Managing Incidental Findings in Human Subjects Research: Analysis and Recommendations

See, e.g., Green D. , “Incidental Findings in Computed Tomography of the Thorax,” Seminars in Ultrasound, CT & MR 26, no. 1 (2005): 14–19; Green D. E. Woodward P. J. , “The Management of Indeterminate Incidental Findings Detected at Abdominal CT,” Seminars in Ultrasound, CT & MR 26, no. 1 (2005): 2–13; Cai Q. , “Incidental Findings of Thickening Luminal Gastrointestinal Organs on Computed Tomography: An Absolute Indication for Endoscopy,” American Journal of Gastroenterology 98, no. 8 (2003): 1734–1737; Pickhardt P. J. , “Computed Tomographic Virtual Colonoscopy To Screen for Colorectal Neoplasia in Asymptomatic Adults,” N. Engl. J. Med. 349, no. 23 (2003): 2191–2200, at 2196; National Institutes of Health, Department of Health and Human Services, State-of-the-Science Statement on Management of the Clinically Inapparent Adrenal Mass (“Incidentaloma”) , February 4–6, 2002, available at <http://consensus.nih.gov/2002/2002AdrenalIncidentalomasos021PDF.pdf> (last visited March 6, 2008); Stedman's Medical Dictionary , 27th ed. (Philadelphia: Lippincott Williams & Wilkins, 2000), “incidentaloma”; Roof K. , “Incidental Findings in a Federally-Sponsored Cancer Screening Program,” Journal of Community Health 24, no. 4 (1999): 305–312; Westbrook J. I. Braithwaite J. McIntosh J. H. , “The Outcomes for Patients with Incidental Lesions: Serendipitous or Iatrogenic?” American Journal of Roentgenology 171, no. 5 (1998): 1193–1196; Chidiac R. M. Aron D. C. , “Incidentalomas: A Disease of Modern Technology,” Endocrinology & Metabolism Clinics of North America 26, no. 1 (1997): 233–253; Parker L. S. Majeske R. A. , “Incidental Findings: Patients' Knowledge, Rights, and Preferences,” Journal of Clinical Ethics 6, no. 2 (1995): 176–179.

See Kohane I. S. Masys D. R. Altman R. B. , “The Incidentalome: A Threat to Genomic Medicine,” JAMA 296, no. 2 (2006): 212–215.

National Human Research Protections Advisory Committee Working Group on Genetics, IRB Guidebook Chapter on Human Genetics Research, Draft 2 , June 27, 2002: At 12, available at <http://www.hhs.gov/ohrp/nhrpac/documents/nhrpac13.pdf> (last visited March 6, 2008) [hereinafter IRB Guidebook].

Ravitsky V. Wilfond B. S. , “Disclosing Individual Genetic Results to Research Participants,” American Journal of Bioethics 6, no. 6 (2006): 8–17, at 8–9; Ravitsky V. Wilfond B. S. , “Response to Open Peer Commentaries on ‘Disclosing Individual Genetic Results to Research Participants’: Defining Clinical Utility and Revisiting the Role of Relationships,” American Journal of Bioethics 6, no. 6 (2006): W10–W12. Compare Parker L. S. , “Rethinking Respect for Persons Enrolled in Research,” ASBH Exchange, 9, no. 2 (2006): 1, 6–7, with Shalowitz D. I. Miller F. G. , “Disclosing Individual Results of Clinical Research: Implications of Respect for Participants,” JAMA 294, no. 6 (2005): 737–740.

See, e.g., Illes J. , “Practical Approaches to Incidental Findings in Brain Imaging Research,” Neurology 70, no. 5 (2008): 384–390; Vernooij M. W. , “Incidental Findings in Brain MRI in the General Population,” N. Engl. J. Med. 357, no. 18 (2007): 1821–1828; Illes J. , “Incidental Findings in Brain Imaging Research,” Science 311, no. 5762 (2006): 783–784; Zalis M. E. , “CT Colonography Reporting and Data System: A Consensus Proposal,” Radiology 236, no. 1 (2005): 3–9, at 7–8.

Lucassen A. Parker M. , “Revealing False Paternity: Some Ethical Considerations.” Lancet 357, no. 9261 (2001): 1033–1035, at 1035; Anderlik M. R. Rothstein M. A. , “DNA-Based Identity Testing and the Future of the Family: A Research Agenda,” American Journal of Law & Medicine 28, nos. 2 & 3 (2002): 215–232, at 221–222; McEwen J. E. , “Genetic Information, Ethics, and Information Relating to Biological Parenthood,” in Murray T. H. Mehlman M. J. , eds., Encyclopedia of Ethical, Legal, and Policy Issues in Biotechnology, vol. 1 (New York: John Wiley & Sons, 2000): 356–363, at 359–360; Friedman Ross L. , “Disclosing Misattributed Paternity,” Bioethics 10, no. 2 (1996): 115–130, at 116–117; Macintyre S. Sooman A. , “Non-Paternity and Prenatal Genetic Screening,” Lancet 338, no. 8771 (1991): 869–871.

Vernooij , supra note 5; Kumra S. , “Ethical and Practical Considerations in the Management of Incidental Findings in Pediatric MRI Studies,” Journal of the American Academy of Child & Adolescent Psychiatry 45, no. 8 (2006): 1000–1006, at 1002; Alphs H. H. , “Findings on Brain MRI from Research Studies of Occupational Exposure to Known Neurotoxicants,” American Journal of Roentgenology 187, no. 4 (2006): 1043–1047, at 1043–1044; Illes J. , “Ethical Consideration of Incidental Findings on Adult Brain MRI in Research,” Neurology 62, no. 6 (2004): 888–890, at 888–889; Kim B. S. , “Incidental Findings on Pediatric MR Images of the Brain,” AJNR American Journal of Neuroradiology 23, no. 10 (2002): 1674–1677, at 1675; Yue N. C. , “Clinically Serious Abnormalities Found Incidentally at MR Imaging of the Brain: Data from the Cardiovascular Health Study,” Radiology 202, no. 1 (1997): 41–46, at 42; Katzman G. L. Dagher A. P. Patronas N. J. , “Incidental Findings on Brain Magnetic Resonance Imaging from 1000 Asymptomatic Volunteers,” JAMA 282, no. 1 (1999): 36–39, at 37. Cf. Weber F. Knopf H. , “Incidental Findings in Magnetic Resonance Imaging of the Brains of Health Young Men,” Journal of Neurological Sciences 240, nos. 1 & 2 (2006): 81–84, at 82–83; Blomgren K. , “Clinical Significance of Incidental Magnetic Resonance Image Abnormalities in Mastoid Cavity and Middle Ear in Children,” International Journal of Pediatric Otorhinolaryngology 67, no. 7 (2003): 757–760, at 758; Lim W.-K. , “Incidental Magnetic Resonance Image Sinus Abnormalities in Asymptomatic Australian Children,” Journal of Laryngology & Otology 117, no. 11 (2003): 969–972, at 969–970.

American College of Radiology Imaging Network, ACRIN 6664 National CT Colonography Trial , Partial protocol, July 7, 2006: At 13 (citing earlier studies), available at <http://www.acrin.org/files/protocol_docs/A6664partial_summary.pdf> (last visited June 15, 2007); Spreng A. , “Importance of Extracolonic Findings at IV Contrast Medium-Enhanced CT Colonography Versus Those at Non-Enhanced CT Colonography,” European Radiology 15, no. 10 (2005): 2088–2095; Yee J. , “Extracolonic Abnormalities Discovered Incidentally at CT Colonography in a Male Population,” Radiology 236, no. 2 (2005): 519–526, at 520–521; Hellström M. Svensson M. H. Lasson A. , “Extracolonic and Incidental Findings on CT Colonography (Virtual Colonoscopy),” American Journal of Roentgenology 182, no. 3 (2004): 631–638, at 631–634; Rajapaksa R. C. Macari M. Bini E. J. , “Prevalence and Impact of Extracolonic Findings in Patients Undergoing CT Colonography,” Journal of Clinical Gastroenterology 38, no. 9 (2004): 767–771, at 768; Ginnerup Pederson B. Sosenkilde M. Christiansen T. , “Extracolonic Findings at Computed Tomography Colonography Are a Challenge,” Gut 52, no. 5 (2003): 1744–1747, at 1745; Gluecker T. M. , “Extracolonic Findings at CT Colonography: Evaluation of Prevalence and Cost in a Screening Population,” Gastroenterology 124, no. 4 (2003): 911–916, at 912; Pineau B. C. , “Prevalence of Extracolonic Findings at Virtual Colonoscopy,” Abstract No. 345, Abstracts Submitted for the 68th Annual Scientific Meeting of the American College of Gastroenterology, printed in American Journal of Gastroenterology 98, no. 9, Supplement 1 (2003): S117; Edwards J. T. Mendelson R. M. Forbes G. M. , “Extracolonic Findings at Virtual Colonoscopy: Implications for Screening Programs,” American Journal of Gastroenterology 96, no. 10 (2001): 3009–3012, at 3010–3011; Hara A. K. , “Incidental Extracolonic Findings at CT Colonography,” Radiology 215, no. 2 (2000): 353–357, at 354. Cf. Khan K. Y. , “Frequency and Impact of Extracolonic Findings Detected at Computed Tomographic Colonography in a Symptomatic Population,” British Journal of Surgery 94, no. 3 (2007): 355–361, at 356; Chin M. , “Computed Tomographic Colonography: Prevalence, Nature, and Clinical Significance of Extracolonic Findings in a Community Screening Program,” American Journal of Gastroenterology 100 (2005): 2771–2776, at 2773.

Illes , “Incidental Findings in Brain Imaging Research,” supra note 5.

42 U.S.C. § 263a (2007) (“Certification of laboratories”).

Lawrenz F. Sobotka S. , “Empirical Analysis of Current Approaches to Incidental Findings,” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 249–255; Wolf S. M. Sobotka S. P. Lawrenz F. P. , “Managing Incidental Findings in Human Subjects Research: Analysis of Current Guidance and Consent Forms,” in progress.

See generally Ensenauer R. E. Michels V. V. Reinke S. S. , “Genetic Testing: Practical, Ethical, and Counseling Considerations,” Mayo Clinic Proceedings 80, no. 1 (2005): 63–73.

IRB Guidebook, supra note 3.

Lucassen Parker , supra note 6, at 1035; McEwen , supra note 6, at 359–360; Ross Friedman , supra note 6, at 116–117; Macintyre Sooman , supra note 6.

Ravitsky Wilfond , “Disclosing Individual Genetic Results to Research Participants,” supra note 4, at 12.

National Heart, Lung and Blood Institute, NHLBI Working Group on Reporting Genetic Results in Research Studies, Meeting Summary , Bethesda, MD, July 12, 2004, available at <http://www.nhlbi.nih.gov/meetings/workshops/gene-results.htm> (last visited June 15, 2007) [hereinafter NHLBI Working Group].

Tests Gene , available at <http://genetests.org> (last visited March 28, 2008). See also Ormond K. E. , “Disclosing Genetic Research Results: Examples from Practice,” American Journal of Bioethics 6, no. 6 (2006): 30–32, at 30.

See Daar A. S. Scherer S. W. Hegele R. A. , “Implications of Copy-Number Variation in the Human Genome: A Time for Questions,” Nature Reviews Genetics 7, no. 6 (2006): 414; see generally ACMG Laboratory Practice Committee Working Group, “ACMG Recommendations for Standards for Interpretation of Sequence Variations,” Genetics in Medicine 2, no. 5 (2000): 302–303.

See Maschke K. J. , “Navigating an Ethical Patchwork: Human Gene Banks,” Nature Biotechnology 23, no. 5 (2005): 539–545, at 539. See also National Human Genome Research Institute (NHGRI), Reaffirmation and Extension of NHGRI Rapid Data Release Policies: Large-scale Sequencing and Other Community Resource Projects, available at <http://www.genome.gov/10506537> (last visited March 28, 2008).

See Kohane Masys Altman , supra note 2, at 214.

Wolf S. M. , Letter, “The Incidentalome,” JAMA 296, no. 23 (2006): 2800–2801, at 2800.

See NHLBI Working Group, supra note 16.

See Illes , “Incidental Findings in Brain Imaging Research,” supra note 5; Kirschen M. P. Jaworska A. Illes J. , “Subjects' Expectations in Neuroimaging Research,”Journal of Magnetic Resonance Imaging 23, no. 1 (2006): 205–209; National Institute of Neurological Disorders and Stroke, Detection and Disclosure of Incidental Findings in Neuroimaging Research , Bethesda, MD, January 6–7, 2005, available at <http://www.ninds.nih.gov/news_and_events/proceedings/ifexecsummary.htm> (last visited March 6, 2008) [hereinafter NINDS Proceedings]; Illes J. , “Discovery and Disclosure of Incidental Findings in Neuroimaging Research,” Journal of Magnetic Resonance Imaging 20, no. 5 (2004): 743–747; Illes , supra note 7; Mamourian A. , “Incidental Findings on Research Functional MRI: Should We Look?” American Journal of Neuroradiology 25, no. 4 (2004): 520–522; Illes J. , “Ethical and Practical Considerations in Managing Incidental Findings in Functional Magnetic Resonance Imaging,” Brain and Cognition 50, no. 3 (2002): 358–365; Kim , supra note 7; Katzman Dagher Patronas , supra note 7; see generally, Kulynych J. J. , “The Regulation of MR Neuroimaging Research,” America Journal of Law & Medicine 33, nos. 2 & 3 (2007): 295–317, at 313–315; Kulynych J. , “Legal and Ethical Issues in Neuroimaging Research: Human Subjects Protection, Medical Privacy, and the Public Communication of Research Results,” Brain and Cognition 50, no. 3 (2002): 345–357.

See Illes , “Incidental Findings in Brain Imaging Research,” supra note 5 at 784.

Alphs , supra note 7, at 1044; Illes , supra note 7, at 888–889; Katzman Dagher Patronas , supra note 7, at 37; Kim , supra note 7, at 1675.

Illes , “Incidental Findings in Brain Imaging Research,” supra note 5.

American College of Radiology Imaging Network, ACRIN Protocol 6664 National CT Colonography Trial, available at <http://www.acrin.org/6664_protocol.html> (last visited June 15, 2007).

Xiong T. , “Incidental Lesions Found on CT Colonography: Their Nature and Frequency,” British Journal of Radiology 78, no. 925 (2005): 22–29, at 26.

Hara et al, supra note 8, at 357.

Limburg P. J. Fletcher J. G. Comment , “Making Sense of CT Colonography-Related Complication Rates,” Gastroenterology 131, no. 6 (2006): 2023–2024.

Siddiki H. , “Incidental Findings in CT Colonography: Literature Review and Survey of Current Research Practice,” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 320–331.

See Hara , supra note 8, at 354; Gluecker , supra note 8, at 912.

Siddiki , supra note 31.

See Chin M. , “Computed Tomographic Colonography: Prevalence, Nature, and Clinical Significance of Extracolonic Findings in a Community Screening Program,” American Journal of Gastroenterology 100, no. 12 (2005): 2771–2776, at 2775; Yee J. , “Extracolonic Abnormalities Discovered Incidentally at CT Colonography in a Male Population,” Radiology 236, no. 2 (2005): 519–526, at 522; Gluecker , supra note 8, at 915; Hara , supra note 8, at 356–357. Cf. Xiong T. , “Resources and Costs Associated with Incidental Extracolonic Findings from CT Colonography: A Study in a Symptomatic Population,” British Journal of Radiology 79, no. 948 (2006): 948–961, at 949; Wagner S. C. , “Picture Archiving and Communication System: Effect on Reporting of Incidental Findings,” Radiology 225, no. 2 (2002): 500–505, at 502–503.

Zalis , supra note 5, at 7–8.

See Xiong , supra note 28, at 23, 26.

Siddiki , supra note 31.

See MacMahon H. , “Guidelines for Management of Small Pulmonary Nodules Detected on CT Scans: A Statement from the Fleischner Society,” Radiology 237, no. 2 (2005): 395–400, at 398.

See Pederson Ginnerup Sosenkilde Christiansen , supra note 8, at 1746–1747; Edwards Mendelson Forbes , supra note 8, at 3011.

See Maschke , supra note 19, at 539; NHGRI, supra note 19.

See generally Wagner , supra note 35.

See, e.g., Verweij M. F. Hamel B. C. , “Unexpected Findings in Identifiable Stored Blood Samples After Analysis Without Consent: Moral Arguments For and Against Disclosure,” Genetic Counseling 13, no. 2 (2002): 115–121 (discussing issues faced by original researchers when secondary analysis leads to “unexpected” finding of potential clinical significance in healthy controls).

See American Society for Human Genetics, “Statement on Informed Consent for Genetic Research,” American Journal of Human Genetics 59, no. 2 (1996): 471–474, at 473; Rothstein M. A. , “Expanding the Ethical Analysis of Biobanks,” Journal of Law, Medicine & Ethics 33, no. 1 (2005): 89–101, at 94.

See 45 C.F.R. § 46.101 (b) (4) (2007) (exempting “research involving the collection or study of existing data…, [or] pathological specimens…if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects”).

Clayton E. W. , “Informed Consent and Biobanks,” Journal of Law, Medicine & Ethics 33, no. 1 (2005): 15–21, at 15–17; Office for Human Research Protections, Guidance on Research Involving Coded Private Information or Biological Specimens , August 10, 2004, available at <http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.pdf> (last visited March 6, 2008) [hereinafter OHRP]; National Bioethics Advisory Commission, Research Involving Human Biological Materials: Ethical Issues and Policy Guidance, vol. 1 (Rockville, MD: August, 1999): At 15–16, 27–29.

See Working Group on Reporting Results of Genetic Research, Offering Individual Results of Genetic Research: Report and Recommendations , April 22, 2006 draft, to be made available at <http://cirge.stanford.edu/library/reporting_results.html> [hereinafter Working Group on Reporting Results]; cf. Cho M. K. , “Understanding Incidental Findings in the Context of Genetics & Genomics,” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 280–285.

National Institutes of Health, Department of Health and Human Services, Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (GWAS) (January 25, 2008), available at <http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html> (last visited March 27, 2008).

45 C.F.R. Part 46 (2007) (“Protection of Human Subjects”).

21 C.F.R. Parts 50, 56 (2007) (“Protection of Human Subjects,” “Institutional Review Boards”).

See, e.g., Emanuel E. J. Wendler D. Grady C. , “What Makes Clinical Research Ethical?” JAMA 283, no. 20 (2000): 2701–2711.

See Richardson H. S. Belsky L. , “The Ancillary-Care Responsibilities of Medical Researchers: An Ethical Framework for Thinking About the Clinical Care that Researchers Owe Their Subjects,” Hastings Center Report 34, no. 1 (2004): 25–33, at 29–31.

See Clayton , supra note 46, at 20; 45 C.F.R. § 164.524 (a) (2007) (describing the right of access of individuals to protected health information).

National Institutes of Health, Protecting Personal Health Information in Research: Understanding the HIPAA Privacy Rule, Access to Protected Health Information, available at <http://privacyruleandresearch.nih.gov/pr_08.asp#8j> (last visited April 7, 2008); National Human Genome Research Institute, “NHGRI Policy Recommendations on Research Privacy Guidelines,” Federal Policy Recommendations Including HIPAA, available at <http://www.genome.gov/11510216> (last visited June 17, 2007).

45 C.F.R. § 46.116 (a) (2007); 21 C.F.R. § 50.25 (a) (2007).

Rothstein M. A. , “Tiered Disclosure Options Promote the Autonomy and Well-Being of Research Subjects,” American Journal of Bioethics 6, no. 6 (2006): 20–21, at 21 (calling for tiered disclosure during the initial informed consent process in which research subjects choose the types of individual genetic results they would want to receive).

See Appelbaum P. S. , “False Hopes and Best Data: Consent to Research and the Therapeutic Misconception,” Hastings Center Report 17, no. 2 (1987): 20–24, at 20.

45 C.F.R. § 46.116 (2007); 21 C.F.R. § 50.25 (b) (5) (2007).

45 C.F.R. § 46.111 (a) (1) (2007); 21 C.F.R. § 56.111 (a) (1) (2007).

45 C.F.R. § 46.111 (a) (2) (2007); 21 C.F.R. § 56.111 (a) (2) (2007).

See Belsky L. Richardson H. S. , “Medical Researchers' Ancillary Clinical Care Responsibilities,” British Medical Journal 328, no. 7454 (2004): 1494–1496; Richardson Belsky , supra note 52, at 32.

See Belsky Richardson , supra note 61 at 1495; Richardson Belsky , supra note 52, at 29–31. For ancillary care falling within the scope of entrustment, the strength of the claim to care depends on further factors: The participant's vulnerability, their uncompensated risks or burdens (i.e., the gratitude owed to them by the researchers), their dependence on the researchers, and the depth of the researcher-participant relationship. Belsky and Richardson, supra note 61 at 1495–1496; Richardson Belsky , supra note 52, at 30–31.

Illes , “Incidental Findings in Brain Imaging Research,” supra note 5, at 783.

Shalowitz Miller , supra note 4, at 738.

Illes , “Incidental Findings in Brain Imaging Research,” supra note 5, at 783.

Beauchamp T. Childress J. , Principles of Biomedical Ethics, 5th ed. (New York: Oxford University Press, 2001): At 173–176.

Grimes v. Kennedy Krieger Inst. , 782 A.2d 807, 834–35, 849–50 (Md. 2001).

Grimes v. Kennedy Krieger Inst. , 782 A.2d 807, 851 (Md. 2001); see also Blaz v. Michael Reese Hosp. Foundation, 74 F. Supp. 2d 803, 805–07 (N.D. Ill. 1999).

See Grimes v. Kennedy Krieger Inst., 782 A.2d 807, 843–44 (Md. 2001)

See Sherman, Silverstein, Kohl, Rose & Podolsky Law Offices, Clinical Trials Litigation, available at <http://www.sskrplaw.com/gene/index.html> (last visited June 17, 2007); Mello M. M. Studdert D. M. Brennan T. A. , “The Rise of Litigation in Human Subjects Research,” Annals of Internal Medicine 139, no. 1 (2003): 40–45.

See Office of Human Research Protections, “Overview,” Compliance Oversight, available at <http://www.hhs.gov/ohrp/compliance/index.html> (last visited June 17, 2007).

See Blaz v. Michael Reese Hosp. Foundation, 74 F. Supp. 2d 803, 805–07 (N.D. Ill. 1999); Grimes v. Kennedy Krieger Inst., 782 A.2d 807, 852 (Md. 2001); Hoffman D. E. Rothenberg K. H. , “Whose Duty Is It Anyway? The Kennedy Krieger Opinion and Its Implications for Public Health Research,” Journal of Health Care Law & Policy 6, no. 1 (2002): 109–147, at 130–131; see also Appelbaum P. S. Rosenbaum A. , “Tarasoff and the Researcher: Does the Duty to Protect Apply in the Research Setting?” American Psychologist 44, no. 6 (1989): 885–894.

See generally Fernandez C. V. Kodish E. Weijer C. , “Informing Study Participants of Research Results: An Ethical Imperative,” IRB 25, no. 1 (2003): 12–19; Partridge A. H. Winer E. P. , “Informing Clinical Trial Participants About Study Results,” JAMA 288, no. 3 (2002): 363–365.

See, e.g., Caulfield T. , “Research Ethics Recommendations for Whole-Genome Research: Consensus Statement,” PLoS Biology 6, no. 3 (2008): 0430–0435; Manolio T. A. , “Taking Our Obligations to Research Participants Seriously: Disclosing Individual Results of Genetic Research,” American Journal of Bioethics, 6, no. 6 (2006): 32–34, at 32–33.

See National Bioethics Advisory Commission, supra note 46, at 72.

Beskow L. M. , “Informed Consent for Population-Based Research Involving Genetics,” JAMA 286, no. 18 (2001): 2315–2321, at 2320.

NHLBI Working Group, supra note 16.

See Clayton , supra note 46, at 20; 45 C.F.R. § 164.524 (a) (2007). Individuals generally have a right of access to their protected health information, with some exceptions. § 164.524 (a) (iii). These include protected health information that is maintained by a covered entity subject to CLIA, to the extent that providing access to this information would be prohibited by law, § 164.524 (a) (iii) (A); or when the covered entity is exempt from CLIA because it is a research lab that does “not report patient-specific results for the diagnosis, prevention or treatment of any disease or impairment of, or the assessment of the health of individual patients,” 42 C.F.R. § 493.3 (b) (2).

See National Institutes of Health, supra note 54; National Human Genome Research Institute, supra note 54.

See Bookman E. B. , “Reporting Genetic Results in Research Studies: Summary and Recommendations of an NHLBI Working Group,” American Journal of Human Genetics Part A 140A, no. 10 (2006): 1033–1040, at 1034–1035; Beskow L. M. , “Considering the Nature of Individual Research Results,” American Journal of Bioethics 6, no. 6 (2006): 38–40, at 39–40. See also Grosse S. D. Khoury M. J. , “What Is the Clinical Utility of Genetic Testing?” Genetics in Medicine 8, no. 7 (2006): 448–450 (discussing definitions of “clinical utility” from narrow (“ability…to prevent or ameliorate adverse health outcomes”) to broad (“considered important to individuals and families”)).

The CLIA regulations exempt research labs only when such labs “do not report patient-specific results for the diagnosis, prevention or treatment of any disease or impairment of, or the assessment of the health of individual patients.” Centers for Medicare & Medicaid Services (CMS), Department of Health and Human Services, Laboratory Requirements, 42 C.F.R. § 493.3 (b) (2) (2008). This may mean that under current regulations, research labs may not report “research results” when these are individual-specific and may be used to assess health or trigger such assessment.

This broad definition of “utility” comports with Grosse and Khoury, supra note 80.

See Dinnett E. M. , Letter, “Offering Results to Research Participants,” British Medical Journal 332, no. 7540 (2006): 549–550, at 550; Fernandez Kodish Weijer , supra note 73, at 13; Fernandez C. V. Skedgel C. Weijer C. , “Considerations and Costs of Disclosing Study Findings to Research Participants,” Canadian Medical Association Journal 170, no. 9 (2004): 1417–1419, at 1417.

NHLBI Working Group, supra note 16.

See Facio F. M. , “One Size Does Not Fit All,” American Journal of Bioethics 6, no. 6 (2006): 40–42, at 41.

Working Group on Reporting Results, supra note 47.

See National Bioethics Advisory Commission, supra note 46, at 72; NHLBI Working Group, supra note 16; Ravitsky Wilfond , “Disclosing Individual Genetic Results to Research Participants,” supra note 4, at 10–11; Caulfield , supra note 74.

See, e.g., Kohane I. S. , “Reestablishing the Researcher-Patient Compact,” Science 316, no. 5826 (2007): 836–837; Church G. M. , “The Personal Genome Project,” Molecular Systems Biology (December 13, 2005); doi: 10.1038/msb4100040.

Cf. Lavieri R. R. Garner S. A. , “Ethical Considerations in the Communication of Unexpected Information with Clinical Implications,” American Journal of Bioethics 6, no. 6 (2006): 46–48; Rothstein , supra note 56; Fernandez C. V. Weijer C. , “Obligations in Offering to Disclose Genetic Research Results,” American Journal of Bioethics 6, no. 6 (2006): 44–46.

See Clayton E. W. Ross L. F. Letter , “Implications of Disclosing Individual Results of Clinical Research,” JAMA 295, no. 1 (2006): 37.

Cf. Rothstein , supra note 56 (discussing “disclosure options” for receipt of research results by participants before research begins).

Richardson Belsky , supra note 52.

See, e.g., IRB Guidebook, supra note 3.

Lawrenz Sobotka , supra note 11; Wolf Sobotka Lawrenz , supra note 11.

The literature on the return of individual research results does not always make this distinction. For example, Shalowitz Miller , supra note 4, at 738, imply that research participants have a right to any information about themselves. Lavieri and Garner suggest that “in all cases for which unanticipated, possibly clinically useful genetic data is obtained, investigators have a moral obligation to let the affected persons know that the results are available,” without limiting this information to research results. Lavieri R. R. Garner S. A. , “Ethical Considerations in the Communication of Unexpected Information with Clinical Implications,” American Journal of Bioethics 6, no. 6 (2006): 46–48.

See National Institutes of Health, Guidance on Reporting Adverse Events to Institutional Review Boards for NIH-Supported Multicenter Clinical Trials , June 11, 1999, available at <http://grants2.nih.gov/grants/guide/notice-files/not99–107.html> (last visited March 6, 2008) (comparing the definitions and reporting requirements for adverse events in the DHHS and the FDA regulations on human subjects research); see generally 21 C.F.R. § 312.32 (a) (2007) (defining “unexpected adverse drug experience”); 45 C.F.R. § 46.103 (b) (5) (2007) (requiring procedures for reporting “unanticipated problems involving risks to subjects”).

See Clayton E. W. , “Informed Consent for Genetic Research on Stored Tissue Samples,” JAMA 274, no. 22 (1995): 1786–1792, at 1790.

See National Bioethics Advisory Commission, supra note 46, at 63.

Working Group on Reporting Results, supra note 47.

An example of this type of incidental finding is described by Verweij Hamel , supra note 43. A sample from an unaffected person in a study on inherited limb malformation was later used in a second study as a “normal” control. However, that study found that the sample contained a sequence variance in a certain gene, mutations of which may cause a primary cardiac disorder. Id. at 116.

See Rothstein , supra note 44, at 95.

See, e.g., Working Group on Reporting Results, supra note 47; Cho , supra note 47; Wade C. H. Kalfoglou A. L. , “When Do Genetic Researchers Have a Duty to Recontact Study Participants?” American Journal of Bioethics 6, no. 6 (2006): 26–27; Ormond , supra note 17, at 31; Rothstein , supra note 44, at 95–96; Ormond K. E. , “‘Duty’ to Recontact Participants in a Population Based Genetic Database: The NUgene Experience,” Genetics in Medicine 6, no. 4 (2004): 261; Clayton E. W. , “Informed Consent for Genetic Research on Stored Tissue Samples,” JAMA 274, no. 22 (1995): 1786–1792, at 1790. Cf. Hunter A. G. W. , “Ethical, Legal, and Practical Concerns About Recontacting Patients to Inform Them of New Information: The Case in Medical Genetics,” American Journal of Medical Genetics 103, no. 4 (2001): 265–276; Knoppers B. M. , “Duty to Recontact: A Legal Harbinger?” American Journal of Medical Genetics 103, no. 4 (2001): 277; Fitzpatrick J. L. , “The Duty to Recontact: Attitudes of Genetics Service Providers,” American Journal of Human Genetics 64, no. 3 (1999): 852–860. Hunter Knoppers Fitzpatrick consider the ethics of recontacting in a clinical genetics setting.

Cf. Wendler D. Emanuel E. , “The Debate Over Research on Stored Biological Samples: What Do Sources Think?” Archives of Internal Medicine 162, no. 3 (2002): 1457–1462. Wendler and Emanuel conducted a survey in an attempt to assess what individuals (both those who had participated in clinical research and contributed samples, and those who had not) think about research on stored samples. They conclude that 88.8% of respondents would want to be informed of results of uncertain clinical significance. Id., at 1457.

See OHRP, supra note 46.

Illes , “Incidental Findings in Brain Imaging Resarch,” supra note 5, at 784; NINDS Proceedings, supra note 23.

Bookman , supra note 80, at 1037. In their summary of the NHLBI Working Group on reporting genetic research results, Bookman consider the costs involved in returning genetic research results to participants. They state that budgets for genetic research studies testing for mutations of known clinical significance should include the funds needed to offer results and to counsel on the meaning of such results. Id. at 1037.

See 42 U.S.C. § 263a(a)-(b); see also Clayton , supra note 46, at 20 (stating that disclosure of research results from non-CLIA approved laboratories might be illegal if recipients “choose to act” on this information).

Ormond , supra note 17, at 30.

See generally Lerman C. , “Genetic Testing in Families with Hereditary Nonpolyposis Colon Cancer,” JAMA 281, no. 17 (1999): 1618–1622, at 1618.

Lawrenz Sobotka , supra note 11; Wolf Sobotka Lawrenz , supra note 11.

Fernandez Kodish Weijer , supra note 73, at 14.

Lawrenz Sobotka , supra note 11; Wolf Sobotka Lawrenz , supra note 11.

See 45 C.F.R. § 46.110 (2007); 21 C.F.R. § 56.110 (2007); Office for Protection from Research Risks, “Protection of Human Subjects: Categories of Research that May Be Reviewed by the Institutional Review Board (IRB) Through an Expedited Review Procedure,” Federal Register, 63, no. 216 (November 9, 1998): 60364–60367, at 60366–60367, available at <http://www.hhs.gov/ohrp/humansubjects/guidance/expedited98.htm> (last visited March 6, 2008).

See Sharp H. M. Orr R. D. , “When ‘Minimal Risk’ Research Yields Clinically-Significant Data, Maybe the Risks Aren't So Minimal,” American Journal of Bioethics 4, no. 2 (2004): W32–W36 (arguing that research that can yield data with implications for the participant's health and welfare may present higher than “minimal risk”).

Downie J. Marshall J. , “Pediatric Neuroimaging Ethics,” Cambridge Quarterly of Healthcare Ethics 16, no. 2 (2007): 147–160, at 152–153; Kumra S. , “Ethical and Practical Considerations in the Management of Incidental Findings in Pediatric MRI Studies,” Journal of the American Academy of Child & Adolescent Psychiatry 45, no. 8 (2006): 1000–1006; Kim , supra note 7.

See 45 C.F.R. § 46.408 (2007) (“Requirements for permission by parents or guardians and for assent by children.”).

45 C.F.R. §§ 46.404–06 (2007).

National Human Research Protections Advisory Committee Children's Workgroup, Clarifying Specific Portion of 45 CFR 46 Subpart D that Governs Children's Research, 2002: At 1, available at <http://www.hhs.gov/ohrp/nhrpac/documents/nhrpac16.pdf> (last visited March 6, 2008).

See American Academy of Pediatrics Committee on Bioethics, “Ethical Issues with Genetic Testing in Pediatrics,” Pediatrics 107, no. 6 (2001): 1451–1455, at 1453–1454.

See id., at 1453.

See Annas G. J. , “Rules for Research on Human Genetic Variation: Lessons from Iceland,” N. Engl. J. Med. 342, no. 24 (2000): 1830–1833, at 1832–1833.

See Knoppers B. M. , “Children and Incompetent Adults in Genetic Research: Consent and Safeguards,” Nature Reviews Genetics 3, no. 3 (2002): 221–224, at 223.

See National Human Research Protections Advisory Committee Workgroup on Decisional Incapacity, Report from NHRPAC on Informed Consent and the Decisionally Impaired , 2002, available at <http://www.hhs.gov/ohrp/nhrpac/documents/nhrpac10.pdf> (last visited March 6, 2008) [hereinafter NHRPAC Report]; National Bioethics Advisory Commission, Research Involving Persons with Mental Disorders that May Affect Decisionmaking Capacity (Rockville, MD: 1998).

45 C.F.R. § 46.102 (c) (2007).

See NHRPAC Report, supra note 123.

Kohane Masys Altman , supra note 2.

Lawrenz Sobotka , supra note 11; Wolf Sobotka Lawrenz , supra note 11.