ClinSeq - Clinical and Behavioral Aspects

ClinSeq - 临床和行为方面

• 批准号: 8948400
• 负责人: Leslie Biesecker
• 金额: $ 61.34万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8948400
• 关键词: American; Attitude; Baseline Surveys; Behavioral; Cardiomyopathies; Caring; Clinical; Clinical Medicine; Clinical Research; Data; Development; Disease; Foundations; Functional disorder; Genes; Genomics; Goals; Image; Incidental Findings; Malignant Neoplasms; Malignant hyperpyrexia due to anesthesia; Manuscripts; Measures; Medical; Medical Genetics; Medicine; Modeling; Molecular; Motivation; Online Systems; Participant; Pathogenicity; Pattern; Phenotype; Predisposition; Publications; Randomized Controlled Trials; Reaction; Recommendation; Research Personnel; Surveys; System; Technology; Test Result; Variant; arm; base; clinically significant; college; design; experience; falls; human disease; improved; interest; new technology; novel; research study

In FY2014 we have substantially advanced the goals and objectives for the ClinSeq clinical and behavioral project by performing the following ongoing substudies. Incidental findings. The topic of incidental findings has exploded onto the clinical and research agenda, to no small extent facilitated by the ClinSeq(c) study. In the prior periods, we piloted incidental findings by identifying cancer susceptibility variants (Johnston et al, 2012), cardiomyopathy and dysrhythmia variants (Ng et al, 2013) and malignant hyperthermia (Gonsalves et al, 2013). We have extending this into a broader project to explore all null variants (novel and known) in genes known to cause human disease in an autosomal dominant pattern and correlating this with phenotype. The analysis for this is completed and a draft manuscript has been submitted.. Indeed, the ClinSeq(c) experience substantially contributed to the recommendations issued by the American College of Medical Genetics on incidental findings (Green et al, 2013). Randomized controlled trial of return of results As sequencing technology is new, it is important to understand how the medical system can take up this technology. As an important foundation for understanding many related questions, we have developed an extensive survey of baseline attitudes towards this sequencing technology. This survey has been completed, analyzed, and a draft publication will be submitted this fall. Our major effort in this domain is that we have initiated a large (n=400), controlled experiment with experimental arms that vary the mode of return of results to compare the classical model of direct clinician interaction with a new mode of web-based results return. This experiment will be key to discovering efficient modes of return of results. We are currently accruing 10 participants per week for this study. We are also exploring participant reactions to variants of uncertain clinical significance. This is a major challenge in genomics and we have designed a trial where we will return variants of unknown significance either above or below the 50% threshold of likelihood of pathogenicity to gauge participant reactions to such variants, and measure their intentions to implement medical care based on these results.

2014 财年，我们通过进行以下正在进行的子研究，大幅推进了 ClinSeq 临床和行为项目的目的和目标。 偶然的发现。 偶然发现的话题已迅速进入临床和研究议程，这在很大程度上得益于 ClinSeq(c) 研究的推动。在之前的时期，我们通过识别癌症易感性变异（Johnston 等，2012）、心肌病和心律失常变异（Ng 等，2013）以及恶性高热（Gonsalves 等，2013）来试验偶然发现。我们已将其扩展为一个更广泛的项目，以探索已知以常染色体显性模式引起人类疾病的基因中的所有无效变异（新颖的和已知的），并将其与表型相关联。对此的分析已经完成，手稿草稿已提交。事实上，ClinSeq(c) 的经验对美国医学遗传学学院就偶然发现提出的建议做出了重大贡献（Green 等人，2013 年）。 结果返回的随机对照试验 由于测序技术是新技术，因此了解医疗系统如何采用该技术非常重要。作为理解许多相关问题的重要基础，我们对这种测序技术的基线态度进行了广泛的调查。 这项调查已经完成和分析，并将于今年秋季提交出版物草案。我们在这一领域的主要努力是，我们发起了一项大型（n=400）受控实验，其实验组改变了结果返回模式，以将直接临床医生交互的经典模型与基于网络的结果的新模式进行比较返回。该实验将是发现有效的结果返回模式的关键。我们目前每周招募 10 名参与者参与这项研究。 我们还在探索参与者对不确定临床意义的变异的反应。 这是基因组学中的一个重大挑战，我们设计了一项试验，我们将返回高于或低于致病性可能性阈值 50% 的未知意义的变异，以衡量参与者对此类变异的反应，并衡量他们实施基于医疗护理的意图。关于这些结果。