Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
ACTIVE_NOT_RECRUITING
NA
289 participants
INTERVENTIONAL
2018-07-25
2027-10-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Genomic sequencing (GS) is considered the 'next step' towards personalized medicine, providing an opportunity to improve the prevention, diagnosis and treatment of disease. Across Canada, clinicians are increasingly using GS to identify treatments and management approaches likely to benefit patients based on molecular makeup, especially in oncology. GS offers increased sensitivity over classic genetic tests. For example, multi-gene sequencing has been shown to increase the sensitivity of identifying clinically actionable mutations in breast cancer patients by 50% to 60% when compared to testing for BRCA1/2 alone. Often breast cancer patients who test negative for BRCA1/2 will be offered GS to identify causative mutations. In addition, GS can also be used to analyze the molecular profile of a patient's tumour (somatic GS) to identify therapeutic targets.
However, the process of decoding the genome an individual or their tumour may incidentally reveal information about inherited predispositions to other cancers and diseases, including genetic variants/changes associated with current (undiagnosed) disease, drug response, risk for future diseases and variants of unknown clinical significance. Increasing policy guidance suggests that 'medically actionable' results should be offered to patients undergoing clinical sequencing, with calls to offer additional incidental results based on patient preferences. There is limited evidence on the psychological harms and clinical benefits of returning incidental GS results to patients.
Psychological distress: Single-gene and multiplex testing for hereditary cancers, neurological and cardiac disease appears to have minimal psychological impacts. A recent study found that few participants report distress from GS results. However, these findings are based on individuals who agreed to be tested for particular genes, and were prepared through counseling or otherwise to receive these results. This may not translate to incidentally-discovered genetic risk, which individuals did not anticipate or choose to learn a priori. Distress related to receiving incidental GS results remains unknown.
Personal utility: Studies suggest that individuals want to learn their GS results because they expect them to offer 'personal utility'. Personal utility is considered an increasingly important precursor of clinical utility, which is believed to offer richer self-knowledge and motivate risk reducing behaviors. Most studies focus on the hypothetical return of incidental GS results, little is known about individuals' actual perceived value of receiving GS results.
Health benefits: Single-gene and multiplex testing for low risk single nucleotide polymorphisms (SNPs) and high penetrance susceptibility alleles appears to influence the uptake of diet and medication changes, risk-reducing surgeries and surveillance. However, these findings are based on individuals who requested testing for selected genes, and may not represent individuals who learn incidental results.
Clinical Utility: Due to the challenges of applying traditional measures of clinical utility (quality adjusted life years, life years gained) in the context of genomic medicine, an 'intermediate outcome' of utility has emerged based on the 'usefulness and added value to patient management decision making,' of results captured by clinical actions or altered medical recommendations. Preliminary evidence shows GS holds great promise to enable personalized treatments and efficient diagnoses, has demonstrated to facilitate diagnosis in cases of rare diseases with unclear etiology, and strong potential to inform personalized drug therapies compatible with patients' genotypes. The utility of germline GS has largely been examined in limited clinical contexts, such as paediatrics and rare diseases. GS results have been shown to alter clinical management, such as by informing specialist referrals. In a study among a small sample of physicians, providers expressed that while they viewed the current utility of GS as low, they expect it to become more commonplace and more useful in the future. The actual and perceived utility of GS will ultimately determine its clinical implementation, and more evidence in broader clinical settings is needed to inform GS' optimal translation into clinical practice.
Economic Analysis: A lack of evidence remains around the costs and cost-effectiveness of GS. Some believe GS has potential to reduce overall healthcare spending by streamlining the diagnostic process enabling tailored treatments, and informing specific prevention efforts. Others, however, believe that GS will increase healthcare expenditures with limited clinical benefits, as sequencing and variant interpretation costs remain high and results may trigger cascades of additional testing and screening procedures. Out-of-pocket costs may be incurred by patients including medications, counseling, and peripheral costs such as lost wages and transportation. Cost-effectiveness studies have predominately been conducted in the context of tumour sequencing for pharmacological applications; the cost-effectiveness of germ-line GS for primary indication has been examined in few clinical contexts. Regarding incidental findings, cost-effectiveness studies have been conducted for fewer than one third of conditions whose disclosure is recommended by the American College of Medical Genetics and Genomics (ACMG). Modelling predicts incidental finding disclosure may be cost-effective for diagnostics but not currently for general population screening. Further investigation into the utility, costs, and cost-effectiveness of GS is necessary to inform health service delivery and funding decisions.
Rationale
It is unknown whether incidental GS results will be perceived as useful, and whether they motivate the intent or uptake of risk-reducing behaviours. The clinical utility of GS results has not been fully explored, and there is a lack of evidence around cost-effectiveness and costs associated with GS to patients and the healthcare system, which poses a barrier to its clinical implementation.
Research Question
Do patients receiving incidental GS results experience higher levels of distress and engage in more risk reducing behaviours? What is the diagnostic yield of GS, and how do GS results influence clinical decision making? What are the short-term and long-term costs associated with receiving GS results to patients and the healthcare system?
Objectives
1. Evaluate the psychological distress of receiving incidental GS results
2. Evaluate the personal utility and impact of receiving incidental GS results on subsequent risk reduction behaviours.
3. Evaluate the clinical utility of GS:
a. Assess the diagnostic yield of GS results: i. Related to primary cancer indication. ii. Medically actionable incidental findings. iii. Incidental findings with implications for reproductive decisions, lifestyle and relatives.
b. Explore the nature and extent of clinical activity triggered by primary and incidental GS results (referrals to specialists, laboratory testing, scans and screens, etc.).
c. Explore patient and provider perspectives of the perceived and actual clinical utility of primary and incidental GS results.
4. Examine the short-term (1 year) and long-term (5 year) costs associated with genomic sequencing:
1. Costs to the healthcare system.
2. Personal costs.
Study procedures
Patients will be recruited from familial cancer clinics in the Greater Toronto Area (GTA), consented by a genetic counselor, and randomized. Following randomization, participants in the intervention arm will have the option to select which categories of incidental results they would be willing to receive, with a genetic counselor. Participants' genomes will be sequenced and interpreted. Results will be returned by a genetic counselor. Referrals will be made based on sequencing results. Outcomes will be measured at multiple time points before and after the return of results.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
HEALTH_SERVICES_RESEARCH
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Incidental Genomic Sequencing Results
Patients in Intervention will receive GS results related to primary indication (cancer) and will be offered the option learning their incidental results, categorized into five "bins" based on a framework by Berg et al.
Incidental Genomic Sequencing Results
Patient will receive GS results related to their primary indication (cancer), as well as the option to learn incidental GS results. Incidental results will be categorized into five "bins" based on Berg et al.'s framework (medically actionable and pharmacogenetic, common disease SNPs, Mendelian conditions, early-onset brain diseases, and carrier status). In pre-test counseling, patients will have the option to select which bins of incidental results they would like to learn, if any.
Primary Indication only
Patients in the control will receive the intervention GS results for Primary Indications only.
GS Results for Primary Indications only
Patients will receive GS results related to the primary indication (cancer) only.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Incidental Genomic Sequencing Results
Patient will receive GS results related to their primary indication (cancer), as well as the option to learn incidental GS results. Incidental results will be categorized into five "bins" based on Berg et al.'s framework (medically actionable and pharmacogenetic, common disease SNPs, Mendelian conditions, early-onset brain diseases, and carrier status). In pre-test counseling, patients will have the option to select which bins of incidental results they would like to learn, if any.
GS Results for Primary Indications only
Patients will receive GS results related to the primary indication (cancer) only.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Received a negative/inconclusive germline single gene test result for a cancer gene mutation (e.g., BRCA1/2, MLH, MSH, PMS, etc.) in the past two years
* Or received a negative/inconclusive germline panel test result
* 18 years old or older
* Speak and read English
Exclusion Criteria
* Currently in active treatment (chemotherapy, radiation, scheduled surgery) - patients who are on Prophylactic Hormonal Therapy (eg tamoxifen) will be included
* Received a positive genetic test for a cancer gene mutation (e.g., BRCA1/2, MLH, MSH, PMS, APC, MUTYH, etc.)
* Have not had single gene germline testing related to their primary cancer condition (e.g., BRCA1/2 for breast/ovarian cancer, MLH, MSH, PMS colorectal cancer, etc.)
* Previously received genomic sequencing for any reason
* Currently pregnant or planning on getting pregnant (Including men whose partner is pregnant or planning). Participants who become pregnant over the course of the study will not be excluded.
* Do not speak or read English
* Under 18 years of age
* Have a family member participating in the study
* Participant in previous study of decision aid (Decision Aid RCT Study or Usability Study).
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Unity Health Toronto
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Yvonne Bombard, PhD
Role: PRINCIPAL_INVESTIGATOR
St. Michael's Hospital and University of Toronto
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Mount Sinai Hospital
Toronto, Ontario, Canada
Princess Margret Cancer Centre
Toronto, Ontario, Canada
Sunnybrook Hospital
Toronto, Ontario, Canada
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Mighton C, Reble E, Sam J, Kodida R, Shickh S, Clausen M, Hirjikaka D, Grewal S, Panchal S, Piccinin C, Aronson M, Ward T, Armel SR, Peck L, Graham T, Silberman Y, Forster N, Capo-Chichi JM, Greenfeld E, Noor A, Cohn I, Morel CF, Elser C, Eisen A, Glogowksi E, Schrader KA, Kim RH, Chan KKW, Thorpe KE, Lerner-Ellis J, Bombard Y; Incidental Genomics Study Team. Opportunistic screening for broad range of medically relevant secondary findings: Laboratory benefits and burdens. Genet Med. 2025 Oct 14:101599. doi: 10.1016/j.gim.2025.101599. Online ahead of print.
Shickh S, Mighton C, Clausen M, Sam J, Hirjikaka D, Reble E, Graham T, Panchal S, Eisen A, Elser C, Schrader KA, Baxter NN, Laupacis A, Lerner-Ellis J, Kim RH, Bombard Y; Incidental Genomics Study Team. Clinical Utility of Genomic Sequencing for Hereditary Cancer Syndromes: An Observational Cohort Study. JCO Precis Oncol. 2024 Dec;8:e2400407. doi: 10.1200/PO-24-00407. Epub 2024 Dec 12.
Shickh S, Clausen M, Mighton C, Gutierrez Salazar M, Zakoor KR, Kodida R, Reble E, Elser C, Eisen A, Panchal S, Aronson M, Graham T, Armel SR, Morel CF, Fattouh R, Glogowski E, Schrader KA, Hamilton JG, Offit K, Robson M, Carroll JC, Isaranuwatchai W, Kim RH, Lerner-Ellis J, Thorpe KE, Laupacis A, Bombard Y; Incidental Genomics Study Team. 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. 2019 Oct 7;9(10):e031092. doi: 10.1136/bmjopen-2019-031092.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
0819
Identifier Type: -
Identifier Source: org_study_id