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

基本信息

批准号：
10640387
负责人：
Sukh Makhnoon
金额：
$ 24.9万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
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/10640387
关键词：
Affect Anxiety Award Behavioral Cancer Patient Classification Clinical Clinical Investigator Clinical Oncology Communication Comprehensive Cancer Center Computerized Medical Record DNA Sequence Alteration Data Decision Making 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 Reading 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 Ursidae Family Validation Variant Work apprenticeship cancer prevention career clinical decision-making clinical translation clinically relevant clinically significant cohort cost design ethnic diversity ethnic minority 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 and ethnic racial minority population screening sociodemographics therapy design tool translational genomics variant of unknown significance

项目摘要

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。的变体不确定意义（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，为有关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者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。