Returning genomic research results to family members raises complex questions. Genomic research on life-limiting conditions such as cancer, and research involving storage and reanalysis of data and specimens long into the future, makes these questions pressing. This author group, funded by an NIH grant, published consensus recommendations presenting a framework. This follow-up paper offers concrete guidance and tools for implementation. The group collected and analyzed relevant documents and guidance, including tools from the Clinical Sequencing Exploratory Research (CSER) Consortium. The authors then negotiated a consensus toolkit of processes and documents. That toolkit offers sample consent and notification documents plus decision flow-charts to address return of results to family of living and deceased participants, in adult and pediatric research. Core concerns are eliciting participant preferences on sharing results with family and on choice of a representative to make decisions about sharing after participant death.
Get full access to this article
View all access options for this article.
References
1.
S. M.Wolfet al., “Returning a Research Participant's Genomic Results to Relatives: Analysis and Recommendations,”Journal of Law, Medicine & Ethics43, no. 3 (2015): 440-463.
2.
S. M.Wolf, B. A.Koenig, and G.Petersen, eds., “Return of Genomic Research Results to a Participant's Family, Including After Death,”Journal of Law, Medicine & Ethics43, no. 3 (2015): 437-593.
3.
See C. R.Breitkopfet al., “Preferences Regarding Return of Genomic Results to Relatives of Research Participants, Including After Participant Death: Empirical Results from a Cancer Biobank,”Journal of Law, Medicine & Ethics43, no. 3 (2015): 464-475; C. R. Breitkopf et al., “Attitudes Toward Return of Genetic Research Results to Relatives, Including after Death: Comparison of Cancer Probands, Blood Relatives, and Spouse/Partners,” Journal of Empirical Research on Human Research Ethics (in press).
4.
On the emerging literature concerning return of results to relatives, including when the proband is deceased, see J. L.Goodmanet al., “Discordance in Selected Designee for Return of Genomic Findings in the Event of Participant Death and Estate Executor,”Molecular Genetics & Genomic Medicine5, no. 2 (2017): 172-176; L. A. Siminoff et al., “Family Decision Maker Perspectives on the Return of Genetic Results in Biobanking Research,” Genetics in Medicine 18, no. 1 (2016): 82-88; L. M. Amendola et al., “Patients’ Choices for Return of Exome Sequencing Results in the Event of their Death,” Journal of Law, Medicine & Ethics 43, no. 3 (2015): 476-485; Wolf et al., supra note 1; K. D. Graves et al., “Communication of Genetic Test Results to Family and Health Care Providers Following Disclosure of Research Results,” Genetics in Medicine 16, no. 4 (2014): 294-301; L. C. Milner, E. Y. Liu, and N. A. Garrison, “Relationships Matter: Ethical Considerations for Returning Results to Family Members of Deceased Subjects,” American Journal of Bioethics 13, no. 10 (2013): 66-67; H. A. Taylor and B. S. Wilfond, “The Ethics of Contacting Family Members of a Subject in a Genetic Research Study to Return Results for an Autosomal Dominant Syndrome,” American Journal of Bioethics 13, no. 10 (2013): 64-65; B. Chan et al., “Genomic Inheritances: Disclosing Individual Research Results from Whole-Exome Sequencing to Deceased Participants' Relatives,” American Journal of Bioethics 12, no. 10 (2012): 1-8; M. A. Rothstein, “Disclosing Decedents' Research Results to Relatives Violates the HIPAA Privacy Rule,” American Journal of Bioethics 12, no. 10 (2012): 16-17; A. L. Bredenoord and J. J. M. van Delden, “Disclosing Individual Genetic Research Results to Deceased Participants' Relatives by Means of a Qualified Disclosure Policy,” American Journal of Bioethics 12, no. 10 (2012): 12-14; A. M. Tassé, “The Return of Results of Deceased Research Participants,” Journal of Law, Medicine & Ethics 39, no. 4 (2011): 621-630; E. Ormondroyd et al., “Communicating Genetics Research Results to Families: Problems Arising When the Patient Participant Is Deceased,” Psycho-Oncology 17, no. 8 (2008): 804-811. See also National Human Genome Research Institute (NHGRI), Informed Consent for Genomics Research, Special Considerations for Genome Research, Considerations for Families, at <https://www.genome.gov/27559024/informed-consent-special-considerations-for-genome-research/> (last visited October 21, 2017).
5.
See National Human Genome Research Institute (NHGRI), Informed Consent for Genomics Research, Special Considerations for Genome Research, Studies Involving Children, at <https://www.genome.gov/27559024/informed-consent-special-considerations-for-genome-research/> (last visited October 21, 2017); J. R.Botkinet al., “Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents,”American Journal of Human Genetics97, no. 1 (2015): 6-21; S. Scollon et al., “Pediatric Cancer Genetics Research and an Evolving Preventive Ethics Approach for Return of Results after Death of the Subject,” Journal of Law, Medicine & Ethics 43, no. 3 (2015): 529-537; E. W. Clayton et al., “Addressing the Ethical Challenges in Genetic Testing and Sequencing of Children,” American Journal of Bioethics 14, no. 3 (2014): 3-9; L. F. Ross et al., “Technical Report: Ethical and Policy Issues in Genetic Testing and Screening of Children,” Genetics in Medicine 15, no. 3 (2013): 234-245; R. C. Green et al., “ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genomic Sequencing,” Genetics in Medicine 15, no. 7 (2013): 565-574.
6.
See K. W.Weitzelet al., “The IGNITE Network: A Model for Genomic Medicine Implementation and Research,”BMC Medical Genomics9, no. 1 (2016): DOI:10.1186/s12920-015-0162-5; M. S. Williams, “Perspectives on What Is Needed to Implement Genomic Medicine,” Molecular Genetics & Genomic Medicine 3, no. 3 (2015): 155-159.
7.
Wolf et al., supra note 1, at 448 (emphasis omitted).
8.
As we stated in our prior paper, “In different contexts, the representative may vary. A Legally Authorized Representative (LAR), Executor, Next-of-Kin, Spouse or Partner, or Parent/Guardian may qualify, depending on applicable federal and state law. HIPAA uses the term ‘personal representative’ to refer to the authorized representative, including after the participant's death.” Wolf et al., supra note 1, at 460. For further discussion, see id., at 441, 443-44, 449, 460, 461 n. 15.
9.
Id., at 448 (emphasis omitted).
10.
See note 3, supra.
11.
Wolf et al., supra note 1.
12.
This project participated in the CSER1 Consortium, whose website was at <https://cser-consortium.org/>. This is now the website for the follow-on CSER2 Consortium, but includes CSER1-generated resources. For a description of the work of the CSER1 Consortium, see R. C.Greenet al., “Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine,”American Journal of Human Genetics98, no. 6 (2016): 1051-1066. For a description of CSER2, see National Human Genome Research Institute (NHGRI), Clinical Sequencing Evidence-Generating Research (CSER2), at <https://www.genome.gov/27546194/clinical-sequencing-exploratory-research-cser/> (last visited October 27, 2017).
These forms and processes may also need to be customized depending on applicable federal and state law. For example, some institutions in which research is conducted may be covered by HIPAA, while others are not. In addition, state law may address privacy and disclosure, as well as who may serve as the research participant's Representative to make decisions about sharing their genomic results when the participant has lost decisional capacity or died. See Wolf et al., supra note 1. The potential legal issues suggest that researchers and their institutions should obtain legal consultation as needed.
15.
See, e.g., G. P.Jarviket al., “Return of Genomic Results to Research Participants: The Floor, the Ceiling, and the Choices in Between,”American Journal of Human Genetics94, no. 6 (2014): 818-826.
Health Insurance Portability and Accountability Act of 1996, Pub. L. No. 104-191, 110 Stat. 1936 (1996), codified at 42 U.S.C. § 300gg and 29 U.S.C. §§ 1181 et seq. and 42 U.S.C. §§ 1320d et seq. See Wolf et al., supra note 1, at n. 17 on HIPAA allowing a family member's physician to obtain an individual's protected health information when relevant to the family member's treatment.
19.
See Wolf et al., supra note 1.
20.
See, e.g., W.Burke, B. J.Evans, and G. P.Jarvik, “Return of Results: Ethical and Legal Distinctions between Research and Clinical Care,”American Journal of Medical Genetics, Part C, Seminars in Medical Genetics166, no. 1 (2014): 105-111; N. P. Arango et al., “A Feasibility Study of Returning Clinically Actionable Somatic Genomic Alterations Identified in a Research Laboratory,” Oncotarget 8, no. 26 (2017): 41806-41814.
21.
Jarvik et al., supra note 15.
22.
See, e.g., National Institutes of Health, Research Involving Individuals with Questionable Capacity to Consent: Points to Consider, at <http://grants.nih.gov/grants/policy/question-ablecapacity.htm> (last visited October 21, 2017); C. Grady, “Enduring and Emerging Challenges of Informed Consent,” New England Journal of Medicine 372, no. 9 (2015): 855-862.
23.
Wolf et al., supra note 1. See also note 8, supra.
24.
Id.
25.
Id., at 451 and n. 69.
26.
Id., at 450.
27.
M.Sabatello and P. S.Appelbaum, “Raising Genomic Citizens: Adolescents and the Return of Secondary Genomic Findings,”Journal of Law, Medicine & Ethics44, no. 2 (2016): 292-304; K. B. Brothers et al., “Practical Guidance on Informed Consent for Pediatric Participants in a Bioreposi-tory,” Mayo Clinic Proceedings 89, no. 11 (2014): 1471-1480; I. A. Holm et al., “Guidelines for Return of Research Results from Pediatric Genomic Studies: Deliberations of the Boston Children's Hospital Gene Partnership Informed Cohort Oversight Board,” Genetics in Medicine 16, no. 7 (2014): 547-552.
28.
U.S. Department of Health and Human Services (DHHS), Protection of Human Subjects, Requirements for Permission by Parents or Guardians and for Assent by Children, 45 C.F.R. § 46.408 (2017). This paper generally refers to permission from both parents (or a guardian), as DHHS states that, “In general, permission should be obtained from both parents before a child is enrolled in research. However, the Institutional Review Board (IRB) may find that the permission of one parent is sufficient for research to be conducted under [Common Rule sections] 46.404 or 46.405. When research is to be conducted under 46.406 and 46.407 permission must be obtained from both parents, unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child.” U.S. Department of Health and Human Services (DHHS), Office for Human Research Protections (OHRP), Research with Children FAQs, at <https://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/children-research/index.html> (last visited October 25, 2017).
29.
U.S. Department of Health and Human Services (DHHS), Protection of Human Subjects, Requirements for Permission by Parents or Guardians and for Assent by Children, supra note 28.
30.
See note 5, supra; S. B.Hufnagelet al., “Adolescent Preferences Regarding Disclosure of Incidental Findings in Genomic Sequencing that Are Not Medically Actionable in Childhood,”American Journal of Medical Genetics170, no. 8 (2016): 2083-2088; B. S. Wilfond, C. V. Fernandez, and R. C. Green, “Disclosing Secondary Findings from Pediatric Sequencing to Families: Considering the ‘Benefit to Families,’” Journal of Law, Medicine & Ethics 43, no. 3 (2015): 552-558.
