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71 Tul. L. Rev. 1211
Tulane Law Review
March, 1997
Michael J. Malinowski Robin J.R. Blatta
Copyright (c) 1997 Tulane Law Review Association; Michael J. Malinowski, Robin J.R.
Blatt
COMMERCIALIZATION OF GENETIC TESTING
SERVICES: THE FDA, MARKET FORCES, AND
BIOLOGICAL TAROT CARDS
Many women fear being diagnosed with breast cancer, and rightfully so. Despite the
capabilities of modern medicine, the cumulative lifetime risk of getting the disease has
risen to one in eight and, despite decades of research, no cures exist. In this Article, the
authors explore the commercialization of so-called breast cancer gene tests, based
upon genetic alterations linked to the disease. Although the authors fully address this
specific technology, they use what constitutes the seminal case of predictive genetic
testing to analyze the adequacy of the existing regulatory framework. The authors
conclude that the present regulatory system is inadequate and places a dangerous
amount of reliance on primary care physicians. Their conclusion is grounded in the
observation that most primary care physicians lack sufficient knowledge about this
evolving investigative technology--which is highly subject to misinterpretation, and,
though potentially helpful to some “high risk” patients, offers questionable clinical value
for the general public. The authors set forth numerous proposals to promote both the
quality and clinical value of predictive genetic testing so that it conforms to public health
standards and can be properly integrated as a reliable component of medical care in
specific situations.
I.Introduction1212II.Today's Technology, Yesterday's Regulations1220 A. Overview of
Genetic Testing Capabilities1222 B. Existing Regulations1229 C. Dangers Arising from
the Premature Use of Genetic Testing1243III.The Seminal Case: BRCA Testing
Services1253 A. Meaningful Assessment of the Commercialization of BRCA Testing
Services1257 B. Some Stories1259 1. A Cancer Survivor's Story1259 2. A Genetic
Counselor's Story1264 3. A Consumer Advocate's Story1272 4. A Corporate
Representative's Story1275IV.Unifying Themes and Diverging Theories on
Regulation1279 A. Continued Deference to Market Forces1279 B. Call for Direct
Regulation1283 C. Drawing Conclusions1286V.Proposals for
Change1287VI.Conclusion1305 Appendix I1308 Appendix II1309
*1212 I. Introduction
OncorMed, Inc. (OncorMed), a small Gaithersburg, Maryland, biotechnology company
involved in general cancer testing, announced in January 1996 that it had begun selling
a testing service1 to identify *1213 the presence of genetic alterations linked to breast
and ovarian cancer.2 Within a few months, Genetics & IVF Institute (IVF) of Fairfax,
Virginia, began to offer a variation of the test3 to any Jewish4 woman *1214 willing to pay
$295.5 OncorMed then expanded its service to include tests for genetic alterations of
BRCA1 and BRCA2 for between $400 and $1,200 (the latter for combinations of the
genetic alterations).6 In the fall of 1996, Myriad Genetic Laboratories, Inc. (Myriad), a
Salt Lake City subsidiary of Myriad Genetics, also began selling a combined test for
several alterations of the two genes for $2,400.7 All of these companies are actively
developing markets for their testing services. According to one report, “[i]n the future,
OncorMed is expected to market its testing service to disease management facilities
and insurance companies, which would benefit from information about patients'
susceptibility to breast and ovarian cancer, as well as other diseases.”8 IVF, Myriad, and
OncorMed have not submitted and do not intend to submit their testing services to the
Food and Drug *1215 Administration (FDA) for review.9 According to their interpretation
of existing FDA and other federal regulations, they are not required to.10
The commercialization of these so-called “breast cancer tests”11 marks the advent of a
generation of predictive12 genetic testing products derived from discoveries reported
intensely in the media during the past several years.13 The public is demanding
more *1216 information about the technology,14 and other commercial and academic
laboratories are introducing their own tests for genetic-influenced disorders that may
help assess future disease risk.15 From a *1217 business perspective, these
laboratories are doing so (1) to generate immediate revenue streams to finance their
scientific research and development (R&D); (2) to amass patient data to determine the
extent to which their tests predict the onset of breast and ovarian cancer for the general
population, thereby giving them the option to sell their tests as kits and charge market
prices rather than simply recouping costs;16 (3) to obtain subject samples for gene
sequencing and outpace their science competitors; (4) to accelerate the development of
more marketable diagnostics, therapeutics, and maybe even gene therapies; and/or (5)
to increase familiarity, acceptability, and demand for such tests among physicians and
the public, and thereby perhaps achieve standard care acceptance and insurance
coverage for their products.17
The precedent set by IVF, Myriad, and OncorMed (as well as academic research
institutions) conceivably affects all Americans directly. More than five thousand genetic
alterations have been identified,18 and estimates are that every person has four or five
genetic alterations linked to serious health conditions.19 Now that a “critical mass” of the
human genome has been mapped through the Human *1218 Genome Project
(HGP),20 linkages between genes and health conditions should increase
exponentially.21 Technology also has made testing for genes associated with health
cheaper and easier, and standard medical practice soon will include much more genetic
testing.22 Kaiser Permanente, the nation's largest health maintenance organization,
already has decided to allow its divisions to offer BRCA genetic testing to its members.23
The danger is that, absent regulatory safeguards and quality controls, the forthcoming
multitude of predictive genetic testing *1219 services will be overused. Even tests that
are good predictors for some people may be overused and misinterpreted by patients,
providers, insurance companies, and employers.24 Biotechnology companies can sell
their testing services outside major research centers and through the broad community
of primary care physicians. This substantiates concern that genetic tests will become
widely available to patients without adequate pretest counseling by providers who either
“interpret” them without appreciation for the technologies' predictive limits or, worse,
leave patients to make their own interpretations. In other words, genetic testing may be
mainstreamed before the predictability of such testing is determined with scientific
accuracy. Such tests may become the equivalent of biological tarot cards, subject, like
the Tarot, to misinterpretation and overreliance.
This Article explores both the patient-care and public-health implications of
commercialization of predictive genetic testing services under the existing regulatory
scheme. A central premise is that regulatory safeguards must be introduced to ensure
that genetic testing is made available only when it carries scientifically valid predictive
value (positive predictive value, or PPV).25 Equally as *1220 important, providers and
patients must be educated about both the technology's limitations and their respective
legal rights and responsibilities.
Part II presents an overview of genetic testing capabilities, existing regulations, and the
dangers of premature use of genetic testing. Part III employs legal storytelling to
illustrate implications of the commercialization of genetic testing services. Part IV
addresses these implications by presenting diverging theories on the appropriate
regulatory response to the advent of commercialized genetic testing services. Part V
sets forth proposals for the responsible commercialization of these technologies.
II. Today's Technology, Yesterday's Regulations
Expansive genetic testing capabilities have been a long time in coming.26 Such
technology was foreseeable at the commencement of the HGP in 1990.27 Concern
about the impact of such testing on *1221 society inspired James Watson, codiscoverer
of the double-helix structure of DNA and the first head of the HGP, to insist at the outset
of the HGP that a respectable percentage of the annual budget be committed to
addressing the project's ethical, legal, and social implications.28
Nevertheless, most public health officials and other regulators, both federal and state,
are only beginning to become aware of the full implications of new genetic
technologies.29 Similarly, the *1222 genotechnology30 industry has just begun to
recognize the need to address ethical concerns regarding the commercialization and
responsible applications of its work.31 As a result, the regulatory infrastructure
necessary for responsible commercialization of genetic technology is being developed
in response to, rather than in anticipation of, its commercialization. The following is an
overview of present genetic testing capabilities, existing regulations, and dangers
arising from the premature commercialization of genetic testing.
A. Overview of Genetic Testing Capabilities
Today the scientific community is experiencing a nature movement as forceful as the
nurture movement that took force in the 1960s and that set the priorities in science for
the decades to follow.32 Behavioral genetics, the nature extreme in genetic medicine, is
a burgeoning field grounded in the belief that molecular genetics even *1223 “points the
way to the future of psychiatry.”33 Recent discoveries linking genes to complex behavior
such as depression34 and nurturing35 are reinforcing this belief.36
Generally, when a gene or biological marker linked to a physical or mental condition is
discovered, the basic scientific capability to test for the presence of that marker is a
given. Thousands of such linkages have been made subsequent to the commencement
of the HGP,37 and at a rate accelerating with the passage of time, to the point that
linkages are being identified almost on a weekly (if not daily) basis.38 Now that a critical
mass of the human genome map has been *1224 completed,39 the pace of such
discoveries is likely to increase exponentially. In fact, although the impact of
environmental factors on the function of genes and physical and mental health must not
be underestimated, an age governed by molecular medicine, in which a patient's actual
and future health can be diagnosed primarily through deciphering genes, is a
conceivable possibility.40
Biotech companies are using such discoveries to develop and commercialize predictive
screening tests for an abundance of health conditions in addition to breast and ovarian
cancer. Recent discoveries include genetic links to Alzheimer's,41 bladder
cancer,42 cervical *1225 cancer,43 colon cancer,44 obesity,45 prostate cancer,46 and tumor
growth associated with a spectrum of common cancers.47 Researchers are even
developing an “Ides of March” genetic test to serve as a crude indicator of a person's life
span.48 By conservative estimates, “some 50,000 gene markers will be developed as a
result of molecular biology and translated in not easy-to-employ biochemical assays,
genetic tests, new drugs, and genetic therapies.”49
Unfortunately, the discovery of genetic alterations linked to many health conditions
comes well before those discoveries can be turned into therapeutics and reliable
predictors of disease in specific *1226 individuals.50 Although the availability of
therapeutics to offset genetic predispositions will make genetic testing much less
controversial, that time is years away for most conditions.51 Similarly, for families other
than those with high occurrence of disease and well-documented pedigrees,
determining predictability is a laborious, subject-intensive process that may take more
than a decade to complete.52
*1227 Nevertheless, a deluge of fully commercialized genetic testing services and kits is
well within sight.53 Even by conservative estimates,54 expectations are that the DNA
testing market (1) for neoplastic (tissue growth) diseases will reach $340 million in 1998;
(2) for infectious diseases will exceed $300 million by 1998; and (3) for genetic diseases
will exceed $65 million by 1998.55 This market could experience a several-fold increase
with the availability of probes for polygenic (multifactorial) diseases.56 To build these
markets, the developers and manufacturers of genetic tests need patient data both (1)
to establish clinical predictability, and (2) to sequence and better understand the most
fundamental intricacies of specific genes. The latter will enhance the predictive
capabilities of resulting tests and perhaps lead to other products, including therapeutics
and even gene therapies. The commercial possibilities, including patient-care
possibilities, create a powerful incentive to make research-stage genetic tests available
to the public.
Many developers and manufacturers of genetic tests now are making investigatory,
predictive genetic testing available to the public. *1228 Although IVF, Myriad, and
OncorMed are commercializing their tests, other companies and research laboratories
are making research-stage genetic tests available in a more discreet manner. In 1994,
the Committee on Assessing Genetic Risks assembled by the Institutes of Medicine
documented pervasive informal genetic testing by research laboratories,57 and the ELSI
Task Force on Genetic Testing has reached similar conclusions regarding both research
and commercial laboratories that report results to patients.58
The emergence of predictive genetic tests with implications for broad segments of the
population, such as the APOE-4 (Alzheimer's) test, is raising concern among public
health officials and providers *1229 who understand the limitations of this technology
and are sensitive to its potential impact on the lives of patients and their
families.59 However, with such understanding comes appreciation for the difficulty of
introducing a satisfactory regulatory response to the multitude of genetic technologies
approaching and entering commerce.60
B. Existing Regulations
Predictive genetic testing services, performed in-house by the tests' developers and
manufacturers, are square pegs in the rubric of federal regulation. The FDA regulates
the production of reagents, probes, or test kits manufactured for use by others in
laboratories and, therefore, genetic tests manufactured and sold for others to
perform.61 *1230 However, manufacturers and private laboratories may avoid the routine
FDA review process for diagnostics and comply with applicable federal regulations by
manufacturing and using their own reagents in-house and selling testing services
through primary care physicians.62 Such reagents are called “home brews” because
they are manufactured and used within the same facility, and a number of such tests are
being developed and made available to the public.63
Home brews may be marketed as established products or, to limit product liability where
clinical efficacy is not yet established, labeled investigatory.64 Although the developers of
investigatory tests are *1231 allowed to charge consumers only enough to recapture
costs, commercialization of these tests enables them to generate a revenue stream,
gather needed patient data, and build standard-care acceptance of their technologies.
Standard-care acceptance means enhanced acceptability among physicians and the
public, limits on product liability, and perhaps insurance coverage.65 Also, the costs of
investigatory tests may be considerable, depending upon the stated research
objective.66
Private laboratories performing genetic testing services also are essentially immune to
federal laboratory-quality assurances imposed by the Health Care Finance
Administration (HCFA) through the Clinical Laboratory Improvement Amendments
(CLIA).67 Under *1232 CLIA, a laboratory must demonstrate analytical validity of its tests
and their components, but there is no clinical validity requirement.68 In other words, the
CLIA validity requirement is satisfied when a genetic test to determine the presence of a
specific genetic alteration does so accurately, even though the test may offer no clinical
predictability.69 There is no required express showing that the alteration tested for has
any bearing on the subject's health. The only CLIA patient-care safeguard on clinical
quality is the requirement that the proposed clinical protocol receive institutional review
board (IRB) approval when an investigatory test enters the human-trial
phase.70 Academic laboratories are required to report to their standing IRBs, but “[t]he
situation with respect to IRBs is murkier for biotechnology companies and commercial
laboratories. They also may consult an IRB of an academic institution with whom they
have ties, or they may form their own IRB--a practice that has the potential for a conflict
of interest.”71
*1233 The general lack of regulatory quality control on genetic tests, which raises
questions about their fundamental reliability,72 is exacerbated by the fact that very few
specific guidelines for these tests have been formally developed and introduced by the
medical profession.73 “[L]ack of consensus about what type of screening should be
offered means that there is also no clear guidance for state policy makers adopting
mandatory screening plans” even on issues such as the testing of fetuses for BRCA1
and BRCA2 variations.74 Also, reliance on state regulation to monitor (in the ongoing
manner necessitated by the research nature of the technology) the quality of genetic
testing services is misplaced for, there too, “the field of laboratory licensure and
monitoring remains in a state of flux.”75
*1234 Perhaps most importantly, circumvention of the FDA review process also may
avoid the FDA's tight control on advertising.76 Advertising carte blanche is a troubling
proposition in the context of providers dealing directly with biotechnology companies
and *1235 institutional laboratories to run extraordinarily novel tests on patient samples.
These are tests that, without predictability defined through scientifically reliable clinical
data, are highly subject to misinterpretation. The dependence of both providers and
their patients on the developers of genetic tests for information--information test
developers are compiling on an ongoing basis from patient data--could not be greater.
Ironically, because test developers are the entities with the most information about their
evolving technology, advertising restrictions that are too intrusive could exacerbate
rather than lessen misinterpretation by cutting providers and their patients off from the
most up-to-date data.77
The FDA, in response to the actions taken by IVF, Myriad, and OncorMed, has
proposed regulations to bring genetic testing services (and home brews in general)
more directly within its purview.78 Specifically, the FDA would like to regulate the active
ingredients used in genetic tests. The FDA's proposal is to classify “active ingredients,”
chemicals or antibodies that are useful only in testing for one specific disease or
condition, as analyte specific reagents (ASRs), which are subject to controls.79 This
labeling would require suppliers *1236 of such active ingredients to register with the
FDA and provide lists of the ASRs they are supplying to laboratories for use in
developing tests. These suppliers then would be held to good manufacturing standards,
which require FDA reporting of all adverse events possibly attributable to
products.80 The FDA also has left open the possibility of directly regulating in-house
genetic testing services at a later date.81
Ironically, however, the advent of commercialization of genetic testing by OncorMed and
Myriad is juxtaposed against weighty political and public pressures on the FDA to
streamline, expedite, and privatize its review process.82 Despite recent self-
reforms,83 this *1237 pressure has been mounting, especially for cancer and AIDS--
diseases that affect millions of people and, not coincidentally, major research and
development (R&D) areas for biotechnology companies.84 *1238 Moreover, the
manufacturers of medical devices and diagnostics are pressuring the FDA by organizing
and calling for reforms favorable to their products.85 The drive to reform the FDA does,
however, have its *1239 opponents, most notably former Commissioner David
Kessler86 and Senator Edward Kennedy.87
*1240 The FDA review process significantly impacts the economy of the United States,
for “[t]he products regulated by the F.D.A. account for 25 percent of the nation's
economic output.”88 Nevertheless, the biotechnology aspect of the FDA reform
movement is grounded in more than the profit motives of biotech companies. With the
exception of predictive genetic testing services, biotechnology products have been more
highly regulated than traditional pharmaceuticals.89 Biotech drugs and therapeutics
generally are classified as biologics and, as such, are subject to requirements imposed
by both the Federal Food, Drug, and Cosmetic Act (FDCA)90 and the Public Health and
Services Act (PHSA).91 Because of fundamental differences in the regulatory
approaches taken under these statutes, an entire dimension of added regulation is
imposed upon biologics. Specifically, “[t]he primary objective of the FDCA is to ensure
the safety and effectiveness of the final product, with controlling the manufacturing
process a secondary concern. In contrast, biologics regulation under the PHSA is
focused on ‘rigid control of the manufacturing process . . . .”’92 The practical effect on
biologics has been that, to reach the market, developers and manufacturers have had to
negotiate an entanglement of licensing and other requirements that front-load their
financial investment.93 Self- *1241 reforms by the FDA to eliminate some of the most
unduly burdensome licensing and other requirements imposed upon biologics have
come too late to quell the organization of the biotechnology industry and frustrated
consumers awaiting products. International competition stemming from the
establishment of the European Medicines Evaluation Agency (EMEA) should inspire
more self-reform by the FDA and perhaps produce a new commitment to international
collaboration in drug review and approval.94
The impact of regulatory uncertainty on the biotech industry has provided an incentive
to “Coase around”95 and reform the existing FDA review process.96 Moreover, the reform
movement is fueled by genuine concern that, “‘[i]n this increasingly complex scientific
world, where the half-life of knowledge is growing shorter and shorter every day, it's
going to be impossible for the F.D.A. to maintain in-house the full range of expertise and
experience that will be needed.”’97 Despite *1242 the short “half-life” of its underlying
science, the work necessary to fully assess clinical applications takes years. These
problems are exacerbated by the FDA's resistance to accept scientific evaluations of
technology by the rest of the industrialized first world, a resistance presumably due to a
belief in the superiority of United States science and scientific capability.98 The success
of the HGP, the globalization of the science community responsible for the
biotechnology revolution, and the realization of meaningful global telecommunications
support the introduction of uniform, international scientific standards for compiling and
evaluating clinical data.99
The strength of the FDA reform movement reduces, but does not make
impossible,100 the likelihood that a comprehensive regulatory response to the
commercialization of genetic testing services will be introduced in the immediate future.
Without such FDA reform, other biotechnology companies will follow the precedent set
by IVF, Myriad, and OncorMed. Dangers arising from the widespread availability of
investigatory, predictive genetic testing services must, *1243 therefore, be identified,
thoughtfully considered, and addressed without further delay.
C. Dangers Arising from the Premature Use of Genetic Testing
Predictive genetic testing services are, in the aggregate, biological tarot cards subject to
misinterpretation by both patients and their physicians.101 The predictive capability of
many genetic tests remains scientifically undefined for the general population.102 This
type of testing must be conclusively distinguished from presymptomatic genetic testing.
The latter constitutes a reliable and meaningful predictor only for a small number of
conditions--conditions usually caused by a single genetic mutation.103 Only these few
conditions, such as Huntington's and Tay Sachs disease, can be diagnosed conclusively
through genetic testing.104 Even when such conditions *1244 can be diagnosed through
genetic testing, the rate of expression may vary; with many genetic conditions, severity
remains an open question.105 Most often there is no available treatment,106 or treatment
exists but is price-prohibitive.107 In addition, in the absence of uniform federal regulatory
oversight, the quality of laboratory performance is questionable.108
*1245 More troubling, due to the absence of adequate clinical data, health care
providers cannot interpret the results of predictive genetic tests for most of their patients
with any reliability even when they are knowledgeable about genetics.109 This
interpretation problem is exacerbated because the current generation of health care
providers does not possess such knowledge.110 Their lack of genetics
education *1246 and the novelty of the technology makes providers dependent upon the
developers and manufacturers of these tests (both commercial and academic
laboratories) for information. This dependency suggests that neither consumers nor
their health care providers can reasonably evaluate the technology. Accordingly, until
this informational asymmetry between providers/patients and biotechnology companies
is decreased through the compilation of clinical data and education, heavy reliance
upon market forces like consumer and provider demand is misplaced. In fact, the
premature commercialization of genetic testing services may create a general climate of
uncertainty that skews incentives for all market participants:
Biotech companies' decisions about what technologies to develop are subject to being
inflated by dependence upon them for information, consumer demand, and the
influence of consumer advocacy groups;111
public demand is subject to being bloated by the aggressive marketing efforts of
biotechnology companies that play off of the cultural icon status of DNA,112 the fact that
the public is accustomed to undergoing testing for reliable health evaluation and
diagnosis, and providers' lack of adequate genetic education;113 and
*1247 providers' decisions to make the technology available may be skewed by fears of
legal liability, the desire to appear knowledgeable about and receptive to health care
technology, pressure from consumers armed with newspaper and magazine stories on
genetic discoveries, and care managers who place severe limits on physicians' time and
pressure to maintain patient enrollment.114
Many of the concerns about the commercialization of genetic testing services are
familiar and apply to other medical technologies. Nevertheless, (1) the fact that
research-stage genetic testing available to the general public is being conducted by
private companies rather than by major research institutions, (2) the absence of reliable
quality controls on in-house testing services, and (3) perceptions and uncertainties
about the predictive capabilities of genetic testing make *1248 these concerns profound
enough to stand alone.115 Specifically, lack of regulatory quality control and the
perceived ability of predictive genetic tests to penetrate well into the future despite the
absence of PPV makes this testing different. Many consumers and providers are more
in awe of the “miracles of modern genetics” than appreciative of its clinical limitations.
The demand for predictive genetic testing services may reflect this faith in genetic
medicine, a tendency to equate investigational genetic tests with reliable, standard-care
diagnostic tests, and the influence of entrepreneurial and academic interests.116 It also
may reflect intolerance for health conditions that deviate from the majority.117
The information generated by predictive genetic tests, regardless of its clinical reliability,
will deeply impact people's lives.118 Some of *1249 those who have opted to undergo
the presymptomatic test for Huntington's, a clinically valid test that conclusively
determines future onset, have experienced detrimental psychological reactions to the
results even when they are negative.119 For those whose results are positive, the suicide
rate is approximately thirty-five percent higher than among the general
population.120 Further, it appears that genetic information already is disrupting the lives
of individuals and their families by subjecting them to discrimination from employers and
insurers.121
Although adequate genetic counseling could, perhaps, enable people to cope better
with genetic information, genetic counseling is *1250 expensive and not necessarily
covered by insurance;122 the United States does not have enough certified, practicing
genetic counselors;123 and health care providers are not knowledgeable enough about
genetics to help stretch these limited resources.124 Because of poor insurance coverage,
costs for investigatory genetic testing are likely to be paid out of the pockets of
consumers, and adequate counseling could increase the costs of testing tenfold.125 But
without mandatory provisions for pre- and post-genetic counseling, the United States is
in danger of repeating its sickle-cell screening mistake, multiplied for a whole spectrum
of conditions.126
Moreover, absent a legal infrastructure to comprehensively protect the public from
discrimination by insurers, people may be paying out of their pockets for tests to
generate genetic information that gets into their medical records and damages their
insurability.127 *1251 Investigatory predictive genetic tests also may endanger the
physical health of patients by creating the possibility of over-
treatment.128 The *1252 United Kingdom has explored the impact of predictive genetic
testing information on the lives of children and concluded that children should not have
genetic diagnoses for late-onset disorders.129
The precedent set by IVF, Myriad, and OncorMed could carry significant implications for
the commercialization of predictive genetic testing services, including widespread
commercialization of investigatory genetic testing services. The BRCA testing services
offered by these companies may shape standards used to evaluate this technology. If a
test has no predecessor, it becomes the governing standard; the most definitive method
or test in existence becomes the “gold standard” against which analytical validation is
measured.130
The availability of BRCA testing services should enable IVF, Myriad, OncorMed, and
their research allies to compile enough clinical data to determine predictability in a
greatly accelerated fashion. These advantages will pressure other biotechnology
companies to make genetic testing available to the public. All of the related science,
including sequencing, could be pushed forward, thereby making more therapeutics and
treatments a viable possibility. Although such benefits to public health may be
considerable, the financial and emotional costs to those who undergo predictive
genetic *1253 testing during the interim will be significant. At what point does this cost
become too high?
The four cornerstone principles of health care are “autonomy, beneficence,
nonmalfeasance, and justice or equity.”131 These are inherently individualized concepts,
meaning that they lead providers to “focus on the specific patient to the exclusion of
other actual or potential patients.”132 Applying these principles to widespread
investigatory, predictive genetic testing raises many questions. One of the most
fundamental is, what should patients be told before they decide to undergo such
testing? The danger is that the answer to this question is left to the provider and to the
protocol established by the test's developer, who has every incentive to encourage use
to gather both patient data and revenue to cover the costs of research.
The following is a more comprehensive analysis of the commercialization of testing
services for BRCA mutations linked to breast and ovarian cancers. First, the prevalence
of breast cancer and the approaches taken by the companies marketing these tests are
addressed in more detail. Next, the regulatory and general health-policy implications of
BRCA testing services are explored through the technique of legal storytelling, which is
applied to identify important public health issues (“issue spot”). The varying stories
presented embody the perspectives--cancer survivor, genetic counselor, health
consumer advocate, and corporate representative--of individuals with personal
experiences dealing with breast cancer, BRCA genetic testing, and the R&D, marketing,
and regulation of medical products.
III. The Seminal Case: BRCA Testing Services
As stated by Dr. Francis Collins, head of the HGP, “[b]reast cancer is the most common
cancer among women in the Western world, with a cumulative lifetime risk of 1 in
8.”133 This year alone, 184,300 women will be diagnosed as having breast
cancer.134 Some *1254 44,300 women will die from the disease.135 Of the women in
whom cancer is diagnosed, 9,200 will not have reached their fortieth birthday, nearly
twice the number of women under forty who were found to have breast cancer in
1970,136 and another 33,000 will be in their forties.137 Breast cancer “is now the leading
cause of death for American women aged forty to fifty-five, and causes women to lose
more years of productive life than any other disease.”138
BRCA testing is available through three schemes, two of which reflect the labeling
options under present regulations.139 The third entails direct marketing without FDA
oversight and restrictions:
For research use only and not for use in diagnostic procedures. NIH is conducting a
BRCA testing study in the Washington-Baltimore area that involves 5,000 Ashkenazi
Jewish volunteers.140 Pursuant to this labeling,141 those participating in the study are not
given their test results.142 For investigational use only. OncorMed has labeled its genetic
testing service accordingly. To comply with the accompanying federal restrictions: (1)
women must be referred for counseling before and after the test is performed; (2)
results must be given by the physician in person; (3) the physician must follow up with
the patient about three months later; (4) the test developer must compile data on an
ongoing basis to determine which aspects of the gene-testing process
need *1255 improvement; and (5) the developer only may charge an amount necessary
to recapture the costs incurred for the stated research objective.143 Many of these
restrictions were developed through an IRB assembled by OncorMed. The IRB was
staffed with experts paid consulting fees144 to develop a protocol for investigational
marketing in compliance with CLIA.145 The sum effect of the work of OncorMed's IRB is
that physicians are given a well-developed protocol for their interactions with patients
regarding the test, and they are instructed to make the testing service available only to
patients with breast cancer or at a high risk of getting the disease.146 The costs charged
for the test fluctuate significantly according to the stated research objective and the
testing undertaken. If the company is attempting to locate a specific mutation, the cost
may be as low as $150; if the data is used for sequencing, that cost may reach
$1,650.147 Independent of FDA Regulations. A BRCA test also is being made available
entirely independent of FDA oversight by IVF Institute. IVF Institute offers its BRCA test
and the results to any woman willing to pay $295.148 Similarly, two of Canada's most
respected universities--McGill University and the University of Toronto--are offering open
access to BRCA testing.149 *1256 Although the occurrence of breast cancer is
epidemic,150 the fear of breast cancer and the potential market for genetic testing
services is exponentially larger.151 Even according to Myriad's own marketing materials,
current data suggests that, of all the women with breast or ovarian cancer, only
approximately five percent carry a BRCA1 mutation.152 Of the approximately 185,000
people diagnosed with breast cancer annually, only five to ten percent inherit the
disease.153 Nevertheless, OncorMed, IVF, and Myriad envision multimillion-dollar
markets for their BRCA tests, and their expectations are well grounded. The market for
cancer diagnostics is big business, that business is growing quickly,154 and “surveys of
women have revealed *1257 an overwhelming interest in being tested to learn their
gene status.”155 As stated by the National Cancer Coalition, “ready or not, genetic tests
are on the threshold of entering everyday practice of medicine.”156
A. Meaningful Assessment of the Commercialization of BRCA Testing Services
Understanding the full implications of commercialization of predictive BRCA testing
services is a necessary prerequisite for defining resulting health-policy issues and
constructing a regulatory response that maximizes public health benefits. Especially in
light of the novelty of this technology, there must be meaningful assessment--in other
words, appreciation of innumerable issues and perspectives, many of them
contradictory. The potential impact of such law on individual lives, society in general,
and the commercial sector responsible for producing health care technology mandates
such an approach.
“Legal storytelling” has been defined by some scholars as a license to describe
personal experiences without the constraints of traditional legal scholarship, which
include an objective tone, extensive footnoting, and reliance upon empirical
research.157 Extremists contend that only those excluded by the legal
academy, *1258 such as people of color and women, have stories to tell.158 They also
argue that reversion to elements of traditional scholarship, such as extensive footnoting,
weakens resulting scholarship.159 Critics of this genre of legal storytelling (the extremist
perimeter of “outsider jurisprudence”160) dismiss such scholarship as anecdotal self-
absorption.161 Many pages have been consumed debating whether this scholarship is
more or less “real” and meaningful than its more traditional counterparts.162
In this Article, the technique of legal storytelling is used to complement traditional-style
scholarship. Absent the extensive clinical data necessary to comprehensively evaluate
the impact of genetic testing capability on the lives of those who undergo it, legal
storytelling is a technique used to thoughtfully assess both the need for and the
potential impact of changes in regulatory law. These stories are offered to illustrate the
practical effects of the commercialization of predictive genetic testing services. The
objective is to engage in legal analysis that is more responsive to the underlying facts
and, therefore, more intellectually rigorous and meaningful. Accordingly, rather than a
substitute for comprehensive empirical data and with full recognition that its utility is
limited by the perspectives of the stories presented, the *1259 technique of legal
storytelling is used as a means to illustrate underlying facts, identify issues, and analyze
public health implications and regulatory considerations.163
B. Some Stories
The effectiveness of the legal storytelling technique is dependent upon the selection of
stories and the manner in which they are presented. The following narratives are in the
words of the subjects who relayed them. They illustrate many of the patient, provider,
and regulatory issues identified above in more objective prose. Varying perspectives,
both complementary and contradictory, are juxtaposed to stimulate issue identification.
Many prospective subjects were considered, and representative subjects were selected.
Interviews with these subjects were audiotaped, transcribed, edited, reviewed by the
subjects for accuracy, and revised accordingly. In content, we have selected
perspectives resulting from first-hand experience with the issue of BRCA genetic
testing. We also have selected arguably contradictory perspectives, such as those of a
consumer advocate and a corporate executive from the biotechnology industry. The
overall objective was to solicit opinions, based upon personal and professional
experiences, on the adequacy or inadequacy of the existing regulatory scheme for
predictive genetic testing, with a particular focus on BRCA testing services.
1. A Cancer Survivor's Story164
In January 1993, at age forty-eight, I was diagnosed with breast cancer. I had a routine
mammogram that had a density on it. A six-month follow-up visit was recommended. I
elected to ask for a second opinion because I was on hormone replacement therapy,
and I knew that this therapy could potentially affect the growth of a tumor if one was
there. I went ahead and had a biopsy, and it was positive. So I had a lumpectomy,
auxiliary dissection, and radiation therapy. Meanwhile, a decision was made to biopsy
the other side. I had some *1260 calcifications which normally wouldn't be of concern
but, because I had a primary tumor on the left, a biopsy of my right breast was
suggested. In fact, I had a precancer on that side. This was treated with a wide excision.
Seven weeks after I finished radiation, I had a colonoscopy and was diagnosed with
advanced colon cancer. I had four positive lymph nodes, so I went on to do a year of
chemotherapy after that.
I have a very strong history of cancer on my father's side of the family. My father, aunt,
uncle, and grandfather had multiple cancers. I have three first cousins who have had
cancer, and my brother also has had two primaries. Having grown up with cancer in my
family, I have always thought about what's at work in our genetic background. I guess it
was always an expectation that some day, eventually, I would probably get cancer. I just
never thought I'd get it as young as I did. I certainly never thought I would get two at
once. You do think about this when you grow up and are surrounded by it. In a way, it
gives you a chance to sort things through and ask yourself, “What would I do if this type
of scenario happens to me?”
One of the reasons I remain optimistic despite the likelihood of my having a genetic
predisposition is that I believe we are more than our genetic inheritance--lifestyle, diet,
and environment all come into play in varying degrees. If you looked at my family
pedigree, you would see that all the family members who had cancer lived in or near a
paper mill town. Those who lived on the coast were cancer-free. There are also large
quartz deposits and, consequently, high radon levels in the paper mill area . . . another
carcinogen, along with the dioxin and other byproducts of the paper-making process. So
I guess I believe that the bottom-line isn't in yet and that, while genetics are important,
there is more to the story.
I had really never thought to myself, “I wish there were a genetic test available so I
could find out whether I'm going to get cancer.” But I will say that, back in 1989, I
became much more aware of genetic testing. I remember saying to my colleagues, “You
know this is what my family history looks like . . . don't you think this is a lot of cancer?”
Since my breast cancer diagnosis, I have thought about whether I would want BRCA1
testing--if I would want to know whether I carry the alterations in the gene linked to
cancer. I don't know that I would want to be tested for BRCA1, and the reason is that my
daughter is twenty-five and my son is twenty-four. As far as I'm concerned, for
me *1261 personally, the die is cast. I've had cancer twice. This is clearly my heritage. I
know I could possibly have it again. I am probably also at elevated risk for both ovarian
and uterine cancer. But I don't know what I would gain if I found out I have an altered
BRCA1 gene because I know I would not have a prophylactic mastectomy. I've had my
children, and I don't know that my daughter would gain anything by knowing either. Her
awareness is already heightened. She will certainly go through pretty rigorous
surveillance, seeing the doctor frequently for breast exams, and there's not a lot else
she can do in terms of prevention.
Both my kids have asked whether it's possible that they have inherited a gene for
cancer. We talk about it a lot. We tend to discuss the colon cancer more than the breast
cancer. We have talked about it and, again, I think BRCA1 for my family is probably not
as big an issue as the colon cancer gene. I do think I would feel differently about genetic
testing for the colon cancer gene for several reasons. If I do have that particular gene, I
would then have the option to think about taking an action--such as having a
hysterectomy. If I actually had the gene, once again, I don't know that anybody can put
numbers on this, but I would be at elevated risk for ovarian and uterine cancers. So for
me, personally, that would be something I could do with that information. I can't think of
anything I could do with the breast cancer information that would be any different from
what I'm doing now.
I think risk is a lot like beauty. It is in the eyes of the beholder. Perhaps because I've
grown up in a family with various, multiple cancers, and my family members have dealt
with it and gotten on with their lives, my perception of risk is maybe a little different than
someone else's might be. I don't know that I could say how I would feel if I had a strong
family history of breast cancer. If my mom or sister had breast cancer, I suspect I'd feel
a lot more threatened than I do now. I would probably also feel more threatened in
terms of my daughter. In my opinion, undergoing this type of testing is a very personal
decision.
I think the whole area of predictive genetic testing is something that we need to
address, because we're going to have a lot more genes coming down the pike. There
are going to be many people who are going to be affected by earlier diagnosis, and all
these discoveries that are coming . . . it just means that there are that many more
people at risk who are going to face these issues and be anxious. I also think one of the
unfortunate down sides of genetic testing is that, for the *1262 average person, it is
extremely difficult to sort out where you fit into this picture . . . if you fit in at all. While
there are high-risk cancer clinics at some major teaching hospitals and research
institutions, not everybody has access to these kinds of services. Not everybody lives in
a metropolitan area.
It's interesting that, although the BRCA1 testing is still relatively new, independent labs
are giving out results. I think it's potentially dangerous to offer predictive genetic tests
without stringent quality control and regulation. Giving out results that aren't accurate
isn't the whole problem. Based on my experience working with researchers who are
extremely careful, even when they set up programs with many safeguards, the issues
that arise for people are still traumatic. This type of genetic testing is not something to
be taken lightly. My personal bias is that this kind of testing must be set up by the
medical profession, ordered by the medical profession, and that members of the
medical profession should be the ones responsible for giving out the results--not
independent labs or companies developing the tests. I mean, if you go to your physician
and you have your annual physical exam, and you have a chest x-ray or a blood test,
the lab doesn't call you and give you your results. I really feel that there should be the
same kind of oversight and development of medical standards for genetic tests that
there are for other types of medical tests, perhaps even more so. A lab shouldn't be
doing genetic testing if it hasn't gone through an approval process for that particular
test.
There are so many things that one needs to know before undergoing genetic testing. I
think one of the biggest challenges of the genetic revolution is the dissemination of
information and education of both the primary care providers and the patients
themselves. It's very tough to sort out all this information. I think it has created a great
deal of concern and a lot of anguish for women who probably aren't even at risk for the
inherited form of breast cancer. Women almost always overestimate their risk.
From a cancer patient's perspective, what I believe is most needed for an individual
prior to this type of genetic testing is time, especially time for genetic counseling. There
also needs to be coordinated peer support so that when an individual is diagnosed with
cancer, no matter what type it is, they can, through their physician, nurse, or social
worker, say, “I would really like to speak with someone who has been through this
decision-making process.” The other issue that concerns me is the point in time that
genetic testing is *1263 discussed. If it's close to diagnosis, you are concentrating on
how you are going to get through the surgery, whether you are going to live through the
treatment, who's going to take care of your kids for five days a week during seven
weeks of radiation, and what's going to happen with your job. That's enough for the
average person. There's a limit to how much you can deal with at one time. We need to
think more about when people are mentally ready to hear the information on genetic
testing and its implications.
I have spoken with many people with cancer over the last few years. I also have had the
advantage, if you want to call it an advantage, of not only talking with people and
growing up in a family with a lot of cancer, but also working in this research area. And
even having dealt with this every day, the decision to undergo genetic testing still takes
a lot of thought. You have to know what the ramifications of that decision are and, let's
face it, there are a lot of potential ramifications. How one perceives the risk of the
ramifications is as important as how you perceive your risk of the disease. For example,
the thought of being without health insurance, particularly if you have children, or the
thought of being denied employment because of something like this is frightening to
most people, and right now these are very real potential ramifications.
One of the issues I came up against when I visited my gynecologist for my annual exam
after I'd been through both diagnoses was insurance coverage. We discussed the fact
that I might be at elevated risk for both uterine and ovarian cancer, and what strategy
we would take on this. He suggested my having a baseline transvaginal ultrasound. I
agreed that I would have the baseline ultrasound and the other baseline test
recommended, which was a blood test called CA125. My insurance carrier refused to
pay for the blood test. Just on general principles, I decided I was going to argue about it.
So I called my doctor and told him what the insurance company said. Essentially, they
said it would not affect patient care, and that's why they wouldn't cover it. So my doctor
wrote a blistering letter saying it absolutely would affect patient care, explaining how I
was at risk and that very positive action would be taken if this value was elevated. They
covered it but made it clear that they were going to pay for this once and only once.
Since then, I do go for a visit every six months and have a pelvic exam, but I'm not
doing routine ultrasounds or blood tests. I could do it if I wanted to, and pay for
it *1264 out of pocket, but I just don't feel that is something I choose to do right now.
What it boils down to for me is, “Am I going to go and ask for a hysterectomy if I have
this colon cancer gene?” I don't know about that answer today. I've had a long time to
think about this. I know a lot, and it's still very difficult for me. So can you imagine the
confusion for the average person who, out of the blue, develops cancer or learns
someone in their family has it? Right now, the colon cancer gene testing is at a stage
where they're verifying their results to be sure that they have completely reproducible
results. Results are not yet being reported to patients. I have had my blood drawn and
provided tissue samples as well. I will be notified when a clinical testing program for
colon cancer is available, and I will make a decision about testing at that time.
In general, I support all the research taking place on gene susceptibility testing. I think
that the quality of most of the research is good, and those researchers working in the
area don't take any of these issues lightly. But I do think that this type of testing must
initially take place in a research setting, to see what the ramifications are, to work out
the kinks, before opening it up to the general public. It will be interesting to see who
hops on this particular bandwagon. I've heard about the marketing of predictive genetic
testing for breast cancer second-hand, and I think that's pretty unconscionable. I know
how volatile it is for people to think about genetic testing. If it takes place outside a
setting with a lot of education and counseling, well, I just think it's unconscionable to do
the test and give out the results. I don't know that there will be any way to keep track of
what the results and the outcome will be. I think that's the other very bad part about
genetic testing for breast cancer. Are companies going to keep any kind of records? Are
they going to do any kind of reporting? What about doing further testing on samples?
Who will have access to the test results? Who will be there to help individuals deal with
the information they receive? There is no doubt that safeguards need to be put in place,
immediately, before it's too late.
2. A Genetic Counselor's Story165
Our center is involved in a number of clinical research projects to offer general
predictive genetic testing to anybody in the local area *1265 who may have a mutation
in a cancer susceptibility gene, BRCA1. One is a general research protocol that allows
us to draw blood on anybody who has cancer to look for an inherited factor. We
consider it a fishing expedition, and it has a pretty low yield. In another program, one of
our predictive genetic testing programs for breast cancer, we only test people who
already have a known mutation in their family, so we're starting with knowing exactly
where in their genome to focus. In this program, we use a three-visit model with
extensive counseling because it is too much to give all of the information necessary in
one visit. We do not do counseling by phone, so individuals who are out of state are
referred elsewhere for counseling and testing. We use a networked group of counselors
that are trained and specialize in cancer genetics.
I'm not aware of any of our researchers having financial ties with the laboratories
performing BRCA1 testing. I really do not think there are any financial incentives among
the researchers within our institution. However, since our laboratory does not have CLIA
approval to perform testing at this time, we have agreements with other laboratories that
are certified to confirm all results independently. So everyone who comes to our
program has two independent tests done on their samples. Two samples of blood are
drawn, and one tube is immediately sent out to the other laboratory. This offsets
concern about a coding error or contamination at the beginning of the process.
In addition, in a separate testing protocol, we have an agreement with a specific
biotechnology company. They will perform the entire sequence of BRCA1 free of charge
and we will provide the pre- and post-counseling. We are one of nine centers with whom
this laboratory is collaborating on this project. It is with the understanding that they will
be allowed to use that data to determine the sensitivity and specificity of their test assay.
Before a lab can offer a test for clinical use and charge for it, and before developers can
do clinical marketing, they have to prove that their analyses reach a level of specificity
and sensitivity that's acceptable. And so we're helping them do that, basically. This is a
time-limited study. Right now, all the people who undergo BRCA1 testing through our
program receive it free of charge since it is part of a research protocol. Very soon, the
commercial labs will be offering testing, and there will be a charge for the laboratory
costs.
The women who come to our BRCA1 program are either concerned about getting
breast cancer or actually have breast cancer. *1266 A lot of those concerned have a
family history of the disease. As a result of the publicity about BRCA1 testing in lay
press journals or newspaper articles, we have recently received a flurry of phone calls.
We also have a cancer risk and prevention clinic at our hospital that attracts a lot of
inquiries. Many of the women who decide to be tested do so because this is an area of
uncertainty that they've been living under. A lot of these women see this as a way of
getting control--they really want to know, and that's a lot of what it comes down to. We
also see people for second opinions.
The majority of patient referrals come from outside providers, such as doctors and
genetic counselors. Although we have the ability to search medical records here at the
hospital to find people who might be at risk, we don't. In fact, even for people who come
into the cancer risk and prevention clinic or who are at the hospital, special permission
is necessary for us to obtain their records. The oncologists at the hospital know about
us so, if they have a breast cancer patient who says, “Yes, my sister also had breast
cancer at the age of forty,” then it's very common that the oncologist will suggest to the
patient that they contact us. Whether an individual with breast cancer follows through on
this depends on the person themselves. Some people want to talk soon after diagnosis,
others really have no interest in doing that at that point.
The people who are eligible for genetic testing are those with significant histories of
breast or ovarian cancer, meaning that they have three or more people in their family
with the disease. It is important for the family history to include more than one
generation and premenopausal cases of breast cancer. And they need to have a living
affected family member that we can test first because, following the classic genetic
model, we need to start with somebody who we assume has the disease. Otherwise, if
the results are negative in the healthy person you're testing, you don't know if you've
even looked at the right gene or the right place on the right gene. So we make a very
big deal about needing to first test somebody who is affected with the disease and has
had their diagnosis confirmed with medical records.
The only exception to that now are Jewish women who have significant histories of
breast or ovarian cancer. For these women, we offer testing for the three known
mutations without testing an affected relative first. Part of what we are currently doing is
mutation testing for the three common mutations in the BRCA gene that occur within the
Ashkenazi Jewish population. I am familiar with the controversy *1267 surrounding the
notion of a “Jewish gene for breast cancer.” I think that, if there is malice in targeting a
racial group, it's very wrong. But I don't think that's the case with BRCA1. This is not the
first time that ethnic backgrounds have been important to think about in genetic
research.
What has struck me most in thinking about our predictive testing program is that we're
starting with people who themselves have had cancer . . . they are the entry point into
the family. These people understand that, really, their daughters and sisters are the
ones who potentially have the most to benefit from this. These are people who have
already had their cancer. We began offering testing with the assumption that an
important reason why people who had the disease would want to be tested would be to
get the explanation of why they got cancer, and that they already would be assuming
that they carry an altered gene. What we found is that cancer patients we have seen are
really much more tortured about the possibility of being a gene carrier and the possibility
that they might in fact have higher chances of getting a second cancer. I've talked with
several people now that have ultimately made the decision not to go forward with testing
because the idea was so distressing to them that, despite the fact that their sister was
really pushing them and wanted to know. When this happens, I tell the person “Look,
you're the one that has to decide because it has direct implications for you. It's okay to
make the decision that is best for you.” So this has been eye-opening. BRCA1 testing
does not provide benign information even for somebody who's had cancer. It is not an
easy decision to make.
You can appreciate then that getting other family members to provide samples for
BRCA1 testing can be complicated. When you deal with families, you encounter all
kinds of different situations. There have been situations where the person in front of you
says, “There's no way that my aunt with cancer will agree to do this . . . I can't even ask
her.” In this case, you are really stuck. You can't offer anything. So there are certain
instances where a person is the gatekeeper for the family, and, if that person does not
want to participate at any time, we can't offer anything further. There have been other
situations where somebody will initially be interested in participating but then change
her mind. We honor that. There's another situation that doesn't come up as often, but it
has happened. The person sitting in front of you says, “My cousin has had cancer,”
we're put in touch with that person and she becomes very enthusiastic
about *1268 participating, and then the person you have been directly dealing with says,
“I don't want to hear any more about this.” But, by that time, we're already working with
other people in the family and will continue to work with them.
Incidentally, we don't tend to see many husbands or fathers coming to the counseling
sessions with the women considering BRCA1 testing. We see a lot of friends,
sometimes family members, but that gets complicated because family members may
also be at risk. You wonder how much they are acting as a companion and how much
they are focusing on their own stuff. Mainly, women come by themselves. We do
encourage women to try to bring somebody when the results are given.
All participants receive a patient information sheet that we've put together about the
genetic testing program itself and another just about the BRCA1 gene and what we
know about it. Because our program is a research program, there are three consent
forms: one to enroll in the program, a second to have blood drawn and analyzed, and a
third to receive results. The initial consent form is mailed to patients before they come in
for their first visit, and they are asked to bring it with them. There's a lot of information in
the consent form that can be looked at beforehand. Women are asked to sign the first
consent form during the first visit, and then at the end of the first visit we'll show them
the blood drawing and analysis consent form. They can either sign it that day, or they
can take it home and think about it. The informed consent process is integral to our
research. All patients that participate in our testing program are told that this is part of a
research protocol, and that they must sign an informed consent document.
Much of the same information is reiterated for all three of the consent forms. We talk
about the implications of results. We talk about the fact that, if there is no mutation, the
person's risk is lowered down to that of the general population. Having a gene alteration
would substantially increase the risks of cancer. We also mention the pros and cons of
testing, including the possible stigmatization of knowing that you have an altered gene.
Insurance concerns are something that are heavily emphasized. We discuss the
possible strain on family relationships, and we talk about the fact that there is no known
medical benefit to being tested.
For some people, there are other definite benefits. It may be that the person needs this
extra information to put them into gear to have surveillance done. People have told us
that they think knowing they *1269 have an alteration would motivate them to plan
better, to take better care of themselves. Now we're looking at the outcome in terms of
behavior. I'm not sure anything changes human behavior, but there are people who
think it will motivate them. Also, a lot of the women who want testing have daughters--
that is a big reason for wanting to be tested. They say “For myself, I don't really care,
but I really am so anxious about my daughters. I really want to know for their sake.” If
the woman has the altered gene, then her daughters have the option of being tested. If
the woman doesn't have it, then her daughters are not at risk for inheriting it.
Providing the results of BRCA1 testing is one of the most difficult aspects of my job. It is
very powerful information. There has to be a lot of thought put into it beforehand, and a
lot of follow-up and TLC (tender, loving care) afterwards. Giving the results can really be
very involved, depending, of course, on the person being tested. For some people, it
takes twenty minutes. That's all the time they want to give us. They just want to go
home and let it sink in. Some people are very private and, whether they are
devastatingly sad or overwhelmingly happy, they don't choose to share that with us.
That's why there is a third follow-up visit. Other people have a million and one questions
or they want and need to express their emotions and, for them, it can be an hour-and-a-
half to a two-hour session. We have set up our protocol to call in a couple days after
giving the test results. If we're really worried, we'll call them that night. If we are not so
worried, we'll wait a couple days and then we'll check on them. There have been
instances where a husband or other companion has come in with the woman when it is
time to receive results. Some are very supportive, others are not as helpful.
The results are given to the person verbally along with a letter that addresses all the
things that we mentioned--the implications of the results, what it means and doesn't
mean, what the concerns are, and the letter stresses that they can always contact us
again. Even if they can't remember what we told them, they have the letter to refer to.
And I tell them that they can either throw it away if they are worried about having
something with their name and results on it, or show it to their health care provider, or
stick it in a file somewhere in their house. The control is up to them. We don't document
results in medical records. The results will be told to the other providers in our high risk
clinic who know not to write it anywhere. Outside our little close-knit group, the providers
are not told. We are more than happy to disclose *1270 the results if we get written
permission to do so, but otherwise it doesn't go anywhere. It is unlikely that an
insurance company would learn about the result because it is completely done in a
research setting.
Because this is powerful information, we have to consider whether someone will be
suicidal after hearing the news. We had one case where the woman was very upset that
she got a normal result (not in the BRCA1 gene, but in a different cancer gene). She
was hoping for abnormal results as her way out of her horrible life--being able to get
cancer and just die. Us telling her, “No, that's not going to happen,” was not good news
for her, so for her we were worried. But I think, in general, we are more concerned about
the people who get an altered gene result. They have filled out some psychiatric
assessments and had a lengthy discussion before the day results are given. So
hopefully we have an idea of their stability and emotional well being before they even
get to this point. It is an important reason why we have a clinical psychologist working
on the project.
I generally do feel comfortable giving out the predictions of breast cancer risk because
of the way that we do it. We're deliberately vague. I am amazed when I hear that
somebody says, “Okay you're forty. By age forty-five, you will have this risk, and at age
fifty your risk will be that.” We just don't know that for certain. We'll give ranges, but
often we downplay the numbers. Remember, for most people, numbers don't mean
anything. You could give the same number to four people and they will all perceive it in
a very different way. For many women in the breast cancer clinic, they are living with so
much feeling of doom and fear that they already know they have a higher risk of cancer.
In fact, for a lot of people, they've over-estimated what their lifetime cancer risk is. So
I'm not sure that they even hear me when I say, “Look, your highest risk is fifty percent.”
Now, for me or you, that sounds like an incredibly high risk, but for these people, that's
quite a drop in what they already think their risks are.
Sometimes I think that being part of this research is a scary place to be because there
are not a lot of models for what we're doing. We see other institutions doing things in
ways that we don't agree with so we can see what it is we don't want to do, but it's very
hard to know how best to do things. For example, I hear from other centers that have
just gone ahead and started doing this type of testing more freely. I know that there are
a few labs that are offering predictive genetic *1271 testing for breast cancer without a
required counseling component. There are a few labs where you can just send money
and a blood sample and the test will be done. There's at least one site that will take
anyone's blood, regardless of whether they have cancer or a striking family history. A
couple of these sites strongly encourage counseling, but I don't know if it's required.
Whenever you work with families, what works for one family doesn't always work for
another, and so you are constantly reevaluating how you're doing things. The first step
in our testing program is to send an invitation letter to families saying “You know, this
altered gene may be in your family. Do you want to know about it?” Well, one person is
going to call and be upset that we didn't give more information in the letter--“As you
know, I've been seen in your center for five years. This is all you can tell me? What do
you mean that I have to have another blood test? You already have my blood.” And then
a second person will get the letter and be devastated by what they are reading into it.
So it's hard to know how much information people really want, and it's hard to be able to
predict that. If there's one thing we've learned, it is that you can't predict how people are
going to react to this information or what people are going to want to hear.
I have confidence in our approach to predictive genetic testing for breast cancer
because we do everything within a group process. We have people with specialties in
oncology, psychology, and genetic counseling. We also have set up an outside ethics
group for our research protocol composed of people not affiliated with the hospital so
that, when we really get stuck or we've done something and we want reassurance that it
was okay, we can go to them. We meet a few times a year and go over the case
histories and how we've resolved it, or how we plan to resolve it, and they give us their
feedback. I think it's really useful, because we do a lot of obsessing about things. Also,
you can get to a point where you're convinced that you're doing the right thing, and
sometimes it's really important for an outside group to look at it and say, “Well, what
about doing it like this instead?” This is important because people do tend to think alike
after working together for a while.
From a laboratory standpoint, I think there has to be some sort of standard to ensure
accuracy of the results. Still, it worries me whenever the word “regulation” is raised. Are
we going to make it difficult, actually impede our ability, to do genetic testing? I
think *1272 there is a fine line sometimes when it comes to regulations. Do we regulate
each genetic test that comes along? Do we just regulate the labs? There are a lot of
things to consider . . . .
3. A Consumer Advocate's Story166
As a statewide consumer advocacy organization, our mission is to increase breast
cancer research funding, improve access to breast cancer care and treatment, and
foster consumer participation in research decisions. Although we are always pleased to
see that researchers are looking for the causes of breast cancer, we are seriously
concerned with the trends in genetic research. There has always been some concern in
our organization about the genetic factors at play in high-risk families. However, only
five to ten percent of women who get breast cancer have a strong family history; most
have no identifiable risk factors. The way in which Jewish women are being recruited for
predictive genetic testing is alarming. BRCA1 is now being referred to as the “Jewish
gene,” and this incredible focus on one particular ethnic group, especially without
education and the support of the community, is appalling.
The way in which genetic research is being portrayed is very distorted. There seems to
be this implication that if you have a test, and it shows that you have an altered BRCA1
gene, you can do something about it. That is not the case; there is still no known proven
intervention for breast cancer. Our organization has received many calls about breast
cancer genetic testing over the past year. There have been many people who are
initially very excited about it, and say that they want to go out and get tested. But when
they learn a little more about what this type of testing can and cannot tell them, they
realize it may not be so great. First of all, it may not tell them anything that would be
actually useful to them. And, psychologically, it can be extremely distressing to them
and their families. Furthermore, there is no protection from discrimination. I think, these
days, everybody understands how precarious health insurance is and that if you were to
be diagnosed with breast cancer, or found to carry an altered BRCA1 gene, you run the
risk of losing your insurance, even your job. There are many people in our group who
make serious life decisions based *1273 on the fear of discrimination. The other
concern is that most causes of breast cancer are not inherited, but occur sporadically,
possibly as a result of environmental influences. We are very concerned about the focus
shifting from the environment almost entirely to genes.
All that really exists now is data. I think that we are in an age where people place a high
value on information. I'm not sure it's knowledge; it's just information. We are a culture
that reveres knowledge and that thinks that science has far more answers than it
probably does.
It is our position that predictive genetic testing for breast cancer is still experimental and
academic. Whether a woman wants to have such testing is an extremely complex
decision that needs to be made by the woman herself and her family. It's a very
personal decision. But we believe that no one should even contemplate this unless they
have up-to-date information and appropriate counseling. Also, nondiscrimination and
confidentiality protections are needed for people who decide to be tested. It is our
position that no genetic testing should take place whether in clinical trials or
commercially without these protections in place. But this is not happening. Right now,
for example, anyone could walk into some of the local hospitals and get tested for
BRCA1. All they need is to be able to pay for the test. It concerns me that this type of
testing is being offered in some settings without professional counseling. Very soon,
wide-scale testing will be made available. The majority of health care professionals
have little knowledge about the research status and ramifications of this type of testing
and little, if any, experience in genetic counseling.
It also concerns me that, through commercially available testing, people are getting
information from the companies who administer the tests. There have been some pretty
aggressive marketing campaigns and literature sent out to recruit people in a way that is
problematic. For example, there is marketing to encourage all Jewish women to get
tested. You can even do it by mail order--by sending in a blood sample and $295 to one
lab in the country. The bottom line is that the companies have a tremendous financial
interest in creating a new market for this product. And some researchers involved in this
area have personal financial interests in the companies. Because I'm a lawyer, I may be
more sensitive to the notion of conflict of interest. At the very least, there should be
some rules regarding disclosure. We also know that one of the companies is marketing
its testing service to *1274 disease management facilities and insurance companies that
would benefit from information about a person's risk for breast cancer. With the
facilitation of computerized access to medical records and the lack of consumer
protections, this is incredibly problematic.
The other major concern of our organization is that gene testing for BRCA1 seems to
not be regulated at all. We have met with the State Attorney General's Office and their
Consumer Protection Division and Civil Rights Division to talk about these issues. It's
problematic, because the resolution of this kind of issue usually occurs at the federal
level. It is my understanding that the FDA could regulate this, but they don't since it's not
a pharmaceutical and not a medical device. Although the FDA is not a perfect agency
and its regulatory powers are being cut back, I think it is critical that they have strong
jurisdiction over this. I don't think industries should ever regulate themselves. This
information has the potential to impact individual lives in so many ways. Inadequate
regulation is a serious public health issue that needs to be addressed.
The issue of informed consent for participating in these studies also is a great concern. I
have reviewed a number of informed consent documents that are being given to
women. The majority of these documents are inadequate, even the ones developed for
clinical trials in large, well-respected institutions with people who are sensitive and
knowledgeable about these issues. We have no idea what happens to people when
they get test results, be they positive or negative results, or if they have any
understanding of what this means to them or for their family members. We have talked
with a few people who have been tested who entered the process understanding the
issues and who were surprised at how they were emotionally impacted by the test. They
thought they were prepared but later admitted they really were not. And the family
issues created by this type of testing are overwhelming. One woman was tested within a
clinical protocol and wanted the test to be blind; she didn't want to know the results. But
after she was tested she received a letter from the facility basically saying, “We have
some bad news for you . . . you are at high risk.” She was strictly doing this because
she thought it would be a contribution to science. Then she was faced with the decision
of whether to tell her daughter. Although some of the research programs have a
psychologist and psychiatrist on board and apparently make an attempt to help sort
through the issues, it sounds like it's just an *1275 attempt. Many women considering
testing feel that these programs still have a long way to go.
Ruth Hubbard167 has a great analogy--she says that if you want to build a skyscraper
you turn that task over to architects. But if you want to decide whether to build the
skyscraper, those are not the people who should make the decision because you will
get the skyscraper no matter what. Consumers really need to be part of the dialogue
before genetic tests are developed.
4. A Corporate Representative's Story168
I work as the education and corporate communications manager for a national genetic
testing company with a very large research and development arm, genomics group, and
clinical trials lab. At our company we do prenatal testing as well as molecular and
biochemical testing. We also do cancer cytogenetics and provide a number of other
genetic laboratory services.
Within our clinical trials lab, we are currently working with a number of collaborators in
the area of BRCA testing. We were not involved in the cloning of the BRCA1 gene.
However, we do develop tests for certain genetically inherited diseases, and we have
the capability with some new technology that we developed to run clinical trials for
academic partners. We also are very much involved in the development of protocols for
the delivery of this type of predictive genetic testing service, including genetic
counseling, which has to be part of BRCA testing. Although protocols for testing are
generally developed by professional medical organizations, we believe that we have the
experience and the data to help these organizations as the BRCA test becomes
available. We develop the protocols for use in conjunction with our academic
collaborators who will be the ones who actually make them available within the
physician community. There's a lot of information that comes forward during a clinical
trial . . . it's not just the mechanics of putting something through the testing process. We
address the many ethical and social implications that arise from the testing process
itself prior to introducing a new genetic test.
Our laboratory does not accept specimens from physicians or consumers interested in
BRCA testing. The specimens that come *1276 through our lab come only from our
collaborators, and they are all research studies. We have chosen not to make this test
commercially available at this time because there are too many unanswered questions.
The protocols for the use of this test have not yet been established, and we believe that
its entry must be done carefully. The development of a predictive genetic test is a very
touchy issue, one that needs a lot of examination and care in the thought process prior
to its entry into the market.
As an example, an important part of any genetic test is the protocol for providing test
results. The findings and report process have to be explained very carefully to a
physician. We do not just provide physicians with a written report that states that the
patient has tested negatively or positively. With genetic disease, there can be familial
and psychological impact, and a lab cannot just print out a report and send it off. The
interpretive process is one of the most important things on any report that comes out of
a genetic diagnostics laboratory. As part of our work, we are examining the way in which
BRCA test results ought to be provided and the type of counseling that may be
necessary to deal with the impact of the information.
An illustration of how well the genetic diagnostics community works together is what
happened when the genetic test, by linkage analysis, for Huntington Disease (HD) first
became available in the early 1980s. A consortium was formed of academic and
commercial geneticists and others who got together expressly to carefully map out the
process for the manner in which testing should be offered. When the gene was
uncovered in 1993, these guidelines were only intensified. HD still is not offered to
anyone except through a carefully controlled clinical protocol. All of our patient samples,
for all genetic tests, come from referring physicians--not directly from consumers.
I have seen one package of marketing literature on BRCA testing from one company
offering the test. The materials do not appear to be very unusual. In fact, I was delighted
to see how responsibly and sensitively they have been handled. The companies that
are announcing and marketing this test, I believe, are now working through IRBs that
have been established within their own companies. There is still much to be determined
before this test is made widely available.
I think, as a whole, the genetics diagnostic industry is very cautious about what tests it
offers and how they are offered. In my *1277 view, the commercial industry is equally as
cautious and conscientious as the academic centers. I think the genetic testing industry
does a very good job of regulating itself. We have a number of organizations that
inspect and license our laboratories. These inspection and licensing procedures involve
a wide range of quality control and assurance issues and standards that we are
required to meet. CLIA, the College of American Pathologists (CAP), the Association of
Certified Medical Geneticists (ACMG), and state licensing agencies have stringent rules
and regulations, and our labs are licensed by all of these organizations. I do not think it
is necessary for the genetic diagnostics industry to be regulated by the FDA.
To my knowledge, no genetic test has to be approved by the FDA, and there are no
FDA guidelines or approval processes on any genetic diagnostic test. The labs that
develop these tests have very rigorous programs of their own. We would not offer any
kind of genetic test without a large amount of data showing efficacy, sensitivity, and
specificity. I don't think there is a need for any additional external review. Any genetic
testing company would be foolish to introduce a test that wasn't technically sound. Think
of the potential for harm, the liability issues, the damage to a lab's reputation, and so on.
Our president presented testimony to the Senate Cancer Committee on the issue of
regulation in late 1995. The Executive Summary states our position on external
regulation:
The dawn of a new era of testing for genetically-based disease is both exciting and
challenging. The prospect of being able to identify individuals at increased risk of cancer
and other devastating diseases--and thereby facilitate prevention and earlier, more
effective treatment--could reduce human suffering to an extent that is unprecedented in
medical history. Our collective efforts towards this goal must be conducted with great
care. The evolution of genetic diagnostics is an interactive process that needs a high
level of flexibility to cope with constant change. Test validation, laboratory performance,
and genetic information must all be addressed in appropriate ways, but excessive
Federal regulation must be avoided. Any framework for validating new genetic tests
must reflect a diversity of issues. For instance, testing for a disease that is caused by a
single genetic defect, like Huntington Disease, raises different validation issues than
testing for cancer, which may involve many genes. Our approach to validating such
tests must be flexible or it will *1278 stifle progress and prevent generations of useful
information for patients. Placing additional regulatory requirements on the process at
this time could undermine the investment required to make these potential clinical
benefits a timely reality. Existing voluntary collaborations between commercial and
academic laboratories and researchers work well and have successfully moved tests
like those for cystic fibrosis (CF) and Huntington Disease (HD) into general use. Cancer
testing is more complex but can be managed in a similar way. Genetic testing laboratory
performance standards are regulated by the College of American Pathologists (CAP)
and the American College of Medical Genetics (ACMG) under the Clinical Laboratory
Improvement Amendment (CLIA) of 1988. Additional regulation of lab performance is
not necessary. Increased education in genetics for primary care physicians and other
health care providers is crucial to the understanding and appropriate use of genetic
tests, but adequate resources do not currently exist. This is an area where the Federal
government can play a useful role. Finally, insurance reform, including elimination of
pre-existing condition exclusions and elimination of lifetime caps, will remove major
limitations to the effective use of genetic diagnostics. Congress should address these
issues in pending health care reform legislation.169
I am not saying that genetic testing should not have any kind of regulation. But I think it
can be imposed upon the community to do some major self-policing. Perhaps certain
additional criteria could be met through the existing regulatory processes (CLIA, CAP,
and so on). But to have the FDA involved in genetic testing would slow the process
unbelievably.
Our market analysis for BRCA shows that there is certainly a large potential market.
However, an additional reason for not offering BRCA testing is patent ownership. To
date, there has been no indication that patent filers are willing to license out for
commercialized diagnostic testing.
By the way, the academic institutions charge for their testing. So there really is not much
difference between us, except that officially we are for-profit and they are not, although
some of them actually are. The major difference is in how services are marketed and
how the two entities are perceived out there in the marketplace. One of our larger
competitors is an academic lab that charges for services and markets *1279 their tests
much more aggressively and directly to physicians than we do.
IV. Unifying Themes and Diverging Theories on Regulation
The preceding stories are linked by an overarching theme: the commercialization of
predictive genetic testing services essentially is being left to market forces, academic
interests, and the judgment of primary care physicians. Beyond this basic message,
however, the stories raise an entanglement of issues and present disagreement about
what, if anything, constitutes the appropriate regulatory response to the
commercialization of predictive genetic testing services. The following is an effort to sort
through these conflicting opinions and draw upon the discussion set forth in Parts II and
III, to present arguments for and against direct regulation of predictive genetic testing
services.
A. Continued Deference to Market Forces
Advocates of regulatory restraint support maintaining the status quo. One of the
strongest arguments in favor of this position is that IRB review coupled with the
incentive to avoid product liability is effective--as made evident by OncorMed's
extensive protocol (attached as App. I). The regulatory effect of legal liability must not be
underestimated, for biotechnology executives are well aware that circumventing the
FDA review process sacrifices the liability limitations associated with the MDA.170 Under
this view, the fact that *1280 some companies, such as IVF, are marketing research-
stage predictive genetic tests without restraint is a problem of lack of enforcement of
existing labeling and other regulations, namely CLIA and professional standards, and
not a legitimate basis for introducing even more regulations. Similarly, to the extent that
physicians are straying from these protocols, failing to properly counsel their patients,
and overusing investigational genetic testing services lacking PPV, they are guilty of
practicing poor medicine and should be disciplined professionally.171 Physician
malpractice, it may be argued, is not a legitimate basis for imposing more regulations on
biotechnology companies. Moreover, to the extent that more regulation is needed, it
should come in the form of stronger good-medicine standards imposed on physicians
and enforcement of those standards.172
The status quo offers some significant public health benefits. First, in addition to
developing protocols, industry is addressing ethical issues associated with the
commercialization of genetic technologies, and perhaps is doing so more effectively
than the government could. Several multinational pharmaceutical companies have
financed ethics programs to address these issues.173 Similarly, many
biotechnology *1281 companies are hiring ethicists and, at least presumably, taking the
advice for which they are paying top dollar.174
Second, the FDA traditionally has relied heavily on the private medical profession when
reviewing new products, and legal liability in the place of FDA involvement (with
resulting limitations on liability for compliance) may result in greater quality
control.175 Conflicts associated with the case-by-case nature of the FDA review process,
the discretion allotted individual agents, and close ties between members of the medical
profession and individual FDA reviewers support proposals to rely upon apolitical
advisory committees instead of existing FDA review mechanisms.176
*1282 Third, even experimental genetic tests may offer clinical benefits to some
patients. These benefits include clarification of risk status, more accurate diagnosis of
symptomatic individuals, detection of carrier status, and guidance for selecting the most
prudent course of surveillance treatment.177 For the first time in decades,
cancer *1283 mortality rates have fallen and, in addition to better treatment, this has
been attributed to both prevention and improved diagnosis.178 Fourth, and perhaps most
persuasive, medical science eventually will solve the predictability problem.179 The
present scheme, which generates patient samples and finances research,180 will most
rapidly move genetic medicine to therapeutics and even gene therapies. More
regulations could have the exact opposite effect.
B. Call for Direct Regulation
Advocates for direct regulation of genetic testing services emphasize that, even though
these tests are much more likely to be misinterpreted than traditional diagnostics due to
(1) the absence of scientifically valid PPV, (2) the lack of physician understanding about
genetics, and (3) the public's interest and faith in genetics enhanced by media
coverage, biotech marketing, and information (or misinformation) from providers, these
tests are subject to much less regulatory oversight.181 From a mental health perspective,
genetic tests for serious diseases may impact patient lives at least as much as
traditional diagnostics with established PPV. This is especially true in the absence of
reliable studies of the impact of genetic information on patients' lives182 and the present
dearth of trained genetic counselors in practice.183 In fact, in the absence of coverage,
consumers demanding access to genetic tests may actively avoid genetic counseling
due to the *1284 costs it adds.184 Over-reliance on negative test results185 and over-
treatment based upon positive test results186 are strong possibilities, if not probabilities.
Also, in the absence of adequate consumer safeguards to ensure genetic privacy and
counseling and awareness of these dangers before the decision to undergo genetic
testing is made, those who subject themselves to genetic testing may find that they also
are subjected to discrimination from employers and insurers.187 In addition, family
members may be subject to discrimination based upon the results of genetic testing
they did not even undergo.188
Advocates for direct regulation also argue that OncorMed's prudence in developing a
thorough protocol cannot be relied upon as established industry practice. Rather than
being representative of long-term industry behavior, these precautions may be a
reflection of the fact that OncorMed is the first biotechnology company to make
predictive genetic testing available outside the major research centers and, as such, it
has been painstakingly careful. Similarly, the influence that drug developers and
manufacturers exercise over scientific research must not be underestimated. Industry
influence is not only *1285 impacting the course of science,189 but is tainting the
safeguard of scientific peer review.190 In this modern age of privatized R&D, academic
institutions and their individual researchers are highly susceptible to the influence of the
biotechnology industry and may even hold royalty interests in the industry's
products.191 Accordingly, *1286 the influence of the biotechnology industry over public
health policy must be checked, not augmented by a carte blanche federal regulatory
approach.
C. Drawing Conclusions
The present regulatory scheme for commercialization of predictive genetic testing
services consists essentially of reliance on market forces, legal liability, and the
judgment of primary care physicians. Through access to patient samples and the
opportunity to capture the costs of research, this approach is financing and advancing
biotechnology research. Innovative therapeutics and gene therapies for life-threatening
and widespread diseases such as breast cancer are becoming vivid possibilities.
Nevertheless, the research-stage nature of predictive genetic tests, such as the existing
tests for BRCA mutations, and resulting uncertainties make these tests currently
unacceptable for broad commercialization.192 Legal liability places the burden of quality
assurance on health care consumers who are the people that need to be
protected,193 and the transaction costs of shaping public health policy through litigation
can be immense. Indeed, several cancer organizations and Jewish community groups
have drafted position statements opposed to the commercialization of predictive breast
cancer testing given the lack of safeguards to ensure oversight and *1287 accuracy,
informed consent, and confidentiality.194 Regulatory safeguards are needed to ensure
that predictive genetic technology, which offers much promise, does not detract from
public health because it is applied in a shortsighted, irresponsible fashion. Regardless
of the failures and shortcomings of FDA regulation of traditional diagnostics, medical
and public health officials must directly address the issue of quality assurance for
predictive genetic testing services. They must introduce and enforce consumer
safeguards tailored to this innovative technology.
V. Proposals for Change
Public health education developed with consumer input must be included in any
strategy to regulate the commercialization of genetic testing services.195 Nevertheless, a
broader strategy is needed. Before sorting through the numerous options,196 medical
and public health officials must determine which approach or combination of
approaches is likely to prove most effective. A fundamental point of differentiation is
between protecting consumers (1) through added market review and approval restraints
that more carefully monitor market access to health care consumers or (2) through the
health care profession as a matter of good-medicine standards. In other words, the two
fundamental regulatory approaches (which may be used conjunctively) are (1) to
introduce restraints to keep health care *1288 products that unduly endanger
consumers off of the market or (2) a “good medicine” regulatory approach that uses
professional self-regulation (peer review and norms) and legal liability. The principles
and recommendations proposed by the National Task Force combine these
approaches, with an emphasis on the good medicine approach:
*1289 Table I
Highlights: Proposed Recommendations of the Task Force on Genetic Testing197
Key Principles Validity and Utility of Genetic TestsAs a prerequisite for acceptance in
clinical practice, data sufficient to demonstrate clinical benefits and risks from both
positive and negative results must be collected. An IRB must approve the protocols
used for genetic tests.198Laboratory Quality and CertificationDespite the CLIA
certification requirement imposed on most clinical laboratories, ‘current regulations do
not adequately ensure the quality of genetic testing.'199Professional Competence in
Genetics‘Health care professionals involved in the provision of genetic tests should be
well-informed about their implications, benefits and risks.'200‘[N]ot all providers in
practice today may have adequate competence to offer and interpret genetic
tests.'201 Rare Genetic Diseases‘At a time when genetic tests for common complex
disorders are increasing, tests for rare disorders may be developed at a slower rate
than in the past.'202Informed Consent and Confidentiality‘Informed consent for a
validation study must be obtained whenever the specimen can be linked to the subject
from whom it came.'203 ‘The responsibility for providing information to the individual lies
with the referring provider, not with the laboratory performing the test.'204 ‘Respect for
personal autonomy is paramount. People being offered testing must understand that
testing is voluntary.'205 ‘Results should be released only to those individuals to whom the
test recipient has consented or subsequently requested in writing.'206 ‘Health care
providers have an obligation to the person being tested not to inform other family
members without the permission of the person tested except in extreme
circumstances.'207Recommendations A Genetics Advisory CommitteeThe Secretary of
HHS should create a federally chartered Advisory Committee on Genetics and Public
Policy (‘Advisory Committee’) whose members should include stakeholders in genetic
testing.208 The Secretary also should utilize an interagency group to assist the Advisory
Committee and develop coordinated and consistent genetic testing policies.209Need for
Interim ActionThe Secretary of HHS should ‘use existing agencies and policies to
ensure that the public will have adequate protection from predictive genetic tests that
have not been adequately validated and whose clinical utility has not been
established.'210 To accomplish this, the Secretary may either (1) use its authority under
the MDA or (2) reimburse under Medicaid and Medicare only when genetic tests are
performed in laboratories that can establish that the test has been clinically validated
and that they are qualified to perform them.211Assuring the Validity and Utility of New
Genetic TestsA National Genetics Board (NGB) should be created ‘to assure the
protection of human subjects in the development of genetic tests with the potential to
predict future disease.'212 ‘NGB would develop a checklist that would enable local IRBs
to identify protocols that meet criteria for stringent scrutiny.'213 The FDA should establish
a Genetics Advisory Panel under the MDA that requires new genetic tests to meet
criteria for stringent scrutiny.214 CDC, in cooperation with NCHGR, should expand
monitoring of genetic disorders to provide data on the validity of tests and post-test
interventions and establish procedures for tracking those who undergo genetic
testing.215 The FDA should grant conditional premarket approval for genetic tests with
the potential to make significant public health contributions and place the burden on
developers to collect data and make it available to the FDA.216 NGB should serve as a
clearinghouse for technology assessments and make recommendations on appro-priate
use of genetic tests.217Assuring Laboratory QualityA national accreditation program of
quality assurance and proficiency testing for genetic tests equivalent to or more
stringent than those of New York State and the College of American
Pathologists/American College of Medical Genetics (CAP/ACMG), should be
established under CLIA. The accreditation program should include proficiency testing
and inspection of laboratories that perform genetic tests.218 Until a national accreditation
program is established under CLIA, the CAP/ACMG Molecular Pathology program,
expanded to encompass all genetic testing methods currently in use, should be
implemented as a national program.219 A Genetic Advisory Committee to CLIA should be
established to help address the deficiencies of CLIA. The work of this committee should
be coordinated with other HCFA programs and the work of FDA, CDC, and other federal
agencies involved in establishing policies for genetic testing.220 CAP/ACMG should seek
input from consumer groups such as the Alliance of Genetic Support Groups and
National Society of Genetic Counselors (NSGC) when setting standards.221 CAP/ACMG
should periodically publish and make public a list of laboratories performing genetic
tests in compliance with its voluntary program.222 ‘Managed care organizations and
other third-party payers should limit reimbursement for genetic tests to the laboratories
on the published list . . . .'223 ‘[E]fforts should be made to harmonize international
laboratory standards to assure the highest possible laboratory quality for genetic
tests.'224Provider Competence ‘The Task Force endorses the recent establishment of a
National Coalition for Health Professional Education in Genetics by the American
Medical Association, the American Nurses Association, and the NCHGR.'225 A core
curriculum in genetics should be developed.226 Certification and other credentialing
mechanisms should be used to promote competency.227 ‘Predictive genetic tests
requiring stringent scrutiny, as previously described, should be among those for which
special credentials are needed.'228 Primary care providers and other nongeneticist
specialists should be involved in genetic testing but only after gaining sufficient training
and knowledge.229 Credentialing bodies such as the Joint Commission on Accreditation
of Healthcare Organizations (JCAHO) and the National Committee for Quality
Assurance (NCQA) should be utilized.230 ‘Except when time is of the essence, such as
with certain prenatal genetic tests, obtaining informed consent and actually performing
the test should be delayed several days after the test is offered and information given to
the patient.'231Rare Genetic Diseases ‘The quality of laboratories providing tests for rare
diseases must be assured, and a comprehensive system to collect data on rare
diseases must be established.'232 ‘The Task Force recommends that NIH give [the NIH
Office of Rare Diseases (ORD)] a mandate to coordinate . . . public and private efforts to
improve awareness of rare genetic diseases.'233 ‘ORD should identify laboratories world-
wide that perform tests for rare genetic diseases, the methodology employed, and
whether the tests they provide are in the investigational stage, or are being used for
clinical diagnosis and decision making.'234 ‘ORD should also be responsible for assuring
that tests for rare genetic diseases, which have been demonstrated to be safe and
effective, continue to be available . . . .'235 ‘[A]ny laboratory performing any genetic test
on which clinical diagnostic and/or management decisions are made should be certified
under CLIA.'236 ‘Directories of laboratories providing tests for rare diseases should
indicate whether or not the laboratory is CLIA-certified and whether it has satisfied other
quality assessments, such as the CAP/ACMG program.'237
In an era of deregulation, and in light of the deficiencies of CLIA and a general failure to
enforce CLIA regulations with any consistency, the good-medicine approach to
protecting consumers should be given careful consideration.238 This provider-centered
approach could prove highly effective for physicians to control consumer access to
predictive genetic testing services. Their involvement is absolute, meaning that
consumers cannot have predictive genetic tests run on their samples without a primary
care physician “middleman” making the procedure available. Lack of physician
knowledge about the predictive services they are discussing with and making available
to their patients, and the resulting lack of appreciation for the limitations of the
technology and its impact on patients' lives, is simply inexcusable. Under no
circumstances should physicians be making health care technology available unless
they fully understand that technology. Patients, too, must be given information regarding
the nature of investigative testing. Appropriate pretest counseling must be mandated.
The willingness of physicians to stray from such basic responsibilities may reflect the
fact that many consumers are paying for investigational genetic testing services out of
their pockets (due to both the refusal of insurers to cover experimental services
and *1295 consumer fears of genetic discrimination). Under this payment arrangement,
physicians do not have to account to insurers and managed-care administrators for the
costs of genetic testing services. Although consumer demand for access to predictive
genetic testing services may become (or already may be) significant, medical and public
health officials cannot accept consumer demand as an excuse for the practice of
substandard medicine.239 Acceptance of such an excuse would carry tremendous
ramifications,240 especially in an age of managed care when physician compensation is
tied to the number of patients a physician maintains. Other potential conflicts of interest
are equally troubling.241 Similarly, the physician-patient relationship does not allow the
benefits from advancements in research, regardless of how profound they may be, to
serve as an acceptable rationale for the practice of irresponsible medicine.242
Implementation of the laboratory quality assurance recommendations of the ELSI Task
Force (meaning a CLIA laboratory accreditation program modeled after the CAP/ACMG
Molecular *1296 Pathology Program) to ensure sequencing proficiency must be
accompanied by comprehensive genetic medicine measures. Medical and public health
officials must introduce and enforce good medicine guidelines that are carefully tailored
to directly address predictive genetic testing services.243 For example, federal regulators
should consider imposing a mandatory minimum PPV standard for genetic testing
services performed outside of major academic research centers when results are made
available to those who undergo the testing. Moreover, written proof of compliance--a
written showing of PPV--should be a prerequisite for charging to recover costs.
Similarly, providers should be required to establish competence in genetics as a
prerequisite for reimbursement for the genetic testing services they provide.244
*1297 Such standards must be introduced nationally to avoid an industry “race to the
bottom” at the state level. Specifically, a failure to introduce national standards is likely
to instill the wrong public-health incentives by rewarding states that adopt a laissez-faire
approach to attract industry. Standards also must be explicit enough to be enforceable.
One of the advantages of express quality standards or codes of practice is that they will
remove the amorphous standard of care (“the rest of the profession is doing it”) defense
to liability.245 With more specific standards in place, physicians will be liable for not
adhering to these standards, regardless of what the rest of the profession is doing.
There is ample support within the medical profession for such standards, most notably
from Francis Collins, head of the HGP.246 Ironically, many medical professionals vocally
oppose making BRCA *1298 testing available to consumers outside the major research
centers, even though the medical profession shares responsibility for this occurrence by
failing to effectively self-regulate.247 Moreover, generating tailored standards at a
national level with professional and consumer input has been made more possible
through recent advances in communication. In fact, in an age of global communication,
it also is possible to review, and perhaps adopt, modified versions of health care quality
standards from abroad for innovative technologies that have been proven effective in
practice.248 One possibility is the U.K.'s standards (and underlying research) regarding
genetic diagnosis for late-onset disorders in children.249
Still, thoughtful standards alone may not be enough to counter the pressures on
providers from consumers, behind-the-scene managed care administrators who want to
keep consumers enrolled while minimizing costs, and industry. Therefore, to make the
genetic-test quality standards imposed on practicing physicians enforceable, the
introduction of codified professional standards must be accompanied by regulatory
restrictions on predictive genetic testing.250 In light of *1299 the public and political
pressures on the FDA, such regulation might best be introduced through the CDC, FTC,
HCFA, or HHS by, for example, modifying CLIA. To minimize duplication of regulatory
efforts, there must be horizontal regulatory coordination at the federal level and vertical
coordination between federal and state efforts. This coordination cannot be
accomplished without the establishment of a federal body with the sole responsibility of
achieving this objective and the political independence and authority to do so.
One logical option is to introduce complementary criteria on research laboratories
(meaning any laboratory performing predictive genetic testing) regardless of whether
the testing they perform is offered as research, investigational, or off-label. Like
physicians, research laboratories control access to predictive genetic testing services, in
that their involvement also is absolute. Accordingly, careful consideration should also be
given to the laboratory-quality principles developed by the ELSI Task Force, which are
attached in part as Appendix II, and the more recent Proposed Recommendations
summarized in Table I. Another option is to introduce uniform proficiency testing
(PT).251 As suggested by the ELSI Task Force, such a requirement could be enforced by
making it a precondition for reimbursement for testing services.252 In its more recent
recommendations, the Task Force has proposed introducing a registry of laboratories in
compliance with national standards, coupled with limiting reimbursement by third-party
payers to tests performed by *1300 laboratories on the list.253 Regardless of what
medical-science, quality-assurance safeguards are introduced on the federal level,
there must be recognition of the fact that genetic science is constantly and rapidly
evolving. Accordingly, all review must be ongoing.254
Federal standards also must be introduced to ensure that the IRB mechanism carries
legitimacy.255 At the very least, the CLIA provisions calling for the use of IRBs and giving
them authority must be expanded to address their composition and to establish
standards for approval of any human research, federally funded or not. In light of the
authority IRBs carry and because they are the primary mechanism assuming the
sufficiency of the scientific process and protecting the rights of participating subjects,
there must be prescribed elements for structuring IRBs that promote impartiality and the
enforcement of good-medicine standards. The discretion allowed institutions when
constructing IRBs must be curtailed.256 Strict *1301 conflict-of-interest and disclosure
requirements are needed, including requirements that any compensation for
participation in IRBs be reported and disclosed publicly. Also, the composition of IRBs
should be regulated to the extent necessary to ensure rigorous, intellectually honest,
and scientifically valid review. The importance of such regulation is made especially
acute by the proposed disbanding of the Recombinant DNA Advisory Committee (RAC),
“a venerable panel of scientists, ethicists and other experts at the National Institutes of
Health that for two decades has shined the spotlight of public accountability on the
genetics revolution.”257 The peer review nature of IRBs suggests that the traditional
research/clinical division in medicine should be bridged for IRB standards by
collaboration between professional organizations that focus on both research *1302 and
clinical aspects of medicine, such as the American Medical Association and the National
Hospital Association.
Even if enacted, reforms that conclusively control the quality of predictive genetic testing
services at the national level through restrictions on their delivery--though a
considerable improvement--still would not be adequate. The burgeoning nature of the
biotechnology industry and the field of biomedical science mandates that there be no
assumption of compliance with and enforcement of such regulations. Instead, public
health officials must assume that consumers will have access to genetic testing and that
genetic information will be generated in an increasing fashion. Accordingly, reforms
such as those proposed above must be accompanied by the introduction of a regulatory
infrastructure to protect consumers from abusive uses of genetic information. Without
such reform, “[a]nswers to the next series of clinical questions may be jeopardized by
the injudicious use of genetic testing by physicians and continued concern about the
possibility of discrimination on the basis of the results.”258
National legislation governing the use of genetic information by insurers also is needed
to overcome both regulatory disparities between the states and the preemptive effect of
the Employee Retirement Income Security Act of 1974 (ERISA).259 Otherwise, those
who choose to undergo genetic testing while a resident of a state limiting the use of
genetic information may find themselves unable to obtain insurance coverage when
they move to another state.260 Such regulation has been introduced to prevent
employers from discriminating on the basis of genetic information.261 Also,
legislation *1303 has been proposed to place similar restrictions on insurers. This
legislation includes the nondiscrimination provision in the health insurance reform bills
that address genetic information and that were passed by the House and Senate during
the last Congress.262 In August 1996, President Clinton signed a version of these bills
into law as the Health Insurance Portability and Accountability Act.263
Nevertheless, absent comprehensive consumer protection from genetic discrimination
at the federal level, the protection of citizens and regulation of the insurance industry
rests well within the purview of the states' public health responsibilities. Moreover, while
Congress has been contemplating protective measures, states have been enacting
them.264 Some states, including Massachusetts, are contemplating innovative
measures.265 State public health officials should promote *1304 legislation to protect
consumers in the absence of federal legislation and supplement any federal protections
that are eventually enacted. State responsiveness and ingenuity is especially needed to
address informed consent for genetic testing and the broader issue of genetic
counseling.266 The best state solutions to these challenges ultimately could become
national ones.
When proceeding to implement reforms such as those identified above, legislators and
medical and public health officials must anticipate the reaction of the biotechnology
industry and proceed with market sensitivity.267 At both the state and federal levels, the
biotechnology industry is recognized as an important sector in the *1305 United States's
economic future,268 and many of the products being developed by that sector could
greatly improve public health. However, the diverse nature of the biotechnology industry
and its multitude of products should enable reforms necessary to ensure the
responsible application of predictive genetic testing services to be enacted, assuming a
market-sensitive approach is followed.
Initiatives to enact such reforms actually may benefit from industry insight or prompt
industry to introduce self-reforms that are equally effective. Although the guiding
incentive of the industry ultimately is profit, that incentive may be used to bring about
the consumer-protection regulation that is needed. For example (albeit to preserve and
increase consumer demand) biotechnology companies have joined patient-advocacy
groups in lobbying policy makers to reform the FDA review process269 and prohibit
insurance companies from using genetic information.270 Similarly, OncorMed developed
its elaborate, thoughtful genetic testing protocols at great expense to “Coase around”
FDA regulations that impede access to consumers and, at times, unduly impede the
advancement of life science. Whichever proposals ultimately are adopted to regulate
the commercialization of predictive genetic testing services, public health officials
should make heavy reference to supportive provisions from responsible protocols
developed by the biotechnology industry and its academic allies both to win industry
support and to quell opposition.
VI. Conclusion
In Oedipus Rex, the character Tiresias has the ability to see into the future as if it were
yesterday. Tiresias's divine gift of vision, however, gives him no ability to change what
he sees. In his words to King Oedipus, “Wisdom is a curse when wisdom does nothing
for the man that has it.”271 Without established PPV, predictive genetic tests offer much
less certainty than Tiresias's vision. Although biomedical *1306 science carries the
promise of therapeutics and gene therapies, in their absence, the present inability to
change the future remains.
This Article has analyzed the commercialization of predictive genetic testing for BRCA
alterations linked to breast and ovarian cancer. Beyond addressing this contemporary
and pressing problem, the objective has been to illustrate the public health implications
of the premature commercialization of this technology, to identify regulatory
shortcomings, and to introduce proposals for change. As has been emphasized
throughout this Article, BRCA testing simply marks the beginning of widespread
predictive genetic testing.
Predictive genetic tests without established PPV are unacceptable for broad
commercialization. Such tests are highly subject to misinterpretation by those who
undergo them and by the health care providers who make them available. They are the
equivalent of biological tarot cards.
Death Justice Wheel of Fortune
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT
DISPLAYABLE
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT
DISPLAYABLE
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT
DISPLAYABLE
TABULAR OR GRAPHIC MATERIAL SET FORTH AT THIS POINT IS NOT
DISPLAYABLE
*1307 Public health officials must directly address the issue of quality assurance for
predictive genetic testing services. They must introduce consumer safeguards tailored
to this innovative technology and, more importantly, they must enforce them. This Article
has proposed numerous regulatory reforms to control access to and the quality of
predictive genetic tests. Many of these proposals center on remaining faithful to the
practice of good medicine.
Advances in biomedical research offer many patients hope, not harm. The threat that
accompanies this medical technology comes from the temptation to use it prematurely
and irresponsibly. Just as physicians should not sell a drug or diagnostic to their
patients that they do not understand (and, therefore, cannot measure the benefits of),
physicians should not be making research-stage predictive genetic tests available
without the precautions necessary to avoid doing harm.
Predictive genetic testing simply is at the vanguard of an era of unprecedented progress
in medicine attributable to genetic science. For centuries, the adage “First, do no harm”
has guided the medical profession. The profession and the adage have endured jolting
advances in medical technology--from anesthesia, to antibiotics, to vaccinations.
Similarly, if contemporary public health officials look to this adage, they will find
guidance. Promoting and enforcing the practice of responsible medicine continues to be
the answer.
*1308 Appendix I
Excerpt from Letter Summary of the OncorMed Protocol272
Patients who are eligible for testing under this protocol are:
1. persons with breast and/or ovarian cancer who have two or more first- or second-
degree* blood relatives (related through a single lineage) with either breast or ovarian
cancer,
2. persons with breast and/or ovarian cancer which developed at an early age (<45
years),
3. persons with breast and/or ovarian cancer with multiple primary cancers or bilateral
disease,
4. males who develop breast cancer at any age,
5. relatives of persons with documented mutations in the BRCA1 or BRCA2 gene.
* first-degree relative: parent, siblings, offspring; second-degree relative: aunt, uncle,
grandparent, grandchild, niece, nephew, half-sibling
Patients who may not be tested are:
1. a person under the age of 18 years,
2. a cognitively impaired person or one who is unable to provide informed consent,
3. someone who has a psychological condition precluding testing.
To test a patient under this protocol, the physician would agree to:
(diamond) Call in or fax the family history to OncorMed before testing. Pathological
verification of the history should be obtained whenever possible.
(diamond) Identify a genetic counselor to evaluate the family history, explain
inheritance, discuss the benefits, risks, limitations, and psychosocial impact of testing; a
medical and surgical oncologist to discuss management options; and a mental health
specialist to help in the decision to test, to provide support during the testing process, or
to help adjust to the results. The patient should be offered these referrals
both *1309 before and after testing. OncorMed can help you locate a genetic counselor
in your area, if needed.
(diamond) Ensure that informed consent is obtained and that the patient receives pre-
and post-test counseling by one or more professionals knowledgeable about the
genetics and management of hereditary breast cancer syndromes.
(diamond) Give the test results to the patient in person and develop a management plan
with the patient.
(diamond) Refer the patient to the specialists you have identified as needed, provide
psychological support, and assist in informing relatives if appropriate.
We have provided a number of items which may help you counsel and test patients
under this protocol.
(diamond) A testing flow diagram which outlines the protocol and which you can keep as
part of your records to document progress though the testing process.
(diamond) A physician Q&A with information on BRCA1 and BRCA2 and on testing
patients.
(diamond) A patient Q&A describing testing which can be given to patients. Encourage
the patient to take the Q&A and the consent home to review prior to agreeing to be
tested.
(diamond) Counseling checklists which you can use to be sure all relevant information is
covered during the pre-and post-test counseling sessions and which can be given to the
patient as a summary of the counseling.
(diamond) A clinical history form and consent which should be signed and returned with
the blood sample if the patient agrees to testing.
Appendix II273
ELSI Task Force Draft Interim Principles for Laboratory Quality
The ELSI Task Force identified 4 categories for considerations related to laboratory
quality: (1) biologic materials and components, meaning the reagents and equipment
used by the laboratory; (2) laboratory start-up, meaning the introductions of new tests;
(3) laboratory practice, *1310 meaning the actual performance of tests, personnel,
internal quality control, and quality assurance mechanisms; and (4) laboratory oversight,
meaning proficiency testing, accreditation, and inspection. The Task Force issued the
following principles:
A. Components and Biologic Materials
Principle II-1: A genetic test must be analytically validated for each analyte it is intended
to measure. It is ultimately the responsibility of each laboratory director to ensure
analytic validity.
. . . [T]here is minimal external oversight of the components used in genetic testing,
except for those in FDA-approved kits or other devices. Although the Task Force is
considering policies to change this picture, for the moment the laboratory supervisor
must be responsible for assuring the performance characteristics of the components
used in the laboratory's testing repertoire. Under the authority of CLIA (or of states that
are at least as rigorous as CLIA), government surveyors are supposed to determine
whether laboratories have developed new tests and, if so, to then review their data for
analytic validation. . . .
Principle II-2: Appropriate specimens from patients, carriers, and controls should be
available through a centralized system in order to facilitate their availability to aid in
analytical validation, improving quality, or other needs.
. . . .
B. Start-Up
Principle II-3: Laboratories can offer new genetic tests only after their analytical and
clinical validity have been established by that laboratory or elsewhere.
. . . .
Principle II-4: Before routinely offering genetic tests that have been clinically validated, a
laboratory must conduct a pilot phase in which it verifies the performance characteristics
of its test.
. . . .
Principle II-5: Prior to beginning routine patient testing, the laboratory must review and
evaluate the data collected in the pilot phase.
. . . .
Principle II-6: Research laboratories that provide physicians with results of genetic tests,
which may be used for clinical decision *1311 making, must validate their tests and be
subject to the same internal and external review as other clinical laboratories.
. . . .
C. Practices
. . . The potential for errors in referral, the choice of an appropriate test, the probabilistic,
predictive, and conditional nature of test results place a greater burden on
communication between the laboratory and the provider ordering and/or receiving
results than is the case for many other types of tests. . . .
Principle II-7: Because of the complexities in assessment and interpretation, requisitions
for genetic tests require more intake information than those for most other clinical
laboratory tests.
. . . If information that is critical to the performance or the interpretation of the test
cannot be obtained, the specimen should be rejected. . . .
Principle II-8: Genetic test results must be written by the laboratory in a form that is
understandable to the nongeneticist health care provider.
. . . Laboratory reports must include sufficient information in order for the referring
provider to interpret the results appropriately to the person tested or, in the case of
minors, to their parents. . . .
Principle II-9: Personnel serving as directors or technical supervisors of genetic testing
laboratories must have formal training in human and medical genetics.
. . . .
Principle II-10: Training programs for laboratory technicians/technologists should include
more human and medical genetics content than is currently available.
. . . Several formal training programs for cytogenetics technical staff are available, but
there are only one or two certificate--or diploma--track genetics training programs for
technicians or technologists in the U.S. . . .
. . . .
D. External Review
Principle II-11: A national accreditation program for laboratories performing genetic
tests, which includes on-site inspection and proficiency testing, is needed to promote
standardization.
. . . .
*1312 Principle II-12: Genetic testing laboratories must participate in proficiency testing
(PT) programs for each of its tests, if available. When no relevant proficiency testing
programs exist, laboratories must, whenever possible, participate in inter-laboratory
comparison programs and help develop them if none exist in their particular area of
testing. Proficiency testing programs should be broadly based since the number of
genetic disorders is very large and the analytical approaches to testing are numerous.
Laboratories and inspectors should use PT results to help a laboratory improve its
quality.
. . . .
In mandatory PT programs, some punitive action is taken if laboratories that “fail” do not
improve their performance on subsequent rounds.
Footnotes
a
The authors are members of the faculty of the Eunice Kennedy Shriver Center for
Mental Retardation. The opinions expressed are solely the authors' unless attributed to
others and are in no way attributable to any of the institutions with which they are
affiliated. Appreciation is due to the law firm of Kirkpatrick & Lockhart LLP for supporting
this project and to our colleagues for their helpful suggestions and other contributions,
including Maureen O'Rourke and members of the Massachusetts Legislature's Special
Committee on Genetic Information Policy. Our special appreciation to Jan Platner, J.D.,
Executive Director of the Massachusetts Breast Cancer Coalition, and the others who
shared their professional and personal experiences with the issues addressed in this
Article. We also thank Patricia Murphy, M.D. with OncorMed, Inc., and Brian Murphy,
Ph.D. with Myriad Genetic Laboratories, Inc., for reviewing an earlier version of this
Article and sharing their vast practical knowledge. In addition, we acknowledge the
contribution of Terenia Guill and Jana Grauberger and their colleagues at the Tulane
Law Review.
1
We employ definitions pertaining to genetic testing adopted by the Task Force on
Genetic Testing, which was created through the Ethical, Legal, and Social Implications
(ELSI) Subprogram of the Human Genome Project (HGP). The ELSI Task Force has
defined “predictive genetic test” as the “test of a person's or fetus's genes or gene
products for the purpose of determining the presence of abnormalities, including carrier
status, that are known to be associated with an increased risk of development of a
disease or disorder.” Meeting Minutes from the Second Meeting of the Task Force on
Genetic Testing 3 (Nov. 14-15, 1995) [hereinafter Meeting Minutes]. As recognized by
the ELSI Task Force, the predictive element of this definition must be underscored:
Genetic tests are already an important part of medical practice. In patients with overt
manifestations of disease, they can rule out mistaken diagnoses or establish the correct
diagnosis promptly, avoiding needless referrals and elaborate workups (e.g. [sic] a test
for cystic fibrosis in a child with recurrent pulmonary infections).
ELSI Task Force on Genetic Testing, Interim Principles 2 (1996). We emphasize the
distinction between predictive genetic testing and presymptomatic diagnostic testing.
The latter assumes predictability. See infra note 12 for further clarification of these
terms. We also recognize that breast cancer is not 100% gender-specific, meaning that
men too may be stricken with the disease. However, for the sake of simplicity and to
reflect the vast majority of breast cancer patients, throughout this Article we use the
female gender to refer to breast cancer patients.
2
The stated purpose of the test is to determine the presence of a specific genetic
alteration, or allele, linked to breast and ovarian cancer. The testing process consists of
extracting DNA from a blood sample and sequencing the DNA to determine whether the
genetic alteration is present. This technology is based upon the discovery that a gene
called BRCA1 (breast cancer 1), found on chromosome 17, codes for a protein that has
a tumor-suppressor function. See Yoshio Miki et al., A Strong Candidate for the Breast
and Ovarian Susceptibility Gene BRCA1, 266 Science 66, 66-71 (1994); Stephen C.
Rubin et al., Clinical and Pathological Features of Ovarian Cancer in Women with
Germ-Line Mutations of BRCA1, 335 New Eng. J. Med. 1413, 1413 (1996) (reporting,
however, that this form of inherited cancer is more responsive to clinical treatment); see
also Frances S. Collins, BRCA1--Lots of Mutations, Lots of Dilemmas, 334 New Eng. J.
Med. 186, 186 (1996) (emphasizing the scientific unreliability of current testing
capability). Alterations in the gene may interfere with the production of this protein or
with the gene's function in some other way, and thus cause an increased risk of
developing breast cancer. Already
more than 130 different mutations have been found in the breast cancer gene. Some
are probably meaningless, and others deadly, but most have not been studied yet.
Standard gene tests available today detect only ... a few of the more common
mutations, so a negative test doesn't guarantee that a woman is safe.
Rick Weiss, Tests' Availability Tangles Ethical and Genetic Codes, Wash. Post, May 26,
1996, at A1; see also D. Shattuck-Eidens et al., A Collaborative Study of 80 Mutations in
the BRCA1 Breast and Ovarian Cancer Susceptibility Gene, 273 JAMA 535, 535-41
(1995) (stating that over 100 distinct mutations of BRCA1 have been identified). A
second gene, known as BRCA2, also has been linked to breast and ovarian cancer.
See Richard Saltus, 2d Cancer Gene Cited in 1 of 100 Ashkenazi Jewish Women,
Boston Globe, Oct. 2, 1996, at A18 (citing Oct. 2, 1996 issue of Nature Genetics). In
early 1997, a third gene, CHK, was lined to breast cancer. See Judy Foreman, Another
Gene with Breast Cancer Role Identified, Boston Globe, Jan. 16, 1997, at A23.
3
IVF uses allele-specific hybridization techniques rather than sequencing.
4
One BRCA1 mutation, 185delAG, is believed to occur in one percent of the people who
are of Ashkenazi (Eastern European) Jewish ancestry. See J.P. Struewing et al., The
Carrier Frequency of the BRCA1 185delAG Mutation is Approximately 1 Percent in
Ashkenazi Jewish Individuals, 11 Nature Genetics 198, 198-200 (1995). Research is
ongoing, as other ethnic groups may be more susceptible to inherited breast cancer
and, further, inherited susceptibility may be offset by environmental factors not yet
identified. Still, according to recent data, one in 50 Ashkenazi women carry at least one
of the BRCA1 and BRCA2 mutations that are believed to raise a woman's susceptibility
to inherited breast and ovarian cancer. See Saltus, supra note 2, at A18. However, only
five to ten percent of incidents of breast cancer are believed attributable to inherited
genes. See id. See generally The Scientific Questions, 18 Persp. Genetic Counseling 4
(1996) (estimating that 10% of breast cancers are due to germline mutations); David S.
Hilzenrath, Md. Firm's Gene Test to Intensify Bioethics Debate, Wash. Post, July 25,
1996, at D14 (describing a service to detect predisposition to breast and ovarian
cancer). For discussion of the danger of “ethnic genetics,” see Ruth Hubbard & Wendy
McGoodwin, The Danger of “Ethnic Genetics,” Boston Globe, Oct. 13, 1995, at 3. See
also E.J. Kessler, The Secret Shake-Up in the Shiduch, Forward, Cancer & Us, July 26,
1996, at 11, 13 (reporting from New York City's Orthodox Jewish Community that,
“[d]iagnosed with breast cancer--a terrifying disease under any circumstances--these
women feel they must hide their trouble, traveling far from home for treatment and
disguising their hospital stays as out-of-town visits, lest the news of their affliction
poison the marriage prospects of their daughters”). It is important to note that OncorMed
has directly addressed some of the implications of singling out Ashkenazi Jews for
BRCA testing through the formation of a special protocol and information packet to
accompany its “Heritage Panel” test, a test for three BRCA mutations found at an
elevated level in families of Ashkenazi Jewish descent. See OncorMed Heritage Panel
Education and Testing Packet (undated) (on file with authors).
5
See Meredith Wadman, Women Need Not Apply, Wash. Post, May 5, 1996, at C3
(reporting that, in collaboration with IVF, Dr. Joseph Schulman is offering the test to
Jewish women referred by a physician for $295); Weiss, supra note 2, at A1.
6
See Hilzenrath, supra note 4, at D14 (“OncorMed ... plans next week to introduce a new
service that will raise the stakes in one of biotechnology's biggest ethical debates ....”);
Ridgely Ochs, New Test Offered for Cancer Gene, Newsday, July 24, 1996, at A7.
7
See Myriad Laboratories, Inc., BRCA1: Genetic Susceptibility for Breast and Ovarian
Cancer 2 (1996); see also Saltus, supra note 2, at A18; Sean Taytigian et al., The
Complete BRCA2 Gene and Mutations in Chromosome 13q-Linked Kindreds, 12 Nature
Genetics 333, 333-37 (1996) (publishing full sequence of BRCA2 breast cancer gene by
Myriad Genetics). To advance compilation of the data needed to raise the clinical value
of its BRCA testing, Myriad has established a registry at the Dana-Farber Cancer
Institute. See Richard Saltus, Gene Test for Cancer Risk is Offered, Boston Globe, Oct.
25, 1996, at A1.
8
OncorMed BRCA1 Testing Service Commercialization Enters Second Phase Through
New IRB Protocol, 39 Blue Sheet 6, 6-7 (1996) [hereinafter OncorMed BRCA1 Testing
Service]. In contrast, Europe is considering an outright ban on the use of genetic
testing information by insurers in the absence of comprehensive self-regulation. See
Insurers Risk Ban Over the Use of Genetic Testing, Daily Express, July 19, 1996,
available in Westlaw, 1996 WL 6714032 [hereinafter Insurers Risk Ban].
9
We note, however, that these companies have taken very different approaches to many
of the patient issues raised in this Article. We commend the work of OncorMed and, in
particular, Dr. Patricia Murphy in developing meaningful protocols for genetic testing.
See App. I.
10
See Proposed Recommendations of the Task Force on Genetic Testing, Meeting Notice,
62 Fed. Reg. 4539, 4544 (1997) (“The Task Force recognizes that developers of genetic
tests who do not rely on federal funds are under no legal obligation to submit protocols
to the proposed NGB and have not always obtained IRB approval for validation
protocols of tests they plan to market as laboratory services.”). However, the FDA has
not completely acceded that it lacks the statutory authority to regulate genetic testing.
See OncorMed BRCA1 Testing Service, supra note 8, at 7 (“Currently, the FDA is not
regulating the testing; the agency maintains that it has such authority but lacks the
resources to review the technology or make and enforce new regulations for the field.”).
11
As discussed fully infra at note 25, the clinical predictive value of these tests for
determining whether an individual who has tested positive for the alleles will suffer
breast cancer in her lifetime has not been determined, except for a very small
percentage of the population.
12
It is important to distinguish predictive genetic testing from reliable presymptomatic
genetic testing, as the meaning of these terms is being muddled in the current genetic
testing debate. The distinction between these terms is certainty, clinically known as
“positive predictive value” (PPV), which is defined infra at note 25. Presymptomatic
genetic testing refers to testing for genetic alterations causative of disorders and often
controlled by a single genetic alteration, prior to the onset of symptoms. Such disorders
include Huntington's Disease and Amyotrophic Lateral Sclerosis (ALS), commonly
known as Lou Gehrig's disease. So-called “predictive” genetic testing is also testing for
genetic alterations linked to health conditions and disorders. However, due to the
influence of other genes and environmental factors over the target health conditions,
predictive genetic testing at most offers the general public estimated chances of actually
developing the health condition.
13
Even years ago, leaders in the field of genetics were responding to “the very real
possibility that the explosion of knowledge in the field of genetics will produce a windfall
of diagnostic and therapeutic technologies.” Philip J. Boyle, Shaping Priorities in
Genetic Medicine, Hastings Center Rep., May-June 1995, supp. at 1; see also Weiss,
supra note 2, at A1 (“New genetic tests are moving rapidly from research laboratories
into doctors' offices, where they are being marketed as a way to predict people's
chances of getting common diseases such as colon cancer, breast cancer and
Alzheimer's disease.”). The truth has become undeniable. “Scores of genetic tests have
been developed for dozens of diseases. Some are used to diagnose existing conditions
and others are used in healthy people to predict the odds that a disease will occur.” Id.
Representative genetic tests in various stages of development include the following:
Medically useful: (a)APC gene, which is linked to familial adenomatous polyposisa
condition that leads to colon cancer; (b)MEN gene, which is linked to multiple endocrine
neoplasia and indicates a very high risk of cancer of the endocrine glands; and (c)RB
gene, which is linked to retinoblastoma-- childhood eye cancer;
More research needed: (a)BRCA1 and BRCA2, which have been linked to breast and
perhaps ovarian cancer; (b)MSH2 and MLH1, which have been linked to hereditary
nonpolyposis colon cancer; and (c)p53, which has been linked to Li-Fraumeni
syndrome, an elevated risk of many cancers; and
Little clinical utility at present: (a)p16, which has been linked to malignant melanoma, a
serious skin cancer; and (b)APOE-4, which has been linked to Alzheimer's disease.
Id.
14
As recognized by Professor Annas, “The gene has become more than a piece of
information; it has become ‘a cultural icon, a symbol, almost a magical force.”’ George
Annas, Genetic Prophecy and Genetic Privacy, Trial, Jan. 1996, at 19, 24-25 (quoting
Dorothy Nelkin & M. Susan Lindee, The DNA Mystique: The Gene as a Cultural Icon 2
(1995)); see also Richard Saltus, Sounding the Alarm, Boston Globe, May 26, 1996,
(Magazine), at 14 [hereinafter Saltus, Sounding the Alarm] (“No longer merely a
scientific schematic, it is now a staple of pop culture. It appears time and again in op-ed
pieces, newspaper and magazine articles, and books that tackle the thorny dilemmas of
the genetic revolution.”). Dr. Richard C. Lewontin, a Harvard scientist who is critical of
present priorities in gene research and also affiliated with the Council for Responsible
Genetics, a consumer group based in Cambridge, Massachusetts, has coined the term
“genomania,” that is, “the idea that almost everything--a baby's chin or nose, someone's
personality quirks, or a preponderance of men in positions of power--can be explained
by genes.” Id. But see Richard Saltus, Early Alzheimer's: Do You Want to Know?,
Boston Globe, July 3, 1995, at 39 [hereinafter Saltus, Early Alzheimer's] (“Recently
developed gene tests ... for inherited predispositions to breast cancer and other cancers
have raised this issue for an increasing number of families. If any conclusion can be
drawn thus far, it's that people are more hesitant and ambivalent about learning their
genetic destiny than anyone expected.”). It is important to emphasize that industry is
attempting to facilitate consumer interest in and demand for genetic testing. For
example, “Myriad is currently establishing a genetic testing and information business to
identify individuals who have inherited gene mutations which increase their risk for
specific illnesses.” Myriad Laboratories, Inc., supra note 7, at 2. The predominant force
that drives consumer demand for a great deal of predictive genetic testing may be social
pressure. See Daniel Callahan, The Genetic Revolution, in Birth to Death: Science and
Bioethics 15 (David C. Thomasma & Thomasine Kushner eds., 1996) (“New medical
technologies rarely remain discretionary for long. If they are not legally imposed on
people, something hard to do in our western society, they can just as effectively be
imposed by social pressure.”).
15
See Assessing Genetic Risks (Lori Andrews et al. eds., 1994) (reporting on pervasive,
informal genetic testing by research); ELSI Task Force on Genetic Testing, supra note 1,
at 2; Paul H. Silverman, Commerce and Genetic Diagnostics Laboratories), Hastings
Center Rep., May-June 1995, supp. at S15 (“The prospect of routine genetic
diagnostics for a wide variety of diseases ranging from rare monogenetic afflictions (for
example, Tay-Sachs) to common polygenic diseases (for example, many cancers) have
attracted the attention of commercial testing laboratories and venture capitalists.”); Joan
Stephenson, Questions on Genetic Testing Services, 274 JAMA 1661 (1995) (“As
scientists pinpoint genes that underlie such diseases as cystic fibrosis and breast
cancer, commercial and academic laboratories are scrambling to provide genetic testing
services aimed at diagnosing gene-related disorders and assessing future disease
risk.”); Ronald Rosenberg, For Matritech, an Encouraging Prognosis, Boston Globe,
Feb. 18, 1996, at 80 (“Matritech and other biopharmaceutical firms are developing a
new generation of simple diagnostic tools, or exams, to track the progress of the cancer
itself in recovering patients.”).
16
See infra note 64 and accompanying text.
17
According to the ELSI Task Force, the four primary forces fueling expansion of the
commercialization and availability of predictive genetic testing are: (1)the reward
structure of science, which encourages immediate reporting of findings; (2)public
demand for progress in the fight of disease; (3)biotechnology companies' objective of
developing markets large enough to make testing profitable; and (4)media coverage of
genetic discoveries. See ELSI Task Force on Genetic Testing, supra note 1, at 4. For a
general discussion of the inconsistency of insurance coverage in the United States for
state of the art medical treatments, see Karen L. Illuzzi Gallinari, Commentary, The
State of the Law on Insurance Coverage for State of the Art Medical Treatments,
Mealey's Lit. Rep.: Bad Faith, Oct. 18, 1995, at 16.
18
A catalog of human genes and genetic disorders has been compiled by Dr. Victor A.
McKusick, doctor of medical genetics and professor at the National Center for Human
Genome Research at John Hopkins University. This catalog, which is updated daily and
available on the World Wide Web, lists more than 5,000 genes/genetic disorders. See
Ellie McCormack, Sought-After Counselors Find It's All in the Genes, Boston Bus. J.,
Apr. 26-May 2, 1996, at 3, 23; see also Do You Really Want to Know?, Nightline (ABC
television broadcast, Apr. 26, 1996) (videotape on file with authors). Consider that, in
1966, this list consisted of just 1,500 entries. Id.
19
“According to the British Medical Association, ‘[g]enetic and part-genetic diseases affect
one in every twenty people by the age of 25 and perhaps as many as two in three
people during their lifetime.”’ Sheila A.M. Mclean, Genetic Screening of Children: The
U.K. Position, 12 J. Contemp. Health L. & Pol'y 113, 114 (1995) (stating also that the
proportion of childhood deaths attributable to genetic factors, wholly or partly, is
approximately 50%) (citing British Medical Association, Our Genetic Future: The
Science and Ethics of Genetic Technology 1 (1992)).
20
The HGP is a three-billion-dollar initiative launched by the federal government to map
the entire human genome by the year 2005. For discussion of the HGP, see generally
Robert M. Cook-Deegan, The Gene Wars 169 (1994); Robert M. Cook-Deegan, Origins
of the Human Genome Project, 5 Risk: Health, Safety & Env. 100 (1994). The impact of
the HGP on the biotechnology industry is addressed in Michael J. Malinowski &
Maureen A. O'Rourke, A False Start? The Impact of Federal Policy on the
Genotechnology Industry, 13 Yale J. Reg. 163, 190-91 (1996).
21
See Detailed Human Physical Map Published by Whitehead-MIT: STS-Based Map
Represents Halfway Point to 100-kb Human Genome Project Goal, Human Genome
News, Jan.-Mar. 1996, at 5 [hereinafter Human Physical Map] (“The new map, which
contains more than 15,000 STS DNA markers spaced an average of 199 kb apart,
covers almost 95% of the entire genome.... Although originally slated for 1988, map
completion by Whitehead-MIT and other groups is expected by the end of this year.”).
The HGP is a “global attempt to identify the blueprint of every individual's genetic
makeup.” Mclean, supra note 19, at 114-15. For a full discussion of the HGP, see
Malinowski & O'Rourke, supra note 20, at 190-93; Michael J. Malinowski, Coming into
Being: Law, Ethics, and the Practice of Prenatal Genetic Screening, 45 Hastings L.J.
1435, 1441-45 (1994). See also infra Part II.A. One of the fundamental goals underlying
HGP is “[t]he rapid transfer of technology to industries that can develop economically
and medically useful applications ... that affects us all.” Robin J.R. Blatt, Conceiving the
Future: The X's and Y's of Genetic Testing in Pregnancy (forthcoming 1997) (on file with
the authors).
22
See Dee Lord, Something in the Genes, ABA J., Apr. 1996, at 86; Richard Saltus, Curbs
on Use of Genetic Information Studied, Boston Globe, Feb. 23, 1996, at 19. The
capability to test for multiple mutations at one time is known as multiplex testing. See
Lori B. Andrews, Prenatal Screening and the Culture of Motherhood, 47 Hastings L.J.
967 (1996) (addressing multiplex testing in the context of prenatal screening). An
advanced form of this technology, Multiple Allele Specific Diagnostic Assay (MASDA),
developed by Genzyme Genetics in Framingham, Massachusetts, makes it possible to
test over 500 patient samples for over 100 known mutations simultaneously. See
Private Communication between Robin Blatt and Judith King, Former Education and
Corporate Communications Manager, Genzyme Genetics (July 1996).
23
According to one report, Kaiser
plans to offer genetic tests to show the predisposition to breast cancer among some of
its 6.8 million members. Kaiser guidelines will lay out the process for getting the test,
and will probably require any candidates to undergo comprehensive counseling in
advance. Patients and their families will be included in a registry and will be followed
afterward to monitor the consequences of the test.
Robert B. Whitcomb, Our Genetically Evolving Future, Providence Journal-Bulletin,
Sept. 5, 1996, at 7B.
24
See Stephenson, supra note 15, at 1661 (stating,
[t]he problem with this development, according to a new survey, is that some of the
laboratories offering genetic testing are bypassing the admittedly vague regulatory
controls or other less formal measures that exist to help assure test validity. Some are
also failing to make it clear to physicians and patients that many such procedures are
still investigational in nature.
); see also Proposed Recommendations of the Task Force on Genetic Testing, Meeting
Notice, 62 Fed. Reg. 4539, 4539-44 (1997). This conclusion is supported by a recent
study, conducted by Dr. Neil Holtzman, that sampled 594 commercial and 425 nonprofit
laboratories (mostly academic institutions) and realized a response rate of
approximately 80%. See id.; see also Barbara Koenig, Gene Tests: What You Know
Can Hurt You, N.Y. Times, Apr. 6, 1996, at A23 (“Unfortunately, nothing prevents
laboratories from offering genetic tests, nor are there any regulations to insure the
quality of the tests.”). Although Dr. Holtzman has not yet published the results of his
survey, according to one interpretation:
The poll revealed that most commercial enterprises that currently market such tests are
doing so without gaining clearance from the Food and Drug Administration (FDA), and
thus there is no guarantee that the laboratory tests are performed properly or that they
are even appropriate for the disease in question. The researchers also found that many
testing organizations are failing to seek approval from institutional review boards--
panels composed of physicians, scientists, ethicists, clergy, and representatives from
the lay community--which hospitals often establish to discuss whether new procedures
or technologies should be put into effect.
The Hazards of Genetic Testing, Harv. Women's Health Watch, Dec. 1995, at 6.
25
As explained by the ELSI Task Force, the penetrance of the genetic factor (genotype) is
the probability that the related condition will appear in the physical makeup (phenotype)
when the genetic factor is present. See ELSI Task Force on Genetic Testing, supra note
1, at 9. “The quantitative measurement of penetrance is [ ] ‘positive predictive value
(PPV) ....”’ Id. The application of PPV to BRCA tests is illustrative of the concept. “The
observed lifetime PPV for breast cancer due to inherited BRCA1 mutations is 85%-90%
in women in high risk families, but some women with these mutations will develop
breast cancer for other reasons.” Id. at 9-10. To accurately determine the PPV, it must
be determined through clinical research what percentage of women with the mutation
will get the disease for other reasons. In other words, what percentage of women
without the mutation will still get the disease? Further, the percentage of women with the
mutation who do not develop the disease must also be determined. Several studies
raise some doubts on inherited risk, suggesting that “environmental factors, such as age
at first childbirth, diet, and exposure to hormones, can alter the effects of the BRCA1
and BRCA2 genes, and other genes may have an impact as well.” Richard Saltus, New
Data Add to Confusion on Breast-Cancer Gene Issue, Boston Globe, Apr. 30, 1996, at
9. Due to the factors that must be considered and the potential importance of interaction
between factors, “[o]btaining data for PPV may take years to accomplish, particularly for
late-onset disorders.” ELSI Task Force on Genetic Testing, supra note 1, at 10. This
BRCA example illustrates that presently the PPV and clinical sensitivity of genetic tests
are intrinsically limited. For example, “[m]any different alleles in the same gene (allelic
diversity) or alleles of different genes (locus heterogeneity) can lead to the same
disease.... Failure of a test to detect all disease-related mutations reduces its clinical
sensitivity.” Id. at 8. A test carries high clinical sensitivity when it is immune from being
skewed by other substances (such as substances in food or drink) and high clinical
specificity when it can determine the exact substance(s) linked with a condition. See id.
at 5-12.
26
Predictions by scientists that genetic technology would greatly improve human health
date back at least 15 to 20 years. See Saltus, Sounding the Alarm, supra note 14, at 14.
27
Strong concerns about the uses of genetic information by insurance companies were
raised by public officials, such as Congressman Obey, during House appropriations
hearings for the HGP back in 1990. See Cook-Deegan, supra note 20, at 169; see also
Departments of Labor, Health and Human Services, Education, and Related Agencies
Appropriations for 1991 pt. 4B, at 887-960. In fact, today's pressing genetic testing
issues were readily foreseeable as early as 1986. See Marne E. Brom, Note, Insurers
and Genetic Testing: Shopping for that Perfect Pair of Genes, 40 Drake L. Rev. 121, 128
(1991) (“In a 1986 survey of biotechnology companies, eight planned to offer genetic
tests as a laboratory service for clinicians and researchers, and six predicted that
diagnostic kits would be available for sale by 1991.”).
28
See Cook-Deegan, supra note 20, at 237.
29
This is true both domestically and abroad. Domestically, the National Institutes of Health
(NIH) and Department of Energy (DOE), though their ELSI program, assembled the
Task Force on Genetic Testing and charged it with completing a report by the end of
1997. See generally ELSI Task Force on Genetic Testing, supra note 1, at 2. Also, the
Clinton Administration recently appointed a fifteen-member National Bioethics Advisory
Commission (NBAC) whose initial studies will cover the appropriateness of patenting
genes and the rights of patients who participate in genetic research. See Jeffrey L. Fox,
US Bioethics Commission Meets, Outlines Agenda, 14 Nature Biotechnology 1533,
1533 (1996) (emphasizing importance placed on genetic privacy issues); Russ Hoyle,
US National Bioethics Commission: Politics as Usual?, 14 Nature Biotechnology 927,
927 (1996) (“[A]n effective bioethics commission must take as its mission the review of
difficult, or ‘big time’ research in public before it is done.”); Eric Convey, Mass. Exec.
Named to Bioethics Panel, Boston Herald, July 25, 1996, at 29 (announcing
appointment to presidential panel to explore ethical issues surrounding the biotech
industry); Charles Craig, National Commission to Study Ethics of Genetic Medicine, 7
BioWorld Today, July 25, 1996, at 1; see also Office of Science and Technology
Assessment, National Bioethics Advisory Comm. Proposed Charter, 59 Fed. Reg.
41,584, 41,584-86 (1994) (announcing the establishment of such a commission); US
Agencies Seek Rules on Human Testing, Boston Globe, Jan. 23, 1997, at A11
(reporting that five Cabinet departments and two agencies agreed to a formula to share
the $1.1 million operational cost). “In Europe, similar commissions are already well
established, from Britain's Nuffield Council on Bioethics (London) and UNESCO's
International Bioethics Committee (Paris) to the European Commission's Group of
Advisers on Ethical Implications of Biotechnology (Brussels).” Hoyle, supra, at 927.
Also, in July 1996, the U.K. government announced the establishment of a Human
Genetics Commission to serve as a strategic body to monitor medical genetics in
response to parliamentary pressure for a unified group with a strategic overview. See
UK Sets Up Human Genetics Commission, Clinica, July 1996, at 1 (describing the
commission as a nonstatutory body consisting of eminent, independent experts who will
report to both health and industry ministers); Michael J. Malinowski, Globalization of
Biotechnology and the Public Health Challenges Accompanying It, 60 Alb. L. Rev. 119,
123-33 (1996). In the United Kingdom, the Medical Research Council is deciding
whether it will publicly fund a search for genes that influence IQ-test results. See David
King, Editorial, Business Gets the Upper Hand; David King Calls for Democratic
Decision-Making, Guardian, May 23, 1996, at 19.
30
Genotechnology is the subset of biotechnology consisting of scientific discoveries
associated with human genetics and the HGP. See Malinowski & O'Rourke, supra note
20, at 191 & n.165. “Genomics” is another descriptive term, used routinely by industry
for this category of technology. See generally Bio ‘96, International Biotechnology
Meeting & Exhibition, Genomics: Impact on Health Care (1996) [hereinafter Bio ‘96] (on
file with authors) (discussing the impact of genomics on health care).
31
The Biotechnology Industry Organization (BIO) recently formed an ethics committee to
deal with privacy and research issues. See Kathleen Day, Genetics Research Begets
Questions; Biotech Industry Seeks Ethics Advice to Deal with Complex Issues, Wash.
Post, May 8, 1996, at A1. This committee
will focus on [the] issue of privacy and on what types of research should and should not
be performed, said BIO President Carl Feldbaum. He said executives from American
Home Products Corp., Genentech Inc. and Genzyme are heading committees on these
and other topics and that the organization is trying to hire a PhD [sic] in philosophy to
become its full-time staff member on ethics issues.
Id. Perhaps even more impressive, Novartis, one of the world's largest life-sciences
companies (formed through the merger of Ciba-Geigy and Sandoz in December 1996),
will voluntarily label its genetically-engineered food products as part of a campaign to
educate the public about the advantages of these products--e.g., a significant reduction
in the use of pesticides and pesticide residues. See Scott Allen, Genetically Altered
Food to be Labeled, Boston Globe, Feb. 25, 1997, at D2.
32
See Saltus, Sounding the Alarm, supra note 14, at 14 (stating,
If “nurture” was the rallying cry of the 1960s, when changing the social environment
through Great Society-style programs seemed the surest way to better lives, the
pendulum has swung back in the last 25 years toward “nature” and the belief that genes
are decisive components of what and who we are and how we behave.
).
33
Erik Parens, Taking Behavioral Genetics Seriously, Hastings Center Rep., July-Aug.
1996, at 13 (citing U.S. Congress, Office of Technology Assessment, Mental Disorders
and Genetics: Bridging the Gap Between Research and Society (1994)) (although
emphasizing the danger of straying away from appreciation for environmental factors,
recognizing that “much research suggests that genetics may help to explain a partial but
significant component of some forms of, for example, schizophrenia, bipolar disorder,
and depression”); see also Richard A. Knox, Study of Mice Links a Gene to Nurturing,
Boston Globe, July 26, 1996, at A1 (reporting that the objective of scientists working in
the field is to identify “molecular handle[s] to try to unravel some of the neuronal circuitry
involved in mediating behavior”); Rick Weiss, Discovery May be Brewing in Search for
Genetic Link to Alcoholism, Wash. Post, July 1, 1996, at A3 (reporting new
breakthroughs in discovering genes relating to alcoholism); Anxiety Linked to Genetics,
N.Y. Times News Service, Nov. 29, 1996 (reporting that “[s]cientists have discovered a
modest but measurable link between anxiety-related behavior and the gene that
controls the brain's ability to use serotonin”); Parens, supra, at 13-18 (“As information
about the genetic component of human behavior increases, so, of course, does the
number of opportunities for its abuse.”).
34
During the spring of 1996, scientists in Edinburgh, Scotland identified a gene linked to
depression that could lead to much more effective treatment. See Nigel Hawkes,
Scientists Identify Gene Linked to Depression; Discovery Prompts Study of Families,
Times London, Mar. 15, 1996, available in Westlaw, 1996 WL 6481302.
35
See Knox, supra note 33, at A1 (reporting that a team consisting of researchers from
Harvard Medical School and Tufts University, through manipulation of a gene called
fosB, have created a strain of mice that seem normal in every way except that they
ignore their newborn offspring).
36
At the present time, “research suggests that genetics may help to explain a partial but
significant component of some forms of, for example, schizophrenia, bipolar disorder,
and depression.” Parens, supra note 33, at 13.
37
For listings of such discoveries over the past several years, see Malinowski, supra note
21, at 1443-44. See also Saltus, Sounding the Alarm, supra note 14, at 14 (“In recent
years, researchers have claimed that homosexuality, schizophrenia, alcoholism, risk
taking, violent behavior, and even basic temperamental traits like shyness are governed
by genetic variations.”).
38
Recent genetic-linkage discoveries have been made both for the tendency to nurture
and the tendency to have strokes. See Peter J. Howe, Gains Reported Toward
Identifying Stroke-Related Genes, Boston Globe, July 30, 1996, at A6 (reporting on
Nature Genetics article and stating that the discovery may create novel opportunities for
diagnosis of potential strokes); Knox, supra note 33, at A1 (noting a gene, FosB, which
is linked to nurturing).
39
See Human Physical Map, supra note 21, at 5 (“The new map, which contains more
than 15,000 STS DNA markers spaced an average of 199 kb apart, covers almost 95%
of the entire genome .... Although originally slated for 1998, map completion by
Whitehead-MIT and other groups is expected by the end of this year.”).
40
See Annas, supra note 14, at 20 (“Molecular medicine, based on deciphering the genes
of a patient instead of diagnosing the patient based on signs and symptoms, is said to
be just around the corner.”); Bio ‘96, supra note 30, at 5 (“[T]he study of genetic
variation will enable the identification of patient sub-populations that may respond
particularly well or poorly to currently-marketed drugs.”); id. at 9 (“Drugs developed
using genomics technology can be expected to offer advantages in specificity that will
result in therapeutics with fewer side effects.”); id. at 16 (“The ability to eliminate
ineffective therapies due to individual therapeutic response will be another way in which
genomics will contribute to the reduction in healthcare costs.... Genomic diagnosis will
provide physicians with a sound basis upon which to prescribe appropriate therapies.”).
41
See Eric M. Reiman et al., Preclinical Evidence of Alzheimer's Disease in Persons
Homozygous for the e4 Allele for Apolipoprotein E, 334 New Eng. J. Med. 752, 752
(1996) (stating that variants of the apolipoprotein E allele appear to account for most
cases of late-onset Alzheimer's disease, and that persons with two copies of one
variation appear to have an especially high risk of dementia); Stephenson, supra note
15, at 1661-62 (“One such test detects APOE-4 (also frequently denoted as APOE4), a
form of the gene that directs the production of cholesterol-carrying protein called
apolipoprotein E. Individuals who possess the APOE-4 gene have an elevated risk for
developing Alzheimer's disease, particularly those who have two copies of the allele.”).
Athena Diagnostics, a biotech company located in Worcester, Massachusetts,
developed the first specific laboratory test for Alzheimer's disease, a disorder which
affects four million Americans. See Richard Saltus, Worcester Firm Touts First Lab Tests
for Alzheimer's, Boston Globe, Mar. 27, 1996, at 47. According to Athena officials, the
company is making the test available as a service under an investigatory protocol,
meaning that, like OncorMed and Myriad, Athena will perform the test in-house for
samples (blood and cerebrospinal fluid, obtained by a spinal tap) submitted by providers
for a fee of $195. See id.; see also Jerry E. Bishop, Test Improves Detection of
Alzheimer's, Wall St. J., July 12, 1996, at B3 (discussing genetic test that may improve
the accuracy of diagnosing Alzheimer's disease). The clinical utility of the test, as
defined by Athena, is that it may be used to distinguish Alzheimer's from other forms of
dementia, some of which can be treated. See id.; see also Saltus, Early Alzheimer's,
supra note 14, at 39 (“With the discovery last week of a gene that causes an aggressive
inherited form of Alzheimer's disease, it will soon be possible to offer a test to people in
at-risk families, where, on average, half the children of any affected parent will get the
gene.”); Saltus, supra, at 47.
42
See Rosenberg, supra note 15, at 80. In comparison with the traditional bladder test
now on the market, this test (1)is performed on a simple urine sample, thereby avoiding
the painful cystoscopy--the insertion of a fiber-optic rod through the urethra and into the
bladder--which is required for the current test; (2)costs $50 rather than $300; and (3)is
much more accurate and, therefore, can detect the earliest signs of cancer. See id.
43
Matritech, a biotech company located in Worcester, Massachusetts, is working on a test
for cervical cancer that would be an improvement to the Pap smear procedure. See Tina
Cassidy, Matritech Says It Will Begin Trials on a More Accurate
Colon Cancer Test, Boston Globe, Apr. 20, 1996, at 25.
44
Trials are being conducted on a colon cancer test that allegedly is more than twice as
sensitive (70% compared to 33%) as the current leading diagnostic test for early-stage
colorectal cancer. See Cassidy, supra note 43, at 25.
45
A gene-signaling system has been discovered through the independent work of two
biotech companies, Amgen and Millennium Pharmaceuticals. Amgen discovered a gene
that makes leptin, an enzyme linked to obesity in rats; Millennium has identified a
genetic receptor for leptin. See Richard Saltus, Piece of Obesity Puzzle Found in
Cambridge: Drug Researchers Locate Key Receptor, Boston Globe, Dec. 29, 1995, at
1. The work of these companies has pushed their competitors, and “researchers have
now found five genes involved in regulating food intake and weight.” Id.
46
At least one biotech company is working on an improved test for prostate cancer. See
Cassidy, supra note 43, at 25.
47
Through research in an extended family with a high incidence of kidney cancer,
scientists have discovered a gene known as FHIT. See Richard Saltus, Gene Eyed in
Many Cancers, Boston Globe, Feb. 25, 1996, at 9. This gene is believed to make a
protein that helps to keep the body's cells dividing in an orderly, regulated way. Control
over cell growth is lost when the gene is damaged by environmental pollutants, diet, or
other factors. See id. The FHIT gene may prove to be an invaluable lead for
understanding how normal cells become malignant in a variety of common cancers,
including those of the esophagus, stomach, and colon; and possibly including ovarian,
cervical, lung, and bone cancers. See id.; see also Cancer Research Yields ‘Time
Bomb’ for Tumors, Boston Globe, Apr. 24, 1996, at 8 (“Cancer researchers have
engineered what they call the first genetic time bomb, set to go off inside tumor cells
when they blow their cover by producing telltale proteins.”).
48
Research involving APOE variations indicates linkages to general susceptibility to
diseases of aging. See Jerry E. Bishop, A Gene Gives a Hint of How Long a Person
Might Hope to Live, Wall St. J., Oct. 19, 1995, at A1 (“If some scientists are correct, the
test may be the forerunner of what could be called the Ides of March tests, a panel of
blood tests that might predict, as the onlooker foretold for Julius Caesar, when one
might die--but not how.”). The researchers responsible for this discovery admit that
APOE is, for any one individual, a “sloppy indicator.” Id. Nevertheless, there is the
possibility that such a test could be used by insurers who engage in grouping. See infra
note 113 and accompanying text.
49
Boyle, supra note 13, supp. at S2.
50
See Mclean, supra note 19, at 116. As recognized by the U.K. House of Commons
Science and Technology Committee, “[w]hile a knowledge of how the gene works, when
established, should, in time, lead to new drug development, through rational drug
design, at present it can take 15 years to develop and gain approval for a new
pharmaceutical product.” Id. (citing 1 Science and Technology Committee, House of
Commons, Human Genetics: The Science and Its Consequences xxxvi (1995)); see
also Boyle, supra note 13, supp. at S2 (
People will be tested for conditions that might never fully express themselves as a
disease, or only express themselves in a mild form. For example, nearly 20 percent of
persons who carry the gene for fragile-X, the most common form of inherited mental
retardation (affecting one in every 2,500 live births), will never express any form of
mental retardation. Yet if parents knew their children's genetic status, they might treat
unaffected children as if they were mentally disabled.
); Saltus, Sounding the Alarm, supra note 14, at 14 (“But today, 15 or 20 years after the
first predictions that gene technology would greatly improve health, scientists have been
far more successful in finding defective genes than in fixing or replacing them.”); infra
Part II.C. Examples of the practical effect of this gap between the discovery of a genetic
linkage to a health condition and treatment derived from that discovery are plentiful:
Genetic researchers, in their quest to understand a terrifying disease, have once again
delivered the means to predict a person's future, but not yet to alter it.
With the discovery last week of a gene that causes an aggressive inherited form of
Alzheimer's disease, it will soon be possible to offer a test to people in at-risk families,
where, on average, half the children of any affected parent will get the gene.
....
Recently developed gene tests for Huntington's disease and for inherited
predispositions to breast cancer and other cancers have raised this issue for an
increasing number of families....
The test for familial, early-onset Alzheimer's might be relevant for 500,000 or more
Americans who are at risk for having the gene ....
Unlike the more common type of Alzheimer's disease, which affects an estimated 4
million people in the United States and generally appears in the late 60s, the 70s or 80s,
the early-onset form can show up even among people in their 30s.
Saltus, Early Alzheimer's, supra note 14, at 39.
51
See Malinowski & O'Rourke, supra note 20, at 174-77 (discussing status of gene
therapy). Dr. Ruth Hubbard and Jonathan Beckwith recognize that, even for conditions
such as Huntington's and multiple sclerosis, which are known to be caused by a single
genetic variation that is responsible for the failure of the cell to make a single protein,
science has not been successful in turning genetic discoveries into treatments.
Multifactorial conditions multiply this complexity. See Saltus, Sounding the Alarm, supra
note 14, at 14.
52
See ELSI Task Force on Genetic Testing, supra note 1; infra Part II.C.
53
The commercial interests developing genetic technologies are nearly as diverse and
plentiful as the underlying discoveries:
Major diagnostic companies (Abbots, Boehringer Mannheim, Miles, Baxter, Beckman,
Becton Dickenson, Ciba-Geigy, Johnson & Johnson, Eastman Kodak, Bio Rad, etc.) are
developing a variety of technologies by inhouse invention and through alliances and
acquisitions....
In addition to the established major commercial players, hundreds of start-up
companies have been formed to exploit various niche diagnostic capabilities generated
in academic research laboratories.
Silverman, supra note 15, supp. at S15; see id. supp. at S17 (“Regardless of the
numerous unknowns in the development of DNA diagnostics, the potential demand for
these services will continue to grow. Attractive financial rewards assure that DNA
diagnostics will become a significant commercial enterprise.”).
54
These estimates, generated during the Spring/Summer of 1995, are conservative
because they predate (1)the precedent for commercialization of genetic testing services
without FDA oversight now being set by OncorMed and Myriad, (2)the advancement of
pending FDA reforms to streamline the FDA review process for biotechnology products,
(3)growth in consumer demand for genetic tests due to both increased media coverage
and marketing efforts on the part of biotechnology companies, and (4)a globalization of
biotechnology and expansion of worldwide markets. See Malinowski, supra note 29, at
123-33.
55
See Silverman, supra note 15, supp. at S16; see also Blatt, supra note 21 (noting that
the revenues presently being generated are from biogenetic analysis for prenatal testing
of chromosome conditions). But see Vicki Glaser, Myriad Pulls IPO from Inhospitable
Market, 15 Nature Biotechnology 14 (1997) (reporting that Myriad pulled its follow-on
public offering, and speculating that lack of investor interest may have been attributable
to below lower-than-anticipated sales figures for its BRCA1 and BRCA2 tests).
56
See Silverman, supra note 15, supp. at S16.
57
See generally Assessing Genetic Risks, supra note 15.
58
See ELSI Task Force on Genetic Testing, supra note 1, at 2-4; see also Richard Saltus,
Survey of Labs New Tests Concerns Genetics Specialists, Boston Globe, Oct. 28, 1995,
at 14 (“Commercial and academic labs are moving so quickly to offer gene tests
predicting future health risks that some are bypassing regulatory and ethical quality
controls, specialists in genetics say.”). According to a survey conducted by Dr. Neil
Holtzman's office at John Hopkins University:
Although any lab performing clinical genetic tests must register with HCFA under the
Clinical Laboratory Improvement Amendments of 1988 (CLIA) [42 C.F.R. § 493.1 (1996)
], the study found that about 10% of responding labs failed to do so. Several labs (8%)
did not use external review (including proficiency testing) to help assure quality. Many
labs intended to market genetic tests to non-geneticist providers, even though most
respondents were of the opinion that such providers knew little about these tests.
Responding labs also tended to view the current regulatory scheme as inappropriate.
Dr. Stephen Hilgartner described the highlights of his follow-up interviews of selected
respondents to Holtzman's survey. He found a variety of commercial genetic testing
activity, ranging from large companies seeking to offer comprehensive test services to
smaller firms developing specific tests for particular market niches.
Meeting Minutes, supra note 1, at 1-2. Other studies, including a study undertaken by
the Genetic Screening Study Group in the spring of 1992, have reached similar
conclusions about the pervasiveness of genetic discrimination. See, e.g., Carol I.
Barash & Joseph S. Alper, A Study on Genetic Discrimination, 8 Genetic Resource 43,
43 (1994) (“The study found that a wide variety of social institutions engage in genetic
discrimination. People reported discriminatory practices by insurance companies (life,
health, disability, and mortgage), in employment (hiring and promotion), by the military,
schools and universities, adoption agencies, and health care providers.”); Lisa N. Geller
et al., Individual, Family, and Societal Dimensions of Genetic Discrimination: A Case
Study Analysis, 2 Science & Engineering Ethics 71, 75 (1996) (concluding that, of the
917 questionnaire respondents, 455 indicated instances of genetic information
discrimination). For anecdotes of genetic information discrimination, see generally id.
In contrast with the United States's incremental approach to protection against genetic
discrimination by insurers, see, e.g., Health Care Portability and Accountability Act, Pub.
L. No. 104-191, 110 Stat. 1936 (1996), European countries are considering an outright
ban on the use of genetic testing information by insurance in the absence of
comprehensive self-regulation. See Insurers Risk Ban, supra note 8.
59
See Stephenson, supra note 15, at 1661-62 (“Concerns about genetic testing have
escalated with the recent emergence of tests that may have implications for large
segments of the population.”).
60
See Boyle, supra note 13, supp. at S2 (“Genetic technologies are by no means a
homogenous lot; they have varied medical and social effects, and are intended for
diverse populations with distinct severity of illnesses, both actual and potential.”).
61
Such tests constitute “diagnostic kits” subject to regulation under the Medical Device
Amendments of 1976 (MDA), 21 U.S.C. § 360k(a) (1994), and the FDA has exercised
some considerable discretion in the area of home testing. See, e.g., Daniel J. Murphy,
FDA Ridiculed for Blocking At-Home Drug Testing, Investors Bus. Daily, Oct. 1, 1994, at
A4 (reporting FDA's prohibition of the sale of drug-testing kits to parents). Pursuant to
the MDA, the FDA regulates medical devices in the context of a classification scheme
that distinguishes among devices based upon the concerns they raise about safety and
effectiveness. The FDA is required to classify each medical device intended for human
use into Class I, II, or III. See 21 U.S.C. § 360(C)(a)(1). Class I devices pose no
unreasonable health risk (general controls that ensure, among other things, safe
labeling and that the produce is safe when used as directed), while Class II devices
carry special controls, such as performance standards necessary to ensure safety and
effectiveness. See id. Class III devices are those represented to be life-sustaining or
life-supporting and those presenting potentially unreasonable risk of illness or injury,
and they require premarket approval to assure safety and effectiveness. The premarket-
approval process requires submission of a premarket-approval application (PMA), which
the FDA must review before it authorizes marketing. However, there is an exception for
diagnostics that are the substantial equivalent of others already approved. See id. §
360k. Still, additional review is required for any change in a device's design. See 21
C.F.R. § 807.81(a)(3)(i) (1996). There also are regulations for device construction and
manufacture, known as good manufacturing practice (GMP) requirements, that
establish detailed requirements for all stages of the manufacturing process. To monitor
compliance, the MDA require factory inspections at least once every two years for Class
III products and post-marketing reporting. See 21 U.S.C. § 360(h); 21 C.F.R. §
803.1-.58.
Because of their complexity, when genetics-based diagnostics are subjected to review,
they generally are labeled Class III devices. See Malinowski & O'Rourke, supra note 20,
at 206. Before developers make these products available to the public, they must apply
for an Investigational Device Exemption (IDE), which is analogous to the Investigational
New Drug Application (IND) required for new drugs. See id. Device manufacturers can
circumvent the IDE requirement by establishing that there is an independent means by
which to confirm the validity of their test.
This may be accomplished (1)through the 510(k) clearance process, by establishing
that the product is the substantial equivalence of a previously marketed product or (2)by
obtaining premarket approval (PMA), which requires a full documentation of safety and
effectiveness and an advisory committee review. However, the general absence of
approved genetic diagnostics on the market makes these exceptions unlikely for
predictive genetic tests. In fact, the manufacturers of such kits should expect added
requirements, such as a requirement that counseling accompany test results. The FDA
imposed such a requirement when approving a home AIDS test in May of 1996. See
Weiss, supra note 2, at A1.
62
See Medical Devices, Classification/Reclassification; Restricted Devices; Analyte
Specific Reagents, 61 Fed. Reg. 10,484 (1996) (to be codified at 21 C.F.R. pts. 809 &
864) (proposed Mar. 14, 1996) (“FDA currently regulates the safety and effectiveness of
diagnostic tests that are traditionally manufactured and commercially marketed as
finished products. However, in-house developed tests have not been actively regulated
by the Agency and the ingredients used in them generally are not produced under FDA
assured manufacturing quality control.”); see also OncorMed BRCA1 Testing Service,
supra note 8, at 7 (reporting on the FDA statement that it has the authority to regulate
but not the needed resources and expertise to actually do so).
63
See FDA Needs to Regulate Genetic “Home Brews,” 14 Nature Biotechnology 1627
(1996) [hereinafter FDA Needs to Regulate]; Stephenson, supra note 15, at 1662. The
ELSI Task Force, in its investigation of genetic testing practices, found that “at least
some companies appear to be circumventing this process by offering genetic testing
services themselves-- using the very probes and other products that would be subject to
FDA regulation if these products were sold to others as part of a kit for the purpose of
genetic testing.” Stephenson, supra note 15, at 1662. The distinction is that, if a
developer performs an assay in its own laboratory, that laboratory may be designated a
reference laboratory, and uncertainty regarding how reliably a third party will perform the
test is removed. See id.; see also ELSI Task Force on Genetic Testing, supra note 1, at
12 (“Often [[[laboratories developing new tests] use home brews as well as reagents
purchased ‘for research use only’ in clinical tests, although neither have been approved
for clinical use.”). Still, as discussed in Part II.C., the results of predictive genetic tests
are prone to misinterpretation by both providers and patients and, therefore, may be
misused clinically.
64
As discussed above, a BRCA test is being marketed without self-restraint by IVF, while
OncorMed is limiting its potential liability by restricting access to its testing service. See
Weiss, supra note 2, at A1. There are two main labeling options for products without
established clinical efficacy:
For research use only and not for use in diagnostic procedures. The manufacturers of
such tests are not permitted to make claims regarding the test beyond statements that
identify and explain its research purpose, and such tests are not supposed to be used
clinically (the results are not supposed to be reported to subjects); and
For investigational use only. Informed consent must be obtained before the test is
performed, and those tested must be apprised of the facts that performance
characteristics are not yet established and data is being collected (the test is being
offered) for that purpose.
See id.; see also Blatt, supra note 21. However, off-label uses of tests, where a test
approved by the FDA for one purpose is used for another, are commonplace. See ELSI
Task Force on Genetic Testing, supra note 1, at 11 (“The Task Force opposes off label
use of genetic tests without independent validation and is exploring new policies to deal
with this problem.”). A prime example of widespread, off-label testing is the use of the
maternal serum alphafetoprotein (MSAFP) screening for the presence of Down's
syndrome. Although the test was initially designed to screen for the presence of neural
tube disorders in the unborn, researchers and labs noticed a correlation between low
MSAFP results and Down's syndrome, thereby creating a new application for its use.
See Blatt, supra note 21. The shortcomings of this labeling system include the following:
(1)despite these requirements, it is not uncommon for laboratories to offer testing
labeled “for research purposes only” to patients and report the results to them; (2)off-
label uses are common; (3)the FDA, although aware of compliance problems in
laboratory genetic medicine, lacks the resources to bring laboratories into compliance
and is hesitant about removing products from the marketplace out of fear of causing
disruption and arousing public and political opposition; (4)compounding this problem,
the FDA is presently in a state of flux and there is a moratorium on new regulations; and
(5)although laboratories are required to be aware of the regulatory status of the
products they use and are expected to use them appropriately, consumers and medical
practitioners are frequently unaware of the regulatory status of the laboratory tests
being performed. See id.
65
See The First BRCA1 Test Hits the Market; Are Oncologists, Patients Ready?, Cancer
Letter, Jan. 26, 1996, at 1, 1-5 [hereinafter First BRCA1 Test Hits the Market].
66
For example, if the stated objective of providing a genetic testing service is gene
sequencing, the cost may increase tenfold. See id. at 2.
67
See 42 C.F.R § 493.1 (1996); Proposed Recommendations of the Task Force on
Genetic Testing, Meeting Notice, 62 Fed. Reg. 4545 (Nat'l Insts. Health 1997) (“Many
tests currently on the market have not been systematically validated nor subject to
external review.... The Task Force is concerned about the lack of Federal law or
regulation covering genetic tests ....”). As enacted, CLIA prescribed general regulations
for medical laboratories, but it applied only to (1)laboratories involved in testing
specimens originating out-of-state and (2)laboratories processing specimens from
individuals on Medicare and Medicaid. CLIA 88 set forth revised regulations that more
uniformly govern laboratory testing involving human samples by establishing general
laboratory standards for personnel, proficiency testing, quality control, and quality
assurance. See generally Summary of United States Product Liability Law (May 24,
1996) (research memorandum prepared by Kirkpatrick & Lockhart LLP, Boston, MA) (on
file with authors).
68
See ELSI Task Force on Genetic Testing, supra note 1, at 14-15.
69
The ELSI Task Force's Subcommittee on Laboratory Quality's “main theme [is] that
genetic testing is unique and better assurance of its quality is needed.” Meeting
Minutes, supra note 1, at 5; see also id. at 6-7, 8 (stating that even the “high complexity”
category under CLIA does not adequately address the unique nature of genetic tests).
The failure of CLIA to address the impact of genetic tests on patient care is addressed
in Boyle, supra note 13, supp. at S7 (“[T]he FDA's standards would consider a test to
screen infants for a genetic anomaly ‘effective’ if it yields an accurate diagnosis, even if
no treatment exists .... Accepting such narrow judgments of effectiveness may ... create
substantial harm by providing information that can cause anxiety, stigmatize, and
promote invidious discrimination.”).
70
See Stephenson, supra note 15, at 1662. An organization planning clinical validation
studies is supposed to file its protocol with a properly constituted IRB competent to
review clinical validation protocols. See Joseph Palca, Institutional Review Boards: A
Net Too Thin, Hastings Center Rep., May-June 1996, at 4. This requirement reflects the
original purpose of IRBs, to protect the autonomy of human subjects participating in
research. See id. For discussion of the increased dependence on IRBs to resolve
genetics issues due to proposed disbandment of the Recombinant DNA Advisory
Committee (RAC), see infra note 257 and accompanying text.
71
Stephenson, supra note 15, at 1662; see infra notes 245-247 and accompanying text
(proposing national IRB standards); Proposed Recommendations of the Task Force on
Genetic Testing, Meeting Notice, 62 Fed. Reg. at 4544 (“The Task Force is concerned
that the high workload of IRBs, their variability in community representation, in
evaluating protocols, and in expertise germane to the review of genetic tests, as well as
the conflicts of interest that can arise in local review, impairs current review of genetic
tests that warrant stringent scrutiny.”). See generally John Abraham, Science, Politics
and the Pharmaceutical Industry: Controversy and Bias in Drug Regulation (1995)
(exploring the capture theory in the context of IRBs, and suggesting that those from the
medical profession who serve on IRBs reap tremendous financial rewards and, due to
revolving-door staffing of IRBs, may even receive R&D funding from the manufacturer
whose products they are reviewing); ELSI Task Force on Genetic Testing, supra note 1,
at 11 (“The Task Force recognizes that IRBs differ widely in their approach to clinical
protocols and in their policies regarding what constitutes research in their purview.”);
Advisory Committee on Human Radiation Experiments, Research Ethics and the
Medical Profession, 276 JAMA 403, 403-09 (1996) (calling for alterations in the IRB
component of the federal system to protect human subjects).
72
See Medical Devices; Classification/Reclassification; Restricted Devices; Analyte
Specific Reagents, 61 Fed. Reg. 10,484 (1996) (to be codified at 21 C.F.R. pts. 809 &
864) (proposed Mar. 14, 1996); FDA Needs to Regulate,” supra note 63, at 1627 See
FDA Needs to Regulate Genetic “Home Brews,” 14 Nature Biotechnology 1627 (1996)
[hereinafter FDA Needs to Regulate]; (
As a result, neither patients nor practitioners have assurance that all ingredients in the
laboratory developed tests are of high quality and capable of producing consistent
results.
[The] FDA is concerned that the present situation with respect to in-house developed
tests, in which these ingredients are essentially unregulated and therefore of
unpredictable quality, may create a risk to the public health.
); see also The Hazards of Genetic Testing, supra note 24, at 6 (reporting on Dr.
Holtzman's survey).
73
But see infra notes 245-246 and accompanying text (addressing how professional
opposition to BRCA testing outside research centers is resulting in initiatives to develop
such guidelines).
74
Andrews, supra note 22, at 991.
75
Blatt, supra note 21(
While almost every state public health department has a laboratory licensing bureau
that is supposed to monitor the quality of laboratory services, many do not have
standards designed specifically for genetic laboratory studies (i.e., DNA analysis) and
performance requirements are not always enforced. Some laboratories have gone for
years without an on-site visit.
). An exception is the State of New York, which has some meaningful laboratory quality
authority that is enforceable and has regulatory language addressing the use of
investigational genetic testing. See Meeting Minutes, supra note 1, at 7 (
New York cannot impose “cease and desist” orders on labs failing to meet voluntary PT
[proficiency testing] standards, and for this reason the state does not recognize the
voluntary lab standards promulgated by the College of American Pathologists [CAP].
However, New York is empowered to revoke a lab's license for ignoring the
recommendations of lab surveyors.
); see also Proposed Recommendations of the Task Force on Genetic Testing, Meeting
Notice, 62 Fed. Reg. at 4545 (discussing how New York requires certification of all
laboratories performing clinical genetic tests on state residents).
76
According to some accounts, FDA officials have all the power and discretion of tax
collectors--discretion enhanced by the ambiguity of the regulations they enforce. See,
e.g., James G. Dickinson, Will Anybody Sue FDA?, Med. Marketing & Media, Oct. 1993,
at 100, 102 (“The Food, Drug and Cosmetic Act's failure to address pharmaceutical
marketing activities that are neither ‘advertisements' nor ‘labeling’ created the gray zone
in which both industry and FDA take liberties. Congress simply failed to foresee the
innovations that modern communication technologies [advertising] could spawn.”). As
explained by Dr. Dickinson:
Advertising alone is defined as “commercial speech” and is thus subject to less First
Amendment protection than labeling or non-commercial speech. But FDA has been able
to tie advertising's statutory dependence on the content of approved labeling to a broad
array of “labeling” materials in such a way that companies “have no freedom of speech
rights when it comes to advertising prescription drugs, compared to the way in which
those rights are commonly understood and interpreted by the courts for other
industries.”
Id. (quoting Richard T. Kaplar, Vice President of the Washington-based Media Institute).
Dr. Dickinson alleges that, “[b]ecause FDA has excessive coercive power in its ability to
approve an advertiser's products for market, and Congress has shown no interest in
balancing FDA's First Amendment incursions, the regulation of drug advertising and
promotion should be handed over to the Federal Trade Commission.” Id. at 103-04. Dr.
Dickinson, citing other authority, contends that the FDA's definition of “deception” is “‘the
basis for the mischief created by the FDA's regulation of advertising”’ because the FDA
declares ads or promotional materials “deceptive” unless they contain a “fair balance.”
Id. at 104 (quoting Kaplar). In practice, according to Dr. Dickinson, “‘any message
promoting some pharmaceutical must also present virtually all negative information
about the product.”’ Id. (quoting Kaplar). Citing a book by Paul H. Rubin, an Emory
University economics professor, Dickinson sets forth the following proposals for reform:
FDA should (1)cancel all recent initiatives restricting promotion of off-label uses;
(2)allow manufacturers to advertise any reasonable claim for which reliable scientific
evidence exists; (3)abolish the “brief summary” requirement for consumer advertising;
and (4)allow unrestricted advertising of drugs, subject only to regulation for “falsity” but
not for “deception” as currently defined.
Id. Nevertheless, the hyping of health-care product features by their manufacturers is a
pervasive problem:
So endemic is the practice of hyping product features the facts clearly don't support that
FDA deputy commissioner Mary K. Pendergast, speaking in October 1994 before the
House Subcommittee on Regulation, Business Opportunities, and Technology, was
moved to uncharacteristically straightforward language. “Promotion of unapproved uses
by company sales representatives,” she stated, “is a major problem.”
Greg Critser, Oh, How Happy We Will Be, Harper's Mag., June 1996, at 39, 47.
77
Historically, advertising of health products accompanied the spread of journalism during
the Civil War and was targeted to reach consumers. See Abraham, supra note 71, at 42.
John Abraham, Science, Politics and the Pharmaceutical Industry: Controversy and
Bias in Drug Regulation (1995However, this was followed very quickly by dependence
by doctors on the “pharmacopoeias” for knowledge about specific drugs and their
measured doses. Soon, drug manufacturers began to make standard preparations
available, and
a close relationship based on mutual interest evolved between the big pharmaceutical
companies in the U.S. and American physicians; the latter could extend their
professional power since only they had the knowledge to prescribe the new science-
based drugs, while the large high technology firms create a unique prescription market,
in which they had a clear advantage over other medicine makers.
Id. In an age of burgeoning medical science, of a deluge of genetics products, and of
competition to attract and retain patients under managed care (by, among other things,
offering them the latest treatments), providers' need for information could not be greater.
Where products are being made available under investigatory protocols, their
developers and manufacturers may be the only entities with such information.
78
See Medical Devices; Classification/Reclassification; Restricted Devices; Analyte
Specific Reagents, 61 Fed. Reg. 10,484 (1996) (to be codified at 21 C.F.R. pts. 809 &
864) (proposed Mar. 14, 1996). But see Weiss, supra note 2, at A1 (“The Food and
Drug Administration, already on the defensive amid corporate claims of over-regulation,
has declared it has the authority to regulate genetic tests but hastens to add that it has
no plans to do so.”); ELSI Task Force on Genetic Testing, supra note 1, at 15 (“The Task
Force has requested a legal opinion from FDA as to whether, if it has the authority to
regulate the development of genetic test services, it can limit the duration of the
investigational stage.”).
79
Although ASRs generally are subjected to general Class I controls, those determined to
carry a high risk may be designated for Class III controls, which include a premarket
approval requirement, or they may be regulated by the Center for Biologics Evaluation
and Research (CBER) because their use presents particularly high risks. See Medical
Devices; Classification/Reclassification; Restricted Devices; Analyte Specific Reagents,
61 Fed. Reg. at 10,484-86.
80
See id.; 21 C.F.R §§ 803.1-.58, 820.1-.198 (1996).
81
In the Proposed Rules, the FDA states:
However, at a future date, the agency may reevaluate whether additional controls ....
may be especially relevant as testing for the presence of genes associated with cancer
or dementing diseases becomes more widely available. Additional controls might
include a broad array of approaches, ranging from full premarket review by FDA to use
of third parties to evaluate analytical or clinical performance of the tests.
Medical Devices; Classification/Reclassification; Restricted Devices; Analyte Specific
Reagents, 61 Fed. Reg. at 10,486.
82
See John Schwartz, FDA Often Blamed for Problems that Aren't Agency's Fault, Wash.
Post., July 15, 1996, at A17 (reporting how the pharmaceutical industry's trade
organization brought 140 disease victims to Washington to lobby for reform); cf.
Matthew Rees, What Makes David Kessler Run?, Wkly Standard, June 3, 1996, at 25
(stating that, rather than a political victim, “the Commissioner of the [FDA] is an
amazingly resourceful political animal”). The most dramatic features of the proposed
FDA reform legislation are privatization of the review process (using private companies
to help review clinical data) and a six-month (180-day) time limit on the review of all
drugs by 1998--a dramatic reduction compared to the average of 12 months. See The
Food and Drug Administration and Accountability Act of 1995, S. 1477, 104th Cong.
(1995) (bill introduced by Sen. Nancy Kassebaum); Malinowski & O'Rourke, supra note
20, at 210-23; Robert Pear, Lawyers and Lobbyists Help Guide Effort by Republicans to
Speed Drug Approvals, N.Y. Times, Mar. 4, 1996, at A15 (“Republicans on the Senate
Committee on Labor and Human Resources and the House Commerce Committee,
joined by some Democrats, have concluded that Congress must revise the F.D.A. laws
to give patients swifter access to new drugs and devices.”); Ronald Rosenberg, Biotech
Group Hits Kennedy's FDA Stance, Boston Globe, Apr. 26, 1996, at 90 (“Citing scientific
advances over the past 50 years, the biotech industry wants to abolish the two-track
approval process for biology-based drugs. That process now requires separate
approvals for a biological drug, its manufacturing process and for every lot or batch
produced.”); see also Jeffrey L. Fox, “Nitty-Gritty” FDA Guidelines Wanted Sooner Not
Later, 14 Nature Biotechnology
698, 698 (1996) (stating that reforms are expected by late summer which will lessen the
burdens on biologics manufacturing). Other proposed reforms include: (1)mandatory
review of all “breakthrough” drugs for killer or untreatable diseases in four months, two
months faster than today; (2)a requirement that the FDA farm out its work to private
companies if it does not meet the proposed review deadlines by 1998; and (3)the
opportunity for companies to petition for automatic approval for sale in the United States
of any therapy that is approved in certain foreign countries if the FDA misses its
deadline (the FDA then would have 30 days to block the sale, by declaring the treatment
unsafe or unproven). See Lauran Neergaard, FDA Resists Claiming Potential for
Dangerous Errors, Boston Globe, Feb. 22, 1996, at 3. The public pressures on the FDA
also have been profound. See, e.g., Editorial, The FDA and Shannon McDermott,
Boston Globe, Apr. 15, 1996, at 10 (“Janet McDermott [, who was brought to
Washington by pharmaceutical trade groups,] is waging a valiant struggle to get
medication that will prevent the seizures suffered by her daughter Shannon. But
Shannon's plight should not encourage support for a bill in Congress that would force
the [FDA] to speed up the approval process for new drugs.”). These forces have joined,
for drug companies have learned the power of teaming up with patients. See Pear,
supra (“Drug companies contribute substantial sums of money to patient-advocacy
groups, but those groups insist that they are not unduly influenced by the money.”). The
FDA reform movement is the culmination of a general trend to deregulate the
commercialization of pharmaceuticals. See Critser, supra note 76, at 40 (“Today, the
American patient is inexorably being transformed into his own pharmacist. The trend is
most apparent in the pages of magazines, with their weirdly text-heavy ads. Less
obvious are the marketing fests taking place in the nation's doctors' offices and
emergency rooms.”).
83
See Bill Clinton & Al Gore, Reinventing Drug and Medical Device Regulations 4-5
(1995) (executive branch/FDA proposals for self-reform); Kenneth B. Lee, Jr. & G.
Steven Burrill, Biotech 97: Alignment, The Eleventh Industry Annual Report 34-36
(1996); For Biotech Firms, FDA Rules Have Much to Please, Boston Globe, Nov. 23,
1996, at 90 (“[B]iotechnology executives are breathing a lot easier these days about
such big up-front investments now that the [FDA] has revamped a host of regulations
governing the industry.”). These proposed reforms, many of which now are in the
process of allegedly being implemented, were referred to by some in the industry as
“the most significant and sweeping in 50 years.” Clinton & Gore, supra, at 4-5. The
reforms included proposals to (1)eliminate requirements that each company seek a
separate license for each facility where it plans to manufacture a drug, (2)eliminate the
requirement that each batch of a biotech-developed drug be sent to the FDA to test, and
(3)impose a 30-day deadline for the FDA to respond to a company that has submitted
additional information requested after the FDA has put a clinical trial on hold. See id.
Many of these proposals have been incorporated into Senator Kassebaum's FDA reform
bill. See supra note 82 and accompanying text; see also Pear, supra note 82, at A15
(reporting that industry experts helped write an FDA bill regarding speeding up approval
for new drugs).
84
See generally Elizabeth C. Price, Teaching the Elephant to Dance: Privatizing the FDA
Review Process, 51 Food & Drug L.J. 651 (1996); Cancer Diagnostics, Med. Tech.
Stock Letter (Piedmont Venture Group, Berkeley, CA), Apr. 18, 1996. “Within days after
the Republicans won control of Congress in 1994, some gay rights groups saw an
opportunity to win speedier access to new, unapproved treatments for AIDS by rewriting
Federal drug laws.” Pear, supra note 82, at A15 (discussing new FDA regulations
regarding new drug approval process); see also Tanya E. Karwaki, Note & Comment,
The FDA and the Biotechnology Industry: A Symbiotic Relationship?, 71 Wash. L. Rev.
821, 821-22, 834-37 (1996) (addressing reform). This strategy appears to be working,
for in response to the political and public pressure, the FDA already has expedited
approval of drugs that fight AIDS and cancer. See Pear, supra note 82, at A15; Laurie
McGinley, FDA to Quickly Clear Merck AIDS Drug, after Approving Abbott's Treatment,
Wall St. J., Mar. 4, 1996, at B3 (“On Friday ... the [FDA] approved Norvir, known
generically as ritonavir. That approval came just 72 days after Abbott filed its
application--the fastest drug approval in the agency's modern history. And it came just
one day after the advisory panel backed its approval.”). It is important to note, however,
that many consumer advocacy groups oppose the “premature” commercialization of
genetic testing:
The National Breast Cancer Coalition, for example, a patients' rights group, opposes
open marketing of a test for the so-called breast cancer gene, BRCA1. At the risk of
sounding as paternalistic as the doctors they often fight against, members said the test's
general ambiguous results may trigger unnecessary panic in many women while
reassuring others who should remain vigilant.
Weiss, supra note 2, at A1.
85
According to the General Accounting Office (Congress's investigator), the average time
required for the approval of new drugs has fallen in the last decade from 33 to 19
months. However, acceleration of FDA review of drugs has not been matched for
diagnostics. See 142 Cong. Rec. S3203 (daily ed. Mar. 29, 1996) (statement of Sen.
Edward Kennedy acknowledging that the review process is slower for medical devices
and various animal vaccines); Neergaard, supra note 82, at 3 (“Today, the FDA spends
six months reviewing breakthrough drugs and 16 months reviewing nonessential
medicines. Medical devices take much longer.”); Pear, supra note 82, at A15 (“The
agency has accelerated the process of reviewing AIDS drugs, but patients with other
life-threatening conditions contend that those drugs receive preferential treatment,” and
the FDA has not had similar success in accelerating approval of devices and food
additives.). See, e.g., FDA Delays Approval of New Test for Diabetics, Boston Globe,
Feb. 27, 1996, at 12 (“Diabetics pleaded with the government yesterday to approve the
first pain-free way to measure blood sugar, but a panel of specialists said there was no
proof the machine works well enough to keep their disease at bay.”); id. (“‘I can't tell you
how frustrating it is to know this device exists but is just out of reach of Bonnie,’ said
Glenn Sklar of Columbia, Md., who draws blood from his 3-year-old's finger six times a
day.”). Some argue that the FDA's approval of Olestra, a fat substitute, reflects
organization of the Grocery Manufacturers of America, see Pear, supra note 82, at A15,
and that the FDA's recent approval of Interneuron's antiobesity drug, the first obesity
drug approval in over 20 years, reflects the FDA's responsiveness to biotechnology. See
Ronald Rosenberg, Antiobesity Drug Cleared by FDA; Available Soon, Boston Globe,
Apr. 30, 1996, at 3 (reporting that Redux, developed by Interneuron Pharmaceuticals
Inc., was the first new obesity drug approved in 22 years). To create a counterpart to
BIO and the Pharmaceutical Research and Manufacturers of America (PHARMA) and a
voice for device manufacturers in the FDA reform movement, the device manufacturers
are organizing. Specifically,
[a]fter years of being lumped with the biotechnology industry, Massachusetts' medical
device companies yesterday announced the formation of their own trade association.
Known as the Massachusetts Medical Device Industry Council, or MassMEDIC, the
group intends to have a voice in pending reforms at the Food and Drug Administration
and in local business and government issues that affect the industry.
Ronald Rosenberg, Medical Device Firms Form Trade Association, Boston Globe, May
7, 1996, at 43 (defining the industry as 200 member companies that employ more than
15,000 people in Massachusetts, create more than three percent of all manufacturing
jobs, and generate collective revenues of $3.5 billion). The formation of MassMEDIC
coincides with enhanced FDA responsiveness to the manufacturers' industry. According
to former Commissioner Kessler, the FDA has shortened the time it takes to review a
device from 134 days in 1994 to 90 days. See id. Presently, the FDA is modifying rules
that govern export licenses for medical device products that have not been approved by
the agency, that govern pilot testing private-industry review of some low-risk medical
devices, and modification of safety and inspection procedures for devices. See id.; see
also Kate C. Beardsley, Medical Devices-Regulation and Reform, in ALI-ABA Course of
Study Materials: Biotech ‘95 Business, Law, and Regulation, Nov. 2-3, 1995, at 255;
FDA Lays Out Plan to Reduce Delays, Costs in Approval Procedures, Boston Globe,
Apr. 4, 1996, at 6 (reporting that FDA has launched a pilot test to determine if outside
groups could assume some of the reviews of routine medical devices now handled by
FDA scientists for low and moderate risk devices like electronic thermometers and
surgical gloves). More specifically, the manufacturers' industry supports proposals that
include: (1)exempting (by moving from Class II to Class I) an additional 125 medical
device categories from premarket notification requirements, thereby exempting a total of
570 categories (about one-third) from this requirement; (2)allowing the export of devices
without an IND exemption; and (3)adopting “an approach similar to that used in the
European Community in which device firms have their device applications reviewed by
a third-party scientific organization accredited by the government.” Id.; see also
Malinowski, supra note 29, at 134-42. Under this approach, “a manufacturer pays a
third-party organization for its review, the third-party organization notifies the
government of the results, the device is marketed without government review, and the
government monitors the device after it is on the market for subsequent safety
problems.” Beardsley, supra, at 280. FDA responsiveness to the device manufacturers'
industry has, however, accompanied new reporting requirements:
The FDA has issued final regulations specifying new requirements for reporting serious
problems with medical devices, as required under the Safe Medical Devices Act of
1990.... It will also provide the necessary assurance of product safety to enable the FDA
to clear innovative devices for marketing more quickly.
....
Under the new requirements, medical facilities must report all serious device-related
injuries or illnesses within 10 days....
Manufacturers have been given 5 days to report to the FDA any device-related incident
that requires immediate action to protect the public health. The time limit for the rest of
the manufacturers' reports to FDA on device-related deaths and serious injuries or
illness is 30 days. This gives manufacturers time to investigate incidents and provide
the FDA with detailed information on adverse events.
Stuart L. Nightingale, From the Food and Drug Administration, 275 JAMA 585, 585
(1996).
86
According to former Commissioner Kessler, the proposed reforms could endanger the
health of Americans. See Neergaard, supra note 82, at 3; Legislation Puts Public Health
at Risk, FDA Chief Tells Panel, Boston Globe, May 2, 1996, at 9. For a detailed
discussion of former Commissioner Kessler's position on this issue, see Malinowski,
supra note 29.
87
See 142 Cong. Rec. S3203 (daily ed. Mar. 29, 1996) (statement of Sen. Edward
Kennedy regarding the FDA Reform Markup); Rosenberg, supra note 82, at 90. In the
words of Senator Kennedy:
Most recently, we reduced the delays in approving prescription drugs with user fees. As
a result, we are now approving drugs faster than the United Kingdom. We have fixed
the drug lag. In fact, the United States approves more important new drugs faster than
any other country in the world.
....
... The [proposed] legislation says you have to examine all of them, all of the drugs
within the 6 months....
So now instead of bringing focus and attention of the gifted and able scientists out at
FDA on those drugs that could be breakthrough drugs in cancer, in AIDS, in hepatitis, in
all kinds of diseases, we are going to divert their attention to looking after the “me-too”
drugs that can make extra bucks for the pharmaceutical companies.
142 Cong. Rec. S3203-04 (daily ed. Mar. 29, 1996).
88
Pear, supra note 82, at A15.
89
See James T. O'Reilly, Food and Drug Administration §§ 13-15 (2d ed. 1993) (detailing
drug regulation, specifically the approval process, safety and quality issues, and
economic and labeling issues); Gary E. Gammerman, Regulation of Biologics
Manufacturing: Questioning the Premise, 49 Food & Drug L.J. 213, 213 (1994) (arguing
that, in retrospect, the divergent regulatory emphasis of the Biologics Act and the FDCA
were appropriate when biologics were crude mixtures or biological extracts); Malinowski
& O'Rourke, supra note 20, at 205.
90
21 U.S.C. § 360k(a) (1994).
91
42 U.S.C. § 262.
92
Malinowski & O'Rourke, supra note 20, at 205-06 (quoting Gammerman, supra note 89,
at 213); see also Gammerman, supra note 89, at 220-26 (analyzing the utility of the
Biologics Act).
93
See Gammerman, supra note 89, at 230-33; Malinowski & O'Rourke, supra note 20, at
205-13, 215-24. Establishment licensure requirements have mandated that products
used in Phase III trials produced in the intended commercial-scale manufacturing facility
and that only the company that manufactures the biologic may obtain and hold the
marketing licenses. Accordingly, in comparison with traditional drug developers, CBER
has forced biotech developers to commit more financial resources to manufacturing
before they know if they have an approvable product. See Gammerman, supra note 89,
at 230-31.
94
See generally John Ashworth, Development of the European Biotechnology Industry, 33
Cal. W.L. Rev. 83 (1996); Malinowski, supra note 29.
95
See Ronald H. Coase, The Problem of Social Cost, in The Firm, the Market and the Law
95, 99 (1988) (arguing that parties will be driven to overcome market interferences,
whether caused by regulations or contractual provisions, to reach maximum
efficiencies).
96
FDA actions have had, and continue to have, a profound impact on the market appeal of
biotechnology. See Malinowski & O'Rourke, supra note 20, at 215-24. This is true even
for relatively “mature” biotech companies with diverse technology, such as Genzyme
Corp., an established biotechnology company located in Cambridge, Massachusetts.
See Steve Bailey & Steven Syre, After the Fall, Boston Globe, Mar. 28, 1996, at 41
(reporting that vote by FDA advisory committee recommending approval for limited uses
of Seprafilm, a membrane product designed to prevent the adhesion of organs and
tissue after some operations, caused a two-day fall in Genzyme stock).
97
Pear, supra note 82, at A15 (quoting Sen. Bill Frist, who is a heart surgeon). A prime
example of the innovative products at issue is Olestra, a fat-based substitute for
conventional fats manufactured by Procter & Gamble. See Nightingale, supra note 85,
at 585. In a flourish of controversy, the FDA approved this drug but imposed enhanced
post-marketing obligations. See Henry Blackburn, Sounding Board: Olestra and the
FDA, 334 New Eng. J. Med. 984, 984 (1996) (“Procter & Gamble will be required to
conduct studies that monitor consumption and examine Olestra's long-term effects. The
FDA's Food Advisory Committee will review these studies in a public meeting within 30
months.”). This decision may be an indication that the FDA is beginning to recognize
that truly innovative products may require more than the FDA's limited resources:
Clearly, the FDA is becoming more aware of the need for epidemiologic studies and
clinical trials with adequate statistical power to detect effects and monitor human safety.
The agency apparently also has the fortitude to stick to its guns, as it has done, for
example, in the cigarette controversy by maintaining that nicotine is an addictive drug.
But the FDA does not have the statutory authority, the staff, or the funding to examine
adequately the benefit and safety of food additives generated by the powerful food
industry and its sophisticated technology. Moreover, there are now serious political
pressures on the FDA, including informal proposals that it become a rubber-stamp
certifying body for industry. There are even threats to abolish the agency. In this climate,
it is understandable, if unfortunate, that the FDA has to set priorities and choose
carefully where to do battle.
Id. at 986.
98
In the words of Senator Barbara Mikulski, a Maryland Democrat, “‘If we can use NATO
weapons, why can't we use drugs from NATO countries?”’ Neergaard, supra note 82, at
3. Despite former Commissioner Kessler's assertions to the contrary, gaps in approval
between the United States and Europe do exist and, at times, are extreme. For
example, although the FDA only recently approved dexfenfluramine, “in Europe, where
it has been used for 10 years, an estimated 10 million patients have been treated with
no epidemiological signal indicating any behavioral problem in clinical usage.” Ronald
Rosenberg, “Take a Pill,” Lose Some Weight, Boston Globe, Apr. 15, 1996, at 91 (noting
that three fat-fighting drugs are entering the United States market: dexfenfluramine by
Interneuron Pharmaceuticals, Inc., known as Redux; sibutramine, with the trade name
Meridia, by Knoll Pharmaceutical, Inc., a unit of BASF Corp; and orlistat, with the trade
name Xenical, by Hoffmann-La Roche, Inc.).
99
See generally Malinowski, supra note 29. Michael J. Malinowski, Globalization of
Biotechnology and the Public Health Challenges Accompanying It, 60 Alb. L. Rev. 119,
123-33 (1996). See also Malinowski & O'Rourke, supra note 20, at 218 (noting that the
FDA standards should be harmonized with international medical standards).
100
A personal observation is that the ongoing work of the ELSI Task Force and consumer
groups such as the National Breast Cancer Coalition and the Jewish Women's Coalition
on Breast Cancer could make this issue a priority on Congress's agenda. See Richard
Saltus, Jewish Women's Group Warns of Risks of Cancer-Gene Testing, Boston Globe,
Jan. 17, 1997, at B2 (reporting on formation of a coalition that includes the Combined
Jewish Philanthropies, National Council of Jewish Women, Beth Israel Deaconness
Medical Center, and Jewish Community Centers of Greater Boston to challenge testing
for inherited breast cancer genes).
101
See ELSI Task Force on Genetic Testing, supra note 1, at 14 (reporting that a test is
ready for routine use only when it has been carefully assessed for (1)sensitivity,
(2)positive PPV, and (3)clinical utility). The ELSI Task Force has identified the following
aspects of genetic testing as bases for special consideration by public health officials
and other policy makers:
predictability seldom approaches certainty; often no independent test is available to
confirm the prediction of a genetic test (only appearance confirms the prediction); no
interventions are yet available; those tested may be subject to psychological distress,
discrimination, and stigmatization; ethnicity may influence genetic makeup; [and] most
health providers have received little training in genetics.
Id. at 3; see also Weiss, supra note 2, at A1 (“Genetic tests differ from many medical
tests because they often provide very vague answers, such as, ‘You have a gene that
gives you a 70 percent chance of getting breast cancer in the next 20 years.”’).
102
See supra note 25 and accompanying text.
103
See supra note 25; see also ELSI Task Force on Genetic Testing, supra note 1, at 8 (“In
only a small proportion of patients with common disorders, such as breast cancer or
malignant melanoma, do inherited mutations at a single gene locus contribute
significantly to the occurrence of the disease.”). Examples of the clinical limitations of
modern genetic science are almost as plentiful as the genetic linkage discoveries that
so captivate the media and the public. Consider the APOE-4 discovery:
Two-thirds of people who develop Alzheimer's later in life have ApoE4. Having just one
copy confers three times the average risk of developing the disease; having two copies
raises the risk to beyond 90% (The risk of developing Alzheimer's disease is 2% at age
65, but about 10% at age 85.) However, many people with Alzheimer's do not carry
even one copy of ApoE4, and some who have two copies of ApoE4 do not develop the
disease.
The Hazards of Genetic Testing, supra note 24, at 6; see Bishop, supra note 48, at A1
(describing blood tests identifying the gene Apoe, which will eventually help determine
how long a person lives).
104
See Stephenson, supra note 15, at 1661 (
The Task Force investigators discovered that while academic laboratories were more
likely than the biotechnology companies to offer tests for single gene disorders, such as
cystic fibrosis, fragile X syndrome, and muscular dystrophy, the latter are far likelier to
be engaged in developing or offering tests for complex genetic disorders, such as
Alzheimer's disease, breast cancer, and hereditary nonpolyposis colon cancer, and in
conducting population testing for such disorders.
).
105
See, e.g., Cook-Deegan, supra note 20, at 242 (discussing clinical heterogeneity in the
context of cystic fibrosis).
106
In the absence of therapeutics and gene therapies, most predictive genetic tests offer
few options:
For example, the only options now available to a woman who learns that she is
predisposed to breast cancer are prophylactic mastectomy (in hopes that cancer would
not develop in the residual amount of breast tissue) or frequent clinical breast exams
and mammograms. Physicians have little to offer in terms of preventive strategies to
patients who discover that they have a markedly increased risk of developing
Alzheimer's disease by virtue of having two copies of the APOE-4 allele.
Stephenson, supra note 15, at 1662; see Hilzenrath, supra note 4, at D14 (“Should the
patient have her breasts or ovaries removed as purely preventive measures, when there
is no guarantee that the surgery would prevent the disease, and no assurance that
cancer would develop in the absence of the surgery?”); Richard Saltus, Genetic
Clairvoyance, Boston Globe, Jan. 8, 1995, (Magazine), at 14 (“One of the lessons
patients and counselors have learned from this experience is that knowing one's genetic
fate is not for everyone-- especially when, as is the case with Huntington's, knowing
what's ahead doesn't help one to avoid it.”).
107
A prime example is the treatment for Gaucher Disease. See Gaucher Disease: Current
Issues in Diagnosis and Treatment, 275 JAMA 548, 548 (1996) (
Despite the success of enzyme therapy, treatment is limited by the cost of the agent.
[This] makes it imperative to determine the lowest effective initial and maintenance
dosages and the most cost-effective dosage for clinical response, to define the
appropriate clinical indications for treatment, and to establish uniform methods to
optimize outcome assessment.
).
108
See Proposed Recommendations of the Task Force on Genetic Testing, Meeting Notice,
62 Fed. Reg. 4539, 4545-46 (1997) (expressing concern over the absence of federal
law and regulation to ensure the laboratory quality of genetic tests). Due to the novelty
of widespread commercialization of predictive genetic testing services, those
scrutinizing them tend to rely heavily on anecdotal evidence. According to one account:
Citing case studies reported to the Task Force, Dr. Holtzman pointed out other
problems: 1)laboratory error in performing and interpreting genetic tests; 2)ordering of
genetic tests for inappropriate reasons; 3)restriction by managed care organizations of
the labs in which tests on their subscribers can be performed; and 4)maintaining
confidentiality of genetic test results.
Meeting Minutes, supra note 1, at 2.
109
See Stephenson, supra note 15, at 1661 (“Interpreting the results of such tests is
difficult, in part because the rate of false negatives is unknown.”); Brom, supra note 27,
at 126. Fully assessing the PPV of existing genetic testing capability for individual
patients could take a decade or more. Moreover, it may be that, in the aggregate,
environmental factors control approximately 50% of physical characteristics, and that
each of us carries multiple genetic predispositions for disease. See id.; cf. ELSI Task
Force on Genetic Testing, supra note 1.
110
See The First BCA1 Test Hits the Market, supra note 65, at 2 (“‘Available data suggest
that many primary care providers lack the knowledge about genetics that's necessary to
educate their patients and ensure informed consent for genetic testing ....”’ (quoting
Caryn Lerman, associate professor of medicine and psychiatry at the Georgetown
University Lombardi Cancer Center)); Proposed Recommendations of the Task Force
on Genetic Testing, Meeting Notice, 62 Fed. Reg. at 4546 (“A provider's need for
knowledge is particularly keen when tests are in transition from research to clinical use
and when clinical utility is still under investigation and there are no established practice
guidelines.”); see also William C. Felch & Donald M. Scanlon, Bridging the Gap
Between Research and Practice, 277 JAMA 155 (1997) (arguing that the research and
provider communities must work together to bring medical technology into patient care).
At the meeting of the National Task Force on Genetic Testing held in April 1996,
representatives of the biotechnology industry placed the responsibility of informed
consumption of genetic testing services on physicians. In response, “Doctors said they
were still getting up to speed in genetics and would be unable to stem the tide of patient
demand if testing were not subject to regulatory restrictions.” Weiss, supra note 2, at
A15; see also ELSI Task Force on Genetic Testing, supra note 1, at 24 (
Several studies have documented the deficiencies in health care providers' level of
knowledge about genetics and genetic tests. As opposed to the results of a serum
sodium or a complete blood count, which the referring physician is competent to
interpret and convey to the patient, genetic test results raise unfamiliar problems about
probabilities, psychological impact, and reproductive implications.
). Concern about the ability of physicians to interpret such tests for their patients is well
founded:
Even though both commercial and academic laboratories are marketing the tests to
physicians who lack any expertise in medical genetics, including obstetricians and
primary care providers, only a minority of the laboratory directors who responded to the
survey said they felt that most physicians can interpret genetic tests adequately for their
patients.
Stephenson, supra note 15, at 1661 (confirming by study of 4,210 Ohio family
physicians). As reported in The Boston Globe, based upon a survey of laboratories:
“A lot of people are getting into genetic testing now who haven't been through human
genetics training,” said Dr. Michael S. Watson of Washington University in St. Louis [an
official of the American College of Medical Genetics]. “This used to be an unprofitable
and esoteric field” when the only genes scientists had identified were those that caused
rare disorders. “Now that we are getting into common diseases” influenced by genes--
including cancer, heart disease and diabetes--“people are jumping into it.”
Saltus, supra note 58, at 14. This problem will be exacerbated with the proliferation of
genetic testing services. See ELSI Task Force on Genetic Testing, supra note 1, at 23
(“As the number of genetic tests proliferate and their usage expands, primary health
care providers and other non-genetics specialists (e.g., [sic] oncologists, neurologists)
will play a major role in the provision of genetic tests.”).
111
Advocacy groups (e.g., for those afflicted by breast cancer and AIDS) may influence
what products are brought to market based upon what they treat rather than their
relative quality. See Boyle, supra note 13, supp. at S5.
112
See Annas, supra note 14, at 25.
113
FDA enforcement of its advertising restrictions has had a profound impact on the
availability of genetic testing within the United States:
While a number of blood tests have been used in other countries, they have been much
less common in the United States. Part of this is the result of Centocor's experience with
their test for CA 15.3, a marker for breast cancer. In 1991, the FDA forced Centocor to
stop selling this test as a research product in the United States and the rest of the world.
Cancer Diagnostics, supra note 84, at 2. As explained above, the precedent set by
OncorMed and Myriad is revitalizing this industry. FDA controls on advertising are
circumvented when laboratories and biotech companies sell investigatory services
rather than kits. See supra note 76 and accompanying text. The relationship between
providers and the entities performing these testing services is one-on-one enough to be
difficult to regulate. See Boyle, supra note 13, supp. at S5. Moreover, at least one study
has challenged the accuracy of the information provided by genetic laboratories and
biotech companies about their tests. According to Dr. Holtzman's study, as interpreted
by one of his colleagues who reached preliminary conclusions based upon a sampling
of consent forms collected,
several grossly overstate the test's accuracy or represent it in a way that is likely to be
misleading. For example, some tests for a single gene did not specify that they only
detected a few of the known mutations and therefore would yield an underestimate of
the false negative rate.... [O]nly half the materials mentioned the availability of genetic
counseling to accompany test results. Victoria Odesina and Nancy Press questioned
whether recipients even understood the information they did receive.
Meeting Minutes, supra note 1, at 2. Some public health officials are also monitoring
and documenting the marketing efforts of biotech companies. According to one such
account,” [p]rivate companies are performing sophisticated market research studies in
order to determine what kinds of new genetic technologies will sell and reap large
profits.... There are numerous reports being issued to generate investment in prenatal
genetic tests.” Blatt, supra note 21.
114
Providers are especially prone to overuse genetic testing technology in the prenatal
context in states recognizing the common-law doctrines of wrongful birth and wrongful
life. See generally Belinda L. Kimble, Wrongful Birth: A Practitioner's Guide to a New
Arrival, 55 Ala. L. Rev. 84 (1994) (recognizing a cause of action for wrongful birth);
Malinowski, supra note 21, at 1497-1513 (demonstrating the need for minimum
bioethics standards); Timothy J. Dawe, Note, Wrongful Life: Time of a “Day in Court”, 51
Ohio St. L.J. 473 (1990) (discussing the elements for these causes of action, their
application, and relevant state statutes, and providing case citations); see also Cook-
Deegan, supra note 20, at 243 (addressing this potential problem in the context of cystic
fibrosis screening); Ellen Wright Clayton, The Dispersion of Genetic Technologies and
the Law, Hastings Center Rep., May-June 1995, supp. at S13-14.
115
See Silverman, supra note 15, supp. at S17 (“While the concerns about developing new
medical technologies are not unique to DNA diagnostics, genetic analysis has the
potential for particularly potent impact on society because of its predictive capacities.”).
116
See Blatt, supra note 21.
117
Advocates for the disabled who challenge the availability of genetic testing argue that
the concept of “disease” is a social construct. See Marsha Saxton, Cost-Benefit/Cost-
Effectiveness Analysis in Genetics, Presentation at the Whitehead Inst. for Biomolecular
Research (Mar. 30, 1996) (on file with authors). There is concern that genetics testing
capabilities could result in less tolerance for deviation from the majority, less
appreciation for life, and a general submission to the prejudices of society. Society could
be cheated of all that can be learned from those born with disabilities, and genetic
testing capabilities will reduce the freedom of choice of prospective parents by putting
more pressure on them to abort. See id.; see also John Seabrook, All in the Genes,
New Yorker, Feb. 12, 1996, at 80 (reviewing Philip Kitcher, The Lives to Come (1996))
(“Eugenics is to the science of biology what the A-bomb was to physics.”); Malinowski,
supra note 21, at 1478-89 (describing how prenatal genetic testing may cause some
parents to abort anything less than a “perfect” baby).
118
See generally Andrews, supra note 22, at 974-91 (discussing how genetic information,
including carrier status, may have a multifaceted impact on people's lives). As stated by
one observer:
Knowing your genetic makeup can also create profound emotional and financial
problems. For example, a spouse might use this information in a custody dispute. Or a
woman might decide not to have children, for fear of passing on the gene. But if she
decides to adopt, will she be approved by an agency? And should a 9-year old girl be
tested for the mutation?
Koenig, supra note 24, at A23. Similarly, another stated:
The ability to predict late-onset diseases, both common (for example, cancer) and
unusual (for example, Huntington's) can result in dramatic changes in life-style.
Premarital genetic analysis can affect the selection of prospective marriage partners, or
even whether one will choose to marry. Genetic analysis is already being used for
decisions on childbearing or adoption. And in prenatal genetic analysis the prospect of
pregnancy termination is confronted directly.
Silverman, supra note 15, supp. at S17.
119
See Andrews, supra note 22, at 976; Silverman, supra note 15, supp. at S17
(discussing market influences on genetic testing); Koenig, supra note 24, at A23; Saltus,
supra note 106, at 14 (“[P]eople who receive good news from a genetic test can be as
seriously troubled as those who discover the worst.”); see also Cook-Deegan, supra
note 20, at 235-36 (discussing the experience of Dr. Nancy Wexler, codiscoverer of the
allele responsible for Huntington's, and her family). Although reliable figures are
unavailable, in January 1995 it was estimated that several hundred people in the United
States and more than 500 in Canada had been tested for the genetic predisposition to
Huntington's. Although the psychological angst condition following testing experienced
by those who test positive has not yet been adequately researched, it appears to
include the following: (1)” [l]ike lottery winners, people who receive the gift of
unexpected genetic health face the quandary of what to do with it”; (2)the results
completely disturb conscious and subconscious views of the future which have shaped
their lives; (3)though each sibling has an equal chance of carrying a parent's genetic
susceptibility to Huntington's, people misinterpret their good fortune as their sibling's
doom, and vice versa; (4)having lived their lives anticipating the worst, individuals may
experience an identity crisis and mourn opportunities they did not pursue; and (5)all
emotional problems blamed on the disease now must be dealt with and family members
and friends no longer will make special allowances. See Saltus, supra note 106, at 14.
As stated by one who underwent this testing:
I don't know who I am or what my goals are .... The whole world is open to me now.
Before, I lived a year at a time; I always had short-range goals. I got my associate's
degree, then my bachelor's, then a master's, and I switched careers so I would be
working for an employer where I would have good benefits and be protected by federal
laws. Now, I don't know what I am going to do--I just know that I'm restless.
Id. To decide whether to take the Huntington's test, Dr. Nancy Wexler asked herself:
“Would I change my job? No, I love what I'm doing. Would I work any less? No. Would I
work any more? I am not sure I can. Would I be any less frantic and obsessional?
Probably not. Would it change personal relationships and friendships? No. There's an
awful lot it wouldn't change.... I'm already happy, how much happier am I going to be?
Part of me realized how happy I am, being part of this whole research process that's
going to make a difference in the future.”
Cook-Deegan, supra note 20, at 236.
120
See Communication between Robin J.R. Blatt and Dr. Patricia Murphy), (January 1997);
see also Andrews, supra note 22, at 976 (stating rate is four times higher).
121
See Andrews, supra note 20, at 984-91; Barash & Alper, supra note 58, at 43; Geller et
al., supra note 58, at 72.
122
Even when counseling is covered, the time constraints placed on genetic counselors
under managed care may be responsible for the profession's high rate of burnout.
123
See ELSI Task Force on Genetic Testing, supra note 1, at 4 (“The number of medical
geneticists and genetic counselors to whom patients can be referred is likely to remain
too small to cope with the potential volume of testing.”). At the present time, the National
Society of Genetic Counselors has an enrollment of only 1,450 members. See
McCormack, supra note 18, at 3. Note, however, that some biotech companies are
employing counselors to act as a resource for providers. For example, Genzyme
Genetics, which has 16 testing labs across the country, employs three counselors. See
id.
124
See supra note 110 and accompanying text.
125
See Michael J. Malinowski, Capitation, Advances in Medical Technology, and the Advent
of a New Era in Medical Ethics, 22 Am. J.L. & Med. 335, 351 & n.106 (1996).
126
The United States's sickle cell screening program was launched in the early 1970s with
good intentions and lots of shortsightedness:
[G]enetic counseling of the individuals tested, and restrictions on the use of the genetic
information obtained from the tests, were not made priorities. As a result, the screening
generated confusion and anxiety among the population. Many identified as carriers of
sickle cell mistakenly thought they were afflicted with the disease. Often, confidentiality
was breached, and in some instances, carriers, not actually possessing the disease,
were denied health insurance. In addition, because no prenatal test was available,
some carriers were told the only prevention for the disease was to avoid having
children.
Brom, supra note 27, at 129 (footnotes omitted).
127
The EEOC has issued a comment in its Enforcement Manual that prohibits employers
from discriminating on the basis of genetic information. See EEOC Compliance Manual
§ 902.8 (1995); see also infra note 263. President Clinton recently signed into law
legislation that includes a prohibition against denying a person, previously insured,
coverage on the basis of genetic information during a change in insurance. See Health
Insurance Portability and Accountability Act, Pub. L. No. 104-191, 110 Stat. 1936 (1996)
(nonetheless, not protecting those presently without insurance against genetic
discrimination and denial of coverage based upon preexisting conditions); see also
Senate Passes Bill on Portable Health Insurance, Boston Globe, Aug. 3, 1996, at A4.
Moreover, approximately 11 states have enacted protective legislation, and there
presently is a flurry of activity at the state level. See Neil A. Lewis, 2 Marines Who
Refused to Comply with Genetic-Testing Order Face a Court-Martial, N.Y. Times, Apr.
13, 1996, at 7 (reporting that “[o]nly 11 states forbid discrimination based on a person's
genetic makeup” and mentioning that bills are pending in 20 other states). Nevertheless,
the danger of genetic discrimination is expanding with the generation of genetic
information from the availability of genetic testing. See Genetic Screening by Insurance
Carriers, 267 JAMA 1207, 1207-09 (1992) ( “Insurers may apply genetic information
inappropriately. Individual risk will be overestimated if the concepts of penetrance and
variable expressivity are not considered.”); Susan O'Hara, Comment, The Use of
Genetic Testing in the Health Insurance Industry: The Creation of a “Biologic
Underclass”, 22 Sw. U. L. Rev. 1211, 1219-24 (1993) (exploring the potential for
discrimination by the health insurance industry arising from genetic testing); Geneticist
Calls for Privacy in Test Results, Boston Globe, Sept. 30, 1995, at 3 (“One study found
100 people who were denied insurance benefits because of genetic risks, and a survey
of families with inherited diseases found 31 percent had been denied coverage even if
they weren't actually ill ....”); Koenig, supra note 24.
In April 1996, representatives of the insurance industry stated publicly at a meeting of
the National Task Force on Genetic Testing that they “would go out of business if they
were restricted from having access to genetic information.” Weiss, supra note 2.
According to some accounts, “Though insurance industry representatives often state
that their companies are not likely to use genetic screening now or in the foreseeable
future, they demand access to this information concerning their applicants if it is
available at professionals' offices, employment settings, or governmental agencies.”
O'Hara, supra, at 1220. The insurance industry already has organized to maximize its
access to underwriting information. “Currently, seven hundred insurance companies
have formed an organization called the Medical Information Bureau (MIB), sharing
information about policy holders in an effort to prevent concealment of underwriting
information.” Id. at 1221. Insurance companies may already be demanding genetic
testing. See generally Geller et al., supra note 58, at 72 (discussing reports of genetic
discrimination); Lee Bowman, Genetic Inheritance Seen as Privacy Issue, Wash. Times,
Apr. 15, 1996, at A10 (According to Dr. Paul Billings of Stanford Medical School, co-
author of a study on genetic discrimination,
[m]ore than 900 people known to have a genetic predisposition for certain diseases but
without any symptoms themselves said they had experienced some form of
discrimination on the job or from insurers, according to the study.... Many more people
also have been denied life or health insurance for refusing to submit tissue for genetic
testing ....
). One response is to flatly exclude genetic information from the insurance process, see
Genetic Screening by Insurance Carriers, supra, at 1207-08, a position supported by
the biotechnology industry. See Lisa Piercey, Kennedy Alleges HIAA Seeks to
Undermine Genetic “Nondiscrimination” Provision, BioWorld Today, May 15, 1996, at 1.
The industry perceives fear of genetic discrimination as an impediment to consumption.
See id. Such an approach is prudent in the context of health insurance for predictive
conditions. We all carry genetic predispositions for disease and, in light of the frequency
of which individuals change jobs and health insurance coverage, the genetic
predisposition factor is “a wash” for all practical purposes. However, such an approach
in the context of life and disability policies (life-long contracts) could price those policies
off of the market due to the problem of adverse selection--individuals with genetic
information may use it to “cheat” the health insurance market by buying added
coverage. Genetic Screening by Insurance Carriers, supra, at 1208.
128
The importance of specificity (this term is defined at supra note 25) in the context of
genetic screening tests for cancers is underscored by the fact that the human body can
be thought of as “one giant precancer”:
As it turns out, virtually all of us have precancerous lesions in our bodies. Autopsy
studies of women who died of something other than cancer reveal that 39 percent of
women between the ages of 40 and 50 have hidden precancer lesions in their breasts--
but only 1 percent of women in this age group are clinically diagnosed with breast
cancer. Likewise, more than 40 percent of men between 60 and 70 have cellular
evidence of prostate cancer that can be found when their tissue is scrutinized under a
microscope, though only 1 percent are actually diagnosed with the disease.
Madeline Drexler, Malignant Predictions, Boston Globe, Feb. 18, 1996, (Magazine), at
9.
129
This conclusion was reached by the Science and Technology Committee of the House
of Commons and the U.K. Working Party of the Clinical Genetics Society. See Mclean,
supra note 19, at 120 (discussing recent report of the U.K. Working Party of the Clinical
Genetics Society) (citing 1 Science and Technology Committee, supra note 50, at
xxxviii). The findings of these entities have been summarized as follows:
Where the diagnosis has no direct impact on the health of the child, they suggest that
testing, and knowledge of test results, have a number of negative implications. For
example, they may lead to the loss of self-esteem, affect the way in which the child is
treated in the family or the wider community, prevent a later exercise of autonomy by
taking the decision about testing out of the hands of the potential adult, and breach
current U.K. policies on the need for counseling before or in the tandem with screening.
Id.
130
See ELSI Task Force On Genetic Testing, supra note 1, at 4-6.
131
Mclean, supra note 19, at 117.
132
Id.; see also Malinowski, supra note 125, at 334-47 (discussing the deontological
tradition of medical ethics).
133
Collins, supra note 2, at 186; see also Hon Fong Louie Mark et al., Clinical and
Research Issues in Breast Cancer Genetics, 26 Annals Clinical & Laboratory Sci. 396,
396 (1996) (“Breast Cancer is the most common form of cancer in women in the U.S.”).
134
See From the CDC: Breast Cancer Incidence and Mortality--United States, 276 JAMA
1293, 1293-94 (1996) [hereinafter Breast Cancer Incidence]; David Plotkin, Good News
and Bad News About Breast Cancer, Atlantic Monthly, June 1996, at 53, 55-58 (relying
upon data provided by the American Cancer Society); see also Dolores Kong,
Mammogram Wars, Boston Globe, May 27, 1996, at 34 (stating that, overall, 180,000
cases of breast cancer are diagnosed in the United States each year); Richard Saltus,
Breast Cancer Testing: Do You Want to Know?, Boston Globe, Mar. 11, 1996, at 25
(“Each year, about 185,000 new cases (4,600 in Massachusetts), and 44,000 deaths
are reported.”). For more information, contact the National Cancer Institute, Cancer
Information Service, 9000 Rockville Pike, EPN 300, Bethesda, MD 20892. The Institute
may be reached by telephone at (800) 4-CANCER (422-6237).
135
See Plotkin, supra note 134, at 55, 58 (relying upon data provided by the American
Cancer Society); see also Kong, supra note 134, at 34; Saltus, supra note 134, at 25.
136
See Plotkin, supra note 134, at 55, 58. The significance of these numbers is
underscored by the fact that malignancy generally grows faster in younger women.
Kong, supra note 134, at 34. Despite advances in detection through mammography,
surgical technique, radiation therapy, and chemotherapy, these advances have not
lessened the likelihood that women will die of breast cancer. See Plotkin, supra note
134, at 76. “In 1935, 26.2 out of every 100,000 women died of breast cancer.... In 1992,
the latest year for which figures are available, the adjusted rate of mortality was 26.2
women per 100,000--the same as 1935.” Id.
137
See Kong, supra note 134, at 34.
138
Plotkin, supra note 134, at 58.
139
See supra note 64.
140 [NIH is conducting a BRCA testing study in the Washington-Baltimore area that
involves 5,000 Ashkenazi Jewish volunteers.]
The recruitment target of 5,000 volunteers was surpassed in just two months. See
Wadman, supra note 5.
141
See supra note 64 (addressing “research” labeling).
142
See Wadman, supra note 5, at C3; Weiss, supra note 2, at A1.
143
See Weiss, supra note 2, at A2. OncorMed continues to revisit and revise its protocol.
As of January 1997, OncorMed also requires physicians to call in or fax patients' family
histories to the company before testing. See OncorMed, Hereditary Breast Cancer
Education and Testing Packet (Jan. 15, 1997).
144
See First BRCA1 Test Hits the Market, supra note 65, at 1-5.
145
See id. at 3-5. A summary of the OncorMed protocol is attached as Appendix I.
146
OncorMed is instructing physicians that its BRCA test is available only to certain at-risk
patients. See App. I.
147
See id. OncorMed offers testing in stages I to III for BRCA1 alterations and stages I and
II for BRCA2 mutations. Each stage tests for different BRCA alterations and carries a
separate cost--from $420 for a Stage I BRCA1 test to $800 for a Stage III BRCA1 test,
and $800 for a Stage II BRCA1 and BRCA2 multiplex test (the tests are done together).
See Hereditary Breast Cancer: Questions and Answers for Patients 3, in OncorMed,
supra note 143.
148
See Wadman, supra note 5, at C3 (discussing a genetic test for breast and ovarian
cancer); Weiss, supra note 2, at A2. Dr. Schulman, who is working in conjunction with
IVF Institute, is making the test available to all Jewish women who have been referred
by a physician. See Wadman, supra note 5, at C3. One of Dr. Schulman's first clients
was his wife, who underwent the test at the age of 38, tested positive and had both of
her breasts removed. See id.
149
See Wadman, supra note 5, at C3 (“In last week's New England Journal of Medicine,
they report that they are offering on-demand testing for the Jewish mutation.”); David S.
Rosenblatt et al., Genetic Screening for Breast Cancer, 334 New Eng. J. Med. 1199,
1199-1200 (1996) (testing for 185delAG is being offered at the University of Toronto and
McGill University).
150
See American Cancer Society, Cancer Facts and Figures (1995). Women in the United
States have an estimated 10% lifetime risk of getting the disease, and the median onset
age is 64.
151
See Koenig, supra note 24, at A23 (after the discovery that 1% of Ashkenazi Jewish
women carry genetic predisposition to breast and ovarian cancer, “a surgeon who
operates on women with breast cancer told me that a day rarely passes when a patient
does not ask about ‘the gene test”’); Weiss, supra note 2, at A1 (“Most important, many
women seem not to realize that it is only if a woman has a clear family history of breast
cancer--usually identified as two or more close relatives with the disease--that the
BRCA1 mutation confers 85% odds of getting breast cancer.”). But see Alison Bass,
Ethnicity Called Factor in Patients' Decisions, Boston Globe, Sept. 14, 1995, at 3 (“For
example, a majority of elderly people of Korean and Mexican descent would prefer not
to be told that they suffer from metastatic cancer, while European-Americans and
African-Americans would rather know the bad news, the study of 800 nursing home
residents found.”); Saltus, supra note 106, at 14 (“Before the HD test became available,
people who were at risk showed strong interest in a predictive test. But when the test
appeared, fewer people than expected actually stepped forward.”).
152
See Myriad laboratories, Inc., supra note 7, at 2; Saltus, supra note 134, at 25 (stating
that inherited mutant genes probably account for 5 to 10 percent of breast cancer
cases, but this inherited type “seems to be more aggressive; it may also appear earlier
than in noninherited cases, sometimes when the woman is in her 20s or 30s”). “About 1
in 200 women in the United States are thought to carry a mutant BRCA1 gene. BRCA1
accounts for about 50 percent of inherited breast cancers, BRCA2, may cause 35
percent, and the remainder are due to undiscovered genes.” Id.
153
See The Scientific Questions, supra note 4, at 4 (stating that it is estimated that 10% of
breast cancers are due to germline mutations); Hilzenrath, supra note 4, at D24
(discussing a news service to detect predisposition to breast and ovarian cancer);
Saltus, supra note 2, at A18.
154
“Today, the cancer diagnostic business alone is a $1 billion industry attracting some
major corporate players and small companies,” and the demand for more reliable ways
of detecting and monitoring cancer is growing with an aging American population. See
Rosenberg, supra note 15, at 80. As stated by a market analyst:
Genetic tests for susceptibility to cancer are a hot area currently, as there have been
many announcements of the discovery of genes which predispose some people to
specific types of cancer. While genetic tests are done using blood, they are more
expensive and difficult than traditional blood tests. Myriad Genetics, one of the genomic
companies, has made a decision to enter this business. They are one of the discoveries
of the BRCA1 gene, which identifies one form of the hereditary risk of breast cancer.
OncorMed is a genetic testing company which also sees an opportunity in cancer
testing, and is acquiring diagnostic rights to discoveries made by others. Additional
cancer genes will be discovered over the next few years, but the acceptance of such
tests will be controversial. Unless the patient will gain some benefit from the knowledge,
there is no justification for an expensive test. In some cases, the knowledge that a
patient has a high risk of cancer could be devastating.
Cancer Diagnostics, supra note 84, at 3.
155
Saltus, supra note 134, at 25.
156
First BRCA1 Test Hits the Market, supra note 65, at 4.
157
See Arthur Austin, Evaluating Storytelling as a Type of Nontraditional Scholarship, 74
Neb. L. Rev. 479, 485-88, 521 (1995) (stating that feminists and members of the racial
critique theory movement profess to speak in a different voice derived from their gender
and race experiences, and that they make no pretense of balance or objectivity); Mary I.
Coombs, Outsider Scholarship: The Law Review Stories, 63 U. Colo. L. Rev. 683, 685
(1992) (discussing the rejection of dispassionate objectivity in favor of narrative
discourse). For a general and thoughtful discussion of the deontological aspect of the
legal storytelling technique, see Toni M. Massaro, Empathy, Legal Storytelling, and the
Rule of Law: New Words, Old Wounds?, 87 Mich. L. Rev. 2099 (1989). See also Anne
M. Coughlin, Regulating the Self: Autobiographical Performances in Outsider
Scholarship, 81 Va. L. Rev. 1229, 1231 (1995) (applying autobiographical narrative to
legal discourse); Angela P. Harris, Foreword: The Jurisprudence of Reconstruction, 82
Cal. L. Rev. 741, 750-54 (1994) (discussing how critical race theory utilizes modern
narratives in its optimistic moments).
158
See Austin, supra note 157, at 487 (stating that both feminists and Racial Critique
Theory people “claim to get special insights from status as victims or outsiders”).
159
See id. at 521 (“The presence of footnotes should not distract from the plot or create
static in the flow of the narrative.”).
160
See Mari J. Matsuda, Looking to the Bottom: Critical Legal Studies and Reparations, 22
Harv. C.R.-C.L. L. Rev. 323, 325 (1987) (recommending a “new epistemological source
for critical scholars: the actual experience, history, culture, and intellectual tradition of
people of color in America”); Deborah L. Rhode, Feminist Critical Theories, 42 Stan. L.
Rev. 617, 622 (1990) (discussing the experience of women's actual circumstances,
such as being dominated, as a way of understanding feminism). The “outsider” group
“encompass[es] various outgroups, including women, people of color, poor people, gays
and lesbians, indigenous Americans, and other oppressed people who have suffered
historical under-representation and silencing in the law schools.” Mari Matsuda,
Affirmative Action and Legal Knowledge: Planting Seeds in Plowed-Up Ground, 11 Harv.
Women's L.J. 1, 1 n.2 (1988).
161
See Austin, supra note 157, at 491 (“Serious scholars revere analysis and objectivity. To
them, subjective advocacy posturing is best left to the National Enquirer. Bias is a form
of fraud.” (footnote omitted)); see also Daniel A. Farber & Suzanna Sherry, Telling
Stories Out of School: An Essay on Legal Narratives, 45 Stan. L. Rev. 807, 853-54
(1993) (discussing the importance of reason and analysis in legal scholarship).
162
See, e.g., Kathryn Abrams, Hearing the Call of Stories, 79 Cal. L. Rev. 971, 1021-27
(1991); Austin, supra note 157, at 523-27; Richard Delgado, On Telling Stories in
School: A Reply to Farber and Sherry, 46 Vand. L. Rev. 665, 668-75 (1993); Farber &
Sherry, supra note 161, at 832-38; Daniel J. Solove, Book Note, Fictions About Fictions,
105 Yale L.J. 1439, 1439-40 (1996) (reviewing L.H. Larue, Constitutional Law as Fiction:
Narrative in the Rhetoric of Authority (1995)).
163
The use of legal storytelling in this Article parallels the storytelling of outsiders. See
Austin, supra note 157, at 505 (“Descriptions by people like Derrick Bell, Richard
Delgado, and Patricia Williams convey the common theme that stories raise
consciousness and serve as a vehicle to educate insiders.” (footnotes omitted)).
164
This story is based upon an interview with a breast and colon cancer survivor who also
is a health care professional.
165
This source is a genetic counselor at a major medical research institution.
166
This story is based upon an interview with Jan Platner, J.D., who is the Executive
Director of the Massachusetts Breast Cancer Coalition (MBC). MBC is located at 85
Merrimac St., Boston, MA 02114. Ms. Platner may be contacted by telephone at 800-
649-6222 or 617-624-0180, or by facsimile at 617-624-0176.
167
Ruth Hubbard is Professor Emerita of Biology at Harvard University.
168
This story is based upon an interview with an executive at a major biotechnology
company.
169
Statement of Elliott D. Hillback, Jr., Pres. & CEO of Integrated Genetics Laboratories,
Inc., before the Senate Cancer Caucus (Sept. 29, 1995).
170
See First BRCA1 Test Hits the Market, supra note 65, at 4 (“Since FDA does not
regulate genetic tests, OncorMed and the companies that will follow it encounter few
regulatory barriers. However, by the same token, their products do not receive the
certification of safety and efficacy that accompanies regulatory approval.”). The MDA
preempts claims for negligence and failure to warn. See 21 C.F.R § 808.1(d)(1996);
H.R. Rep. No. 853, at 45 (1976) (legislative history). If manufacturers comply with FDA
requirements and do not commit fraud, state law claims generally are preempted. See
supra note 61; see also Lars Noah, Amplification of Federal Preemption in Medical
Device Cases, 49 Food & Drug L.J. 183, 211 (1994) (“By virtue of the express
preemption provision in the MDA, medical devices are unique among products which
are subject to regulation by the FDA.”). But see Marianne Lavelle, Medical Device
Makers' Liability Shield is Dented, Nat'l L.J., July 8, 1996, at A1 (reporting on Supreme
Court holding in Medtronic, Inc. v. Lohr, 116 S. Ct. 2240 (1996), that FDA regulation
(MDA) does not necessarily preempt consumer suits over faulty medical devices);
Marianne Lavelle, High Court Medical Devices Ruling Muddles Matters, Nat'l L.J., Sept.
30, 1996, at A9 (reporting that “[c]ourts have split sharply in their readings of a 1996
Supreme Court decision that many had hoped would clear up the issue of when federal
regulatory law preempts actions based on state tort and other law”). However, liability
for clinical trials is raising. See Michael Traynor, As Manufacturers Seek Approval for
More New Pharmaceuticals, Issue Such as the “Learned Intermediary” Rule Will
Emerge in Litigation involving Clinical Trials, Nat'l L.J., Nov. 18, 1996, at B6.
171
“About half of people with a family history of breast or ovarian cancer are likely to
request genetic susceptibility (BRCA1) testing when available ....” Breast/Ovarian
Cancers (Genetics): Many People Prefer Not to Know if They Have Gene Linked to
Cancers, Cancer Res. Wkly, July 15, 1996, available in 1996 WL 2286313 (reporting on
study conducted by the Lombardi Cancer Center, Georgetown University, that
emphasizes the importance of relaying information about genetic tests themselves to
patients). Following the discovery that one percent of Ashkenazi Jewish women carry
genetic predisposition to breast and ovarian cancer and despite consumer demand for
the test, “almost all leading scientists and two major commercial testing laboratories
agreed informally not to offer the test for the mutation to the general public because
widespread testing would do more harm than good.” Koenig, supra note 24, at A23.
That consensus was broken, however, by Dr. Joseph D. Schulman, Director of IVF. Dr.
Holtzman, Chair of the ELSI Task Force, asserts that Dr. Schulman is “hoodwinking”
women by making the IVF test widely available. See Wadman, supra note 5, at C3. The
National Breast Cancer Coalition and the National Action Plan on Breast Cancer agree
that testing should be confined to research settings. See id.
172
Consider that the United Kingdom, in comparison with the United States, regulates
more experimental medical technology through good medicine standards. See Veronica
Henry, Problems with Pharmaceutical Regulation in the United States, 14 J. Legal Med.
617, 637-38 (1993) (“In Great Britain, investigational and experimental drug use
requires certification and licensing; however, therapeutic use, by which physicians
administer drugs to their patients, is excluded from the certification requirement.”).
173
For example, in the Fall of 1995, SmithKline Beecham (London-based) gave Stanford
University $1 million to start an ethics program in genetics, and the Hastings Center has
launched a program called “Values and Biotechnology” with the financial support of
Monsanto Co. See Day, supra note 31, at A1.
174
Biotech companies are voluntarily and directly addressing ethics issues arising from the
commercialization of their technologies. See id. Human Genome Sciences, Inc. has
hired former opera diva Beverly Sills, who has two children with birth defects and years
of service as chairman of the March of Dimes. “All over the biotech industry, companies
are hiring ethicists to try to get a jump on these humanistic tangles. Many people in an
industry that has the potential to make reality of science fiction are following the rule of
look before you leap.” Id.
175
See, e.g., Claudia MacLachlan, Spine-Tingling Dispute: Bone Screw Suit Places FDA in
4-Way Squeeze, Nat'l L.J., Jan. 8, 1996, at A1 (“‘One of the standard defenses is to
wrap your arms and legs around the ankles of some FDA person and say they knew--
and a lot of times that is true.”’ (quoting William W. Vodel, head of FDA practice at
Washington D.C.'s Arnold & Porter)). Recently, the FDA was pulled into “a four-way
crossfire over the way it lets medical devices be used without formal approval.... The
FDA has also been accused of relying on the advice of doctors allegedly on the take
from makers of devices the doctors had tested.” Id.; see In re Orthopedic Bone Screw
Products Liability Litigation, 79 F.3d 46 (7th Cir. 1996). This case, which involved the
use of screws to affix metal plates to the vertebrae of some 300,000 people despite
rejections by the FDA of this use in 1984 and 1985, has highlighted the fact that the
FDA cannot always be relied upon as an assurance of quality control. MacLachlan,
supra, at A1. The problem is that standard of care acceptance may be realized without
the FDA. On October 4, 1992, the FDA announced in the Federal Register that it had
discovered that the plate and screw devices were in widespread use and considered
standard of care by surgical community. At that time, the FDA requested a study by
orthopedic professional groups and makers of the spinal implants and, based upon the
reported results, the FDA liberalized use. Accusations that the study was corrupt are
now the subject of a case brought by plaintiffs against the device's manufacturers.
Specifically, attorneys for the plaintiffs in a products liability case over the device later
accused the FDA of relying “in part on medical reports from doctors who stood to profit
from the device.” MacLachlan, supra, at A1.
176
See Claire L. Ahern, Drug Approval in the United States and England: A Question of
Medical Safety or Moral Persuasion?--The RU-486 Example, 17 Suffolk Transnat'l. L.
Rev. 93, 93 (1994) (“Advancements in the pharmaceutical industry have revealed the
magnitude of these dissimilarities and the negative effects that result when United
States drug officials allow nonscientific considerations to affect their analysis of
promising new drugs.”); Henry, supra note 172, at 637-38, (comparing the U.S. and U.K.
systems and concluding that “[t]he British system is more objective and expeditious than
the American system.... The American system needs to enhance utilization of apolitical
advisory committees in the decisionmaking process, much the same way this has been
done in the British system.”). But see generally Abraham, supra note 71, at 246 (“The
close institutional relationship between the regulators and the pharmaceutical firms in
the U.K. has been associated with a sympathetic view of scientific data from the
pharmaceutical industry on the part of the Government scientists and scientific
advisers.”). See also J. Worth Estes, Book Review, 334 New Eng. J. Med. 609, 609
(1996) (reviewing John Abraham, Science, Politics and the Pharmaceutical Industry:
Controversy and Bias in Drug Regulation (1995)) (“Because the British government
wishes to ensure the success of its pharmaceutical industry, its regulatory agencies
tend to be protective rather than adversarial, as they are in the United States, where the
government is required to be more concerned about protecting patients than about
protecting the firms that manufacture medicines.”).
177
See ELSI Task Force on Genetic Testing, supra note 1, at 14 (“A test with a lower
sensitivity might have value in certain circumstances, but the organization offering the
test must make clear what the limitations are in order to enable providers and
consumers to make informed decisions about appropriateness.”); Olufunmilayo I.
Olopade, Editorial, Genetics in Clinical Cancer Care--The Future is Now, 335 New Eng.
J. Med. 1455, 1455 (“It is no longer unusual for women with newly diagnosed breast
cancer to seek genetic testing before choosing between mastectomy and lumpectomy
combined with radiation therapy.”); see also id. at 11 (“A direct DNA test can be used to
diagnose a genetic disease in symptomatic individuals, predict future disease in healthy
people, detect carriers and also for prenatal diagnosis.”); Saltus, supra note 134, at 25
(noting that some women already diagnosed with breast cancer perhaps could benefit
from testing to make decisions regarding treatment); Wadman, supra note 5, at C3
(“They say negative tests have already allowed them to tell women scheduled for
preventative breast removal that they don't need the surgery.”); Weiss, supra note 2, at
A1 (
For some carefully selected women already diagnosed with breast cancer, a positive
test can indicate the need for more aggressive therapy. And for a woman whose mother
or sister had breast cancer from a BRCA1 mutation, a negative test can provide some
reassurance. What remains unproved, however, is that the test has any value for the
more than 95% of women who do not fit into those categories.
). The breast cancer testing issue has caused division among feminist scholars, some of
whom feel that impeding the accessibility of genetic tests constitutes paternalism. See
Wadman, supra note 5, at C3 (discussing the availability to Jewish women of a genetic
test for breast and ovarian cancer); Weiss, supra note 2, at A1. In the words of one
woman who was told that she could not have her BRCA1 test results:
Do they really believe that women who test positive are going to immediately race to the
nearest operating room to summarily demand the removal of both breasts and ovaries--
procedures which, in any event, would require the concurrence of a surgeon? They are
underestimating our intelligence to the millionth degree .... Strangely, men considering
surgery for prostate cancer don't seem to receive this kind of counsel, even though the
benefits of surgery haven't been proven and the operation usually leaves men impotent,
incontinent or both.
Wadman, supra note 5, at C3.
178
See Breast Cancer Incidence, supra note 134, at 1293-94 (reporting that the overall
death rate from cancer fell approximately 3% between 1991 and 1995, and the rate of
breast cancer fell 6.3 percent).
179
See Saltus, supra note 134, at 25 (arguing that, with time, the tests will be more
scientifically reliable and easier to interpret, and that there also will be more health care
uses for the information).
180
These research funds are coming out of the pockets of consumers, for most insurance
companies will not cover the costs of such experimental health care. See Boyle, supra
note 13, supp. at S5 (“While exact data on private insurance coverage are scarce, most
genetic services--preventive, screening, and counseling--are not covered because the
interventions are considered either ‘investigational’ or ‘not medically necessary.”’).
181
See generally supra Parts II.B & C.
182
See ELSI Task Force on Genetic Testing, supra note 1, at 33 (“People at risk of disease
in high risk families may have built up a complex mechanism to deal with the perception
that they are affected.... Genetic counseling can be extremely time-consuming.”).
However, Kaiser Permanente currently is developing a clinical practice guideline for
BRCA1 testing and introducing a confidential patient registry to ensure long-term follow
up. See BRCA1: Are You Ready for Clinical Testing?, Persp. Genetic Counseling,
Summer 1996, at 12.
183
See Malinowski, supra note 125, at 351-52 & n.104.
184
Many new predictive genetic tests are investigational and, therefore, often are paid for
out of consumers' pockets. See Blatt, supra note 21 (“While genetic counseling is
necessary to make informed decisions about clinical genetic tests, as a sole service, it
is often not covered by insurance.”). Accordingly, it is unlikely that consumers are going
to seek out counseling due to the added cost. See Malinowski, supra note 125, at 351 &
n.106; see also First BRCA1 Test Hits the Market, supra note 65, at 3 (“While it may be
difficult to find two people who agree on all aspects of what is to be done, virtually all the
opponents of immediate commercialization of genetic testing agree that counseling
patients before and after they are tested is anything but a straightforward matter.”).
185
See Wadman, supra note 5, at C3 (“Scientists argue that testing in nonresearch settings
is fraught with peril. Negative test results, they say, could lull women into a false sense
of security, when in truth 90 to 95 percent of breast and ovarian cancers aren't inherited
but occur spontaneously.”).
186
The investment in technology to identify breast cancer has not been accompanied by
similar investment to understand its growth and spread. See Plotkin, supra note 134, at
54-55. The failure to appreciate cell growth differences in breast cancer, coupled with
mammography, may have resulted in over-diagnosis and treatment--including
unnecessary mastectomies. See id. at 70. The end result is that breast cancer is twice
as likely to be diagnosed today as it was 60 years ago, but mammography studies show
no overall difference in mortality from breast cancer between treatment and control
groups. See id. at 69 (citing Swedish, Irish, and Canadian studies). Widespread BRCA
testing could greatly exacerbate this problem.
187
See generally supra note 58. See also Barash & Alper, supra note 58, at 43; Geller,
supra note 58, at 71.
188
See Act Concerning Genetic Testing and Privacy and Medical Underwriting, N.J. S.B.
695 & 854, at § 2.d (1996) (“An analysis of an individual's DNA provides information not
only about an individual, but also about the individual's parents, siblings and children,
thereby impacting family privacy, including reproductive decisions.”).
189
There is fear in the United States that creativity and objectivity in basic science is being
lost due to the privatization of R&D. Rather than allowing researcher discretion and the
raising of a general floor in science, basic science is being directed by corporate
decisions to pursue and develop research discoveries solely according to their
commercial viability. See, e.g., Abraham, supra note 71, at 245 (“Since the career
structure of academic medics rewards them for publications, there is an institutional
incentive for such medics to work co-operatively with an industry that can provide the
funding for publishable research.”); Christine Gorman, Has Gene Therapy Stalled?,
Time, Oct. 9, 1995, at 62, 62-63 (noting that, while gene therapy holds extraordinary
promise, enthusiasm and financial pressures may have caused a premature push to
market that is sacrificing basic science and human safety for a quick return on
investment). See also Malinowski & O'Rourke, supra note 20, at 187 (discussing the
concern that the alliance nature of the biotech industry may be skewing the course of
basic science). This concern has been substantiated in part by a study published in the
New England Journal of Medicine based upon data collected from 2,052 faculty
members from October 1994 to April 1995. According to the study, “faculty members
receiving more than two thirds of their research support from industry were less
academically productive than those receiving a lower level of industrial support” and
“faculty members who have research relationships with industry are more likely to
restrict their communication with colleagues.” David Blumenthal et al., Participation of
Life-Science Faculty in Research Relationships with Industry, 335 New Eng. J. Med.
1734, 1734 (1996).
190
See Ralph T. King, Jr., Bitter Pill: How a Drug Firm Paid For University Study, Then
Undermined It, Wall St. J., Apr. 25, 1996, at A1. There is anecdotal evidence that
industry is tampering with scientific integrity. The “Synthroid affair” exemplifies the
danger of industry-financed research. A manufacturer paid $250,000 to finance research
to establish that cheaper drugs were not as effective as its product. When the
researcher attempted to publish findings of bioequivalency between the drug and other,
much cheaper drugs, the manufacturer worked aggressively to discredit the research.
See id. (“The Synthroid affair illustrates what some leading scientists decry as
increasingly frequent corporate attacks on open scientific debate, at a time when
industry-supported research is crucial because of a shrinking government role in
medical research.”). Similarly, “[i]n a recent article in the New England Journal of
Medicine, Steven A. Rosenberg, chief surgeon of National Cancer Institute, cited what
he said were four instances of promising research being squelched or slowed by
corporate sponsors' demands for secrecy to preserve possible competitive advantage.”
Id.
191
See David Blumenthal et al., Relationships Between Academic Institutions and Industry
in the Life Sciences--An Industry Survey, 334 New Eng. J. Med. 368, 368 (1996)
(“Ninety percent of companies conducting life-science research in the United States had
relationships involving the life sciences with an academic institution in 1994. Fifty-nine
percent supported research in such institutions, providing an estimated $1.5 billion, or
approximately 11.7 percent of all research-and-development funding received that
year.”); see also Steven A. Rosenberg, Secrecy in Medical Research, 334 New Eng. J.
Med. 392, 392-93 (1996) (
The conduct of medical research is in increasing jeopardy.... Secrecy about methods
and results has become a common and accepted practice....
The increasing involvement of for-profit biotechnology companies in medical research
has provided new sources of funding, but with this involvement has come an emphasis
on the ethical and operational rules of business rather than on those of science.
).
192
See Mark et al., supra note 133, at 405 (“Predictive testing should be considered
investigational, and testing for purposes other than health care should be
discouraged.”). Despite the truth of the statement, it has become almost cliché in circles
of genetic experts to say that we should have learned from the sickle cell experience in
the early 1970s in which a screening program caused widespread anxiety and many
breaches of confidentiality. See Brom, supra note 27, at 129; supra note 126.
193
Law should be used to prevent predictable problems and minimize the harm. See
Annas, supra note 14, at 22 (rejecting laissez-faire strategy to let the market determine
which genetic tests are done on the grounds that law should be used to prevent
problems and “lawsuits for breaches of privacy have not often been pursued (because
the private
information is usually made known to even more people in the process)”). As observed
by Professor Paul Starr, “[t]he very circumstances of sickness promote acceptance of
[physicians'] judgment.” Paul Starr, The Social Transformation of American Medicine 5
(1982).
194
See, e.g., American Cancer Society, Massachusetts Division, Genetic Testing: Patient
Privacy and Discrimination Considerations (1995); Draft Statement, The Jewish
Women's Coalition on Breast Cancer (1996) (“The recent identification of a genetic
variation that may predict breast cancer is provoking immense anxiety and obscuring
vital information.”); Draft Statement, Hadassah, BRCA1 Gene, Genetic Testing and
Insurance Discrimination (1996) ( “Hadassah is ... concerned that this new genetic
information or individual's requests for genetic counseling services may result in higher
health insurance premiums, changes in terms or conditions, or outright denial or
cancellation of coverage.”); Massachusetts Breast Cancer Coalition, What You Need to
Know Before Considering Genetic Testing for Heritable Breast Cancer 1-2 (1996)
(identifying the following considerations: (1)the potential advantage of the test to an
individual is limited, (2)there is no known effective prevention for breast cancer, (3)a
positive test result does not mean that you will get breast cancer, (4)a negative test
result does not mean that you will not get breast cancer, and (5)getting tested may carry
psychological, social, financial, and legal ramifications).
195
See generally Blatt, supra note 21.
196
The mechanism for regulation recognized by the ELSI Task Force includes: (1)adoption
of industry-wide codes or policy statements; (2)recommendations from professional
societies; (3)extension of existing state or federal regulations to cover unique areas of
genetic testing; and (4)new legislation. See ELSI Task Force on Genetic Testing, supra
note 1, at 37.
197
This summary is based upon Proposed Recommendations of the Task Force on
Genetic Testing, Meeting Notice, 62 Fed. Reg. 4539, 4539-47 (1997).
198
See id. at 4540.
199
Id.
200
Id.
Michael J. Malinowski & Robin J.R. Blatt, Commercialization of Genetic Testing
Services: The Fda, Market Forces, and Biological Tarot Cards, 71 Tul. L. Rev. 1211,
1212–312 (1997)
