[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 <a href="http://
ww2.med.jhu.edu/tfgtelsi">http://
ww2.med.jhu.edu/tfgtelsi</a>.

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 href="/cdn-cgi/l/email-protection#b0c4d6d7c49dbad1f0c7d5dcd3d8dcd9dedb9ec7d5dcd3d89edad8c59ed5d4c5">tfgt-
<span class="__cf_email__" data-cfemail="c4a584b3a1a8a7aca8adaaafeab3a1a8a7aceaaeacb1eaa1a0b1">[email protected]</span></a>. 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.

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    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.
    <bullet> 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.
    <bullet> 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.
    <bullet> 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.
    <bullet> 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

    <bullet> 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.
    <bullet> 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

    <bullet> 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

    <bullet> 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

    <bullet> 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

    <bullet> 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.
    <bullet> 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.
    <bullet> 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

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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.
    <bullet> 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.
    <bullet> 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:
    <bullet> 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.
    <bullet> 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.
    <bullet> 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


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