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.

项目摘要 虽然在人群中识别携带“可采取行动的”变异的个人的价值， 筛查他们的亲属（即级联筛查）是广泛认可的，有许多 在执行这一进程和研究这样做的最佳办法方面的障碍。一是 返回基因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、知情同意书语言、当地IRB考虑因素以及后勤、可行性， 以及成本问题等等。其次，即使在非常大的人群研究中， “可采取行动的”变体通常很少，因此很难研究传播的最佳方法 以任何系统的方式对结果和家庭成员进行筛查。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一名个体，携带与长QT相关的KCNQ 1突变 综合征1型（LQT 1），一种与糖尿病相关猝死相关的特征。KCNQ 1被认为 被美国医学遗传学学会（ACMG）认为是“可诉的”，因为适当的预防措施 治疗可用（β-受体阻滞剂）。该突变（p.Thr224Met; rs 199472706）高度富集 在阿米什社区由于创始人效应。我们建议采用混合方法进行研究， 实施定量干预措施，以提高级联筛查和定性筛查的采用率 访谈的目的是深入了解：结果返回过程的影响，为什么参与者 选择或选择不启动级联筛选的家庭成员，以及如何干预 影响他们的决定。在目标1中，我们将实施简化的级联筛查干预措施， 为家庭成员提供免费的、邮寄的、基于唾液的测试。主要结局是发生率 实施简化筛查前后级联筛查的采用情况 干预次要结果是之前向家庭成员披露的比率， 之后，知情的家庭成员在之前与之后接受筛查的比例，以及 接受临床建议。在目标2中，我们将对30名先证者进行深入访谈， 45家庭成员评估：了解基因检测结果和级联筛查，如何 做出关于进行或不进行级联筛查的决定，以及诱发， 影响级联筛查采用的扶持性和基于需求的主题。该人群 提供了一个独特而强大的机会，以评估和制定战略， 对发现有“可采取行动”的遗传变异的个人提供结果，并加强对 他们的家人。