Abstract
We aimed to describe patient preferences for a broad range of secondary findings (SF) from genomic sequencing (GS) and factors driving preferences. We assessed preference data within a trial of the Genomics ADvISER, (SF decision aid) among adult cancer patients. Participants could choose from five categories of SF: (1) medically actionable; (2) polygenic risks; (3) rare diseases; (4) early-onset neurological diseases; and (5) carrier status. We analyzed preferences using descriptive statistics and drivers of preferences using multivariable logistic regression models. The 133 participants were predominantly European (74%) or East Asian or mixed ancestry (13%), female (90%), and aged > 50 years old (60%). The majority chose to receive SF. 97% (129/133) chose actionable findings with 36% (48/133) choosing all 5 categories. Despite the lack of medical actionability, participants were interested in receiving SF of polygenic risks (74%), carrier status (75%), rare diseases (59%), and early-onset neurologic diseases (53%). Older participants were more likely to be interested in receiving results for early-onset neurological diseases, while those exhibiting lower decisional conflict were more likely to select all categories. Our results highlight a disconnect between cancer patient preferences and professional guidelines on SF, such as ACMG’s recommendations to only return medically actionable secondary findings. In addition to clinical evidence, future guidelines should incorporate patient preferences.
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The data set analysed during the current study are available from the corresponding author upon reasonable request.
References
Ackerman SL, Koenig BA (2018) Understanding variations in secondary findings reporting practices across U.S. genome sequencing laboratories. AJOB Empir Bioeth, 9(1): 48–57. https://doi.org/10.1080/23294515.2017.1405095
Bennette CS, Trinidad SB, Fullerton SM, Patrick D, Amendola L, Burke W, Veenstra DL (2013) Return of incidental findings in genomic medicine: measuring what patients value--development of an instrument to measure preferences for information from next-generation testing (IMPRINT). Genet Med, 15(11): 873–881. https://doi.org/10.1038/gim.2013.63
Best MC, Butow P, Savard J, Jacobs C, Bartley N, Davies G, Newson AJ (2022) Preferences for return of germline genome sequencing results for cancer patients and their genetic relatives in a research setting. Eur J Hum Genet. https://doi.org/10.1038/s41431-022-01069-y
Bishop CL, Strong KA, Dimmock DP (2017) Choices of incidental findings of individuals undergoing genome wide sequencing, a single center’s experience. Clin Genet 91(1):137–140. https://doi.org/10.1111/cge.12829
Bombard Y, Clausen M, Mighton C, Carlsson L, Casalino S, Glogowski E, Laupacis A (2018) The Genomics ADvISER: development and usability testing of a decision aid for the selection of incidental sequencing results. Eur J Hum Genet 26(7):984–995. https://doi.org/10.1038/s41431-018-0144-0
Bombard Y, Clausen M, Shickh S, Mighton C, Casalino S, Kim THM, IGS Team (2020) Effectiveness of the Genomics ADvISER decision aid for the selection of secondary findings from genomic sequencing: a randomized clinical trial. Genet Med 22(4):727–735. https://doi.org/10.1038/s41436-019-0702-z
Boycott K, Hartley T, Adam S, Bernier F, Chong K, Fernandez BA, Canadian College of Medical Geneticists (2015) The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists. J Med Genet 52(7):431–437. https://doi.org/10.1136/jmedgenet-2015-103144
Cassidy MR, Roberts JS, Bird TD, Steinbart EJ, Cupples LA, Chen CA, Green RC (2008) Comparing test-specific distress of susceptibility versus deterministic genetic testing for Alzheimer's disease. Alzheimers Dement 4(6):406–413. https://doi.org/10.1016/j.jalz.2008.04.007
de Wert G, Dondorp W, Clarke A, Dequeker EMC, Cordier C, Deans Z, European Society of Human Genetics (2021) Opportunistic genomic screening. Recommendations of the European Society of Human Genetics. Eur J Hum Genet 29(3):365–377. https://doi.org/10.1038/s41431-020-00758-w
Harrell FE, Lee KL, Mark DB (1996) Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15(4):361–387. https://doi.org/10.1002/(SICI)1097-0258(19960229)15:4%3c361::AID-SIM168%3e3.0.CO;2-4
Harrell Jr FE (2023) rms: Regression Modeling Strategies. R package version 6.1–1. https://CRAN.R-project.org/package=rms
Hehir-Kwa JY, Claustres M, Hastings RJ, van Ravenswaaij-Arts C, Christenhusz G, Genuardi M, Robinson PN (2015) Towards a European consensus for reporting incidental findings during clinical NGS testing. Eur J Hum Genet, 23(12): 1601–1606. https://doi.org/10.1038/ejhg.2015.111
Holmes-Rovner M (2007) International patient decision aid standards (IPDAS): beyond decision aids to usual design of patient education materials. Health Expect 10(2):103–107. https://doi.org/10.1111/j.1369-7625.2007.00445.x
Kaphingst KA, Facio FM, Cheng MR, Brooks S, Eidem H, Linn A, Biesecker L. G (2012) Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet, 82(5): 408–415. https://doi.org/10.1111/j.1399-0004.2012.01909.x
Kaphingst KA, Ivanovich J, Lyons S, Biesecker B, Dresser R, Elrick A, Goodman M (2018) Preferences for learning different types of genome sequencing results among young breast cancer patients: role of psychological and clinical factors. Transl Behav Med, 8(1): 71–79. https://doi.org/10.1093/tbm/ibx042
Mackley MP, Blair E, Parker M, Taylor JC, Watkins H, Ormondroyd E (2018) Views of rare disease participants in a UK whole-genome sequencing study towards secondary findings: a qualitative study. Eur J Hum Genet 26(5):652–659. https://doi.org/10.1038/s41431-018-0106-6
Marcheco B, Bertoli AM, Rojas I, Heredero L (2003) Attitudes and knowledge about presymptomatic genetic testing among individuals at high risk for familial, early-onset Alzheimer’s disease. Genet Test 7(1):45–47. https://doi.org/10.1089/109065703321560930
Meiser B, Butow P, Davies G, Napier CE, Schlub TE, Bartley N, members of the Psychosocial Issues in Genomics in Oncology (PiGeOn) Project (2022) Psychological predictors of cancer patients' and their relatives' attitudes towards the return of genomic sequencing results. Eur J Med Genet 65(6):104516. https://doi.org/10.1016/j.ejmg.2022.104516
Mighton C, Carlsson L, Clausen M, Casalino S, Shickh S, McCuaig L, IGS Team (2019) Development of patient "profiles" to tailor counseling for incidental genomic sequencing results. Eur J Hum Genet 27(7):1008–1017. https://doi.org/10.1038/s41431-019-0352-2
Miller DT, Lee K, Chung WK, Gordon AS, Herman GE, Klein TE, ACMG Secondary Findings Working Group (2021) ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. https://doi.org/10.1038/s41436-021-01172-3
Nelson WL, Han PK, Fagerlin A, Stefanek M, Ubel PA (2007) Rethinking the objectives of decision aids: a call for conceptual clarity. Med Decis Making 27(5):609–618. https://doi.org/10.1177/0272989X07306780
O’Connor AM (1995) Validation of a decisional conflict scale. Med Decis Making 15(1):25–30. https://doi.org/10.1177/0272989X9501500105
O'Connor A (2006) Ottawa Decision Support Framework to address decisional conflict. Retrieved from www.ohri.ca/decisionaid
O'Connor A (2010) User Manual-Decisional Conflict Scale. Retrieved from: https://decisionaid.ohri.ca/docs/develop/User_Manuals/UM_Decisional_Conflict.pdf
Ploug T, Holm S (2017) 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
R Core Team (2020) R: A language and environment for statistical computing. R Foundation for Statistical Computing, V., Austria. https://www.R-project.org/. In.
Raghuram Pillai P, Prows CA, Martin LJ, Myers MF (2020) Decisional conflict among adolescents and parents making decisions about genomic sequencing results. Clin Genet 97(2):312–320. https://doi.org/10.1111/cge.13658
Regier DA, Peacock SJ, Pataky R, van der Hoek K, Jarvik GP, Hoch J, Veenstra D (2015) Societal preferences for the return of incidental findings from clinical genomic sequencing: a discrete-choice experiment. CMAJ 187(6):E190-197. https://doi.org/10.1503/cmaj.140697
Ronald E, Richard S (2007) Patient-centered communication in cancer care: promoting healing and reducing suffering. Communication, 222.
Shahmirzadi L, Chao EC, Palmaer E, Parra MC, Tang S, Gonzalez KD (2014) Patient decisions for disclosure of secondary findings among the first 200 individuals undergoing clinical diagnostic exome sequencing. Genet Med 16(5):395–399. https://doi.org/10.1038/gim.2013.153
Shickh S, Clausen M, Mighton C, Casalino S, Joshi E, Glogowski E, Bombard Y (2018) Evaluation of a decision aid for incidental genomic results, the Genomics ADvISER: protocol for a mixed methods randomised controlled trial. BMJ Open 8(4): e021876. https://doi.org/10.1136/bmjopen-2018-021876
Shickh S, Clausen M, Mighton C, Gutierrez Salazar M, Zakoor KR, Kodida R, IGS Team (2019) Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial. BMJ Open 9(10):e031092. https://doi.org/10.1136/bmjopen-2019-031092
Shickh S, Rafferty SA, Clausen M, Kodida R, Mighton C, Panchal S, IGS Team (2021) The role of digital tools in the delivery of genomic medicine: enhancing patient-centered care. Genet Med. https://doi.org/10.1038/s41436-021-01112-1
Shickh S, Hirjikaka D, Clausen M, Kodida R, Mighton C, Reble E, Bombard Y (2022) Genetics adviser: a protocol for a mixed-methods randomised controlled trial evaluating a digital platform for genetics service delivery. BMJ Open, 12(4): e060899. https://doi.org/10.1136/bmjopen-2022-060899
Smith LA, Douglas J, Braxton AA, Kramer K (2015) Reporting incidental findings in clinical whole exome sequencing: incorporation of the 2013 ACMG recommendations into current practices of genetic counseling. J Genet Couns 24(4):654–662. https://doi.org/10.1007/s10897-014-9794-4
van El CG, Cornel MC, Borry P, Hastings RJ, Fellmann F, Hodgson SV, ESHG Public and Professional Policy Committee (2013) Whole-genome sequencing in health care: recommendations of the European Society of Human Genetics. Eur J Hum Genet 21(6):580–584. https://doi.org/10.1038/ejhg.2013.46
Wright MF, Lewis KL, Fisher TC, Hooker GW, Emanuel TE, Biesecker LG, Biesecker BB (2014) Preferences for results delivery from exome sequencing/genome sequencing. Genet Med 16(6):442–447. https://doi.org/10.1038/gim.2013.170
Wynn J, Martinez J, Duong J, Chiuzan C, Phelan JC, Fyer A, Chung WK (2017) Research participants' preferences for hypothetical secondary results from genomic research. J Genet Couns, 26(4): 841–851. https://doi.org/10.1007/s10897-016-0059-2
Ziniel SI, Savage SK, Huntington N, Amatruda J, Green RC, Weitzman ER, Holm IA (2014) Parents' preferences for return of results in pediatric genomic research. Public Health Genomics, 17(2): 105–114. https://doi.org/10.1159/000358539
Acknowledgements
The authors are grateful to the patients who participated in this study. This research was funded by the Canadian Institutes of Health Research. Incidental Genomics Team members to be indexed in PubMed: Yvonne Bombard (PI), Susan R. Armel, Melyssa Aronson, Nancy N. Baxter, Kenneth Bond, José-Mario Capo-Chichi, June C. Carroll, Timothy Caulfield, Marc Clausen, Tammy Clifford, Iris Cohn, Irfan Dhalla, Craig C. Earle, Andrea Eisen, Christine Elser, Michael Evans, Emily Glogowski, Tracy Graham, Elena Greenfield, Jada G. Hamilton, Wanrudee Isaranuwatchai, Monica Kastner, Raymond H. Kim, Andreas Laupacis, Jordan Lerner-Ellis, Chantal F. Morel, Michelle Mujoomdar, Abdul Noor, Kenneth Offit, Seema Panchal, Mark E. Robson, Adena Scheer, Stephen Scherer, Kasmintan A. Schrader, Terrence Sullivan, Kevin E. Thorpe. Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada. Department of Surgery, University of Toronto, Toronto, ON, Canada. Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia. Institute of Health Economics, Edmonton, AB, Canada. Laboratory Medicine Program, University Health Network, Toronto, ON, Canada. Faculty of Law, University of Alberta, Edmonton, AB, Canada. School of Public Health, University of Alberta, Edmonton, AB, Canada. Health Law Institute, University of Alberta, Edmonton, AB, Canada. School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada. The Hospital for Sick Children, Toronto, ON, Canada. St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada. Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. Memorial Sloan Kettering Cancer Center, New York, NY, United States. Canadian Agency for Drugs and Technologies in Health, Ottawa, ON, Canada
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YB was supported by a CIHR New Investigator Award during this study (#136664). SS received support from the Canadian Institutes of Health Research (#425969).
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Conception and design: YB, SS. Data collection and analysis: SS, KET, AS, CM, MC, YB, CE, AE, LW, SP, TW, JCC, EG, KAS, JLE, RHK, Incidental Genomics Study Team. Writing-original draft: SS, AS. Writing-critical revisions: SS, AS, MC, CM, CE, AE, LW, SP, TW, JCC, EG, KAS, JLE, RHK, KET,YB, Incidental Genomics Study Team. Final approval: SS, AS, MC, CM, CE, AE, LW, SP, TW, JCC, EG, KAS, JLE, RHK, KET, YB, Incidental Genomics Study Team.
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This study was performed in line with the principles of the Declaration of Helsinki. The Research Ethics Boards of St. Michael’s Hospital (REB #16–052), Mount Sinai Hospital (REB #16–0054-E), and Sunnybrook Health Science Centre (REB #198–2016) Research Ethics Boards approved this study.
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Shickh, S., Sebastian, A., Clausen, M. et al. Great expectations: patients’ preferences for clinically significant results from genomic sequencing. Hum Genet 142, 553–562 (2023). https://doi.org/10.1007/s00439-023-02543-3
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DOI: https://doi.org/10.1007/s00439-023-02543-3