Comparing Direct vs Indirect Methods for Cascade Screening

Study Overview
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Brief Summary
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An important aspect of successful genomic medicine implementation is developing effective approaches for screening at-risk family members after probands are identified, also known as cascade screening. Most cascade screening studies conducted to date have been conducted outside the US, and very few studies have used a rigorous approach involving a comparator group or randomized controlled design. A major question in the field is how to most effectively implement cascade screening, given commonly cited communication barriers, while respecting privacy among probands and family members. This study will conduct a randomized controlled trial to assess direct contact of relatives by study team members vs indirect, or proband-initiated, contact. We will assess efficacy of the cascade screening intervention, patient-centered outcomes regarding mental, physical, and psychosocial outcomes in probands and family members, and implementation evaluation outcomes. Individuals who are known to carry the KCNQ1 Met224Thr or APOB Arg3527Gln variant will be eligible to participate. After providing consent and being deemed eligible, individuals will be randomized in a 1:1 manner into the direct or indirect contact of family members arm of the study. The randomization will be stratified by variant to ensure equal representation of each variant in the study arms. Individuals in the indirect arm will be instructed to contact their first-degree family members about the opportunity to be screened. They will be provided with a disease-specific pamphlet and a family letter explaining the cascade screening. In the direct arm, probands will be advised that the study staff will be contacting their family members. They will be instructed to also contact their family members prior to the study team contacting them. Approximately two weeks after this meeting with the proband, the study staff will mail letters to eligible first-degree family members of the probands. If we do not hear back from individual family members, we will follow-up with another letter, telephone call, or home visit. The information contained in the letters will be the same information for both the direct and indirect arms of the study. All interested family members will receive pre-test counseling and free, in-home, saliva-based genetic testing, and post-test counseling.

Official Title
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Comparing Direct and Indirect Methods for Cascade Screening in Familial Hypercholesterolemia (FH) and Long QT Syndrome (LQTS)

Conditions
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Ethics, Long QT Syndrome, Familial Hypercholesterolemia, Genetic Testing

Intervention / Treatment
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* Behavioral: Direct contact of family members for cascade screening of relevant variants


Participation Criteria
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Eligibility Criteria
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Proband Inclusion Criteria: KCNQ1 Thr224Met or APOB R3527Q carrier 18 years or older Proband Exclusion Criteria: None Family Inclusion Criteria: 1st degree relative of a KCNQ1 Thr224Met or APOB Arg3527Gln carrier Family Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 18 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: Screening
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Direct contact<br>Study team contact of family members | Behavioral: Direct contact of family members for cascade screening of relevant variants<br>* Study team members will directly contact potentially impacted family members to offer genetic testing of relevant variant.<br>|
| No Intervention: Indirect contact<br>Proband initiated contact of family members | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uptake of cascade screening among all first-degree relatives | Proportion of first-degree relatives who undergo testing/All eligible first-degree relatives | Through study completion: approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of new cases detected among all first-degree family members | New cases/All eligible first-degree family members | Through study completion: approximately 4 years | 
| Perceived alignment of ethical principles questionnaire | Among probands and family members | up to 6 months | 
| Anxiety regarding method of contact questionnaire | Among probands and family members | up to 6 months | 
| Perceived pressure to undergo testing/share health information questionnaire | Among probands and family members | up to 6 months | 
| Knowledge of disease and variant questionnaire | Among probands and family members | up to 6 months |