Cancer Health Assessments Reaching Many

Study Overview
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Brief Summary
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The CHARM (Cancer Health Assessment Reaching Many) study will assess the utility of clinical exome sequencing and how it affects care in diverse populations. The study population includes adults at risk for hereditary cancer syndromes. The primary objective is to implement a hereditary cancer risk assessment program in healthy 18-49 year-olds in primary care settings within a vertically integrated health delivery system (Kaiser Permanente) and a federal qualified health center (Denver Health). The investigators will assess clinical exome sequencing implementation and interpretation, as well as tailored interactions for low health literacy including a contextualized consent process, and a modified approach to results disclosure and genetic counseling. The investigators will also assess the clinical utility (healthcare utilization and adherence to recommended care) and personal utility of primary and additional results from clinical exome sequencing, and evaluate the ethical and policy implications of considering personal utility of genomic information decisions for health care coverage.

Detailed Description
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Aim 1. Implement a hereditary cancer risk-assessment program in healthy 18-49-year-old adults in primary care settings, with stakeholder input, and offer exome sequencing to clarify risk. Aim 1A. Identify and recruit 880 adult participants at-risk of a hereditary cancer syndrome. Aim 1B: Generate medical exome sequence data and interpret variants. Aim 1C: Disclose findings from medical exome sequencing, incorporate results into the electronic medical record (EMR), and facilitate downstream patient management and coordination of care with the provider. Aim 1D. Engage stakeholders to tailor and optimize the program in diverse populations. Aim 2. Evaluate and tailor for diverse populations the critical interactions in the program, including the consent process, choices for reporting additional findings, and the response to results disclosure. Aim 2A. Design, implement, and assess a contextualized consent process to support informed decision-making about participation in research about medical exome sequencing. Aim 2B. Design, implement, and compare a novel decision aid in the second half of the study for selecting the optional categories of additional findings with the approach we developed in CSER1 that offered a category checklist. Aim 2C. Design, implement, and compare a modified (communication-focused) approach to results disclosure, genetic counseling, and decision making with a standard (information-focused) approach. Aim 3. Evaluate the clinical utility (including personal utility) of using exome sequencing to diagnose individuals with hereditary cancer syndromes and provide additional findings. Aim 3A: Measure the yield of reportable findings for hereditary cancer syndromes and additional findings. Aim 3B: Evaluate subsequent healthcare utilization for all study participants and adherence to recommended care among individuals who are identified with a hereditary cancer syndrome in diverse settings. Aim 3C. Assess the personal utility of exome sequencing, including primary and additional findings. Aim 4. Address pragmatic and ethical challenges to the integration of genomic medicine into clinical and health systems decision-making. Aim 4A: Develop and pilot a system that integrates genomic, clinical, and healthcare utilization data to inform clinicians and patients acting on genomic information and to reduce care gaps in patient management. Aim 4B: Advance the analysis of the ethical and policy implications of incorporating personal utility of genomic information into the decision framework for healthcare coverage.

Official Title
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Exome Sequencing in Diverse Populations in Colorado & Oregon

Conditions
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Hereditary Cancer Syndrome

Intervention / Treatment
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* Other: Modified genetic counseling
* Other: Traditional genetic counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kaiser Permanente Northwest or Denver Health patient Screens as high risk for a hereditary cancer syndrome via the risk assessment tool algorithms OR have unknown family history on either their mother or father's side of the family (or both) No known prior testing for familial mutations predisposing them to Lynch syndrome or hereditary breast and ovarian cancer English or Spanish speaker Exclusion Criteria: Participant self-reported prior testing for Lynch syndrome (LS) or Hereditary Breast and Ovarian Cancer (HBOC) syndrome or identified as having previous comprehensive testing via Kaiser Permanente data files Not an English or Spanish speaker Unable to provide informed consent Don't want results placed in their medical record

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All participants will receive exome sequencing. The randomization will be into one of two types of genetic counseling - traditional and modified.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Traditional genetic counseling<br>This will be typical genetic counseling that a patient would receive in a traditional genetic counseling setting. | Other: Traditional genetic counseling<br>* After participants at high risk for a hereditary cancer syndrome receive exome sequencing, they will receive traditional genetic counseling to help them understand the results.<br>|
| Experimental: Modified genetic counseling<br>This will be genetic counseling that is modified for a lower literacy patient and will include fewer technical terms and less complicated genetic information. | Other: Modified genetic counseling<br>* After participants at high risk for a hereditary cancer syndrome receive exome sequencing, they will receive modified genetic counseling to help them understand the results.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive findings for hereditary cancer syndromes | Number of people found to have a pathogenic variant in one of the cancer genes associated with Lynch syndrome or hereditary breast and ovarian cancer | Within one month of specimen receipt at the laboratory | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive findings for other medically actionable genetic conditions | Number of people with pathogenic variants found in genes related to medically actionable hereditary conditions | Within one month of specimen receipt at the laboratory | 
| Positive findings for a selected list of carrier conditions | Number of people with pathogenic variants found in genes related to common carrier conditions | Within one month of specimen receipt at the laboratory | 
| Comparison of Healthcare Utilization measured via Electronic Medical Record (EMR) data | Downstream healthcare utilization of specific recommended procedures (e.g., colonoscopy, mammography, surgery) will be compared between participants in the traditional genetic counseling arm, the modified genetic counseling arm, and patients at high risk for a hereditary cancer syndrome that do not join the study (usual care) | Within 12 months of participant receiving information about their hereditary cancer syndrome risk | 
| Participant understanding of recommended care | Measurement of participant's understanding of the recommended care based on their genetic test result will be assessed using a validated survey tool | 2 weeks post result disclosure, 6 months post result disclosure | 
| Participant understanding of genetic test results | Measurement of patient's understanding of the genetic test results will be assessed using a validated survey tool | 2 weeks post result disclosure, 6 months post result disclosure | 
| Participant satisfaction of genetic counseling | Measurement of the patient's satisfaction of genetic counseling will be assessed using a validated survey tool | 2 weeks post result disclosure, 6 months post result disclosure | 
| Family communication | Measurement of the degree to which participants shared their genetic test results with various family members will be assessed using a validated survey tool | Baseline, 2 weeks post result disclosure, 6 months post result disclosure | 
| Personal utility | Measurement of the participant's perceived utility of obtaining genetic testing and counseling will be assessed using validated survey tools that assess lifestyle behaviors and self-reported health/quality of life. | Baseline, 2 weeks post result disclosure, 6 months post result disclosure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lynch syndrome, Hereditary breast and ovarian cancer