Return of Results & Secondary Findings
The return of results and the dilemma of what to do with incidental, or secondary, findings is another area of concern. This issue is not unique to genomics however, as the technology advances and the cost of sequencing decreases the amount of genomic data being generated is increasing, as is the likelihood of discovering secondary findings. These findings can be complex and sensitive because of the potential to impact other family members.
Despite the pace at which knowledge of the human genome is being discovered there is still much debate over which results are actionable and new findings and different interpretations are making it difficult to develop standard recommendations.
In 2013, the American College of Medical Genetics (ACMG) published a list of medically actionable secondary findings that they recommended should be searched for and reported during clinical exome and genome sequencing. Some researchers chose to follow these recommendations, however, others cautioned against the ACMG list because of concerns that only a small percentage of those that had genetic variants associated with disease would actually manifest with disease. In 2016, the ACMG published an updated list of medically actionable findings to return but there is still no universal consensus and researchers, clinicians, bioethicists and others continue to debate what, how and when is best practice for the return of results.
Most of the current guidelines have been developed by clinical, scientific and ethical experts however there are a growing number of studies in the literature that are investigating the preferences of the general public, patients and research participants as well as the studying the impact of receiving results. It is expected that a greater understanding of these preferences, alongside the views of experts, will influence the future development of return of results policies.
Resources on Return of Results & Secondary Findings
ASHG Position Statement - Bombard Y, Brothers KB, Fitzgerald-Butt S, Garrison NA, Jamal L, James CA, et al. The Responsibility to Recontact Research Participants after Reinterpretation of Genetic and Genomic Research Results. The American Journal of Human Genetics. 2019;104(4):578-95. https://doi.org/10.1016/j.ajhg.2019.02.025
David KL, Best RG, Brenman LM, Bush L, Deignan JL, Flannery D, et al. Patient re-contact after revision of genomic test results: points to consider—a statement of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine. 2019;21(4):769-71. https://doi.org/10.1038/s41436-018-0391-z
Carrieri D, Howard HC, Benjamin C, Clarke AJ, Dheensa S, Doheny S, et al. Recontacting patients in clinical genetics services: recommendations of the European Society of Human Genetics. European Journal of Human Genetics. 2018. http://doi.org/10.1038/s41431-018-0285-1 . [Epub ahead of print]
National Academies of Sciences, Engineering, and Medicine. (2018). Returning Individual Research Results to Participants: Guidance for a New Research Paradigm. Washington, DC: The National Academies Press. https://doi.org/10.17226/
Botkin, Belmont, Berg, Berkman, Bombard, Holm, . . . Mcinerney. (2015). Points to Consider: Ethical, Legal, and Psychosocial Implications of Genetic Testing in Children and Adolescents. The American Journal of Human Genetics, 97(1), 6-21. https://doi.org/10.1016/j.ajhg.2015.05.022
Green, R. C., Berg, J. S., Grody, W. W., Kalia, S. S., Korf, B. R., Martin, C. L., … Biesecker, L. G. (2013). ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 15(7), 565–574. http://doi.org/10.1038/gim.2013.73
Watson, M. (2013). American College of Medical Genetics and Genomics. Incidental findings in clinical genomics: a clarification. Genetics in Medicine. 15. 664-666. http://doi.org/10.1038/gim.2013.82
Kalia, S., Adelman, K., Bale, S., Chung, W., Eng, C., Evans, J., Herman, G., Hufnagel, S. B., Klein, T., Korf, B., McKelvey, K., Ormond, K., Richards, C., Vlangos, C., Watson, M., Martin, C., & Miller, D. (2017). Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genetics in Medicine, 19 (2). http://dx.doi.org/10.1038/gim.2016.190
Carla G Van El, Martina C Cornel, Pascal Borry, Ros J Hastings, Florence Fellmann, Shirley V Hodgson, . . . Guido M W R De Wert. (2013). Whole-genome sequencing in health care. European Journal of Human Genetics, 21(6), S1-S5. http://doi.org/10.1038/ejhg.2013.46
Gert Matthijs, Erika Souche, Mariëlle Alders, Anniek Corveleyn, Sebastian Eck, Ilse Feenstra, . . . Peter Bauer. (2015). Guidelines for diagnostic next-generation sequencing. European Journal of Human Genetics, 24(1), 2-5. http://doi.org/10.1038/ejhg.2015.226
Wright, C., Middleton, A., Burton, H., Cunningham, F., Humphries, S., Hurst, J., . . . Firth, H. (2013). Policy challenges of clinical genome sequencing. British Medical Journal, 347(7935), 20. https://doi.org/10.1136/bmj.f6845
Knoppers, B., Zawati, M., & Sénécal, K. (2015). Return of genetic testing results in the era of whole-genome sequencing. Nature Reviews. Genetics, 16(9), 553-9. http://doi.org/10.1038/nrg3960
Wright CF, Middleton A, Barrett JC et al. Returning genome sequences to research participants: Policy and practice [version 1; referees: 2 approved]. Wellcome Open Res 2017, 2:15. http://doi.org/10.12688/wellcomeopenres.10942.1
NIH National Human Genome Research Institute. 2018. Return of Research Results. [ONLINE] Available at: https://www.genome.gov/27569049/return-of-research-results/
Ryan, K., De Vries, A., Uhlmann, R., Roberts, G., & Gornick, W. (2017). Public’s Views toward Return of Secondary Results in Genomic Sequencing: It’s (Almost) All about the Choice. Journal of Genetic Counseling, 26(6), 1197-1212. http://doi.org/10.1007/s10897-017-0095-6
Saskia C Sanderson, Michael D Linderman, Sabrina A Suckiel, Randi Zinberg, Melissa Wasserstein, Andrew Kasarskis, . . . Eric E Schadt. (2017). Psychological and behavioural impact of returning personal results from whole-genome sequencing: The HealthSeq project. European Journal of Human Genetics, 25(3), 280-292. http://doi.org/10.1038/ejhg.2016.178
Thomas Ploug, & Søren Holm. (n.d.). Clinical genome sequencing and population preferences for information about 'incidental' findings-From medically actionable genes (MAGs) to patient actionable genes (PAGs). PLoS ONE, 12(7). E0179935. https://doi.org/10.1371/journal.pone.0179935
Wynn, J., Martinez, J., Duong, J., Chiuzan, C., Phelan, J., Fyer, C., . . . Chung, L. (2017). Research Participants’ Preferences for Hypothetical Secondary Results from Genomic Research. Journal of Genetic Counseling, 26(4), 841-851. https://doi-org.ezproxy.library.uq.edu.au/10.1007/s10897-016-0059-2
Smit, A., Keogh, L., Hersch, J., Newson, A., Butow, P., Williams, G., & Cust, A. (2016). Public preferences for communicating personal genomic risk information: A focus group study. Health Expectations, 19(6), 1203-1214. https://doi.org/10.1111/hex.12406
Graves, K., Sinicrope, P., McCormick, J., Zhou, Y., Vadaparampil, S., & Lindor, N. (2015). Public Perceptions of Disease Severity but Not Actionability Correlate with Interest in Receiving Genomic Results: Nonalignment with Current Trends in Practice. Public Health Genomics, 18(3), 173-183. https://doi.org/10.1159/000375479
Ziniel, S., Savage, S., Huntington, N., Amatruda, J., Green, R., Weitzman, E., . . . Holm, I. (2014). Parents' Preferences for Return of Results in Pediatric Genomic Research. Public Health Genomics, 17(2), 105-14. https://doi.org/10.1159/000358539
Juli Murphy Bollinger, John F.P. Bridges, Ateesha Mohamed, & David Kaufman. (2014). Public preferences for the return of research results in genetic research: A conjoint analysis. Genetics in Medicine, 16(12), 932-939. https://doi.org/10.1038/gim.2014.50