A Community-Based Approach to Overcoming Barriers to Cascade Screening for Long QT Syndrome

克服长 QT 综合征级联筛查障碍的基于社区的方法

• 批准号: 9788511
• 负责人: AMBER L BEITELSHEES
• 金额: $ 23.53万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-19 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788511
• 关键词: Address; Adrenergic beta-Antagonists; American; Amish; Arrhythmia; Behavioral; Blood; Blood Tests; Cardiac; Caring; Clinical; Communities; Complex; Consent; Consent Forms; County; Coupled; Data; Development; Disclosure; Disease; Effectiveness; Family; Family member; First Degree Relative; Founder Effect; Frequencies; Future; Genes; Genetic; Genetic Diseases; Genetic Enhancement; Genetic screening method; Genotype; Growth; Image; Individual; Information Dissemination; Inherited; Institutional Review Boards; Intervention; Interview; Laboratories; Language; Link; Logistics; Long QT Syndrome; Medical; Medical Genetics; Methods; Motivation; Mutation; Participant; Patients; Persons; Phase; Population; Population Study; Preventive therapy; Preventive treatment; Procedures; Process; Recommendation; Recording of previous events; Reporting; Research Personnel; Risk; Saliva; Sampling; Study Subject; Sudden Death; Test Result; Testing; Variant; actionable mutation; base; care systems; carrier testing; cost; disorder risk; expectation; experience; follow-up; genetic variant; genome sequencing; high risk; improved; insight; medical schools; member; outcome forecast; primary outcome; proband; research study; screening; screening guidelines; secondary outcome; standard of care; trait; uptake; whole genome

PROJECT SUMMARY While the value of identifying individuals in the population who carry `actionable' variants and screening their relatives (i.e. cascade screening) is widely acknowledged, there are numerous barriers in implementing this process and studying the optimal approaches for doing this. First, the feasibility of returning genetic results is complex as it depends on many issues, including the community expectations, consent form language, local IRB considerations, and logistical, feasibility, and cost issues, among others. Second, even in very large population studies, the frequency of `actionable' variants is typically so low that it is difficult to study optimal approaches for dissemination of results and screening of family members in any systematic way. We have identified 124 Amish individuals in Lancaster County, PA, harboring a mutation in KCNQ1 that is associated with long QT syndrome type 1 (LQT1), a trait linked to arrhythmia-associated sudden death. KCNQ1 is regarded by the American College of Medical Genetics (ACMG) as `actionable' since appropriate preventative treatment is available (beta-blockers). This mutation (p.Thr224Met; rs199472706) is highly enriched in the Amish community due to a founder effect. We are proposing a mixed methods study that will implement a quantitative intervention aimed at improving uptake of cascade screening and qualitative interviews aimed at gaining insights into: the impact of the return of results process, why participants choose or choose not to initiate cascade screening of family members, and how the intervention impacts their decisions. In Aim 1 we will implement a simplified cascade screening intervention that offers free, mail-in, saliva-based testing of family members. The primary outcome is the rate of uptake of cascade screening before versus after the implementation of the simplified screening intervention. The secondary outcomes are the rate of disclosure to family members before versus after, the proportion of informed family members who get screened before versus after, and the uptake of clinical recommendations. In Aim 2 we will perform in-depth interviews of 30 probands and 45 family members to assess: understanding of genetic test results and cascade screening, how decisions are made regarding pursuing or not pursuing cascade screening, and predisposing, enabling, and need-based themes that influence uptake of cascade screening. This population provides a unique and powerful opportunity to evaluate and formulate strategies for returning genetic results to individuals discovered to have `actionable' genetic variants and enhancing screening of their family members.

项目总结 虽然在人群中识别携带“可起诉”变种和 筛查其亲属(即层叠筛查)得到了广泛的认可，有无数 实施这一进程和研究实现这一进程的最佳方法方面的障碍。首先， 返回遗传结果的可行性是复杂的，因为它取决于许多问题，包括 社区期望，同意书语言，当地IRB考虑，以及后勤，可行性， 以及成本问题等。第二，即使在非常大的人口研究中， 可操作的变种通常如此之低，以至于很难研究传播的最佳方法 以任何系统的方式对结果进行评估和对家庭成员进行筛选。我们已经确认了124名阿米什人 宾夕法尼亚州兰开斯特县的个体携带与长QT相关的KCNQ1突变 1型综合征(LQT1)，一种与心律失常相关的猝死有关的特征。KCNQ1被视为 被美国医学遗传学学会(ACMG)评为可操作的，因为适当的预防措施 治疗是可用的(β-受体阻滞剂)。这种突变(p.Thr224Met；rs199472706)高度丰富 在阿米什社区，由于创始人效应。我们提出了一项混合方法研究，将 实施量化干预，旨在提高层叠筛查和定性筛查的接受度 访谈的目的是深入了解：返回结果过程的影响，为什么参与者 选择或选择不启动家庭成员级联筛查，以及如何进行干预 影响他们的决策。在目标1中，我们将实施简化的级联筛查干预 提供免费的、邮寄的、基于唾液的家庭成员测试。主要结果是 简化筛查实施前后的层叠筛查情况 干预。次要结果是之前向家庭成员披露的比率与 之后，知情的家庭成员在之前和之后接受筛查的比例，以及 对临床建议的理解。在目标2中，我们将对30名先驱进行深入采访，并 评估45个家庭成员：了解基因检测结果和级联筛查，如何 作出关于进行或不进行层叠筛查的决定， 支持和基于需求的主题，影响级联筛查的采用。这群人 提供了一个独特而强大的机会来评估和制定基因恢复策略 对被发现具有可操作的遗传变异的个人的结果，并加强筛查 他们的家人。