Many genetic tests are performed at specialized laborato-ries; by June 2002, there were 534 specialized laboratories thattested for 933 diseases.
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.
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.
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.”
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