Case Study: European Union
The European Union faces the dual challenge of developing adequate standards for genetic testing while bridging national, social, and linguistic differences. Accordingly, the best description of the current quality assurance situation in the European Union is one of fragmentation; national policies differ widely on areas such as requirements for laboratory accreditation, clinical genetic requirements, and novel genetic test evaluation. Given the number and diversity of countries in the EU, it is understandably difficult to come to a consensus about how to synchronize quality assurance of genetic tests. The challenge for Europe appears to be one of harmonizing standards, so that not only are all genetic tests in the EU held to certain minimum standards, but laboratories performing genetic tests can also collaborate on issues such as best practices and rare genetic diseases across national borders.
The scope of genetic tests within the European Union is itself unclear. A recent search on the European Directory of DNA Diagnostic Laboratories (EDDNAL)found 353 laboratories performing diagnostic tests (as of June 2004), but a survey performed by the European Commission's Institute for Prospective Technologies (IPTS) for their seminal report, Towards Quality Assurance and Harmonization of Genetic Testing Services in the EU , suggests that the number may be much larger. A lack of knowledge about the number of patients having tests performed across Europe is also acknowledged; however, the EU survey makes clear that genetic services and their usage are growing in the European Union. Largely, these tests are for monogenic (or single-gene) disorders, and their type is determined mostly by the genetic illnesses that are most prevalent within the community in question.
Quality assurance within genetic testing laboratories is guided largely by a network of external quality assurance providers, which provide laboratories with genetic test samples and feedback based on the laboratory's analysis of the sample, both in the form of individual reports and group feedback that can lead to standardized guidelines. These providers vary in the number of tests schemes (programs that test laboratory proficiency by examining testing results on a standardized sample) available and geographical scope The European Commission's European Molecular Genetics Quality Network (EMQN) and the Cystic Fibrosis Thematic Networkare among the largest providers, and both have received funding from the EU. The EMQN was funded by the EC until 2002 (the CF network is still funded), but participants in EMQN external quality assurance schemes continued to increase through 2003 despite the end of funding from this source. Participating EMQN laboratories now pay fees .
The gaps in the regulation between EU countries can be fairly wide. For example, in the United Kingdom, considerable groundwork had been established for the protection of quality in genetic tests; the Human Genetics Commission (HGC)and the Former Advisory Committee on Genetic Testing (ACGT)have made significant recommendations related to genetic testing oversight [3,4]. The United Kingdom National External Quality Assurance System (UK NEQAS) is a major external quality assurance provider, and serves laboratories both inside and outside the United Kingdom. Additionally, the Clinical Molecular Genetics Society (CMGS) has developed a set of substantial quality assurance and best practice guidelines, upon which the EMQN based its preliminary quality assurance strategies . However, there are several other European Union nations, such as Spain and the Slovak Republic, that have no specific recommendations or best practice guidance for genetic testing [6,7]. It is unclear exactly why, however, these discrepancies exist.
The Organization for Economic Co-operation and Development's (OECD) report, Genetic Testing: Policy Issues for the New Millennium , noted what seems to be the prime concern in genetic testing quality assurance: the lack of laboratory regulation, and the low numbers of laboratories participating in external quality assurance schemes in the EU. A second survey performed by the IPTS in its report notes that those laboratories participating in external quality assurance schemes may participate in very few schemes . Because these schemes are not compulsory, there may be little impetus for a laboratory to participate, particularly if they are costly, since participation in the external quality assurance programs can require membership or testing fees. Additionally, there are concerns about inadequate or non-existent genetic counseling of patients and tests that do not meet standards for clinical validity and utility.
Concerns have also been raised about inadequate coverage of rare genetic disorders, which can occur too infrequently for a single laboratory to develop standards specifically for detecting and reporting these genetic abnormalities. To address this issue, samples are often sent to laboratories in another country where facilities do exist. However, because of discrepancies between laboratories within EU member states regarding quality, reporting, and payment mechanisms, it may be difficult for samples to be examined in a different country. An additional concern, related to the testing of rare disorders, is the regulation of test made in-house by clinical laboratories, or proprietary laboratory tests, which are often the only kind of tests for rare genetic ailments. Currently, tests that are manufactured outside the laboratory are subject to regulation under the In-Vitro Diagnostic Directive 98/79/EC; however, there is ambiguity as to whether tests developed in-house are subject to the same regulations.
The IPTS, the European Society of Human Genetics (ESHG), and the European Commission's Expert Group on Genetic Testing have all expressed the need for harmonizing quality standards within genetic testing [1,8,9]. As previously stated, there is little information about which laboratories perform which tests, so it is quite clear that a comprehensive network of laboratories still has yet to be formulated. The OECD and the IPTS have noted that current external quality assurance measures could be augmented through the expansion of current programs, and that an overarching harmonization of regulation would help in the exchange of information and samples across borders. The IPTS recommends the development of a European "platform" to maintain quality across the EU member states, that would set up a minimum standard for genetic testing laboratories, and both the ESHG and the EC Expert Group on Genetic Testing suggest further regulatory framework for quality assurance with genetic testing. However, how this expansion is to take place, who would be responsible for its management, and the details of its mechanism have not been fully articulated.
The ESHG and the EC Expert Group make further recommendations related to the rights of the patient, stressing issues of informed consent, protection of medical information (including genetic material), children and genetic tests, and the expansion of counseling [8,9]. Though it is somewhat harder to quantify if and where failures in protecting these rights are taking place, they too are central to maintaining quality assurance.
Additionally, it may be beneficial in the longer term for other jurisdictions, such as the Latin American countries, to participate in similar harmonization activities, as they may benefit more from this model than from one developed for a single country (e.g. the United States), because Latin American countries face similar challenges regarding the sufficient availability of testing samples. It may be possible as well to preliminarily include developing countries within the umbrella of a European cross-national quality assurance plan. Indeed, the EQMN has included countries outside Europe within it schemes, such as South Africa and Israel. Perhaps, given multiple regional or continental networks of quality assurance, international groupings can themselves interact to produce a truly worldwide harmonization of quality.
It remains to be seen how genetic testing and its regulation will grow in the coming decades; both are very much in their early years throughout the globe, including within the EU. It is notable, however, that the OECD and EU have played increasingly important roles in the development of standards and regulations across national borders. Because of the nature of genetic testing, and the requirements for sample and information sharing (particularly for rare genetic disorders), non-governmental organizations and standard-setting organizations, like the International Standards Organization , may play a more important role in setting normative guidelines for quality assurance in genetic testing laboratories.
It is difficult to determine what the future holds for genetic testing. Genetic testing as it currently exists may evolve to be very different in the future -- as tests for disease susceptibility for more complex disorders like diabetes and cancer become more prominent, regulation of genetic testing must remain dynamic to account for the rapid evolution of this field. Although current solutions must address current problems, these solutions must be dynamic enough to account for the evolving field of genetic testing and genomics.
- 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.
- European Molecular Genetics Quality Network. EMQN Newsletter. April 2003. Available at: http://www.emqn.org/Assets/uploadpdfs/emqn_news_issue10.pdf Accessed May 27th, 2004.
- http://www.hgc.gov.uk Accessed May 20th, 2004.
- United Kingdom's Human Genetics Commission. Laboratory Services for Genetics. Available at: http://www.dh.gov.uk/assetRoot/04/01/92/40/04019240.pdf Accessed May 27th, 2004.
- Organization for Economic Co-Operation and Development. Genetic Testing: Policy Issues for the New Millennium. Paris: Organization for Economic Co-Operation and Development. 2000. 6. Regulatory Developments in Genetic Testing in Spain. Available at: http://www.oecd.org/document/21/0,2340,en_2649_34537_2430869_1_1_1_1,00.html Accessed May 20th, 2004.
- Regulatory Developments in Genetic Testing in the Slovak Republic. Available at: http://www.oecd.org/document/58/0,2340,en_2649_34537_2430842_1_1_1_1,00.html Accessed May 20th, 2004.
- Müller CR. Quality Control in Mutation Analysis: the European Molecular Genetics Quality Network (EMQN). Eur J Pediatr. 2001. 160(8):464-7.
- McNally E, Cambon-Thomsen A. Report on the Ethical, Legal and Social Aspects of Genetic Testing: Research, Development and Clinical Applications. Brussels: The European Commission. Available at: http://www.europa.eu.int/comm/research/conferences/2004/genetic/index_en.htm Accessed May 25th, 2004.