Incidental Genomics

NCT03597165 | Active Not Recruiting

• 1 other identifier: 0819
• Study Type: interventional
• Target: 289
• Locations: 1 country
• Sites: 3

Brief Summary

Health care providers (HCP) are increasingly using genomic sequencing (GS) to diagnose diseases and target treatment for patients. However, GS may incidentally reveal inherited risks for thousands of current and future diseases. Guidelines recommend HCP inform patients of incidental GS results. GS is a relatively new technology, raising many questions about its adoption in clinical care, including: What are the psychological harms, health outcomes, clinical utility and economic costs of receiving primary and incidental GS results? We will use a randomized controlled trial (RCT) to evaluate whether patients receiving incidental GS results will report higher levels of distress and more risk reducing behaviors compared to patients receiving GS for their primary indication alone. We will explore the personal utility of GS via in-depth interviews with a subset of patients. Clinical utility for cancer and incidental results will be evaluated through diagnostic yield, clinical actions triggered by GS results and in-depth interviews with a subset of patients and providers. The economic impact will be evaluated in two ways: (a) health service use will be assessed retrospectively using billing records from the Institute of Clinical Evaluative Sciences (ICES); and, (b) participants' personal costs incurred as a result of GS will be assessed via surveys. Participants will be adult cancer patients who have received negative single gene or panel test results and who have been determined by their health care provider to be a candidate for GS.

Conditions

Cancer

Keywords

Incidental Findings; Genomic Sequencing; Randomized Controlled Trial; Clinical Utility; Personal Utility

Outcome Measures

Primary Outcomes (1)

• Hospital Anxiety and Depression Scale (HADS)

  Our primary outcome is distress, measured by the Hospital Anxiety \& Depression Scale (HADS) using a validated cut-off of \>11 on either the anxiety or depression subscale. The Hospital Anxiety and Depression Scale measures clinically significant anxiety and depression. There are two subscales, anxiety (7 items) and depression (7 items). Scores on each subscale range from 0-21, with higher scores indicating worse outcome (higher anxiety or depression). Subscale scores are not combined for a total score. (PMID: 6880820, 25005549)

  2 weeks after return of results

Secondary Outcomes (8)

• Impact of Event Scale-Revised (IES-R)

  1 year following return of results.

• Multi-Dimensional Impact of Cancer Risk Assessment (MICRA)

  1 year following return of results.

• Adapted Behavioral Risk Factor Surveillance System (BRFSS) Questionnaire

  1 year following return of results.

• SF-12

  1 year following return of results.

• Genetic Self Efficacy (GSE)

  1 year following return of results.

Other Outcomes (13)

• Perceived Utility

  1 year following return of results.

• Clinical actions triggered by genomic sequencing results

  1 year following return of results.

• Impact of genomic sequencing results on reproductive behaviors

  1 year following return of results.

Study Arms (2)

Incidental Genomic Sequencing Results

EXPERIMENTAL

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.

Other: Incidental Genomic Sequencing Results

Primary Indication only

ACTIVE COMPARATOR

Patients in the control will receive the intervention GS results for Primary Indications only.

Other: GS Results for Primary Indications only

Interventions

Incidental Genomic Sequencing Results OTHER

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.

Incidental Genomic Sequencing Results

GS Results for Primary Indications only OTHER

Patients will receive GS results related to the primary indication (cancer) only.

Primary Indication only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Affected with Cancer
• 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
• years old or older
• Speak and read English

You may not qualify if:

• Are in advanced stage cancer (stage 4 /metastatic cancer)
• 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).

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (3)

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

Princess Margret Cancer Centre

Toronto, Ontario, Canada

Location

Sunnybrook Hospital

Toronto, Ontario, Canada

Location

Related Publications (3)

• 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.

  PMID: 41104539 DERIVED

• 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.

  PMID: 39666930 DERIVED

• 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.

  PMID: 31594892 DERIVED

MeSH Terms

Conditions

Neoplasms

Study Officials

• Yvonne Bombard, PhD

  St. Michael's Hospital and University of Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2018
• First Posted: July 24, 2018
• Study Start: July 25, 2018
• Primary Completion: January 15, 2021
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 6, 2023

Record last verified: 2023-12

Locations

CA (3)