[Federal Register Volume 65, Number 239 (Tuesday, December 12, 2000)]
[Notices]
[Pages 77631-77633]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-31523]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


Secretary's Advisory Committee on Genetic Testing

AGENCY: Office of the Secretary, DHHS.

ACTION: Request for public comment on a proposed template of genetic 
test information for use by health professionals.

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SUMMARY: The Secretary's Advisory Committee on Genetic Testing (SACGT) 
was chartered to advise the Department of Health and Human Services on 
the medical, scientific, ethical, legal, and social issues raised by 
the development and use of genetic tests. SACGT recently completed its 
first report, Enhancing the Oversight of Genetic Tests (available at 
http://www4.od.nih.gov/oba/sacgt.htm). SACGT stated in the report's 
overarching principles that genetics education of health professionals 
and the public about the appropriate use, interpretation, and 
understanding of genetic test results is critical to the successful 
implementation of genetic testing into health care.
    To inform and educate health professionals on genetic testing and 
their appropriate uses, SACGT is developing a template of essential 
information elements about genetic tests. A SACGT working group, 
composed of SACGT members and ad hoc experts, identified seven key data 
elements about a genetic test that may be valuable to health 
professionals considering using a genetic test for patient care. At its 
November 2-3, 2000 meeting, SACGT reviewed the proposed genetic test 
information template and recommended public comment be solicited. After 
consideration of public comments, SACGT's final draft of the template 
will be submitted to the Assistant Secretary of Health for transmittal 
to the Secretary of Health and Human Services.

DATES: The public is encouraged to provide written comments on the 
proposed genetic test information template by January 31, 2001. The 
following mailing address should be used: SACGT, National Institutes of 
Health, 9000 Rockville Pike, Building 1, Room 103, Bethesda, Maryland, 
20892. SACGT's facsimile number is 301-496-9839. Comments can also be 
sent via e-mail to [email protected]. All public comments received will 
be available for public inspection at the SACGT office between the 
hours of 8:30 a.m. and 5:00 p.m.

FOR FURTHER INFORMATION: Questions about this request for public 
comment can be directed to Dr. Susanne Haga, by e-mail 
([email protected].) or telephone (301-496-9838). The proposed template 
will also be posted on SACGT's website for review and comment.

SUPPLEMENTARY INFORMATION: Decades of genetics research have brought 
about many important medical and public health advances. The pace of 
discovery

[[Page 77632]]

in this area has enabled scientists to make rapid progress in 
understanding the role of genetics in many common yet complex diseases 
and conditions, such as heart disease, cancer, and diabetes. It also 
has increased knowledge that may lead to the development of new tests 
to identify these disease conditions in individuals, sometimes before 
symptoms occur. According to GeneTests, a genetic testing laboratory 
directory, genetic testing is clinically available for more than 400 
diseases or conditions in more than 200 laboratories in the United 
States, and investigators are exploring the development of tests for an 
additional 338 diseases or conditions. However, most of the current 
genetic testing is for single gene disorders such as Huntington disease 
and cystic fibrosis.
    Genetic tests can be performed for a number of purposes. Moreover, 
a test can be used in more than one way, such as when a test used for 
diagnostic purposes is also used to predict risk of disease. SACGT 
included the following types of testing within its definition: (1) An 
analysis performed on human DNA, RNA, genes, and/or chromosomes to 
detect heritable or acquired genotypes, mutations, phenotypes, or 
karyotypes that cause or are likely to cause a specific disease or 
condition; and (2) the analysis of human proteins and certain 
metabolites, which are predominantly used to detect heritable or 
acquired genotypes, mutations, or phenotypes. The purposes of both 
these types of genetic tests include directing clinical management, 
screening of newborns, predicting risks of disease, identifying 
carriers, and establishing prenatal or clinical diagnoses or prognoses 
in individuals, families, or populations. Not included in this 
definition are tests that are used primarily for other purposes, but 
that may contribute to diagnosing a genetic disease (e.g., blood smear, 
certain serum chemistries), and tests conducted exclusively for 
forensic identification purposes.
    In the past, many tests were developed to detect or confirm rare 
genetic diseases. More recently, tests have been developed to detect 
mutations that may be involved in or contribute to more common, complex 
conditions (such as breast, ovarian, and colon cancer and 
cardiovascular disease), the effects of which generally do not appear 
until later in life. Optimally, these tests are used to predict a 
person's predisposition to disease where there is a family history of 
the disease, and, in general, such tests are not recommended for 
individuals without such a history. However, in the future, the use of 
predictive tests may expand and be offered to individuals without a 
family history of certain diseases and conditions, e.g., common adult-
onset disorders.

Proposed Template of Genetic Test Information

    Due to the wide range of genetic tests, their multiple uses and 
complexities, and the rapidity with which they are being developed and 
introduced into clinical practice, health professionals should be 
knowledgeable about the basic elements of a genetic test to ensure 
their appropriate use. A SACGT working group developed a template of 
seven key essential data elements about genetic tests that could serve 
as a framework for an informational fact sheet. This fact sheet would 
be analogous to reference books or fact sheets describing intended 
uses, risks, and benefits of drugs for health professionals. Fact 
sheets for genetic tests could help encourage important information 
exchanges between health professionals who order genetic tests and 
laboratorians who provide the testing services. Information that is 
known about a genetic test in these seven areas should be included or 
referenced on the fact sheet. Equally important, when data are not 
available for a given element, the absence of such data should be 
specifically noted. It will also be important for the fact sheets to be 
updated periodically to reflect new scientific or clinical data. If the 
Food and Drug Administration (FDA) or other oversight bodies become 
involved in the review of genetic tests prior to clinical introduction, 
the approved claims of the test should be stated as well.
    The seven elements relate to the following areas: purpose of the 
test; clinical condition for which the test is performed; definition of 
the test; analytical validity, clinical validity, and clinical utility 
of the test; cost of the test and billing/reimbursement information. 
The seven elements are described in detail below along with the 
proposed sources for each element.
    A. Purpose of the Test. SACGT proposes that the purpose of the test 
and the appropriate settings for offering the test should be clearly 
described. Examples of categories of test purposes could include 
predictive, carrier, prenatal, preimplantation, newborn, and diagnostic 
testing. Each category of test use represents a different test, even 
when the laboratory measurement(s) are the same. Therefore, all 
appropriate categories should be clearly described.
    SACGT suggests that the laboratory providing the testing services 
should define the proper use of the test. Peer-reviewed literature as 
well as the laboratory's own data should be used to substantiate the 
appropriateness of the intended use(s) of a test. In addition, relevant 
clinical, professional, and health policy communities and government 
agencies should contribute to defining the appropriate uses of genetic 
tests through the development of practice standards and guidance 
documents.
    B. Clinical Condition for Which Test is Performed. SACGT recommends 
that the clinical condition for which the test is to be performed be 
described. The prevalence or incidence of the disease or condition, its 
clinical manifestations, and prognosis to the extent known should be 
included in the description of the clinical condition. The testing 
laboratory should cite the clinical condition as part of its 
description of the intended use(s) of the test. Peer-reviewed 
literature should be referenced as appropriate. In addition, relevant 
clinical, professional, and health policy communities and government 
agencies should contribute to describing clinical manifestations, 
prevalence, and prognosis as appropriate.
    C. Definition of Test. SACGT proposes that the specific laboratory 
measurement(s) of the test, e.g., specific mutation, metabolite, enzyme 
activity, be described in the information template for health 
professionals. The description should be written in a language that 
would be understandable to non-laboratorians. A description of what the 
test measures may also assist health professionals in interpreting the 
results.
    D. Analytical Validity. SACGT recommends that information regarding 
the analytical validity of a test be provided in the information 
template to health professionals. SACGT believes that a genetic test 
should demonstrate analytical validity before the test is used for 
clinical purposes. Analytical validity is defined as the ability of a 
test to measure or detect the analyte it is intended to measure or 
detect. An analyte is defined as the substance measured by a laboratory 
test, e.g., DNA--mutation, allele, or chromosome, metabolites, or 
enzyme activity. Analytical validity includes analytical sensitivity 
(the probability that a test will detect an analyte when it is present 
in the sample) and analytical specificity (the probability that a test 
will be negative when an analyte is absent from a sample). Health 
professionals as well as patients should know whether a test can 
accurately detect the presence or absence of its intended target.
    SACGT proposes that the laboratory providing the testing services 
supply specific information related to its assay.

[[Page 77633]]

As with other elements, peer-reviewed literature may be referenced to 
substantiate claims of test performance.
    E. Clinical Validity. SACGT proposes that information on the 
clinical validity of a test be provided to health professionals. SACGT 
defines clinical validity as the accuracy with which a laboratory 
measurement predicts the presence or absence of a clinical condition. 
For diagnostic, prenatal, and carrier tests, accuracy could be 
expressed as clinical sensitivity (the probability a person with the 
disease, or who will get the disease, will have a positive result), 
clinical specificity (the probability that a test will be negative in a 
person who does not have or will not get the disease), positive 
predictive value (the probability that a person with a positive result 
has, or will get, the disease), and negative predictive value (the 
probability that a person with a negative test result does not have, or 
will not get, the disease). For predictive tests, SACGT proposes to 
define accuracy as the prediction of expressivity (the range of 
phenotypes associated with positive and negative test results) and age-
related penetrance (likelihood of disease at a given age in test-
positive individuals). In addition, health professionals should be made 
aware of other factors, such as environment or lifestyle, that may 
influence the development or prognosis of a disease or condition in an 
individual with a positive test result, as they may assist in their 
clinical management approaches.
    SACGT suggests that the testing laboratory should define clinical 
validity as relevant to the proposed uses of the test. Peer-reviewed 
literature as well as the laboratory's own data should be used to 
substantiate the claims of clinical validity of the test. Information 
about the clinical validity should include, as necessary, a statement 
about the limitations of the available data. For example, if a test has 
been evaluated in only high-risk families, the absence of population-
based data should be noted. More detailed consideration of clinical 
validity through research studies and clinical experience may 
contribute to the development of practice standards over time by the 
professional, medical, and health policy communities.
    F. Clinical Utility. SACGT proposes that information relating to 
the clinical utility of a test be provided to health professionals. 
SACGT defines clinical utility as the contribution of the test result 
to improved outcome in the person tested. Clinical utility usually 
reflects the efficacy of clinical interventions for persons with 
positive test results. However, even when no interventions are 
available to treat or prevent the disease or condition, there may be 
other benefits associated with the knowledge of positive or negative 
test results.
    If a clinical intervention is available for individuals who test 
positive for the disease or condition, this information should be 
provided to health professionals, along with the level of evidence 
regarding its efficacy. Other potential benefits associated with the 
knowledge of test results should also be described.
    SACGT has not identified a specific source that would be 
responsible for providing information related to clinical utility. 
References to peer-reviewed literature or contact information for 
professional or patient advocacy organizations in the relevant field 
could be listed. Health professionals should also be active in 
investigating possible clinical interventions or preventive strategies. 
In-depth consideration of clinical utility through research studies and 
clinical experience will contribute to the development of practice 
standards and guidelines over time by professional medical and health 
policy communities and patient and disease advocacy organizations.
    G. Cost of Test and Billing/Reimbursement Information. SACGT 
suggests that the testing laboratory provide information to health 
professionals on the cost of the test. At present, some genetic tests 
are very expensive, though, as technology advances and the use of these 
tests increases, it is expected that costs will decrease. If possible, 
the laboratory could also provide any information on billing and 
reimbursement policies for the test. For example, the laboratory may 
indicate which CPT codes should be used for billing purposes. In 
addition, since patients may wish to pay for the test directly due to 
concerns related to the confidentiality and privacy of test results, 
information on direct payments should be included. SACGT recognizes 
that laboratories may have limited information regarding reimbursement 
policies since these are variable and often decided over time by third-
party payors. Many health insurers provide information on their 
reimbursement policies via their web-site or customer information 
services.

Questions on Which Comment Is Being Solicited

    1. Do the proposed elements sufficiently address the relevant 
information that should be made available to health professionals about 
a genetic test? Are there other elements that should be added to the 
template? If so, please define the element and propose a specific 
source for the element.
    2. Are the proposed sources of information appropriate for each 
element?
    3. Who should provide information regarding the clinical utility of 
a genetic test?
    4. Would this information template be useful to you? If so, how?
    5. How would this information best be disseminated to health 
professionals?
    6.If FDA becomes involved in the oversight of genetic tests, much 
of the content of the proposed fact sheets will be considered during 
FDA's review process. In the interim, what other review mechanisms 
should be considered to ensure the accuracy of the material provided in 
the information sheets?

    Dated: December 6, 2000.
Sarah Carr,
Executive Secretary, Secretary's Advisory Committee on Genetic Testing.
[FR Doc. 00-31523 Filed 12-11-00; 8:45 am]
BILLING CODE 4140-01-P