An integrated and diverse genomic medicine program for undiagnosed diseases

项目负责人/主要研究者（最后，第一，中间）：Shashi，Vandana 摘要 本管理补充的目的是使杜克临床研究中心增加患者数量 评估，并继续和扩大我们正在进行的研究，以促进UDN参与的患者， 经历健康差距（定义为生活在农村医疗服务不足地区（MUA）和/或属于 种族/少数民族）。我们的目标是：具体目标1：全面评估七个 未确诊疾病的新患者：经过精简高效的申请审核，全部被受理 患者将接受全面和量身定制的UDN评估，包括面对面，远程医疗或混合 评价。至少40%的入选者将是健康差异患者。探索性次级目标1： 从内部转诊患者中确定与UDN应用相关的患者因素，并提供 适应，以促进他们的UDN的应用和参与。所有内部转诊至 来自杜克医疗服务提供者的UDN将前瞻性地进行关于实际障碍/促进因素的调查， 基因组知识和不信任此外，对于属于健康状况的内部转诊患者子集， 差异人口，我们将有两个适应，以促进UDN参与：（a）转诊后，如果他们是 如果同意，研究团队将与患者/家属讨论UDN流程，以解决研究问题 并提供UDN申请和医疗记录收集方面的帮助。(b)对于所有接受的患者， 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鉴定新的 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， 相关的家庭成员，与我们的表型不可知的方法（特别是有用的，以确定新的候选 基因）。最近更新我们的管道应该增加我们的成功，确定诊断和新的 候选人我们将对选定的GS阴性病例进行RNAseq和光学基因组作图。具体 目标3：以北卡罗来纳州、多阿邦各县为重点，了解初级保健协调员对转诊/参与 UDN/基因组医学为他们未确诊的患者。与NC AHEC合作，我们将前往四个 区域AHEC在NC MUAs，我们目前收到的申请很少，提供一个研讨会， 包括一个关于未确诊疾病的教育会议（有继续教育学分）和一个互动的 与PCP讨论，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/促进因素以及（c）可以克服障碍的战略。 这些数据将被评估并与DMCC和网络共享。 OMB编号0925-0001/0002（修订版03/2020批准至02/28/2023）页码继续格式页码

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