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A model for the return and referral of all clinically significant secondary findings of genomic sequencing
  1. Rita Kodida1,
  2. Emma Reble1,
  3. Marc Clausen1,
  4. Salma Shickh1,2,
  5. Chloe Mighton1,2,
  6. Jordan Sam1,
  7. Nicole Forster3,
  8. Seema Panchal4,5,
  9. Melyssa Aronson5,6,
  10. Kara Semotiuk5,6,
  11. Tracy Graham5,7,
  12. Yael Silberman7,
  13. Susan Randall Armel5,8,
  14. Jeanna M McCuaig5,8,
  15. Iris Cohn9,
  16. Chantal F Morel3,10,
  17. Christine Elser4,10,
  18. Andrea Eisen7,
  19. June C Carroll11,12,
  20. Emily Glogowski13,
  21. Kasmintan A Schrader14,15,
  22. Vanessa Di Gioacchino4,16,
  23. Jordan Lerner-Ellis16,17,
  24. Raymond H Kim8,10,
  25. Yvonne Bombard1,2
  26. on behalf of the Incidental Genomics Study Team
    1. 1 Genomics Health Services & Policy Research Program, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada
    2. 2 Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, Ontario, Canada
    3. 3 Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Toronto, Ontario, Canada
    4. 4 The Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada
    5. 5 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
    6. 6 Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada
    7. 7 Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
    8. 8 Division of Medical Oncology & Hematology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
    9. 9 Division of Clinical Pharmacology & Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada
    10. 10 Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    11. 11 Department of Family & Community Medicine, University of Toronto, Toronto, Ontario, Canada
    12. 12 Granovsky Gluskin Family Medicine Centre, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada
    13. 13 GeneDx, Gaithersburg, Maryland, USA
    14. 14 British Columbia Cancer Agency, Vancouver, British Columbia, Canada
    15. 15 Department of Medical Genetics, The University of British Columbia, Vancouver, British Columbia, Canada
    16. 16 Pathology & Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada
    17. 17 Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada
    1. Correspondence to Dr Yvonne Bombard, Genomics Health Services & Policy Research Program, Li Ka Shing Knowledge Institute, St Michael's Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada; yvonne.bombard{at}utoronto.ca

    Abstract

    Secondary findings (SFs) identified through genomic sequencing (GS) can offer a wide range of health benefits to patients. Resource and capacity constraints pose a challenge to their clinical management; therefore, clinical workflows are needed to optimise the health benefits of SFs. In this paper, we describe a model we created for the return and referral of all clinically significant SFs, beyond medically actionable results, from GS. As part of a randomised controlled trial evaluating the outcomes and costs of disclosing all clinically significant SFs from GS, we consulted genetics and primary care experts to determine a feasible workflow to manage SFs. Consensus was sought to determine appropriate clinical recommendations for each category of SF and which clinician specialist would provide follow-up care. We developed a communication and referral plan for each category of SFs. This involved referrals to specialised clinics, such as an Adult Genetics clinic, for highly penetrant medically actionable findings. Common and non-urgent SFs, such as pharmacogenomics and carrier status results for non-family planning participants, were directed back to the family physician (FP). SF results and recommendations were communicated directly to participants to respect autonomy and to their FPs to support follow-up of SFs. We describe a model for the return and referral of all clinically significant SFs to facilitate the utility of GS and promote the health benefits of SFs. This may serve as a model for others returning GS results transitioning participants from research to clinical settings.

    • genetics
    • genetic testing
    • genetic counseling

    http://dx.doi.org/10.1136/jmg-2022-109091

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      Footnotes

      • Collaborators Incidental Genomics Study Team: Yvonne Bombard (Principal Investigator) (Genomics Health Services & Policy Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada. Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada), Susan Randall Armel (Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada), Melyssa Aronson (Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada), Nancy Baxter (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), Kenneth Bond (Institute of Health Economics, Edmonton, AB, Canada), José-Mario Capo-Chichi (Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada. Laboratory Medicine Program, University Health Network, Toronto, ON, Canada), June C. Carroll (Department of Family & Community Medicine, University of Toronto, Toronto, ON, Canada. Granovsky Gluskin Family Medicine Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada), Timothy Caulfield (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), Marc Clausen (Genomics Health Services & Policy Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada), Tammy J. Clifford (School of Epidemiology & Public Health, University of Ottawa, Ottawa, ON, Canada), Iris Cohn (Division of Clinical Pharmacology & Toxicology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada), Irfan Dhalla (Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada. Department of Medicine, University of Toronto, Toronto, ON, Canada. Li Ka Shing Knowledge Institute, Unity Health Toronto, St. Michael’s Hospital, Toronto, ON, Canada. Institute for Clinical Evaluative Sciences, Toronto, ON, Canada. Health Quality Ontario, Toronto, ON, Canada), Craig C. Earle (Department of Medicine, University of Toronto, Toronto, ON, Canada), Andrea Eisen (Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada), Christine Elser (The Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Department of Medicine, University of Toronto, Toronto, ON, Canada), Michael Evans (Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada), Emily Glogowski (GeneDx, Gaithersburg, MD, USA), Tracy Graham (Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada), Elena Greenfeld (Kolomietz) (Pathology & Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada), Jada G. Hamilton (Memorial Sloan Kettering Cancer Center, New York, NY, USA), Wanrudee Isaranuwatchai (Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada. Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada), Monika Kastner (Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada. Department of Family & Community Medicine, University of Toronto, Toronto, ON, Canada. Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada), Raymond H. Kim (Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Department of Medicine, University of Toronto, Toronto, ON, Canada. Division of Clinical & Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada. Ontario Institute for Cancer Research, Toronto, ON, Canada.), Andreas Laupacis (Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada. Department of Medicine, University of Toronto, Toronto, ON, Canada. Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada), Jordan Lerner-Ellis (Pathology & Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada), Chantal F. Morel (Fred A. Litwin Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Department of Medicine, University of Toronto, Toronto, ON, Canada), Michelle Mujoomdar (Canadian Agency for Drugs & Technologies in Health, Ottawa, ON, Canada), Abdul Noor (Pathology & Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada), Kenneth Offit (Memorial Sloan Kettering Cancer Center, New York, NY, USA), Seema Panchal (The Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada), Mark E. Robson (Memorial Sloan Kettering Cancer Center, New York, NY, USA), Stephen W. Scherer (Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. Department of Medicine, University of Toronto, Toronto, ON, Canada. The Centre for Applied Genomics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada), Adena Scheer (Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada. Department of Surgery, University of Toronto, Toronto, ON, Canada), Kasmintan A. Schrader (BC Cancer Agency, Vancouver, BC, Canada. Department of Medical Genetics, The University of British Columbia, Vancouver, BC, Canada), Terrence Sullivan (Institute of Health Policy, Management & Evaluation, University of Toronto, Toronto, ON, Canada) and Kevin E. Thorpe (Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada).

      • Contributors Conceptualisation: RK, ER, MC, YB, and RHK. Methodology: YB, RHK, MC, RK, ER, SS, NF, SP, MA, TG, SRA, IC, CFM, CE, AE, JCC, EG, KAS and JLE. Project administration: MC. Resources: RK, ER, MC, YB, RHK, SS, SP, MA, TG, SRA, IC, CE, AE, JCC and JLE. Supervision: YB. Visualisation: YB, MC, RK, ER and RHK. Writing—original draft: RK, ER, MC, YB and RHK. Writing—review and editing: RK, ER, MC, YB, RHK, SS, CM, NF, SP, MA, TG, SRA, IC, CFM, CE, AE, JCC, EG, KAS, JLE and Incidental Genomics Study Team.

      • Funding This study was supported by a Foundation Grant from the Canadian Institutes of Health Research and a Quality of Life Grant from the Canadian Cancer Society Research Institute awarded to YB and members of the Incidental Genomics Study Team (grant numbers 143310 and 705665, respectively). YB was supported by a New Investigator Award from the Canadian Institute of Health Research during the conduct of this study. RHK was supported by the Princess Margaret Cancer Foundation and the Bhalwani Family Charitable Foundation.

      • Competing interests None declared.

      • Provenance and peer review Not commissioned; externally peer reviewed.