Multilevel investigation of uncertain and reclassified genomic variants in clinical oncology

项目总结/摘要 该奖项的首要目标是为申请人准备一个独立的，持续的计划， 研究，结合心理社会，行为和临床概念和方法，以了解和 设计干预措施，指导临床翻译不确定和重新分类的基因组变异。的变体 不确定意义（VUS）会引入不确定性，并可能混淆患者的临床决策， 提供商VUS也经常被重新分类，特别是在种族/少数民族人群中， 临床决策。然而，围绕不确定因素的影响和结果的证据不足， 重新分类的变体对这些遗传变体的更广泛的临床翻译提出了挑战。等 理解在临床肿瘤学中特别重要，因为突变携带者的鉴定可以 显著改变癌症预防、筛查、手术建议和治疗。K99阶段是 旨在增加候选人的先前的研究经验，通过课程，学徒和 指导阅读与具体培训：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， 来自六个医疗保健系统的电子医疗记录数据，这些医疗保健系统为一个 不同种族/人种的患者人群。目标1（K99期）调查了全国肿瘤学样本 供应商了解他们的做法有关的变量重新分类和重新联系。目标2（K99阶段） 访谈患者，以确定重新分类相关的心理健康的维度。目标3（R 00 阶段）使用来自aim 2和现有文献的数据开发和试验一种测量基因组 患者的不确定性。目的4（R 00期）评价变异重新分类的临床效用。这项工作将 产生证据，为各种重新分类的机构和专业实践提供信息。采取 总之，这项研究的结果将结合背景，并为未来的纵向研究提供工具， 确定接受不确定的基因测试结果的行为，心理和临床后果。 这个项目是申请人的长期研究目标的开发和测试的关键组成部分 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 将基因组学应用于各种卫生系统和服务不足的人群。该奖项将提供 培训，指导和研究经验，将作为申请人的职业生涯的基础， 独立资助的临床研究者，致力于改善翻译基因组学的健康结果 代表性不足的少数民族。

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.