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

Abstract

IntroductionGenomic 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 analysisWe 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 disseminationThis 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 numberNCT03597165.

Genetics Adviser: a protocol for a mixed-methods randomised controlled trial evaluating a digital platform for genetics service delivery

“…We will recruit participants from the control arm of the parent study (group #1) The Health Outcomes, Utility and Costs of Returning Incidental Genomics Findings (NCT#03597165; ‘Incidental Genomics’ trial described elsewhere). 20 Control arm participants from the parent trial included adult patients with cancer who underwent genomic sequencing and only received results for their primary indication (cancer). To supplement this sample, we will also recruit patients from cancer genetics clinics at Mount Sinai Hospital (MSH), Princess Margaret Cancer Centre (PMCC) and Sunnybrook Health Sciences Centre (SHSC) located in Toronto, Ontario, Canada (group #2).…”

“…Previous participants in the control arm of the Incidental Genomics Trial 20 who have given permission to be recontacted for future related research AND patients with:…”

“…We will recruit participants from the control arm of the parent study (group #1) The Health Outcomes, Utility and Costs of Returning Incidental Genomics Findings (NCT#03597165; ‘Incidental Genomics’ trial described elsewhere) 20. Control arm participants from the parent trial included adult patients with cancer who underwent genomic sequencing and only received results for their primary indication (cancer).…”

“…If they or relatives participated in previous studies related to the Genomics Adviser including: the usability of the original Genomics Adviser9; the RCT of the Genomics Adviser13 15; or the intervention arm of the Incidental Genomics Trial, in which they would have used the Genomics Adviser to select their preferred clinically significant findings 20…”

“…Group #2: we will recruit additional patients from genetics clinics at MSH, PMCC and SHSC who have already had panel testing for a cancer diagnosis and are eligible for genomic sequencing, similar to previous trials 13 20. The procedure for recruitment will be the same at all participating clinics.…”