An integrated and diverse genomic medicine program for undiagnosed diseases

针对未确诊疾病的综合且多样化的基因组医学计划

• 批准号: 10869526
• 负责人: VANDANA SHASHI
• 金额: $ 30.46万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10869526
• 关键词: Address; Administrative Supplement; Area Health Education Centers; Candidate Disease Gene; Caring; Collaborations; Collection; Communication; Continuing Education; County; Data; Diagnosis; Disease; Education; Educational workshop; Eligibility Determination; Enrollment; Ensure; Evaluation; Family; Family member; Feedback; Future; Genetic; Genome Mappings; Genomic medicine; Genomics; Goals; Health Personnel; Hybrids; Knowledge; Literature; Medical Records; Medically Underserved Area; Monitor; North Carolina; Optics; Outcome; Patient Participation; Patients; Persons; Phase; Phenotype; Primary Care Physician; Principal Investigator; Process; Provider; Publishing; Reporting; Research; Role; Rural; Schedule; Site; Specialist; Surveys; Technology; Time; Travel; Update; clinical research site; community engagement; distrust; ethnic minority; exome; experience; flexibility; genome sequencing; health disparity; health disparity populations; interest; meetings; novel; parent grant; patient-level barriers; primary care provider; programs; prospective; provider factors; racial minority; rural area; success; telehealth; transcriptome sequencing

Program Director/Principal Investigator (Last, First, Middle): Shashi, Vandana Abstract The goals of this administrative supplement are for the Duke clinical site to increase the number of patients evaluated, and to continue and expand our ongoing studies to facilitate UDN participation by patients who experience health disparities (defined as living in rural medically underserved areas (MUA) and/or belonging to racial/ethnic minorities). Our aims for this supplement are: Specific Aim 1: Comprehensively evaluate seven new patients with undiagnosed diseases: After streamlined and efficient application review, all accepted patients will receive comprehensive and tailored UDN evaluations, with in-person, telehealth or hybrid evaluations. At least 40% of those enrolled will be patients with health disparities. Exploratory sub-aim 1: Prospectively ascertain patient factors pertinent to UDN application from internally referred patients and offer adaptations to facilitate their UDN application and participation. All patients who are internally referred to the UDN from Duke Health providers, will be prospectively administered surveys on practical barriers/facilitators, genomic knowledge and distrust. Additionally, for the subset of internally referred patients who belong to health disparity populations, we will have two adaptations to facilitate UDN participation: (a) after referral, if they are agreeable, the study team will discuss with the patients/families, the UDN process to address study concerns and offer assistance with the UDN application and medical record collection. (b) For all accepted patients, customized accommodations will be provided to mitigate practical barriers. Specific Aim 2: Analyze the genomic sequencing data of patients and utilize adjunct technologies to provide diagnoses and identify novel candidate genes. We will perform research analysis of the genomic sequencing data on the seven patients and relevant family members, with our phenotype-agnostic approach (especially useful to identify novel candidate genes). Recent updates to our pipeline should increase our success in identifying diagnoses and novel candidates. We will pursue RNAseq and optical genome mapping for selected GS negative cases. Specific Aim 3: Focusing on NC MUA counties, obtain PCPs’ perspectives on barriers to referral/participation in the UDN/genomic medicine for their undiagnosed patients. In partnership with the NC AHEC, we will travel to four regional AHECs in NC MUAs from which we currently receive few applications, to provide a workshop that includes an educational session on undiagnosed diseases (with continuing education credit) and an interactive discussion with the PCPs, to gather perspectives on (a) the need for genomic medicine in their practice, (b) barriers/facilitators to patient referral and participation and (c) strategies that could overcome the barriers. These data will be assessed and shared with the DMCC and the network. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page

项目主任/首席调查员(最后、第一、中间)：Vandana Shashi 摘要 这一行政补充的目标是杜克临床站点增加患者数量 评估，并继续和扩大我们正在进行的研究，以促进以下患者参与UDN 经历健康差距(定义为生活在医疗服务不足的农村地区和/或属于 种族/少数民族)。本增刊的目标是：具体目标1：全面评估七个 新的未诊断疾病患者：经过简化和有效的申请审查，全部接受 患者将接受全面的、量身定制的UDN评估，包括面对面、远程医疗或混合评估 评估。在这些参与者中，至少有40%将是健康差距较大的患者。试探性次级目标1： 从内部转诊患者中前瞻性地确定与UDN应用相关的患者因素，并提供 修改以便利其统一数字域名的应用和参与。所有在内部转诊至 来自杜克大学卫生服务提供者的UDN，将是关于实际障碍/促进者的前瞻性调查， 基因组知识和不信任。此外，对于属于健康的内部转诊患者子集 对于不平等的人口，我们将有两种适应来促进普遍定期人口的参与：(A)在转诊之后，如果他们是 同意的情况下，研究小组将与患者/家属讨论UDN过程，以解决研究问题 并在UDN申请和病历收集方面提供帮助。(B)就所有获接纳的病人而言， 将提供定制的住宿，以减少实际障碍。具体目标2：分析 患者的基因组测序数据并利用辅助技术提供诊断和识别新的 候选基因。我们将对这7名患者的基因组测序数据进行研究分析，并 相关的家庭成员，使用我们的表型不可知的方法(特别有助于确定新的候选人 基因)。我们管道的最新更新应该会增加我们在识别诊断和新技术方面的成功 候选人。我们将对选定的GS阴性病例进行RNAseq和光学基因组图谱绘制。特定的 目标3：重点关注北卡罗来纳州的MUA县，了解初级保健医生对转诊/参与的障碍的看法 为他们的未确诊患者提供UDN/基因组医学。在与NC AHEC的合作下，我们将前往四个 我们目前收到的申请很少的NC MUA的地区性AHEC，以提供一个研讨会， 包括关于未确诊疾病的教育会议(有继续教育学分)和互动 与初级保健医生进行讨论，以收集关于(A)在其实践中需要基因组医学的观点，(B) 患者转诊和参与的障碍/促进者以及(C)可以克服这些障碍的战略。 将对这些数据进行评估，并与DMCC和网络共享。 OMB编号0925-0001/0002(批准的第03/2020版至2023年2月28日)续页格式页