Perspective
Risks of Presymptomatic Direct-to-Consumer Genetic Testing
N Engl J Med 2010; 363:1100-1101September 16, 2010
- Article
Geneticists have long cited the risks of direct-to-consumer (DTC) genetic testing, highlighting the danger for consumers who make complex medical decisions without adequate clinical guidance. On May 10, 2010, the Food and Drug Administration (FDA) voiced its concern by sending a letter informing Pathway Genomics that its DNA testing and interpretation service “appears to meet the definition of a device” and may therefore require FDA approval.1
The letter was prompted by the announcement by Pathway Genomics and Walgreens of the impending marketing of an over-the-counter testing kit to analyze genetic risk and provide information regarding more than 70 diseases or traits. Although similar tests are already marketed online, the availability of consumer-initiated genetic testing through the largest U.S. drugstore chain represented a major leap. After receiving the FDA's letter, Walgreens postponed plans to carry the device. The FDA has since issued similar letters to 19 additional companies.1
The agency seeks to protect the public from the “unreasonable risk of harm if the tests are not analytically and clinically accurate so that individuals are misled by incorrect test results or unsupported clinical interpretations.” In 1997, a task force that was appointed by the federal Working Group on Ethical, Legal, and Social Implications of Human Genome Research laid out three criteria2 for assessing the safety and efficacy of genetic tests: analytic validity, meaning that a test is positive when a particular sequence is present and negative when it is absent; clinical validity, meaning that the test is positive in people with a given disease and negative in those without the disease and that positive results predict disease and negative results predict its absence; and clinical utility, meaning that the test's benefits outweigh the risks. The FDA will undoubtedly apply these principles to DTC tests, but whether data from genomewide association studies are sufficient to prove clinical validity and what benchmarks will be used for clinical utility remain uncertain.
In 2004, the FDA approved the Roche AmpliChip, a test that analyzes DNA for 29 different CYP2D6 and CYP2C19 genetic variants. With 99% accuracy and well-established allele-specific metabolic activity, the device has proven analytic and clinical validity. The FDA deemed it acceptable for aiding “clinicians in determining therapeutic strategy and treatment doses,” despite the dearth of prospective data showing clinical utility.3 If the FDA simply extrapolates the standards used for the AmpliChip to DTC genetic tests, several companies may be able to proceed without much delay. However, it is not clear whether these physician-targeted standards can be generalized for consumer end users.
The FDA's actions have temporarily halted a new era of privately funded DNA-based population screening. Before ad hoc screening is resumed for Americans with the means and desire to pay for such tests, care should be exercised to avert unintended consequences.
When population screening for medical conditions is independent of any defined individual risk, the screening program should adhere to established principles in order to avoid undue harm and expense: there must be a suitable and acceptable test addressing an important health problem that has a recognizable latent or early symptomatic state, a well-understood natural history, and an accepted and available treatment or intervention.4,5 Most genetic screening currently cannot meet such expectations. More important, DTC genetic screening may place a substantial burden on the health care system without providing demonstrable benefit.
What should happen, for instance, when a 30-year-old man with no relevant signs, symptoms, or family history shows his doctor a genetic test result indicating that he has an elevated risk of prostate cancer? Should his prostate-specific antigen level be measured? An ultrasound obtained? A biopsy performed? What level of risk should trigger further testing? What are the liability risks of not pursuing a diagnostic evaluation? As the number of conditions for screening expands, so will the cost to our health care system and the risk of iatrogenic harm to patients.
The Government Accountability Office issued an investigative report on July 22, 2010, citing deceptive marketing practices, erroneous medical management advice from DTC genetic-testing companies, and a lack of standardization of results among companies. Discordant results from four DTC companies analyzing identical DNA samples highlight the need for standards — clinically valid tests for the same condition should yield concordant results.
The potential harms of DTC genetic testing include the loss of protections for patients offered by established health care delivery systems (e.g., doctor–patient confidentiality and beneficence), invalid analytic or clinical results from medical devices, and population screening without consensus on interpretation and follow-up. These risks must be balanced against the potential benefits of innovation. The government's role in this arena should include both regulation and the funding of collaborative research that enables the optimal use of genetic information.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
This article (10.1056/NEJMp1006029) was published on August 18, 2010, at NEJM.org.
Source Information
From the Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston (J.P.A., M.A.G., M.F.M.); and the Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA (J.P.A.).
- References
References
1
Food and Drug Administration. Medical devices. Letters to industry. (Accessed August 2, 2010, at http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/ucm111104.htm.)
2
Holtzman NA. Promoting safe and effective genetic tests in the United States: work of the task force on genetic testing. Clin Chem 1999;45(5):732-8. (Also available at http://www.genome.gov/10001733.)
3
Food and Drug Administration. Medical devices. Roche AmpliChip Cytochrome P450 Genotyping test and Affymetrix GeneChip Microarray Instrumentation System — K042259. (Accessed August 2, 2010, at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm078879.htm.)
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Wilson JMG ,Jungner G . Principles and practice of screening for disease. WHO Chron 1968;22:473-4835
Andermann A ,Blancquaert I ,Beauchamp S ,Dery V . Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years. Bull World Health Organ 2008;86:317-319
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- Citing Articles (10)
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Alanna Kulchak Rahm, Heather Spencer Feigelson, Nicole Wagner, Anh Quynh Le, Eve Halterman, Nadine Cornish, James W. Dearing. (2012) Perception of Direct-To-Consumer Genetic Testing and Direct-To-Consumer Advertising of Genetic Tests among Members of a Large Managed Care Organization. Journal of Genetic Counseling
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C. S. Bloss, B. F. Darst, E. J. Topol, N. J. Schork. (2011) Direct-to-consumer personalized genomic testing. Human Molecular Genetics 20:R2, R132-R141
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Tariq Ahmad, Deepak Voora, Richard C. Becker. (2011) The pharmacogenetics of antiplatelet agents: towards personalized therapy?. Nature Reviews Cardiology 8:10, 560-571
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Paul E. Drawz, John R. Sedor. (2011) The genetics of common kidney disease: a pathway toward clinical relevance. Nature Reviews Nephrology 7:8, 458-468
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Claire Julian-Reynier. (2011) Prédisposition génétique aux cancers du sein et de l’ovaire. médecine/sciences 27:6-7, 657-661
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Michael V. Holmes, Seamus Harrison, Philippa J. Talmud, Aroon D. Hingorani, Steve E. Humphries. (2011) Utility of genetic determinants of lipids and cardiovascular events in assessing risk. Nature Reviews Cardiology 8:4, 207-221
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George C Zografos, Dimitrios H Roukos. (2011) Innovative biomarker development for personalized medicine in breast cancer care. Biomarkers in Medicine 5:1, 73-78
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Dimitrios H Roukos. (2011) Innovation versus evidence: to trust direct-to-consumer personal genomic tests?. Expert Review of Molecular Diagnostics 11:1, 1-4
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Christos Katsios, Dimosthenis E. Ziogas, Theodore Liakakos, Odysseas Zoras, Dimitrios H. Roukos. (2010) Translating Cancer Genomes Sequencing Revolution into Surgical Oncology Practice. Journal of Surgical Research
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Jennifer K. Wagner. (2010) Understanding FDA Regulation of DTC Genetic Tests within the Context of Administrative Law. The American Journal of Human Genetics 87:4, 451-456
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