The Genomic Medicine at VA Study (GenoVA)

Boston VA Research Institute, Inc.

Status: Enrolling

Conditions: Breast Cancer; Coronary Artery Disease; Atrial Fibrillation; Type 2 Diabetes; Prostate Cancer; Colorectal Cancer

Treatments: Diagnostic Test: Polygenic risk score (PRS)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT04331535

0594

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,076 estimated patients

Sex: All

Ages: 50 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1,076 participants in 4 patient groups

Polygenic risk score (PRS) - high risk stratum

Experimental group

Description:

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.

Treatment:

Diagnostic Test: Polygenic risk score (PRS)

Usual care (UC) - high risk stratum

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: Polygenic risk score (PRS)

Polygenic risk score (PRS) - average risk stratum

Experimental group

Description:

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.

Treatment:

Diagnostic Test: Polygenic risk score (PRS)

Usual care (UC) - average risk stratum

Active Comparator group

Description:

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..

Treatment:

Diagnostic Test: Polygenic risk score (PRS)