Multilevel investigation of uncertain and reclassified genomic variants in clinical oncology

项目摘要/摘要 这一奖项的首要目标是为申请者准备一个独立的、持续的 结合心理社会、行为和临床概念和方法的研究，以了解和 设计干预措施，指导不确定和重新分类的基因组变异的临床翻译。的变种 不确定意义(VUS)带来不确定性，并可能混淆患者的临床决策 供应商。VU也经常被重新分类，特别是在种族/少数民族人口中，并可告知 临床决策。然而，围绕不确定和不确定因素的影响和结果的证据不足 重新分类的变异对这些遗传变异的更广泛的临床翻译提出了挑战。是这样的 理解在临床肿瘤学中尤其重要，因为识别突变携带者可以 显著改变癌症预防、筛查、手术建议和治疗。K99阶段是 旨在通过课程学习、学徒和培训来增加候选人以前的研究经验 经过特殊培训的定向读物：1)临床健康信息学，2)心理测量学和调查 方法论；3)先进的定性方法。拟议的研究将收集患者报告和 来自六个医疗保健系统的电子病历数据，这些系统为 种族/民族多元化的患者群体。目标1(K99阶段)调查全国肿瘤学样本 让供应商了解他们在变种、重新分类和重新联系方面的做法。目标2(K99阶段) 访谈患者以确定重新分类与心理社会幸福感相关的维度。目标3(R00 阶段)使用来自Aim 2的数据和现有文献来开发和试运行一种测量基因组的仪器 患者的不确定性。目的4(R00期)评估变异重分类的临床应用。这项工作将 生成证据，为机构和专业实践提供关于不同重新分类的信息。已被占用 总而言之，这项研究的发现将与背景相联系，并为未来的纵向研究提供工具 确定接受不确定的基因检测结果的行为、心理和临床后果。 该项目是申请者开发和测试长期研究目标的关键组成部分 干预措施(在提供者、患者和医疗保健系统层面)，以促进临床翻译 将基因组学应用于不同的卫生系统和服务不足的人群。拟议的奖励将提供 作为申请者职业生涯基础的培训、指导和研究经验 独立资助的临床研究员，致力于改善翻译基因组学的健康结果 对于未被充分代表的少数群体。

PROJECT SUMMARY/ABSTRACT The overarching goal of this award is to prepare the applicant for an independent, sustained program of research that incorporates psychosocial, behavioral, and clinical concepts and methods to understand and design interventions to guide clinical translation of uncertain and reclassified genomic variants. Variants of uncertain significance (VUS) introduce uncertainty and can confuse clinical decision making for patients and providers. VUS are also frequently reclassified, especially in racial/ethnic minority populations, and can inform clinical decision making. However, insufficient evidence around the influences and outcomes of uncertain and reclassified variants presents a challenge for more diffuse clinical translation of these genetic variants. Such understanding is particularly important in clinical oncology, as identification of mutation carriers can significantly alter cancer prevention, screening, surgery recommendations, and treatment. The K99 phase is designed to augment the candidate's prior research experience though coursework, apprenticeships and directed readings with specific training in: 1) clinical health informatics, 2) psychometrics and survey methodology, and, 3) advanced qualitative methods. The proposed research will collect patient reported and electronic medical record data from six healthcare systems that provide clinical genetic services to a racially/ethnically diverse patient population. Aim 1 (K99 phase) surveys a national sample of oncology providers to understand their practices related to variant reclassification and recontact. Aim 2 (K99 phase) interviews patients to identify dimensions of reclassification associated psychosocial well-being. Aim 3 (R00 phase) uses data from aim 2 and existing literature to develop and pilot an instrument to measure genomic uncertainty in patients. Aim 4 (R00 phase) evaluates the clinical utility of variant reclassification. This work will generate evidence to inform institutional and professional practice around variant reclassification. Taken together, the findings from this study will contextualize, and provide tools for a future longitudinal study to determine the behavioral, psychosocial, and clinical consequences of receiving uncertain genetic test results. This project is a critical building block for the applicant's long-term research goal to develop and test interventions (at the levels of provider, patient and healthcare system) to facilitate the clinical translation of genomics into diverse health systems and into underserved populations. The proposed award will provide training, mentorship and research experience that will serve as the foundation for the applicant's career as an independently funded clinical investigator dedicating to improving health outcomes in translational genomics for underrepresented minority populations.