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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：
9648330
负责人：
AMBER L BEITELSHEES
金额：
$ 19.66万
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 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9648330
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 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 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.

项目总结