Phillip C. Ross is a summer associate at Robinson, Bradshaw & Hinson, P.A. and a rising third-year student at Wake Forest University School of Law.

Many health care providers and other individuals and entities who deal with sensitive patient information may assume that if they comply with the Health Insurance Portability and Accountability Act (“HIPAA”), they need not worry further about the proper use or disclosure of patient data. However, a recent Michigan Court of Appeals decision served as a reminder to those individuals and entities that they must not only ensure compliance with HIPAA, but also any state laws that are more demanding than HIPAA.

HIPAA establishes regulations for the use and disclosure of Protected Health Information (“PHI”) held by “covered entities” (pdf) and “business associates.” PHI is any information held by a covered entity related to health status, provision of health care, or payment for health care that can be linked to an individual.

In Isidore Steiner, DPM, PC v. Marc Bonanni, No. 294016 (Mich. Ct. App. Apr. 7, 2011), the Michigan Court of Appeals held that HIPAA acts as a federal “floor” in establishing standards for the privacy of patients’ PHI. Although Bonanni was decided under Michigan law—and thus is not binding on other states—the decision is likely to be consistent among courts in other states.

The reason? HIPAA explicitly provides that where a state law is more protective of patients’ PHI than the applicable provision of HIPAA—that is, where the state law is more “stringent”—the state law will prevail (pdf).

Breaking Down Bonanni. In Bonanni, the Family Foot Center (the “Center”)—a covered entity—sought to enforce a non-compete agreement with one of its former physicians (Dr. Marc Bonanni). The Center believed that Dr. Bonanni had solicited its patients in violation of the agreement, and as part of pre-trial discovery, the Center requested Dr. Bonanni’s patient lists. Dr. Bonanni objected to this request, asserting that HIPAA and Michigan law protected this information from disclosure unless the Center first gained the consent of the patients in question. The Center filed a motion to compel the disclosure of this information, and the Michigan Court of Appeals chose to apply Michigan law instead of HIPAA.

Generally, HIPAA requires patient consent for the disclosure of PHI, just like Michigan law. However, with respect to responding to a subpoena or discovery request, HIPAA and Michigan law are in conflict. While a HIPAA exception allows for an entity to disclose an individual’s PHI without a written authorization in this situation, Michigan law contains no such exception. In Bonanni, the Court held that Michigan’s law provided more stringent protections than HIPAA for the PHI at issue, and so it applied Michigan privilege law in denying the Center’s discovery motion.

What Bonanni Teaches Us About PHI. The Bonanni ruling certainly limits the information that physicians can release during legal proceedings in Michigan. This will also likely be true in other states with similar discovery laws, as evidenced by a recent California Supreme Court ruling upholding a lawsuit (pertaining to the disclosure of medical records to a credit reporting agency) brought under a state medical information statute with provisions more stringent than HIPAA (Brown v. Mortensen (pdf), Case No. S180862 (Cal. Jun. 16, 2011)). There, too, the court held that HIPAA “authorized and encouraged further state regulation” in matters of patient medical privacy.

However, individuals and entities in every state deal with PHI in many other mediums and contexts outside of a discovery request during litigation, and Bonanni’s broader lesson is that HIPAA serves only as a federal floor when it comes to patient privacy provisions.

For instance, a Health Information Exchange (“HIE”) (also known as a Health Information Organization (“HIO”)) deals with PHI through the use of electronic health records (“EHRs”). An EHR contains sensitive patient data—including certain demographic information that would identify the patient—and it follows the patient to any and all hospitals to which he or she goes. The HIE/HIO pulls in data relating to that patient from the insurance company or government agency, from hospitals and physician offices, labs, pharmacies and other sources of clinical and administrative data. Then, the HIE/HIO provider may, among other things, analyze the patient information and derive alerts and recommendations to turn the data into actionable information. The benefits of such a program are wide-ranging, from simply reducing paper to creating an accessible information portal that enables physicians to coordinate care, use clinical research to devise the best treatments, encourage prevention and better manage chronic conditions.

In short, the effective use of EHRs by HIE/HIOs and other HIPAA covered entities is central to the continued progress of personalized medicine. Nevertheless, while an EHR program may provide a number of important benefits, it is also susceptible to PHI security issues under HIPAA and/or any other “more stringent” state laws, which could present the same state law preemption issue addressed in Bonanni.

For example, if an HIE/HIO—or any other entity subject to HIPAA—wished to use PHI in the course of conducting research, HIPAA would allow (pdf) such a use of PHI with individual authorization, or without individual authorization under limited circumstances. State law, however, may not be as flexible, and many states may lack a research exception to the use of PHI or may require different standards for individual authorization. In such a scenario, the more stringent state law is likely to prevail, restricting the ability of the HIE/HIO or other HIPAA-covered organization to use PHI to conduct research, no matter how important.

As shown by this hypothetical, despite the importance of PHI to the development of EHRs and the advancement of research essential to personalized medicine’s progress, Bonanni and Brown each make clear that that individuals and companies utilizing PHI must consider more than just HIPAA compliance. In fact, those individuals and entities who operate at a regional or national level would need to consider multiple (or even all) states as part of an effective compliance strategy.

Individuals and entities who deal with PHI should contact a qualified attorney who will undertake a detailed analysis of the applicable federal, state, and local laws prior to making any disclosure, transmission, or other use of PHI. By considering all sources of law, and not just the federal rule, health care providers, researchers and technology developers can minimize the inherent risk in dealing with PHI and work towards full compliance with privacy laws.

Following its passage in the Senate, the legislation promptly stalled in the House of Representatives and, several months and numerous committee hearings later, that is where it remains. Fierce lobbying and political maneuvering have thrown multiple key provisions of the reform legislation into doubt. Leading areas of debate include the constitutionality of a proposed change from a “first-to-invent” to a “first-to-file” patent system and a provision that would allow the patent office to retain user fees to fund its own operations.

While it remains unclear whether patent reform will actually occur, the latest round of legislative wrangling has introduced one proposal of particular interest to Genomics Law Report readers. Among 86 pages of proposed amendments (pdf) to H.R.1249 (the House version of the patent reform legislation) offered earlier this week is a provision that, if adopted, would provide an infringement safe harbor for second opinion genetic diagnostic testing.

Permitting Second Opinions in Certain Genetic Diagnostic Testing. Introduced as part of the Manager’s Amendment (pdf) submitted by Representative Lamar Smith (R-TX), the proposal is conceptually simple. It would create a new Section 287(d) under the Patent Act to establish a safe harbor for second opinion genetic diagnostic testing providers, much like the safe harbor that already exists at Section 287(c) for medical practitioners’ performance of medical activities.

Under certain conditions (more on those below),  performing a genetic test “solely for the purpose of providing the individual with an independent confirmation of results” previously obtained from a patented diagnostic test would not subject the second opinion test provider to infringement liability under the Patent Act. The safe harbor provision would not actually define second opinion testing as non-infringing behavior—the act of performing the second opinion test could still constitute infringement under Section 271 of the Patent Act—but it would eliminate the normal infringement remedies (Sections 281, 283, 284 and 285) from the patent owner’s arsenal.

The actual legislative proposal, of course, is slightly more complex. Here is the full text:

Sec. 27. PERMITTING SECOND OPINIONS IN CERTAIN GENETIC DIAGNOSTIC TESTING

(a) IN GENERAL. – Section 287 of title 35, United States Code, is amended by adding at the end the following:

(d)(1) With respect to a genetic diagnostic test provider’s performance of, or offering to perform, a confirming genetic diagnostic test activity that constitutes infringement of a patent under section 271(a) or (b) of this title, the provisions of section 281, 283, 284 and 285 of this title shall not apply against the genetic diagnostic test provider with respect to such confirming genetic diagnostic test activity.

(2) For the purposes of this subsection:

(A) The term “confirming genetic diagnostic test activity” –

(i) means the performance of a patented genetic diagnostic test, by a genetic diagnostic test provider, on an individual solely for the purpose of providing the individual with an independent confirmation of results obtained from another test provider’s prior performance of the test on the individual, where such prior test was performed by, or under license from, the owner of the patent that is infringed by the acts specified in paragraph (1), and where independent confirmation of the prior test is not available from another test provider under a license from the patent owner; but

(ii) does not include –

(I) the performance of a patented genetic diagnostic test on an individual for the purpose of monitoring or reconfirming the individual’s medical or genetic status over time, for therapeutic treatment selection or determining responsiveness to treatment, and for other purposes that require repeated genetic diagnostic testing of the individual;

(II) the use of a patented machine or article of manufacture in violation of such patent;

(III) the use of a patented composition of matter that is commercially available to the genetic diagnostic test provider; and

(IV) the practice of a patented process other than the process of testing claimed in the patent owner’s patent referred to in paragraph (I).

(B) The term “genetic diagnostic test provider” means any person or entity that performs a confirming genetic diagnostic test activity, and includes a clinical laboratory or other health care entity at which, on behalf of which, or in association with which the confirming genetic diagnostic test activity is conducted, such as a nursing home, hospital, university, medical school, health maintenance organization, group medical practice, or medical clinic.

(C) The term “patented genetic diagnostic test” means a patented diagnostic method that is specific to the detection of a mutation or a pattern of mutations of one or more particular genes in an individual, as well as the use of a patented composition of matter, or the practice of a patented use of a composition of matter, where such composition of matter is specific to and necessary for the practice of the diagnostic method and is not commercially available to the genetic diagnostic test provider. When performed in the course of a confirming genetic diagnostic test activity, such term is not limited to the particular embodiments of the patented diagnostic method or composition of matter that were practiced by or under the authority of the patent owner in providing the prior genetic diagnostic test.

(D) The term “independent confirmation” is not limited to the replication of the results of a prior genetic diagnostic test, and includes providing the individual with information that is not otherwise available from the provider of such prior test and that affirms, clarifies, disproves, corroborates, or otherwise aids the individual in interpreting the results of such prior test, including in instance where such results were inconclusive.

(3) The infringer shall have the burden of establishing the limitation on remedies under paragraph (1), including the production of contemporaneous documentary evidence proving, or tending to prove, that the diagnostic test activity meets the definition of a confirming diagnostic test activity under paragraph (2)(A) at the time the confirming diagnostic test activity was performed.

(b) EFFECTIVE DATE. – The amendment made by subsection (a) shall take effect on the date of the enactment of this Act and shall apply to confirming diagnostic test activity performed on or after such date.

A Safe Harbor’s Uncertain Waters. A close examination of the text reveals that, however simple its intent, if passed as drafted the second opinion safe harbor would leave genetic testing developers and providers, patent holders and courts with considerable uncertainty about the safe harbor’s appropriate interpretation and application.

Perhaps the easiest way to identify many of the unclear and (likely) controversial provisions of the second opinion safe harbor provision is to read the amendment proposed by Rep. Smith side-by-side with the amendment-to-the-amendment (pdf) proposed by Representative Debbie Wasserman Schultz (D-FL) who, as Patent Docs notes, first offered the second opinion safe harbor amendment on the House floor in April.

An examination of the first three amendments suggested by Rep. Wasserman Schultz reveals the high degree of uncertainty and controversy embedded in the current second opinion safe harbor proposal:

WS Amendment #1. As proposed by Rep. Smith, Section 287(d)(2)(A)(i) limits a “confirming genetic diagnostic test activity” subject to the safe harbor protections to those situations where independent confirmation is “not available from another test provider under a license from the patent owner.” That would seem to close the safe harbor except when there was, in fact, only a single licensed provider of a particular test (as is currently the case with Myriad Genetics and its diagnostic test for mutations in the BRCA1 and BRCA2 genes). The safe harbor would appear to be inapplicable in any scenario in which there were two providers.

It is unclear, however, whether this would be the case even if both “test providers” offered the exact same test using the exact same laboratory procedures (would that even be a truly confirmatory test?) or if the multiple test providers were controlled by a common entity. Also uncertain is when a test would be considered “available” for purposes of the safe harbor provision. Would the requirement of availability require that the test be “affordable and readily accessible to the patient” or simply “available in some form, to some patients at some price”?

Rep. Wasserman Schultz addresses these concerns in her own amendment by simply striking the requirement that the test be unavailable except from the sole test provider, which would appear to broaden the provision to apply even in situations where the patents were licensed on a non-exclusive basis to multiple genetic testing providers.

WS Amendment #2. Rep. Smith’s version of the safe harbor provision would also not apply where a genetic diagnostic test was used for “therapeutic treatment selection” (Section 287(d)(2)(A)(ii)(I)). While that term is not defined, it could be interpreted broadly to exclude from the second opinion safe harbor any genetic diagnostic test the results of which could cause a new or modified clinical course of care.

Such a reading would dramatically limit the scope and relevance of the safe harbor, since most patients, providers and payers are likely to pursue a second opinion only in those situations where a different test result would alter the course of the patient’s care.

In her own amendments, Rep. Wasserman Schultz’s proposal simply strikes the “therapeutic treatment selection” limitation.

WS Amendment #3. In addition to the “therapeutic treatment selection” exception to the safe harbor, Section 287(d)(2)(A)(ii)(I) would also exclude genetic tests “for the purpose of monitoring or reconfirming the individual’s medical status over time” or for any other purpose that required “repeated genetic diagnostic testing.” The presumed intent is to avoid depriving the rights-holder (the patent owner or its licensee) from serving as the first option for any re-testing conducted later in time.

Rep. Wasserman Schultz’s proposal retains this language, but provides an exception-to-the-exception that would permit an infringing genetic diagnostic test to take advantage of the safe harbor, even for repeated diagnostic testing, if the test “utilizes different technologies or has performance characteristics that are sufficiently different from the patented tests that the results can provide information not provided by the patented test.”

The goal would appear to be the encouragement of second opinion testing using non-identical genetic tests (“different technologies or…performance characteristics”), although it is unclear whether this would operate in conjunction with Rep. Wasserman Schultz’s first amendment to prevent the developer of a separate and patented diagnostic test from enforcing its rights when its test was performed following any previous diagnostic test covering the same condition.

All told, Rep. Wasserman Schultz offers ten amendments to the language proposed by Rep. Smith, including this “Rule of Construction”:

The amendment made by subsection (a) [the second opinion safe harbor amendment] shall not be construed to reflect any expression by the Congress with respect to the patentability of genetic material or genetic diagnostic testing.

Will Congress Intervene in the Gene Patent Controversy? It remains highly uncertain whether Congress will manage to pass any patent reform legislation during its current session. Furthermore, should patent reform become a reality, there is no guarantee that the second opinion exemption will be retained. The safe harbor for genetic diagnostic testing was not included in the version of the legislation the Senate passed in March and, even if the House manages to include the provision in its version of the legislation, it could easily be removed during the reconciliation process.

Finally, even if Congress is ultimately able to reach an agreement, the questions about how to interpret and apply a second opinion safe harbor are unlikely to end there. They would almost certainly carry over from Congress to the courts if and when companies and individuals begin seeking shelter in the new safe harbor, should it ever materialize.

Despite these several barriers to the adoption of a second opinion safe harbor for genetic diagnostic testing, the possibility that change could come to the personalized medicine patent landscape should not be entirely ignored.

It is no coincidence that the safe harbor proposal comes just one year after the now-defunct Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS) published its controversial report on Gene Patents and Licensing Practices and Their Impact on Patient Access to Genetic Tests (pdf). In that report, SACGHS found that “when there is a patent-enforcing sole provider [of a genetic test], patients cannot obtain independent second-opinion testing” and, as a result, recommended several statutory changes, including “the creation of an exemption from liability for infringement of patent claims on genes for anyone making, using, ordering, offering for sale, or selling a test developed under the patent for patient-care purposes.”

And Rep. Wasserman Schultz’s “Rule of Construction” notwithstanding, the safe harbor proposal must also be viewed as a direct Congressional reply to the ongoing and widely publicized Myriad gene patent litigation. The Myriad litigation was initiated more than two years ago by a diverse group of plaintiffs, including several women seeking genetic testing for mutations linked to breast and ovarian cancer. The plaintiffs’ complaint (pdf) included the allegation that Myriad Genetics’ patents and licensing practices operated to prevent women from “obtaining information about their health risks from anyone other than” Myriad, including denying women access to second opinion testing. As the Myriad litigation enters its third year, some members of Congress are undoubtedly feeling pressure to address the effects of gene patents in the practice and development of personalized medicine using more expeditious means.

[Update, 6/16: The American Civil Liberties Union (ACLU), the group largely responsible for coordinating the Myriad litigation, is leading a group of organizations in opposition to the proposed amendment (pdf). The ACLU-led coalition argues that the proposed second opinion safe harbor “would fail to block all patent holder objections to [second opinion] testing, fails to address the many other limitations on scientific research arising out of the issuance of [gene patents], and risks allowing gene patent holders to argue that Congress implicitly endorses the validity of such patents.” The group urges Congress to reject the amendment to avoid creating “unintended harms to patients, medical professionals and genetic researchers.” According to the ACLU’s letter, the American Medical Association has also written separately to Congress to oppose the amendment. The swift response from organizations like the ACLU, the AMA and others suggests that the second opinion safe harbor may be closer to becoming a reality than was previously suspected.]

Although the second opinion safe harbor proposal seems unlikely to pass at this time, at least in its current form, Whether the safe harbor proposal passes or not, it should serve as a stark reminder that even as patent attorneys and biotechnology companies anxiously await the Federal Circuit’s ruling in Myriad—which could come any day now and significantly alter the personalized medicine patent landscape—Congress will continue to loom in the background, with the ability at any moment to completely rewrite the rules of the game.

Personalized Medicine’s Perception Gaps. A new report released this week by the biopharmaceuticals company Quintiles (pdf) examines the perspectives of four key stakeholder groups – biopharma executives (n=200), managed care executives (n=153), physicians (n=503) and patients (n=1,000) – across a wide range of personalized medicine issues.

The report contains a number of interesting statistical nuggets about how these groups perceive their strengths, weaknesses and future role in the advancement of personalized medicine. These include the following:

• Only 44% of biopharmaceutical executives believe that their organization provides “readily available” outcomes data to demonstrate the value of medications;
• Healthcare professionals generally agree (65%) that patients who seek out information on their own achieve better health outcomes, but more than a third (36%) believe that patients are more frequently misinformed than they were five years ago;
• Fewer than half (44%) of doctors surveyed are optimistic that the quality of healthcare will be significantly improved over the coming decade; and
• At least a third of payers (33%) and biopharma execs (38%) believe that personalized medicine will have a negative effect on job and healthcare discrimination (this despite the passage of 2008 legislation (GINA) designed to prevent discrimination on the basis of genetic information in both cases).

Perhaps the most surprising finding of all is that patients appear to be largely unfamiliar with the entire concept of personalized medicine. Only 24% of patients surveyed had previously even heard of “personalized medicine,” indicating that healthcare companies and providers alike have considerable work remaining in order to bring personalized medicine into the mainstream.

The report concludes that there is “considerable misalignment among healthcare stakeholders on various aspects of the healthcare universe.” According to the report, physicians are frustrated by payers, payers are frustrated by a complex and ill-suited regulatory regime, biopharma executives are torn between maximizing health outcomes and maximizing value to shareholders and patients are “viewed by all groups as not doing enough to improve their own healthcare.”

Clinical Trial Innovations. One major barrier to the development of increasingly personalized therapies is clinical trial recruitment. The more personalized the therapeutic or diagnostic tool in development, the more difficult it is to locate patients who satisfy the trial’s enrollment criteria.

Enter PatientsLikeMe, the patient-driven health platform, which this week announced a new feature to help match patients with clinical trials more effectively. PatientsLikeMe’s new tool will query a government database of ongoing clinical trials (ClinicalTrials.gov) and “automatically match up members of the website with every clinical trial they may be eligible for based on their conditions and location.”

Also this week, pharmaceutical giant Pfizer announced a new form of “virtual” clinical trial which, according to NatureNews, will lower barriers to clinical trial enrollment by allowing “participants to receive medication, video-conference with clinicians, and report symptoms in the comfort of their own home.”

The announcements from Pfizer and PatientsLikeMe are just the latest in a serious of innovations seeking to leverage digital and social media tools to encourage more widespread and efficient personalized medicine research.

Personalized Medicine and Cancer. Despite the many challenges it faces – from scientific complexity to regulatory, reimbursement and intellectual property regimes ill-equipped to accommodate innovation – the present and future of personalized medicine was on display this past week as thousands gathered in Chicago for the annual American Society of Clinical Oncology (ASCO) meeting (see previous news).

To help us keep up with the latest developments in oncology, Luke Timmerman of Xconomy offered a detailed wrap-up of the major developments announced at ASCO by U.S. companies. In addition, at the Consumer Genetics Conference in Boston this past week, Illumina CEO Jay Flatley announced cuts in the company’s pricing for individual whole-genome sequencing, including an attractive $10,000 price point for tumor-normal pair sequencing of cancer patients. Finally, Matthew Herper of Forbes elegantly recapped outgoing ASCO president George Sledge’s big-picture perspective on “cancer’s new era of promise and chaos.”

Whatever the challenges, it remains clear that opportunities abound for personalized medicine companies and investors. A new survey from PwC’s Health Research Institute found that consumers are willing to spend approximately $13.6 billion per year of their own money on healthcare services. It found further that more than three-quarters (76%) of the Fortune 50 is comprised of either healthcare companies or companies with a health division.

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

• Troubling: 1/3 of managed care execs think personalized medicine will have negative effect on job/healthcare discrimination #quintiles
• Sad that more than 56% of MDs think that quality of healthcare will improve over next decade #quintiles
• MDs agree (65%) that patients who seek out information achieve better health outcomes, but 36% worry about patient misinformation #quintiles
• Also, managed care execs appear to have a dramatically inflated view of the value they add in educating/understanding patients #quintiles
• Note that only 44% of biopharma execs say outcomes data readily available to support value of new medications #quintiles cc @wilbanks
• Quintiles healthcare report is goldmine of data on MD, pharma, managed care & patient views http://bit.ly/jBNzx5 HT @cwhogg
• 76% of Fortune 50 companies are in healthcare or have a health division: http://bit.ly/iZaw6x HT @FierceHealth
• Re: last tweet, HIPAA as a floor, & not preemptive, will make compliance/sharing more difficult cc @wilbanks @danielg280
• Michigan court rules state law trumps HIPAA data disclosure/privacy provisions: http://bit.ly/jmeCkE
• The @Forbes NGS piece is garbage, but @matthewherper’s piece on genomic medicine & cancer remains a #mustread: http://onforb.es/iuOHrX
• Glad to see it. Hopefully would-be investors read to bottom. RT @matthewherper: I added my thoughts on the post. We agree (not surprising.)
• Health app accelerator @Rock_Health funds 11 startups, including @genomera: http://bit.ly/jWoJcI HT @InVivoBlogEllen
• Includes this gem: “[NGS] will also open door to creating superhumans w/ unusual intelligence or physical skills.” Really? @matthewherper?
• Unimpressed by @Forbes NGS article which amounts to advert for two cos ($ILMN, $LIFE) in which author holds shares: http://onforb.es/mr2jpx
• HHS releases add’l details on NIH reorg needed to produce NCATS, incl. proposed budget of $722M: http://bit.ly/makQKQ
• More clinical trial innovation: $PFE’s online-only trial aims to lower participation barriers: http://bit.ly/kX5P7B HT @bmahersciwriter
• Cont. innovation from @patientslikeme, using ClinicalTrials.gov to improve patient recruitment: http://bit.ly/joJuiP by @RyanMFierce
• My #sonyc slides from last night are online: http://bit.ly/ldIXMO Did my best to cover personal genomics in 5 slides.
• MT @LouWoodley: If you missed last night’s #sonyc on Science+Law it is now online: http://bit.ly/l4QCsO HT @science3point0
• RT @BiotechPatent: SCOTUS affirms clear & convincing standard for invalidity defense in #patent challenge http://tinyurl.com/44ga9b8
• Belated update re: House hearing on FDA med device approvals, feat. testy exchange with Shuren: http://bit.ly/m6TrhL HT @dgmacarthur
• Prev article on AUS nobel / genome publication mistakenly implies US law (GINA) prohibits life insurers from using genetic info. It doesn’t.
• RT @dgmacarthur: Awesome – Australian Nobel Laureate announces plan to publish his complete genome on the internet: http://bit.ly/j8yJyi
• Agenda here: http://bit.ly/jRmhfd Anybody live-tweeting? RT @FierceMedDev: Hatch, Hamburg, Shuren speaking at MDMA.
• Interesting. 63% (n=2137) said “yes” to FMR1. RT @PHGFoundation: Should babies be screened for untreatable disorders? http://bit.ly/k50xx8
• RT @DailyNewsGW: Roche, Merck Partner on Cancer Therapy Diagnostics: http://bit.ly/kRaB7o
• Genetic privacy may be doomed, as @razibkhan argues (http://bit.ly/jKKUY0). Question is, will that matter and, if so, what are our options?
• “Suggests online collection of self-reported data in recontactable cohort may be viable method for broad & deep phenotyping in large pop’n”
• MT @mary_carmichael: Just read @23andMe GWAS replications paper-in-progress. Neat stuff there. Congrats, @nkeriks! http://bit.ly/m0YJwb
• RT @dgmacarthur: Post on the wondrous Cambridge BioResource by @elainewestwick: http://bit.ly/ljKGjp (I’m in there too!)
• Wonderful time at #sonyc event on science & law w/ @SLSingh et al. Thx to @LouWoodley @JeanneGarb @j_timmer & rest of @S_O_NYC for invite.
• Although, to be fair, $10K for tumor/normal pair does represent a more significant price drop for $ILMN. #cgc2011
• Wonder how much extra $ILMN capacity is due to emergence of $GNOM, which is targeting $4K by 2nd half of ’11: http://bit.ly/iNrqo3 #cgc2011
• The fact that the WGS floor only dropped $2K (non-clinical drop is $10K) may be better indicator of ILMN capacity #cgc2011
• Here’s today’s $ILMN presser on WGS pricing: http://bit.ly/l9IPmB Compare to last June: http://bit.ly/j8KLeu #cgc2011
• Wish I could be at (or at least following along) #cgc2011. Follow @wimufi @davidpendletonk @RDGene & others for live tweets
• Ready for the $1K genome? 3 great posts @genomesunzipped: http://bit.ly/l7kQYEhttp://bit.ly/iqnH6vhttp://bit.ly/jfYNj1
• Pfizer ($PFE) investing $100m in Boston research collab; another attempt to bridge “valley of death”: http://bo.st/iFUcip by @Globecarolynyj
• Done panicking cell phone users, WHO shifts focus to genomic “grand challenges” for developing world: http://bit.ly/mfucTd
• Another NGS play: “sequencing by expansion” RT @DailyNewsGW: Stratos Genomics Raises $2.1M: http://bit.ly/jCzLXX
• Looking forward to participating in tonight’s #sonyc panel on Science & the Law w/ @SLSingh et al. http://bit.ly/koLQ6c
• Sen. Sanders introduces legislation (again) to reward new drugs with cash prizes, not patents: http://bit.ly/lcgm5S
• Updating the DTC Debate: Trial by PR, More FDA Letters, the Problem of Pleiotropy & New RUO Guidance http://bit.ly/jXJzHh
• RT @EdwardWinstead: RT @matthewherper: Cancer’s new era of promise and chaos. #ASCO11 #genomics http://onforb.es/jNZVtr
• Chicago for #ASCO11 to discuss current state of DTC genetic testing. For those not here, an update: http://bit.ly/jXJzHh
• RT @Sagebio: disclose full results and data to address epidemic of false claims; J. Ioannidis in SciAm http://bit.ly/jsaxDZ
• Rescheduled House committee hearing on FDA/medical devices to be held tomorrow: http://bit.ly/iDRdzz
• Follow @DNAlawyer for #UVAGEL tweets http://bit.ly/jcnHFv Muin Khoury arguing “no sci foundation” for personal genomics, incl. PGx?
• RT @dgmacarthur: More press-release scare-mongering about personal genomics – my response: http://bit.ly/j0VWxf
• NYU opening Center for Genomics and Systems Biology tomorrow: http://bit.ly/jnYIbB HT @DailyNewsGW cc @S_O_NYC
• Looks like a great program. RT @DNAlawyer: UVA GEL symposium is tomorrow and Thursday. I’ll be there. http://bit.ly/jcnHFv
• Interesting GINA proposed as a model. Focus on use makes sense; outright ban doesn’t. Health & genetic data must be used, just used properly
• NYT examines health data privacy, re-identification & control. http://nyti.ms/jlgEeu HT @FierceHealth
• MT @mary_carmichael: Study: “strong link b/w happiness & 5-HTT:” http://bit.ly/mHXjP3 More news, green jelly beans cause acne: xkcd.com/882/
• ESHG annual conf starts today, incl. plenty of anti-DTC genetic testing sentiment: http://bit.ly/iZ7fnd HT @shwu
• FDA mtg to nominally focus on analytical validity for NGS. But that’s only one part of broader debate re: FDA & next gen of clinical tools.
• More FDA: on 6/23, FDA holding public meeting on use of NGS platforms in clinical setting: http://1.usa.gov/liUKNg
• Summary of April’s FDA strategic priorities plan by@GENbio: http://bit.ly/iRhcZa Very high level, funding a challenge.
• amednews on the coming regulation of FDA medical apps: http://bit.ly/lshHTQ HT @GeneSherpas cc @mobilehealth
• Asked as an aside: how would FDA regulate Dr. Watson? (Not as far off as it appears. WGS Dx software coming soon, poses similar challenge.)
• For more on Dr. Watson, highly recommend this Feb piece from @PGxReporter: http://bit.ly/iF3VNC Major need: better data collection, sharing
• IBM’s Watson now “as good as smartest second year med student”; widespread use still 8-10 yrs out http://onforb.es/llIAO2
• 1st issue (& t-shirts) already out. RT @wilbanks: Citizen Science Quarterly, a CC licensed journal. via @doctorow http://bit.ly/lLGYjw
• British Columbia court rules against anonymous sperm & egg donation. Will rest of Canada follow suit? Will US be next? http://bit.ly/jTJADw
• Here’s the link to the survey on “the informational aspects of genetic tests” (takes ~5 min): http://bit.ly/kZjjdD
• Genetics of CF severity, a survey of DTC customers and the value of a genetic diagnosis from @genomesunzipped: http://bit.ly/mTYMQi
• Telomeres predicting lifespan? Blackburn: “that’s just silly, isn’t it?” Interview w/ @NatureNews on future of field: http://bit.ly/kEmbwp
• Update on Patent Reform Act progress in Congress from @GENbio: http://bit.ly/jZHH0l
• Poor job by NYT failing to link DNA fish fraud story to earlier teen citizen scientists http://nyti.ms/jh49yA @matthewherper @leonidkruglyak
• RT @DailyNewsGW: $MYGN Teams with Topin to Market OnDose to Oncologists: http://bit.ly/merPqJ
• $GNOM continues to raise more $, talk expansion: http://bit.ly/mwUb06
• Facebook & pharma seeking to sort out social medial policy: http://bit.ly/lek4cG
• RT @wilbanks: Bob Cook-Deegan, a living legend in the gene wars, talks about gene patents. Read. http://bit.ly/lT2n3O
• And on a Friday to boot. RT @Duncande: With my full genome sequenced (by PGP at Harvard & $GNOM), I’ve been designated “PGP 13″ – lucky 13!
• Good question MT @blaine_5: DTC ELSI issue: why aren’t bone marrow donors informed of risk of genomic analysis by bone marrow recipients?
• Authors: “to delay policy-making decisions until all poss qs answered wrt DTC unrealistic given state of field.” I agree. HT @eurogene
• Good NEJM back-&-forth re: Bloss, @EricTopol, et al.’s Feb article on effect of DTC genetic testing: http://bit.ly/lhhqbj
• Genetic Technologies Sues 10 Firms for Infringement on a Method to Determine Haplotype: http://bit.ly/imgHmE HT @blaine_5
• Inspection, Compliance Data Disclosure to Be Widened by U.S. FDA: http://bloom.bg/mJEyCi
• Survey: 2/3 of small med device & Dx firms prefer EU in seeking 1st regulatory approval. Shuren: “we’re on it”: http://bit.ly/kIjqkD
• RT @PGxReporter: In latest PGx pact w/ Population Genetics, Quintiles aims to save Pharma money & time http://bit.ly/lFbogm
• RT @PHGFoundation: Retention of cleared suspects’ DNA by police ruled unlawful http://bit.ly/lRfyIN
• +1 RT @genetics_blog: neat RT @moorejh: Topic map of all grants awarded by the #NIH in 2010 http://is.gd/IfzuzG
• Good, but won’t WGS soon obviate need for mult tests? RT @westr @DivaBiotech: New Genetic Testing Tech for IVF Embryos http://bit.ly/iHNBPc
• Nuffield launches public consultation on ethical/social issues arising from emerging biotechnologies: http://bit.ly/lf07df
• RT @rzeiger: Interesting Google job to run internal health + wellness programs. Ping me if u want to learn more http://goo.gl/ULPvF
• RT @girlscientist @ClinSeqNews: HudsonAlpha Researchers to Sequence Immune Repertoires of 10K Indiv. for 100 Diseases http://bit.ly/kQmHH3
• From Toll House cookies to gastrointestinal diagnostics. RT @DailyNewsGW: Nestle Health Science Buying Prometheus Labs: http://bit.ly/kp1IkI
• RT @InSequence: Life Tech, Gen-Probe to Collaborate on FDA Clearance for Dx Assays on CE Sequencer: http://bit.ly/jH9YiK
• The license out as the biotech end game? MT @ldtimmerman: How to make $ in biotech beyond IPO, M&A http://bit.ly/kczVun
• A new model for @23andMe? @ldtimmerman reports it is rebranding itself as “a research company”? http://bit.ly/k8ImME
• RT @matthewherper: Biopharm execs: We want to focus on the future, but investors won’t let us. http://ow.ly/51GRS
• The challenge of therapeutic success. Or “Innovations of today increase cost of innovations tomorrow”: http://bit.ly/ltLLoj HT @MishaAngrist
• GLR Post: Patent Update: Looking Beyond Section 101 & Continued Murkiness of Method Patents: http://bit.ly/ii5arT
• Precision Quality DNA (recent FDA letter: http://1.usa.gov/mgciWO) has strong feelings re: DTC reg: http://fda.pqdna.com
• Looking forward to some great brainstorming at “The Future of Pathology in Personalized Medicine”: http://bit.ly/ll5LqQ
• Great @DanielSolove column: “Why Privacy Matters Even if You Have ‘Nothing to Hide’”: http://bit.ly/lXG6O7 HT @MishaAngrist
• “The Privacy Challenge in Online Prize Contests” in NYT http://nyti.ms/kFVVgt w/ a HT to @23andMe’s consent form.
• What does the future hold for biotech & VCs? Interesting Q&A in Nature’s bioentrepreneur: http://bit.ly/ki35i3
• First VT, now CA. RT @FierceHealth: Another state considers single-payer #health system http://bit.ly/lTvRec
• RT @FierceBiotech @ScottKirsner: VCs on boards of directors: 1 not enough but > 2 is dangerous. Like martinis. -Bob Higgins @HighlandCapital
• Good. incls dedicated investment to improving reimbursement. RT @DailyNewsGW: UK Groups Investing in Pers Med Projects: http://bit.ly/lbORVW
• +1 RT @matthewherper: Should we just let athletes use performance-enhancers? Why we’re dopes about doping: http://ow.ly/4Zqc9
• Yes, re: NIH budget cuts RT @drjonboyg: the @Battelle & UMR reports show how short sighted that is given huge economic impact of NIH funding
• Collins comments on BGI at end of article also interesting. Maybe NIH funding bump if China viewed as more of a threat?
• Looming NIH budget cuts “sobering”; may drive grant success rate to “lowest in history”: http://bit.ly/jt14vo
• RT @WSJHealthBlog: The CDC’s zombie apocalypse juggernaut: next up, a video contest…..http://on.wsj.com/kShypJ cc @kashhill
• My anecdotal data similarly bleak. RT @DNAlawyer: Anecdotal data: only 2 of my undergrad students @ Duke heard of GINA before I covered it.
• Two comments: 1) pre-06/07 DTC surveys tough to compare to post-07 DTC surveys (diff products). 2) wish some actual data on GINA awareness.
• Oregon has collected data on state-led pop’n surveys of genetic testing use/awareness: http://1.usa.gov/mTMmRj HT @ewencallaway
• RT @dgmacarthur: Joe Pickrell’s discusses potential artefacts in the Science RNA-editing paper at @genomesunzipped: http://bit.ly/jUVz6t
• Note $MYGN’s planned EU expansion to begin in Germany. New Gene/Myriad headed for conflict? Prev GLR: http://bit.ly/fylYeL
• NewGene’s NGS-Based BRCA1 & BRCA2 test coming to France, Germany http://bit.ly/lXZmxk HT @MattMealiffeMD @BRCAscoop
• Missed ind. research results (IRR) & incidental findings (IF) conf (http://bit.ly/epMlQm)? Great live tweets by @genome_gov et al. #ifirr
• RT @bigs: keep liking NIH’s Kathy Hudson more & more. ‘what we want is for every (person) to be a (research participant) as well’ #IRBreform
• RT @Erika_Check: Pickrell will be posting more on possible artifacts in DNA/RNA mismatch study tomorrow @GenomesUnzipped.
• RT @Erika_Check: DNA/RNA mismatch story getting more interesting. Joe Pickrell: “many of the results reported are potentially artifactual”
• Surprised? RT @GENbio: Pres bioethics panels sometimes choose topics driven by political pressure than scientific need http://bit.ly/iIYhdN
• NIDS Eyes Next-Gen Sequencing Needs: http://bit.ly/mRQohw
• Looking forward to @crossborderbio ongoing series on “Valuation and Other Biotech Mysteries”: http://bit.ly/j8Sb5R
• RT @matthewherper: @BiotechPatent This Forbes writer thinks the idea that medical prices are closely connected to dev costs is wrong.
• Forbes columnist takes aim at impending medical device tax: http://onforb.es/jJdYIb HT @BiotechPatent
• Stem Cells: The growing pains of pluripotency: http://bit.ly/m077oj Excellent, comprehensive piece by @Erika_Check
• RT @LifeSciVC: Good to see positive trend. RT @nvca: Venture Capital Performance Continues to Improve http://bit.ly/klA8fi cc @JCainHart
• Intrigued by @HelicosUnveiled (http://bit.ly/iqLNz5) which appears to be unsanctioned PR for Helicos. Other exs of this?
• RT @EdwardWinstead: Timely… Eric Lander at NIH 5/20 11:30 a.m.: From the ‘Genetic Code’ to the ‘Genetic Code’ webcast
• Enough frustration to actually produce change? RT @NatureNews: US panel calls for reform in human subject protection http://goo.gl/fb/kS28S
• RT @MattMealiffeMD: RT @adamfeuerstein: The thing you will mostly notice about #ASCO11 abstracts is that there isn’t a ton of new data.
• RT @genome_gov: Joseph Thankuria – Informed Consent, Biobanking, and Data distribution in the Personal Genome Project #ifirr
• I look fwd to “intense criticism” forecast by @dgmacarthur. MT @Erika_Check: DNA/RNA mismatches challenge central dogma http://bit.ly/ijeWvd
• A personal genomics challenge from @blaine_5 to @genomesunzipped readers (& the rest of you as well): http://bit.ly/jUeXqB
• Telome Health suggesting monthly telomere checkups? http://bit.ly/ldvZpD (see sidebar) Great business model if you can sell it.
• Yes. Life, disability & long-term not covered by GINA (state rules vary) RT @drjonboyg: @genomicslawyer except for long term life insurance!
• Also, I don’t understand the confusion/concern about telomere testing (DTC or otherwise) & discrimination. Clearly covered by GINA.
• On DTC telomeres, #1 I would not be surprised to see another round of “come meet with us” letters from the FDA.
• While the Post tackles DTC athletics, the NYT is featuring an even newer DTC fad: telomere testing: http://nyti.ms/kKtk77
• Canada pursuing its own version of GINA (genetic nondiscrimination legislation): http://bit.ly/iA8bjC HT @mikesgene
• Medco Drug Trend Report predicts cancer drug spending could rise up to 15%/year through 2013: http://bit.ly/ioLIPn
• RT @MichelleNMeyer: @drjonboyg & @genome_gov live tweeting conf on return indiv research results (IRRs) & incidental findings (IFs) #ifirr
• HT to CDC for realizing that best way to teach emergency preparedness is via zombie apocalypse: http://on.wsj.com/kkAD0W
• Rob Stein tackles DTC genetic testing for child athletes in today’s Post: http://wapo.st/lsrkpH AIBS just received FDA ltr
• PGP-1K continues progress. MT @Duncande: It’s official, my complete genome has been sequenced! Thx to PGP (@PGorg) & $GNOM
• Chinese biotechs wrestle with transparency, cultural hurdles (NBT): http://bit.ly/jw3zcU (And you think it’s tough here)
• Interesting post on @23andMe, data sharing and “the altruism instinct”: http://bit.ly/jHfkG1
• More med companies adopting social media (& policies), but 52% say lack of FDA guidance impeding uptake: http://bit.ly/jC1tE0
• RT @MishaAngrist: ENCODE gets ENGORGED http://bit.ly/kvs7S7
• 1K genomes project update from @InSequence: http://bit.ly/lesrH3 WGS & exomes for 1K ppl, another 1K+ on the way
• Genomic Health repaid $800K in royalties due to Incyte’s failure to maintain IP: http://bit.ly/j3H1PN Lesson: pay the PTO on time
• U of Washington, Pharmigene resolve IP dispute around warfarin dosing, agree to license: http://bit.ly/joZucZ
• RT @ldtimmerman: Hood: I despair whether in US we can sequence enough ppl, families. China will. IRBs too much of an obstacle here isb2011p4
• RT @ldtimmerman: Schadt talked all about PacBio machine, not Mt. Sinai, or Sage, to this high-science audience #isb2011p4
• Good overview in NBT of NGS providers & why they are eying clinical seq as their next market opp: http://bit.ly/lYUGRS
• RT @PGxReporter: Medco to Evaluate Clinical Utility of AssureRx’s PGx Test in Guiding Psychiatric Treatment: http://bit.ly/lWZWvL
• RT @dgmacarthur: How a @23andMe test profoundly changed a woman’s life in two very different ways: http://bit.ly/jbO7Yq
• #ASCO11 abstracts come out today. @brianreid has a modest proposal to ‘socialize’ the process for 4,000+ abstracts: http://bit.ly/lZMCzy
• Upcoming debate b/w Phil Sharp & Stephen Friend (moderated by @ldtimmerman) on pro/con of open source biology: http://bit.ly/jshQ77
• European Society of Cardiology says Europe needs a “single, coordinated” system for regulating medical devices: http://bit.ly/iCelNF
• Some candid advice from @LifeSciVC on how to pitch a biotech startup to VCs: http://onforb.es/jwO8LP
• Genetics as Culture in a Consumerist Age: http://bit.ly/kPvgiX Submit a poster/presentation & come join me in Innsbruck.
• Some good talks over the weekend at #ISB2011P4, tweeting supplied by @ldtimmerman, @finchtalk, etc.
• RT @MishaAngrist: Does Pac-Bio have a PR problem? http://bit.ly/jUAFar $PACB
• Here’s @ldtimmerman detailed take to the Schadt/$PACB/Mt. Sinai move: http://bit.ly/k2xjI8 Good to see more genomics $/talent coming to NYC
• AMP position statement recommends against using brand names in companion Dx labeling: http://bit.ly/mjbpPi by @SampleGW
• RT @Sagebio: “a brilliant rebel in the field of genomics” A. Pollack on Eric Schadt move to Mnt Sinai http://nyti.ms/lIwJ7S
• RT @RyanMFierce: More buyouts to come? RT @FierceBiotech: PerkinElmer acquires Labtronics, buyouts pile up. http://bit.ly/l5owst
• Short @techreview piece on another nanopore-based seq play, Noblegen: http://bit.ly/kqAs25 Gaudy goal: 30 genomes, 15 min
• Lumigenix FDA/DTC letter (http://1.usa.gov/jxBtS6) far more conciliatory in tone than similar letters last summer (http://bit.ly/aGpLU0)
• Australian DTC company @Lumigenix receives FDA inquiry letter: http://1.usa.gov/jxBtS6
• Health Insurers Making Record Profits as Many Postpone Care: http://nyti.ms/k1jwBs via @twilli2861
• Summary of Battelle report on economic impact from Human Genome Project from @drjonboyg / @genome_gov: http://1.usa.gov/itBVMr
• RT @JohnCFierce: In-depth article from Forbes on the development of India’s biotech hubs. http://onforb.es/iesQxC
• Verghese op-ed (http://nyti.ms/mD8twZ) led to post on ‘iPatient’ (http://bit.ly/lqqR5M). Lots of work to do redefining what “patient” means.
• Hah RT @bmahersciwriter: I’m so tempted to buy plush microbes from the CSHL gift shop. Wife: What did you bring me? Me: Chlamydia. bg2011
• Detailed summary of FutureMed Day 1 from @Medgadget http://bit.ly/kq1XIc HT @daniel_kraft & congrats to @tgoetz on his new company, 1+1 Labs
• RT @matthewherper: Beating Moore’s Law Since January 2008! My post on bg2011 http://ow.ly/4U4u8
• In context, this is incredible. MT @lukejostins: GM on 1000 Genomes Project. Now have 1094 whole-genome, 977 exomes, 1542 2.5M chips BG2011
• MT @dgmacarthur: GM: Feb 2000, 98% of SNPs in sequenced individual were novel. Now # is down to ~1%. bg2011 (Gabor Marth on 1K Genomes proj)
• 41yo woman w/ BRCA mutation & recent history of Breast Cancer (NEJM): http://bit.ly/isJG0O Interesting patient perspective on testing, risks
• How to calculate your own Alzheimer’s risk, based on genetic and environmental data http://bit.ly/jZ5Dlh @genomesunzipped by @lukejostins
• RT @dgmacarthur: Key message from the meeting so far: we are assigning function to non-coding variation at an astonishing rate. bg2011
• Great idea. See @matthewherper’s latest for related. RT @bigs: Teller proposes ‘sequencing the human lifestyle’ in add. to genome #futuremed
• RT @matthewherper: What should we sequence after the genome? Mark Changizi has an interesting answer: http://onforb.es/iqmBu6
• Also includes working catalog of other public genomic data RT @razibkhan: Ashkenazi 23andMe v3 genotype for the taking: http://bit.ly/iCiKPE
• RT @genome_gov: Watch NHGRI’s Advisory Council meeting May 16, 8:30 a.m. Webcast: http://bit.ly/jsFeIA. Agenda: http://1.usa.gov/mvmMTs.
• GLR Post: New Diagnostic Guidelines & DTC Testing for Alzheimer’s Disease: http://bit.ly/mHDi6Y
• SAS forming “think tank” to look at how healthcare & life sciences cos use its analytics software: http://bit.ly/ldjJeW via @RyanMFierce
• Latest on Fabrazyme dispute: patients allege Genzyme diverting ltd drug supply to European patients: http://bit.ly/kMs3nG
• Good q. Payors have leverage, GH knows it. RT @MattMealiffeMD: can you be both payors “agent” & “neutral arbiter”? http://bit.ly/jpt0KB
• CardioDx closes out Series E to the tune of $60M, will focus on expanding reimbursement coverage: http://bit.ly/k2uvyp
• Generation Health program tackles two key challenges: lack of transparency (runs in both directions) & lack of data. Here’s hoping it works.
• Generation Health launches ambitious pilot program to bridge the gap b/w Dx providers & payors: http://bit.ly/jpt0KB
• MT @dgmacarthur: analyses of early @iontorrent data by @pathogenomenick (http://bit.ly/miHnoj) & Keith Robison (http://bit.ly/jYemtG)
• Interesting @NatureNews piece on Anil Potti & how scientists view & manage their online reputations: http://bit.ly/iHFAx8
• $GNOM update: a backlog of genomes (>2k) & plans for aggressive pricing, new machines & ~1K genomes/month by year end: http://bit.ly/mCeeJC
• RT @PGxReporter: Continuing Push to Diversify Offerings, Myriad Licenses Chronix’s Early Cancer Detection Technology: http://bit.ly/ijzK1t
• Is public’s (not scientists’) reluctance to question Bin Laden DNA ID evid. of genetic exceptionalism? http://bit.ly/jCG7me by @Erika_Check
• VA db a great potential resource. Too bad it’s relatively closed & researcher-only (i.e., no EHR linking or participant data return)
• Veterans Affairs to create genomic research database with 1M vets: http://bit.ly/m6zWSg via @PGxReporter
• RT @MishaAngrist: Of 113 med devices recalled from 05-09, 80 (71%) fast-tracked by FDA: http://bit.ly/jLNN2s (via journalistsresource.org)
• $800B or not, Jim Evans says expectations for personalized genomic info remain too high: http://bit.ly/e0eBdA HT @MishaAngrist
• RT @bmahersciwriter: Great piece dissecting the logic of an $800bn return on investment for the human genome http://bit.ly/jW0pAO
• $LIFE-funded study: $800bn = economic impact of human genome project http://on.wsj.com/lnmQkL Report http://bit.ly/mAXixa
• CDER chief Woodcock says FDA expects to issue biosimilar guidance this year: http://reut.rs/j5nlCi
• RT @lukejostins: A conversation with @elainewestwick about sharing data, newborn screening and carrying cystic fibrosis http://bit.ly/mQjdBa
• Settlement in MA wrongful birth case: http://bit.ly/jZSXBt For past GLR coverage: http://bit.ly/9u060V
• RT @InSequence: Granting PacBio’s Reexamination Request, USPTO Invalidates All Four Helicos Patents: http://bit.ly/mT4fZF
• Study on how info affects DTC genetic testing decision: http://bit.ly/ki7QqR Anybody read/have the underlying study?
• RT @dgmacarthur: Have a burning question to ask genome visionary George Church (@geochurch)? Ask away: http://bit.ly/kHX0bF (via @ianholmes)
• PerkinElmer acquires Geospiza (@finchtalk), beefing up software for DNA analysis http://bit.ly/jGYiiM by @ldtimmerman
• Recent case further evid Fed Cir may leave 101 open, tighten other patentability criteria. See: http://bit.ly/gba0FI
• Fed Cir recently invalidated pair of DNA diagnostic patents: http://bit.ly/l411JS Will try to get analysis on GLR nxt wk
• The latest PGM vs. MiSeq ad from @iontorrent is out: http://youtu.be/gStCvyGpnRU Prev discussion here: http://bit.ly/fTkxlD
• Second rd of #FDADTC comments now appearing on regulations.gov (search FDA-20111-N-0066). Expect more in coming days.
• ZyGem, Lockheed developing portable forensic DNA platform: http://bit.ly/kha4Nj Goal: ID next Bin Laden in field in < 1 hr.
• GLR Post: News Roundup: Biotech Funding & LDT Regulation: http://bit.ly/jYTzWz
• This piece on Sulston, the human genome project & the Wellcome Trust by @markgfh is simply fantastic: http://bit.ly/miiX4X
• RT @dgmacarthur: .@nilshomer has joined the genome sharing gang – his @23andMe data are publicly available under CC0: http://bit.ly/lfLM22
• GLR Post: The Next Social Media Revolution Will Occur In…Personalized Medicine? http://bit.ly/lMimh7
• BRACAnalysis drives $MYGN revenues higher; company expects Euro launch in ’12: http://bit.ly/jyQ5Yj
• Supreme Court Case on Script Data Sale Presents ‘Gray Area’ for PBM Personalized Rx Efforts: http://bit.ly/lygTKo
• FTC continues fight against pay-for-delay drug deals, chairman calls them “outrageous”: http://bloom.bg/msSVrG
• RT @crossborderbio: Based on survey of clinical research site pros RT @JohnCFierce: top 10 CROs in CenterWatch survey: http://bit.ly/moqDGu

(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.

Biotech Funding: No Bubble, New Models and the IPO Option. Despite speculation that a recent rise in venture capital investments is indicative of a bubble, to be followed soon by a plunge in available investment capital, venture capital investments in the life sciences are holding steady, both in total dollars and in the size of an average financing. Thus, says Bruce Booth, a partner at Atlas Venture and author of Life Sci VC, there appears to be no bubble to debate, at least not in the life sciences. Booth observes that overall funding is “down considerably from the recent highs in 2007 and 2008” and, while other industries may be experiencing fewer but larger financings, “the data doesn’t support a frothy market for LS venture financings these days.”

Still,biotechnology innovation is neither easy nor cheap, leading venture firms to explore new product development and financing models. Large pharmaceutical companies, meanwhile, are also seeking to reinvent how they develop products in the face of a looming “patent cliff”. As the patents protecting many branded pharmaceuticals begin to expire, as will happen with Pfizer’s cholesterol drug Lipitor later this year, sales of these lucrative drugs will decline due to aggressive competition from generic pharmaceutical manufacturers. While not everyone is convinced that the patent cliff is a real phenomenon, real or not, big pharma certainly appears to be facing pressure to find new ways to identify and develop therapeutics.

The result, writes Ryan McBride of Fierce Biotech, is that VCs and big pharma are joining forces.

Pharma giants like Eli Lilly and Monsanto are collaborating directly with venture firms in an attempt to develop new products more efficiently. As McBride reports, Eli Lilly has announced plans to invest up to $150 million in external venture capital funds (including CMEA Capital) and Monsanto is collaborating with Atlas Venture (Booth’s firm) to identify new and early-stage biotech investment opportunities. Another example of VC/pharma collaboration is Enlight Biosciences, the drug discovery and development company founded by PureTech Ventures and funded by six major pharmaceutical companies (Abbott Laboratories, Eli Lilly, Johnson & Johnson, Merck, Novartis and Pfizer).

Even if some of these alternative biotech product development models prove to be successful, the end game for early-stage biotech investors remains murky. In his most recent post, Booth looks at the latest crop of biotech IPOs (since January 2010). Far from being the exit event early-stage investors might have hoped for, Booth finds that recent IPOs require significant additional participation from pre-IPO investors, affirming the prevailing wisdom that, at least in biotechnology, “IPOs are just financing events, and tough ones at that.” Just another reminder that an IPO may not be the right approach for every company.

LDT Regulatory Debate Continues. Since announcing last summer its intention to dramatically expand its oversight of laboratory developed tests (LDTs) by regulating them as medical devices, the FDA has yet to publicly propose a specific plan to bring LDTs under its purview. That does not mean, of course, that the issue has died. The FDA, Congress and industry groups are all considering several alternative approaches designed to modify – and hopefully to improve – how LDTs are regulated.

In a recent Boston Globe op-ed, Mara Aspinall of On-Q-ity and Brook Byers of Kleiner, Perkins, Caufield & Byers, “propose the creation of a dedicated FDA Center for Advanced Diagnostics Evaluation and Research [CADER] staffed with molecular diagnostics experts from all the relevant fields” as a preferred alternative to regulation of molecular diagnostics (many of which would likely qualify as LDTs) as medical devices within the existing FDA regulatory infrastructure. Although Aspinall and Byers do not refer to it by name, their proposal is another effort to promote a piece of legislation under development within the office of Senator Orrin Hatch (R-UT) that would create a separate regulatory pathway for so-called “advanced personalized diagnostics,” including the creation and funding of CADER within the FDA. Both Aspinall and Byers have previously indicated their support for the Hatch bill, which has yet to be introduced in Congress.

Meanwhile, at least one laboratory group is set to ask Congress to take a very different approach to LDT regulation.  According to Pharmacogenomics Reporter, the American Clinical Laboratory Association has “conceptually agreed” to ask Congress to modify two pieces of existing legislation – the Federal Food, Drug, and Cosmetic Act (FFDCA) and the Clinical Laboratory Improvement Amendments (CLIA) – to specify that the regulation of LDTs will be overseen by the Centers for Medicare & Medicaid Services (CMS) and not by the FDA. As Turna Ray writes for Pharmacogenomics Reporter, “ACLA’s plan to take its case to Congress suggests a deepening rift among disparate players in the diagnostics industry about how tests based on emerging technologies and marketed under complex business models should be regulated.”

Back in January, when we previewed the year ahead in personal genomics, we wrote the following:

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

With more than one third of 2011 in the books, and both a Congressional recess and the FY2012 budget battle looming, there seems little cause to alter that analysis.

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

• RT @FierceBiotech: Clinical, regulatory jobs top biotech’s “must-hire” list. http://bit.ly/m2zmKT
• RT @LifeSciVC: Dirty little secret of Biotech IPOs: Insider participation http://bit.ly/inPyW0
• 2011 CAP Policy Mtg live tweets from @CAPDCAdvocacy, incl. Gutierrez re: LDT oversight (though apparently not saying anything new so far).
• Additional detail from @Erika_Check on how DNA confirmed Osama’s death: http://bit.ly/kPHTkX
• FDA, FCC both working to improve development, approval process for wireless devices: http://bit.ly/jJEEez
• RT @InSequence: Illumina Starts Shipping 600 Gb HiSeq Reagent Kits; Takes First Orders for MiSeq: http://bit.ly/m4M1ji
• RT @InheritedHealth: We are excited to announce that @InformedDNA has acquired @InheritedHealth: http://ow.ly/4J7kM
• Wide-ranging overview of genomic data protection developments in @GenomeTechMag, incl. in DTC context: http://bit.ly/iDvXDt
• GLR Post: Forensic DNA Fights Terrorism: http://bit.ly/kiFcDs
• More on the Bin Laden DNA ID. It happened fast, but not *that* fast, according to @NerdyChristie: http://bit.ly/jHf9Lz
• Brook Byers & Mara Aspinall (two Hatch Bill backers) argue for new MDx regulatory, reimbursement model http://bit.ly/mFSWVM
• Part of the problem in Germany is that recent law (the GenDG) is so unclear. More here: http://bit.ly/gXMgkg
• RT @dgmacarthur: Germany debating changes to laws on preimplantation genetic diagnosis: http://bit.ly/k58SoX (from @PHGFoundation)
• Lab Group to Ask Congress for Statutory Changes to Keep LDTs Under CLIA: http://bit.ly/mKfoNg
• “We embrace openness,” says $PACB in describing new SMRT data analysis software: http://bit.ly/kdEnKH HT @dgmacarthur
• RT @PHGFoundation: Progress and challenges for the Encyclopedia of DNA elements http://bit.ly/luOUB9
• Bin Laden was identified by matching DNA to sample taken from sister’s brain: http://bit.ly/mtmNsW HT @MishaAngrist @RebeccaSkloot
• RT @dgmacarthur: Today is the last day to submit comments to the FDA on DTC genetics! A reminder from @genomesunzipped: http://bit.ly/lsUJ93
• RT @PGxReporter: ASCO and CollabRx Partner to Develop Online Apps for Cancer Treatment Targeted to Molecular Subtypes: http://bit.ly/jEKMqH
• Blackstone Entrepreneurs Network launches in NC’s RTP: http://bit.ly/dVnjRJ HT @DukeGEN cc @JCainHart
• NIH trims grants 1-3% in wake of budget cuts: http://bit.ly/eNkVM4 by @ScienceInsider
• Re: Kathy Hudson talk, @DNAlawyer reports “7 Proposed reforms to human research participant protections (to be pub. soon), incl. #IRBreform”
• $MYGN to acquire Rules-Based Medicine for $80M in attempt to expand companion/molecular Dx portfolio: http://bit.ly/m89GPG
• Incl analysis from @dgmacarthur RT @ldtimmerman: PacBio, after 7 years and $580m, ships 1st commercial DNA sequencer http://bit.ly/kdMW93
• RT @MichelleNMeyer: live tweeting symposium on Medicine & Culture: Genetic Determinism Then & Now: Confronting Legacy of Eugenics #Ackerman
• Will Hudson provide update today on NIH’s genetic test registry? http://bit.ly/esM7PG Hope @DNAlawyer will fill us in.
• $LIFE fell just short of Q1 revenue estimates: http://bit.ly/ePV179 $ILMN didn’t: http://bit.ly/gC01NA
• PGP Newsletter #5: congrats to @geochurch on Bower Award. Exciting times ahead for @PGorg: http://tinyurl.com/62a23pq
• Deadline Monday. MT @23andMe: Public Comments Due on Possible FDA Regulation of DTC Genetic Testing: http://bit.ly/hzz4ja
• NY leaders seek new biotech development model. (Rightly) looking to @ncbiotech for guidance. http://bit.ly/g1aewp @GENbio
• FDA rejects Aricept patch for Alzheimer’s disease: http://bit.ly/hhq9Yg
• SCOTUS hearing case on Rx data-mining today: http://n.pr/f78dnU Likely broader ramifications for commercial data-mining.
• RT @LifeSciVC: RT @biotechworld: VCs, Big Pharma join forces to tackle market challenges http://bit.ly/gfec8f
• Newsweek piece (http://bit.ly/gBlnN9) about BGI includes eye-popping statistics about Chinese seq giant & hints of what’s still to come.
• U.S. Effort to Remove Drug CEO Jolts Firms: http://on.wsj.com/i6hMi2 via WSJ re: gov’t attempt to remove $FRX CEO
• RT @dgmacarthur: Very cool – sequencing tech startup Oxford @nanopore has raised £25 million/$41m in new funding: http://bit.ly/f4Iyr9
• Today is Genetic Equity Awareness day in VT: http://bit.ly/hCqYaV More momentum for this legislation? http://bit.ly/i9fIT5
• More from WB: initiates coverage on $GNOM (outperform: http://bit.ly/hUbvJG) & $PACB (market perform: http://bit.ly/h76j0a)
• WGS market analysis fr William Blair, incl. $GNOM, $LIFE, $ILMN & $PACB: http://bit.ly/emYypW Overall, very positive.
• Very nice. “ALS Study Shows Social Media’s Value as Research Tool”: http://on.wsj.com/heMK3k by @patientslikeme paper: http://bit.ly/guma4c
• Fantastic! RT @girlscientist: IDNA Day at @HudsonAlpha–public welcome to walk possibly world’s largest DNA molecule: http://is.gd/O0feLu
• More on $LIFE/$ILMN advertising. RT @matthewherper: DNA sequencing firm apes Apple’s computer ads. http://ow.ly/4FE23
• Now: “Genetic knowledge, whether the high priests like it or not, is going to be a crowd-sourced phenomenon.” (4/4)
• Then: “personalized genomics will struggle to say anything useful at all, for the simple reason that it will be too personal.” (3/4)
• When it comes to personalized genomics, Matt Ridley (@mattwridley) has clearly had a change of heart over the past 6 mos. (2/4)
• Compare “The Failed Promise of Genomics” http://on.wsj.com/dnWRQO & “Your Genes in an Envelope? More, Please” http://on.wsj.com/hU8yqa (1/4)
• RT @ldtimmerman: VCs turn up the heat on Capitol Hill to get FDA to move faster, be more predictable http://bit.ly/ePp2AD
• RT’ing = preaching to converted? RT @ldtimmerman: BayBio’s annual conference, tweet by tweet. http://bit.ly/ghc53a #baybio2011
• EMRs for genetic research. Great potential but sig current EMR limitations: http://bit.ly/hYdV0o summary: http://bit.ly/eBGT9u HT @drjonboyg
• MT @EdwardWinstead: MassGenomics discusses consent protocols & counseling w/r/t WGS of 2 cancer patients http://bit.ly/i07BYk cc #IRBreform
• Great event. Thx to @zittrain for tremendous panel moderation. RT @PGorg: Ethics & genetics in the digital age http://hvrd.me/gOOkLO
• RT @InVivoBlogChris: In Search of a Golden Mean: balancing innovation and execution in biopharma: http://bit.ly/eiU1rv
• Scientists Must Change Their Culture to Bring About Better Healthcare: http://bit.ly/gWl9Pq by @finchtalk in @Xconomy, recapping #sagecon
• Congrats! RT @markgfh Recombination procedure worked! Anna Martha Henderson born this morning, a robust 9lb 2oz!
• RT @FierceBiotech: VC report: Rounds get fatter as the number of deals shrinks. http://bit.ly/idbscH
• RT @MishaAngrist: The State of Mutation Curation featuring @dgmacarthur http://bit.ly/g8hic5
• Most damning to “genetics crisis” argument? @dgmacarthur & @lukejostins taking apart Latham’s rebuttal in comments: http://bit.ly/ffvsTi
• Debunking some “totally & completely absurd” hype & fear re: mobile health regulation: http://bit.ly/eSBQNa @mobilehealth
• RT @genomesunzipped: The Genome Hasn’t Failed, or The Many and Varied Errors in a Genetic Denialism Article http://bit.ly/gH3UWm
• More here: http://bit.ly/fTkxlD MT @dgmacarthur: New Ion Torrent attack ad: http://bit.ly/hDwyqI
• RT @matthewherper just got served an ion torrent ad while reading questionablecontent.com. Don’t know what this means, but feel weird abt it
• RT @FierceBiotech: CROs scramble as Big Pharma lines up strategic partnerships. http://bit.ly/g5Arow
• RT @23andMe: Call to Participate in a New Study on Social Networking and Personal Genomics: http://bit.ly/fYI9Ze
• Discussion of educating vs. informing ignores longitudinal science com. Not every story need be self-contained. #soNYC
• Schmidt recs skepticalscience.com for those who want one line rebuttals for Crazy Uncle Joe’s science denialism #soNYC
• Ropeik: Default is not to trust. “To be wary is to survive.” How to build trust? Circumstances, esp fear #soNYC
• Schmidt: it’s a good thing we don’t have automatic trust in pub/priv institutions. But, more diff to get public health/sci msgs out. #soNYC
• Schmidt: ppl we need to reach are ones in middle, whose minds aren’t made up & who know a sound bite != whole story #soNYC
• Agreed, esp in policy roles. RT @LouWoodley: Science needs to be aware of who it picks as its spokespeople – some are polarising #sonyc
• Schmidt: why don’t scientists just stay in ivory towers & ignore controversy? When Congress drags you to DC, you don’t have a choice. #soNYC
• Now it’s time for Q&A at #soNYC. If you’re watching online, Tweet your questions at those of us in the room.
• Schmidt: Republicans today don’t not like science. They love science. They just don’t like the results. #soNYC
• Gavin Schmidt (NASA) makes great pt: climatologists largely reluctant & relatively recent public policy participants #soNYC
• #sonyc getting underway w/ @LouWoodley, @j_timmer & many, many more. You can follow along live: http://bit.ly/gacfov
• Excited to have found my way to Weiss 305 @ Rockefeller for first #soNYC event. Great & growing crowd.
• RT @JohnCFierce: Duke, Coulter Foundation create $20M endowment for translational research work http://bit.ly/dNGWTS cc @JCainHart
• GLR Post: Next-Gen Sequencing Heading to Madison Avenue? http://bit.ly/gKszNF
• RT @LifeSciVC: Big Academic-Pharma Deals: A threat or opportunity for early stage VC? http://bit.ly/f7lnAW
• Good opt-in approach RT @blaine_5: Genetic genealogy company DNA Heritage ceases operations & transfers to FTDNA: http://tinyurl.com/3bsczbv
• RT @dgmacarthur: On the advantages of the @CompleteGenomic genome factory approach: http://bit.ly/g7ovb0
• RT @genomesunzipped: I’m an Ion Torrent! Next-generation sequencing companies adopt viral advertising strategies: http://bit.ly/ezluS6
• RT @matthewmarkus: “The Practice of Law in the Era of ‘Big Data’” http://goo.gl/AFzPO via @bigdata
• RT @FierceBiotech: When nanotech meets biotech. http://bit.ly/eQPZOg
• RT @InSequence: Source BioScience Expanding Next-Gen Sequencing Services, Moving into Cancer Dx: http://bit.ly/dN8ioS
• RT @CompleteGenomic: new blog post covers 1st impressions & benefits of a factory approach to human genome sequencing (http://bit.ly/fDLiDI)
• Spontaneous #IRBreform proto-conference demos power of @twitter. Challenge: integrate w/ efforts of #sagecon, others to turn ideas to action
• Absolutely. Same with work overseas. But the solution is not to drive everything away from public funding. That ignores need for #IRBreform
• Course, this is what we should have at present, so question is how we get there from here. Think involving individuals will help #IRBreform
• Ultimate need: dispense with pro forma IRB oversight & consider appropriate protections for specific individuals/projects #IRBreform
• (Incidentally, the fact that these conversations are even happening is a major improvement over where we were a few years ago #IRBreform)
• Thankfully, we have some groups already helping diversify, including @PGorg, @genomera, @DIYgenomics, etc. NIH, others are aware #IRBreform
• Traditional model (inc. no return) works well sometimes. Other times (need for GxE linked data, citizen science, etc) it doesn’t #IRBreform
• What we need is more diversity in how scientific research, especially in personalized medicine, is conceived. #IRBreform
• Parents favor genetic tests that might detect children’s susceptibility to common diseases: http://1.usa.gov/edsvJe via @genome_gov
• Where did FDA say that? RT @bmahersciwriter: Despite interest in DTC genetic testing for kids, FDA says it’s a bad idea http://bit.ly/efYyDy
• Weekly Roundup: FDA Regulations (510k, Dx, WGS & EHR), Science Funding & Newborn Screening: http://bit.ly/h89Lvc
• NYT: guidelines allow for earlier definition, stratification of Alzheimer’s: http://nyti.ms/fm1whM
• MT @bmahersciwriter: Look out, cliff! RT @matthewherper: None of 10 most popular drugs in US are brands: http://ow.ly/4Dhi2

When NIH refused to act, a larger group filed a class action lawsuit (pdf) in Pennsylvania federal court against Genzyme and Mt. Sinai for damages allegedly caused by their inability to get prescribed dosages of Fabrazyme^®.   As we reported last month, the suit raises novel legal theories and faces an uncertain future. (Earlier this month Genzyme filed a motion to dismiss (pdf) the lawsuit.)

Additional Supply Delays Prompt Rehearing Request. The patients have now gone back to NIH, asking for a rehearing of their march-in petition in light of new evidence. Their lawyer, C. Allen Black (who is also co-counsel in the class action), points out that that the supply problems have gotten worse because of another contamination incident at Genzyme’s Allston, Massachusetts facility. As a result, Genzyme pushed back its anticipated resumption of “normal supply” of Fabrazyme^® from early 2011 to the second half of 2011.

However, Genzyme acknowledges that even that target date depends on:

the expected approval of our new manufacturing facility in Framingham, Massachusetts. Until this new facility is approved, Fabrazyme^® inventory remains low and supply will be vulnerable to disruption due to unforeseen manufacturing events such as this one.

The Genzyme announcement also declines to give specific information about regional differences in supply, advising patients to contact their company representatives.

As the Fabry patients’ new NIH march-in petition contends, all of this is hardly grounds for optimism about renewed supplies. In denying the original petition, the NIH seemed to be relying on the likelihood that Genzyme would resume normal production long before any other manufacturer would be able—or willing, given the cost of producing a biologic like Fabrazyme^®—to get up and running. As the NIH reasoned in denying the original petition (pdf):

A march-in proceeding resulting in the grant of patent use rights to a third party will not increase the supply of Fabrazyme^® in the short term because years of clinical studies and regulatory approval would be required before another manufacturer’s product could become available to meet patients’ needs in the United States….Finally, Genzyme has indicated that it expects the production of Fabrazyme^® to be back to full supply levels in the first half of 2011.

The NIH added, however:

Notwithstanding the foregoing, NIH will continue to carefully monitor the shortage of Fabrazyme^® and will re-evaluate this determination immediately upon receiving any information that suggests progress toward restoring the supply of Fabrazyme^® to meet patient demand is not proceeding as represented.

The NIH now has exactly that—“information suggesting progress toward restoring the supply of Fabrazyme^® to meet patient demand is not proceeding as represented”—and, if taken at its word, can be expected to give serious consideration to the Fabry patients’ petition for rehearing.

The Right Time to March In? The primary rationale for denying the original march-in petition was that, even with a forced NIH license, no competitor would be able to bring a Fabrazyme^® substitute to market before Genzyme would be able to alleviate the shortage on its own. However, as delays continue to mount, that argument seems increasingly dubious.

The NIH has also worried, particularly in denying previous march-in petitions, about the consequences of forcing biotech investors to continually weigh the possibility of government encroachment on the proprietary rights they thought they had purchased. But as the Fabrazyme^® situation becomes increasingly dire—a drug shortage with ongoing detrimental consequences to Fabry patients—the NIH must seriously consider two key questions:

(1) Would marching in here really send a troubling signal to the broader marketplace, given the significant and ongoing delays that have led to this point? and

(2) If marching in would fail to provide a meaningful remedy to these Fabry patients, then under what circumstances would the government’s march-in rights under Bayh-Dole constitute a viable remedy?

As we asked when the Fabry patients’ original petition was denied, if NIH refuses to march in here, will it ever?

The NIH has promised to evaluate new information that could change its determination “as quickly as possible to determine whether our decision should be modified.” The Fabry community and the biotech community now await the NIH’s response.

UK Insurers Continue Moratorium on Predictive Genetic Tests. In 2008 the United States passed the Genetic Information Nondiscrimination Act (GINA). Title I of GINA prohibits health insurers from using genetic information to deny coverage or to set premiums or payment rates. Title II of GINA addresses the use and misuse of genetic information by employers. In the United Kingdom, which provides universal health coverage through the government-funded National Health Service (NHS), discussion of genetic nondiscrimination has largely focused on the employment context (see, e.g., the 2009 report on Genomic Medicine from the House of Lords). To date, however, the United Kingdom has not enacted a formal prohibition on the use of genetic information by either employers or insurers.

Although the U.K. lacks a formal counterpart to GINA, in 2001 the Association of British Insurers (ABI) and the government’s Department of Health did establish a voluntary moratorium on the use of predictive genetic testing by insurers. According to the ABI:

The moratorium means the results of a predictive genetic test will not affect a consumer’s ability to take out any type of insurance other than life insurance over £500,000. Above this amount, insurers will not use adverse predictive genetic test results unless the test has been specifically approved by the Government. Only around 3% of all policies sold are above these limits. The only test that is approved is for Huntington’s Disease.

The moratorium was initially scheduled to expire in 2011. It was extended until 2014 in 2008 and, this past week, it was extended again, to 2017. The moratorium is scheduled to be revisited again in 2014.

Myriad Oral Argument. As regular GLR readers already know, the latest development in the Myriad gene patent litigation occurred on Monday. The Federal Circuit heard oral argument in the case, which will likely be the last public step before the three judge panel issues its opinion in several months. We’ve already discussed here at the GLR what we learned from the Myriad oral argument, but there has been excellent coverage of the case elsewhere as well. At the Pharmacogenomics Reporter, Turna Ray explored the somewhat confusing position Myriad took at oral argument with respect to the relationship between the company’s BRCA patents and whole-genome sequencing. In addition, the lead up to the oral argument also produced some interesting analyses, including at The Atlantic, where Andrew Cohen provided a play-by-play account of the events to date, and at Nature.com, where Shobita Parthasarathy focuses on how Myriad, regardless of its outcome, has produced “a more democratically engaged patent system.”

One other patent-related note: for those who are wondering what a government shutdown later today might mean for the US Patent Office, Patently-O has the answer. [Update: Nature also has an excellent high-level overview of how a shutdown will affect various government agencies, including the NIH and the FDA.]

Breast Cancer’s Complexity. Finally, a recent study from researchers at Washington University in St. Louis serves as a reminder that our knowledge of breast cancer, despite the ongoing litigation over the BRCA1 and BRCA2 genes, is still woefully incomplete. Scientists led by Matthew Ellis have sequenced the whole genomes of fifty patients’ breast cancer tumors along with matching DNA from the same patients’ healthy cells. They presented these results at the Annual Meeting of American Association for Cancer Research on April 2nd and revealed that most of the 1700 genetic mutations discovered were unique to individual patients’ tumors and only three occurred in 10% or more of the patients.

The sample was from patients in clinical trials of estrogen-lowering drugs known as aromatase inhibitors. Patients who are not responsive to such drugs have lower survival rates, but scientists do not know what causes these differences. One such association was for the breast cancer suppressor gene MAP3K1, which produces a protein that accelerates programmed cell death. MAP3K1 mutations were associated with the aromatase inhibitor-sensitive–more favorable–type of disease and were present in about 10% of the tumors. This result may be beneficial for pharmacogenomics research aimed at targeting particular types of breast cancers – similar to the research that led to the Genentech drug, Herceptin.

The next step will be to repeat the experiment with a much larger sample size (at 1,000 tumors), an indication of just how far we have to go when it comes to truly understanding how diverse cancers operate in equally diverse individuals.  Additional coverage is available from GenomeWeb and The Wall Street Journal.

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

• RT @GenomeWeb_News: Macquarie Begins Coverage of five clinical labs, incl Genomic Health, Myriad Genetics: http://bit.ly/g1JS7n
• Using BRACAnalysis as companion Dx RT @GenomeWeb_News: Myriad Partners with BioMarin on PARP Inhibitor: http://bit.ly/fMVasv
• More on Myriad & WGS by @pgx_reporter (http://bit.ly/eleiCG) but, really, no clear guidance in oral argument & doubtful in opinion either.
• RT @daphnezohar: Taking a closer look at the significance of statistical significance http://on.wsj.com/gDOkTF
• MT @CompleteGenomic: We’ve added 29 human genome sequences to public repository. 69 avail now <http://bitly.com/gyvaVo>
• RT @GENbio: Translational Research Is the NCATS’ Meow for Growing NIH’s R&D Role http://bit.ly/goYKfo
• Genetic data & no use for it *right this second*? Throw it away, obviously. @MishaAngrist w/ a too-rare blogging foray: http://bit.ly/fA6rNY
• For the full HGC report & recommendations – which are perfectly sensible – on carrier screening see here: http://bit.ly/hLkLeI
• Carrier screening a “modern version of eugenics” & “immensely dangerous”: http://bbc.in/f77iR1 Big, scary words for short, cursory BBC story
• MT @dgmacarthur: My carrier test op-ed (http://thetim.es/guUD0n) & excellent piece by @markgfh (http://thetim.es/guUD0n) – both £, sadly!
• RT @FierceBiotech: Gene-patent courtroom drama plays out in Washington. http://bit.ly/dSxcja
• GLR Post: What We Learned From the Myriad Oral Argument: http://bit.ly/gRUaiB (Short version: wait until June)
• RT @NatureNews: Patent dispute threatens US Alzheimer’s research http://goo.gl/fb/MH9vN
• RT @dgmacarthur: Computation guru Stephen Wolfram had his genome sequenced by $ILMN, found little of interest: http://bit.ly/ewNNhs
• RT @JohnCFierce: WSJ adds its own bleak assessment of biotech IPO market. Weak demand gives pharma an edge. http://on.wsj.com/fECZOe
• RT @bioitworld: UK insurers renew moratorium on using predictive genetic tests (except Huntington’s) http://bit.ly/eX4akZ
• Not first time in ’11 contingency plan developed. RT @ScienceInsider: NIH’s ‘Secret Plans’ for a Government Shutdown: http://bit.ly/i9TG71
• RT @ldtimmerman: Welcome to New York post from @xconomy NY editor Arlene Weintraub @awjourn http://bit.ly/g1ti4A
• HHMI announces $60M grant competition challenging universities to “think creatively” about science education: http://bit.ly/f02DHm
• RT @GenomeWeb_News: Oppenheimer Revises Revenue Estimates for Life Technologies: http://bit.ly/f1YPRj
• RT @GenomeWeb_News: Goldman Sachs Adjusts Illumina EPS, Revenue Estimates: http://bit.ly/gxvT20
• Welcome to NYC! RT @Xconomy: Xconomy opens in New York City, the sixth hub in our expanding network: http://bit.ly/hhP1Oz
• Audio from Myriad gene patent oral argument is now available online: http://bit.ly/dMLSYK
• RT @InSequence: Cancer Genome Atlas Aims to Sequence 3,000 Tumor/Normal Pairs by Year-End: http://bit.ly/h3sIgH
• RT: @ipwatchdog WH to hold Startup America Roundtable in St. Paul on April 6th http://bit.ly/h5xlcs includes reducing barriers roundtable
• RT @GenomeWeb_News: Ion Torrent Certifies Ambry Genetics: http://bit.ly/geT9vf
• Hard question to which there is no current answer RT @23science: will FDA send VU a letter too? http://bit.ly/hWijEt
• Vanderbilt’s ambitious attempt to integrate EHRs & genomic data/research for cancers: http://bit.ly/hWijEt Much more like this needed.
• RT @23andMe: DTC Genetic Tests and the Future of Regulation: Make Your Voices Heard: http://bit.ly/g8ECDz #FDADTC
• GLR (Re)Post: A Spectator’s Guide to Today’s Oral Argument in Myriad Gene Patent Litigation: http://bit.ly/eqbjz9
• Next step: repeat with 1,000 more. RT @NatureNews: Fifty genome sequences reveal breast cancer’s complexity http://goo.gl/fb/f5Hxk
• RT @GenCounsNews: Collaboration among multiple Alzheimer’s research groups leads to id of new genes http://nyti.ms/exEFSC
• Update to the @PGorg website includes publicly available copies of revised consent forms: http://bit.ly/hC2YH1
• RT @mikesgene: Post-Doctoral Position at Center for Genetic Research Ethics and Law http://bit.ly/dRlNXq #genome #GE3LS
• (And congrats to @shwu on the author credit for the 24th chromosome. Can a nobel be far behind for such a momentous discovery?)
• Heh. RT @23andMe: Blog Post- 23andMe Discovers 24th Chromosome, Changes Name to 24andMe: http://bit.ly/eSmZSG
• Isn’t seeming “pointless but cool” a great result for a new ad? re: Ion Torrent’s tilt-shift video ad: http://bit.ly/hVOSpP HT @dgmacarthur
• Friday Links @genomesunzipped: @23andMe confirms identical twinnery; tell FDA what you think about DTC genetics: http://bit.ly/eReQPD
• RT @shwu: All #FDADTC presentations and comments (submitted by Mar 1 deadline) now available at http://1.usa.gov/i24b7F
• RT @InSequence: Grants Drive 47 Percent Growth in Helicos 2010 Revenues, but Add’l Funds Needed to Stay Afloat: http://bit.ly/eFhMTj
• GLR Post: Weekly Roundup: Science Funding, DTC and Medical Device Caucusing http://bit.ly/ih9Fod
• GLR Post: A Spectator’s Guide to Monday’s Oral Argument in Myriad Gene Patent Litigation: http://bit.ly/eqbjz9
• Mayo petitions Supreme Court for cert (again): http://bit.ly/gizf6T After most recent ruling (http://bit.ly/gvBOVx) a grant seems unlikely.
• House version of Patent Reform Act closely tracks Senate’s, with a few key exceptions: http://bit.ly/eQNHN0 by @patentlyo

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.

Robert Cook-Deegan contributed to this commentary. Dr. Cook-Deegan is

The past few months have brought a number of significant research and commercial developments in the BRCA diagnostic testing market, particularly in Europe. These developments have been met by enigmatic comments from the management of Myriad Genetics, the sole provider of commercial BRCA diagnostic testing in the United States and a defendant in ongoing and closely-scrutinized gene patent litigation. What can these recent developments tell us about Myriad’s future plans in both Europe and the U.S.?

The Next Generation of BRCA Testing. Myriad’s current BRCA diagnostic test, BRACAnalysis (pdf), uses a combination of two traditional technologies—Sanger sequencing and PCR—to identify mutations associated with a significant risk of breast cancer and/or ovarian cancer in the BRCA1 and BRAC2 genes. Although Myriad has dabbled with next-generation sequencing technologies, Myriad has yet to announce any concrete plans to apply any of the increasingly numerous and powerful next-generation sequencing technologies to its BRACAnalysis testing.

Others, however, are moving rapidly in exactly this direction.

In April 2010, Mary-Claire King and her colleagues at the University of Washington published a paper in PNAS (pdf) that described the massively parallel sequencing of 21 genes, including BRCA1 and BRCA2, but also 19 other genes that, when mutated, confer an increased risk of breast and/or ovarian cancer. They offered their research as “proof of principle for the application of solution capture and next-generation sequencing to mutation detection for patients at high risk of breast cancer.” A next-generation sequencing approach to breast cancer testing, they determined, could successfully detect far more deleterious mutations in far more relevant genes than the Myriad test detects, and could do so at a fraction of the cost of the commercial BRCA testing performed by Myriad in the United States.

Next, in October 2010, Stephen Salzberg and Mihaela Pertea published what they described as a “Do-it-yourself” approach to BRCA diagnostic testing. The Salzberg Screen, as it is known, analyzes previously obtained genomic sequence data (e.g., from whole-exome or full-genome sequence data, which is commercially available) for BRCA mutations by querying publicly available resources. Salzberg and Pertea freely acknowledged that a primary motivation in supplying the Salzberg Screen was “to empower any individual…to test for [BRCA] mutations and circumvent [Myriad’s] gene patents.” In assessing the Salzberg Screen and its impact on Myriad we noted that Salzberg and Pertea were taking a “calculated gamble” in this regard. The test separates the crucial steps of sequencing and interpretation, arguably avoiding direct infringement claims for many of Myriad’s broadest patents, although arguments based on inducement of infringement might remain viable. We wrote then that Salzberg and Pertea were likely gambling that Myriad simply lacked the stomach to initiate any additional BRCA-based litigation and, at least so far, their gamble appears to have paid off.

Importantly, the integration of next-generation sequencing data in BRCA testing is not just a subject for medical journals. It is also beginning to find its way into clinical and commercial applications.

This past October, two European research hospitals—Ghent University Hospital in Belgium and the University of Leeds Institute of Molecular medicine in the United Kingdom—announced plans to use next-generation sequencing technology to perform diagnostic sequencing for BCRA1, BRCA2 and other genes. And just this past week, a British company called NewGene announced plans to sequence the entire coding region of BRCA1 and BRCA2 genes for UK patients with a family history of breast cancer.

Both NewGene and the research laboratories intend to utilize so-called next-generation sequencing technology in performing BRCA diagnostic testing. Both New Gene and Ghent University Hospital employ the Roche 454 GS-FLX pyrosequencing platform, while Leeds is proceeding with Illumina’s Genome Analyzer.

Finally, last month, at the Advances in Genome Biology and Technology (AGBT) meeting, GenomeQuest announced a “clinical diagnostics reporting” service for whole-genome sequence data. Like the Salzberg Screen, GenomeQuest utilizes a software-based approach to analyzing already existing whole-genome or whole-exome sequence data. Unlike the Salzberg Screen, however, GenomeQuest’s product is explicitly commercial and intended for clinical diagnostics, including hereditary breast cancer.

A common motivation in each case is a desire to reduce the cost of diagnostic testing, and particularly of BRCA testing. The cost of Myriad’s BRACAnalysis test in the United States varies somewhat by payer but is generally in the $3,000 to $4,000 range (Myriad actually raised the cost of its test by several hundred dollars after last spring’s district court ruling invalidating a number of its key BRCA patents), with the possibility of significant additional costs where follow-up testing is needed.

The expectation among Myriad’s competitors, including commercial offerings from NewGene and GenomeQuest, is that next-generation sequencing can significantly reduce cost (as well as turnaround time) while maintaining or even increasing the accuracy and degree of coverage. NewGene, for example, has reported a median test cost of under $1,000. Similarly, GenomeQuest has touted the ability of its product to “perform every known genetic test in the GeneTests compendium in one single protocol that costs about as much as a single genetic test,” echoing a point we (and plenty of others) have been making for years: there is a fundamental tension between the falling cost of whole-genome sequencing and the continuing high cost of single-gene diagnostic tests.

Is a Commercial Confrontation Brewing? Not all of the recent developments in BRCA testing represent a near-term, or even a long-term, commercial challenge to Myriad’s business. But developments which appear first in the pages of scientific journals or, as in the case of the Ghent and Leeds tests, in the University hospital setting, are certainly capable of showing up in commercial offerings before long. More immediately, NewGene’s stated intent is to expand its test’s availability beyond the United Kingdom to the rest of the European market and, ultimately, to come to the United States. GenomeQuest, of course, is already available in the United States.

So what about Myriad? For the moment, Myriad remains the exclusive commercial provider of targeted BRCA diagnostic testing in the United States. A major concern, however, is the company’s extreme reliance on the sales of a single product (BRACAnalysis) in a single market (the United States). Thus far, Myriad has achieved comparatively modest success developing a market for its other products (which include diagnostic tests for colorectal and uterine cancer, melanoma and pancreatic cancer) within the United States and for any of its products (including BRACAnalysis) outside of the United States. Currently, BRACAnalysis testing accounts for a striking 88% of the company’s nearly $400 million in annual revenues, with only 2% of those sales occurring ex-US. Myriad’s limited geographic reach, its heavy reliance on BRACAnalysis testing and current and projected competition from a growing array BRCA testing providers utilizing next-generation sequencing represent several of the key factors which caused Goldman Sachs to initiate its coverage of Myriad Genetics last month with a “Sell” rating (pdf).

Myriad, for its part, has taken some steps to address these concerns, in particular by seeking to expand its presence in Europe. Last July, the company created a new position—Executive Vice President of International Operations—in support of what Myraid’s CEO Peter Meldrum declared was the company’s “goal of building a significant presence in Europe by the end of 2012.” The subject of Myriad’s European expansion surfaced again this past January, with Meldrum making several intriguing remarks to investors during a routine earnings call. First, Meldrum indicated that Myriad plans to set up a central lab in Germany to process BRCA samples from all across Europe. That represented a change in plans from July’s announcement in which the company declared its intent to pursue its international strategy on a country-by-country and product-by-product basis—a necessity, given that each country has its own healthcare and reimbursement system.

A Change in Myriad’s Patent Policy? But the real eyebrow-raiser came when Meldrum was asked about Myriad’s patent enforcement policy as it seeks to enter the European market. Meldrum’s response: “if I had my druthers, I would not want to go into a new market in a heavy-handed fashion trying to enforce patents.” He suggested that Myriad might choose instead to rely on its “other competitive advantages that may make such [patent] enforcement unnecessary.”

The exact status and strength of Myriad’s patents in Europe has been cause for uncertainty for quite some time now. Myriad’s five European patents were narrowed significantly by the European Patent Office (EPO) several years ago and, as a result, are thought to provide less protection than the company’s United States patents (which are themselves under attack). A “European patent” is in fact a bundle of national patents issued by a central authority, the EPO; individual infringement suits have to be brought in national courts, one case at a time, which opens up the possibility of local political influence, as well as considerable delay and expense. Moreover, France, Belgium, and Switzerland all changed their laws in recent years to enable a form of compulsory licensing. They did so with Myriad’s BRCA patents explicitly part of the policy debate and rationale for change. Germany has not yet modified its laws in a similar fashion, and is where Myriad plans to build its base, but any attempt to enforce patent rights there could well precipitate the kind of intense firestorm of criticism that swept Australia when Myriad’s licensee there tried to enforce patent rights in 2008, and led Myriad to offer to revoke one of its Australian patents.

As a result, whatever the infringement analysis when examining a particular European competitor’s offering against Myriad’s European patents (and, as we have noted previously, whether or not next-generation sequencing approaches would infringe Myriad’s patents is not at all clear), the practical prospects for Myriad becoming the sole provider of diagnostic BRCA testing in Europe based on patent enforcement are somewhere between slim and none. Even if Myriad were to engage in a country-by-country patent battle and win far-from-assured victories in each case, the company could still lose the war for payment. Myriad would have to fight on a second front with a variety of national health systems holding the power of coverage and reimbursement decisions.

Which perhaps is what Myriad and Meldrum have recognized in citing the company’s “other competitive advantages that may make such [patent] enforcement unnecessary” in Europe. So just what are these “other competitive advantages”? Meldrum highlighted two for investors: speed and accuracy. Regarding speed, he claimed a two week turnaround time for Myriad versus up to a year for current European tests, although it should be noted that NewGene claims a 4-6 week turnaround for its BRCA sequencing product. With respect to accuracy, Meldrum claimed a 2% rate of finding variants of unknown significance (VUS) at Myriad—which seems low—versus a 30% VUS rate for the European tests—which seems high. In light of these advantages, Meldrum concluded on the January call, “I don’t believe that trying to enforce the patents is either a good idea or warranted at this time.”

So what might all of this mean for Myriad’s near-term commercial plans and patent enforcement policies? One option is to take Meldrum’s comments at face value. Around the world, in the popular press and in the eyes of many patients and healthcare providers, Myriad has been widely criticized for enforcing its patent monopolies with respect to BRCA genes and testing. If Myriad believes it can compete successfully in Europe without relying on its patent monopoly, why risk a further public relations backlash by filing patent infringement suits? In addition, one would think that Myriad’s dealings with the many European regulatory and payment authorities—which are unavoidable and will be difficult in their own right—would be less confrontational without pending patent litigation.

Against this background, Meldrum’s comments might be read as an effort to put a positive spin on the specter of growing concern over the degree of practical and legal protection Myriad’s BRCA patents will provide in the future.

The Point of Patents? But there is another layer of meaning to consider. Suppose that Meldrum is right about Myriad’s huge advantages in speed and accuracy. What explains those advantages? At least with respect to interpreting VUS results, such an advantage would derive, in all likelihood, from Myriad’s vast—and currently proprietary—database of BRCA test data, including VUS data. Data that Myriad generally doesn’t share, at least not anymore.

Until 2004, Myriad contributed VUS data to the Breast Cancer Information Core (BIC) mutation database—and publicly touted (pdf) those contributions. The BIC is an open access resource maintained by the National Human Genome Research Institute (NHGRI) to coordinate the detection, interpretation and dissemination of breast cancer mutation data. After November 2004, however, Myriad stopped depositing additional VUS data into the BIC (and has largely ceased publishing its VUS data in peer-reviewed literature, which would have a similar effect).

With that bit of background in mind, a cynic might read Meldrum’s comments like this:

While exploiting our U.S. patent monopoly over the past two decades we accumulated a unique database of relevant DNA sequence and clinical data. Now our U.S. patents are threatened, and many of them are expiring in the next few years anyway. And our international patents aren’t worth trying to enforce. We run a really efficient sequencing lab, and we’ve spent years getting agreements with hundreds of payers for our main BRACAnalysis test. So our new business plan is to combine production efficiencies and expand payment agreements, leveraging our unique proprietary data to retain US market share and enter international markets.

We take pains to emphasize that here we are speculating and, even if Myriad did go this route, there would be nothing strictly contrary to patent law in its doing so. Still, leveraging a proprietary database from a decade’s patent monopoly would be troubling, and would further damage Myriad’s reputation with patients, healthcare providers and the scientific and policy communities.

Among other things, such a strategy would run contrary—at least in spirit—to a policy against extending patent monopolies beyond their terms. In addition, the hoarding of immensely important clinical data does not seem likely “to promote the Progress of Science and useful Arts”—the Constitutional purpose of the patent system—and would provide ample additional ammunition to critics who claim that the current biotechnology patent landscape fails to properly balance commercial interest against those of science and society.

More practically, the current political climate is characterized worldwide, and especially in the United States, by calls for fiscal responsibility and an increasingly close scrutiny of government expenditures. Nowhere is this more true than in healthcare, where spiraling costs place pressure on national health systems (as well as private insurers) to separate effective modes of care from those which are merely expensive. There is little question as to the efficacy of Myriad’s current BRACAnalysis product. But should the company seek to extend its decades-long patent monopoly by restricting access to clearly relevant medical and scientific data, at a potentially considerable cost to both payers and the healthcare system, Myriad’s current and comparatively narrow patent issues might well take a back seat to more pressing economic and political concerns.

Still, for the moment, all of that is speculation. When it comes to Myriad’s actual plans, our best guess is that even Myriad itself has yet to decide exactly how it will proceed in the coming months. What Myriad does in Europe and/or in the United States will undoubtedly be dictated in large part by continuing shifts in the commercial landscape on both continents, as well as whatever happens next in the gene patent litigation, slated for oral argument at the Federal Circuit on April 4 (pdf).

Stay tuned.