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.
Aim 1:
Aim 1 will assess efficacy of the approaches on uptake of cascade screening. The primary
outcome will assess uptake of cascade screening among all first-degree relatives of the
probands. We will compare the proportion first-degree relatives who undergo screening out
of all eligible relatives in the direct vs indirect arms of the study. Secondary outcomes
will asses rate of detection of new cases among all first degree family members. We will
have good power to detect a clinically meaningful difference of 15% between he direct and
indirect arms of the study.
These cascade screening efficacy endpoints address the question of whether contacting
family members for probands improves the uptake of testing among family members.
Aim 2:
Aim 2 will assess patient-centered outcomes in both probands and family members that
address how the intervention of direct contact of family members impacts participants'
mental, physical, or psychosocial outcomes. For this aim surveys will be given to the
probands and family members approximately one week after contact of family members has
occurred and at the end of the study. The secondary outcomes associated with this aim
include: perceived alignment of ethical principles, anxiety regarding method of contact,
perceived pressure to undergo testing (family members only), and knowledge of disease. We
will also assess health behaviors such as taking recommended preventative medications
(beta-blockers and statins), lifestyle modifications, and seeing health care providers.
These outcomes will be assessed by validated and study-created surveys assessed 1-week
post implementation and at the end of study.
These patient-centered outcomes assess the extent to which the intervention allows for
autonomous decision making and is associated with acceptable psychosocial outcomes.
Aim 3:
Aim 3 will perform qualitative assessments of the intervention to evaluate implementation
outcomes in the direct vs indirect arms of the study. We will include interviews among 15
probands randomized to the direct arm, 15 probands randomized to the indirect arm, 15
family members who undergo cascade screening from the direct arm (carriers and
non-carriers), 15 family members who undergo cascade screening from the indirect arm
(carriers and non-carriers), and 15 family members who decline cascade testing (from
direct arm and from indirect arm but informed by a proband, thus allowing us to invite
them to participate). We will also interview study staff to understand facilitators and
challenges across patient and organizational factors.
Implementation reach, dosage, and fidelity will be based on proportions and
means/standard deviations for relevant quantitative variables (e.g., number of genetic
counseling visits scheduled and completed). Outreach approach's acceptability, barriers,
and facilitators will be based on descriptive analyses using interview data. Data
analyses will be based on a codebook, consensus coding and consensus narrative
Qualitative interviews will be transcribed verbatim and analyzed using NVivo 11.0. The
research team will conduct standard content analysis and systematic comparison of data
between the two intervention groups; acceptability, appropriateness, patterns in
facilitators/barriers, implementation quality, and early sustainment.
In sum, these interviews will provide more in-depth understanding of the ethical
implications of our intervention and evaluation of the implementation process by relevant
stakeholders.
