Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Save to My Library
Look up keyword
Like this
0Activity
0 of .
Results for:
No results containing your search query
P. 1
Genetic Testing and Issues of Ethics, Accuracy, and Usefulness.pdf

Genetic Testing and Issues of Ethics, Accuracy, and Usefulness.pdf

Ratings: (0)|Views: 1 |Likes:
Published by pieterinpretoria391
Genetic Testing and Issues of Ethics,
Accuracy, and Usefulness
Genetic Testing and Issues of Ethics,
Accuracy, and Usefulness

More info:

Categories:Types, Research
Published by: pieterinpretoria391 on Apr 08, 2013
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

04/08/2013

pdf

text

original

 
lab
oratory
med
icine
>july
2002
>
number7
>
volume33
©
501
featurefeature
Genetic Testing and Issues of Ethics, Accuracy, and Usefulness
Frances Katz
Genetic Testing and Issues of Ethics, Accuracy, and Usefulness
Frances Katz
Despite continuing conversations about the pros and consof genetic testing, a number of tests are in active use by clinicians ...Despite continuing conversations about the pros and consof genetic testing, a number of tests are in active use by clinicians ...
 
lab
oratory
med
icine
> july
2002
>
number7
>
volume33
502
©
̇
feature
̈
Many genetic tests are performed at specialized laborato-ries; by June 2002, there were 534 specialized laboratories thattested for 933 diseases.
1
Most of this activity has been generatedwithin the last decade and a half, beginning roughly with thedetermination in 1989 that tendencies for cystic fibrosis (CF)could be identified. In 1991, the American College of MedicalGenetics (ACMG) was incorporated to give national representa-tion to the providers of genetic services and patients with geneticdisorders and to speak for the emerging specialty of medical ge-netics in organizations and agencies concerned with medicalservice, certification, and regulatory issues. By 1996, the ACMGhad gained full membership in the American Medical Associa-tion (AMA) House of Delegates, and the AMA had passed thelaboratory current procedural terminology (CPT) codes.
2
Concerns about how genetic tests might be used triggeredthe formation of the Task Force on Genetic Testing, created bythe National Institutes of Health - Department of Energy Work-ing Group on Ethical, Legal, and Social Implications of HumanGenome Research. This group started meeting in 1991 and pub-lished its final report in September of 1997. The 80-page reportaddressed the need for ensuring safety and effectiveness of newgenetic tests, ensuring the quality of laboratories performing ge-netic tests, and improving providers’understanding of genetictesting.
3
The group was drawn from organizations with a stakein genetic testing. This group invited 5 agencies within the De-partment of Health and Human Services (HHS) to send nonvot-ing liaison members to the Task Force.One of the early realizations of the Task Force was that thegap between the cutting edge and the usefulness of geneticstests would have to be managed. The report states that “in thenext few years, a greater burden for offering genetic testingwill fall on providers who have little formal training or experi-ence in genetics.” There are more providers with broaderknowledge in 2002, and the understanding of the relationshipbetween genes and disease has improved greatly since 1997.However, as the baseline knowledge moves rapidly, test devel-opment is under pressure to keep up. The focus of the Task Force was to recommend policies to reduce the likelihood of damaging effects from genetic tests.At the same time that the federal agencies were developingpolicies on genetics testing and the various concerns of theirconstituents were becoming clearer, advisory committees suchas the SACGT (Secretary’s Advisory Committee on GeneticTesting) were also being formed. State governments were alsobecoming active, passing laws and recommendations across thespectrum of genetic testing and its impact on employment, insur-ance, and health care.In 1998, SACGT included 13 members and made recom-mendations on issues including the oversight of genetic testing,patent issues affecting genetic testing, and genetic non-discrimination legislation. The report of the advisory commit-tee was issued in July 2002, with requests for public commentspublished in the Federal Register on December 7, 2000.Thirty-four comments were received by the group anddiscussed at the February 2001 meeting; most questions dealtwith the appropriateness of the criteria and issues regardingclassification.The recommendations were made before the humangenome mapping was completed. Genetic tests were defined bythe Task Force to mean the analysis of human DNA, RNA, chro-mosomes, proteins, or other gene products to detect disease-re-lated genotypes, mutations, phenotypes, or karyotypes forclinical purposes. Such purposes include prediction of diseaserisks, identification of carriers, monitoring, diagnosis or progno-sis, and establishing genetic identity. These clinical purposes donot include tests conducted purely for research. Although familyhistory can be a very important screening tool to determine theneed for genetic testing, this was not included in the definitionof a genetic test.The Task Force expressed concerns about predictive uses of genetic tests performed in healthy or apparently healthy people orfetuses for the purpose of determining the presence of alterationsthat are associated with an increased risk of disease. Becausemany genetic tests to diagnose disease in symptomatic individualscan also be used to predict disease in healthy individuals, it wasdifficult to limit discussion about the validation, quality, or deliv-ery of genetic tests only to their predictive uses. The Task Forcerecommended excluding tests for somatic cell mutations unlesssuch tests are capable of detecting germline mutations.The SACGT developed a document, issued on August 4,2000, titled “Development of a Classification Methodology forGenetic Tests: Conclusions and Recommendations of the Sec-retary’s Advisory Committee on Genetic Testing.”
4
The docu-ment listed methodologies based on 4 criteria that would placegenetic tests into 2 levels of review. The criteria were: test vol-ume, whether the test would be used for population-based test-ing, whether the test is diagnostic or predictive; the availabilityof an intervention, the predictive value of the test, and the po-tential for medical or social harm associated with the test. Dur-ing SACGT’s February 2001 meeting, the Food and DrugAdministration’s (FDA) plans for pre-market review of genetictests was presented. Further information on FDA’s pre-marketactivity for tests was presented during the May 2001 SACGTmeeting, and the advisors concluded that the classification ac-tivity should remain inactive.
Genetic Tests Today 
A large number of genetic tests are being used for a wide vari-ety of applications. There are a number of consensus statementsregarding certain tests that have been developed and published bythe ACMG. These include:
Statement on Use of Apolipoprotein E Testing for  Alzheimer’s Disease
The conclusion was that at the present time it is not recom-mended for use in routine clinical diagnosis nor should it beused for predictive testing. Studies to date indicate that theapolipoprotein E (APOE) genotype alone does not provide suffi-cient sensitivity or specificity to allow genotyping to be used asa diagnostic test. Because Alzheimer’s disease develops in the
 
absence of APOE epsilon-4 and because many with APOE ep-silon-4 seem to escape disease, genotyping is not recommendedfor use as a predictive genetic test. The results of a collaborativestudy under way will clarify some of these issues. WhetherAPOE genotypes have other uses in the management of Alzheimer’s diesease will become apparent over the next fewyears. Published in
 JAMA
, 1995.
Genetic Susceptibility to Breast and Ovarian Cancer: Assessment, Counseling, and Testing Guidelines
These Guidelines were published in 1999 by the ACMG,funded by a grant from the New York State Department of Health to the ACMG foundation.
Laboratory Standards and Guidelines for Population-Based Cystic Fibrosis Carrier Screening
The committee recommends that CF carrier screening beoffered to non-Jewish Caucasians and Ashkenazi Jews, and bemade available to other ethnic and racial groups who will be in-formed of CF detection possibility through educationalbrochures, the informed consent process, and/or other efficientmethods. For example, Asian-Americans and Native Americanswithout significant Caucasian admixture should be informed of the rarity of the disease and the very low yield of the test in theirrespective populations. Testing should be made available toAfrican-Americans, recognizing that only about 50% of at-risk couples will be detected. An educational brochure and a consentform which recites this information, as well as a sign-off forthose choosing not to be tested after reading these materials, wasprepared by the Working Group on Patient Education andInformed Consent. The recommendation was that preconceptiontesting be encouraged whenever possible, although it was alsorecognized that for practical purposes, testing will often onlyoccur in the prenatal setting.
Statement on Factor V Leiden Mutation Testing
Which methodology should be used: factor V Leiden DNAtesting or functional activated protein C (APC) resistance test-ing? When appropriate clinical care requires testing for the fac-tor V Leiden allele, either direct DNA-based genotyping or aLeiden-specific functional assay is recommended. Patients whotest positive by a functional assay should then be further studiedwith the DNA test for confirmation and to distinguish heterozy-gotes from homozygotes. Patients on heparin therapy or withknown lupus anticoagulant should proceed directly to moleculartesting if the modified functional assay is not used. When rela-tives of individuals known to have factor V Leiden are tested,the DNA method is recommended. Opinions and practices re-garding factor V Leiden testing vary. Some physicians advocatetesting of all patients with venous thrombosis except when ac-tive malignancy is present. Other physicians exclude testing of patients over the age of 60 in the absence of a family history of thrombosis or a previous thrombotic event. There is growingconsensus that testing should be performed in at least the follow-ing circumstances (these are the same general recommendationsfor testing for any thrombophilia): age <50; any venous throm-bosis; venous thrombosis in unusual sites (such as hepatic,mesenteric, and cerebral veins); recurrent venous thrombosis;venous thrombosis and a strong family history of thromboticdisease; venous thrombosis in pregnant women or women takingoral contraceptives; relatives of individuals with venous throm-bosis under age 50; myocardial infarction in female smokersunder age 50.Testing may also be considered in the following situations:venous thrombosis, age >50, except when active malignancy ispresent; relatives of individuals known to have factor V Leiden;or knowledge that they have factor V Leiden may influencemanagement of pregnancy and may be a factor in decision-mak-ing regarding oral contraceptive use. Women with recurrentpregnancy loss, unexplained severe preeclampsia, placentalabruption, intrauterine fetal growth retardation, or stillbirth arerecommended for testing. Knowledge of factor V Leiden carrierstatus may influence management of future pregnancies. Ran-dom screening of the general population for factor V Leiden isnot recommended.
Technical and clinical assessment of fluorescence insitu hybridization (FISH): an ACMG-ASHG positionstatement
5
The conclusions of the Test and Technology Transfer Com-mittee, accepted by the ACMG Board of Directors (March2000), is that FISH testing be considered a highly useful andaccurate test for the diagnosis of microdeletion and for the iden-tification of unknown material in the genome. In disorders inwhich FISH testing provides results not possible from standardcytogenetic testing, the testing is stand-alone and should be ac-cepted as such. Microduplication analysis can be a useful test fordisorders in which tandem duplication is among the mutation
lab
oratory
med
icine
> july
2002
>
number7
>
volume33
503
©
̇
feature
̈
[
I
1
] Scientist Viktor Barski of the Russian Engelhardt Institute of MolecularSciences studies the computer data from an Argonne-developedmicrochip used to speed sequencing of the human genome.
Photocourtesy of Argonne National Laboratory.

You're Reading a Free Preview

Download
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->