Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot
Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot
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DOI：
10.1016/j.ajhg.2018.07.018
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发表时间：
2018-09-06
影响因子：
9.8
通讯作者：
Biesecker, Leslie G.
中科院分区：
文献类型：
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作者：
Sapp, Julie C.;Johnston, Jennifer J.;Biesecker, Leslie G.
虽然关于在临床环境中恢复次级基因组发现的共识已经达成，但在研究环境中关于这样的发现的争论仍然存在。我们为研究外显子组数据开发了一种混合的研究-临床翻译基因组学过程，并结合了CLIA验证的二次发现分析。来自美国国立卫生研究院10个研究所的11名内部调查人员对这一过程进行了试验。对18名参与者的近1200名个体进行了测序，并确定了14项次要发现。阳性二次发现由遗传咨询师按照标准化方案返回，包括转介对参与者本地的二次发现进行专科后续护理。在收到积极报告4个月后，对13名参与者进行了面谈。这些参与者报告说，在吸收他们的结果的过程中，他们的心理痛苦最小。在13人中，9人报告获得了推荐的卫生保健服务。107名收到负面调查报告的参与者在收到报告4个月后进行了调查。他们对二次调查结果的阴性表现出很好的理解，大多数人对该报告表示放心(%)。然而，显著的少数人(高达17%)对主要和次要发现的区别表示困惑。这项试验表明，将符合CLIA的二次研究结果结合到研究测序中是可行的，损害最小。参与者处理了二次发现的惊喜，大多数人都跟踪了推荐的后续行动，但一些负面发现将二次发现和主要发现混为一谈。还需要额外的工作来了解后续护理的障碍，并帮助参与者区分二次发现和主要发现。
While consensus regarding the return of secondary genomic findings in the clinical setting has been reached, debate about such findings in the research setting remains. We developed a hybrid, research-clinical translational genomics process for research exome data coupled with a CLIA-validated secondary findings analysis. Eleven intramural investigators from ten institutes at the National Institutes of Health piloted this process. Nearly 1,200 individuals were sequenced and 14 secondary findings were identified in 18 participants. Positive secondary findings were returned by a genetic counselor following a standardized protocol, including referrals for specialty follow-up care for the secondary finding local to the participants. Interviews were undertaken with 13 participants 4 months after receipt of a positive report. These participants reported minimal psychologic distress within a process to assimilate their results. Of the 13, 9 reported accessing the recommended health care services. A sample of 107 participants who received a negative findings report were surveyed 4 months after receiving it. They demonstrated good understanding of the negative secondary findings result and most expressed reassurance (64%) from that report. However, a notable minority (up to 17%) expressed confusion regarding the distinction of primary from secondary findings. This pilot shows it is feasible to couple CLIA-compliant secondary findings to research sequencing with minimal harms. Participants managed the surprise of a secondary finding with most following recommended follow up, yet some with negative findings conflated secondary and primary findings. Additional work is needed to understand barriers to follow-up care and help participants distinguish secondary from primary findings.