Genomic resource centre

Case Study: United States of America

Situation

The United States of America stands as a leader in genetic testing - but with the blessings of an increasingly accurate and broad range of genetic tests comes the responsibility to provide oversight for these tests. As such, the United States must be particularly vigilant with regard to quality; to accomplish this task, it has involved a wide variety of public and private sector entities to develop a national framework of quality assurance for genetic testing. The United States also faces the issue of quality within the context of a nation that does not have universal health coverage. Improving equity in the American healthcare system at large underlies the issue of quality throughout healthcare delivery, and hence is an issue for potentially expensive genetic tests. In response, mechanisms for equitable access and improved quality assurance for genetic tests are being considered and developed in the United States.

Already, genetic testing is a major element within healthcare in the United States. The European Commission reported in September 2003 that the National Institutes of Health (NIH)-funded directory for laboratories performing genetic tests, "Genetests", had nearly 650 types of genetic tests, whereas only 273 were reported by the UK Genetic Testing Network (UKGTN). That number was 711 as of May 2004, which does not include the 340 tests that are being used for research only [1,2]. It has been noted that genetic test usage is on the rise, at nearly a 30% increase annually, with 175,000 tests being performed in 1996; that number is likely to be far greater now [3].

Regulation of genetic testing laboratories is currently under the umbrella of the Clinical Laboratory Improvement Amendments (CLIA), which extends federal regulation over nearly all US clinical laboratories. CLIA requires laboratories to participate in quality control and quality assurance schemes, provides some proficiency testing, though not for genetic testing, and requires laboratory inspections [4]. CLIA does not currently have a genetics specialty, because at the time of CLIA's development genetic testing was not clinically advanced [5]. While CLIA is responsible for most oversight within laboratory testing, some states perform their own proficiency evaluations. Currently, the quality of genetic testing kits manufactured external to the clinical laboratory (i.e. tests that are purchased by the clinical laboratory from an outside provider) are regulated by the United States Food and Drug Administration (FDA). Genetic tests developed "in-house" (i.e. within the clinical laboratory) are subject to FDA regulation as well, though the FDA has not yet chosen to enforce regulations on these tests. Reagents used to create these tests are, however, being regulated, and the marketing of these "home-brews" directly to consumers is prohibited.

Laboratories may conduct voluntary genetic testing proficiency evaluations through professional organizations such as the College of American Pathologists (CAP) College of American Pathologists (CAP) or the American College of Medical Genetics (ACMG). In 1997, the National Institutes of Health Department of Energy (NIH-DOE) Task Force on Genetic Testing reported that approximately 85% of genetic testing laboratories participated in these schemes [6]. CAP and others have formulated guidelines for best practices for laboratories performing these tests. Similar professional organizations, such as the American Society of Human Genetics and the National Society of Genetic Counselors (NSGC), along with patient advocacy groups and others, have developed standards for clinical geneticists concerning informed consent, counselling practices, appropriateness of tests, and other issues.


Challenges

The 1997 NIH-DOE report on genetic testing noted several areas of quality assurance within genetic testing that needed improvement, acknowledging that current oversight was not sufficient to provide adequate quality control in genetic testing [6]. The concerns mentioned in the report vary, but issues of test development, quality within both the clinical setting and the laboratory, and rare disorders are the focus. Nevertheless, the report stresses overarching principles of ensuring informed consent, maintaining confidentiality, and protecting against possible genetic discrimination.

There is contention about the state of quality assurance within genetic testing laboratories. In 1999, a survey of 245 genetic testing laboratories was conducted in order to evaluate the current state of genetic testing quality assurance within laboratories in the United States [3]. Among other things, the report indicated that several laboratories may have inadequate quality standards, according to responses gleaned from questions about common laboratory procedures and setup. However, the results of a similar, second survey were published that same year, which indicated that poor health outcomes resulting from these tests were very low, and those that occurred tended to occur in pre-testing phase (i.e. prior to laboratory analysis), not in the laboratory [7]. Information about failures within the clinical phase are not as readily available; nevertheless, there have been some indications that procedures are sometimes performed inappropriately - for example, some prenatal screening for cystic fibrosis may be performed without inappropriate consideration of the risk posed by amniocentesis to a developing fetus [8].

The Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS), previously called the Secretary’s Advisory Committee on Genetic Testing (SACGT), was formed in response to the NIH-DOE report on genetic testing. This body, which has been the guiding policy body for oversight in genetic testing, has very recently begun drafting a report on its priorities, listing "genetic non-discrimination legislation and the development of recommendations on coverage and reimbursement of genetic technologies and services" as its highest priorities [9]. Though it is not yet clear whether unequal access to genetic tests has already had an impact in the United States, inequalities within the American healthcare system in general are widely acknowledged and will certainly have an impact on genetic testing accessibility [10].


Solutions

Among the recommendations of the Task Force was one to the Clinical Laboratory Improvement Advisory Committee (CLIAC) to study relevant quality issues in genetic testing and to consider the development of a genetic testing specialty under CLIA. In response, CLIA filed a notice of intent with the Federal Register in 2000 to create the specialty; however, it does not appear that this specialty has yet been put into affect [11].

In 1999, The Centers for Disease Control and Prevention's Public Health Practice Program Office, Division of Laboratory Systemsdeveloped recommendations for quality assurance of genetic tests, primarily at the analytic phase (i.e. the phase which takes place in the laboratory itself). These recommendations included a call for further research to create standardized samples for quality assurance and proficiency testing, the development of supplementary proficiency evaluation programs to supplement existing ones, the establishment of disease-specific consortia for networking and information transmission, creation of a database for laboratory issues related to genetic testing, and support of training programs for those involved with genetic testing [12,13]. Further analysis is warranted to discover to what extent these recommendations have been implemented.

The SACGT formulated a number of recommendations pertaining to the quality of genetic tests, acknowledging the many sides of this issue, and describing various organizations that play a part in assuring quality [14,15]. Now, as the SACGHS, the committee has begun work on reports on direct-to-patient sale of genetic tests, education in genetics, and coverage and reimbursement of genetic technologies. Additionally, the SACGHS has acknowledged issues such as pharmacogenomics and patent as important within the sphere of quality assurance [9].


Conclusion

As the potential of genetic testing and genomics unfolds, the United States will likely find itself on the cutting edge of regulation. Already, laboratories in the United States can perform the greatest variety of genetic tests worldwide, but it remains to be seen how well these tests will be evaluated. While other nations must often cut across international borders to increase the variety of testing samples for a laboratory to make a genetic test available to a patient (European countries, for example), the United States seems to have a marked advantage because it does not have neither national barriers to hurdle, nor differing regulatory frameworks to overcome. However, it also appears that fundamental inequities in the US healthcare system may handicap efforts to insure equality and non-discrimination in genetic tests.

Likely, the way quality assurance develops in the United States will have an effect internationally, as evidenced by the many foreign laboratories that currently participate in CAP quality assurance schemes and list themselves in United States directories like "Genetests" [2,16]. This may grant impetus to the United States to expand its existing quality assurance programs in locations that do not have access to adequate quality assurance schemes, as well as to extend the United States' laboratory network to more foreign laboratories. The United States, in any case, must be a part of international dialogue concerning genetic testing; as issues that are inherently international in focus become increasingly prominent, the United States will likely play a leading role in the creation of standards.

It is worth noting that ongoing discussions about quality assurance have taken place through the SACGT and now through SACGHS, including, among other things, on how tests developed by clinical laboratories themselves, should be regulated by the FDA and how tests should be classified and summarized for the administering physicians [17]. The Secretary's Committee has committed to a wider perspective on the societal implications of genetic testing, which will likely become increasingly necessary as genetic tests grow in their impact and complexity. It is difficult to predict how successful these efforts to ensure quality will be, especially in light of the lack of knowledge about the efficacy of policy decisions surrounding previously addressed quality concerns of somewhat lesser scope, such as laboratory procedures and ensuring proper genetic counselling. Nevertheless, as genetic testing becomes a more powerful and common clinical tool, so must analysis and regulation of quality grow to examine and control genetic testing's expanding societal impact.


References

  • Ibarreta D, Bock AK, Klein C et al. Towards Quality Assurance and Harmonisation of Genetic Testing Services in the EU. European Communities. Available at: http://www.jrc.es/home/publications/publication.cfm?pub=1124 Accessed May 25th 2004.
  • www.genetests.com
  • McGovern MM, et al. Quality Assurance in Molecular Genetic Testing Laboratories. Jama. 1999;281:835-840. - says something about increasing numbers of genetic tests.
  • Organization for Economic Co-Operation and Development. Genetic Testing: Policy Issues for the New Millennium. Paris: Organization for Economic Co-Operation and Development. 2000.
  • Schwartz MK. Genetic Testing and the Clinical Laboratory Improvement Amendments of 1988: Present and Future. Clin Chem. 1999;45:739-745.
  • Holtzman NA, Watson MS, eds. Promoting Safe and Effective Genetic Testing in the United States: Final Report on the Task for on Genetic Testing. Washington, DC: 1997. Available at: http://www.genome.gov/10001733 Accessed May 11th 2004.
  • Hofgartner WT, Tait JF. Frequency of problems during clinical molecular-genetic testing. Am J Clin Pathol. 1999;112:11-3.
  • Concar, D. Test Blunders Risk Needless Abortions. New Scientist, 2003. May: 4-6.
  • Drafts Availble at: http://www4.od.nih.gov/oba/SACGHS/meetings/June2004/SACGHSJun2004.htm Accessed May 20th, 2004.
  • Cohen JJ. Disparities in Health Care: An Overview. Acad Emerg Med. 2003 10:1155-60.
  • United States Department of Health and Human Services. Notice of intent: genetic testing under the Clinical Laboratory Improvement Amendments. Fed Regist 2001 65: 25928-25934.
  • Williams LO, Cole EC, Lubin IM, et al. Quality Assurance in Human Molecular Genetics Testing. Arch Pathol Lab Med. 2003;127:1353-1358.
  • Williams LO, Cole EC. General Recommendations for Quality Assurance Programs for Laboratory Molecular Genetic Tests, Final Monograph. Atlanta: Division of Laboratory Systems, Public Health Practice Program Office, Centers for Disease Control and Prevention. Available at: http://www.phppo.cdc.gov/dls/pdf/genetics/dyncor.pdf. Accessed May 18th 2004.
  • United States Department of Health and Human Services, Secretary's Advisory Committee on Genetic Testing. Enhancing the Oversight of Genetic Tests: Recommendations of the SACGT. Available at: http://www4.od.nih.gov/oba/sacgt/sacgt.htm. Accessed May 19th 2004.
  • United States Department of Health and Human Services, Secretary's Advisory Committee on Genetic Testing. A Public Consultation on the Oversight of Genetic Tests. Available at: http://www4.od.nih.gov/oba/sacgt/sacgt.htm. Accessed May 19th 2004
  • Cox SM, Faucett WA, Chen B et al. International Genetic Testing. Gen in Med. 2003;5:176-182
  • http://www4.od.nih.gov/oba/sacgt/sacgtmtg.htm
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