Genetic gatekeepers: Regulating direct-to-consumer genomic services in an era of participatory medicine

Food and Drug Law Journal

Volumn 67, Issue 4, 2012, Pages 475-524

  Palmer, Jessica Elizabeth ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

ALZHEIMER DISEASE; CHROMOSOME ANALYSIS; DIRECT TO CONSUMER GENOMIC SERVICE; DNA DETERMINATION; DNA SEQUENCE; ENVIRONMENTAL FACTOR; GENE MUTATION; GENETIC ASSOCIATION; GENETIC COUNSELING; GENETIC SCREENING; GENETIC VARIABILITY; GENOTYPE; HEALTH EDUCATION; HEALTH SERVICE; HUMAN; HUNTINGTON CHOREA; LABORATORY TEST; MEDICAL DEVICE; MEDICAL INFORMATION; MEDICAL RESEARCH; PATIENT AUTONOMY; PERSONALIZED MEDICINE; PHARMACOGENOMICS; PHENOTYPE; PRACTICE GUIDELINE; PROTEIN ANALYSIS; REVIEW; RNA ANALYSIS; SAFETY; SINGLE NUCLEOTIDE POLYMORPHISM; SOCIAL NETWORK;

ADVERTISING AS TOPIC; CONSUMER PARTICIPATION; GENETIC TESTING; GOVERNMENT REGULATION; HUMANS; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION;

EID: 84873192103     PISSN: 1064590X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (589)

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3. GAO, GAO-10-847T, DIRECT-TO-CONSUMER GENETIC TESTS: MISLEADING TEST RESULTS ARE FURTHER COMPLICATED BY DECEPTIVE MARKETING AND OTHER QUESTIONABLE PRACTICES 1 (2010) [hereinafter 2010 DTC INVESTIGATION].
4. Id.
5. Direct-to-Consumer Genetic Testing and the Consequences to the Public Health: Hearing before the Subcommittee on Oversight and Investigations of the House Energy and Commerce Committee, 112th Cong. (July 22, 2010) (Statement of Gregory Kutz, Managing Director, Forensic Audits and Special Investigations, GAO).
6. Id.
7. Id. (Statement of Rep. Phil Gingrey).
8. Id. (Statement of Jeff Shuren, Director, Center for Devices and Radiological Health, FDA).
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10. Gina Kolata, Capacity of Genome to Predict is Limited, N.Y. TIMES D5 (Apr. 3, 2012) ("[e]ven if you know everything about genetics, prediction will remain probabilistic and not deterministic" (quoting David Altschuler)).
11. Genetic exceptionalism is the practice of treating genetic information as unique, such that it warrants greater regulation or protection than other health information. See, e.g., Michael J. Green & Jeffrey Botkin, "Genetic Exceptionalism" in Medicine: Clarifying the Differences Between Genetic and Nongenetic Tests, 138 ANN. INTERN. MED 571, 572 (2003);
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14. See, e.g., Andrew S. Robertson, Taking Responsibility: Regulations and Protections in Direct-to-Consumer Genetic Testing, 24 BERKELEY TECH. L. J. 213, 238 (2009) (arguing that FDA should treat DTC services "with medical purposes" as medical devices requiring approval).
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17. This Article will call individuals who purchase DTC genome services "consumers," rather than "patients." Although "consumer" lacks the ethical dimension usually associated with health care, see, e.g., Raisa B. Deber et al., Patient, Consumer, Client, or Customer: What Do People Want to Be Called? 8 HEALTH EXPECTATIONS 345, 345-47 (2005), DTC genomic services do not provide health care, not all DTC users are patients, and genetic information has intangible value apart from any medically actionable implications. As Dan Vorhaus has noted, FDA itself has used both "patient" and "consumer" in its letters to DTC companies - sometimes in the same paragraph.
18. Dan Vorhaus, What Five FDA Letters Mean for the Future of DTC Testing, GENOMICS LAW REPORT (June 11, 2010), http://bit.ly/a16QoI (last visited Apr. 29, 2012).
19. See, e.g., Caroline Wright et al., People Have A Right To Access Their Own Genetic Information, GENOMES UNZIPPED (Nov. 3, 2011), available at http://bit.ly/iiVpGC (last visited Apr. 29, 2012);
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21. Cynthia Marietta & Amy L. McGuire, Direct-to-Consumer Genetic Testing: Is It the Practice of Medicine? 37 J. L. MED & ETHICS 369, 370 (2009) ("we agree that competent adults generally have a right to purchase available information about themselves and their DNA").
22. Cf. Richard A. Merrill, Genetic Testing? A Role for FDA, 41 JURIMETRICS 63, 65 (2000) ("[T]he FDCA's product-focused requirements provide an odd-fitting framework for regulating what is basically an information service.").
23. Rui Chen et al., Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes, 148 CELL 1293, 1293 (2012).
24. See, e.g., Andrew C. von Eschenbach, Navigating the Molecular Revolution: FDA Leadership in a Time of Transition, in PERSPECTIVES ON RISK AND REGULATION: THE FDA AT 100, 149-56, at 18 (Arthur Daemmrich & Joanna Radin, eds., 2007) (discussing FDA's Critical Path Initiative, intended to leverage "advances in genomics and proteomics" in a "health care system of the future [that] will be not only personalized but also predictive, preemptive, and more participatory").
25. Lisa Krieger, UC Berkeley Drops Plans to Release Personal Genetic Information to Incoming Freshmen, SAN JOSE MERCURY NEWS (Aug. 12, 2010) (quoting Dean Mark Schlissel's response to a Department of Public Health ruling that the University of California, Berkeley, could not test incoming freshman for "noncontroversial" genetic variants as an educational exercise).
26. See SEC'Y'S ADVISORY COMM. ON GENETICS, HEALTH, AND SOC'Y, U.S. SYSTEM OF OVERSIGHT OF GENETIC TESTING: A RESPONSE TO THE CHARGE OF THE SEC'Y OF HEALTH AND HUMAN SERVS 17 (2008) [hereinafter SACGHS OVERSIGHT REPORT].
27. See also What is Genetic Testing?, GeneTests Med. Genetics Information Resource, http://www.ncbi.nlm.nih.gov/projects/GeneTests/static/concepts/primer/ primerwhatistest.shtml (last visited Apr. 29, 2012).
28. Eric S. Lander, Initial Impact of the Sequencing of the Human Genome, 470 NATURE 187 (2011).
29. See, e.g., Lauren B. Solberg, Over the Counter but Under the Radar: Direct-to-Consumer Genetic Tests and FDA Regulation of Medical Devices, 11 VANDERBILT J. ENT. & TECH. L. 711, 713 (2009) ("Genetic tests offer consumers a figurative crystal ball");
30. Juliana Han, The Optimal Scope of FDA Regulation of Genetic Tests: Meeting Challenges and Keeping Promises, 20 HARV. J. L. & TECH. 423, 423 (2007) ("Soon, [genetic] tests will function as medical crystal balls, forecasting risks of disease years into the future.").
31. See generally JAMES THOMPSON & MARGARET THOMPSON, GENETICS IN MEDICINE 4-6 (Robert L. Nussbaum, Roderick R. McInnes & Huntington F. Willard eds., 6th ed. 2004).
32. Lander, supra note 21, at 188.
33. See generally THOMPSON & THOMPSON, supra note 23, AT 17-19.
34. Lander, supra note 21, at 187-88.
35. Isaac S. Kohane & Russ B. Altman, Health-Information Altruists - A Potentially Critical Resource, 353 N. E. J. MED. 2075, 2075 (2005).
36. See generally THOMPSON & THOMPSON, supra note 25, AT 51-63.
37. Id., at 240-42.
38. PAULA STEPHAN, HOW ECONOMICS SHAPES SCIENCE 88 (2012).
39. Id.
40. Lander, supra note 21, at 191.
41. "SNPs" is pronounced "snips." NIH, What Are Single Nucleotide Polymorphisms (SNPs)? GENETICS HOME REFERENCE (APR. 24, 2012), http://ghr.nlm.nih.gov/handbook/genomicresearch/snp.
42. Id.; Lander, supra note 21, at 191.
43. See SACGHS OVERSIGHT REPORT 60. Because SNPs are much smaller than genes, testing for SNPs is usually described as "genotyping" or "screening" rather than gene "sequencing."
44. See generally NIH, Microarray Technology, GENETICS HOME REFERENCE (Apr. 24, 2012), http://ghr.nlm.nih.gov/glossary=microarraytechnology.
45. Published studies typically report the likelihood that an individual with a given health disorder has a certain SNP genotype as an "odds ratio" (the odds of an individual with a variant having the disorder, divided by the odds of an individual without the variant having the disorder). These studies sometimes confuse lay readers, because odds ratios are not equivalent to relative risk. See Lisa M. Schwartz, Steven Woloshin, & H. Gilbert Welch, Misunderstandings About the Effects of Race and Sex on Physicians 'Referrals for Cardiac Catheterization, 341 N.E.J.M. 279, 280-82 (1999) (describing how mainstream media outlets misunderstood a genetic study and misreported its findings on risk). In this paper, "risk" and "genetic risk" are used in the general, nontechnical sense most familiar to lay audiences.
46. Lander, supra note 21, at 191.
47. Id. at 193.
48. A. Cecile J. W. Janssens et al., A Critical Appraisal of the Scientific Basis of Commercial Genomic Profiles Used to Assess Health Risks and Personalize Health Interventions, 82 AM. J. HUM. GEN. 593, 593 (2008).
49. Peter Kraft et al., Beyond Odds Ratios - Communicating Disease Risk Based on Genetic Profiles, 10 NATURE REV. GEN. 264 (2009).
50. Ross, supra note 10, at 142.
51. Caroline Fiona Wright & Mark Kroese, Evaluation of Genetic Tests for Susceptibility to Common Complex Diseases: Why, When and How? 127 HUMAN GENETICS 125, 127 (2010);
52. Muin J. Khoury et al., The Scientific Foundation for Personal Genomics: Recommendations from a National Institutes of Health-Centers for Disease Control and Prevention Multidisciplinary Workshop, 11 GENETICS IN MED. 561, 561 (2009).
53. See generally SACGHS OVERSIGHT REPORT 67-72.
54. Id. 85-91;
55. Khoury, supra note 42, at 561-62.
56. See generally SACGHS OVERSIGHT REPORT 115-31;
57. Khoury, supra note 42, at 562-63.
58. GENETESTS MED. GENETICS INFORMATION RESOURCE, http://www.ncbi.nlm.nih. gov/sites/GeneTests/ (last visited Apr. 29, 2012).
59. See, e.g., Pauline C. Ng, Sarah S. Murray, Samuel Levy & J. Craig Venter, An Agenda for Personalized Medicine, 461 NATURE 724, 724 (2009) (reporting high accuracy and greater than 99.7% agreement in raw genotype data reported by 23andMe and Navigenics);
60. PERSONALIZED MEDICINE COALITION (PMC), PERSONAL GENOMICS AND INDUSTRY STANDARDS: SCIENTIFIC VALIDITY (July 2008) (23andMe, Navigenics, and deCODE estimated that their genotype data had 99% accuracy) available at http://bit.ly/KpJenC (last visited Apr. 29, 2012).
61. See, e.g., Monica R. McClain et al., A Rapid-ACCE Review of CYP2C9 and VKORC1 Alleles Testing to Inform Warfarin Dosing in Adults at Elevated Risk for Thrombotic Events to Avoid Serious Bleeding, 10 GENETICS IN MED. 89 (2008) (applying the ACCE framework to pharmacogenomic markers);
62. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group, Recommendations from the EGAPP Working Group: Testing for Cytochrome P450 Polymorphisms in Adults With Nonpsychotic Depression Treated With Selective Serotonin Reuptake Inhibitors, 9 GENETICS IN MED. 819, 820 (2007) (similar).
63. Khoury, supra note 42, at 561-64.
64. See, e.g., SACGHS OVERSIGHT REPORT 4.
65. DHHS, Personalized Health Care, http://www.hhs.gov/myhealthcare/ (last visited Apr. 29, 2012).
66. See von Eschenbach, supra note 18, at 151.
67. DHHS, PERSONALIZED HEALTH CARE: OPPORTUNITIES, PATHWAYS, RESOURCES, 2, 7-8, 9-12 (2007).
68. Id. at 13.
69. SEC'Y'S COMM. ON GENETICS, HEALTH, AND SOC'Y, REALIZING THE POTENTIAL OF PHARMACOGENOMICS: OPPORTUNITIES AND CHALLENGES 9 (2008), available at http://oba.od.nih.gov/oba/sacghs/reports/sacghs-pgx-report.pdf.
70. Id. 1-2; see also id. at 15-16 (discussing how genetics affects dosing of the blood thinner warfarin).
71. Shu-Feng Zhou, Polymorphism of Human Cytochrome P450 2D6 and its Clinical Significance: Part I, 48 CLINICAL PHARMACOKINETICS 689, 691 (2009).
72. Shu-Feng Zhou, Polymorphism of Human Cytochrome P450 2D6 and its Clinical Significance: Part II, 48 CLINICAL PHARMACOKINETICS 761, 792 (2009).
73. Id.
74. See, e.g., Leslie Sinclair, Med Check, 47 PSYCHIATRIC NEWS 30, 30 (JAN. 20, 2012) (reporting that FDA had updated the required labeling for Orap (pimozide) to recommend CYP2D6 genotyping for patients receiving high doses).
75. See Barbara J. Evans, Seven Pillars of a New Evidentiary Paradigm: The Food, Drug, and Cosmetic Act Enters the Genomic Era, 85 N. D. L. REV. 468 (2010) (discussing how variable treatment response undercuts FDA's premarket clinical trial requirements).
76. See SEC'Y'S COMM. ON GENETICS, HEALTH, AND SOC'Y, supra note 55, at 26-28;
77. FDA, Draft Guidance for Industry and Food and Drug Administration Staff-In Vitro Companion Diagnostic Devices 6-7 (July 14, 2011).
78. Barbara J. Evans, Distinguishing product and practice regulation in personalized medicine, 81 CLINICAL PHARMACOLOGY & THERAPEUTICS 288, 288-90 (2007).
79. Oncotype DX Overview, GENOMIC HEALTH, http://www.oncotypedx.com/en-US/ Breast/PatientsCaregiversInvasive/OncotypeDX/Overview (last visited May 31, 2012).
80. See Evans, Seven Pillars, supra note 61, at 460-61 (2010) (discussing the role of genomic medicine in enhancing predictive judgments and prognosis).
81. Carlos D. Bustamante, Esteban González Burchard & Francisco M. De La Vega, Genomics for the World, 475 NATURE 163, 164 (2011).
82. See, e.g., Nicholas J. Roberts et al., The Predictive Capacity of Personal Genome Sequencing, Sci. TRANSL. MED. (2012) (estimating that for most individuals, whole genome sequencing would have little predictive value, and that "in the best-case scenario," ninety percent of patients "might be alerted to a clinically meaningful risk for at least one disease");
83. Kolata, supra note 9;
84. Jocelyn Kaiser, A Reality Check for Personal Genomes, SCIENCENOW (Apr. 2, 2012), http://news.sciencemag.org/sciencenow/2012/04/a-reality-check-for- personal-gen.html ("'we're not going to have a huge impact' on the average person with genome sequencing" (quoting Harvard University epidemiologist Peter Kraft)).
85. Clifton Bogardus, Missing Heritability and GWAS Utility, 17 OBESITY 209, 210 (2009).
86. SEC'Y'S COMM. ON GENETICS, HEALTH, AND SOC'Y, REALIZING THE POTENTIAL OF PHARMACOGENOMICS: OPPORTUNITIES AND CHALLENGES 29-30 (2008), available at http://oba.od.nih.gov/oba/sacghs/reports/sacghs-pgx-report.pdf.
87. Wright & Kroese, supra note 42, at 128.
88. IOM INTEGRATION WORKSHOP SUMMARY 43 ("genotyping can be cheaper, easier, and more effective than testing one gene at a time");
89. Id. at 48 (at the $ 1,000 price point, "sequencing a person's entire genome will be nearly as inexpensive as a single genetic test").
90. IOM INTEGRATION WORKSHOP SUMMARY 40.
91. Id. (noting "the medical staff would rather not have [patients'] medical record[s] populated with genomic information of uncertain clinical utility").
92. STEPHAN, supra note 30, at 88.
93. John Markoff, Breaking a Gene Barrier, N.Y. TIMES B1 (Mar. 8, 2012) (reporting intense competition in the whole-genome sequencing services sector).
94. See also Andrew Pollack, A Genome Deluge, N.Y. TIMES B1 (Dec. 1, 2011) ("It costs more to analyze a genome than to sequence a genome.").
95. Steven L. Salzberg & Mihaela Pertea, Do-it-yourself Genetic Testing, 11 GENOME BIOL. 404 (2010) ("once an individual's genome has been sequenced, it becomes a resource that can be re-tested as new disease-causing mutations are discovered").
96. See I.S. Kohane, D.R. Masys, & R.B. Altman, The Incidentalome: A Threat to Genomic Medicine, 296 J. AM. MED. ASS'N 212 (2006).
97. See Am. Coll. Med. Genetics & Genomics, Policy Statement: Points to Consider in the Clinical Application of Genomic Sequencing (March 27, 2012), http://www.acmg.net/StaticContent/PPG/Clinical-Application-of-Genomic- Sequencing.pdf ("When interpreting secondary findings, or results that are generated in the course of screening asymptomatic individuals, it is critical... to avoid burdening the health care system and consumers with what could be very large numbers of false positive results.").
98. Nicholas Wade, Genome of DNA Discoverer Is Deciphered, N.Y. TIMES (June 1, 2007).
99. Heidi Carmen Howard & Pascal Borry, Is there a doctor in the house? The presence of physicians in the direct-to-consumer genetic testing context, 3 J. COMMUNITY GENETICS 105, 105 (2012).
100. See, e.g., Kathy Hudson et al., ASHG Statement on Direct-to-Consumer Genetic Testing in the United States, 81 AM. J. HUMAN GENETICS 635, 635 (2007).
101. Caroline F. Wright & Daniel G. MacArthur, Direct-to-Consumer Genetic Testing, in MOLECULAR GENETICS AND PERSONALIZED MEDICINE at 215, 215 (D.H. Best & J.J. Swensen, eds. 2012).
102. Terms of Service, 23ANDME, https://www.23andme.com/legal/tos/ (last visited Apr. 29, 2012).
103. 23andMe Store, 23ANDME, https://www.23andme.com/store/cart (last visited Apr. 29, 2012);
104. Our Products, deCODEme, https://www.decodeme.com/store (last visited Apr. 29, 2012).
105. Jennifer K. Wagner, Jill D. Cooper, Rene Sterling & Charmaine D. Royal, Tilting at Windmills no Longer: a Data-Driven Discussion of DTC DNA Ancestry Tests, GENETICS IN MED. (Mar. 1 2012).
106. Id.;
107. see, e.g., Homepage, FAMILYTREEDNA, http://www.familytreedna.com/ (last visited Apr. 29, 2012).
108. Wagner et al., supra note 85.
109. FamilyTreeDNA genotypes SNPs associated with physical traits like "earwax," "baldness," "longevity," and "freckling;" it describes these tests as "Factoids" "best used as 'cocktail conversation' starters." Types of Tests, FAMILYTREEDNA, http://www.familytreedna.com/faq/answers.aspx?id=8#883 (last visited Apr. 29, 2012).
110. GAO, GAO-06-977T, NUTRIGENETIC TESTING: TESTS PURCHASED FROM FOUR WEB SITES MISLEAD CONSUMERS (2006) [hereinafter 2006 DTC INVESTIGATION].
111. Smart Genetics briefly entered the field in 2008 with an Alzheimer's test, but exited after a patent dispute. Erika Check Hayden, Alzheimer's Tests Under Fire, 455 NATURE 1155, 1155 (2008). Graceful Earth, which also sells dietary supplements, still offers an Alzheimer's test.
112. Katie Skeehan, Christopher Heaney, & Robert Cook-Deegan, Impact of Gene Patents and Licensing Practices on Access to Genetic Testing for Alzheimer's Disease, 12 GENETICS IN MED. S71 (2011).
113. Direct-to-Consumer Genetic Testing Companies, GENETICS AND PUBLIC POLICY CENTER (updated May 27, 2009), http://www.dnapolicy.org/resources/ DTCcompanieslist.pdf.
114. Pascal Borry, Martina C. Cornel & Heidi C. Howard, Where are you going, where have you been: a recent history of the direct-to-consumer genetic testing market, I J. COMMUNITY GENETICS 101 (2010).
115. Direct-to-Consumer Genetic Testing Companies, GENETICS AND PUBLIC POLICY CENTER (updated Aug 11, 2011), http://www.dnapolicy.org/resources/ DTCTableAug2011Alphabydisease.pdf.
116. PATHWAY GENOMICS, https://www.pathway.com/about-us (last visited Apr. 29, 2012).
117. See, e.g., Andrew Pollack, Firm Brings Gene Tests to Masses, N.Y. TIMES B1 (Jan. 28, 2010) (describing Counsyl's pre-pregnancy carrier screening service).
118. Id. (quoting Counsyl's CEO as saying "[o]ne of our goals is to make this like the home pregnancy test"). Alberto Gutierrez, Director of OIVD, credited FDA's 2010 letter to Pathway Genomics with prompting Counsyl to "change their business model" and leave the DTC space.
119. Mary Carmichael, Why the FDA Is Cracking Down on Do-It-Yourself Genetic Tests: An Exclusive Q&A, NEWSWEEK (June 11, 2010).
120. Ordering a Test, ILLUMINA, http://www.everygenome.com/for-doctors/ ordering-a-test.ilmn (last visited Apr. 29, 2012).
121. FAQs, KNOME, http://www.knome.com/company/faqs/ (last visited Apr. 29, 2012).
122. See Daniel MacArthur, deCODEme opens its doors to free data upload from 23andMe customers, WIRED.COM (Dec. 17, 2009, 8:45 AM), http://www.wired.com/ wiredscience/2009/12/deCODEme-opens-its-doors-to-free-data-upload-from-23andMe- custorners ("the value of genome scans is not in the actual generation of the data (this is a straightforward procedure), but in the breadth and quality of the interpretation service.");
123. see also Annelien L. Bredenoord & Johannes J. M. van Delden, Research Ethics in Genomics Research: Feedback of Individual Genetic Data to Research Participants, in HUMAN MEDICAL RESEARCH 127, 133-34 (J. Schildmann et al., eds, 2012) ("Whereas whole genome 'sequencing' results in raw sequencing data, whole genome 'analysis' processes these data into intelligible information.").
124. PMC, supra note 47, at 2-3.
125. There have been some exceptions; for example, in 2009, deCODE Genetics briefly sought to recruit 23andMe consumers by offering to interpret their raw data for free. See supra note 99.
126. FAQs, KNOME, http://www.knome.com/company/faqs/ (last visited Apr. 29, 2012).
127. Promethease, SNPEDIA (updated Apr. 14, 2012), http://www.snpedia.com/ index.php/Promethease.
128. Sandra Soo-Jin Lee & LaVera Crawley, Research 2.0: Social Networking and Direct-To-Consumer (DTC) Genomics, 9 AM. J. BIOETHICS 35, 37 (2009).
129. Press Release, 23ANDME, 23andMe Receives Funding from the National Institutes of Health to Evaluate Web-Based Research on the Genetics of Drug Response (Dec. 16, 2010), available at https://www.23andme.com/about/press/ 20101216/.
130. See, e.g., Chuong B. Do et al., Web-Based Genome-Wide Association Study Identifies Two Novel Loci and a Substantial Genetic Component for Parkinson's Disease, 7 PLOS GENETICS e1002141 (June 23, 2011);
131. Nicholas Eriksson et al., Web-Based, Participant-Driven Studies Yield Novel Genetic Associations for Common Traits, 6 PLOS GENETICS e1000993 (June 24, 2010) (reporting novel associations for traits like the tendency to sneeze in bright sunlight and the inability to smell asparagus metabolites in urine).
132. Consent Document, 23ANDME, https://www.23andme.com/about/consent/ (last visited Apr. 29, 2012).
133. See, e.g., Terms of Service, 23ANDME, https://www.23andme.com/about/tos/ (warning that consumers will not be compensated for "research or commercial products that may be developed by 23andMe or its collaborating partners") (last visited Apr. 29, 2012).
134. See Anne Wojcicki, An Update to 23andMe Customers, The Spittoon (Jan. 8, 2012 12:57 AM), http://spittoon.23andme.com/2012/01/08/an-update-to-23andme- customers/.
135. See, e.g., Heidi Ledford, Life Hackers, 467 NATURE 650, 651 (2010).
136. Thomas Goetz, Practicing Patients, N.Y. TIMES MAGAZINE, 32 (Mar. 23, 2008);
137. Lee & Crawley, supra note 104, at 38 (comparing PatientsLikeMe and 23andMe).
138. Goetz, supra note 111.
139. Id.
140. John M. Conley, Adam K. Doerr, & Daniel B. Vorhaus, Enabling Responsible Public Genomics, 20 HEALTH MATRIX 325 (2010).
141. Important Considerations, PERSONAL GENOME PROJECT, (Apr. 22, 2011), http://www.personalgenomes.org/considerations.html. The PGP was founded by Harvard Medical School Professor George Church, who later co-founded Knome.
142. Sage Bionetworks, Draft Informed Consent Form, Portable Legal Consent for Public Genomics Research, available at http://weconsent.us/consentform (last visited Apr. 29, 2012) (differentiating "common genomic research" like the PLC-PGR from "public genomic research" like the Personal Genome Project);
143. see also Editorial, Your Data are not a Product, 44 NATURE GENETICS 357 (Mar. 28, 2011).
144. About Us, GENOMERA, http://genomera.com/about (last visited Apr. 29, 2012);
145. see also Elie Dolgin, Personalted Investigation, 16 NATURE MED. 953, 953-56 (2010).
146. Melanie Swan, Scaling Crowdsourced Health Studies: the Emergence of a New Form of Contract Research Organization, 9 FUTURE MED. 223, 223-24 (2012).
147. Elie Dolgin, Personalized Investigation, 16 NATURE MED. 953, 955 (2010).
148. Howard & Borry, supra note 80, at 106-07.
149. Lee & Crawley, supra note 104, at 38-39.
150. Consent Document, 23ANDME, https://www.23andme.com/about/consent/ (last visited Apr. 29, 2012).
151. Dolgin, supra note 119, at 955.
152. See, e.g., Adam Higginbotham, Secrets of my DNA, WIRED 108, 114-15 (Mar. 2011) (participatory genomics organizers used their 23andMe data in conjunction with blood tests to conduct a small-scale study of vitamin metabolism).
153. Richard Tutton & Barbara Prainsack, Enterprising or Altruistic Selves? Making up Research Subjects in Genetic Research, 33 SOCIOLOGY OF HEALTH & ILLNESS 1081, 1090 (2011) (describing 23andMe's model of the patient as "the 'enterprising self who is addressed through a discourse of democratisation and empowerment, and who has the right to information as a value in itself"); accord Higginbotham, supra note 124, at 117 ("Someone need be motivated only by self-interest - "Does Centrum work for me?" -to contribute their valuable genetic data to a study" with public benefit).
154. Higginbotham, supra note 124, at 111;
155. Elie Dolgin, Personalized Investigation, 16 NATURE MED. 953, 954 (2010).
156. See also Brendan Maher, Nature Readers Flirt with Personal Genomics, 478 NATURE 19 (2011) (of 1,588 survey respondents, mostly scientists, 18% had their genomes analyzed in some way; half of them had used 23andMe to do it).
157. Kaushik Sunder Rajan, Two Tales of Genomics, in REFRAMING RIGHTS: BIOCONSTITUTIONALISM IN THE GENETIC AGE at 193, 196, 201, 210 (Sheila Jasanoff, ed. 2011).
158. Id. at 201.
159. Swan, supra note 118, at 223;
160. Eriksson, supra note 106.
161. See Higginbotham, supra note 124, at 111-12 ("If you found a family that avoided diabetes, despite having all the risk factors, that would be [significant]. It's something that scientists can't just do sitting in a laboratory. This is one of the few things where scientists really need citizen science." (quoting George Church, founder of PGP)).
162. Victoria Colliver, Another Look at Avastin and Who it Might Benefit, S.F. CHRONICLE AI (Apr. 14, 2012) (quoting Philippe Bishop, vice president of Genentech).
163. Personal Genome Project Study Guide, Part VI: Project Literacy, Lesson 11: Participating in the Personal Genome Project, PERSONAL GENOME PROJECT, http://www.pgpstudy.org/projectlit/participating/participating7.htm (last visited Apr. 29, 2012).
164. Lee & Crawley, supra note 104, at 38;
165. Katherine Wasson, Direct-to-Consumer Genomics and Research Ethics: Should a More Robust Informed Consent Process Be Included? 9 AM. J. BIOETHICS 56, 56 (2009).
166. Swan, supra note 118, at 223-5.
167. John M. Conley, Adam K. Doerr, & Daniel B. Vorhaus, Enabling Responsible Public Genomics, 20 HEALTH MATRIX 325 (2010). Several studies over the past few years have indicated that deidentified patient information or genetic study information can be reidentified by filtering it or combining it with other data sources.
168. EHe Dolgin, Personalized Investigation, 16 NATURE MED. 953, 955 (2010).
169. Isaac S. Kohane & Russ B. Altman, Health-Information Altruists - A Potentially Critical Resource, 353 N. E. J. MED. 2075 (2005).
170. Editorial, Your Data Are Not a Product, 44 NATURE GENETICS 357 (MAR. 28, 2011).
171. See, e.g., Swan, supra note 118, at 226.
172. The Health Insurance Portability and Accountability Act (HIPAA) requires disclosure of personal information to research participants, but only in limited circumstances.
173. Matthew P. Gordon, A Legal Duty to Disclose Individual Research Findings to Study Subjects? 64 FOOD & DRUG L. J. 250-52 (2009) (describing disclosure guidelines from the National Bioethics Advisory Commission and National Heart, Blood, and Lung Institute, both of which "set the bar for disclosure at (or near) clinical utility"). Nondisclosure is conceptually related to "medical paternalism," which authorizes physicians to withhold information from patients in exceptional cases. Id.
174. PGP Consent Form 9, PERSONAL GENOME PROJECT (approved Feb. 21, 2012) available at http://www.personalgenomes.org/consent/PGP-Consent-Approved- 02212012.pdf ("Once the PGP has completed the analysis of your specimen(s), the PGP will make the data available to you via a password protected area on the PGP website. This information is for research purposes only. You may not use this data for any medical or clinical purpose unless the data are first confirmed by a licensed healthcare professional... One month after you are notified of your specimen analysis data, or at your option immediately, these will be made available on the PGP's public website and database.").
175. TUTTON & PRAINSACK, supra note 125, at 1090.
176. Juli Murphy Bollinger et al., Public Preferences Regarding the Return of Individual Genetic Research Results: Findings From a Qualitative Focus Group Study, 14 GENETICS IN MED. 451, 451 (2012).
177. Swan, supra note 118, at 226.
178. Annelien L. Bredenoord & Johannes J. M. van Delden, Research Ethics in Genomics Research: Feedback of Individual Genetic Data to Research Participants, in HUMAN MEDICAL RESEARCH 127, 128-29 (J. Schildmann et al., eds., 2012). The debate about disclosing genetic data with uncertain utility parallels the debate about FDA regulation of DTC genome services. Both debates start from the presumption that disclosure/access has benefits and risks, and typically focus on clinical utility as the measure of potential benefits. Id. at 133. Study designers also must consider the potential harms of disclosure to the study protocol itself.
179. See infra Part IV.B.
180. GAO, 2010 DTC INVESTIGATION, supra note 3, at 10.
181. Carlos D. Bustamante, Esteban González Burchard & Francisco M. De La Vega, Genomics for the World, 475 NATURE 163, 163 (2011);
182. see also Mike Bamshad, Genetic Influences on Health: Does Race Matter? 294 J. AM. MED. ASSOC. 937, 937 (2007) ("[T]he paucity of data on gene-disease associations in individuals of African ancestry is disturbing").
183. Bustamante at al., supra note 149, at 164.
184. Id. at 165.
185. Daniel MacArthur, Personal Genomics: No Longer Just For White Folks, WIRED (JULY 26, 2011 10:26 AM), http://www.wired.com/wiredscience/2011/07/ personal-genomics-no-longer-just-for-rich-white-folks/.
186. Robertson, supra note 11, at 242.
187. See, e.g., James P. Evans & Jonathan S. Berg, Next-Generation DNA Sequencing, Regulation, and the Limits of Paternalism 306 J. AM. MED. ASSOC. 2376, 2376 (2011);
188. Am. Coll. Med. Genetics, A CMG Statement on Direct-to-Consumer Genetic Testing (Apr. 7, 2008);
189. Eur. Soc. Human Genetics, Press Release, DTC genetic tests neither accurate in their predictions nor beneficial to individuals (May 30, 2011), available at http://bit.ly/m88dhf (63% of European clinical geneticists surveyed thought DTC genome services should be banned).
190. Howard & Borry, supra note 80, at 109-10 (arguing that insufficient medical supervision could cause overuse of genetic tests and give patients a false sense of security).
191. Thomas Goetz, Is Your DNA Dangerous to Your Health? HUFFINGTON POST (July 18, 2010 9:00 AM), http://www.huffingtonpost.com/thomas-goetz/dna-test-is-your- dna-dang-b-616568.html.
192. Khoury et al., supra note 42, at 560.
193. IOM INTEGRATION WORKSHOP SUMMARY 50;
194. See also Elaine R. Mardis, The $1,000 genome, the $100,000 analysis? 2 Genome Med. 84 (2010), http://genomemedicine.com/content/2/11/84.
195. Justin P. Annes, Monica A. Giovanni, & Michael F. Murray, Risks of Presymptomatic Direct-to-Consumer Genetic Testing, 363 N.E.J. MED. 1100, 1101 (2010).
196. See, e.g., Rob Stein, Genetic testing mix-up reignites debate over degree of federal regulation needed, WASH. POST (July 17, 2010) (describing a laboratory mix-up that resulted in misidentification of eighty-seven consumers' 23andMe data).
197. Ng et al., supra note 47, at 724 (reporting more than 99.7% agreement between 23andMe and Navigenics).
198. See, e.g., Eur. Soc. Human Genetics, supra note 154 (reporting that information supplied by deCODEme predicted risks of greater than 100% - an impossibility, regardless of interpretive variation for five of eight diseases).
199. GAO, 2010 DTC INVESTIGATION, supra note 3.
200. Ng et al., supta note 47, at 724;
201. see also PERSONALIZED MEDICINE COALITION, PERSONAL GENOMICS AND INDUSTRY STANDARDS: SCIENTIFIC VALIDITY (July 2008) (detailing common standards and differences between the predictive methodologies of 23andMe, Navigenics, and deCODE) available at http://bit.ly/KpJenC (last visited Apr. 29, 2012).
202. PMC, supra note 47, at 2-3.
203. 23andMe Letter to Heads of FDA and NIH, THE SPITTOON (Jul. 6, 2010, 11:13 PM), http://spittoon.23andme.com/2010/07/06/23andme-letter-to-heads-of-fda-and- nih/.
204. See, e.g., David Magnus, Mildred K. Cho & Robert Cook-Deegan, Direct-to-Consumer Genetic Tests: Beyond Medical Regulation? 1 GENOME MED. 17, 17.2 (2009).
205. See, e.g., Christina R. Lachance et al., Informational Content, Literacy Demands, and Usability of Websites Offering Health-Related Genetic Tests Directly to Consumers, 12 GENETICS IN MED. 304, 304 (2010);
206. see also supra note 36 (discussing the confusing relationship of odds ratios and risk ratios).
207. Id., at 309.
208. But see David Kaufman et al., Direct From Consumers: A Survey of 1,048 Customers of Three Direct-to-Consumer Personal Genomic Testing Companies About Motivations, Attitudes, and Responses to Testing, AM. SOC. HUMAN GENETICS MEETING (2010) ("88% of DTC customers agreed their risk report was easy to understand").
209. See generally Kohane, Masys, & Altman, supra note 77.
210. Robertson, supra note 11, at 242.
211. See, e.g., Solberg, supra note 22 at 720-21;
212. Green & Botkin, supra note 10, at 573.
213. Cinnamon S. Bloss, Nicholas J. Schork, & Eric J. Topol, Effect of Direct-to-Consumer Genomewide Profiling to Assess Disease Risk, 364 N.E.J. MED. 524, 532 (2011) ("We found no evidence that learning the results of [Navigenics'] genomic risk testing had any short term psychological, behavioral, or clinical effects on the study subjects.");
214. R. C. Green et al., Disclosure of APOE Genotype for Risk of Alzheimer's Disease, N. ENGL. J. MED. 361, 245-254 (2009) (subjects who tested positive for increased risk of Alzheimer's had negative feelings, but no clinically significant psychological distress);
215. but see Howard & Borry, supra note 80, at 107 (disputing the relevance of the Green study to DTC testing, because its subjects received medical supervision and counseling).
216. GAO, 2006 DTC INVESTIGATION, supra note 89. 23andMe and its peers do not sell personalized nutritional products to consumers, but by juxtaposing DTC genome services with disreputable nutrigenomics companies in its 2010 testimony, GAO unfortunately created the impression that all DTC companies engage in deceptive marketing.
217. SACGHS OVERSIGHT REPORT 131, 137;
218. Krieger, supra note 19 (describing bioethicist George Annas' concerns that testing college students for a gene "linked to alcohol metabolism could influence students' alcohol consumption").
219. Id.;
220. Frueh et al., The Future of Direct-to-Consumer Clinical Genetic Tests 12 NATURE REVIEWS GENETICS 511, 511 (2011) (women who test negative for breast cancer mutations may stop getting mammograms, and "such an ill-informed action could be fatal").
221. Carmichael, supra note 96.
222. Andrew Pollack, F.D.A. Faults Companies on Unapproved Genetic Tests, N.Y. TIMES (June 11, 2010) ("It is not unknown for women to take out their ovaries if they are at high risk of ovarian cancer" (quoting Alberto Gutierrez, Director of OIVD)); see also Solberg, supra note 22, at 721 (noting that some women with BRCA mutations will undergo prophylactic double mastectomies, and "[a]n inaccurate test result could therefore be devastating").
223. See, e.g., J.S. Roberts et al, Genetic Risk Assessment for Adult Children of People with Alzheimer's Disease: the Risk Evaluation and Education for Alzheimer's Disease (REVEAL) Study, 18 J. GERIATRIC PSYCHIATRY & NEUROLOGY 250, 254 (2005) (Alzheimer's risk information motivated engagement in risk-reducing activities like exercise).
224. See, e.g., Donald H. Taylor et al., Genetic Testing For Alzheimer's And Long-Term Care Insurance, 29 HEALTH AFFAIRS 102, 102 (2010) (individuals at increased risk of Alzheimer's are more likely to purchase long-term care insurance);
225. cf. Roberts et al., supra note 179 at 252-54 (subjects desired Alzheimer's risk information primarily for "reasons related to advance planning and emotional coping with the threat of disease").
226. Am. Coll. Med. Genetics & Genomics, supra note 78.
227. Frueh et al., supra note 176, at 514.
228. See infra notes 376-380 and accompanying text.
229. deCODE Genetics, an Icelandic company, has already gone bankrupt once.
230. SACGHS OVERSIGHT REPORT 13-15 (describing the mandates of the Secretary's Advisory Committee on Genetic Testing (SACGT) and its successor, the Secretary's Advisory Committee on Genetics, Health and Society (SACGHS)).
231. GAO, 2006 DTC INVESTIGATION, supra note 89.
232. Magnus et al., supra note 167.
233. Untitled Letters, formerly known as Information Letters, request that a recipient voluntarily correct a violation without threatening enforcement action. PETER BARTON HUTT, RICHARD A. MERRILL, & LEWIS A. GROSSMAN, FOOD AND DRUG LAW: CASES AND MATERIALS 1339 (3d ed. 2007).
234. Rob Stein, Walgreens Won't Sell Over-the-Counter Genetic Test After FDA Raises Questions, WASH. POST (May 13, 2010);
235. Letter from James L. Woods, Deputy Director, Patient Safety and Product Quality Office of In Vitro Diagnostic Device Evaluation and Safety, FDA, to James Plante, Founder and CEO, Pathway Genomics Corp., May 10, 2010, available at http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/ucm211866.htm.
236. Pollack, supra note 15.
237. Carmichael, Q&A, supra note 96 (quoting Alberto Gutierrez, Director of OIVD).
238. See infra notes 284-286 and accompanying text.
239. GAO, 2010 DTC INVESTIGATION, supra note 3.
240. Direct-to-Consumer Genetic Testing and the Consequences to the Public Health: Hearing before the Subcommittee on Oversight and Investigations of the House Energy and Commerce Committee, 112th Cong. (July 22, 2010).
241. Cf. David Castle & Nola M. Ries, Ethical, Legal and Social Issues in Nutrigenomics: The Challenges of Regulating Service Delivery and Building Health Professional Capacity, 62 Mutation Res. 138, 140 (2007) ("the [2006] GAO report has some serious methodological flaws that undermine many, if not all of its criticisms. For example, the report is premised on an incorrectly deterministic view of genetics").
242. Dan Vorhaus, "From Gulf Oil to Snake Oil": Congress Takes Aim at DTC Genetic Testing, GENOMICS L. REP. (July 22, 2010), http://www. genomicslawreport.com/wp-content/plugins/as-pdf/generate.php?post=4008.
243. FDA, March 8-9, 2011: Molecular and Clinical Genetics Meeting Announcement (updated Apr. 6, 2011), http://www.fda.gov/AdvisoryCommittees/ Calendar/ucm242537.htm (announcing a meeting to "discuss and make recommendations on scientific issues concerning direct to consumer (DTC) genetic tests that make medical claims").
244. ROUNDTABLE ON TRANSLATING GENOME-BASED RESEARCH FOR HEALTH, INSTITUTE OF MEDICINE, GENOME-BASED DIAGNOSTICS: CLARIFYING PATHWAYS TO CLINICAL USE: WORKSHOP REPORT 12-14 (Nat. Acad. Press 2012) [hereinafter IOM PATHWAYS WORKSHOP SUMMARY].
245. DHHS, Request for Comments on Issues of Privacy and Access With Regard to Human Genome Sequence Data, 77 Fed. Reg. 18247, 18247 (Mar. 27, 2012) (requesting comment on, inter alia, "balancing individual and societal interests with regard to the sharing of and access to large-scale human genomic data. . . who should have access to these data and who should control access; models and mechanisms for governing access to genomic information").
246. DHHS, PERSONALIZED HEALTH CARE: OPPORTUNITIES, PATHWAYS, RESOURCES, 32-36 (2007).
247. Margaret A. Hamburg & Francis S. Collins, The Path to Personalized Medicine, 363 NEW ENG. J. MED. 301, 304 (2010).
248. FDA, ADVANCING REGULATORY SCIENCE AT FDA: A STRATEGIC PLAN 10-13 (Aug. 2011), available at http://www.fda.gov/regulatoryscience.
249. See infra Part III.A.
250. Pub. L. No. 75-717, 52 Stat. 1040 (1935).
251. Peter Barton Hutt, A Brief History of the Regulation of In Vitro Diagnostic Products, in IN VITRO DIAGNOSTICS: THE COMPLETE REGULATORY GUIDE 1, 1 (Scott D. Danzis & Ellen J. Flannery eds., 2010).
252. Id. at 2 (quoting FD&C Act §§ 201(g), (h); 21 U.S.C. §§ 321(g), (h)).
253. PETER BARTON HUTT, RICHARD A. MERRILL, & LEWIS A. GROSSMAN, FOOD AND DRUG LAW: CASES AND MATERIALS 969 (3d ed. 2007).
254. Peter Barton Hutt, A Brief History of the Regulation of In Vitro Diagnostic Products, in IN VITRO DIAGNOSTICS: THE COMPLETE REGULATORY GUIDE 1, 5 (Scott D. Danzis and Ellen J. Flannery eds., 2010).
255. 394 U.S. 784 (1969). The Bacto-Unidisk product was a paper disc impregnated with antibiotics, which was exposed to a patient sample. The disc helped clinicians identify the best antibiotic to administer to the patient. The Supreme Court accepted the agency's determination that the disc was a drug, reasoning that "the word 'drug' is a term of art for purposes of the Act, encompassing far more than the strict medical definition of that word," and that the FDCA "is to be given a liberal construction consistent with the Act's overriding purpose to protect the public health."
256. Hutt, supra note 205, at 4.
257. 414 F. Supp. 660, 664 (D.N.J. 1975), aff'd mem., 535 F.2d 1248 (3d Cir. 1976).
258. 414 F. Supp. at 664.
259. Hutt, supra note 205, at 4.
260. FD&C Act § 201(h)-(h)(2) (emphasis added).
261. FD&C Act § 201(h)(3).
262. Peter Barton Hutt, Richard A. Merrill, & Alan M. Kirschenbaum, The Standard of Evidence Required for Premarket Approval Under the Medical Device Amendments of 1976, 47 FOOD & DRUG L.J. 605, 628 (1992);
263. see also Eric R. Claeys, The Food and Drug Administration and the Command-and-Control Model of Regulation, 49 St. Louis U. L.J. 105, 115-17 (2004).
264. See Clinical Reference Lab. v. Sullivan, 791 F. Supp. 1499, 1508 (D. Kan. 1992), aff'd in relevant part sub nom. United States v. Undetermined Number of Unlabeled Cases, 21 F.3d 1026 (10th Cir. 1994) (deferring to FDA's determination that specimen collection containers sent to and from a clinical laboratory were medical devices under the 1976 Amendments). The district judge explained that Congress disapproved of Ova II and intended to correct it in the 1976 Amendments. Id. (citing House Comm. on Interstate and Foreign Commerce, Medical Device Amendments of 1976, H.R. Rep. No. 853, 94th Cong., 2d Sess. 9, 14 (1976)).
265. Gail H. Javitt, Drugs and Vaccines for the Common Defense: Refining FDA Regulation to Promote the Availability of Products to Counter Biological Attacks, 19 J. CONTEMP. HEALTH L. & POL'Y 37, 98 (2002).
266. DANIEL CARPENTER, REPUTATION AND POWER: ORGANIZATIONAL IMAGE AND PHARMACEUTICAL REGULATION AT THE FDA 414-26 (2010).
267. Id.
268. United States v. Rutherford, 442 U.S. 544, 555-60 (1979).
269. FDA, Draft Guidance for Industry and Food and Drug Administration Staff - Mobile Medical Applications (July 21, 2011).
270. FDA, supra note 222 ("software that calculates a drug dose based on a patients height, weight, mass, and other patient-specific information [is regulated] as a 'Drug Dose Calculator' under 21 CFR 868.1890").
271. See 45 Fed. Reg. 60576, 60579 (1980) ("The most important factors [FDA] will consider in determining the intended use of a particular product are the labeling, advertising, and other representations accompanying the product."); Meaning of intended uses, 21 C.F.R. § 801.4 (2011).
272. FDA, Device Classification, available at http://www.fda.gov/ MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/default. htm (last visited Apr. 29, 2012). The device classification process is codified in 21 C.F.R. §§ 862-92 (2011).
273. 21 C.F.R. § 878.4460 (2011).
274. 21 C.F.R. § 880.2920 (2011).
275. 21 C.F.R. § 870.1120 (2011).
276. 21 C.F.R. § 862.1155 (2011).
277. 21 C.F.R. § 886.5925 (2011).
278. Bruce Patsner, New "Home Brew " Predictive Genetic Tests Present Significant Regulatory Problems, 9 HOUS. J. HEALTH L. & POL'Y 237, 247 (2009).
279. Id.
280. Hurt, Merrill, & Kirschenbaum, supra note 216, at 607-09. The 1976 Amendments allowed certain types of Class III devices already on the market ("preamendment devices") to be cleared through the less stringent 501(k) process, until FDA issues regulations requiring PMAs or reclassifies them.
281. GAO, MEDICAL DEVICES: FDA SHOULD TAKE STEPS TO ENSURE THAT HIGH-RISK DEVICE TYPES ARE APPROVED THROUGH THE MOST STRINGENT PREMARKET REVIEW PROCESS, 10 (2009), available at http://www.gao.gov/assets/290/284882.pdf. FDA has been criticized for continuing to allow preamendment devices to be cleared under the less stringent 501(k) process. Id.
282. Peter Barton Hurt, Turning Points in FDA History, in PERSPECTIVES ON RISK AND REGULATION: THE FDA AT 100, 14-28, at 18 (Arthur Daemmrich & Joanna Radin, eds. 2007).
283. FDA, Labeling Requirements-Misbranding, available at http://www.fda.gov/ MedicalDevices/DeviceRegulationandGuidance/Ovemew/DeviceLabeling/ GeneralDeviceLabelingRequirements/ucm052190.htm, (last visited Apr. 29, 2012). The jurisdictional prerequisite of a connection with interstate commerce is presumed.
284. FD&C Act § 709, 21 U.S.C. § 379a.
285. FD&C Act § 302.
286. FD&C Act §§ 201(k), (m);
287. FDA, Labeling Requirements - Misbranding, supra note 235.
288. FD&C Act § 520(e). A device may be restricted "if, because of its potentiality for harmful effect or the collateral measures necessary to its use, the Secretary determines that there cannot otherwise be reasonable assurance of its safety and effectiveness." Id.
289. 21 C.F.R. § 801.109. While most prescription devices are also restricted, the categories are not identical. See, e.g., Becton Dickinson v. FDA, 589 F.2d 1175, 1181 (2d Cir. 1978);
290. Patsner, supra note 231.
291. PETER BARTON HUTT, RICHARD A. MERRILL, & LEWIS A. GROSSMAN, FOOD AND DRUG LAW: CASES AND MATERIALS 1017 (3d ed. 2007). § 522 postmarket surveillance requirements, as modified by recent legislation, apply only to devices "the failure of which would be reasonably likely to have serious adverse health consequences."
292. See FDA, Postmarket Surveillance Under Section 522 of the Federal Food, Drug and Cosmetic Act (Apr. 25, 2006), available at http://www.fda.gov/ MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm072517.htm.
293. Peter Barton Hurt, The State of Science at the Food and Drug Administration, 60 ADMIN. L. REV. 431, 445 (2008).
294. See also Evans, Seven Pillars, supra note 61, at 419 (2010) (arguing that to cope with genomic technology, FDA must abandon its focus on premarket approval and prioritize postmarket information collection and monitoring).
295. 21 CRR. § 809.3(a) (2011).
296. FDA, Guidance for Industry and FDA Staff: In Vitro Diagnostic QVD) Device Studies - Frequently Asked Questions 6 (June 25, 2010). IVDs are overseen by the FDA Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD). Id.
297. See Gail H. Javitt, Erica Stanley & Kathy Hudson, Direct-to-Consumer Genetic Tests, Government Oversight, and the First Amendment: What the Government Can (and Can't) Do to Protect the Public's Health, 57 OKLA. L. REV. 251, 271-72 (2004).
298. Jeffrey Gibbs, Regulatory Pathways for Clearance or Approval of IVDs, in IN VITRO DIAGNOSTICS: THE COMPLETE REGULATORY GUIDE 43, 57 (Scott D. Danzis and Ellen J. Flannery eds., 2010).
299. See generally Gibbs, supra note 245, at 43-68.
300. See also 21 C.F.R. §§ 862, 864, 866 (2011) (existing IVD classifications).
301. Id. at 45 (noting that in 2005, OIVD cleared 434 501(k)s, but approved only nine PMAs).
302. Id. at 51-52. If there is no predicate device suitable on the market, the applicant may request de novo classification. Id. at 52-53. While FDA has exempted many Class I and II devices from 501(k), the exemption does not apply to IVDs for "noninvasive testing" and/or "use in screening or diagnosis of familial or acquired genetic disorders," which presumably includes DTC genetic tests. 21 C.F.R. § 880.9 (2011).
303. Gibbs, supra note 245, at 52-53.
304. 21 C.F.R. § 860.7(c)(1) (2011).
305. 21 C.F.R. § 860.7(d)(1) (2011).
306. 21 C.F.R. § 860.7(e)(1) (2011).
307. Gibbs, supra note 245, at 58 (in general, "a test with an intended use claim of 'ruling in' a disease will be reviewed differently than 'ruling out.'").
308. FDA, Guidance for Industry and Food and Drug Administration Staff: Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications (Mar. 27, 2012), available at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/ GuidanceDocuments/UCM29379.pdf.
309. Id.
310. Patsner, supra note 231, at 247.
311. FDA, 510(k) Substantial Equivalence Determination Decision Summary for Roche AmpliChip CYP450 microarray for identifying CYP2D6 genotype (510(k) Number k042259), http://www.accessdata.fda.gov/cdrh-docs/reviews/K042259.pdf (last visited Apr. 29, 2012).
312. See supra Part I, notes 38-46, and accompanying text.
313. SACGHS OVERSIGHT REPORT 97 ("the law and regulations do not define clinical validity as a parameter to be reviewed by FDA. Instead, FDA is charged with assessing the safety and effectiveness of the device or test").
314. SACGHS OVERSIGHT REPORT 135;
315. IOM PATHWAYS WORKSHOP SUMMARY 8.
316. SACGHS OVERSIGHT REPORT 115.
317. Id. at 135;
318. IOM PATHWAYS WORKSHOP SUMMARY 35.
319. Gibbs, supra note 245, at 54.
320. IOM PATHWAYS WORKSHOP SUMMARY 35 (paraphrasing Alberto Gutierrez, Director of OIVD).
321. Justin P. Annes, Monica A. Giovanni, & Michael F. Murray, Risks of Presymptomatic Direct-to-Consumer Genetic Testing, 363 N.E.J. MED. 1100, 1100 (2010) ("The FDA deemed [Roche's test] acceptable for aiding 'clinicians in determining therapeutic strategy and treatment doses,' despite the dearth of prospective data showing clinical utility.");
322. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group, Recommendations from the EGAPP Working Group: Testing for Cytochrome P450 Polymorphisms in Adults With Nonpsychotic Depression Treated With Selective Serotonin Reuptake Inhibitors, 9 GENETICS IN MED. 819, 820 (2007) ("The FDA extensively reviewed the technical performance of [Roche's] assay; review of clinical validity was limited, and clinical utility was not evaluated.").
323. FDA, supra note 257;
324. FDA, Class II Special Controls Guidance Document: Drug Metabolizing Enzyme Genotyping System - Guidance for Industry and FDA Staff (Mar. 10, 2005), http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ ucm077933.htm ("Prospective clinical testing to determine clinical validity may not be necessary for validation of DME genotyping systems, if there is an established scientific framework and sufficient body of evidence supporting the clinical validity and utility of your device.").
325. FDA, supra note 170.
326. Hutt, supra note 208, at 7.
327. FDA, Oversight of Laboratory Developed Tests; Public Meeting; Request for Comments, 75 Fed. Reg. 34,463, 34,463 (June 17, 2010);
328. Ellen Flannery & Scott Danzis, FDA Plans to Regulate Laboratory Developed Tests as Devices, 7 J. Med. Device Reg. 63, 63 (2010).
329. Gail H. Javitt & Kathy Hudson, Federal Neglect: Regulation of Genetic Testing, 22 ISSUES IN SCI. & TECH. 59, 61(2006).
330. Id.
331. Patsner, supra note 231 at 255, 265 ("an entire industry of diagnostic drug assays and genetic tests has developed outside the penumbra of FDA regulatory oversight").
332. SACGHS OVERSIGHT REPORT 39 (2008) ("although BRCA tests are widely used to predict patients' future risk of breast and ovarian cancer, no BRCA test has been approved by FDA.").
333. Evans, Seven Pillars, supra note 61, at 419, 465 (2010) ("Over 90% of genetic tests currently on the market are lab-developed tests (LDTs) regulated under CLIA and not regulated by FDA.").
334. Ellen Flannery & Scott Danzis, FDA Plans to Regulate Laboratory Developed Tests as Devices, 7 J. MED. DEVICE REG. 63, 63 (2010).
335. Jeffrey N. Gibbs, The Past, Present, and Future of ASRs, IVD TECHNOLOGY (Nov. 1, 2003), available at http://www.ivdtechnology.com/article/past-present- and-future-asrs.
336. FDA, Guidance for Industry and FDA Staff. Commercially Distributed Analyte Specific Reagents (ASRs): Frequently Asked Questions. (2007), available at http://www.fda.gov/cdrh/oivd/guidance/1590.pdf. See generally 21 C.F.R. § 864.4020 (definition and classification of ASRs), § 809.30 (restrictions on sale, distribution and use), and § 809.10(e) (labeling).
337. Id.
338. FDA, Draft Guidance for Industry, Clinical Laboratories, and FDA Staff: In Vitro Diagnostic Multivariate Index Assays 2 (Sept. 7, 2006). The draft guidance was revised in 2007.
339. FDA, Draft Guidance for Industry, Clinical Laboratories, and FDA Staff: In Vitro Diagnostic Multivariate Index Assays (July 26, 2007).
340. Id.
341. Id.
342. FDA, News Release: FDA Clears Breast Cancer Specific Molecular Prognostic Test (Feb. 6, 2007) (describing the clearance of the MammaPrint test based on "data from a study using tumor samples and clinical data from 302 patients at five European centers.").
343. Mya Thomae, Are Multiplex Assays Approvable? 3 BIOANALYSIS 1791, 1791-94 (2011);
344. Ellen Flannery & Scott Danzis, FDA Plans to Regulate Laboratory Developed Tests as Devices, 7 J. MED. DEVICE REG. 63, 66 N.9 (2010).
345. FDA, Oversight of Laboratory Developed Tests; Public Meeting; Request for Comments, 75 Fed. Reg. 34,463, 34,463-64. (June 17, 2010). FDA subsequently reopened the comment period until September 15, 2010.
346. 75 Fed. Reg. 51,280.
347. Id.
348. Id.
349. SACGHS OVERSIGHT REPORT 107 ("Very few LDTs... are reviewed by FDA, and the agency does not currently have sufficient resources to carry out such reviews for all tests if existing review mechanisms are used.").
350. See, e.g., David Filmore, LabCorp Pulls OvaSure, But Charges FDA With Overreaching, The Gray Sheet (Oct. 27, 2008) (describing FDA's 2008 warning letter informing LabCorp that its OvaSure biomarker test was not an LDT, because it was "designed, developed, and validated" by Yale researchers, not the clinical laboratory);
351. Patsner, supra note 231 at 267.
352. See infra notes 307-329 and accompanying text.
353. Letter from Alberto Gutierrez, Director, Office of In Vitro Diagnostic Device Evaluation and Safety, FDA, to Anne Wojcicki, CEO, 23andMe (June 10, 2010) ("FDA does not consider your device to be a laboratory developed test because [it] is not developed by and used in a single laboratory"); Letter from Alberto Gutierrez, Director, Office of In Vitro Diagnostic Device Evaluation and Safety, FDA, to Earl M. Collier, CEO, deCODE Genetics (June 10, 2010) (similar); Letter from Alberto Gutierrez, Director, Office of In Vitro Diagnostic Device Evaluation and Safety, FDA, to Jorge Conde, CEO, Knome, Inc. (June 10, 2010) (similar).
354. See, e.g., Ericksson et al., supra note 106, at 2 (summarizing 23andMe's process).
355. See infra Part III, notes 413-415 and accompanying text.
356. HS OVERSIGHT REPORT 180-181 (IVDMIAs include "a device that integrates a patient's age, gender, and genotype of multiple genes to predict risk of or diagnose a disease or condition"; however, it is unclear when multiple interpretation tasks are combined in different locations if they constitute an IVDMIA.);
357. Magnus, supra note 167 (stating that there is "only a thin line" between IVDMIAs and DTC genomic services).
358. FDA, Draft Guidance for Industry and FDA Staff - Commercially Distributed In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only: Frequently Asked Questions (June 1, 2011), available at http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ ucm253307.htm.
359. Gibbs, Past, Present, and Future, supra note 276.
360. Hutt, supra note 205, at 8. See also 21 C.F.R. § 812.2(c) (2011).
361. FDA, supra note 294.
362. 21 C.F.R. § 809.10(c)(1)(i) (2011). IVDs in the clinical research stage of product development are exempted for investigational study or testing purposes under the investigational device exemption (IDE) regulation, 21 C.F.R. part 812, or as Investigational Use Only ("IUO") devices under 21 C.F.R. § 812.2(c)(3) (2011).
363. FDA, supra note 294.
364. Alex Philippidis, Diagnostic Market Stakeholders Take Aim at FDA's RUO/IUO Draft Guidance, GENETIC ENG'G & BIOTECHNOLOGY NEWS (July 6, 2011), available at http://www.genengnews.com/insight-and-intelligenceand153/ diagnostic-market-stakeholders-take-aim-at-fda-s-ruo-iuo-draft-guidance/ 77899428/.
365. Our Technology and Standards, 23ANDME, https://www.23andme.com/ howitworks/ (last visited Apr. 29, 2012) ("We utilize the Illumina OmniExpress Plus Research Use Only Chip which has been customized for use in all of our products and services by 23andMe.").
366. Letter from Alberto Gutierrez, Director, OIVD, FDA, to Mr. Jay T. Flatley, President and CEO, Illumina, Inc. (June 10, 2010).
367. FDA Draft Guidance, supra note 297.
368. Philippidis, supra note 300.
369. Id.
370. Letter from Chairman Joseph R. Pitts, House of Representatives Committee on Energy and Commerce Subcommittee on Health, to FDA Commissioner Margaret A. Hamburg (Mar. 19, 2012).
371. Hutt, supra note 205, at 7.
372. CMS, Clinical Laboratory Improvement Amendments (CLIA), available at http://www.cms.hhs.gov/Regulations-and-Guidance/Legislation/CLIA/index.html.
373. Id.
374. Id. FDA makes these complexity determinations. 42 C.F.R. § 493.17(c)(1)(i) (2011).
375. Id.
376. GAO, CLINICAL LAB QUALITY: CMS AND SURVEY ORGANIZATION OVERSIGHT SHOULD BE STRENGTHENED 8-10 (2006). See also Ellen Flannery & Scott Danzis, FDA Plans to Regulate Laboratory Developed Tests as Devices, 7 J. Med. Device Reg. 63, 63 (2010) ("New York... requires that all LDTs be approved by state authorities before they may be used in testing specimens from state residents.");
377. SACGHS Oversight Report 35 ("New York State has specific standards for genetic testing, but Washington State does not.").
378. 42 C.F.R. § 493.1253 (2011).
379. SACGHS OVERSIGHT REPORT 3.
380. 42 C.F.R. § 493.1241(a) (2011).
381. GAO, CLINICAL LAB QUALITY, supra note 312.
382. SACGHS OVERSIGHT REPORT 32.
383. Neil A. Holtzman, Promoting Safe and Effective Genetic Tests in the United States: Work of the Task Force on Genetic Testing, 45 CLINICAL CHEMISTRY 732, 736 (1999). The final report of the Task Force is available at http://www.genome.gov/10001733.
384. SACGHS OVERSIGHT REPORT 14.
385. Kathy Hudson et al., ASHG Statement on Direct-to-Consumer Genetic Testing in the United States, 81 AM. J. HUMAN GENETICS 635, 636 (2007).
386. SACGHS OVERSIGHT REPORT 31.
387. CMS, Direct Access Testing (DAT) and the Clinical Laboratory Improvement Amendments (CLIA) Regulations, available at http://www.cms.hhs.gov/Regulations- and-Guidance/Legislation/CLIA/Downloads/directaccesstesting.pdf (last visited April 14, 2012).
388. SACGHS OVERSIGHT REPORT 15.
389. SACGHS OVERSIGHT REPORT 111, 108.
390. Id. at 113-114
391. Id. at 111-113
392. Id. at 113.
393. Id. at 6, 111.
394. Letter from the Secretary's Advisory Committee on Genetics, Health, and Society to Secretary Michael O. Leavitt (April 30, 2008).
395. See Anne V. Maher & Lesley Fair, FTC's Regulation of Advertising, 65 FOOD & DRUG L.J. 589, 602-05 (2010).
396. Id. at 603.
397. Maher & Fair, supra note 330, at 610.
398. Id. at 590.
399. FTC v. QT, Inc., 512 F.3d 858, 861 (7th Cir. 2008).
400. FTC, Federal Trade Commission Substantiation Policy Statement, 104 F.T.C 840 (adopting factors from Pfizer, Inc., 81 F.T.C. 23 (1972)).
401. Maher & Fair, supra note 330, at 607.
402. Javitt & Hudson, supra note 270, at 65.
403. FTC, FTC Facts for Consumers: At-Home Genetic Tests: A Healthy Dose of Skepticism May Be the Best Prescription (July 2006), available at http://www.ftc.gov/bcp/edu/pubs/consumer/health/hea02.shtm.
404. GAO, 2010 REPORT, supra note 3, at 1.
405. SACGHS OVERSIGHT REPORT 113.
406. Id.
407. EGAPP Working Group Recommendations, EGAPP (updated Feb. 29, 2012), http://www.egappreviews.org/recommendations/index.htm.
408. SACGHS OVERSIGHT REPORT 112-13.
409. Press Release, NIH, Confused By Genetic Tests? NIH's New Online Tool May Help (Feb. 29, 2012) (noting that GTR will include "the purpose of each genetic test and its limitations; the name and location of the test provider; whether it is a clinical or research test; what methods are used; and what is measured") available at http://www.nih.gov/news/health/feb2012/od-29.htm.
410. NIH, NIH Genetic Testing Registry Fact Sheet (Feb. 29, 2012), http://oba.od.nih.gov/oba/gtr/GTR-Fact-Sheet-2-28-12.pdf.
411. Genetics Home Reference: Your Guide to Understanding Genetics Conditions, NIH (Apr. 16, 2012), http://ghr.nlm.nih.gov/.
412. Wyeth v. Levine, 555 U.S. 555, 567 (U.S. 2009) (internal quotations and citation omitted).
413. See generally Marietta & McGuire, supra note 15.
414. SACGHS OVERSIGHT REPORT 37.
415. See supra note 312 (citing examples of state regulation of clinical laboratory tests).
416. See Genetics & Pub. Pol'y Ctr., Survey of Direct-to-Consumer Testing Statutes and Regulations, (June 2007), http://www.dnapolicy.org/resources/ DTCStateLawChart.pdf (last visited Apr. 29, 2012) (explaining that although federal regulations do not require CLIA laboratories to obtain physician authorization, state law often does); see also Conley, supra note 114, at 36-41 (describing the impact of state regulation on public genomics research).
417. Magnus et al., supra note 167, at 17.1-17.2 (2009).
418. Andrew Pollack, California Licenses 2 Companies to Offer Gene Services, N. Y. TIMES C3 (Aug. 19, 2008).
419. Krieger, supra note 19.
420. Robert Sanders, UC Berkeley alters DNA testing program, UC BERKELEY NEWSCENTER (Aug. 12, 2010), available at http://newscenter.berkeley.edu/2010/08/ 12/dna-change/.
421. Id.
422. Magnus et al., supra note 167, at 17.2-17.3 (2009).
423. Dan Vorhaus & Jennifer K. Wagner, Alabama's "Genetic Information Privacy Act" & the Ongoing Need for Personal Genomics Leadership, GENOMICS L. REP. (FEB. 16, 2012), http://www.genomicslawreport.com/index.php/ 2012/02/16/alabamas-genetic-information-privacy-act-the-ongoing-need-for- personal-genomics-leadership.
424. Patsner, supra note 231, at 266.
425. Robert VerBruggen, The FDA 's Genetic Paternalism, NATIONAL REVIEW (March 23, 2011 4:00 AM), available at http://bit.ly/h1zW7t; see a/so Goetz, supra note 156. But see Evans & Berg, supra note 154, at 2377 (arguing that "medicine is, to at least some extent, an inherently paternalistic endeavor simply because of an inevitable asymmetry in knowledge").
426. See supra Part I.F.
427. E.g., GAO, 2010 REPORT, supra note 3, at 8 (genomic services are "promising for research, but the application is premature").
428. Timothy Caulfield, DTC Genetic Testing: Pendulum Swings and Policy Paradoxes, 81 CLINICAL GENETICS 4 (2012).
429. See, e.g., Stephen E. Ross & Chen-Tan Lin, The Effects of Promoting Patient Access to Medical Records: A Review, 10 J. AM. MED. INFORMATICS ASS'N 129, 129 (2003) (finding that while few patients sought their records, "patient-accessible medical records are unlikely to cause harm in medical patients and have the potential for modest benefits").
430. Id., 131-36.
431. Patient Access: Centers for Medicare & Medicaid Services, CLIA Program and HIPAA Privacy Rule; Patients' Access to Test Reports, 76 Fed. Reg. 56,712, 56,714 (Sept. 14, 2011) ("in an effort to increase direct patient access rights... upon a patient's request, CLIA regulations would allow laboratories to provide direct patient access to completed test reports").
432. DHHS, supra note 53.
433. CARPENTER, supra note 219, at 79-80.
434. Id. at 215-16.
435. Id.
436. Id. at 414.
437. Id. at 411.
438. Id. at 418-22.
439. Id. at 417-18.
440. Id. at 423.
441. Serra Schlanger, Filling in the Cracks: Improving the Regulation of Direct-to-Consumer Genetic Tests, 14 J. HEALTH CARE L. & POL'Y S1, S19-24 (2011);
442. Jennifer A. Gniady, Regulating Direct-to-Consumer Genetic Testing: Protecting the Consumer Without Quashing a Medical Revolution, 76 Fordham L. Rev. 2429, 2453-54 (2008);
443. Mary Pendergast, Statement To Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee, March 8-9, 2010 Meeting, FDA-2011-N-0066 (Mar. 1, 2010) (Ms. Pendergast, a former FDA official and medical device consultant, has advised 23andMe).
444. Gniady, supra note 376, at 2454; see also Schlanger, supra note 376, at S20.
445. Gary Blonston, Home HIV Test Wins Support, Opposition - FDA Advisory Committee Wrestles With Proposal, SEATTLE TIMES (June 23, 1994) (quoting Bruce Decker, president of the Health Policy Research Foundation).
446. Schlanger, supra note 376, at S19-24.
447. Id. at S25; Pendergast, supra note 376.
448. Ross, supra note 10, at 142-43 (comparing HIV exceptionalism with genetic exceptionalism). 382 Schlanger, supra note 376, at S29 (observing that both tests could cause "dramatic health-related decisions").
449. Pendergast, supra note 376.
450. Schlanger, supra note 376, at S25; Green & Botkin, supra note 10, at 573.
451. See Pendergast, supra note 376 ("I cannot conceive of any information that a consumer could learn through a genetic test that would be as important as HIV status."). Even if this does not hold true with respect to dominant single-gene disorders like Huntington's disease, predictive SNP chip testing does not typically test for, or report on, single-gene disorders like Huntington's.
452. Cf. Shobita Parthasarathy, Breaking the Expertise Barrier: Understanding Activist Strategies in Science and Technology Policy Domains, 37 Sci. PUB. POL'Y, 355, 356-57 (2010) ("proposals to incorporate citizen participation in [science and technology] policy... have had limited impact" because "insiders often argue that the average person operates at a knowledge 'deficit' and cannot properly comprehend the complex issues under discussion").
453. DENNIS THOMPSON, POLITICAL ETHICS AND PUBLIC OFFICE 173 (1987).
454. See generally RICHARD H. THALER & CASS R. SUNSTEIN, NUDGE: IMPROVING DECISIONS ABOUT HEALTH, WEALTH, AND HAPPINESS (2008).
455. See, e.g., Bloss, supra note 173.
456. FD&C Act § 201(h)(2).
457. Cf. SACGHS OVERSIGHT REPORT 119 (suggesting that predictive testing may increase "medicalization of previously unknown conditions and risk factors linked to important health conditions"); Marietta & McGuire, supra note 15, at 371 ("It could be argued that testing asymptomatic persons for disease risk does not constitute a diagnosis... because no disease or pathology exists," but "this 'assumes a limited view of medicine'" (quoting Han, supra note 22)).
458. Id.
459. See, e.g., United States of America v. 25 Cases, More or Less, of an Article of Device... "Sensor Pad for Breast Self-Examination," 942 F.2d 1179 (7th Cir. 1991) (rejecting as "untenable" a "screening/diagnosing distinction" that would mean a breast exam pad "used before actual diagnosis" was not a device);
460. cf. U.S. v. Undetermined Number of Unlabeled Cases, 21 F.3d 1026 (10th Cir. 1994) (holding that sample containers for HIV testing were devices, even when used for insurance risk assessment rather than medical treatment).
461. James T. O'Reilly, Losing Deference in the FDA's Second Century: Judicial Review, Politics, and a Diminished Legacy of Expertise, 93 CORNELL L. REV. 939, 947-48 (2008).
462. E.g., FDA, Executive Summary, Molecular and Clinical Genetics Panel, 5 (Mar. 8-9, 2011), available at http://www.fda.gov/downloads/AdvisoryCommittees/ CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ MolecularandClinicalGeneticsPanel/UCM245660.pdf.
463. Bamshad, supra note 149, at 937.
464. Id.
465. Id. at 937, 940 (explaining the difference between race and ancestry); see also generally Rick A. Kittles & Kenneth M. Weiss, Race, Ancestry and Genes: Implications for Defining Disease Risk, 4 ANNUAL REV. GENOMICS & HUMAN GENETICS 33 (2003) ("race reflects deeply confounded cultural as well as biological factors, and a careful distinction must be made between race as a statistical risk factor and causal genetic variables").
466. Bamshad, supra note 149, at 944-45.
467. 23andMe, offers both ancestry and health services, and apparently sequences the same SNPs for both. Our Technology and Standards, 23ANDME, https://www.23andme.com/howitworks/ ("We utilize the Illumina OmniExpress Plus Research Use Only Chip which has been customized for use in all of our products and services... ") (last visited April 29, 2012).
468. It is unclear how many of the DTC ancestry companies permit consumers to download raw SNP data, but interestingly, only one quarter of them expressly limit the "intended use" of their services to "recreational, educational, or entertainment purposes." Wagner et al., supra note 85.
469. See supra notes 290-291, and accompanying text.
470. See FDA Docket No. 2006-P-0402, Citizen Petition of Washington Legal Foundation (Sept. 28, 2006) (challenging FDA authority over LDTs, with the express exclusion of DTC tests); FDA Docket 1992-P-0405, Citizen Petition of Hyman, Phelps & McNamara, P.C. (Oct. 22, 1992).
471. See Comments of Hyman, Phelps & McNamara, P.C., in Support of Wash. Legal Found. Citizen Petition 2-9 (Mar. 23, 2007);
472. FDA Docket No. 2006-P-0402, Citizen Petition of Wash. Legal Found. 8-11 (Sept. 28, 2006).
473. Accord Richard A. Merrill, Genetic Testing? A Role for FDA, 41 JURIMETRICS 63, 64 (2000) ("A prescription for a genetic test, to be performed by a laboratory that brews its own assays... surely falls near the outer periphery of FDA's historical authority.").
474. See Han, supra note 22, at 431-32.
475. See. e.g., SHOBITA PARTHASARATHY, BUILDING GENETIC MEDICINE: BREAST CANCER, TECHNOLOGY, AND THE COMPARATIVE POLITICS OF HEALTH CARE 129-32 (2007) (DESCRIBING MYRIAD GENETICS' NATIONAL ADVERTISING CAMPAIGN FOR ITS BRACANALYSIS BREAST CANCER RISK TESTS).
476. See supra notes 276-278 and accompanying text (discussing the ASR rule).
477. See Comments of Hyman, Phelps and McNamara, P.C., in Support of Washington Legal Foundation Citizen Petition 9-25 (March 23, 2007);
478. FDA Docket No. 2006-P-0402, Citizen Petition of Washington Legal Foundation 15-17 (Sept. 28, 2006).
479. Ellen Flannery & Scott Danzis, FDA Plans to Regulate Laboratory Developed Tests as Devices, 7 J. MED. DEVICE REG. 63, 63 (2010).
480. See generally K.M. Lewis, Informal Guidance and the FDA, 66 FOOD & DRUG L.J. 507, 520, 540-41 (2011).
481. United States v. Franck's Lab, Inc., 816 F. Supp. 2d 1209, 1253 (M.D. F1a. 2011). An appeal to the was pending at the time this paper was submitted. 11th Cir. No. 11-15350-BB.
482. E.g., Letter from Alberto Gutierrez, Director, OIVD, FDA, to Jorge Conde, CEO, Knome, Inc. (June 10, 2010).
483. Beyond its untitled letters, FDA has not clarified why DTC services are not LDTs. FDA may also have concerns about other aspects of DTC services, such as mailing sample containers directly to consumers, reporting results directly to consumers, or using gene chips meant for research use only. Cf. Stein, supra note 189 (citing an unnamed FDA official, explaining that Pathway Genomics' service required approval because "it involved consumers collecting their own DNA").
484. See, e.g., Statement of Jeff Shuren, supra note 8 (noting that LDTs "often require complex software and may incorporate automated interpretation in lieu of expert interpretation"); Magnus et al., supra note 167.
485. Technology Overview, KNOME, http://www.knome.com/technology/ (last visited Apr. 29, 2012) (describing Knome's "genome informatics engine" kGAP).
486. Mallorye Allison, Illumina's Cut-Price Genome Scan, 27 NATURE BIOTECHNOLOGY 685 (Aug. 8, 2009) ("Knome... the only other company currently marketing whole-genome scans to consumers, charges $99,500 for KnomeCOMPLETE");
487. Andrew Pollack, F.D.A. Faults Companies on Unapproved Genetic Tests, N.Y. Times (June 11, 2010) ("Knome [] offers consumers a complete sequence of their DNA").
488. Press Release, Knome and Seq Wright to Offer Personal Genomics Services Through CLIA-Certified Laboratory BUSINESS WIRE (June 10, 2009, 04:55) available at http://bit.ly/KgZORv.
489. Letter from Alberto Gutierrez to Jorge Conde, supra note 413 ("[Knome] described KnomeCOMPLETE™ as consisting of a software program that analyzes genetic test results that are generated by an external laboratory in order to generate a patient specific test report. Thus, the KnomeCOMPLETE™ is a diagnostic device and subject to all applicable requirements of the Act.").
490. Id.
491. Carmichael, Q&A, supra note 96 (quoting Alberto Gutierrez).
492. Mary Carmichael, DNA Dilemma: The Full Interview With the FDA on DTC Genetic Tests, NEWSWEEK (Aug 5, 2010)
493. See FDA supra note 222.
494. Id.
495. Id. (FDA considers such software "mobile medical apps," but intends to exercise enforcement discretion over software that can "automate common medical knowledge available in the medical literature" or "allow individuals to self-manage their disease or condition," even if that software is a medical device.).
496. Promethease, SNPEDIA (updated Apr. 14, 2012), http://www.snpedia.com/ index.php/Promethease.
497. Cf. Donald H. Taylor et al., Genetic Testing For Alzheimer's And Long-Term Care Insurance, 29 HEALTH AFFAIRS 102, 106 (2010) (if "Alzheimer's disease risk is not reported directly" by a DTC service, "it can be inferred" with "freely available Internet resources such as SNPedia.").
498. Salzberg & Pertea, supra note 76, at 404.
499. Interpretome, STANFORD UNIVERSITY, http://esquilax.stanford.edu/ (last visited Apr. 29,2012).
500. See, e.g., Benjamin M. Good, Salvatore Loguercio & Andrew I. Su, Linking Genes to Diseases With a SNPedia-Gene Wiki Mashup, BIO-ONTOLOGIES SIG (July 19, 2011) available at http://bio-ontologies.knowledgeblog.org/250 (describing a software tool for answering the question "Based on what we know now, what genes are linked to which diseases?").
501. Salzberg & Pertea, supra note 76, at 404, 406 ("In creating this software, we are not violating the BRCA patents directly but any user would be..."). Interestingly, Salzberg & Pertea's paper openly criticized "restrictive" gene patents because "any individual should be allowed to interrogate his or her genome for all mutations of interest," but never mentioned FDA.
502. Carmichael, DNA Dilemma, supra note 422 ("The question with 23andMe has been whether their claims were medical claims or not... Now clearly [they] are medical claims." (quoting OIVD Director Alberto Gutierrez)); Statement of Jeff Shuren, supra note 8 (DTC tests "meet the statutory definition of a medical device on the basis of the manufacturers' claims about the test results").
503. Statement of Jeff Shuren, supra note 8.
504. Carmichael, DNA Dilemma, supra note 422.
505. See FDA, Executive Summary, Molecular and Clinical Genetics Panel, 5 (Mar. 8-9, 2011), available at http://l.usa.gov/hqkllo (identifying three types of genetic tests: clinical tests for the purpose of 'diagnosis, prevention, or treatment'; tests for research; and tests 'that do not carry medical claims, such as ancestry or forensic tests.' FDA disclaimed authority over the third category only).
506. See supra notes 224-245, and accompanying text.
507. Adapted from FDA, Medical Claims on Labeling and Promotional Materials of Infant Mattresses and Infant Positioners Distributed in the United States (March 13, 2000).
508. For an insightful general discussion of First Amendment doctrine with relation to expert knowledge, including medical knowledge, see ROBERT C. POST, DEMOCRACY, EXPERTISE, AND ACADEMIC FREEDOM: A FIRST AMENDMENT JURISPRUDENCE FOR THE MODERN STATE (2012).
509. See, e.g., Kevin Ouetterson, Higher First Amendment Hurdles for Public Health Regulation, N. E. J. MED. E131 (APR. 23, 2012).
510. See generally David Orentlicher, The Commercial Speech Doctrine in Health Regulation: The Clash Between the Public Interest in a Robust First Amendment and the Public Interest in Effective Protection From Harm, 37 AM. J. L. MED. 299 (2011).
511. See, e.g., Pearson v. Shalala, 164 F.3d 650 (D.C. Cir. 1999).
512. Javitt, Stanley & Hudson, supra note, at 254.
513. Sorrell v. IMS Health Inc., 131 S. Ct. 2653, 2666-67 (U.S. 2011) (internal quotations and citations omitted).
514. Id. at 2676.
515. Id.
516. Id.; see also Orentlicher, supra note 440, at 310 (asserting that "[t]he data mining laws [at issue in Sorrell] regulate economic transactions between data mining companies and their customers, not the content of their expression.").
517. Among the many differences between these situations, it is especially important to note that patient privacy was not an issue in Sorrell. Had the "speech" implicated privacy concerns, the Court's analysis might have turned out differently.
518. POST, supra note 438, at 43. For an interesting discussion of the "right to receive" aspect of First Amendment doctrine in the context of gene patents, see Krysta Kauble, Patenting Everything Under the Sun, 58 U.C.L.A. L. REV. 1123 (2011).
519. POST, supra note 438, at 55-60.
520. Sorrell v. IMS Health Inc., 131 S. Ct. at 2671.
521. For an in-depth analysis of the intellectual property infrastructures undergirding innovation, see BRETT M. FRISCHMANN, INFRASTRUCTURE: THE SOCIAL VALUE OF SHARED RESOURCES 253-314 (2012).
522. SACGHS OVERSIGHT REPORT 97;
523. SEE ALSO ID., AT 120 (NOTING SUBTLE DIFFERENCES BETWEEN FDA'S USE OF THE TERM "EFFECTIVENESS" AND THE USE OF "EFFECTIVENESS" IN STUDIES OF CLINICAL UTILITY).
524. See, e.g., Robertson, supra note 11; Han, supra note 22 at 438-41 (arguing that FDA should not regulate a genetic test's "predictive value" to patients); Green & Botkin, supra note 10, at 573 ("Tests that should be handled with caution include those that identify stigmatizing diseases, substantially affect family members, lack acceptable and effective treatments, and have results that are difficult for clinicians to interpret.").
525. SACGHS OVERSIGHT REPORT 115.
526. Id. at 117.
527. IOM PATHWAYS WORKSHOP SUMMARY 8 (quoting Daniel Hayes of the University of Michigan Comprehensive Cancer Center).
528. Marietta & McGuire, supra note 15 at 373.
529. SACGHS OVERSIGHT REPORT 127.
530. See, e.g., Bogardus, supra note 68, at 210 ("[T]here is not likely to be clinical utility of the GWAS results (for BMI and type 2 diabetes at least) in the foreseeable future in populations of European descent.")
531. Gordon, supra note 141, at 252.
532. Gordon, supra note 141, at 252 (quoting HHS, Response of the Department of Health and Human Services to NBAC's Report Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, at 23 (2001), available at http://aspe.hhs.gov/sp/hbn/hbm.pdf).
533. Id.
534. Wright & MacArthur, supra note 82, at 230.
535. See, e.g., supra note 126 (summarizing reasons NATURE READERS OBTAINED DTC TESTING).
536. Michael Convente, Our Genome Decoded: How Companies Like 23andMe Are A dvancing the Field of Personal Genomics, DAILY KOS (Mar. 30, 2011), http://www.dailykos.com/story/2011/03/30/961626/-Our-Genome-Decoded-How- Companies-Like-23andMe-Are-Advancing-the-Field-of-Personal-Genomics.
537. SACGHS OVERSIGHT REPORT 122;
538. IOM INTEGRATION WORKSHOP SUMMARY 5 (attributed to Leslie Biesecker of NHGRI).
539. But see Evans & Berg, supra note 154 (observing that over "80% of individuals who are intimately familiar with Huntington disease choose not to pursue presymptomatic testing").
540. Transcript, March 8, 2011 Meeting of the Molecular and Clinical Generics Panel, Medical Devices Advisory Committee, CDRH, FDA, 290-98.
541. See supra Part LF.
542. SACGHS OVERSIGHT REPORT 187.
543. Frueh et al., supra note 176.
544. Pollack, supra note 178.
545. Solberg, supra note 22.
546. Transcript, March 8, 2011 Meeting of the Molecular and Clinical Genetics Panel, Medical Devices Advisory Committee, CDRH, FDA, 298-303.
547. See, e.g., Terms of Service, 23ANDME, https://www.23andme.com/about/tos/ (last visited Apr. 29, 2012): "You should not change your health behaviors solely on the basis of information from 23andMe. Make sure to discuss your Genetic Information with a physician or other health care provider before you act upon the Genetic Information resulting from 23andMe Services. For most common diseases, the genes we know about are only responsible for a small fraction of the risk. There may be unknown genes, environmental factors, or lifestyle choices that are far more important predictors. If your data indicate that you are not at elevated genetic risk for a particular disease or condition, you should not feel that you are protected."
548. Kirell Lakhman, Should Clinical Labs Rejoice Over FDA Panel's DTC Genetic-Test Recommendations? GENOME WEB (Mar. 11, 2011) http://www.genomeweb. com/blog/should-clinical-labs-rejoice-over-fda-panels-dtc-genetic-test- recommendations (split FDA advisory panel recommended that DTC tests should only be accessible through doctors).
549. Evans & Berg, supra note 154.
550. Wright & Kroese, supra note 42, at 129-130
551. SACGHS OVERSIGHT REPORT 85.
552. Wright & Kroese, supra note 42, at 130.
553. Bustamante et al., supra note 66.
554. Accelerated review, coupled with insufficient resources, time, and evidence, has caused problems for FDA before. When FDA contracted review of "old" drugs under the 1962 Kefauver-Harris Amendments to the National Academy of Sciences, the process was flawed by insufficient documentation of efficacy, time constraints, and procedural inconsistencies, leading to "findings [that] were more in the nature of educated opinions than of definitive scientific facts." SHEILA JASANOFF, FIFTH BRANCH: SCIENCE ADVISERS AS POLICYMAKERS 217-19 (1990). These deficiencies elicited misgivings from panelists about "being in a position to adjudicate for the country, with all its varied opinions and patterns for practice." Id. Industry challenged the findings, but as usual, courts deferred to FDA's expertise. Id.
555. Wright & Kroese, supra note 42, at 127.
556. An abbreviated version of ACCE is used in the UK; if FDA were able to streamline and standardize an ACCE module for use in safety and efficacy review, premarket approval of genomic tests might be more feasible.
557. See supra, Part III.C.
558. Cf. von Eschenbach, supra note 18.
559. Solberg, supra note 22, at 738-39.
560. See, e.g., Khoury et al., supra note 42, at 561-62.
561. Javitt & Hudson, supra note 270, at 61.
562. SACGHS OVERSIGHT REPORT 113; seealso id. at 30-31, 111-114.
563. Id. ("FDA's risk-based regulatory authority and regulatory processes[] should be expanded").
564. SACGHS OVERSIGHT REPORT at 94 (citing Judy Yost, CMS, personal communication).
565. See Side-by-Side Comparison of CUA and HR 3207, Modernizing Laboratory Test Standards for Patients Act, available at http://acla.com/sites/default/ files/CLIA%20v%20Burgess%20side-by-side%20FINAL.pdf (last visited Apr. 29, 2012).
566. See supra notes 316-329 and accompanying text.
567. H.R. 3207: Modernizing Laboratory Test Standards for Patients Act of 2011, available at http://www.govtrack.us/congress/bills/112/hr3207 (last visited Apr. 29, 2012).
568. 23ANDME, https://www.23andme.com/health/ (last visited Apr. 29, 2012) (emphasis added) (small type underneath indicates that "risk genes" "refers to specific genetic risk variants.").
569. BRCA Cancer Mutations (Selected), 23ANDME, https://www.23andme.com/ health/BRCA-Cancer/ (last visited Apr. 29, 2012) (the three mutations are 185delAG in BRCA1, 5382insC in BRCA1, and 6174delT in BRCA2).
570. BRACAnalysis Technical Specifications, MYRIAD GENETIC LABS (Feb. 2012), http://www.myriad.com/lib/technical-specifications/BRACAnalysis-Technical- Specifications.pdf.
571. See, e.g., Gel Tested to See What Your Genetics Say About Breast Cancer, 23ANDME, https://www.23andmecom/health/Breast-Cancer/ (last visited Apr. 29, 2012);
572. BRCA Cancer Mutations (Selected), 23ANDME, https:/Avww.23andme.com/ health/BRCA-Cancer/ (last visited Apr. 29, 2012) ("the BRCA mutations covered by this report are only three of hundreds . . . their absence does not rule out the possibility that you may carry another cancer-causing variation");
573. BRCA Cancer Mutations (Selected) Technical Report, 23ANDME, https://www.23andme.com/health/BRCA-Cancer/techreport/BRCA (last visited Apr. 29, 2012) ("Hundreds of mutations have been reported in the BRCA1 and BRCA2 genes. 23andMe provides data for only three...").
574. Get tested to learn what your genetics say about: Type 2 Diabetes, 23ANDME, https://www.23andme.com/health/Type-2-Diabetes/ (last visited Apr. 29, 2012) ("The heritability of type 2 diabetes is estimated to be 26%.").
575. Health Reports: By Ethnicity, 23ANDME, https://www.23andme.com/health/ ethnicity/ (last visited Apr. 29, 2012).
576. Hudson et al., supra note 81, at 635.
577. Cf. 21 C.F.R. 812.2(c)(3) (2011). See also FDA, Guidance for Industry and FDA Staff: In Vitro Diagnostic (IVD) Device Studies - Frequently Asked Questions 11 (June 25, 2010) (allowing research use of diagnostic only insofar as it does not "influence patient treatment or clinical management decisions before the diagnosis is established by a medically established product or procedure.").
578. See, e.g., Kaufman, supra note 169 (66% of DTC consumers felt the services should be available without government oversight, but wanted an organization like FTC to monitor companies' claims for accuracy).
579. Because the practice of medicine exception only applies to legally marketed products, even physicians can't use an FDA-prohibited drug or device off-label. See FD&C Act § 906 (21 U.S.C. § 396) ("Nothing in this [Act] shall be construed to limit or interfere with the authority of a health care practitioner to prescribe or administer any legally marketed device to a patient for any condition or disease within a legitimate health care practitioner-patient relationship. . . .");
580. cf. Gonzales v. Raich, 545 U.S. 1, 28 (2005) ("the dispensing of new drugs, even when doctors approve their use, must await federal approval").
581. See also R.S. Stafford, Off-Label Use of Drugs and Medical Devices: A Review of Policy Implications, CLINICAL PHARMACOLOGY & THERAPEUTICS (Apr. 4, 2012).
582. PERSONALIZED MEDICINE COALITION, PERSONAL GENOMICS AND INDUSTRY STANDARDS: SCIENTIFIC VALIDITY (July 2008) available at http://bit.ly/KpJenC (last visited Apr. 29, 2012).
583. 23andMe Letter to Heads of FDA and NIH, THE SPITTOON (Jul. 6, 2010, 11:13 PM), http://spittoon.23andme.com/2010/07/06/23andme-letter-to-heads-of-fda-and- nih/.
584. See generally Evans, Seven Pillars, supra note 61.
585. FDA, THE SENTINEL INITIATIVE: A NATIONAL STRATEGY FOR MONITORINO MEDICAL PRODUCT SAFETY (2008).
586. Evans, Seven Pillars, supra note 61, at 462.
587. SACGHS OVERSIGHT REPORT 121.
588. Cf. Randall S. Stafford, Regulating Off-Label Drug Use - Rethinking the Role of the FDA, 358 N.E.J. MED. 1427 (2008) (arguing that FDA should consider "systematically collecting postmarketing data to quantify the harms and benefits of common off-label uses").
589. See, e.g., Ted Greenwald, DNA Sequencing For Fun And Profit: A Low-Cost Platform For Garage Biotech, FORBES (DEC. 31, 2011).