Cancer Health Assessments Reaching Many (CHARM)

September 10, 2025 updated by: Kaiser Permanente

Exome Sequencing in Diverse Populations in Colorado & Oregon

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

967

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80204
        • Denver Health
    • Oregon
      • Portland, Oregon, United States, 97227
        • Kaiser Permanente Center for Health Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 49 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Traditional genetic counseling
This will be typical genetic counseling that a patient would receive in a traditional genetic counseling setting.
Other: Traditional genetic counseling
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.
Experimental: Modified genetic counseling
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive Findings for Hereditary Cancer Syndromes
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 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
For each person, the test result was available within approximately one month of the receipt of that person's specimen at the laboratory.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive Findings for Other Medically Actionable Genetic 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 people with pathogenic variants found in genes related to medically actionable hereditary conditions (other than cancer)
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
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 people with pathogenic variants found in genes related to common carrier conditions
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
Time Frame: Within 12 months of participant receiving information about their hereditary cancer syndrome risk
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.
Within 12 months of participant receiving information about their hereditary cancer syndrome risk
Participant Understanding of Recommended Care
Time Frame: 2 weeks post result disclosure, 6 months post result disclosure
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
Time Frame: 2 weeks post genetic result disclosure
"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.
2 weeks post genetic result disclosure
Participant Satisfaction of Genetic Counseling
Time Frame: 2 weeks post genetic results disclosure
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.
2 weeks post genetic results disclosure
Family Communication
Time Frame: Assessed 6 months post result disclosure
Measurement of the degree to which participants shared their genetic test results with various family members will be assessed using a validated survey tool
Assessed 6 months post result disclosure
Personal Utility of Genomic Sequencing (Qualitative Interview Only)
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.
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.
Qualitative interviews were conducted within 1 month of results disclosure; a subset of these participants were interviewed again at 6 months post-results disclosure.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kaiser Permanente

Collaborators

Dana-Farber Cancer Institute
Columbia University
Emory University
University of Washington
Seattle Children's Hospital
University of California, San Francisco
National Human Genome Research Institute (NHGRI)
Denver Health and Hospital Authority

Investigators

  • Principal Investigator: Michael Leo, PhD, Center for Health Research, Kaiser Permanente Northwest
  • Principal Investigator: Benjamin S Wilfond, MD, Seattle Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 15, 2018

Primary Completion (Actual)

August 20, 2020

Study Completion (Actual)

February 1, 2022

Study Registration Dates

First Submitted

January 11, 2018

First Submitted That Met QC Criteria

February 2, 2018

First Posted (Actual)

February 8, 2018

Study Record Updates

Last Update Posted (Estimated)

September 11, 2025

Last Update Submitted That Met QC Criteria

September 10, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2U01HG007292-05 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Genotype and Phenotype data will be uploaded to ANVIL. Variant data will be uploaded to ClinVar.

IPD Sharing Time Frame

Data will be loaded to ANVIL and ClinVar at least annually beginning in 2018.

IPD Sharing Access Criteria

Subject to ANVIL and ClinVar regulations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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