Assessing Genetic Risks Implications for Health and Social Policy (1994) / Chapter Skim
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3 Laboratory Issues in Human Genetics
3 Laboratory Issues in Human Genetics
Pages 116-145
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From page 116... ...
Errors have been documented in newborn screening (Holtzman et al., 1986; Hannon and Adam, 1991; Adam and Hannon, 1992) , in biochemical genetic testing (Hommes et al., 1990)
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From page 117... ...
, would not be covered by this definition. Because the field of genetic testing is developing very rapidly, few systematic data are available on how many genetic tests are being done, who is doing them, or how well they are being done (Meaney, 19921.
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From page 118... ...
Only New York State has specific legislation and regulations dealing with laboratories providing the full range of genetic tests, including DNA tests. State Assessments of Laboratories Providing Genetic Tests New York State began mandatory regulation of genetic testing when it established the first program assessment for cytogenetics laboratories in the United States in 1972, with cytogenetics proficiency testing beginning in 1974 (Willey, 19921.
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From page 119... ...
NOTE: Witnesses at the July 23, 1992, hearing included three panels: (1 ) Heidi Hoyt, Washington, D.C., and "Kim" of Illinois (both patients reporting their experiences with genetic testing)
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From page 120... ...
Maryland has regulations requiring genetic testing and screening laboratories to demonstrate "continuing satisfactory performance" in external proficiency testing programs where they exist. The only approved laboratory for newborn screening in Maryland is the state laboratory, which participates in the U.S.
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From page 121... ...
CORN's national proficiency testing programs include alpha-fetoprotein, biochemical genetics, hemoglobinopathies and newborn screening, and most recently, DNA-based tests. The College of American Pathologists developed guidelines, criteria, and methods for quality control and standards for clinical laboratories.
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From page 122... ...
. National Voluntary Biochemical Genetics Laboratory Proficiency Testing Program This voluntary program was established in 1985 by Frits Hommes and the Southeastern Region Genetics Group (SERGG)
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. CDC does run a voluntary proficiency testing program for newborn screening tests discussed below.
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From page 124... ...
Many diagnostic laboratories do not now participate in voluntary quality assurance and proficiency testing in genetics. One incentive for such participation would be to publish the results of voluntary quality evaluations by laboratory name, as is now done by the National Tay-Sachs Disease and Allied Disorders Association, Inc., which publishes results of the quality assessment conducted by the International Tay-Sachs Disease Quality Control Reference Standards and Data Collection Center.
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From page 125... ...
(Some specialties are microbiology, chemistry, pathology, and hematology.) Laboratories must participate in proficiency testing programs for each specialty in which they perform tests and for which proficiency programs have been established.
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From page 126... ...
Moreover, no proficiency testing for cytogenetic laboratories is required, although well-established programs (e.g., New York State and CAP) have been operating for years.
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From page 127... ...
To ensure high quality in'tests for rare disorders that are seldom performed, the genetics community, under CORN and the American College of Medical Genetics, could take the lead in fostering centralization of these tests. Once centralization occurs and the volume of specific tests performed by the central laboratory increases, a stronger argument can be made that external proficiency testing is economical and efficient.
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From page 128... ...
The technologies used for the detection of most disease-related genotypes have not been submitted to FDA; these include biochemical reagents and DNA probes used in tests for CF, Huntington disease, muscular dystrophy, fragile X syndrome, and other disorders. Premarket Approval of Medical Devices Before a medical device can be legally marketed for in vitro diagnostic use, its sponsor (manufacturer, university, or individual scientist)
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From page 129... ...
is reassuringly comprehensive, the FDA could interpret substantial equivalence too broadly, permitting a manufacturer to avoid the premarket approval process by claiming, for instance, that a DNA test marketed to detect sickle cell carriers was substantially equivalent to electrophoretic tests already on the market. Once marketed to detect carriers, the DNA test, unlike the electrophoretic test, could also be used for prenatal diagnosis.
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From page 130... ...
The safety of medical devices must be demonstrated prior to premarket approval, but demonstration of effectiveness can be postponed for 18 months. To qualify, no comparable devices to treat or diagnose the condition can
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From page 131... ...
The committee notes that, for many genetic tests involving direct determination of disease-causing mutations, the only confirmation that is possible is the clinical appearance of the disease, which may not happen until many years after the test is performed. In reply to the committee's inquiries, FDA wrote that obtaining an "approved Investigational Device Exemption (IDE)
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From page 132... ...
Because many new genetic tests will be for rare diseases, the collection of adequate data to establish safety and effectiveness will take a long time, probably longer than the 30-month time limit given by FDA for devices on an accomn~odation list. For tests performed only occasionally, "provisional premarket approval" should be given (see below)
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From page 133... ...
Data on the quality of programs participating in CDC's voluntary program show substantial error rates, in excess of 5 percent false negatives (Holtzman et al., 1986; Adam and Hannon, 19921. CDC has consulted HCFA concerning approval of the CDC newborn screening proficiency testing program as a provider of proficiency testing under CLIA88; at present, CLIA88 regulations cover only one of the ten newborn screening tests, hypothyroidism (using thyroxine and thyroid stimulating hormone)
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None of the current newborn screening tests has gone through the FDA's full premarket approval process. Tests for PKU and congenital hypothyroidism (for which all 50 states screen)
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From page 137... ...
A specific training unit on genetic testing should be included in HCFA's educational training program for inspectors, and the same training should be required of inspectors in agencies deemed by HCFA capable of performing inspections. In addition to these steps, HCFA could determine that existing proficiency programs for genetic tests satisfy its standards; HCFA could deem these proficiency testing programs to be required by laboratories providing those tests until such time as other programs are developed (see previous section on voluntary programs and Box 3-2 in this chapter)
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From page 138... ...
HCFA should examine the proficiency testing programs for genetic screening tests described earlier in this chapter and, if they meet its criteria, deem them acceptable. The committee recommends that HCFA create a new specialty of clinical genetics into which it can incorporate the existing subspecialty of clinical cytogenetics, and also create new subspecialties of biochemical and molecular genetics.
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From page 139... ...
should be provided by the manufacturer of genetic test kits through the laboratory from which the physician orders the test. Ensuring the Safety of New Tests Because genetic tests seldom will have perfect sensitivity or specificity, particularly when used for predictive purposes, because of the novelty of some genetic testing technologies, and because of the possibilities of misinterpretation of test results, full premarket approval is needed for all new genetic tests; that is, genetic tests should be in Class III.
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From page 140... ...
Once provisional premarket approval has been granted, however, the laboratories performing the test could charge a fair market price for the device or test kit. The committee recommends that people receiving the test during this provisional period be informed that the safety and effectiveness of the test have not
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From page 141... ...
IRBs used by commercial organizations should also have a broad, unbiased membership. Compliance with FDA requirements for premarket approval and approved investigational device exemption is essential to ensuring safe and effective use of a genetic test, just as compliance with CLIA88 is essential for any laboratory performing genetic tests for clinical purposes.
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From page 142... ...
To speed the widespread availability of investigational devices of limited marketability, FDA should grant provisional premarket approval, as described earlier, when adequate preliminary evidence of safety and effectiveness has been collected. In addition, the NIH and private funding agencies should support meritorious studies designed to assess the safety and effectiveness of investigational genetic testing devices.
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From page 143... ...
In addition, the Clinical Laboratory Improvement Advisory Council should appoint a subcommittee on genetics to make recommendations on improving the quality of laboratories performing genetic tests under CLIA88. REFERENCES Adam, B., and Hannon, W
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From page 144... ...
1991. Identified problems found in the voluntary newborn screening proficiency testing program conducted by the Centers for Disease Control.
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1992b. Testimony on genetic testing before House Subcommittee on Human Resources and Intergovernmental Relations, Committee on Government Operations, U.S.
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