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A Framework for Analyzing the Ethics of Disclosing Genetic Research Findings

Published online by Cambridge University Press:  01 January 2021

Lisa Eckstein ,
Jeremy R. Garrett  and
Benjamin E. Berkman
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Extract

Over the past decade, there has been an extensive debate about whether researchers have an obligation to disclose genetic research findings, including primary and secondary findings. There appears to be an emerging (but disputed) view that researchers have some obligation to disclose some genetic findings to some research participants. The contours of this obligation, however, remain unclear.

As this paper will explore, much of this confusion is definitional or conceptual in nature. The extent of a researcher's obligation to return secondary and other research findings is often limited by reference to terms and concepts like “incidental,” “analytic validity,” “clinical validity,” “clinical relevance,” “clinical utility,” “clinical significance,” “actionability,” and “desirability.” These terms are used in different ways by different writers to describe obligations in different sorts of cases.

Type
Independent
Information
Journal of Law, Medicine & Ethics , Volume 42 , Issue 2 , Summer 2014 , pp. 190 - 207
Copyright
Copyright © American Society of Law, Medicine and Ethics 2014

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References

For a discussion of these ethical principles and their implications for disclosure obligations, see Bredenoord, A. L. et al., “Disclosure of Individual Genetic Data to Research Participants: The Debate Reconsidered,” Trends in Genetics 27, no. 2 (2011): 41–47; Bredenoord, A. L. Onland-Moret, N. C. Van Delden, J. J., “Feedback of Individual Genetic Results to Research Participants: In Favor of a Qualified Disclosure Policy,” Human Mutation 32, no. 8 (2011): 861–867.CrossRefGoogle Scholar
Kollek, R. Petersen, I., “Disclosure of Individual Research Results in Clinico-Genomic Trials: Challenges, Classification and Criteria for Decision-Making,” Journal of Medical Ethics 37, no. 5 (2011): 271–275.CrossRefGoogle Scholar
Dressler, L. G. Smolek, S. Ponsaran, R. Markey, J. M. Starks, H. Gerson, N. Lewis, S. et al., “IRB Perspectives on the Return of Individual Results from Genomic Research,” Genetics in Medicine 14, no. 2 (2012): 215–222, at 220.CrossRefGoogle Scholar
Green, R. C. Berg, J. S. Grody, W. W. Kalia, S. S. Korf, B. R. Martin, C. L. McGuire, A. L. et al., “ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing,” Genetics in Medicine 15, no. 7 (2013): 565–574.CrossRefGoogle Scholar
Burke, W. Matheny Antommaria, H. A. H. Bennett, R. Botkin, J. Wright Clayton, E. Henderson, G. E. Holm, I. A. et al., “Recommendations for Returning Genomic Incidental Findings? We Need to Talk!” Genetics in Medicine 15, no. 11 (2013): 854–859.CrossRefGoogle Scholar
Presidential Commission for the Study of Bioethical Issues, Anticipate and Communicate: Ethical Management of Incidental and Secondary Findings (Presidential Commission for the Study of Bioethical Issues, December 2013), available at <http://bioethics.gov/sites/default/files/FINALAnticipate-Communicate_PCSBI_0.pdf>(last visited April 10, 2014).(last+visited+April+10,+2014).>Google Scholar
Id., at 28–29.Google Scholar
This distinction is frequently traced back to Gallie's discussion of “essentially contested concepts” and to Rawls' elaboration of related issues in A Theory of Justice. Gallie, W. B., “Essentially Contested Concepts,” Proceedings of the Aristotelian Society 56 (1956): 167–198. Rawls, J., A Theory of Justice (Cambridge, MA: Harvard University Press): At Chap. 32.CrossRefGoogle Scholar
A list of these journal articles is available from the authors on request.Google Scholar
Christenhusz, G. M. Devriendt, K. Dierickx, K., “Secondary Variants – in Defense of a More Fitting Term in the Incidental Findings Debate,” European Journal of Human Genetics 21, no. 12 (2013): 1331–1334.CrossRefGoogle Scholar
Tabor, H. K. Berkman, B. E. Chandros Hull, S. Bamshad, M. J., “Genomics Really Gets Personal: How Exome and Whole Genome Sequencing Challenge the Ethical Framework of Human Genetics Research,” American Journal of Medical Genetics Part A, 155 (2011): 2916–2924.CrossRefGoogle Scholar
Wolf, S. M. Lawrenz, F. P. Nelson, C. A. Kahn, J. P. Cho, M. K. Wright Clayton, E. Fletcher, J. G. et al., “Managing Incidental Findings in Human Subjects Research: Analysis and Recommendations,” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 219–248. For examples of uptake, see Richardson, H. S., “Incidental Findings and Ancillary-Care Obligations,” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 256–270; Simon, C. M. Williams, J. K. Shinkunas, L. Brandt, D. Daack-Hirsch, S. Driessnack, M., “Informed Consent and Genomic Incidental Findings: IRB Chair Perspectives,” Journal of Empirical Research on Human Research Ethics: An International Journal 6, no. 4 (2011): 53–67; Van Ness, B., “Genomic Research and Incidental Findings,” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 292–297.CrossRefGoogle Scholar
Wolf, S. M. Crock, B. N. Van Ness, B. Lawrenz, F. Kahn, J. P. Beskow, L. M. Cho, M. K. et al., “Managing Incidental Findings and Research Results in Genomic Research Involving Biobanks and Archived Data Sets,” Genetics in Medicine 14 (2012): 361–384, at 364; Wolf, S. M., “Introduction: The Challenge of Incidental Findings,” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 216–218; see Wolf, et al., supra note 12; Richardson, , supra note 12, at 258. See also Parker, L. S., “Best Laid Plans for Offering Results Go Awry,” American Journal of Bioethics 6, no. 6 (2006):22–23. (“Restricted by the study's hypothesis or research question.”).CrossRefGoogle Scholar
Knoppers, B. M. Dam, A., “Return of Results: Towards a Lexicon?” Journal of Law, Medicine & Ethics 39, no. 4 (2011): 577–582.CrossRefGoogle Scholar
Miller, F. G. Mello, M. M. Joffe, S., “Incidental Findings in Human Subjects Research: What Do Investigators Owe Research Participants?” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 271–279.CrossRefGoogle Scholar
Terry, S. F., “The Tension Between Policy and Practice in Returning Research Results and Incidental Findings in Genomic Biobank Research,” Minnesota Journal of Law, Science & Technology 13, (2012): 691–925, at 705.Google Scholar
Cho, M. K., “Understanding Incidental Findings in the Context of Genetics and Genomics,” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 280–285, at 281. See also Kohane, I. S. Taylor, P. L., “Multidimensional Results Reporting to Participants in Genomic Studies: Getting It Right,” Science Translational Medicine 2, no. 37 (2010): 37cm19, at 2.CrossRefGoogle Scholar
Hens, K. Nys, H. Cassiman, J. J. Dierickx, K., “The Return of Individual Research Findings in Paediatric Genetic Research,” Journal of Medical Ethics 37, no. 3 (2011): 179–183; Knoppers, B. M. Rioux, A. Zawati, M. H., “Pediatric Research ‘Personalized’? International Perspectives on the Return of Results,” Personalized Medicine 10, no. 1 (2013): 89–95.CrossRefGoogle Scholar
See Richardson, , supra note 12, at 258.Google Scholar
Id.Google Scholar
See Wolf, et al., supra note 12 Equivalent constraints are included in Wolf, supra note 13.Google Scholar
See Knoppers, Dam, , supra note 14, at 580; Miller, Mello, Joffe, , supra note 15; Knoppers, Rioux, Zawati, , supra note 18.Google Scholar
See Knoppers, Dam, , supra note 14, at 580.Google Scholar
See Kohane, Taylor, , supra note 17, at 2.Google Scholar
See Wolf, , supra note 13, at 216.Google Scholar
See Knoppers, Dam, , supra note 14, at 580.Google Scholar
See Wolf, et al., supra note 12. Emphasis added.Google Scholar
Parker, L. S., “The Future of Incidental Findings: Should They Be Viewed as Benefits?” Journal of Law, Medicine & Ethics 36, no. 2 (2008): 341–351, at 341.CrossRefGoogle Scholar
Id., at 342.Google Scholar
See Wolf, et al., supra note 12; Wolf, , supra note 13, at 216.Google Scholar
See Richardson, , supra note 12, at 258.Google Scholar
Id.Google Scholar
Id.Google Scholar
Ravitsky, V. Wilfond, B. S., “Disclosing Individual Genetic Results to Research Participants,” American Journal of Bioethics 6, no. 6 (2006): 8–17; see Wolf, et al., supra note 13; Bookman, E. B. Langehorne, A. A. Eckfeldt, J. H. Glass, K. C. Jarvik, G. P. Klag, M. Koski, G. et al., “Reporting Genetic Results in Research Studies: Summary and Recommendations of an NHLBI Working Group,” American Journal of Medical Genetics Part A, 140A (2006): 1033–1040; Knoppers, B. M. Joly, Y. Simard, J. Durocher, F., “The Emergence of an Ethical Duty to Disclose Genetic Research Results: International Perspectives,” European Journal of Human Genetics 14, no. 11 (2006): 1170–1178; Miller, F. A. Christensen, R. Giacomini, M. Robert, J. S., “Duty to Disclose What? Querying the Putative Obligation to Return Research Results to Participants,” Journal of Medical Ethics 34, no. 3 (2008): 210–213 (using the term “data veracity”); Holm, I. A. Taylor, P. L., “The Informed Cohort Oversight Board: From Values to Architecture,” Minnesota Journal of Law, Science & Technology 13, no. 2 (2012): 669–925; Parker, L. S., “Returning Individual Research Results: What Role Should People's Preferences Play?” Minnesota Journal of Law, Science & Technology 13, no. 2 (2012): 449–925.CrossRefGoogle Scholar
See Ravitsky, Wilfond, , supra note 34, at 10.Google Scholar
See Wolf, et al., supra note 12, at 237.Google Scholar
See Bookman, et al., supra note 34, at 1034.Google Scholar
Fernandez, C. V. Weijer, C., “Obligations in Offering to Disclose Genetic Research Results,” American Journal of Bioethics 6, no. 6 (2006): 44–46.CrossRefGoogle Scholar
See Bredenoord, et al., supra note 1, at 45.Google Scholar
See Dressler, et al., supra note 3, at 219.Google Scholar
See Ravitsky, Wilfond, , supra note 34, at 10; Miller, F. G. Shalowitz, D. I., “Disclosing Individual Results of Clinical Research: Implications of Respect for Participants,” JAMA 294, no. 6 (2005): 737–740; Holm, Taylor, , supra note 34.CrossRefGoogle Scholar
See Knoppers, et al., supra note 34, at 1175.Google Scholar
See Fernandez, Weijer, , supra note 38, at 45; Dressler, L. G. Juengst, E. T., “Thresholds and Boundaries in the Disclosure of Individual Genetic Research Results,” American Journal of Bioethics 6, no. 6 (2006): 18–20.CrossRefGoogle Scholar
Fabsitz, R. R. McGuire, A. Sharp, R. R. Puggal, M. Beskow, L. M. Biesecker, L. G. Bookman, E. et al., “Ethical and Practical Guidelines for Reporting Genetic Research Results to Study Participants Updated Guidelines from a National Heart, Lung, and Blood Institute Working Group,” Circulation: Cardiovascular Genetics 3, no. 6 (2010): 574–580, at 577.Google Scholar
See Cho, , supra note 17, at 282.Google Scholar
See Knoppers, Dam, , supra note 14, at 579.Google Scholar
Klitzman, R., “Questions, Complexities, and Limitations in Disclosing Individual Genetic Results,” American Journal of Bioethics 6 (2006): 34–36.CrossRefGoogle Scholar
See, e.g., Knoppers, Dam, , supra note 14, at 579; Ravitsky, Wilfond, , supra note 34; Bookman, et al., supra note 34; Murphy, J. Scott, J. Kaufman, D. Geller, G. LeRoy, L. Hudson, K., “Public Expectations for Return of Results from Large-Cohort Genetic Research,” American Journal of Bioethics 8 (2008): 36–43; Parker, , supra note 34.CrossRefGoogle Scholar
See Bookman, et al., supra note 34, at 1034.Google Scholar
See Ravitsky, Wilfond, , supra note 34, at 11.Google Scholar
See Bookman, et al., supra note 34, at 1034. See also Ormond, K. E., “Disclosing Genetic Research Results: Examples from Practice,” American Journal of Bioethics 6, no. 6 (2006): 30–32.CrossRefGoogle Scholar
See Murphy, et al., supra note 48.Google Scholar
See Parker, , supra note 34.Google Scholar
See Ormond, , supra note 51, at 31.Google Scholar
See Wolf, et al., supra note 12, at 231; Holm, Taylor, , supra note 34; Van Ness, , supra note 12.Google Scholar
See Wolf, et al., supra note 12, at 231.Google Scholar
See Cho, , supra note 17, at 282.Google Scholar
See, e.g., Dressler, Juengst, , supra note 43; Bredenoord, et al., supra note 1.Google Scholar
Beskow, L. M. Burke, W., “Offering Individual Genetic Research Results: Context Matters,” Science Translational Medicine 2, no. 38 (2010): 38cm20.CrossRefGoogle Scholar
See Knoppers, Dam, , supra note 14, at 580. Similarly, Matthew Gordon describes “individual findings that are medically useful in the sense that there is some action that can be taken to prevent or ameliorate the condition indicated by the finding:” Gordon, M. P., “A Legal Duty to Disclose Individual Research Findings to Research Subjects,” Food and Drug Law Journal 64, no. 1 (2009): 225–260.Google Scholar
See Bookman, et al., supra note 34.Google Scholar
See Bredenoord, Onland-Moret, Van Delden, , supra note 1, at 865.Google Scholar
Id.Google Scholar
See Ravitsky, Wilfond, , supra note 34, at 11 (emphasis added).Google Scholar
See Wolf, et al., “Managing Incidental Findings in Human Subjects Research,” supra note 12.Google Scholar
Id.Google Scholar
See Fernandez, Weijer, , supra note 38; 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.CrossRefGoogle Scholar
Brief, E. Mackie, J. Illes, J., “Incidental Findings in Genetic Research: A Vexing Challenge for Community Consent,” Minnesota Journal of Law, Science & Technology 13, no. 2 (2012): 541–558.Google Scholar
McGeveran, W. Fatehi, L. McGarraugh, P., “Deidentification and Reidentification in Returning Individual Findings from Biobank and Secondary Research: Regulatory Challenges and Models for Management,” Minnesota Journal of Law, Science & Technology 13, no. 2 (2012): 485–539.Google Scholar
See Wolf, et al., supra note 12, at 225.Google Scholar
Shalowitz, D. I. Miller, F. G., “Communicating the Results of Clinical Research to Participants: Attitudes, Practices, and Future Directions,” PLoS Medicine 5, no. 5 (2008): 0714–0720.CrossRefGoogle Scholar
See Kohane, Taylor, , supra note 17, at 2–3.Google Scholar
See Knoppers, et al., supra note 34, at 1174–1175.Google Scholar
Knoppers, B. M. Laberge, C., “Return of ‘Accurate’ and ‘Actionable’ Results: Yes!” American Journal of Bioethics 9, no. 6 (2009): 107–109.CrossRefGoogle Scholar
See Kohane, Taylor, , supra note 17, at 2.Google Scholar
Pullman, D. Hodgkinson, K., “Genetic Knowledge and Moral Responsibility: Ambiguity at the Interface of Genetic Research and Clinical Practice,” Clinical Genetics 69, no. 3 (2006): 199–203, at 202.CrossRefGoogle Scholar
Id.Google Scholar
McGuire, A. L. Caulfield, T. Cho, M. K., “Research Ethics and the Challenge of Whole-Genome Sequencing,” Nature Reviews: Genetics 9, no. 2 (2008): 152–156, at 153.Google Scholar
Renegar, G. et al., “Returning Genetic Research Results to Individuals: Points-to-Consider,” Bioethics 20, no. 1 (2006): 24–36.CrossRefGoogle Scholar
See Kollek, Petersen, , supra note 2, at 272.Google Scholar
Westbrook, M. J. et al., “Mapping the Incidentalome: Estimating Incidental Findings Generated through Clinical Pharmacogenomics Testing,” Genetics in Medicine 15, no. 5 (2013): 325–331.CrossRefGoogle Scholar
See Renegar, et al., supra note 79.Google Scholar
See Miller, et al., supra note 34.Google Scholar
See Knoppers, Dam, , supra note 14, at 579.Google Scholar
Abdul-Karim, R. Berkman, B. E. Wendler, D. Rid, A. Khan, J. Badgett, T. Chandros Hull, S., “Disclosure of Incidental Findings From Next-Generation Sequencing in Pediatric Genomic Research,” Pediatrics 131, no. 3 (2013): 564–571, at 567–568.CrossRefGoogle Scholar
See, e.g., Miller, et al., supra note 34; O'Daniel, J. Haga, S. B., “Public Perspectives on Returning Genetics and Genomics Research Results,” Public Health Genomics 14, no. 6 (2011): 346–355, at 353; Wolf, et al., supra note 12.Google Scholar
Affleck, P., “Is It Ethical to Deny Genetic Research Participants Individualised Results?” Journal of Medical Ethics 35, no. 4 (2009): 209–213, at 210.CrossRefGoogle Scholar
See Gordon, , supra note 60, at 229. See also Wolf, et al., supra note 12, who advocate broadening “utility” to include “what a research participant would find useful, recognizing not only treatment utility but also health or reproductive information utility.”.Google Scholar
See Beskow, Burke, , supra note 59. A similar definition is adopted in Wolf, et al., supra note 13, at 373.Google Scholar
See Ormond, , supra note 51, at 30.Google Scholar
See Ravitsky, Wilfond, , supra note 34. See also Shalowitz, , supra note 41, at 739.Google Scholar
See Terry, , supra note 16.Google Scholar
Matsui, K. Lie, R. K. Kita, Y. Ueshima, H., “Ethics of Future Disclosure of Individual Risk Information in a Genetic Cohort Study: A Survey of Donor Preferences,” Journal of Epidemiology 18, no. 5 (2008): 217–224, at 221.CrossRefGoogle Scholar
See Terry, , supra note 16, at 713.Google Scholar
See Fabsitz, et al., supra note 44, at 575–576.Google Scholar
See Wolf, et al., supra note 13, at 373.Google Scholar
See Murphy, et al., supra note 48.Google Scholar
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. See also Parker, , supra note 34.CrossRefGoogle Scholar
See Parker, , supra note 34.Google Scholar
See Miller, Mello, Joffe, , supra note 15.Google Scholar
See Wolf, et al., supra note 12, at 233. See also Wolf, et al., supra note 13, at 371.Google Scholar
See Terry, , supra note 16, at 706.Google Scholar
See Matsui, et al., supra note 93, at 222.Google Scholar
See Kohane, Taylor, , supra note 17, at 2–3.Google Scholar
See discussion in Gliwa, C. Berkman, B. E., “Do Researchers Have an Obligation to Actively Look for Genetic Incidental Findings?” American Journal of Bioethics 13, no. 3 (2013): 32–42, at 32.CrossRefGoogle Scholar
See, e.g., Affleck, , supra note 87: “For the purposes of this paper, a research ‘result’ is simply regarded as a new piece of information that may relate to a particular individual.”.Google Scholar
Notably, a threshold question in this regard is whether a given piece of information constitutes a “finding,” the answer to which is likely to vary across different contexts and perspectives. The information that would constitute a “finding” for a scientist conducting research would likely be quite different to the level of certainty required for a clinician treating a patient.Google Scholar
Parens, E. Appelbaum, P. Chung, W., “Incidental Findings in the Era of Whole Genome Sequencing?” Hastings Center Report 43, no. 4 (2013): 16–19, at 18.CrossRefGoogle Scholar
Stedman's Medical Dictionary, s.v. “Clinical,” Lathrop Stedman, T., ed. (Baltimore: Williams & Wilkins, 1995).Google Scholar
See Beskow, Burke, , supra note 59.Google Scholar
See Ravitsky, Wilfond, , supra note 34.Google Scholar
See Brief, Mackie, Illes, , supra note 68.Google Scholar
Wolf, et al., “Managing Incidental Findings in Human Subjects Research,” supra note 12.Google Scholar
See Knoppers, et al., supra note 34.Google Scholar
See Matsui, et al., supra note 93.Google Scholar
See Fabsitz, et al., supra note 44.Google Scholar
See Murphy, et al., supra note 48, using the phrase “categories of action.”.Google Scholar
See Beskow, Burke, , supra note 59.Google Scholar
See Ormond, , supra note 51.Google Scholar
Merriam-Webster, s.v. “Volition,” available at <http://www.merriam-webster.com/dictionary/volition>(last visited April 11, 2014).(last+visited+April+11,+2014).>Google Scholar
See Parker, , supra note 34.Google Scholar
See Green, et al., supra note 4.Google Scholar