ClinSeq - Clinical and Behavioral Aspects

在2013财年，我们通过执行以下正在进行的子研究，大幅推进了ClinSeq(C)临床和行为项目的目标和目标。 偶然发现。 偶然发现的话题已经迅速进入临床和研究议程，这在很大程度上受到ClinSeq(C)研究的推动。在之前的一段时间里，我们通过在ClinSeq(C)参与者中识别癌症易感性变异来试点偶然发现(Johnston等人，2012年)。在此期间，我们扩大了这一努力，将其扩展到一个关于心肌病和心律失常变体的新项目(Ng等人，在出版社)和第二个关于恶性体温过高的项目(Gonsalves等人，在出版社)。我们正在将其扩展到一个更广泛的项目中，以常染色体显性模式探索已知的导致人类疾病的基因中的所有零变异(新的和已知的)，并将其与表型相关联。该项目将延长至下一个报告期。事实上，ClinSeq(C)的经验在很大程度上促进了美国医学遗传学学院发布的关于偶然发现的建议(Green等人，2013年)。 调查参与者的态度和知情同意。 由于测序技术是一项新技术，了解患者将如何理解和采用这项技术是很重要的。为此，我们对参与者进行了调查，以了解参与研究的动机(Facio等人，2012a)和获得结果的意图(Facio等人2012b)。我们还对他们进行了调查，以衡量他们的理解深度，这是相当高的(Kaffingst等人，2013年)。最后，我们写了一篇理论论文，为ClinSeq(C)等研究提出了一种新的知情同意方法，这些研究为临床研究生成了假设(Facio等人，2013年)。在接下来的一年里，我们对这项测序技术的基线态度进行了广泛的调查。 返回结果。 我们目前正在确定参与者中已知的致病基因变异。对于已知的显性特征，我们将按确定的方式返回这些特征，并对参与者进行定性访谈，以评估他们的反应和他们计划如何使用结果。此外，我们正在计划一项大型的对照实验，实验臂改变结果的返回模式，以比较传统的临床医生直接交互模式和基于网络的结果返回的新模式。

In FY2013 we have substantially advanced the goals and objectives for the ClinSeq(c) 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 period, we piloted incidental findings by identifying cancer susceptibility variants in ClinSeq(c) participants (Johnston et al, 2012). In this period, we have expanded this effort by extending it into a new project on cardiomyopathy and dysrhythmia variants (Ng et al, In Press) and a second project on malignant hyperthermia (Gonsalves et al, In Press). We are 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. This project will extend into the next reporting period. 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). Surveying participant attitudes and informed consent. As sequencing technology is new, it is important to understand how patients will understand and take up this technology. To that end, we have surveyed our participants to understand the motivations for participating in the study (Facio et al, 2012a) and the intentions to receive results (Facio et al 2012b). We have also surveyed them to gauge the depth of their understanding, which was quite high (Kaphingst et al., 2013). Finally, we have written a theoretical paper that proposes a novel approach to informed consent for studies like ClinSeq(c), which generate hypotheses for clinical research (Facio et al, 2013). For the upcoming year, we have developed an extensive survey of baseline attitudes towards this sequencing technology. Return of results. We are currently identifying known pathogenic gene variants in our participants. For the known dominant traits, we are returning those as they are identified and are performing qualitative interviews on the participants to gauge their reactions and how they plan to use the results. In addition, we are planning a large, 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.