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

Introduction Genomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to the return of incidental results, w...

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Main Authors: Mark Robson, Christine Elser, Wanrudee Isaranuwatchai, Melyssa Aronson, Salma Shickh, Marc Clausen, Chloe Mighton, Mariana Gutierrez Salazar, Kathleen-Rose Zakoor, Rita Kodida, Emma Reble, Andrea Eisen, Seema Panchal, Tracy Graham, Susan Randall Armel, Chantal F Morel, Ramzi Fattouh, Emily Glogowski, Kasmintan A Schrader, Jada G Hamilton, Kenneth Offit, June C Carroll, Raymond H Kim, Jordan Lerner-Ellis, Kevin E Thorpe, Andreas Laupacis, Yvonne Bombard
Format: Article
Language:English
Published: BMJ Publishing Group 2019-10-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/10/e031092.full
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author Mark Robson
Christine Elser
Wanrudee Isaranuwatchai
Melyssa Aronson
Salma Shickh
Marc Clausen
Chloe Mighton
Mariana Gutierrez Salazar
Kathleen-Rose Zakoor
Rita Kodida
Emma Reble
Andrea Eisen
Seema Panchal
Tracy Graham
Susan Randall Armel
Chantal F Morel
Ramzi Fattouh
Emily Glogowski
Kasmintan A Schrader
Jada G Hamilton
Kenneth Offit
June C Carroll
Raymond H Kim
Jordan Lerner-Ellis
Kevin E Thorpe
Andreas Laupacis
Yvonne Bombard
author_facet Mark Robson
Christine Elser
Wanrudee Isaranuwatchai
Melyssa Aronson
Salma Shickh
Marc Clausen
Chloe Mighton
Mariana Gutierrez Salazar
Kathleen-Rose Zakoor
Rita Kodida
Emma Reble
Andrea Eisen
Seema Panchal
Tracy Graham
Susan Randall Armel
Chantal F Morel
Ramzi Fattouh
Emily Glogowski
Kasmintan A Schrader
Jada G Hamilton
Kenneth Offit
June C Carroll
Raymond H Kim
Jordan Lerner-Ellis
Kevin E Thorpe
Andreas Laupacis
Yvonne Bombard
author_sort Mark Robson
collection DOAJ
description Introduction Genomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to the return of incidental results, which refer to genetic variants uncovered during testing that are unrelated to the primary disease under investigation, but of potential clinical significance. High-quality evidence evaluating health outcomes and costs of receiving incidental results is critical for the adoption of genomic sequencing into clinical care and to understand the unintended consequences of adoption of genomic sequencing. We aim to evaluate the health outcomes and costs of receiving incidental results for patients undergoing genomic sequencing.Methods and analysis We will compare health outcomes and costs of receiving, versus not receiving, incidental results for adult patients with cancer undergoing genomic sequencing in a mixed-methods randomised controlled trial. Two hundred and sixty patients who have previously undergone first or second-tier genetic testing for cancer and received uninformative results will be recruited from familial cancer clinics in Toronto, Ontario. Participants in both arms will receive cancer-related results. Participants in the intervention arm have the option to receive incidental results. Our primary outcome is psychological distress at 2 weeks following return of results. Secondary outcomes include behavioural consequences, clinical and personal utility assessed over the 12 months after results are returned and health service use and costs at 12 months and 5 years. A subset of participants and providers will complete qualitative interviews about utility of incidental results.Ethics and dissemination This study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System that provides ethical review and oversight for multiple sites participating in the same clinical trial in Ontario.Results from the trial will be shared through stakeholder workshops, national and international conferences, and peer-reviewed journals.Trial registration number NCT03597165.
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spelling doaj-art-e7accc7008cb4557aedde14946a0023c2025-08-20T02:37:58ZengBMJ Publishing GroupBMJ Open2044-60552019-10-0191010.1136/bmjopen-2019-031092Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trialMark Robson0Christine Elser1Wanrudee Isaranuwatchai2Melyssa Aronson3Salma Shickh4Marc Clausen5Chloe Mighton6Mariana Gutierrez Salazar7Kathleen-Rose Zakoor8Rita Kodida9Emma Reble10Andrea Eisen11Seema Panchal12Tracy Graham13Susan Randall Armel14Chantal F Morel15Ramzi Fattouh16Emily Glogowski17Kasmintan A Schrader18Jada G Hamilton19Kenneth Offit20June C Carroll21Raymond H Kim22Jordan Lerner-Ellis23Kevin E Thorpe24Andreas Laupacis25Yvonne Bombard2615 Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA3 Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, CanadaHealth Intervention and Technology Assessment Program, Mueang Nonthaburi, Nonthaburi, Thailand7 Zane Cohen Centre, Sinai Health System, Toronto, Ontario, Canada2 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, CanadaGenomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, CanadaGenomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael`s Hospital, Unity Health Toronto, Toronto, Ontario, Canada2 Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael`s Hospital, Toronto, Ontario, Canada3 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, CanadaGenomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, CanadaGenomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada6 Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada3 Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada4 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada4 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada4 Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada10 Department of Laboratory Medicine, St. Michael`s Hospital, Toronto, Ontario, Canada9 GeneDx Inc, Gaithersburg, Maryland, USA5 Department of Medical Genetics, The University of British Columbia, Vancouver, British Columbia, Canada15 Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA116 Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York City, New York, USADepartment of Family Medicine, Sinai Health, Toronto, Ontario, Canada2 Ontario Institute for Cancer Research, Toronto, Ontario, Canada11 Division of Diagnostic Medical Genetics, Mount Sinai Hospital Pathology and Laboratory Medicine, Toronto, Ontario, Canadaassistant professor; head of biostatisticsprofessorGenomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael`s Hospital, Unity Health Toronto, Toronto, Ontario, CanadaIntroduction Genomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to the return of incidental results, which refer to genetic variants uncovered during testing that are unrelated to the primary disease under investigation, but of potential clinical significance. High-quality evidence evaluating health outcomes and costs of receiving incidental results is critical for the adoption of genomic sequencing into clinical care and to understand the unintended consequences of adoption of genomic sequencing. We aim to evaluate the health outcomes and costs of receiving incidental results for patients undergoing genomic sequencing.Methods and analysis We will compare health outcomes and costs of receiving, versus not receiving, incidental results for adult patients with cancer undergoing genomic sequencing in a mixed-methods randomised controlled trial. Two hundred and sixty patients who have previously undergone first or second-tier genetic testing for cancer and received uninformative results will be recruited from familial cancer clinics in Toronto, Ontario. Participants in both arms will receive cancer-related results. Participants in the intervention arm have the option to receive incidental results. Our primary outcome is psychological distress at 2 weeks following return of results. Secondary outcomes include behavioural consequences, clinical and personal utility assessed over the 12 months after results are returned and health service use and costs at 12 months and 5 years. A subset of participants and providers will complete qualitative interviews about utility of incidental results.Ethics and dissemination This study has been approved by Clinical Trials Ontario Streamlined Research Ethics Review System that provides ethical review and oversight for multiple sites participating in the same clinical trial in Ontario.Results from the trial will be shared through stakeholder workshops, national and international conferences, and peer-reviewed journals.Trial registration number NCT03597165.https://bmjopen.bmj.com/content/9/10/e031092.full
spellingShingle Mark Robson
Christine Elser
Wanrudee Isaranuwatchai
Melyssa Aronson
Salma Shickh
Marc Clausen
Chloe Mighton
Mariana Gutierrez Salazar
Kathleen-Rose Zakoor
Rita Kodida
Emma Reble
Andrea Eisen
Seema Panchal
Tracy Graham
Susan Randall Armel
Chantal F Morel
Ramzi Fattouh
Emily Glogowski
Kasmintan A Schrader
Jada G Hamilton
Kenneth Offit
June C Carroll
Raymond H Kim
Jordan Lerner-Ellis
Kevin E Thorpe
Andreas Laupacis
Yvonne Bombard
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://bmjopen.bmj.com/content/9/10/e031092.full
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