Effectiveness of the Genomics ADvISER decision aid for the selection of secondary findings from genomic sequencing: a randomized clinical trial.
Yvonne Bombard, Marc Clausen, Salma Shickh, Chloe Mighton, Selina Casalino, Theresa H M Kim, Sarah M Muir, Lindsay Carlsson, Nancy Baxter, Adena Scheer, Christine Elser, Andrea Eisen, Seema Panchal, Tracy Graham, Melyssa Aronson, Carolyn Piccinin, Talia Mancuso, Kara Semotiuk, Michael Evans, June C Carroll, Kenneth Offit, Mark Robson, Jada G Hamilton, Emily Glogowski, Kasmintan Schrader, Raymond H Kim, Jordan Lerner-Ellis, Kevin E Thorpe, Andreas Laupacis, Incidental Genomics Study Team
Author Information
Yvonne Bombard: Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. yvonne.bombard@utoronto.ca. ORCID
Marc Clausen: St. Michael's Hospital, Toronto, ON, Canada.
Salma Shickh: Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
Chloe Mighton: Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
Selina Casalino: St. Michael's Hospital, Toronto, ON, Canada.
Theresa H M Kim: The Hospital for Sick Children, Toronto, ON, Canada.
Sarah M Muir: St. Michael's Hospital, Toronto, ON, Canada.
Lindsay Carlsson: University Health Network, Toronto, ON, Canada.
Nancy Baxter: Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
Adena Scheer: St. Michael's Hospital, Toronto, ON, Canada.
Christine Elser: University Health Network, Toronto, ON, Canada.
Andrea Eisen: Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Seema Panchal: Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada.
Tracy Graham: Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Melyssa Aronson: Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada.
Carolyn Piccinin: Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada.
Talia Mancuso: Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Kara Semotiuk: Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada.
Michael Evans: St. Michael's Hospital, Toronto, ON, Canada.
June C Carroll: Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada.
Kenneth Offit: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Mark Robson: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jada G Hamilton: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Emily Glogowski: GeneDx, Gaithersburg, MD, USA.
Kasmintan Schrader: Department of Molecular Oncology and Hereditary Cancer Program, BC Cancer Agency, Vancouver, BC, Canada.
Raymond H Kim: The Hospital for Sick Children, Toronto, ON, Canada.
Jordan Lerner-Ellis: Mount Sinai Hospital, Sinai Health System, Toronto, ON, Canada.
Kevin E Thorpe: Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Andreas Laupacis: Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
PURPOSE: To evaluate the effectiveness of the Genomics ADvISER (www.genomicsadviser.com) decision aid (DA) for selection of secondary findings (SF), compared with genetic counseling alone. METHODS: A randomized controlled trial (RCT) was conducted to evaluate whether the Genomics ADvISER is superior to genetic counseling when hypothetically selecting SF. Participants were randomized to use the DA followed by discussion with a genetic counselor, or to genetic counseling alone. Surveys were administered at baseline and post-intervention. Primary outcome was decisional conflict. Secondary outcomes were knowledge, preparation for, and satisfaction with decision-making, anxiety, and length of counseling session. RESULTS: Participants (n = 133) were predominantly White/European (74%), female (90%), and ≥50 years old (60%). Decisional conflict (mean difference 0.05; P = 0.60), preparation for decision-making (0.17; P = 0.95), satisfaction with decision (-2.18; P = 0.06), anxiety (0.72; P = 0.56), and knowledge of sequencing limitations (0.14; P = 0.70) did not significantly differ between groups. However, intervention participants had significantly higher knowledge of SF (0.39; P < 0.001) and sequencing benefits (0.97; P = 0.01), and significantly shorter counseling time (24.40 minutes less; P < 0.001) CONCLUSIONS: The Genomics ADvISER did not decrease decisional conflict but reduced counseling time and improved knowledge. This decision aid could serve as an educational tool, reducing in-clinic time and potentially health care costs.
Bombard Y, Robson M, Offit K. Revealing the incidentalome when targeting the tumor genome. JAMA. 2013;310:795–796.
[DOI: 10.1001/jama.2013.276573]
Kalia SS, Adelman K, Bale SJ, et al. 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. Genet Med. 2017;19:249–255.
[DOI: 10.1038/gim.2016.190]
Parsons DW, Roy A, Yang Y, et al. Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors. JAMA Oncol. 2016;2:616–624.
[DOI: 10.1001/jamaoncol.2015.5699]
Green RC, Berg JS, Grody WW, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013;15:565–574.
[DOI: 10.1038/gim.2013.73]
Mackley MP, Fletcher B, Parker M, Watkins H, Ormondroyd E. Stakeholder views on secondary findings in whole-genome and whole-exome sequencing: a systematic review of quantitative and qualitative studies. Genet Med. 2017;19:283–293.
[DOI: 10.1038/gim.2016.109]
Tabor HK, Stock J, Brazg T, et al. Informed consent for whole genome sequencing: a qualitative analysis of participant expectations and perceptions of risks, benefits, and harms. Am J Med Genet A. 2012;158A:1310–1319.
[DOI: 10.1002/ajmg.a.35328]
Birch P, Adam S, Bansback N, et al. DECIDE: a decision support tool to facilitate parents’ choices regarding genome-wide sequencing. J Genet Couns. 2016;25:1298–1308.
[DOI: 10.1007/s10897-016-9971-8]
Birch PH. Interactive e-counselling for genetics pretest decisions: where are we now? Clin Genet. 2015;87:209–217.
[DOI: 10.1111/cge.12430]
Sanderson SC, Suckiel SA, Zweig M, Bottinger EP, Jabs EW, Richardson LD. Development and preliminary evaluation of an online educational video about whole-genome sequencing for research participants, patients, and the general public. Genet Med. 2016;18:501–512.
[DOI: 10.1038/gim.2015.118]
Bombard Y, Clausen M, Mighton C, et al. The Genomics ADvISER: development and usability testing of a decision aid for the selection of incidental sequencing results. Eur J Hum Genet. 2018;26:984–995.
[DOI: 10.1038/s41431-018-0144-0]
Shickh S, Clausen M, Mighton C, et al. Evaluation of a decision aid for incidental genomic results, the Genomics ADvISER: protocol for a mixed methods randomised controlled trial. BMJ Open. 2018;8:e021876.
[DOI: 10.1136/bmjopen-2018-021876]
O’Connor A. Ottawa Decision Support Framework to address decisional conflict: Ottawa Health Research Institute; 2006.
Fiallos K, Applegate C, Mathews DJH, Bollinger J, Bergner AL, James CA. Choices for return of primary and secondary genomic research results of 790 members of families with Mendelian disease. Eur J Hum Genet. 2017;25:530–537.
[DOI: 10.1038/ejhg.2017.21]
Moher D. CONSORT: an evolving tool to help improve the quality of reports of randomized controlled trials. Consolidated Standards of Reporting Trials. JAMA. 1998;279:1489–1491.
[DOI: 10.1001/jama.279.18.1489]
O’Daniel JM, Lee K. Whole-genome and whole-exome sequencing in hereditary cancer: impact on genetic testing and counseling. Cancer J. 2012;18:287–292.
[DOI: 10.1097/PPO.0b013e318262467e]
Miller FA, Hayeems RZ, Bytautas JP, et al. Testing personalized medicine: patient and physician expectations of next-generation genomic sequencing in late-stage cancer care. Eur J Hum Genet. 2014;22:391–395.
[DOI: 10.1038/ejhg.2013.158]
Berg JS, Adams M, Nassar N, et al. An informatics approach to analyzing the incidentalome. Genet Med. 2013;15:36–44.
[DOI: 10.1038/gim.2012.112]
Johnson K, Kieran S, Riordan S, Dunn B, Nixon K. Genomic counseling guide. Chicago, IL: National Society of Genetic Counselors; 2014.
O’Connor AM. Validation of a decisional conflict scale. Med Decis Making. 1995;15:25–30.
[DOI: 10.1177/0272989X9501500105]
Stacey D, Légaré F, Lewis K, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev. 2014;28:CD001431.
Biesecker BB, Lewis KL, Umstead KL, et al. Web platform vs. in-person genetic counselor for return of carrier results from exome sequencing: a randomized clinical trial. JAMA Intern Med. 2018;178:338–346.
[DOI: 10.1001/jamainternmed.2017.8049]
Green MJ, Peterson SK, Baker MW, et al. Effect of a computer-based decision aid on knowledge, perceptions, and intentions about genetic testing for breast cancer susceptibility: a randomized controlled trial. JAMA. 2004;292:442–452.
[DOI: 10.1001/jama.292.4.442]
Kuppermann M, Norton ME, Gates E, et al. Computerized prenatal genetic testing decision-assisting tool: a randomized controlled trial. Obstet Gynecol. 2009;113:53–63.
[DOI: 10.1097/AOG.0b013e31818e7ec4]
Carlson LM, Harris S, Hardisty EE, et al. Use of a novel computerized decision aid for aneuploidy screening: a randomized controlled trial. Genet Med. 2018;21:923–929.
[DOI: 10.1038/s41436-018-0283-2]
O’Connor AM, Tugwell P, Wells GA, et al. A decision aid for women considering hormone therapy after menopause: decision support framework and evaluation. Patient Educ Couns. 1998;33:267–279.
[DOI: 10.1016/S0738-3991(98)00026-3]
Kaphingst KA, Facio FM, Cheng MR, et al. Effects of informed consent for individual genome sequencing on relevant knowledge. Clin Genet. 2012;82:408–415.
[DOI: 10.1111/j.1399-0004.2012.01909.x]
Holmes-Rovner M, Kroll J, Schmitt N, et al. Patient satisfaction with health care decisions. Med Decis Making. 1996;16:58–64.
[DOI: 10.1177/0272989X9601600114]
Bennett C, Graham ID, Kristjansson E, Kearing SA, Clay KF, O’Connor AM. Validation of a preparation for decision making scale. Patient Educ Couns. 2010;78:130–133.
[DOI: 10.1016/j.pec.2009.05.012]
Spielberger C, Gorsuch R, Lushene R, Vagg P, Jacobs G. Manual for the State–Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press; 1983.
Julian LJ. Measures of anxiety: State–Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), and Hospital Anxiety and Depression Scale-Anxiety (HADS-A). Arthritis Care Res (Hoboken). 2011;63(Suppl 11):S467–S472.
[DOI: 10.1002/acr.20561]
Wakefield CE, Meiser B, Homewood J, et al. A randomized controlled trial of a decision aid for women considering genetic testing for breast and ovarian cancer risk. Breast Cancer Res Treat. 2008;107:289–301.
[DOI: 10.1007/s10549-007-9539-2]
O’Connor A. User manual: decisional conflict scale. Ottawa Hospital Research Institute; 1993 https://decisionaid.ohri.ca/docs/develop/User_Manuals/UM_Decisional_Conflict.pdf [Updated 2010].
Pacyna JE, Radecki Breitkopf C, Jenkins SM, et al. Should pretest genetic counselling be required for patients pursuing genomic sequencing? Results from a survey of participants in a large genomic implementation study. J Med Genet. 2018;56:317–324.
[DOI: 10.1136/jmedgenet-2018-105577]
Sanderson SC, Loe BS, Freeman M, et al. Development of the Knowledge of Genome Sequencing (KOGS) questionnaire. Patient Educ Couns. 2018;101:1966–1972.
[DOI: 10.1016/j.pec.2018.07.011]
Wang C, Gonzalez R, Milliron KJ, Strecher VJ, Merajver SD. Genetic counseling for BRCA1/2: a randomized controlled trial of two strategies to facilitate the education and counseling process. Am J Med Genet A. 2005;134a:66–73.
[DOI: 10.1002/ajmg.a.30577]
Sutton EJ, Kullo IJ, Sharp RR. Making pretest genomic counseling optional: lessons from the RAVE study. Genet Med. 2018;20:1157–1158.
[DOI: 10.1038/gim.2017.240]
Vadaparampil ST, Cragun D. Shared decision making: Implications for return of results from whole-exome and whole-genome sequencing. Transl Behav Med. 2018;8:80–84.
[DOI: 10.1093/tbm/ibx048]
Mighton C, Carlsson L, Clausen M, et al. Development of patient “profiles” to tailor counseling for incidental genomic sequencing results. Eur J Hum Genet. 2019;27:1008–1017.
[DOI: 10.1038/s41431-019-0352-2]
Graham ME, Westerberg BD, Lea J, et al. Shared decision making and decisional conflict in the management of vestibular schwannoma: a prospective cohort study. J Otolaryngol Head Neck Surg. 2018;47:52.
[DOI: 10.1186/s40463-018-0297-4]
