[Federal Register Volume 62, Number 20 (Thursday, January 30, 1997)]
[Notices]
[Pages 4539-4547]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-2286]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Proposed Recommendations of the Task Force on Genetic Testing;
Notice of Meeting and Request for Comment
AGENCY: National Institutes of Health, HHS.
ACTION: Notice.
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SUMMARY: The Task Force on Genetic Testing was created by the National
Institutes of Health (NIH)-Department of Energy (DOE) Working Group on
Ethical, Legal, and Social Implications of Human Genome Research to
make recommendations to ensure the development of safe and effective
genetic tests, their delivery in laboratories of assured quality, and
their appropriate use by health care providers and consumers. The Task
Force reviewed genetic testing in the United States, promulgated
interim principles consonant with its goals (``Interim Principles'',
available at http://ww2.med.jhu.edu/tfgtelsi), and has taken public
comments into consideration in revising them. Over the past eight
months the Task Force has discussed policies to implement several of
its principles. It now submits proposed recommendations for public
comment. These proposed recommendations are available at http://
ww2.med.jhu.edu/tfgtelsi.
DATES: To assure consideration by the Task Force, comments must be
received on or before March 10. The Task Force will meet on March 17
from 8:00 a.m. to recess and on March 18 from 8:00 a.m. to adjournment
at approximately 12:00 noon. The meeting will take place at the
Doubletree Inn at the Colonnade, 4 West University Parkway, Baltimore,
Maryland, (410) 235-5400. Time permitting, guests will have the
opportunity to speak on comments already submitted, but no formal time
is being set aside. A final report, including the principles and
recommendations, together with background information and comments,
will be issued shortly after the meeting.
ADDRESSES: Written comments should be sent to Neil A. Holtzman,
M.D.,M.P.H., Genetics and Public Policy Studies, The Johns Hopkins
Medical Institutions, 550 N. Broadway, Suite 511, Baltimore MD, 21205-
2004, faxed to Dr. Holtzman at 410-955-0241, or e-mailed to a@welchlink.welch.jhu.edu. Individuals who plan to attend the March 17-
18 meeting and need special assistance, such as sign language
interpretation or other reasonable accommodations, should contact Dr.
Holtzman in advance of the meeting.
Background
Scientific breakthroughs have greatly accelerated the discovery of
genes which, when altered by mutation, result in disease or in
increased risk of disease. When these mutations occur in the germline
(sperm or egg), they can be passed from one generation to the next.
These basic research discoveries lead readily to the development of
tests for inherited mutations. The number of DNA-based genetic tests
and the volume of testing are increasing steadily. This has been
accomplished in part by the work of the new biotechnology industry.
[[Page 4540]]
Aware of the potential for harm as well as benefits, the National
Center for Human Genome Research (NCHGR/NIH) set aside from its
inception a portion of its appropriation for consideration of ethical,
legal, and social implications of human genome research. As part of its
joint program with NCHGR, the Department of Energy (DOE) also set aside
a portion of its appropriation. This initiative to anticipate problems
in order to maximize benefits and prevent or minimize harm, of which
the Task Force on Genetic Testing is one activity, is unprecedented in
the development and application of new biomedical technologies. The
principles and recommendations of the Task Force represent an attempt
to build on successes and prevent problems of the past and present from
continuing in the future. Some past and present problems will be
described in the final report of the Task Force.
For the most part, genetic testing in the United States has
developed successfully, providing more options for avoiding,
preventing, and treating inherited disorders. This success is largely
the result of testing being undertaken in genetic centers or in
consultation with geneticists and genetic counselors. In the next few
years, the use of genetic testing is likely to expand rapidly while the
number of genetic specialists will remain essentially unchanged. This
means that a greater burden for making genetic testing decisions will
fall on providers who have had little formal training or experience in
genetics. The problems they will encounter in providing genetic tests
are seldom encountered in other areas of medicine.
Much of medical practice and medical testing is provided
for people who are already ill. Genetic testing will increasingly be
used to predict risks of future disease in healthy people. Telling
healthy people about future risks can heighten uncertainty and cause
psychological distress.
For many other disorders, interventions are available to
cure, prevent or ameliorate the condition. This is not the situation
for many disorders for which genetic testing is possible. Positive
results of some tests confront patients with difficult reproductive
decisions. These are personal decisions that should not be unduly
influenced by providers or society.
Few other tests provide information on the risk of future
disease to healthy relatives of the person being tested. Providers have
little guidance in communicating genetic risks to relatives and,
simultaneously, keeping results confidential.
Differences in the frequency of disease-related mutations
among ethnic groups can influence the appropriateness of providing some
genetic tests, and heighten concern about discrimination and
stigmatization.
In addition, the predictions made by genetic tests are not always
certain and often no independent test is available to confirm the
prediction. Test uncertainty is not unique to genetic tests. However,
the psychological and physical effects of testing are often greater for
imperfect genetic tests when no treatment is available or when
interventions of unproven efficacy are life-long or irreversible.
Key Principles
The Task Force enumerated principles to address many of the
problems raised by predictive genetic tests. Its proposed
recommendations are an effort to implement several of these principles,
highlighted below:
Validity and Utility of Genetic Tests
Before a genetic test can be generally accepted in
clinical practice, data must be collected to demonstrate the benefits
and risks that accrue from both positive and negative results. The
primary responsibility for data collection falls on test developers.
For many tests, however, data collection must continue after tests are
introduced into practice.
Protocols for the clinical validation of genetic tests
must receive the approval of an institutional review board (IRB). At
present, IRBs have the principal responsibility for the protection of
subjects participating in validation studies. The Task Force is
concerned that current limitations of IRBs might impair review of
genetic testing protocols.
Laboratory Quality and Certification
A national accreditation program for laboratories
performing genetic tests, which includes on-site inspection and
proficiency testing, is needed to promote standardization across the
country. Although most laboratories providing clinical laboratory tests
are certified under the Clinical Laboratory Improvement Amendments
(CLIA) of 1988, current regulations do not adequately ensure the
quality of genetic testing. Professional organizations have developed
more appropriate quality assessment of genetic tests than is required
under CLIA, but laboratories performing genetic tests are not required
to use these voluntary accreditation mechanisms.
Professional Competence in Genetics
Health care professionals involved in the provision of
genetic tests should be well-informed about their implications,
benefits and risks. Students preparing for careers in health care and
current health care providers themselves are not being taught enough
about human genetics and genetic testing. Consequently, not all
providers in practice today may have adequate competence to offer and
interpret genetic tests. Related problems are the lack of standards for
formal assessment of new genetic testing technologies and the limited
impact of current efforts to establish clinical guidelines for when and
how genetic tests should be offered.
Rare Genetic Diseases
The development and maintenance of tests for rare genetic
diseases must be encouraged. 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. Some that have been
available may be more difficult or impossible to obtain. Many
physicians do not have access to the best available information and
resources to identify and manage rare diseases, or know where to turn
for help.
Informed 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.
When specimen identifiers are retained in either coded or uncoded form,
the opportunity exists of being able to contact subjects even if the
intent of the original protocol is not to do so.
Health care providers must describe the features of the
genetic test, including potential consequences, to potential test
recipients prior to the initiation of predictive testing in clinical
practice. Individuals considering genetic testing should be told the
purposes of the test, the chance it will give a correct prediction, the
implications of test results and the options, and the benefits and
risks of the process. The responsibility for providing information to
the individual lies with the referring provider, not with the
laboratory performing the test.
It is unacceptable to coerce or intimidate individuals or
families regarding their decision about genetic testing. Respect for
personal autonomy is paramount. People being offered testing must
understand that testing is voluntary. Whatever decision they make,
their care should not be jeopardized. Information on risks and
[[Page 4541]]
benefits must be presented fully and objectively. A non-directive
approach is of the utmost importance when reproductive decisions are a
consequence of testing or when the safety and effectiveness of
interventions following a positive test result have not been
established. Obtaining written informed consent helps to assure that
the person agrees to testing voluntarily.
Results should be released only to those individuals to
whom the test recipient has consented or subsequently requested in
writing. Means of transmitting information should be chosen to minimize
the likelihood that results will become available to unauthorized
persons or organizations. Under no circumstances should results be
provided to any outside parties, including employers, insurers,
government agencies, without the test recipient's written consent.
Unless potential test recipients can be assured that the results will
not fall into unauthorized hands, some will refuse testing for fear of
losing insurance or employment.
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. Disclosure by
providers to other family members is appropriate only when the person
tested refuses to communicate information despite reasonable attempts
to persuade him or her to do so, and when failure to give that
information has a high probability of resulting in irreversible or
fatal harm to the relative. When test results have serious implications
for relatives, it is incumbent on providers to explain to people who
are tested why they should communicate the information to their
relatives.
Recommendations
A Genetics Advisory Committee
The Task Force joins the NIH-DOE Joint Committee to Evaluate
Ethical, Legal, and Social Implications Program of the Human Genome
Project in recommending that the Secretary of Health and Human Services
(HHS) create, in the Office of the Secretary, a federally chartered
Advisory Committee on Genetics and Public Policy (hereafter the
Advisory Committee) whose members should include the stakeholders in
genetic testing. The Secretary should establish formal liaison between
the Advisory Committee and an already-established HHS interagency group
considering policies of the Department relevant to the development and
provision of genetic tests. In addition to assisting the Advisory
Committee, this interagency group should develop coordinated and
consistent genetic testing policies in the Department. The two
committees whose creation is recommended later in this document, one to
advise the Food and Drug Administration (FDA) on assuring the validity
and utility of new genetic tests, the other to advise the Clinical
Laboratory Improvement Advisory Committee on assuring the quality of
laboratories performing genetic tests, should report to the Advisory
Committee through the interagency group.
Need for Interim Action
The Task Force recognizes that the formation of the Advisory
Committee could take some time. It is also aware that organizations
have on occasion developed and offered genetic tests without always
collecting data on test validity and utility and without external
review. Consequently, the public is not being adequately protected.
The Task Force recommends that the Secretary of HHS 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. It
suggests two possibilities:
(1) FDA uses its acknowledged authority under the Medical Device
Amendments of 1976 (21 USC 321-392) to the Food, Drug, and Cosmetic
Act (21 USC 301-392), to ensure that all organizations developing
new, predictive genetic tests submit protocols to an institutional
review board (IRB).
(2) The Health Care Financing Administration (HCFA) establish
policies under Medicare and Medicaid to reimburse for certain
genetic tests (see below) only when they are performed in
laboratories that can provide evidence that (a) the test has been
clinically validated (based on published information or information
provided by the test developer) or that it is participating in a
systematic validation plan, and (b) they are qualified to provide
such tests (see below, Laboratory Quality). Once HCFA adopts such
policies it is likely that other third-party payers will quickly
follow.
The Task Force makes a similar recommendation to the Department of
Defense for reimbursement under the Civilian Health and Medical Program
Uniform Services (CHAMPUS).
The need for stringent scrutiny of certain predictive genetic
tests. The Task Force has sought to find ways to identify tests that
are more likely to pose significant risks in their developmental stage
and when they enter clinical practice. It recognizes that existing
resources for scrutinizing tests are limited. Consequently, the Task
Force has attempted to identify characteristics of tests and diseases
that raise the greatest concern and can be used to prioritize tests for
stringent scrutiny. These characteristics include, but are not
necessarily limited to:
A test's potential for predicting serious future disease
in healthy people (or their offspring). Even if a test developer's
intended use of the test may not be for predictive purposes, the
potential for such use, as is the case for DNA-based genetic tests,
increases the level of scrutiny needed. The absence of a confirmatory
test heightens the scrutiny a test needs.
Test uncertainty. When only healthy people with positive
test results will develop the disease and when all people with positive
results will develop it, less scrutiny is needed than when these
conditions are not fulfilled.
The safety and effectiveness of clinical interventions in
those with positive test results of predictive tests. Unless the safety
and effectiveness of clinical interventions for those with positive
test results have been established, people who test positive cannot be
confident that interventions will prevent the disease or improve its
outcome if it does occur.
Other characteristics that might play a role in prioritizing are:
the frequency of occurrence of the disorder(s) detected by the test
under review, the use of the test for population screening, whether the
disorder(s) detected occur more frequently in some ethnic groups than
others, and whether the reliability of the test under routine clinical
laboratory conditions has been established.
There are several junctures at which these characteristics should
be applied to specific tests. The first occurs in the review of
protocols for investigating the validity and utility of new tests.
Subjects participating in trials or pilot programs to establish
validity and utility must be adequately protected, particularly when
they will be notified of the results or simply when personal
identifiers will be retained with the specimens. The protocol must have
sufficient scientific merit to justify the participation of subjects.
The characteristics provided above could be used by IRBs as a checklist
to make sure that the protocol addresses important issues in test
development. For instance, if applicants fail to present data on test
uncertainty, they should be required to supply that information or, if
it is unavailable, to collect the requisite data. A grading system
could be devised so that protocols exceeding a certain score would be
designated as requiring ``stringent scrutiny.'' Alternatively, the
characteristics can be layered in an
[[Page 4542]]
algorithm or decision tree. (See Figure) For instance, if a test has
the potential to predict future disease and there is no confirmatory
test, the next step in deciding whether it needed stringent scrutiny
would be the extent of test uncertainty. If this was unknown, data
collection would be needed. Once data were collected, the next question
is the safety and effectiveness of interventions in those with positive
results. If the benefit:risk ratio of intervention is high and test
uncertainty is low, the test would not require close scrutiny. Even if
test uncertainty is low, close scrutiny would be needed if the safety
and effectiveness of interventions had not been established.
BILLING CODE 4140-01-P
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[GRAPHIC] [TIFF OMITTED] TN30JA97.000
BILLING CODE 4140-01-C
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The second juncture occurs when a test developer believes the test
is appropriate for clinical use. Review by an organization independent
of the developer is needed to ensure that the public will benefit from
the test. The Task Force is concerned that the number of tests might
overwhelm external review processes and needlessly delay the
availability of tests of potential benefit. To reduce the likelihood of
backlogs, the criteria should be used to set priorities for stringent
scrutiny. Tests of low priority would enter clinical practice without
scrutiny but could be considered again at the third juncture.
The third juncture occurs when the test is clinically available and
there are concerns that (1) it will not be used when it is indicated,
(2) it will be used for inappropriate indication(s), or (3) that more
data on validity and utility are needed. The same set of criteria can
be used to set priorities for post-marketing surveillance requirements
and establishing guidelines for test use.
The Task Force recognizes that as information and experience is
gained, the scrutiny a test needs is likely to diminish. As further
scientific and technical advances occur, other criteria may become more
important and other types of tests may then need stringent scrutiny.
Assuring the Validity and Utility of New Genetic Tests
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. The Task Force
urges the Office of Protection of Human Subjects from Research Risks,
with input from the proposed Advisory Committee, to address these
problems. The Task Force is also concerned that organizations that do
not use federal funds for the research and development of genetic tests
that will be marketed as services may not seek outside review from an
independent IRB. The Task Force is also concerned that data needed
after tests enter clinical practice may not be collected.
The Task Force urges the proposed Advisory Committee to recommend
to the Secretary the creation of a National Genetics Board (NGB) whose
goal would be to assure the protection of human subjects in the
development of genetic tests with the potential to predict future
disease. NGB members should be broadly representative of stakeholders
in genetic testing, including but not limited to test developers
(manufacturers and clinical laboratories), consumers, professional
societies, health care providers, and insurers. Some of its members
must be scientists capable of reviewing scientific protocols. The Board
should have its own staff.
NGB would develop a checklist that would enable local IRBs to
identify protocols that meet criteria for stringent scrutiny. NGB would
function along the lines of one of the following models, each of which
each has advantages and disadvantages. The Task Force did not reach
consensus on which model NGB should follow. The Task Force is
especially interested in public comments on the alternatives.
(1) NGB reviews all protocols requiring stringent scrutiny. This
assures that expert assessment with broad input will be consistently
obtained and conflicts of interest will be minimized. However, if local
IRBs also review protocols before or after they are sent to the NGB,
funding or activation of the protocols could be delayed. NGB approval
would be required before federal funds are awarded. NGB should also be
available to review protocols from commercial organizations developing
genetic tests without federal funds.
(2) NGB has the discretion to choose which protocols among those in
need of stringent scrutiny it will review. Those protocols which NGB
elects not to review will be sent back to the local IRB for review.
Based on its selective review, NGB will issue advisories to local IRBs
to assist them in the review of similar protocols. Under this model,
the advantages of the first model are reduced, but so is NGB's work
load; local IRBs retain greater authority. Delays are likely as
protocols move between local IRBs and NGB.
Under both model (1) and (2), local IRBs could also request NGB
review of other genetic testing protocols. Based on its available
resources and backlog, NGB could decide whether or not to review these
protocols. NGB could also assume responsibility for the primary review
for the protection of human subjects of multi-center and other
collaborative studies for the validation of genetic tests.
(3) NGB focuses on generic policy issues and sets general
guidelines for review. It is available for consultation and advice, but
has no mandatory review function. Protocols that a local IRB believes
raises novel and problematic issues could be sent to NGB for analysis
and comment. The advantages and disadvantages of this approach are
similar to those described for the second model; the likelihood of
consistent review is further reduced, but as review is entirely the
responsibility of the local IRBs, delays are less likely.
Role of FDA. 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. If tests requiring stringent scrutiny were
regulated by FDA, even if they were to be marketed as services, then
under existing regulations (21 CFR part 56), protocols for clinical
validation would have to be submitted to an IRB regardless of whether
they came from federally-funded organizations or not. Although the FDA
acknowledges its authority under the Medical Device Amendments to
regulate genetic tests marketed as services, it has chosen not to do
so. (Under the CLIA, clinical laboratories must demonstrate analytical
validity of their tests but there is no statutory or regulatory
requirement for them to establish the clinical validity or utility of
clinical laboratory tests.)
The Task Force recommends that FDA:
(1) Establish a Genetics Advisory Panel under the Medical Devices
Amendments (21 USC 321-392) which would advise FDA on: (a) Strategies
for prioritizing genetic tests; (b) the scientific, ethical, and social
merits of applications FDA receives for marketing genetic tests; and
(c) other matters germane to genetic testing. In carrying out its first
function, this panel could consult with the proposed NGB if it is
established, but it should not delay formulating its strategies until
that time.
(2) Adopt a strategy to prioritize predictive genetic tests
according to the degree of scrutiny they need.
(3) Publicize the requirements it develops for tests requiring
stringent scrutiny.
(4) Require that new genetic tests meeting criteria for stringent
scrutiny be regulated under the Medical Device Amendments (21 USC 321-
392; 21 CFR parts 200 et seq.) regardless of whether their sponsor's
intention is to market them as services or as kits.
Although a majority of the Task Force supported all of these
recommendations, a consensus was not reached on the fourth. The Task
Force is especially interested in public comments on this
recommendation.
Data collection. The data needed to definitively establish the
validity and utility of a genetic test may take so long to collect that
if test developers could
[[Page 4545]]
not market their tests they would be deterred from developing them.
Data collection is also a problem for rare genetic diseases for which
data from several sources will have to be collected to establish the
validity and utility of testing. Without a formal plan and procedure
for prospective data collection, data will undoubtedly be lost and the
time to reach definitive conclusions will be prolonged.
The Centers for Disease Control and Prevention (CDC), in
cooperation with NCHGR, should expand the monitoring of genetic
disorders in order to provide data on the validity of tests and post-
test interventions. It should establish procedures for tracking healthy
individuals with positive test results, as well as those diagnosed with
inherited disorders, to learn more about (1) test validity, (2) the
natural history of such disorders, and the (3) safety and effectiveness
of interventions. The collection of this data should be undertaken in
cooperation with local providers and consultants in genetics and other
relevant specialties. At all times the confidentiality of the data
collected must be protected.
For tests for which long periods of data collection are needed, FDA
should grant conditional premarket clearance or approval before all
necessary data are collected to make promising new technologies
available to the public and enable test developers to obtain an
adequate return on their investment in test development. Developers
would be responsible for continuing to collect data as in the premarket
phase and make it available to FDA. When sufficient data are collected,
FDA will decide whether or not to grant unconditional approval.
Conditional premarket approval should be granted to tests when FDA
considers it likely that the test will prove to make an important
contribution to the prevention or management of the disorder. Under
this circumstance, third-party payers, including government programs
such as Medicare, Medicaid, and CHAMPUS, should reimburse for the test
once it has been conditionally approved. Managed care organizations
should also cover tests given conditional approval.
Technology assessment. Many tests currently on the market have not
been systematically validated nor subject to external review. New tests
that go through these processes will be modified under clinical
conditions.
Technology assessment is important to guide providers and consumers
in the use of genetic tests, but is unlikely to be undertaken by
existing technology assessment agencies because genetic tests do not
entail huge expenditures of health care dollars. NGB should serve as a
clearinghouse for technology assessments of genetic tests that are
about to enter, or already are used in, clinical practice. It could
secure and coordinate assessments of those technologies it considers in
need of stringent scrutiny and coordinate assessments to avoid
unnecessary duplication. NGB could also make recommendations on
appropriate use of genetic tests with input from relevant professional
societies as well as consumer groups.
Assuring Laboratory Quality
The Task Force is concerned about the lack of Federal law or
regulation covering genetic tests except for cytogenetic tests,
limitations of existing voluntary quality assurance and proficiency
testing programs, inadequate assessment of the pre-and post-analytic
phases of testing, and the absence of public information about
laboratories satisfactorily performing genetic tests under existing
voluntary assessments.
CLIA has no standards specific to genetic tests except for
cytogenetics. Currently New York State requires certification of all
laboratories performing clinical genetic tests on state residents. The
College of American Pathologists/American College of Medical Genetics''
(CAP/ACMG) Molecular Pathology accreditation program is also designed
to assess performance on the special problems of genetic tests, placing
greater emphasis on the pre-and post-analytic phases of testing than
other programs. However, CLIA-certified laboratories performing genetic
tests are not required to be assessed by the CAP/ACMG program. If they
are not, genetic tests could be accredited under CLIA without being
specifically assessed. Furthermore, laboratories that participate in
CAP/ACMG's Molecular Pathology program do so voluntarily and not under
CAP's regulatory (``deemed'') authority under CLIA. (Under CLIA, HCFA
has the authority to grant deemed status equivalence to an outside
organization that has a quality assurance and proficiency testing
survey program with standards equal to or greater than CLIA's. CAP's
general proficiency testing program has been ``deemed'' equivalent by
HCFA.) As CLIA has not established standards specifically for genetic
tests, it has no authority to approve the CAP/ACMG Molecular Pathology
program.
Differences between state law and Federal laws and regulations (and
among different nations), create overlapping and often duplicative
requirements for laboratories. The Task Force recommends that a
national accreditation program of quality assurance and proficiency
testing for genetic tests equivalent to or more stringent than those of
New York State and CAP/ACMG, should be established under CLIA. This
accreditation program should include proficiency testing and inspection
of laboratories performing genetic tests. Quality assurance includes:
(a) The skill and training of laboratory staff; (b) evidence of
successful execution of the complex techniques involved in genetic
testing to produce a correct and verifiable test result; and (c)
assessment of pre-testing and post-analytic phases of testing.
Until such time as a national accreditation program is established
under CLIA, the CAP/ACMG Molecular Pathology program, expanded to
encompass all methods currently in use in genetic testing, might itself
serve as the national program, and should be accessible to any
laboratory providing clinical genetic testing. When a national program
is established the CAP/ACMG Molecular Pathology program should have
deemed status.
The Task Force recommends the establishment of a Genetics Advisory
Committee to the Clinical Laboratory Improvement Advisory Committee
(CLIAC) to help address the deficiencies of CLIA in assuring the
quality of genetic tests. The work of this genetics committee should be
reported to the Advisory Committee on Genetics and Public Policy
through the interagency group previously discussed. The work of the
proposed CLIAC advisory committee should also be coordinated with other
HCFA programs, as well as FDA, CDC, and other Federal agencies involved
setting genetic testing policies.
Pre-test education and post-test counseling components of clinical
laboratory tests are critically important parts of the laboratory test
to physicians who are not generally well informed about genetic tests.
Preanalytic components include the information about the test that
laboratories make available to providers and consumers and the informed
consent documents and processes that laboratories may require.
Postanalytic components include the information (interpretation) given
with the test result and counseling services provided or arranged by
laboratories. In any quality assurance program, closer scrutiny is
needed of pre-and post-test analytic components of genetic testing than
current assessment programs provide. The Task Force recommends that
CAP/ACMG seek advice and input from consumer groups such as the
Alliance of Genetic
[[Page 4546]]
Support Groups, as well as from the National Society of Genetic
Counselors (NSGC), on standards for the quality of pre-and post-
analytic components of genetic testing.
The Task Force recommends that CAP/ACMG periodically publish, and
make available to the public, a list of laboratories performing genetic
tests satisfactorily under its voluntary program. The Task Force
recognizes that CAP is not currently required to publish, and has not
published, the names of laboratories performing satisfactorily in the
CAP/ACMG voluntary Molecular Pathology program. Until such time as a
program is established under CLIA, publication will enable providers
and consumers to select approved laboratories and will also serve as an
incentive for laboratories to participate in the CAP/ACMG quality
assessment program. This information should be disseminated using the
Internet and other media accessible to consumers and providers.
Managed care organizations and other third-party payers should
limit reimbursement for genetic tests to the laboratories on the
published list of those satisfactorily performing genetic tests.
Implementation of this recommendation will be especially important as
more managed care organizations move to restrict access to laboratory
services for their members to a single contracted laboratory (which may
or may not be on the list of qualified laboratories).
The Task Force recommends that efforts should be made to harmonize
international laboratory standards to assure the highest possible
laboratory quality for genetic tests. At present, no mechanism exists
to create international standards of laboratory quality and proficiency
for genetic tests. Current United States regulations require any
foreign laboratories performing clinical laboratory tests on U.S.
residents to hold a CLIA certificate even if their nation's laboratory
standards are more stringent that those of CLIA (e.g., as is the case
with Canada).
Provider Competence
The Task Force wants to ensure that non-geneticist providers
adequately appreciate many of the general issues that should be
considered and discussed in offering, providing, and interpreting
predictive genetic tests. These issues include: (1) Who should be
offered a specific test; (2) the benefits and risks of each test; (3)
the need for, and the content of informed consent, and how consent
should be administered; (4) an explanation of test results; and (5)
familiarity with genetic counseling strategies and principles. 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.
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.
The Coalition should work in consultation with its member
organizations, including non-genetics professional societies, to
encourage the development of core curricula in genetics, with an
emphasis on having individual professional organizations determine
their own needs in the design and execution of the programs. It should
also encourage input by consumers in the development of these
curricula. The Coalition should serve as a registry of, and
clearinghouse for, information about various curricula and educational
programs, grants, and training pilot programs in genetics education. By
providing educational resources, it should encourage professional
societies to track the effectiveness of their respective educational
programs. The Coalition should disseminate information on available
programs in order to avoid inefficient duplication.
The Task Force strongly recommends that board examinations used for
physician and specialty certification increase both the quality and the
quantity of questions related to genetics. This should further
stimulate the teaching of genetics to medical students, as well as
residents in many specialties. The scores on these questions should
serve as feedback to improve curricula.
Ultimately, implementation of these first two recommendations will
improve the provision of care. The remaining recommendations are
directed at short-term needs.
For those specialties which both require periodic passage of an
examination for recertification and whose practitioners are likely to
order predictive genetic tests, examinations for recertification should
include questions on medical genetics and genetic testing, including
predictive testing.
Hospitals and managed care organizations should use credentialing
and other mechanisms (such as prior authorization) to limit the
offering of certain predictive genetic tests to genetic health care
professionals and physicians who have demonstrated their competence in
dealing with the issues enumerated above. Successful completion of
continuing education courses could be required to demonstrate
competence. (The National Coalition for Health Professional Education
in Genetics should be able to provide information on available programs
for learning about the relevant issues.)
Predictive genetic tests requiring stringent scrutiny, as
previously described, should be among those for which special
credentials are needed. As professional experience is gained with tests
for certain disorders, special credentialing may no longer be required,
but other new genetic tests may take their place. Third-party payers
could also establish policies that allow only properly credentialed
providers to be reimbursed for their role in providing tests.
The Task Force is of the opinion that primary care providers and
other non-geneticist specialists can and should be involved in genetic
testing. However, they must first gain sufficient familiarity with the
issues involved. In some cases, providers should work closely with
genetic health care professionals who can serve as experienced
repositories of in-depth information about many aspects of genetic
testing. Several laboratories already require this collaboration. In
this rapidly changing field, providers should maintain their knowledge
of genetics throughout their professional lives.
Credentialing bodies such as the Joint Commission on Accreditation
of Healthcare Organizations (JCAHO) and the National Committee for
Quality Assurance (NCQA) should assure that hospitals and other health
care organizations develop continuous quality improvement programs
focusing on genetic testing. Systematic and periodic medical record
review, with feedback to providers, is one means of assuring
appropriate use of genetic tests. Such review should assess the extent
to which providers' records for frequently-ordered predictive genetic
tests are in accord with per-determined criteria. These criteria should
include, but not be limited to, appropriate indications for offering
the test, offering the test when it is indicated, and documentation of:
informed consent when appropriate, the test result, information given
to the patient, and the patient's response. Mechanisms should be in
place to assure that review procedures will not infringe on the
confidentiality of the medical records.
Except when time is of the essence, such as with certain prenatal
genetic tests, obtaining informed consent and actually performing the
test should be
[[Page 4547]]
delayed several days after the test is offered and information given to
the patient. This would give people considering testing the opportunity
to absorb information about the test, contemplate the implications of
testing, and discuss testing with others.
Rare Genetic Diseases
Physicians who encounter patients with symptoms and signs of rare
genetic diseases should have access to the best available information
about rare genetic diseases. This will enable them to include such
diseases in their differential diagnosis, to know where to turn for
assistance in clinical and laboratory diagnosis, and to find
laboratories that test for rare 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. Although
these are issues that relate primarily to the diagnosis of patients
with symptoms and signs, they have major implications for predictive
testing in asymptomatic relatives who may be at risk of disease or who
are carriers of alleles for the disease and whose future children may
be at risk.
The Task Force is aware of a number of efforts to address one or
more of these issues, including the availability of disease-based
databases on research projects by the NIH Office of Rare Diseases
(ORD), on information for consumers and providers by the National
Organization of Rare Disorders, the Alliance of Genetic Support Groups
and its member organizations, and by the American Academy of
Pediatrics, and on clinical laboratories providing tests through the
Helix National Directory (available to providers only). In addition,
the Society for Inherited Metabolic Disorders is compiling information
for providers on diagnostic evaluations of rare disorders, and the ACMG
is developing databases on tests that should be used for diagnosis of
specific disorders.
The Task Force recommends that NIH give ORD a mandate to coordinate
these public and private efforts to improve awareness of rare genetic
diseases. Such coordination is important to avoid unnecessary
duplication, to use expertise most efficiently and to address the
concerns of the various groups. ORD could serve as a gateway for
provider and public inquiries about these disorders.
In cooperation with other organizations, and on a regular basis,
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. Laboratories should notify ORD
about impending cessation of their testing so that provisions for a
transition to other laboratories can be made.
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 if and when their developers leave
the field, and no other laboratory is prepared to offer the test, and/
or the methodology is too complex to be readily adopted by other
laboratories. The Task Force urges that additional funds be
appropriated for ORD to undertake this expanded role.
In accordance with current law, the Task Force is of the opinion
that any laboratory performing any genetic test on which clinical
diagnostic and/or management decisions are made should be certified
under CLIA. If specimens must be sent to a non-CLIA licensed research
facility, the referring physician must be made aware of the
investigative nature of the test.
The Task Force recognizes that the current CLIA certification
process may place a heavy burden on some laboratories doing small
numbers of diagnostic tests for rare diseases. Several laboratories
currently performing these tests are primarily engaged in research,
with the tests stemming from their research efforts. Without
accommodation, some tests may cease to be available. Therefore, the
Task Force recommends that the proposed Genetics Advisory Committee to
CLIAC explore means to simplify compliance with CLIA without
sacrificing quality, just as accommodations have been made for rare
genetic disease testing within the New York State Department of Health
laboratory permit process. Recognizing current deficiencies under CLIA
in the assessment of genetic tests (discussed above), the Task Force
also encourages CAP/ACMG to make its clinical accreditation programs
available to low-volume laboratories that are unaffiliated with a
hospital, and modify its procedures to accommodate such laboratories.
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.
The recommendation made earlier, calling on the CDC to expand its
data monitoring capabilities, is intended to include rare diseases.
Collecting data on rare diseases will require coordinating data from
multiple sources. It is particularly needed to validate tests, describe
the natural history of rare diseases and determine the safety and
effectiveness of interventions to prevent disease or ameliorate its
severity.
(Catalogue of Federal Domestic Assistance Program No. 93.172, Human
Genome Research.)
Elke Jordan,
Executive Secretary, National Advisory Council for Human Genome
Research.
[FR Doc. 97-2286 Filed 1-29-97; 8:45 am]
BILLING CODE 4140-01-P
