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Incidental Genomics

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ClinicalTrials.gov Identifier: NCT03597165
Recruitment Status : Recruiting
First Posted : July 24, 2018
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
St. Michael's Hospital, Toronto

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.

Condition or disease Intervention/treatment Phase
Cancer Other: Incidental Genomic Sequencing Results Other: GS Results for Primary Indications only Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: The Health Outcomes, Utility, and Costs of Returning Incidental Genomic Findings
Actual Study Start Date : July 25, 2018
Estimated Primary Completion Date : August 15, 2020
Estimated Study Completion Date : July 1, 2025

Arm Intervention/treatment
Experimental: 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.
Other: 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.

Active Comparator: Primary Indication only
Patients in the control will receive the intervention GS results for Primary Indications only.
Other: GS Results for Primary Indications only
Patients will receive GS results related to the primary indication (cancer) only.




Primary Outcome Measures :
  1. Hospital Anxiety and Depression Scale (HADS) [ Time Frame: 2 weeks after return of results ]
    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)


Secondary Outcome Measures :
  1. Impact of Event Scale-Revised (IES-R) [ Time Frame: 1 year following return of results. ]
    The Impact of Event Scale-Revised (IES-R) is a standardized, validated scale that measures symptoms of traumatic stress. The IES-R comprises of three subscales: Intrusion (8 items), Avoidance (8 items), and Hyperarousal (6 items). The IES-R yields a total score that ranges from 0-88, with higher scores indicating worse outcomes. Scores on the Intrusion subscale range from 0-32, with higher scores indicating worse outcomes. Score on the Avoidance subscale range from 0-32, with higher scores indicating worse outcomes. Scores on the Hyperarousal subscale range from 0-24, with higher scores indicating worse outcomes. (PMID: 23243796)

  2. Multi-Dimensional Impact of Cancer Risk Assessment (MICRA) [ Time Frame: 1 year following return of results. ]
    The Multi-Dimensional Impact of Cancer Risk Assessment (MICRA) is a 25-item standardized, validated scale that measures the impact of result disclosure from genetic tests. There are three subscales: Distress (6 items), Uncertainty (9 items) and Positive Experiences (4 items). Total scores range from 0-125, with higher scores indicating worse outcome. Scores on the Distress subscale range from 0-30, with higher scores indicating worse outcome. Scores on the Uncertainty subscale range from 0-45, with higher scores indicating worse outcome. Scores on the Positive Experiences Subscale range from 0-20, with higher scores indicating worse outcomes. (PMID: 12433008)

  3. Adapted Behavioral Risk Factor Surveillance System (BRFSS) Questionnaire [ Time Frame: 1 year following return of results. ]
    We will assess the intended use and actual adoption of risk-reducing behaviours and preventative services across all RCT participants using CDC's Behavioural Risk Factor Surveillance System (BRFSS) questionnaire. We have adapted the BFRSS to examine whether the receipt of GS results influences participants' intent to adopt, and actual self-reported adoption of: screening, prophylactic surgery, dietary changes, reduced alcohol intake, increased exercise, adherence/changes to medication, and smoking cessation (beyond those taken due to their cancer diagnosis). Self-reported actual or intended use of these behaviours will be ascertained over the telephone. Higher scores indicate higher uptake of health behaviours.

  4. SF-12 [ Time Frame: 1 year following return of results. ]
    The SF-12 scale measures quality of life. The SF-12 has 12 items that address physical and mental functioning. Physical and mental health composite scores range from 0 to 100, with 0 indicating the lowest possible level of health, and 100 indicating the highest possible level of health.

  5. Genetic Self Efficacy (GSE) [ Time Frame: 1 year following return of results. ]
    Consistent with the Extended Parallel Process Model (EPPM) which suggests that that higher risk results could motivate individuals to adopt risk-reducing behaviors if they perceive an increased risk of disease, as long as self-efficacy is also high, we will assess genetic self-efficacy using a standardized, validated measure (PMID: 20884465).

  6. Risk Perception [ Time Frame: 1 year following return of results ]
    Consistent with the Extended Parallel Process Model (EPPM) which suggests that that higher risk results could motivate individuals to adopt risk-reducing behaviors if they perceive an increased risk of disease, as long as self-efficacy is also high, we will assess risk perception. Participants will be asked to report their perceived likelihood of developing diseases related to their incidental results. For each disease risk, scores range from 1 to 5, and higher scores indicate higher perceived risk. (PMID: 16969872, 24131974)

  7. Qualitative interviews with a subset of patients [ Time Frame: 9-12 months following return of results ]
    We will use in-depth interviews with patients to provide further insights into the ways in which incidental results impact the quality of life and health outcomes of cancer patients receiving incidental results. Patient interviews will explore: reasons for learning incidental GS results, to whom, how and why results have been communicated, perceived utility and impact of incidental results for personal, familial or life planning.

  8. Qualitative interviews with a subset of practitioners [ Time Frame: 9-12 months following return of results ]
    Provider interviews will explore: improvements to patient management and treatment decisions on the basis of their patients' incidental results and their perceptions of the clinical, familial and personal benefits or harms of these results for patients. Interviews will also explore providers' views on any physical or physiological impacts that receipt of incidental results have had on patients.


Other Outcome Measures:
  1. Perceived Utility [ Time Frame: 1 year following return of results. ]
    Perceived utility of genomic sequencing results will be measured using a scale from Lupo et al. Scale values range from 0-24, with higher scores indicating higher perceived utility of genomic sequencing results. (PMID: 27019659).

  2. Clinical actions triggered by genomic sequencing results [ Time Frame: 1 year following return of results. ]
    Patient charts will be reviewed. The number and type of medical recommendations following GS will be quantified.

  3. Impact of genomic sequencing results on reproductive behaviors [ Time Frame: 1 year following return of results. ]
    Participants will be asked about whether their genomic sequencing results have impacted their reproductive decisions or reproductive planning through questions adapted from Bombard et al. (PMID: 27256091).

  4. Decisional Conflict Scale (DCS) [ Time Frame: 1 year following return of results. ]
    This standardized, validated measure will assess decisional conflict. Possible scores range from 0 to 100, with higher scores indicating higher decisional conflict (worse outcome). There are three subscales: Uncertainty, Informed, and Values Clarity. Scores on each subscale range from 0-100, with higher scores indicating worse outcome. (PMID: 7898294)

  5. Diagnostic yield [ Time Frame: Immediately after sequence analysis. ]
    Immediately after sequence analysis is complete, will record the number and frequencies of deleterious germline mutations related to the patients' phenotype over, and by subgroup: phenotype, extent of family history, transmission type, pathogenic/likely pathogenic, deleterious germline mutations known to be recurrently mutated by cancer type.

  6. Health Information National Trends Survey (HINTS) (Adapted) [ Time Frame: 1 year following return of results. ]
    An adapted version of the HINTS questionnaire will assess how participants use and access health information. (https://hints.cancer.gov/)

  7. Economic impact of GS results [ Time Frame: 5 years following return of results. ]
    Billing records held at the Institute for Clinical Evaluative Sciences (ICES) will be accessed to obtain information related to resource use following return of results, including physician visits, hospital visits, additional testing, and diagnostic tests.

  8. Costs incurred by participants - survey questions [ Time Frame: 1 year following return of results. ]
    Participants will be asked to report personal costs associated with GS results, including out-of-pocket medications as well as peripheral costs such as transportation and lost wages.

  9. Communication of genomic sequencing results to relatives [ Time Frame: 1 year following return of results. ]
    Communication of genomic sequencing results to relatives will be assessed through questions adapted from Bombard et al. that indicate which relatives they have communicated their results to (PMID: 27256091).

  10. Cascade genetic testing among relatives [ Time Frame: 1 year following return of results. ]
    Participants will be asked about which relatives, to their knowledge, have received genetic testing as a result of learning the participant's genome sequencing results.

  11. Cascade health behaviors among relatives [ Time Frame: 1 year following return of results. ]
    Participants will be asked about which relatives, to their knowledge, have changed their health behaviors as a result of the participant's genome sequencing results.

  12. Perceptions of uncertainties in genomic sequencing (PUGS) scale [ Time Frame: 1 year following return of results. ]
    This standardized, validated measure assesses perceptions of uncertainty. Scores range from 1 to 5, with higher scores indicating higher perceptions of uncertainty. (PMID: 27925165)

  13. Tolerance of ambiguity scale [ Time Frame: 1 year following return of results. ]
    This scale measures participants' tolerance of ambiguity. Scores range from 7 to 49, with higher scores indicating higher tolerance for ambiguity. (PMID: 8231339)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 18 years old or older
  • Speak and read English

Exclusion Criteria:

  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03597165


Contacts
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Contact: Marc Clausen, MA 416-864-6060 ext 77397 Marc.Clausen@unityhealth.to

Locations
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Canada, Ontario
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada
Contact: Marc Clausen, MA    416-864-6060 ext 77397    Marc.Clausen@unityhealth.to   
Principal Investigator: Jordan Lerner-Ellis, PhD         
Sub-Investigator: Christine Elser, MD         
Sub-Investigator: Melyssa Aronson, MS         
Princess Margret Cancer Centre Recruiting
Toronto, Ontario, Canada
Contact: Marc Clausen, MA    416-864-6060 ext 77397    Marc.Clausen@unityhealth.to   
Principal Investigator: Raymond Kim, MD/PhD         
Sunnybrook Hospital Recruiting
Toronto, Ontario, Canada
Contact: Marc Clausen, MA    416-864-6060 ext 77397    Marc.Clausen@unityhealth.to   
Principal Investigator: Andrea Eisen, MD         
Sponsors and Collaborators
St. Michael's Hospital, Toronto
Investigators
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Principal Investigator: Yvonne Bombard, PhD St. Michael's Hospital and University of Toronto

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: St. Michael's Hospital, Toronto
ClinicalTrials.gov Identifier: NCT03597165    
Other Study ID Numbers: 0819
First Posted: July 24, 2018    Key Record Dates
Last Update Posted: September 18, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by St. Michael's Hospital, Toronto:
Incidental Findings
Genomic Sequencing
Randomized Controlled Trial
Clinical Utility
Personal Utility