The Genomic Medicine at VA Study
Purpose
This trial will determine the clinical effectiveness of polygenic risk score testing among patients at high genetic risk for at least one of six diseases (coronary artery disease, atrial fibrillation, type 2 diabetes mellitus, colorectal cancer, breast cancer, or prostate cancer), measured by time-to-diagnosis of prevalent or incident disease over 24 months.
Conditions
- Coronary Artery Disease
- Atrial Fibrillation
- Type 2 Diabetes
- Colorectal Cancer
- Breast Cancer
- Prostate Cancer
Eligibility
- Eligible Ages
- Between 50 Years and 70 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Age 50-70 years at enrollment - No known diagnosis of the following conditions, initially screened by the International Classification of Disease (ICD) codes or other electronic health record (EHR) data using validated methods and then confirmed with potential patient-participants during recruitment: coronary artery disease, atrial fibrillation, type 2 diabetes, colorectal cancer, breast cancer, prostate cancer
Exclusion Criteria
- Patients will be ineligible if they: - Have a known diagnosis of at least one of the six diseases of interest - Are younger than age 50 or older than age 70 - Are pregnant - Are incarcerated or institutionalized
Study Design
- Phase
- N/A
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Randomized clinical trial comparing polygenic risk score (PRS) testing and reporting to delayed reporting
- Primary Purpose
- Screening
- Masking
- Single (Outcomes Assessor)
- Masking Description
- Participants are randomized to have them and their primary care providers receive their PRS results at baseline (PRS) or after 24 months (usual care, UC). Randomization is stratified by PRS results: A high-risk stratum consists of all participants with at least one PRS indicating high risk, while the remaining participants comprise the average-risk stratum. Participants who do not receive their results at baseline are blinded to whether they have all average-risk PRS results or any high-risk PRS results. Outcomes assessors and data analysts will be blinded to randomization and PRS results status.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Polygenic risk score (PRS) - high risk stratum |
Patient-participants in the PRS-high arm and their providers will receive their high-PRS results at baseline, along with educational resources about the results. |
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|
Active Comparator Usual care (UC) - high risk stratum |
Patient-participants in the UC-high arm and their providers will receive their high-PRS results after a 24-month observation period, along with educational resources about the results. |
|
|
Experimental Polygenic risk score (PRS) - average risk stratum |
Patient-participants in the PRS-average arm and their providers will receive their average-PRS results at baseline, along with educational resources about the results. |
|
|
Active Comparator Usual care (UC) - average risk stratum |
Patient-participants in the UC-average arm and their providers will receive their average-PRS results after a 24-month observation period, along with educational resources about the results.. |
|
Recruiting Locations
Boston, Massachusetts 02130-4817
More Details
- Status
- Recruiting
- Sponsor
- Boston VA Research Institute, Inc.
Detailed Description
One of the most pressing controversies in genomics today is the clinical utility of polygenic risk scores (PRS). Broadening the scope of genomic risk testing beyond monogenic diseases, PRS combine information from hundreds or even millions of genetic loci, each with a very small effect size on the risk of common complex disease. The result is a continuous quantitative risk factor for susceptibility to conditions such as coronary artery disease (CAD), type 2 diabetes (T2D), and breast cancer. Compared to rarer monogenic disease variants, PRS have greater transformative potential for public health and healthcare in their ability to identify much larger proportions of the population at significantly elevated risk for disease, facilitating evidence-based prevention and management. Moreover, their prediction ability has vastly improved compared to earlier PRS that included only a limited number of genetic variants. However, while the associations between PRS and a wide range of common diseases are well established (clinical validity), the potential impact of this information on patient health outcomes (clinical utility) remains contested and understudied. This study will examine the effectiveness and implementation outcomes from the use of PRS for 6 common diseases that are screened for by PCPs and have established prevention strategies: CAD, AFib, T2D, colorectal cancer, prostate cancer, and breast cancer. This trial has two aims: Aim 1: Conduct a randomized controlled trial (RCT) to determine the clinical effectiveness of PRS among patients at high genetic risk for at least one disease, measured by changes in clinical management (process outcomes) and time to diagnosis of prevalent or incident disease (clinical outcome) over 24 months. Aim 2: Measure high-priority genomic medicine implementation outcomes, including primary care provider (PCP) knowledge and beliefs about PRS, patient activation in healthcare, medication adherence, and costs.