Personal genome testing: Test characteristics to clarify the discourse on ethical, legal and societal issues

Bunnik et al. BMC Medical Ethics 2011, 12:11 http://www.biomedcentral.com/1472-6939/12/11 DEBATE Open Access Personal genome testing: Test characteristics to clarify the discourse on ethical, legal and societal issues Eline M Bunnik1, Maartje HN Schermer1* and A Cecile JW Janssens2 Abstract Background: As genetics technology proceeds, practices of genetic testing have become more heterogeneous: many different types of tests are finding their way to the public in different settings and for a variety of purposes. This diversification is relevant to the discourse on ethical, legal and societal issues (ELSI) surrounding genetic testing, which must evolve to encompass these differences. One important development is the rise of personal genome testing on the basis of genetic profiling: the testing of multiple genetic variants simultaneously for the prediction of common multifactorial diseases. Currently, an increasing number of companies are offering personal genome tests directly to consumers and are spurring ELSI-discussions, which stand in need of clarification. This paper presents a systematic approach to the ELSI-evaluation of personal genome testing for multifactorial diseases along the lines of its test characteristics. Discussion: This paper addresses four test characteristics of personal genome testing: its being a non-targeted type of testing, its high analytical validity, low clinical validity and problematic clinical utility. These characteristics raise their own specific ELSI, for example: non-targeted genetic profiling poses serious problems for information provision and informed consent. Questions about the quantity and quality of the necessary information, as well as about moral responsibilities with regard to the provision of information are therefore becoming central themes within ELSIdiscussions of personal genome testing. Further, the current low level of clinical validity of genetic profiles raises questions concerning societal risks and regulatory requirements, whereas simultaneously it causes traditional ELSIissues of clinical genetics, such as psychological and health risks, discrimination, and stigmatization, to lose part of their relevance. Also, classic notions of clinical utility are challenged by the newer notion of ‘personal utility.’ Summary: Consideration of test characteristics is essential to any valuable discourse on the ELSI of personal genome testing for multifactorial diseases. Four key characteristics of the test - targeted/non-targeted testing, analytical validity, clinical validity and clinical utility - together determine the applicability and the relevance of ELSI to specific tests. The paper identifies and discusses four areas of interest for the ELSI-debate on personal genome testing: informational problems, risks, regulatory issues, and the notion of personal utility. Background In discussions on ethical, legal and societal issues (ELSI) surrounding genetic testing, there is no longer any single satisfying definition of what constitutes ‘a genetic test’. Practices of genetic testing are becoming more and more heterogeneous, not only with regard to the setting and * Correspondence: 1 Dept. of Medical Ethics and Philosophy of Medicine, Erasmus University Medical Center, Office AE-340, PO Box 2040, 3000 CA Rotterdam, The Netherlands Full list of author information is available at the end of the article purpose of testing, but also with regard to the technical aspects of the tests themselves. Some of these technical differences between genetic tests are ethically significant or have implications for legal or societal issues. Therefore, a clear understanding of the relevant test characteristics of genetic tests is a necessity for any meaningful discussion of the ELSI surrounding genetic testing. Over the last decades, new technologies for genetic testing have been developed that differ in many respects from those used in traditional clinical genetic testing for monogenic diseases. One important development is the © 2011 Bunnik et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Bunnik et al. BMC Medical Ethics 2011, 12:11 http://www.biomedcentral.com/1472-6939/12/11 advent of personal genome testing on the basis of genetic profiling for the prediction of common multifactorial diseases. Multifactorial diseases, such as cardiovascular diseases [1], age-related macular degeneration [2], type 2 diabetes [3], clinical depression [4], and many types of cancer [5], are caused by intricate interplays of multiple genetic factors and non-genetic factors. Through an analysis of those genetic factors, an individual’s genetic susceptibility to multifactorial diseases can be determined. Personal genome testing companies are currently offering such risk prediction services directly-to-consumer, thereby raising a range of new ELSI. With this paper, we aim to clarify the relations between the more technical characteristics of a genetic test and the ELSI with which the test is associated. We believe that a thorough understanding of the technical characteristics of personal genome tests themselves forms a necessary basis for all further ELSI-discussions in the field. Our focus on the test characteristics implies that, in this paper, we will not be able to discuss other aspects that are relevant to ELSI-discussions, such as characteristics of the diseases tested for, or the settings in which tests are offered. Although there are moral differences, for example, between the offering of personal genome tests by private companies and the offering of the same tests by public health care systems, or between testing for diseases for which there are treatment options available and testing for diseases for which there are no such options, these differences are not the main subject of this paper. As personal genome tests are currently offered almost exclusively in a direct-to-consumer context, we take that context as the background to our discussion. First, we will introduce the practice of personal genome testing. In the second section, we will distinguish and briefly discuss the following four key test characteristics of genetic testing: from targeted to non-targeted testing, analytical validity, clinical validity and clinical utility. The third section of the paper discloses and discusses four major areas of implications of these test characteristics for the ELSI-debate. Discussion I Personal genome testing Personal genome testing for multifactorial diseases is conducted on the basis of genetic profiling. In a genetic profile, multiple genetic variants are combined that are associated with increased or decreased risks for a particular multifactorial disease. Presently, single nucleotide polymorp (...truncated)