By Kevin E. Noonan --
The ACLU championed its efforts in the AMP v. Myriad case as being another instance of the group fighting for the rights of the many and the powerless against corporate America and the oligarchical few. In a paradox, it now seems that the fruits of their efforts are to have empowered just those whom it has traditionally opposed, and that the question of whether personalized medicine will become widely available is in the hands of insurance companies and large diagnostic testing providers (who traditionally have not needed to rely on patent protection in view of their economic clout).
To better appreciate the irony it is useful to compare the history of the most successful personalized medicine effort to date, Myriad's BRCA gene tests for breast and ovarian cancer, with an alternative history premised on the Supreme Court's Myriad decision being rendered 10-15 years earlier that it was. Absent the prohibitions produced by the Myriad decision, Myriad had its patent exclusivity to rely upon in building its BRCA gene testing business. This began in 1997, three years before the announcement of the results of the Human Genome Project. At that time, genetic testing was in its infancy, and at best BRCA gene testing was considered "experimental": Myriad did not have anything other than genealogical data showing an association of genetic variants in the descendants of women who had dies of breast cancer, and had identified a few dozen specific variants. The reliability of the testing could also be reasonably brought into question because Myriad detected several "variants of unknown significance" (VUS), where the genetic sequence identified in a particular patient was different from the "typical" genetic sequence, but there was insufficient genealogical information. In addition, women having the BRCA gene mutation who suffer from breast or ovarian cancer are a small subset of the totality of breast or ovarian cancer sufferers, with frequencies in line with other diseases having a heritable genetic propensity.
Into this situation came Myriad, who armed with its patent exclusivity was able to obtain investors who permitted it to grow the business of testing women for the genetic mutations that indicated a high likelihood of developing cancer. (It should also be appreciated that the increased risk of breast or ovarian cancer for women bearing a BRCA gene mutation is much higher than is the case for other cancers, making this an anomaly for genetic diagnostic tests.) The investment was not only in laboratories, lab technicians and supplies; Myriad had to enlist a nationwide network of genetic counselors to provide women with the information they would need should their test indicate a propensity (~90%) for developing breast or ovarian cancer, as well as educating ob/gyn doctors about the test. While the latter can be discounted as marketing, Myriad also had to take on public and private insurers to have them pay for the test, and this needed to be done on a state-by-state basis. Indeed, acceptance of Myriad's BRCA test as being significantly reliable as to deserve coverage varied from state to state over the past 18 years since Myriad's BRCA gene patents were obtained.
None of this was (solely) altruism, of course; Myriad was running a business. But whether society benefited from Myriad's efforts can best be considered by comparison to that alternative history, where Myriad did not have exclusivity over BRCA gene tests.
This history can be predicated on an earlier enunciation of the Supreme Court's decision, or more easily by presuming that Mary Claire King or other researchers cloned the BRCA genes before Myriad and, as they have stated did not protect the genes or diagnostic methods by patenting. Under this scenario the gene sequences would have been freely available to anyone, particularly university and academic medical centers, such as New York University (where Dr. Harry Ostrer, one of the named plaintiffs in the Myriad case, was practicing) or the University of Pennsylvania (where other plaintiffs, Drs. Kazakian and Ganguly were working), as well as commercial entities. However, without patent exclusivity, the only commercial concerns capable of providing the service would have been unlikely to entertain the possibility, due in part to the high hurdles and costs associated with garnering acceptance from payors at that time. (Myriad didn't have a choice because BRCA testing for breast and ovarian cancer was a core business.)
Under these circumstances the role of providing genetic testing would likely have fallen to academic sources. This raises a few problems regarding the goal of making such testing broadly available and affordable. The first is geographic: while residents of cities and other locations that are the sites of major medical centers would likely have had access to BRCA gene testing it is less likely that less geographically accessible areas would have had such access. Women residing in and around Boston, or New Haven, or New York, or Philadelphia, or Washington, or Atlanta, or Dallas, or Houston, or San Diego, or Los Angeles, or San Francisco, or Portland, or Seattle, or Denver, or Rochester (MN), or Madison (WI), or Chicago, or Detroit, or Cleveland, or Buffalo, or Cincinnati, or Pittsburgh or St. Louis would have access. But women in Appalachia, or the Four Corners region of the Southwest, or rural Idaho, or Montana, or Arkansas or the Dakotas, would need the kind of outreach Myriad provided -- is it reasonable to expect any of the hospitals in metropolitan areas far from these more remote (and typically impoverished) regions of the country?
Perhaps more fundamentally, is genetic diagnostic testing as performed by Myriad the best use of academic medical facilities? Academic medicine, like most academic pursuits is involved in discovering causes of disease and developing new treatments. It is also not well adapted to the type of rote performance of thousands or millions of tests under circumstances where no errors are tolerated. It is hard to contemplate university or medical center counsel being comfortable with academic or even clinical labs performing such tests; inevitably, any such testing would come in conflict (for resources, personnel, lab space) with the traditional purpose of such labs and testing, being ancillary to providing optimal patient care. And this is as it should be: patients look to these hospitals and the physicians populating them as being primarily concerned with helping them get well (while acknowledging the reality that finances and in some cases profit enter into the equation).
But if the goal is the widest proliferation of diagnostic genetic testing then the question is, what is the best way to accomplish it. The idea that academic research and medicine will be able to do so is a fantasy for at least the reasons set forth above; more importantly, such researchers are best utilized in identifying the genetic causes of disease. Thus, the question comes down to whether small, academic-based start-up biotech and diagnostic companies or larger, more corporate diagnostic testing labs will monopolize the space. As the Myriad example illustrates, start-ups must have reliable patent protection in order to establish the protocols, networks, and reimbursement infrastructure needed to sustain such a business, while the larger diagnostic companies do not. The economic advantages these larger companies have will typically be enough for them to out-compete a startup, even one with better understanding of the science and technology. This is true upon inspection: for the startup one or a few genetic tests may be the only product they have to sell, while larger, more established diagnostic testing labs have a much larger product list (and much longer history with diagnostic customers) to sustain them while they adapt to a disruptive new technology like genomic testing.
Even with this economic clout success is not certain, because part of the impetus for startup companies such as Myriad to aggressively advocate for payors to reimburse patients for the testing stem from the reality that this is usually the only way such companies will survive. Larger companies have far less motivation for new technology (think Xerox/IBM vs. Microsoft/Apple) even if there is perceived profit in it. One example of this situation is reflected in a paper in Genetics in Medicine from the American College of Medical Genetics and Genomics published February 25, 2015. In this paper, the College provides a policy statement, arguing that payors should be willing to reimburse genetic testing costs even when the effects of these tests on clinical outcome in unclear:
Clinical utility for genetic tests was discussed in 1998 by the US Task Force on Genetic Testing. The Task Force specifically stated that "the development of tests to predict future disease often precedes the development of interventions to prevent, ameliorate, or cure that disease in those born with genotypes that increase the risk of disease. Even during this therapeutic gap, benefits might accrue from testing. "http://www.genome.gov/10001733. In the broadest sense, "clinical utility" refers to the likelihood that a given intervention (in this case, genetic information) will lead to an improved health outcome (http://www.phgfoundation.org/tutorials/clinicalUtility/) or to whether a test can provide information about diagnosis, treatment, management, or prevention of a disease that will be helpful to a consumer. http://ghr.nlm.nih.gov/handbook/testing/validtest. Establishing an etiological diagnosis is generally asserted to no longer be sufficient to claim clinical utility. Further, evidence that physicians change their management of a patient based on an etiological diagnosis is said to lack clinical utility unless clinical outcomes research has demonstrated that such changes in an individual's treatment will result in benefit. http://www.palmettogba.com/palmetto/moldx.nsf/MolDX_Manual.pdf. Moreover, coverage decision-making policy is now driven by a narrowed perspective that clinical benefit accrues only to the individual receiving the services. [emphasis added]
The College disagrees with this "narrow view" that only tests directly related to improved clinical outcomes should be recompensed. The article expresses the view that such testing should be considered for its "effects on diagnostic or therapeutic management, implications for prognosis, health and psychological benefits to patients and their relatives, and economic impact on health-care systems." Examples include those familiar to anyone who has taken Myriad's BRCA test: not only the benefit of an individual knowing her genetic status, but how that knowledge impacts the likelihood that her relatives will also have the test and know their risk (something for which Myriad charged much less than the widely reported $3,000-4,000 for the BRCA gene test). "Current models" of these benefits "define utility as either (i) clinical benefit specific to the individual receiving the service or (ii) "personal" benefit because it applies to other family members or because the result may suggest interventions that are less well defined. Grosse & Khoury, 2006, "What is the clinical utility of genetic testing?," Genet Med 8:448–450; Robson et al., 2010, American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol 28:893–901. This paradigm "frames the utility of genetic and genomic information too narrowly and fails to acknowledge that information regarding significant genetic risks can enable highly actionable -- indeed, life-saving -- interventions for individuals and their family members," according to the College. Further:
As genetic and genomic information increasingly enables disease prevention and reproductive planning, a narrow focus on medical benefit only to the individual originally tested and diagnosed is apparent as a construct of an obsolete system in which care is provided only to those with overt disease and that clinical benefit can be achieved only when a therapeutic option (i.e., a drug) is available.
Contrary to the predictions of the ACLU and many on its side of the debate, the Myriad decision has not led to an idyllic world of genetic diagnostics (an outcome aided by the Court's other decision negatively affecting the competitive position of startup companies, Mayo v. Prometheus). It will be instructive to see how BRCA gene testing progresses in the aftermath of Myriad "giving up the ghost" on its efforts to maintain a modicum of exclusivity with the Federal Circuit's invalidation of many of Myriad's remaining genetic testing claims. Many companies, including some large diagnostic testing labs, have entered these waters, but it is too soon to know how reimbursement, costs and accessibility are affected.
There is one way that a small company can maintain its exclusivity which forms Myriad's only remaining competitive advantage. Taking advantage of being the "first mover" in this space, Myriad has accumulated a large database of undisclosed "variants of unknown significance" (VUS) in the BRCA genes, the significance of which is not unknown to Myriad. Thus, even now an ob/gyn is faced with the quandary of advising a patient to have the "Brand X" test (which may be cheaper although how much cheaper is an unanswered question) or the Myriad test. If the patient has a widely known BRCA gene mutation all is well (for the physician), because she now knows how to advise her patient. If, on the other hand, the patient's genetic report contains one or several VUS's then the only responsible course would be to have the patient's sample retested (or at least reevaluated). Any benefits accruing from having the test available from parties other than Myriad thus evaporates.
Of course the larger companies have the same capacity and perhaps even moreso, which leads to the possibility that such companies will simply avail themselves of this model and keep all diagnostic testing information to themselves. In either case, the final result of the ACLU's overheated efforts will be that large corporate entities will "own" your DNA, and there will be nothing anyone can do about it. Which is something of a paradox, if not amounting to an irony.