Development of recommendations and policies for genetic variant reclassification

制定遗传变异重新分类的建议和政策

• 批准号: 9791351
• 负责人: Paul Stuart Appelbaum
• 金额: $ 72.72万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-24 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9791351
• 关键词: Address; Adoption; Advocate; Affect; Agreement; Algorithms; Amendment; American; Area; Automobile Driving; Benign; Caring; Classification; Client; Clinical; Communities; Computing Methodologies; Consensus; Consultations; Data; Databases; Development; Diagnosis; Disadvantaged; Economics; Ethical Issues; Ethics; Family Cancer History; Focus Groups; Foundations; Future; Genes; Genetic; Genetic screening method; Genome; Genomics; Goals; Guidelines; Health; Health Personnel; Heart Diseases; Individual; Insurance; Laboratories; Legal; Medical; Medical Genetics; Minor; Modeling; Neurologic; Neurologist; Oncologist; Paper; Parents; Pathogenicity; Patients; Physicians; Policies; Positioning Attribute; Professional Organizations; Provider; Recommendation; Recontacts; Reporting; Resolution; Risk; Series; Specific qualifier value; Surveys; Test Result; Testing; Time; Update; Variant; Work; adverse outcome; base; clinical decision-making; clinically significant; cost; data to knowledge; design; economic impact; ethnic diversity; ethnic minority population; exome; genetic counselor; genetic variant; genomic data; health economics; medical schools; medical specialties; meetings; operation; prevent; racial minority; whole genome; working group

Project Abstract As genomic sequence data are being produced faster and at lower cost, the most significant challenge in clinical genetic testing today is variant classification. Currently, there are marked differences in variant classification among clinical laboratories, with clinically significant discrepancies in 29% of variants interpreted. Variants that were previously categorized as pathogenic are now known to be benign with the increasing availability of more ethnically diverse reference data, and this is issue is more common for individuals of non-European ancestry. At the same time, a substantial percentage of variants are classified as of unknown significance (VUS), with inadequate data to prove or disprove a pathogenic association with a medical condition. Progress in interpreting genomic data, however, will lead to greater agreement on how to call variants that are currently subject to discrepant classifications and the question arises about how will that information about reclassification of variants reach patients and their health care providers. There is currently no definitive guidance from professional organizations or opinion leaders about how to handle variant reclassification, and the field seems uncertain how to respond. Stakeholders including laboratories, providers, patients, and payers likely have different perspectives and opinions. To provide an empirical foundation for this critical discussion and develop guidance for the field, we will conduct a series of activities including focus groups and online surveys with 3 key stakeholder groups: patients, providers, and the laboratories. We will have three working groups to define the legal, ethical, and economic aspects to consider and develop possible solutions. We will host an annual meeting with experts on genetics, clinical laboratory operations, reimbursement, health economists, regulatory and legal issues, and ethics, along with clinicians and patient advocates, to provide guidance for the project, to review the data and develop a set of options and a final set of recommendations to address this issue. We will seek input on possible solutions from stakeholders through an online survey and arrive at final recommendations that we will present to the genomics community and to board of the American College of Medical Genetics and Genomics to guide the adoption of an acceptable and responsible policy in for this rapidly changing area.

项目摘要 随着基因组序列数据的生成速度更快且成本更低，最重要的是 当今临床基因检测面临的挑战是变异分类。目前，有标记 临床实验室之间变异分类的差异，具有临床意义 29% 的变体解释存在差异。之前分类为的变体 随着种族多样性的增加，致病性现已被认为是良性的 参考数据，这个问题对于非欧洲血统的人来说更为常见。在 同时，很大一部分变体被归类为意义未知 （VUS），没有足够的数据来证明或反驳与医学的致病关联 健康）状况。然而，解释基因组数据的进展将导致就如何解释基因组数据达成更大的共识。 调用当前分类不一致的变体，并且出现以下问题 有关变异重新分类的信息将如何传达给患者及其医疗保健人员 提供商。目前尚无专业组织或意见的明确指导 领导者如何处理变体重新分类，而该领域似乎不确定如何处理 回应。包括实验室、提供者、患者和付款人在内的利益相关者可能有不同的看法 观点和意见。为这一批判性讨论提供实证基础 制定该领域的指导，我们将开展一系列活动，包括焦点小组和 与 3 个主要利益相关者群体进行的在线调查：患者、提供者和实验室。我们将 设立三个工作组来定义需要考虑和考虑的法律、道德和经济方面 制定可能的解决方案。我们将举办由遗传学、临床专家参加的年度会议 实验室操作、报销、健康经济学家、监管和法律问题以及道德规范， 与临床医生和患者倡导者一起，为项目提供指导，审查数据 并制定一套选项和一套最终建议来解决这个问题。我们将 通过在线调查征求利益相关者对可能解决方案的意见，并得出最终结论 我们将向基因组学界和美国委员会提出建议 医学遗传学和基因组学学院指导采用可接受的和 针对这个快速变化的领域制定负责任的政策。