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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SCREENING
Masking
SINGLE
Enrollment
967
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.
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.
Denver Health
Denver, Colorado, United States
Kaiser Permanente Center for Health Research
Portland, Oregon, United States
Positive Findings for Hereditary Cancer Syndromes
Number of people found to have a pathogenic (P) or likely pathogenic (LP) variant in one of the cancer genes associated with Lynch syndrome or hereditary breast and ovarian cancer
Time frame: For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory.
Positive Findings for Other Medically Actionable Genetic Conditions
Number of people with pathogenic variants found in genes related to medically actionable hereditary conditions (other than cancer)
Time frame: For each person, the test result was available within approximately one month of the receipt of that person's specimen 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
Time frame: For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory.
Number of Participants With 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 CHARM participants who received at least one actionable risk management recommendation from study genetic counselors and those who did not receive an actionable risk management recommendation.
Time frame: 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
Time frame: 2 weeks post result disclosure, 6 months post result disclosure
Participant Understanding of Genetic Test Results
"Perceived understanding of results" This novel 5-item measure asked, "Thinking about only your cancer genetic test result, please rate how strongly you agree or disagree with each of the following statements." The 5 items were assessed on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). A principal-axis factor analysis strongly supported a 1 factor solution (accounting for 65.4% of the variance in these items), providing evidence for structural validity, and a Cronbach's α of 0.90, providing strong evidence for internal consistency. The scale was scored using the mean; thus, the possible scores can range from 1 to 5, with higher scores indicating greater understanding.
Time frame: 2 weeks post genetic result disclosure
Participant Satisfaction of Genetic Counseling
This novel measure consisted of 4 items adapted from the Patient Assessment of Communication Effectiveness scale, 8 items developed by the consortium related to participants' overall satisfaction with the results and experience of results disclosures, and 6 items that focused on key elements of modified genetic counseling. Items were measured on a 5-point Likert scale (1 = strongly disagree to 5 = strongly agree). Using principal-axis factor analyses using oblique rotation, we found the 3-factor solution (accounting for 62.5% of the variance in the items) to provide adequate simple structure with conceptually meaningful factors and thus, created subscale scores for each set of items (6 loaded on each factor): "genetic counseling relationship score", "communication difficulty score", and "communication ease score". The possible mean scores can range from 1 to 5, with higher scores indicating a better outcome.
Time frame: 2 weeks post genetic results 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
Time frame: Assessed 6 months post result disclosure
Personal Utility of Genomic Sequencing (Qualitative Interview Only)
Participant's perceived utility of obtaining genetic testing and genetic counseling were assessed. Data collection used semi-structured qualitative interviews. Analyses were conducted using a modified grounded theory approach and explored the five utility domains of the model: clinical, emotional, behavioral, cognitive, and social. The analysis examined how well this multifaceted perceived utility model applied to the responses provided during the interviews. The qualitative data was not quantified in any way and can not be represented in a tabular format.
Time frame: Qualitative interviews were conducted within 1 month of results disclosure; a subset of these participants were interviewed again at 6 months post-results disclosure.
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