Good morning, Madam Chairwoman and members of the Subcommittee. My colleagues and I at
the Department of Health and Human Services (DHHS) appreciate your interest in genetic
testing. Thank you for the opportunity to describe our major activities that bear on the
validity and utility of this emerging technology.
The Promise of Genetic Testing
The ongoing explosion of new knowledge about the structures and functions of human
genes and new laboratory technology for analysis of genetic material is yielding a wealth
of new tests for genetic traits. These tests offer more than improved capability for
diagnosing existing disease. They also offer unprecedented means to estimate future
disease risks for a currently healthy individual and for his/her offspring and, where an
effective preventive intervention is available, to initiate medical or behavioral steps to
reduce that risk.
Hundreds of genetic tests already are in routine use for diagnosis of disease. Most of
them are in the form of clinical laboratory services - some of which are marketed directly
to the public. Many more genetic tests are under development, and their number and variety
are expected to grow rapidly within the next decade.
These advances stem in large part from research conducted and funded by agencies of the
DHHS, especially the National Institutes of Health (NIH). In particular, the Human Genome
Project - a joint venture of the NIH, the Department of Energy, and collaborators in the
United Kingdom and elsewhere around the world - promises vast new insights in human
biology and, thus, extraordinary advances in medicine and public health. Dr. Collins' testimony discusses the current status of this
Potential Harms from Genetic Tests
Yet, for all its promise, genetic testing can result in considerable harm. A test may
be flawed and measure something other than that which it is purported to measure - thereby
producing erroneous information. A test's
result, though accurate, may be poorly or incorrectly characterized with respect to its
clinical meaning - thereby giving health care providers and/or patients a false sense of
confidence in the finding, whether positive or negative. Information about a genetic test
may be communicated inaccurately or incompletely from laboratorians to health care
providers and/or from providers to patients. Health care providers may employ a genetic
test inappropriately - for example, employ a test that has little or no likelihood of
benefitting the patient. Such shortcomings, individually or in combination, could
compromise the quality of care or mislead patients with respect to their health status.
Even when a test is highly accurate and the clinical significance of the result is well
understood, the outcome may do more to create anxiety for the patient than to provide
reassurance. This can occur when an apparently healthy individual tests positive for a
genetic marker associated with a disease that may or may not develop at some future time -
perhaps for many years - and for which no validated preventative intervention is
available. For example, a positive result from a test for one of the genes associated with
breast cancer does not predict with certainty that the disease ever will emerge - much
less when. Nor does a negative result mean that the disease never will emerge. Both
provider and patient need to consider the pros and cons of performing genetic tests in the
absence of clinical symptoms and make their decision on a case-by-case basis.
Last, but far from the least, the potential harms associated with genetic testing are
not limited to the clinical milieu. Health care providers, employers, insurance companies,
or others may handle information about genetic tests without adequate attention to privacy
and confidentiality. As a consequence, individuals may be denied needed and deserved
insurance coverage, or be discriminated against by current or prospective employers, or
suffer psychosocial harms such as increased anxiety and altered family relationships.
The opportunities and challenges associated with genetic testing are discussed
thoroughly in the report entitled "Promoting
Safe and Effective Genetic Testing in the United States
- the principal product of the Task Force on Genetic Testing, which was commissioned
jointly by the National Institutes of Health and the Department of Energy. The Task Force
report is an invaluable resource for government, academia, and industry. The report
outlines a set of overarching principles to guide the development and use of genetic tests
and provides thoughtful recommendations in several areas: ensuring the safety and
effectiveness of new genetic tests, ensuring the quality of laboratories performing
genetic tests, improving providers'
understandings of genetic testing, and ensuring the availability of effective genetic
tests for rare inherited disorders.
DHHS Oversight of Genetic Testing
The findings and recommendations of the Task Force are highly relevant to DHHS' responsibilities for overseeing genetic tests. Three
distinct statutory authorities are involved: the Medical Devices Amendments of 1976 to the
Food, Drug and Cosmetic Act, the Clinical Laboratory Improvement Amendments (CLIA) of 1988
to the Public Health Service (PHS) Act, and those provisions of the PHS Act that govern
the protection of human subjects of research. I will summarize each of these three
authorities as they relate to issues raised the Task Force.
First, genetic tests are in vitro diagnostic devices and, thus, are subject to
regulation by the Food and Drug Administration (FDA) as medical devices. To date, FDA has
required pre-market review and approval for genetic tests packaged and sold as kits but
has not actively regulated commercial, laboratory-based genetic testing services - which
sometimes are referred to as "home brews".
Second, the CLIA statute, enacted by Congress to ensure the quality of laboratory
testing in the U.S., regulates all sites at which testing is performed on specimens
derived from the human body for health purposes. The requirements such laboratories must
meet are based on test complexity; the more complex the procedure, the more stringent the
requirements. Although a few CLIA requirements specifically address genetic tests, such
tests generally are covered under the major CLIA standards for quality control, quality
assurance, personnel qualifications, proficiency testing, and patient-test management.
Thus, CLIA provides for regulation of the personnel, the procedures, and the environments
in which genetic tests are performed. CLIA does not, however, provide for regulation of
individual tests. In particular, laboratories that perform genetic tests on human
specimens and provide test results to either the person tested or his/her health care
provider are subject to regulation under CLIA by the Health Care Financing Administration
(HCFA) and the Centers for Disease Control and Prevention.
Third, DHHS regulations for the protection of human research subjects may be applicable
to human clinical trials of new or improved genetic tests. DHHS oversight comes into play
if the trial is funded in whole or in part by a DHHS agency and/or if the trial is
conducted with the intent to develop the test for commercial use. The Office of Protection
from Research Risks, NIH, oversees the protection of human research subjects in
DHHS-funded research. FDA oversees the protection of human research subjects in trials of
investigational devices, drugs, or biologics being developed for commercial use.
Laboratories, however, are not required to comply with these provisions since they provide
a service and are not considered to be performing research.
Recent Relevant Actions by DHHS Agencies
Since the publication of the Task Force report in September, 1997, DHHS agencies -
individually or collectively - have taken several important steps to foster the
development and appropriate use of high-quality genetic tests. I will discuss each one
Secretary's Advisory Committee on Genetic
Testing. In June, 1998, Secretary Shalala chartered this new advisory body in accord
with the terms of the Federal Advisory Committee Act and assigned to the NIH the
responsibility for providing staff services to the Committee. The costs of this
secretariat are to be shared among the pertinent DHHS agencies. Formation of such a
Committee was the primary recommendation of the Task Force on Genetic Testing.
The following excerpts from the Charter summarize its background and function:
AThe Department of Health and Human Services
(DHHS) has a vital role in safeguarding public health while fostering the development of
valid genetic tests and facilitating their availability and beneficial use for medical and
public health purposes. The several agencies within the Department that help carry out
this role must collectively address the broad array of important and complex policy issues
raised by genetic testing. To assist in addressing these cross-cutting policy issues, the
Secretary's Advisory Committee on Genetic
Testing identifies policy issues raised by genetic testing and makes policy and procedural
recommendations to the Secretary on how such issues should be addressed."
AThe Secretary=s Advisory Committee on Genetic Testing shall advise
and make recommendations to the Secretary through the Assistant Secretary for Health on
all aspects of the development and use of genetic tests."
Toward ensuring appropriate coordination of genetic testing activities and policies
among pertinent DHHS advisory bodies, the Secretary's
Committee is to include among its appointed members at least one current member of the
Clinical Laboratory Improvement Advisory Committee and at least one current member of the
Medical Devices Advisory Committee.
During the latter part of 1998, through a notice in the Federal Register, DHHS
solicited nominations for membership on the Secretary's
Committee. The solicitation produced 173 nominations. A DHHS interagency staff group
assessed the qualifications of the nominees in relation to the requirements of the
Committee charter and prepared alternative slates for consideration by the Assistant
Secretary for Health and the Secretary. The Secretary intends to announce the first set of
appointments to the Committee in the near future. FDA is also in the process of chartering
a panel under the Medical Device Advisory Committee to assess tests in kits for human
Quality of Active Ingredients Used in Laboratory-Based Genetic Tests. In November,
1998, the FDA promulgated a final rule -- "Medical
Devices; Classification/ Reclassification; Restricted Devices; Analyte Specific Reagents"-- which introduced minimal FDA regulatory oversight
of commercial, laboratory-based testing services. This rule specifies general controls for
the active ingredients - also known as analyte specific reagents(ASRs) - of "home brew"
assays. The controls cover registration and listing, quality systems requirements, and
post-market reporting requirements. The rule also establishes labeling requirements for
both ASRs and the "home brew" tests developed using them. It further restricts
use of ASRs to facilities registered under CLIA as high complexity laboratories. With only
a few exceptions, ASRs are exempt from premarket review. Currently, FDA applies its ASR
requirements uniformly to all "home brew" tests, including genetic tests.
However, FDA has preserved its flexibility to reassess this decision in the light of its
further consideration of the recommendations of the Task Force on Genetic Testing and
advice from the Medical Devices Advisory Committee and the Secretary's Advisory Committee on Genetic Testing.
Potential Refinements to CLIA Regulations. Late last year, the Clinical Laboratory
Improvement Advisory Committee offered a wide-ranging set of recommendations for refining
CLIA regulations in areas applicable to genetic testing. Among the topics addressed are
definitions of genetic tests, informed consent, re-use of tested specimens,
confidentiality of information about genetic tests, clinical information needed to
establish the appropriateness of genetic testing, qualifications and responsibilities of
laboratory personnel, quality control, specimen integrity, proficiency testing, validation
of genetic tests, reporting requirements, and record retention. HCFA and CDC will assess
these recommendations in the context of the continuing development of the overall DHHS
regulatory framework for genetic tests and genetic testing.
Development and Dissemination of Information on Genetic Tests. As the number and
variety of genetic tests increase, so will the need for data on their validity and
utility. The Task Force on Genetic Testing recognized this emerging need and offered
several recommendations for addressing it.
Late in 1998, the CDC and several collaborating organizations took an important step in
this direction by launching the Human Genome Epidemiology Network (HuGE Net). The goals of
the Network, as reported last year in the American Journal of Epidemiology, are three: to
promote global collaboration in the development and dissemination of peer-reviewed
epidemiologic information on human genes; to develop an updated and accessible knowledge
base on the World Wide Web; and to promote the use of this knowledge base by health care
providers, researchers, industry, government, and the public for making decisions
involving the use of genetic tests and services for disease prevention and health
In a related effort during the past year, an interagency DHHS staff group has been
assessing possible ways to achieve systematic national data collection on the validity and
utility of genetic tests. This effort is driven by the realization that a comprehensive
understanding of many, perhaps most, genetic tests may not be possible until the test has
been used for a considerable period of time, in different population groups, and in a wide
variety of clinical contexts. In the coming months, the DHHS group intends to expand its
discussions to include representatives from other government agencies as well as academia,
industry, health care providers, genetic counselors, and patient advocates. The objective
of these broader discussions will be to identify promising approaches to national data
base development - especially pilot projects that lend themselves to voluntary
Considerations regarding Privacy/Confidentiality and Professional/Public Education.
As indicated in Dr. Collins' statement, the
National Human Genome Research Institute (NHGRI), NIH has continued its longstanding
distinguished leadership in addressing ethical, legal, and social issues associated with
the Genome Project in particular and the burgeoning field of genomics research in general.
Through sponsorship of studies and workshops and through participation in other public
fora, NHGRI has been at the forefront of efforts to raise public awareness regarding
actual and potential instances of genetic discrimination by health insurers and employers.
NHGRI also has been a prominent contributor to efforts to enhance the genetics-related
components of primary and continuing education for health care providers and genetic
In conclusion, Madam Chairwoman, DHHS agencies view genetic testing as a technology
that is capable of enhancing medicine and public health in ways that we only could dream
about heretofore. We will continue to work toward ensuring the validity and utility of
genetic tests as we continue to foster their development and use. We value the findings
and recommendations provided by the Task Force on Genetic Testing and look forward to
drawing further upon this guidance as, in consultation with the Secretary's Advisory Committee on Genetic Testing, we strive to
make the most effective and efficient uses of our current oversight authorities.