Randomized trial of universal vs. guideline-directed germline testing among young adults with cancer

年轻癌症患者中通用生殖系检测与指南指导生殖系检测的随机试验

• 批准号: 10596783
• 负责人: Steven Joffe
• 金额: $ 14.36万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10596783
• 关键词: Address; Adherence; Adoption; Affect; Age; Algorithms; Area; Biology; Cancer Patient; Cancer Prevention Intervention; Caring; Cause of Death; Characteristics; Clinical; Code; Communication; Communities; Computerized Medical Record; Consensus; Data; Deposition; Development; Diagnosis; Diagnostic; Disease; Elderly; Elements; Face; Family; Family member; Feedback; Frequencies; Funding; GB virus C; Genetic; Genetic Predisposition to Disease; Genetic Processes; Genetic Risk; Genomic medicine; Genomics; Goals; Group Meetings; Guidelines; Health; Hospitals; Individual; Information Services; Infrastructure; Inherited; Institution; Instruction; Interdisciplinary Study; International; Intervention; Interview; Knowledge; Laboratories; Libraries; Link; Logic; Malignant Neoplasms; Measures; Medicine; Modeling; Mutation; Participant; Patients; Phenotype; Physicians; Policies; Predisposition; Process; Protocols documentation; Provider; Publications; Questionnaires; Randomized Controlled Trials; Relative Risks; Report (document); Reporting; Risk; Sampling; Series; System; Test Result; Testing; Time; United States; Variant; automated algorithm; base; cancer risk; cancer therapy; clinical decision support; dashboard; data standards; discrete data; ethnic minority; evaluation/testing; follow-up; genetic counselor; genetic disorder diagnosis; genetic panel test; genetic testing; genomic data; implementation barriers; improved; medically underserved population; meetings; member; novel strategies; outreach; patient health information; patient-level barriers; precision medicine; programs; racial minority; randomized trial; recruit; screening; screening guidelines; standard of care; success; variant of unknown significance; web site; young adult

Cancer is the leading nontraumatic cause of death among young adults. In individuals under age 40, cancer has a distinct biology and often has an underlying genetic etiology. However, consensus guidelines driven by phenotypic characteristics fail to identify many young adult patients with inherited genetic risk, in part due to their complexity and to lack of data on mutation frequency. We likely vastly underestimate the frequency and spectrum of germline susceptibility in young adults with cancer, knowledge of which would have far-reaching implications both for their treatment and follow-up care and for the diagnosis and management of relatives. Thus, better strategies for diagnosing inherited risk among young adults with cancer are needed. Further, genetic testing rates among relatives of those identified with inherited cancer risk range from 50-60%; interventions to overcome the barriers that patients and relatives face, so they can take appropriate screening and risk-reducing measures, must be developed and tested. Finally, there is a critical need to integrate genetic evaluation and test results into the electronic medical record (EMR) to facilitate tailored clinical decision support for both clinicians and patients. The present proposal seeks to overcome the limitations of current data and models of care through two Specific Aims. First, we will conduct a randomized controlled trial among 1421 young adults with cancer, one-third of whom will be members of racial or ethnic minorities or medically underserved groups, to compare rates of ascertainment of genetic risk between guideline-driven, phenotype- directed genetic testing (current standard of care) and universal cancer panel genetic testing. Working with the Penn Medicine Nudge Unit and Information Services, we will develop EMR-based algorithms for automatic patient referral and clinical decision support, driven by discrete genetic test results ported into the EMR via HL7, that will include ‘active choice’ nudges, direct-to-patient alerts, and physician dashboards that minimize physician burden. We will compare adherence to screening recommendations among participants to that among historical controls. Second, we will compare the impact of the two up-front testing strategies among patients, enhanced by a novel strategy of direct team outreach to at-risk relatives, on ascertainment of genetic risk among family members. We also will conduct qualitative interviews with a diverse sample of patients, relatives, and family groups to describe the critical interactions that facilitate or impede communication about risk and cascade testing within families and to explore the acceptability of direct clinical team outreach to at- risk relatives. The proposed study promises to immediately alter national standards of care and payer policies by identifying the preferred approach to evaluating young adult cancer patients for genetic risk through a rigorous randomized trial, while measuring ascertainment among both patients and their relatives. In addition, beyond its potential to change standards of care, the study will generate shareable EMR-based code, algorithms, and models that will further enhance the sustainability of the proposed approach.

癌症是年轻人死亡的主要非创伤性原因。40岁以下的人，癌症 具有独特的生物学特征，通常具有潜在的遗传病因。然而，共识指导方针的驱动下， 表型特征无法识别许多具有遗传遗传风险的年轻成年患者，部分原因是 它们的复杂性和缺乏突变频率的数据。我们可能大大低估了频率， 年轻癌症患者的生殖系易感性谱，了解这一点将具有深远的意义。 这对他们的治疗和后续护理以及对亲属的诊断和管理都有影响。 因此，需要更好的策略来诊断年轻癌症患者的遗传风险。此外，本发明还 遗传性癌症患者亲属的基因检测率为50-60%; 干预措施，以克服患者和亲属面临的障碍，使他们能够采取适当的筛查 和降低风险的措施，必须加以开发和测试。最后，迫切需要整合遗传学， 将评估和测试结果输入电子病历（EMR），以便于定制临床决策 支持临床医生和患者。本提案力求克服现有数据的局限性 通过两个具体目标的护理模式。首先，我们将在1421名受试者中进行随机对照试验， 患有癌症的年轻人，其中三分之一将是少数种族或少数民族成员， 服务不足的群体，比较指南驱动的，表型- 定向基因检测（当前的护理标准）和通用癌症小组基因检测。会同 Penn Medicine Nudge Unit和Information Services，我们将开发基于EMR的自动算法， 患者转诊和临床决策支持，由离散基因检测结果驱动，通过 HL 7将包括“主动选择”轻推、直接针对患者的警报和医生仪表板， 医生负担我们将比较参与者对筛查建议的依从性， 历史对照。第二，我们将比较两种预先测试策略在 患者，加强了一种新的战略，直接团队外展到危险的亲属，对确定遗传 家庭成员的风险。我们还将对不同样本的患者进行定性访谈， 亲属和家庭群体，以描述促进或阻碍沟通的关键互动， 家庭内的风险和级联测试，并探讨直接临床团队外展到 风险亲戚这项拟议中的研究承诺将立即改变国家护理标准和付款人政策 通过确定评估年轻成年癌症患者遗传风险的首选方法， 严格的随机试验，同时测量患者及其亲属之间的确定性。此外，本发明还提供了一种方法， 除了改变护理标准的潜力外，该研究还将产生可共享的基于EMR的代码， 算法和模型，这将进一步提高所提出的方法的可持续性。