Million Veteran Program Return of Actionable Results

Study Overview
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Brief Summary
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The purpose of the Million Veteran Program- Return of Actionable Results (MVP-ROAR) Study is to develop a process to return medically actionable genetic results to living MVP participants nationwide and to determine the impact of doing so on medical management and outcomes and Veteran quality of life.

Detailed Description
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The Million Veteran Program - Return of Actionable Results (MVP-ROAR) Study is a randomized controlled trial of immediate vs. delayed (after 6 months) return of medically actionable, clinically confirmed genetic testing results. MVP participants with a medically actionable variant in their MVP chip genotype data will be contacted and offered the opportunity to receive clinical confirmation of this result through a research protocol. First, a non-randomized pilot trial will be conducted among 10 eligible MVP participants, followed by a randomized controlled trial of immediate vs. delayed clinical confirmation and reporting, delivered to participants nationwide via telegenetic counseling. Three hypotheses will be tested: Hypothesis 1 (LDL-C change): LDL-C reduction after 6 months will be greater in the Immediate Results arm compared to the Delayed Results arm (primary outcome) Hypothesis 2 (LDL-C target): The proportion of participants meeting clinically significant LDL-C targets (<100mg/dL for primary prevention and <70 mg/dL for secondary prevention) at 6 months will be greater in the Immediate Results arm than in the Delayed Results arm (secondary outcome) Hypothesis 3 (Pharmacotherapy): the proportion of participants with an intensification of lipid-lowering pharmacotherapy will be greater in the Immediate Results arm than in the Delayed Results arm (secondary outcome)

Official Title
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Million Veteran Program Return of Actionable Results

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Genetic: Result disclosure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Living enrollee in MVP Is identified to have a pathogenic or likely pathogenic variant in the gene(s) of interest in MVP genotype data Exclusion Criteria: Previously underwent genetic testing for the condition of interest Is incarcerated Is pregnant

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate Results<br>Participants in the Immediate Results arm will receive their genetic testing results from a genetic counselor at baseline following randomization. | Genetic: Result disclosure<br>* Disclosure of clinically confirmed, medically actionable genetic testing results and post-test genetic counseling session.<br>|
| Experimental: Delayed Results<br>Participants in the Delayed Results arm will receive their genetic testing results from a genetic counselor 6 months after randomization. | Genetic: Result disclosure<br>* Disclosure of clinically confirmed, medically actionable genetic testing results and post-test genetic counseling session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C change | Change in LDL-C after 6 months. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL-C target | The proportion of participants meeting clinically significant LDL-C targets (< 100mg/dL for primary prevention and <70 mg/dL for secondary prevention) at 6 months. | 6 months | 
| Pharmacotherapy | The proportion of participants with an intensification of lipid-lowering pharmacotherapy, a composite outcome including prescription of new monotherapy, dose escalation of existing pharmacotherapy, and addition of one or more medications to existing pharmacotherapy. | 6 months |