Multilevel investigation of uncertain and reclassified genomic variants in clinical oncology

临床肿瘤学中不确定和重新分类的基因组变异的多层次研究

• 批准号: 10705219
• 负责人: Sukh Makhnoon
• 金额: $ 19.51万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705219
• 关键词: Affect; Anxiety; Award; Behavioral; Cancer Patient; Classification; Clinical; Clinical Investigator; Clinical Oncology; Communication; Comprehensive Cancer Center; Computerized Medical Record; Confusion; DNA Sequence Alteration; Data; Decision Making; Dedications; Development; Diffuse; Dimensions; Early Diagnosis; Early treatment; Ensure; Foundations; Frequencies; Fright; Funding; Future; Genetic Services; Genomic medicine; Genomics; Goals; Guidelines; Health; Health system; Healthcare Systems; Human; Individual; Institutional Practice; Intervention; Interview; Investigation; Knowledge; Length; Literature; Longitudinal Studies; Malignant Neoplasms; Measures; Medical; Medical Genetics; Mentorship; Methods; Minority Groups; Oncology; Operative Surgical Procedures; Outcome; Patient Care; Patient Outcomes Assessments; Patients; Perception; Phase; Practice Guidelines; Prevalence; Professional Practice; Program Sustainability; Provider; Psychometrics; Public Health Informatics; Qualitative Methods; Recommendation; Recontacts; Reporting; Research; Risk; Sampling; Site; Source; Structure; Subgroup; Surgical Management; Survey Methodology; Surveys; Test Result; Testing; Time; Training; Uncertainty; Underrepresented Minority; Underserved Population; United States; Update; Validation; Variant; Work; apprenticeship; cancer prevention; career; clinical decision-making; clinical translation; clinically relevant; clinically significant; cohort; cost; design; ethnic diversity; ethnic minority population; evidence based guidelines; experience; genetic technology; genetic testing; genetic variant; genome sequencing; improved; instrument; mutation carrier; novel; patient population; psychosocial; psychosocial wellbeing; racial diversity; racial minority population; screening; sociodemographics; therapy design; tool; translational genomics; variant of unknown significance

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.

项目概要/摘要 该奖项的总体目标是让申请人为独立、持续的项目做好准备 结合心理社会、行为和临床概念和方法来理解和 设计干预措施来指导不确定和重新分类的基因组变异的临床转化。的变种 不确定意义（VUS）引入不确定性，可能会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/族裔少数群体中，并且可以告知 临床决策。然而，关于不确定性和不确定性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转化提出了挑战。这样的 理解在临床肿瘤学中尤为重要，因为突变携带者的识别可以 显着改变癌症预防、筛查、手术建议和治疗。 K99相是 旨在通过课程、学徒和实习来增强候选人之前的研究经验 经过以下方面特定培训的定向阅读：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，这些系统为患者提供临床遗传服务 种族/民族多样化的患者群体。目标 1（K99 阶段）调查全国肿瘤学样本 提供商了解他们与变体重新分类和重新联系相关的做法。目标2（K99阶段） 采访患者以确定与社会心理健康相关的重新分类的维度。目标 3（R00 阶段）使用来自目标 2 的数据和现有文献来开发和试验一种测量基因组的仪器 患者的不确定性。目标 4（R00 阶段）评估变异重新分类的临床效用。这项工作将 生成证据为围绕变体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实际情况，并为未来的纵向研究提供工具 确定收到不确定的基因检测结果的行为、心理和临床后果。 该项目是申请人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）以促进临床转化 基因组学进入不同的卫生系统和服务不足的人群。拟议的奖项将提供 培训、指导和研究经验，这将成为申请人职业生涯的基础 独立资助的临床研究人员致力于改善转化基因组学的健康结果 对于代表性不足的少数群体。