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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要而识别携带“可行”变体的人群中的个人的价值和广泛认识到他们的亲戚（即级联筛查），有很多实施此过程并研究这样做的最佳方法的障碍。首先，返回遗传结果的可行性很复杂，因为这取决于许多问题，包括社区期望，同意语言，本地IRB考虑以及后勤，可行性，和成本问题等。其次，即使在非常大的人口研究中， “可操作”的变体通常很低，以至于很难研究传播的最佳方法以任何系统的方式对家庭成员的筛查。我们已经确定了124阿米什人宾夕法尼亚州兰开斯特县的个人，在KCNQ1中有一个与长QT相关的突变综合征1型（LQT1），这是与心律不齐相关的猝死有关的特征。 KCNQ1被考虑由美国医学遗传学学院（ACMG）作为“可行”，因为适当的预防性可用治疗（Beta-Blockers）。该突变（P.TH224met; rs199472706）高度丰富由于创始人的效果，在阿米什人社区中。我们提出的混合方法研究将实施旨在改善级联筛查和定性吸收的定量干预措施旨在获得见解的访谈：结果返回过程的影响，为什么参与者选择或选择不启动家庭成员的级联筛查，以及如何干预影响他们的决定。在AIM 1中，我们将实施简化的级联筛查干预措施提供家庭成员的免费，邮寄，基于唾液的测试。主要结果是在实施简化筛选后与级联筛查的吸收干涉。次要结果是在与家人之前向家庭成员的披露率之后，在与之后进行筛选的知情家庭成员的比例，吸收临床建议。在AIM 2中，我们将对30个证据进行深入的访谈， 45个家庭成员要评估：了解基因测试结果和级联筛查，如何关于追求或不进行级联筛查，易感性的决定启用影响级联筛查吸收的基于需求的主题。这个人口提供了一个独特而有力的机会来评估和制定返回遗传的策略结果的结果被发现具有“可行”的遗传变异并增强筛查的个人他们的家人。