively multiplex/WGS testing #FDADTC)
• Netto: Very difficult to separate these two. Ultimately, have to look at each test independently. #FDADTC
• Netto: clarifying, again, that genetic tests *will* be regulated. Issue whether MDs involved in order/interp. #FDADTC
• Ransohoff: is idea that if risk isn’t great, DTC bar gets lowered? Gutierrez: yes, but still concerned w/ truth & accuracy of claims #FDADTC
• Gutierrez: this is q for today. What are DTC test sponsor’s responsibilities? How can FDA mitigate risk & help ppl understand test? #FDADTC
• Ransohoff how will genetic test complexity be digested by cos/FDA before reaching indiv? If MDs can’t understand, is anything DTC? #FDADTC
• (This is the akin to the notion of personal utility that the panel seemed not-so-interested in when discussing DTC yesterday. #FDADTC)
• Panelist (Hersch): future risk can be clinically significant b/c it makes people to make all kinds of decisions about what they do. #FDADTC
• Philip: some of those claims could be prevention claims – which would be clinically significant. #FDADTC
• Mahowald: how is a test clinically significant when somebody could not become symptomatic for decades? (Or is already symptomatic?) #FDADTC
• Philip: even in asymptomatic pop’n, need to lay out intended use. FDA looks at if in target pop’n test will give clin. sig. res. #FDADTC
• Mahowald: What constitutes clinical use? For long-term risk assessment, w/ clinical application long in future, is that clinical? #FDADTC
• Panelist (Mahowald): still trying to get a handle on intended use. Intended use refers to clinical indication? #FDADTC
• Philip: We’ll look @ analytical validation for future tech (incl. WGS), but need input re: validation (analytical/clinical) of tests #FDADTC
• FDA (Philip): we know WGS is at the door; have started looking at validating this technology. E.g. have cleared 60 mutations for CF. #FDADTC
• Panelist (Tsongalis): how will you move from SNP/single-trait testing to massive multiplexing, whole-genome sequencing? #FDADTC
• Gutierrez: In end, we will make public our reviews, incl. bases we found something sub equivalent (510(k) and/or safe & effective. #FDADTC
• Gutierrez: cos will offer reg submissions; FDA will work w/ cos to shape those. Point of mtg, to help FDA do this #FDADTC
• Gutierrez: FDA on record of saying that DTC genetic testing should be regulated. Talking w/ cos about how to comply #FDADTC
• (A bunch of back-and-forth between panel and FDA – particularly Gutierrez. Will try to summarize for #FDADTC)
• Seems likely for non-clinical, incl. n-c DTC RT @RDGene: Gutierrez states that some low risk genetic tests may be considered Class 1 #FDADTC
• Gutierrez: considering how to down-regulate where possible ;have considered panels to help set correct reg (in context of LDTs) #FDADTC
• Gutierrez: FDA regulates based on risk. Depends on intended use; try to not make extra work for ourselves, get to appropriate risk #FDADTC
• Panel q from Hejazi (industry rep): asking how agency intends to regulate genetic tests? #FDADTC
• Gutierrez: part of FDA’s mission, since 1976, to regulate all in vitro diagnostics for safety, efficacy. Genetic tests included. #FDADTC
• Panel q: what prompted FDA to start regulating prescription genetic tests (IVD tests)? #FDADTC
• (Job got in the way of #FDADTC this morning. Back in the room now & catching up thanks to tweets from @aliciaault and @RDGene)
• GLR Post: Looking Ahead After the FDA’s DTC Meeting: http://bit.ly/hiK5te #FDADTC
• After very long day at #FDADTC, here are my 1st thoughts: http://bit.ly/hiK5te Take-away for DTC proponents: don’t panic.
• Quick & on point RT @dgmacarthur: My attempt to piece together the early events from day one of the #FDADTC meeting: http://bit.ly/fVNcsy
• RT @MishaAngrist: “Making movies” My take on the FDA-23andMe-Congressional Hearings contretemps. http://bit.ly/dOyi22 #FDADTC
• That’s the close of the #FDADTC discussion for today. Panelists reminded once against not to discuss subject matter of mtg outside of panel
• Query: is personal utility (i.e., satisfaction) other side of anxiety? If anxiety considered shouldn’t personal utility be as well? #FDADTC
• Boughman: avoid paternalism: distinguish between data showing anxiety vs. anticipation of anxiety #FDADTC
• Lipkin: data on anxiety doesn’t meet criteria for clinical significance Waterson: but tests weren’t for serious traits like BRCA #FDADTC
• Next q for panel: should anxiety be considered in assessment of safety and effectiveness? #FDADTC
• Waterson: “sense I’m getting from committee” is to not include personal utility in considering clinical significance #FDADTC
• Ransohoff: personal utility is important, but also very susceptible to marketing manipulation. #FDADTC
• FDA clarifying for panel statutory definition of clinical significance. Netto: on that definition, no evid of clinical sig for DTC #FDADTC
• (Waterson: does FDA have statutory authority to consider personal utility? Mansfield: “assume that we do.” #FDADTC)
• Next panel question: should personal utility be incorporated in considerations of “clinically significant results”? #FDADTC
• Important clarification from panel: is “physician” the individual’s physician, or a company physician? #FDADTC
• House is consistent voice of disagreement; thinks patients sophisticated enough to understand when clinical consult needed #FDADTC
• (Most panelists seem to think that, regardless of DTC ordering, results should be returned through physician #FDADTC)
• Ng: any result w/ a high predictor a person will develop a disease, w/ clinical utility, needs to be funneled through physician #FDADTC
• Mansfield: “routing through physician” means report results to physician *only*; MD decides whether/how to pass to patient #FDADTC
• (Waterson offers that ordering must be by provder; two panelists quickly disagree – if reviewed by provider then ordering DTC OK #FDADTC)
• Next question for panel: are there tests that can be ordered DTC as long as results are reviewed by clinician? #FDADTC
• Waterson: “I don’t know if I’m getting a clear sense” on nutrigenetic testing. Concerns around testing claims, not test themselves #FDADTC
• Mansfield: clarifies again that for all tests FDA intends to regulate to ensure analytical/clinical validity. Q is avail of DTC path #FDADTC
• Panel is treating “nutrigenetic” as a bit of a catch-all category for testing that seems “health-related,” but maybe not clinical #FDADTC
• Shamburek: thinks generally low risk, but still concerned about underlying analytical/clinical validity of nutrigenetic tests #FDADTC
• Nutrigenetic discussion turning to MTHFR-folate testing, recommendations. #FDADTC (panel jumping around quite a bit right now)
• Final part of question #1: what about nutrigenetic tests? Should those be available DTC w/out clinician guidance? #FDADTC
• Continue to think Waterson (#FDADTC panel chair) oversimplifying range of views, opinions raised by panel. To be fair he has impossible task
• Waterson: “getting the panel’s sense again that [PGx] should, for time being, be under MD/provider purview” #FDADTC
• Boughman: asks for clarification from FDA re: labeling for PGx tests. Mansfield: most PGx tests described not req (but see Abacavir) #FDADTC
• Panelist: aren’t there Hep-c, HIV tests offered DTC? Mansfield: over-the-counter, not DTC. (Promises to clarify distinction tom.) #FDADTC
• Next category: PGx testing. Does risk of offering PGx tests DTC outweigh the benefits? #FDADTC
• Mansfield: we’re looking for weight of risks/benefits of DTC channel, not whether the tests are safe. #FDADTC
• Hejazi: if we req genetic testing through physician, what about ppl who do not have a physician/hc coverage? How do they get data? #FDADTC
• Mansfield: we cannot consider cost of test in determining regulation. Panel: cost as means of data avail still part of pro/con #FDADTC
• Tiffany House (patient rep): can’t wait to have all of the answers, b/c we will never have all of the answers #FDADTC
• RT @DNAlawyer: FYI Shuren’s testimony in July said FDA focuses on tests “intended for use” http://1.usa.gov/dSXqfQ not possible medical use
• (And a helpful clarification from Mansfield: what matters is *intended* use, not clinical significance. #FDADTC)
• (What’s not clear from FDA: is it *possible* clinical use or *intended* clinical use that labels a test “clinical” for #FDADTC purposes?)
• Panelist rightly challenges Mansfield. You cannot necessary separate out clinical from non-clinical. #FDADTC
• Mansfield: clarifying what FDA does / does not consider clinical DTC tests (FDA not interested in non-clinical tests) #FDADTC
• (Boughman’s arg seemed to be data is too complex for DTC delivery. Interested consumers should work through trad’l HC channels #FDADTC)
• Joann Boughman, ASHG: do consumers have “right to know”? Not ready for DTC. Motivated ppl can advocate through traditional HC system #FDADTC
• Panel now considering DTC w/out clinical involvement for susceptibility testing (FDA’s ex: APOE/Alzheimer’s) #FDADTC
• (Waterson has twice declared “consensus” despite disagreement from other panelists, as well as less than half the panel weighing in #FDADTC)
• Waterson (chair): again declares consensus on pre-symptomatic testing-through docs, not DTC. #FDADTC
• (One theory: #FDADTC panel gravitating twd Huntington’s b/c monogenic, bright-line disease/test? Easier to analyze, ‘tho not good DTC model)
• Panel does seem in agreement that Huntington’s testing shouldn’t be DTC (Curious if this is even avail DTC? Anyone know?) #FDADTC
• Mary Mahowald arguing that some pre-symptomatic testing (incl. BRCA) could be offered DTC, in some circumstances #FDADTC
• (Exs FDA provided for panel to consider for pre-symptomatic testing category: BRCA, Huntington’s #FDADTC)
• Not sure we reached any consensus, but moving on: value of offering pre-symptomatic genetic testing DTC w/out clinician involved #FDADTC
• (A critical point, added as a clarification, from Gutierrez. No “enforcement discretion” for genetic testing. Issue is avail of DTC #FDADTC)
• Gutierrez: clarifies that whether FDA will regulate companies is *not* on table. Issue is whether the DTC pathway will remain open #FDADTC
• Several panelists object to “consensus”. Led by Tiffany House, panel’s lone patient rep. Concerned some MDs won’t prescribe tests. #FDADTC
• Waterson (chair) concludes there is a consensus that carrier testing should not be DTC for now. #FDADTC
• (Get sense panelists are feeling rushed, pressured to make recommendation on very complex area/very quickly. AG trying to reassure #FDADTC)
• Alberto Gutierrez, OIVD: what FDA looking for is general concepts; is it possible to move ahead w/ DTC in these categories or not? #FDADTC
• Panelist: 5-10 years before able to make definitive determinations; caution first, then make recommendations much later #FDADTC
• Several panelists: even w/in category of carrier testing, must go through each test one-by-one & make DTC determination-No shortcuts #FDADTC
• First comments from panels industry rep, Shahram Hejazi (http://bit.ly/dGXLcp) – focus on clinical validity #FDADTC
• (Last tweet was confusing: the panel is 22 ppl. Going to be tough to build consensus from such a large group. But good discussion #FDADTC)
• Not surprisingly, appears to be no clear consensus from the panel on appropriateness of DTC carrier testing (of nearly 2 dozen ppl) #FDADTC
• Tiffany House (patient rep on panel; Int’l Pompe Association) supports DTC availability provided there is full, complete disclosure #FDADTC
• Panel discussion fairly wide-ranging; panel chair (John Waterson, Children’s Hospital Oakland) doing a good job trying to focus #FDADTC
• Panel to consider each question in context of 1) carrier, 2) pre-symptomatic, 3) susceptibility, 4) PGx & 5) nutrigenetic testing #FDADTC
• First #FDADTC question is, essentially, what are risks/benefits of offering different types of DTC genetic tests w/out clinician involvement
• #FDADTC resumes. The panel is now going to be discussing the first of two charged questions (see: http://1.usa.gov/hvZmc9)
• Good panel q moving us away from discussion about how to interpret genetic information to where consumers belong in the picture #FDADTC
• Gulcher: GWAS is essentially over; we’re now into WGS. (Notes decode sequencing Icelandic population-2,500 WGS, imputation of rest) #FDADTC
• Back-and-forth re: DTC genetic testing & risk prediction w/out family history, etc. Gulcher: add’l info valuable; panel skeptical #FDADTC
• Gulcher of deCode response: DTC genetic test not a substitute for traditional clinical guidance; a supplemental service #FDADTC
• Response to panel q, JG of CRG criticizing DTC companies for only providing “part of the whole”; genetic data, but not FH, env data #FDADTC
• Unfortunately, no. Public mtg not as public as it might be. RT @bigs: .@genomicslawyer is there a video feed for #FDADTC?
• panelist q: any lawsuits against @23andMe claiming damage? Gould: no, none. #FDADTC
• Q re: non-paternity disclosure through DTC testing. AG: that’s part of the risks we disclose in consent to test process #FDADTC
• AG: thinks DTC well positioned to collect long-term outcomes data; outcomes data reporting a good form of oversight #FDADTC
• Panelist offering two anecdotes of patients who came with @23andMe data; one positive outcome, one misinterpretation. #FDADTC
• True, generally. But clinical blurs that line RT @DNAlawyer: In commerce setting, the q is capacity to consent, not informed consent #FDADTC
• AG of @23andMe: genetic testing can be used to confirm/contradict family history; also many customers who are adopted & have no FH #FDADTC
• Panel: “the cheapest genetic test is a good family history”; how does this compare to DTC genetic testing #FDADTC
• (These are important questions; clear need for stronger identity verification mechanisms in DTC genetic testing #FDADTC)
• Panel now asking about DTC genetic testing of minors, disabled adults – others who cannot provide informed consent. #FDADTC
• (For background, here’s the recent GLR post on this issue – surreptitious genetic testing: http://bit.ly/eAncsm #FDADTC)
• Panel q: how can we be sure that DNA being tested was provided by person purchasing the test? Challenge of identity verification. #FDADTC
• Panel distinguishing b/w studies testing for anxiety due to DTC (we have some) & long-term outcome DTC studies (we have none) #FDADTC
• Panel grilling Gulcher of deCode re: whether DTC results in harms. Gulcher agrees we need more long-term data, but no harms so far. #FDADTC
• AG: data owned by consumer; can be downloaded directly “Your data is your data” @23andMe also conducts opt-in research, internal R&D #FDADTC
• #FDADTC panelists now have opportunity to question the last group of speakers. First q, to AG: where does DTC data go & who owns it? #FDADTC
• AM: arguing for increase in funding, genetic testing training for nurses. (Another good point, but not sure FDA’s decision) #FDADTC
• AM: concerned about CLIA’s lack of PT for genetic testing, different pathways for IVD kits, LDTs (imp points, but more #FDALDT than #FDADTC)
• AM: focus on 1) role of nurses (largest HC gropu) in genetic testing, 2) who should order & 3) ANA perspective on DTC model #FDADTC
• Now up, Ann Maradiegue, George Mason (http://bit.ly/hpA5kY), presenting on behalf of American Nurses Association #FDADTC
• DK: major limitations of the study – no longitudinal data; pressing need to collect more / longitudinal / outcomes data #FDADTC
• DK now providing more detail re: how GPPC evaluated DTC misunderstanding. 4% confused about high-risk, 7% confused about low-risk. #FDADTC
• DK: limitations of survey – single point-in-time, no follow-up; no data on specific tests, only aggregate data #FDADTC
• (Here’s a better link to the GPPC data presented at ASHG in 2010: http://bit.ly/hdoAK0 #FDADTC)
• Now up, David Kaufman, JHU Genetics & Public Policy Center. Discussing DTC survey results from 2010 ASHG mtg: http://bit.ly/eTofcV #FDADTC
• JG reading directly from CRG’s public record comments. You can find those here: http://bit.ly/dGvMH5 (so won’t live-tweet this one) #FDADTC
• Now up, Jeremy Gruber, Pres of Council for Responsible for Genetics #FDADTC
• LB: market forces will ultimately eliminate genetic tests that are not valuable; but (reasonable) oversight still needed #FDADTC
• (LB’s def of genetic test is a single indication/intended use. Result: many tests will be dozens->hundreds->thousands of tests #FDADTC)
• LB: high-risk tests should not be DTC; low- & moderate-risk tests should be registered w/ FDA & be conducted in a CLIA lab #FDADTC
• (LB outlining a proposal for DTC regulation that sounds very similar to risk-based approach FDA discussed for LDTs last summer #FDADTC)
• LB: FDA interested in protecting public health; arguing “empowering individuals to maintain good health is in the public interest” #FDADTC
• (Note Interleukin is one of a very few publicly traded companies offering clinical DTC genetic testing – possibly the only one? #FDADTC)
• Now up, Lewis Bender, CEO of Interleukin Genetics (co offers single-condition DTC tests) #FDADTC
• AG: “genetic information provided DTC should be held to the same standards as genetic information provided in a clinical setting.” #FDADTC
• AG: urging flexible, forward-looking policy & regulation. Proposing a working group for defining clinical validity #FDADTC
• AG: regulation needs to be based on data, not on unsubstantiated fears/concerns; also need to recognize benefits of DTC #FDADTC
• AG: we have >75K genotyped customers, and we have no evidence that there are real, demonstrable risks from DTC genetic testing #FDADTC
• AG: we believe people have a “fundamental right” to access their own DNA. That right incl accurate, reliable genetic information #FDADTC
• AG: we consider ourselves industry leaders w/ regard to transparency, but always room for improvement. Opp for better edu, clarity #FDADTC
• AG: we use definitions/disclaimers – we are clear about what we do/do not test for; highlighting info comm tools #FDADTC
• AG: highlight the likely transition from genotyping to whole-genome sequencing; will impact how we think of validity #FDADTC
• AG: reg framework for all genetic testing cos (not just DTC) need clear standards for analytical, clinical validity #FDADTC
• You can find AG/@23andMe slides here: ( http://bit.ly/dLnFzJ ) AG: working w/ FDA on regulation, believe we have a path to approval #FDADTC
• Now up, Ashley Gould, GC of @23andMe #FDADTC (for those not here, the public presentations are very short, rushed)
• JG sharing his personal encounter with genetic testing/healthcare. Information DTC, but actual treatment requires clinician #FDADTC
• Written public comments in favor of DTC: http://1.usa.gov/eB9gMe (Mary Pendergast), http://1.usa.gov/ffgVf7 (Kevin Davies) #FDATDTC HT @shwu
• #FDADTC resumes with public presentations. First is from Jeff Gulcher of @decodegenetics re: DTC genetics for common diseases
• Damn good question. RT @wimufi: FDA staff not supposed to discuss topic, among themselves or with public, during lunch … Why? #FDADTC
• (Taking a lunch break at #FDADTC. “Open public hearing” starts after lunch. See: http://1.usa.gov/evayRl)
• (On physicians and genetic testing, take a look at this from @pgx_reporter: http://bit.ly/eBaokC – although not necessarily DTC
• Q: what about studies examining response of physicians to genetic testing results, incl DTC? CB: not aware of anything specific #FDADTC
• Q: how was @Navigenics chosen as the test for the Scripps study? CB: @EricTopol approached major DTC companies, Navi was interested #FDADTC
• CB says findings are consistent w/ existing lit on impact of genetic testing (not just DTC). (That’s true, but very ltd data) #FDADTC
• Panel pressing CB on very short (3 mo) time between testing & follow-up. CB agrees it’s a very fair point #FDADTC
• CB: overall result of DTC genetic testing in the Scripps population? Not a large impact one way or the other #FDADTC
• CB: sharing test results w/ physician was associated w/ some changes (e.g., exercise); sharing w/ GCs did not. But needs follow up #FDADTC
• CB: sharing test results with healthcare providers? Only 10% sought (free) genetic counseling; >25% shared results w/ physician #FDADTC
• CB: changes in behavior as result of screening? plenty of intent to change, but not nearly as much actual change #FDADTC
• CB: showing data on anxiety levels resulting from testing for different sub-groups; general lack of increase in anxiety in cohort #FDADTC
• CB: 5,000 enrolled, 3,400 viewed results, just over half were avail for follow up #FDADTC
• CB: a second disclaimer, while showing @Navigenics screenshots, that Scripps did not evaluate the Navi product itself #FDADTC
• (CB describing use of Navigenics test in Scripps study; keep in mind that this was the test version circa 2008 #FDADTC)
• CB: also unlike Multiplex Initiative, Scripps study was not free to participants – prices ranged from ~$150-$500 #FDADTC
• CB: sample was limited, not selected from within known population (as was the case with Multiplex Initiative) #FDADTC
• CB: emphasizes that the study did not evaluate the Navigenics test that was used for SGHI (incl. clinical validity, etc. of test) #FDADTC
• CB: lack of data on consumer response to DTC; that’s where Scripps Genomic Health Initiative (SGHI) comes in http://1.usa.gov/fDJyoy #FDADTC
• CB: presenting data from the Scripps/NEJM DTC study. Starting with overview of “personal consumer genetics” #FDADTC
• Final speaker of the morning: Dr. Cinammon Bloss speaking about recent Scripps/NEJM (http://bit.ly/hUIuBi) HT @EricTopol
• CM: MI emphasized that genetics only part of the story; need to also have full family history, talk to healthcare provider #FDADTC
• CM: MI was free, used a limited set of markers/traits, all participants were insured. #FDADTC
• CM: BUT the Multiplex Initiative has several crucial differences from current commercial DTC genetic tests. #FDADTC
• CM: public *should* be able to understand limits of genetic testing. (We are obliged to give them info needed to understand) #FDADTC
• CM: recommendations from Multiplex Initiative for DTC? DTC “may be OK” if appropriate presentation of results, pros/cons & support #FDADTC
• CM: take home messages: 3) testers can understand the limits of tests, feedback following testing #FDADTC
• CM: take home messages: 1) lots of self-selection in pop’n 2) effective communication provides adequate support #FDADTC
• CM: not a high level of emotions resulting from participating, but where expressed they were general positive #FDADTC
• CM: w/ prompting, “virtually everyone” could describe whether or not they had a particular variant for a particular health condition #FDADTC
• CM: followed up with participants to evaluate their unprompted/prompted recall of pers results from MI – great idea #FDAMTC
• CM: low-education, male were traits that reduced participation in MI #FDADTC
• CM: taking pains to point out that MI was not a study of the “worried well”, though did have high understanding of genetics #FDADTC
• CM: detailed review of multiplex initiative study aims, designs #FDADTC (Background info here: http://1.usa.gov/hXOUzX)
• CM: involved oversampling of traditionally under-represented groups in genetic testing #FDADTC
• CM: Multiplex Initiated in light of arrival of DTC. Develop an ideal pop’n sample: eliminate barriers, ensure informed consent #FDADTC
• Now up: Colleen McBride, NHGRI, talking about Multiplex Initiative #FDADTC
• (I’m speaking next at #FDADTC so won’t be Tweeting – I can multi-task, but not quite that well. My slides are here: http://bit.ly/fcPUyI)
• NW ultimately making standard arg. for involvement of healthcare providers in DTC. But her exs, evidence leave much to be desired #FDADTC
• True. RT @aliciaault: Wexler did start out describing her biases on testing: family hist of HD & basic bias against industry. #FDADTC
• Panel member pressing NW on her paternalistic stance – denying individuals access to genetic information. #FDADTC
• NW: people don’t understand genetic testing; we need to pull back on all of this. No more “spit parties” #FDADTC (The rhetoric continues)
• (Respect NW’s contributions to science but cannot credit her understanding or analysis of where DTC is or what it’s motivations are #FDADTC)
• NW accuses DTC of “raping the human genome project” (did I possibly hear that correctly? can anyone confirm?) #FDADTC
• NW: DTC companies should be closed and DTC should be eliminated. DTC preys on our worst aspects, prey on snobbery & the rich #FDADTC
• (For ref: MyGeneProfile is a Singapore-based company & a pure scam. #FDADTC needs to address this, but hardly representative of industry)
• NW now moving on to GAO report on DTC genetic testing #FDADTC
• (Disappointed that NW drawing all of her conclusion about state, risks of DTC from MyGeneProfile #FDADTC)
• (My opinion: irresponsible of NW. Not a US company, not representative of DTC. Not even sure MyGeneProfile is an actual company. #FDADTC)
• NW is now showing MyGeneProfile (complete genetic scam, see @dgmacarthur: http://bit.ly/f58AYH) as representative of risks of DTC #FDADTC
• NW drawing direct line b/w exp. of friend w/ HD who committed suicide to DTC tests on shelves of Wal-Mart. I can’t make that jump #FDADTC
• NW speaking broadly about HD testing concerns. Share many, but agree w/ @lindaavey that not best model w/ which to debate #FDADTC oversight
• That doesn’t surprise me – I don’t know of any. RT @DNAlawyer: @genomicslawyer No huntington DTC test at of 5/2010: http://bit.ly/dSSAIf
• (Not aware of any providers offering testing for Huntington’s DTC. #FDADTC)
• NW: describing guidelines for Huntington’s Disease testing, including privacy & informed consent requirements. #FDADTC
• (RT @mary_carmichael: As #FDADTC gets hashed out, @virginiahughes takes a thoughtful tour of her @23andMe results: http://bit.ly/hqTwxM)
• NW focusing on Huntington’s disease gene discovery, a process in which she was instrumental. #FDADTC
• NW now describing her involvement in, history of the Hereditary Disease Foundation: http://bit.ly/gBF15R #FDADTC
• NW speaking personally, with own biases/fears. But believes those are shared by everyone with DNA. (Not sure I agree. At all.) #FDADTC
• Now up at #FDADTC, Dr. Nancy Wexler, Columbia: “Toxic Information: Handle With Care”
• (GLR post from 1 year ago, on why markers of DTC industry failure aren’t really: http://bit.ly/dtqTes Analysis hasn’t changed since #FDADTC)
• SH: thinks the fact we have no data is indicative of lack of enforcement – regulation improves data-gathering #FDADTC
• Q for SH: do we know anything about volume of cross-border activity for DTC genetic testing? SH: no. (I’d give same answer) #FDADTC
• Q for SH: why does UK have such a light touch on DTC? SH: historical (e.g., eugenics) & cultural factors are stronger elsewhere #FDADTC
• Questions from panel to SH focusing on appropriateness of clinical utility as a standard for DTC genetic testing regulation #FDADTC
• SH’s closing thought: “let’s try to avoid disaster” (although not clear what, exactly, the disaster to be averted is) #FDADTC
• (I disagree fairly strongly w/ SH on that point. @23andMe continues to raise money, deCodes bankruptcy not tied to DTC, etc. #FDADTC)
• SH: arguing DTC doesn’t work by pointing to Sciona struggles, @23andMe layoffs & @decodegenetics bankruptcy. #FDADTC
• SH: thinks enforcement will grow if DTC market grows, but SH skeptical that DTC will stick. Thinks business model entirely unproven #FDADTC
• SH’s conclusions: # of DTC companies, countries regulating DTC both increasing. But rulemaking, guidance does not equal enforcement #FDADTC
• SH: like SACGHS, HGC now being wound up. UK may be unique in world in diminishing its oversight of DTC over the past 15 years #FDADTC
• SH: key issue of divergence: tests need to be delivered w/ clinical supervision? (Agree: the most contentious issue in US too) #FDADTC
• SH: main reason HGC went with guiding principles as opposed to (binding) code of practice? Nobody to enforce code of practice #FDADTC
• SH: the revised HGC recommendations were designed with an int’l market in mind, along with participation from DTC industry #FDADTC
• HGC updated its report, recommendations last year w/ “A Common Framework of Principles for DTC genetic testing http://bit.ly/ePPe6j #FDADTC
• SH describing story of Sciona, HGC public consultation on DTC genetic testing (see: http://bit.ly/eOVKf7) #FDADTC HT @eurogene @RDGene
• SH shifting now to soft law approaches: voluntary codes of practices, guidelines, etc. UK has engaged this route frequently #FDADTC
• (Australia’s model is what FDA’s LDT guidance could very well resemble see: http://bit.ly/b8Fr3j #FDADTC)
• SH: TGA participates in standard setting, can intervene if there is a concern. #FDADTC
• SH: AUS classed LDTs as med devices; high-risk reviewed by TGA (FDA equiv); med- & low-risk registered w/ TGA, eval by industry. #FDADTC
• SH now looking at Australia’s new IVD regulatory framework; restricts certain types of IVD self-testing (incl. genetic traits) #FDADTC
• SH: European Commission has suggested there might need to be special measures for DTC genetic testing #FDADTC
• SH’s overview of EU device regulations – the current ones aren’t very good; but European Commission attempting to strengthen #FDADTC
• SH: if we want to stop “bad tests getting on the market” we need to look to IVD regulations. Comparing EU, AUS, US #FDADTC
• SH: does not know of any enforcement activity of genetic testing regs in any of these countries, apart from South Korea #FDADTC
• SH: common themes: restrictions on who can test, standards on genetic testing, some tests more imp than others (e.g., screening) #FDADTC
• SH: South Korea apparently has a blanket ban on DTC genetic testing #FDALDT
• (Incidentally, I agree with SH: sometimes surprisingly difficult to get info on int’l regulatory developments, esp outside of EU #FDADTC)
• SH now flitting out of Europe & over to South Korea (although caveats that he has not confirmed the data); SK banning some tests #FDADTC
• SH: most recent piece of legislation is Germany’s genetic diagnosis act. (For detailed GLR coverage, see here: http://bit.ly/gXMgkg) #FDADTC
• (Most of the legislation/regulation SH is discussing also share common themes of informed consent, clinician involvement, bioethics #FDADTC)
• (Note that most of the legislation SH is discussing is quite old, esp by DTC timelines – e.g., Belgium’s dates from ’87 #FDADTC)
• SH now shifting to nat’l legislation efforts on genetic testing (mostly in Europe) – whirlwind tour #FDADTC
• SH: Current status of CoE protocol? So far only 5 member states have signed protocol, & only 1 has ratified. So not yet implemented #FDADTC
• SH: CoE generally permits genetic testing only w/ direct clinical supervision; some exceptions, but not if clear clinical importance #FDADTC
• SH’s next stop: Council of Europe Additional Protocol on Genetic Testing (2008, see http://bit.ly/i8ReIE) #FDADTC
• SH: OECD now discussing how to revise guidelines. One q: is WGS opening up new issues that require revision? (My answer: absolutely) #FDADTC
• SH: int’l treaties standards developed. Starting w/ proposal from OECD (see: http://bit.ly/fS7I27) & supplement implementation #FDADTC
• SH tackling recent developments from all over the world – Germany, UK, Japan, Aus. (Ambitious proj, given diversity of approaches) #FDADTC
• SH: what are our options? Do nothing; ban it; or set some rules (feat. a slide with 10 commandments. FDA guidance from on high?) #FDADTC
• SH: outlining gaps in regulations, including devices, labs. Many countries don’t have anything as comprehensive as CLIA. #FDADTC
• SH: where does DTC fit in existing regulatory landscape: med devices (FDA), lab devices (CLIA), codes of practice (soft law) #FDADTC
• SH: DTC has become focal point for regulation of genetic testing – a debate that dates to at least the 90s (IOM report) #FDADTC
• Now up at #FDADTC, Dr. Stuart Hogarth, Kings College on “Regulating consumer genetics – an overview of global trends”
• DTC company @23andMe has posted its presentation materials in advance of #FDADTC meeting: http://bit.ly/dLnFzJ
• TM: “I’m not that familiar with the type of claims these [DTC] companies are making” #FDADTC
• Thankfully, #FDADTC panel now pressing TM for how DTC is using this GWAS data, whether DTC cos’ claims match the data
• (TM finishes w/, by my count, a single tangential ref to DTC. Think a missed opportunity to tie NHGRI’s scientific expertise to #FDADTC)
• TM: several limitations of GWAS-identified markers for risk assessment – non-determinitive, don’t explain full variability, etc. #FDADTC
• TM now moving on to “the case of the missing heritability” at #FDADTC, with nice HT to @bmahersciwriter
• (TM’s comments on GWAS/SNP discovery also yet to address relationship to DTC – what is being tested, quality of testing, etc. #FDADTC)
• (TM’s talk on history/state of GWAS quite comprehensive. Let’s hope she turns forward to WGS tech, implications before time is up #FDADTC)
• “Cue Music: stuck in a (regulatory) moment. The FDA & oversight of DTC genetic tests” http://bit.ly/eCKjvv @DNAlawyer’s thoughts on #FDADTC
• TM now discussing HapMap. Diving deep into underlying science (although slides on HapMap, seq cost, GWAS associations 4 years old) #FDADTC
• TM: providing the panel with a high-level overview of GWAS methodology, progress over past 5-10 years. (Reflects diversity of #FDADTC panel)
• Now up at #FDADTC, Teri Manolio from NHGRI. Starts w/ scientific basis – relationship between GWAS and DTC
• Panel q: what is a “medical claim”? LM: any claim that arises from a device deemed to be a medical device under FDA regs #FDADTC
• (So does that mean LM/FDA have determined that anything DTC is inherently a medical device & subject to related regulations? #FDADTC)
• LM: we have “already determined” that “enforcement discretion” is not an appropriate model for DTC testing #FDADTC
• LM: very difficult for FDA to track the DTC market; continually having to scan the web & other sources to determine who is out there #FDADTC
• Panel q for LM: how “massive” is this DTC problem, really? LM: were far more companies; believe a number have left DTC model behind #FDADTC
• (Overall, LM’s talk comprehensive background, well-balanced. FDA hitting right notes at opening of #FDADTC)
• Panel q to LM: is the consumer the person ordering the test, or the person whose DNA is tested? LM: expects them to be the same… #FDADTC
• (You can find full text of 3 questions to #FDADTC panel on pg 4/6 here: http://1.usa.gov/h6WYm3)
• LM: 3 primary qs to panel: risks/benefits of (1) clinical DTC w/out MD, (2) possible misunderstanding, (3) scientific standards #FDADTC
• LM: so why is FDA here? To here discussion/perspectives from panel, public. Wants discussion of “difficult issues” in #FDADTC
• LM: FDA must do this while keeping up with technology, promoting innovation #FDADTC
• LM: regardless of who orders a test, it is essential that FDA determine medical claims are correct & valid #FDADTC
• LM: WGS now “widely available” – WGS platforms’ performance not well understood; none are cleared by FDA #FDADTC [though cos working on it]
• LM providing overview of tests avail DTC, incl. clinical/non-clinical distinction. FDA focused on tests meeting def of med device #FDADTC
• (Good to see Mansfield acknowledge inevitability of WGS, changes in DTC models/marketplace. #FDADTC)
• LM: number of DTC companies has “likely narrowed” due to FDA’s oversight; but technologies (inc. WGS) are changing the field #FDADTC
• LM: working w/ DTC companies to comply with medical device regulations; has been a challenge for both FDA & companies #FDADTC
• LM: “There is a place for DTC genetic testing, but appropriate oversight should apply to [protect individuals]” #FDADTC
• LM: today, DTC remains as business model. Aware of various public positions pro/con on DTC. #FDADTC
• LM: on 2010 GAO report – “FDA briefed generally, not aware of specific findings in advance of House hearing” #FDADTC http://bit.ly/bfF7we
• LM: 2010, FDA sends numerous more “letters to industry” – many companies exit DTC market, others develop compliance plans w/ FDA #FDADTC
• LM: 2010, FDA learns of Pathway/Walgreens (http://bit.ly/uZQa9), sends “letter to industry” & meets w/ Pathway. Concl: DTC = risks #FDADTC
• LM: in 2009, FDA began sending “it has come to our attention letters” and meeting with DTC companies – cos claimed LDT status #FDADTC
• (For a fuller overview of the background Mansfield is providing, see this post http://bit.ly/hfZquo #FDADTC)
• LM: 2007, we moved beyond nutrigenetic; CLIA issues; state (NY/CA) enforcement #FDADTC
• LM: starting off the history of DTC, all the way back to…2006. (We haven’t been at this all that long) #FDADTC
• Mansfield: def of DTC: tests ordered directly by individual, w/out prescription; results received by individual without help of MD #FDADTC
• Now up, Dr. Liz Mansfield: “Why are we here? History and current landscape of DTC genetic tests” #FDADTC
• (Unfortunately, there is no live webcast at #FDADTC)
• Kicking off #FDADTC mtg here in DC: http://bit.ly/iiJIC0 Right now, reviewing exec summary: http://1.usa.gov/h6WYm3
• Also, for those who are interested, I’ve posted my #FDADTC slides in advance of tomorrow’s talk: http://bit.ly/fcPUyI
• GLR Post: Charting a Path for DTC Oversight: http://bit.ly/iiJIC0 My thoughts in advance of the #FDADTC meeting
• RT @dgmacarthur: I adopt a tone of cautious optimism in advance of tomorrow’s FDA meeting on DTC genetics: http://bit.ly/fSkRYl
• Meeting materials for tomorrow’s #FDADTC mtg here: http://1.usa.gov/i24b7F If anybody knows of a webcast link, please lmk.

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

• Interesting. Dx version would be welcome: MT @BiotechPatent: Bipartisan Congressional #MedTech Caucus launches website: http://bit.ly/fbUeil
• RT @matthewherper: A Cancer Patient’s Quest Hits DNA Pay Dirt — or why Kathy Giusty and 38 genomes are so important. http://ow.ly/4lEuE
• RT @LifeSciVC: Not all about Tech; >200 new healthcare, wellness & life sci startups on AngelList. Pretty cool. @naval http://ow.ly/4l3wW
• RT @pgx_reporter: Celera Will Add to Quest’s MDx Capabilities; But Reimbursement Questions Cloud Revenue Contribution: http://bit.ly/gxJOOZ
• Part 2 of @Xconomy guest post on who will pay for drug development: http://bit.ly/gpvD3j
• RT @genomesunzipped: How does adding extra genetic information change our disease risk? @anderson_carl finds out: http://bit.ly/g6X4C3
• RT @ldtimmerman: SV Life Sciences, flush w/new $500m fund, on the hazard of having lots of dough when VC is struggling. http://bit.ly/ekMwbu
• Venture capitalists (via NVCA) concerned about impact of patent reform on inventors, start-ups: http://bit.ly/ed4cqA Cont. to wait on House.
• GLR Post: Considering the Impact of Yet Another Proposal for Genetic Legislation http://bit.ly/egqzi8
• RT @InSequence: BGI’s Sequencing Projects Tackle Genetic Roots of Cancer and Disease, Reference Organism Assembly: http://bit.ly/fatypL
• What’s next for CardioDx? CAD test adoption (here & in BRIC countries) + more/predictive tests. But no IPO: http://bit.ly/hoXNCs
• AMA lashes out against DTC genetic testing: a “weapon” & the “unauthorized practice of medicine”: http://bit.ly/dGeMJk HT @5amsolutions
• RT @GenomeInstitute: @GenomeInstitute’s Dr. Elaine Mardis interviewed about latest breast cancer sequencing work http://bit.ly/hwK5Rr
• Sequence Analysis 101: A newbie’s guide to crunching next-gen seq data: http://bit.ly/gVX6CL feat @dgmacarthur HT @gw_dailyscan
• Who’s Going to Pay for Future Drug Development (Part 1): http://bit.ly/fGV0Q8 in @Xconomy
• RT @dgmacarthur: Cool – @23andMe has used its participant data to find novel genetic associations with Parkinson’s: http://bit.ly/fvYENB
• Alnylam, UMass, and Others Settle RNAi Patent Litigation: http://bit.ly/dRjafg (from 3/15)
• Missed @Xconomy interview by @BVBigelow w/ social networking researcher James Fowler, who is working w/ @23andMe: http://bit.ly/esnwEV
• Thoughts from CardioDx, Genomic Health & others on challenges of commercializing genomic diagnostics (from 3/16): http://bit.ly/e1r6F6
• A reminder from @DNAlawyer that not all gov’t regulation (incl. #FDADTC) is necessarily authorized or unchallengeable: http://bit.ly/hBPzO9
• RT @GenomeWeb_News: AstraZeneca, @Sagebio Partner on Cancer Therapeutic Development: http://bit.ly/dIrFdK
• Last wk’s House jobs forum reminder some in DC see #FDADTC regulation as inhibiting job creation: http://bit.ly/fjLXwJ cc @PathwayGenomics
• Report from @PHGFoundation: Fair access to genetics needed in mainstream medical services http://bit.ly/dSSD7k
• RT @drjonboyg: get this job & be my boss. MT @girlscientist: Job open: NHGRI, Chief Policy & Program Analysis Branch http://is.gd/FBHOED
• Guest Post by @Navigenics GC: “Breast Cancer Counseling: Personalizing Med. Beyond BRCA Testing” http://tinyurl.com/65tct3o cc @alliejanson
• A new DTC entrant: RT @Lumigenix: Until 3/31 our Introductory kit is only $99 USD (normally $279). http://bit.ly/fVU7UK
• RT @genomesunzipped: Analysing your own genome, bloggers respond to the FDA and more reporting on bogus GWAS results http://bit.ly/fP4FtK
• RT @InSequence: BioNanomatrix Pockets $23.3M in Series B Funding http://bit.ly/fO9jHb
• BTW, that may be 1st attempt I’ve seen at valuing a personal genome. $20/day + 10% of earnings for an @kennethreitz clone
• Another github genome, this time with an extremely forward-thinking (& ambitious) license provision: http://bit.ly/i5h6Ev
• Looking forward to the first Science Online NYC event next month: http://bit.ly/eAr3tX cc @S_O_NYC #sonyc
• More $ for OCR necessary? 250 breaches affecting >500 ppl (http://1.usa.gov/bxVDO3) & >10K total breaches say yes.
• OCR requests an additional $5.6M for HIPAA/HITECH enforcement: http://bit.ly/eMBBFp
• RT @PersonalizedMed: Take home msg from HUGO 2011 Dubai: global community in #genomicmedicine engaged , growing, active, entrepreneurial
• An admittedly cynical take on angel investing RT @JCainHart: The Top 12 Lies Angels Tell | http://read.bi/fTzZHM
• A first look at HBM’s survey of ’10 Biotech M&A trends by @LifeSciVC: http://bit.ly/eEw5ie More deals, smaller buyers, worrying multiples
• A look at Europe’s complicated regulatory environment for genetic testing in EJHG: http://bit.ly/gT8AEI congrats to lead author @eurogene
• Good to see BGI (@BGI_Events) taking on ethical challenges of WGS & personal genomics: http://bit.ly/erSNKs cc @PGorg
• RT @GenomeWeb_News: JGI Taking Proposals for Sequencing Projects: http://bit.ly/hU2zfv
• RT @GenomeWeb_News: Ambry Genetics, LABS Partner on Genetic Testing: http://bit.ly/hniLM5
• “The Structure of the MedTech Innovation Ecosystem” http://bit.ly/eqogIh Interesting slidedeck by Josh Makower HT @dgmacarthur
• Obama to push for privacy bill of rights (http://on.wsj.com/fG3THT). Will it encompass genetic privacy rights (http://bit.ly/i9fIT5)?
• Uninformed Consent: Tech Solutions for Faulty Permissions in Health Care http://bit.ly/gloWak in @sciam HT @jasonbobe
• GLR Post: Is the Genetics Rights Movement Picking Up Steam? http://bit.ly/i9fIT5 (review of VT legislative proposal)
• RT @CAPDCAdvocacy: AMA releases proposed molecular pathology codes for stakeholder review: http://tinyurl.com/45uw32w
• Including a “buy” for $MYGN: RT @GenomeWeb_News: Investment Firm Jefferies resumes coverage on 8 MDx & other firms: http://bit.ly/gzi0JD
• Having struck out w/ Bayh-Dole (http://bit.ly/ge6VUZ), Fabry patients file class action suit against $GENZ, Mt. Sinai: http://bit.ly/ghc6bE
• Agreed! A great day & very timely discussion. RT @PersonalizedMed: @genomicslawyer thanks for a great day today @DukeIGSP
• RT @girlscientist: Genetics Society of America launches “fully open access journal, with data availability” http://www.g3journal.org
• Wonder who’s buying at $9,500. RT @shwu: “Consumers can’t decode genomics-based tests on their own” says survey: http://bit.ly/fm9LNO
• RT @GENbio: North Carolina & MD trying to create new funds designed to assist life science start-ups. http://bit.ly/fcnXrV cc @JCainHart
• RT @LifeSciVC: More on $50M Slate drug cost to NDA “Choose your Own Numbers: Crowdsourcing Cost-to-Produce a new Drug?” http://bit.ly/hMya4G
• $GNOM Expects to Ship >500 Genomes in Q1, Plans to Break $5K Genome Price by Year-End: http://bit.ly/fsTnFc via @InSequence
• RT @EdwardWinstead: Making Genome Sequencing Part of Clinical Care http://bit.ly/eBFFtL by @emilysinger via @EricTopol
• RT @ldtimmerman: Gates Foundation makes 1st direct equity investment in a biotech co, Liquidia Technologies. http://bit.ly/fwyfIq
• RT @David_Dobbs: Buckle up. RT @dgmacarthur: Watching James Watson present to packed house … in Francis Crick auditorium @sangerinstitute.
• RT @pgx_reporter: Goldman Analyst: $MYGN’s Stock Buyback Suggests Slowing Organic Growth: http://bit.ly/fqXDnR
• RT @dgmacarthur: Five more @23andMe data-sets in the public domain: @manuelcorpas and family follow @genomesunzipped: http://nblo.gs/f6YjM
• RT @genomesunzipped: Our raw genetic data are now officially in the public domain, under Creative Commons CC0: http://bit.ly/gWDiUR
• RT @jasonbobe: GET 2011 @ UPenn, speakers incl Goldstein (Duke), Pe’er (Columbia), Drmanac (CGI) & Church (Harvard): www.getconference.org
• Dell survey: Patients like idea of health IT & digital data (81%), even as concerned about privacy (69%) http://bit.ly/fNjoI2 HT @cwhogg
• Sad but true: “best-case scenario” RT @NatureNews Modest cuts for science in Senate compromise bill http://goo.gl/fb/BXkxN
• TED not on today’s agenda? Go see @MishaAngrist at BIL instead: http://on.wsj.com/gQFI0y
• RT @genomesunzipped: Inbreeding around the world, gene-environment interactions and sales of genetic tests: http://bit.ly/dYp6y6
• RT @FierceBiotech: Careers in biotech ranked as the No. 1 happiest job in America. http://on.msnbc.com/hJpa98
• RT @GenomeWeb_News: Europe, EMBL Pledge Continued Partnership: http://bit.ly/g8csIF
• RT @MattMealiffeMD: #FoGMIV: increasing # of studies show N=1 seq of individual pt’s tumors yield info w/ at least quasi-clinical importance
• Fighting Gravity in Venture-Backed Biotech Returns: http://bit.ly/g8G7Ds by @LifeSciVC
• RT @bigs: RT @raymondmccauley: Audience doc: Why “patients”, “consumers”, “organizers”? We’re all just people, looking at ourselves. #FoGM11
• RT @GenomeWeb_News: Patent Reform on Cusp of Senate Passage: http://bit.ly/hgLX5I
• RT @InSequence: Affymetrix Dismisses Lawsuit against PacBio, Former Employees: http://bit.ly/g6r78H

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.

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.

The first day was divided into three roughly equal parts: background presentations from the FDA and invited speakers, a second set of “public presentations” by companies and individuals who requested time to present their views and, finally, public deliberations by the Molecular and Clinical Genetics Panel (“MCGP”). Tomorrow will feature more public presentations, several more sessions of MCGP deliberations and, at the end of the meeting, recommendations from the MCGP to the FDA on the questions presented (pdf) by the FDA.

A Familiar Feeling to Day One. The first two sessions, which featured presentations to the MCGP, followed a fairly familiar script. Opponents of clinical DTC genetic testing worried that incorrect or misinterpreted tests could produce harmful outcomes, and questioned whether there was anything of value to be gained from the tests in the first place. Proponents argued that the DTC model empowered patients to explore their genetic selves without any ill effects. For those who attended or followed last summer’s two-day public meeting to discuss the FDA’s proposal to regulate laboratory developed tests (LDTs), much of the conversation echoed what was said on day two of that meeting during the direct-to-consumer (DTC) session.

At Genetic Future, Daniel MacArthur has done a very nice job of summing up the morning session, which included a well-balanced presentation from Dr. Elizabeth Mansfield, OIVD’s Director of Personalized Medicine, on the past and present of DTC genetic testing regulation, and a whirlwind tour of global trends in consumer genetics regulation by Dr. Stuart Hogarth of King’s College London. There was also some particularly strident anti-DTC rhetoric, which was followed by my own presentation urging both the FDA and the MCGP to provide clear and forward-looking DTC oversight.

The MCGP’s (Likely) Recommendations to the FDA. The purpose of all of the presentations, however, was merely to arm the MCGP with the necessary background information and context to deliberate and, tomorrow afternoon, offer a set of recommendations to the FDA on the appropriate regulatory strategy for clinical DTC genetic tests. When the MCGP hands out its recommendations I will, unfortunately, be on an airplane. But based on what transpired today, I have some strong suspicions about what the MCGP’s recommendations will entail.

First and foremost, I fully expect the MCGP to note, likely more than once, that given the complexity of the questions put to it by the FDA it should be afforded far more time to deliberate and research prior to making any recommendations. Particularly in today’s afternoon session, several panelists appeared frustrated by the FDA’s request to offer up or down votes on broad questions without being afforded adequate time to understand, let alone fully debate, all of the pertinent issues. However, given that the MCGP has met only once previously, despite being chartered in 2008 (pdf), additional deliberation is almost certainly not in the cards.

If taking time out for further debate isn’t an option, what is the MCGP likely to recommend? Based on today’s deliberations, I think it’s a safe bet that the MCGP will advise the FDA to (1) demand clear proof of analytical and clinical validity for all genetic tests and (2) require that most, or perhaps even all, genetic tests with demonstrated or potential clinical significance be (to use the FDA’s terminology) “routed through a clinician.” The format (21 panelists, with very limited time to discuss a large number of issues) makes anything resembling true “consensus” elusive, although a majority (but not all) of the panelists did appear to agree on those two general points.

In other words, I think the odds strongly favor an MCGP recommendation to the FDA that clinical (as defined by the FDA, which is itself a separate issue) direct-to-consumer genetic testing, when offered without a requirement that a clinician participate in the ordering, receipt and interpretation of the test, be removed from the marketplace. At least for the time being.

The (Likely) Significance of the MCGP’s Recommendations to the FDA. Of course, I could be wrong. The MCGP could surprise us all and offer a ringing endorsement of DTC genetic testing, citing individual autonomy, a need to pursue innovative models of genetics research and consumer education and an increasingly engaged and intelligent consumer cohort as reasons for the FDA to keep its hands off of DTC genetic testing. And pigs could fly.

Whatever the MCGP’s recommendations, whether for or against DTC genetic testing, my advice will be the same: move on.

Throughout the day the FDA was clear that it was asking the panel for assistance with a fairly narrow set of questions. Not on the table: whether DTC genetic tests will be regulated. They will be, at least for analytical and clinical validity. Exactly what that regulation will look like will be heavily influenced by how the FDA ultimately decides to regulate LDTs. For purposes of the MCGP’s recommendations, the FDA appears to be interested solely in the narrower question of when, if at all, a genetic test should be offered directly to consumers.

Even on this question, which is clearly an important one for the DTC industry, 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. Barring something completely unexpected tomorrow, I’m standing by my prediction (most recently here and here) that industry-wide DTC regulation by the FDA in 2011 is unlikely. Whether or not that’s a good thing, however, remains to be seen.