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.

Shickh S1,2, Clausen M2, Mighton C1,2, Gutierrez Salazar M2,3, Zakoor KR3, Kodida R2, Reble E2, Elser C4,5, Eisen A6, Panchal S5, Aronson M7, Graham T6, Armel SR8, Morel CF4,9, Fattouh R10,11, Glogowski E12, Schrader KA13,14, Hamilton JG15, Offit K15, Robson M15,16, Carroll JC17,18, Isaranuwatchai W1,19, Kim RH4,20, Lerner-Ellis J3,11, Thorpe KE21,22, Laupacis A4,23, Bombard Y24,2; Incidental Genomics Study Team.

Author information

1: Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.
2: Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
3: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
4: Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
5: Marvelle Koffler Breast Centre, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
6: Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
7: Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
8: Familial Breast Ovarian Cancer Clinic, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
9: Fred A. Litwin Centre in Genetic Medicine, University Health Network, Toronto, Ontario, Canada.
10: Department of Laboratory Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.
11: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
12: GeneDx, Elmwood Park, New Jersey, USA.
13: Department of Molecular Oncology and Hereditary Cancer Program, BC Cancer Agency, Vancouver, British Columbia, Canada.
14: Department of Medical Genetics, The University of British Columbia, Vancouver, British Columbia, Canada.
15: Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA.
16: Breast Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA.
17: Ray D Wolfe Department of Family Medicine, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario, Canada.
18: Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada.
19: Centre for exceLlence in Economic Analysis Research (CLEAR), Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
20: Division of Medical Oncology and Hematology, University Health Network, Toronto, Ontario, Canada.
21: Applied Health Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.
22: Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
23: Department of Palliative Care, St. Michael's Hospital, Toronto, Ontario, Canada.
24: Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada yvonne.bombard@utoronto.ca.

Abstract

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.