Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland.
JAMA Intern Med. 2018 Mar 1;178(3):338-346. doi: 10.1001/jamainternmed.2017.8049.
A critical bottleneck in clinical genomics is the mismatch between large volumes of results and the availability of knowledgeable professionals to return them.
To test whether a web-based platform is noninferior to a genetic counselor for educating patients about their carrier results from exome sequencing.
DESIGN, SETTING, AND PARTICIPANTS: A randomized noninferiority trial conducted in a longitudinal sequencing cohort at the National Institutes of Health from February 5, 2014, to December 16, 2016, was used to compare the web-based platform with a genetic counselor. Among the 571 eligible participants, 1 to 7 heterozygous variants were identified in genes that cause a phenotype that is recessively inherited. Surveys were administered after cohort enrollment, immediately following trial education, and 1 month and 6 months later to primarily healthy postreproductive participants who expressed interest in learning their carrier results. Both intention-to-treat and per-protocol analyses were applied.
A web-based platform that integrated education on carrier results with personal test results was designed to directly parallel disclosure education by a genetic counselor. The sessions took a mean (SD) time of 21 (10.6), and 27 (9.3) minutes, respectively.
The primary outcomes and noninferiority margins (δNI) were knowledge (0 to 8, δNI = -1), test-specific distress (0 to 30, δNI = +1), and decisional conflict (15 to 75, δNI = +6).
After 462 participants (80.9%) provided consent and were randomized, all but 3 participants (n = 459) completed surveys following education and counseling; 398 (86.1%) completed 1-month surveys and 392 (84.8%) completed 6-month surveys. Participants were predominantly well-educated, non-Hispanic white, married parents; mean (SD) age was 63 (63.1) years and 246 (53.6%) were men. The web platform was noninferior to the genetic counselor on outcomes assessed at 1 and 6 months: knowledge (mean group difference, -0.18; lower limit of 97.5% CI, -0.63; δNI = -1), test-specific distress (median group difference, 0; upper limit of 97.5% CI, 0; δNI = +1), and decisional conflict about choosing to learn results (mean group difference, 1.18; upper limit of 97.5% CI, 2.66; δNI = +6). There were no significant differences between the genetic counselors and web-based platform detected between modes of education delivery in disclosure rates to spouses (151 vs 159; relative risk [RR], 1.04; 95% CI, 0.64-1.69; P > .99), children (103 vs 117; RR, 1.07; 95% CI, 0.85-1.36; P = .59), or siblings (91 vs 78; RR, 1.17; 95% CI, 0.94-1.46; P = .18).
This trial demonstrates noninferiority of web-based return of carrier results among postreproductive, mostly healthy adults. Replication studies among younger and more diverse populations are needed to establish generalizability. Yet return of results via a web-based platform may be sufficient for subsets of test results, reserving genetic counselors for return of results with a greater health threat.
clinicaltrials.gov Identifier: NCT00410241.
临床基因组学的一个关键瓶颈是大量结果与能够解读这些结果的专业知识人员之间的不匹配。
测试基于网络的平台在向接受外显子组测序的患者传递携带者结果方面是否不劣于遗传咨询师。
设计、设置和参与者：这是一项在国立卫生研究院的纵向测序队列中进行的随机非劣效性试验，从 2014 年 2 月 5 日至 2016 年 12 月 16 日进行，旨在比较基于网络的平台与遗传咨询师。在 571 名符合条件的参与者中，1 至 7 个杂合变体在导致隐性遗传表型的基因中被识别。在队列入组后、试验教育后以及 1 个月和 6 个月后，对主要是有生育能力的、表示有兴趣了解自己携带者结果的、已绝经的参与者进行了调查。主要采用意向治疗和符合方案分析。
一个集成了携带者结果教育和个人检测结果的基于网络的平台被设计用来直接与遗传咨询师的披露教育相平行。这些课程分别需要平均（SD）21（10.6）和 27（9.3）分钟。
主要结果和非劣效性边界（δNI）：主要结局和非劣效性边界（δNI）是知识（0 到 8，δNI=−1）、特定测试的困扰（0 到 30，δNI=+1）和决策冲突（15 到 75，δNI=+6）。
在 462 名（80.9%）提供同意并随机分组的参与者中，除了 3 名（n=459）参与者在接受教育和咨询后完成了调查外，其余所有参与者均完成了调查；398 名（86.1%）参与者完成了 1 个月的调查，392 名（84.8%）参与者完成了 6 个月的调查。参与者主要是受过良好教育的、非西班牙裔白人、已婚的父母；平均（SD）年龄为 63（63.1）岁，246 名（53.6%）是男性。在 1 个月和 6 个月的评估中，网络平台与遗传咨询师相比是非劣效的：知识（平均组差异，−0.18；97.5%CI 的下限，−0.63；δNI=−1）、特定测试的困扰（中位数组差异，0；97.5%CI 的上限，0；δNI=+1）以及选择了解结果的决策冲突（平均组差异，1.18；97.5%CI 的上限，2.66；δNI=+6）。在披露率方面，遗传咨询师和网络平台之间没有检测到显著差异，向配偶（151 对 159；相对风险[RR]，1.04；95%CI，0.64-1.69；P>.99）、子女（103 对 117；RR，1.07；95%CI，0.85-1.36；P=0.59）或兄弟姐妹（91 对 78；RR，1.17；95%CI，0.94-1.46；P=0.18）。
这项试验表明，在已绝经、主要是健康的成年人中，基于网络的携带者结果传递是非劣效的。需要在更年轻和更多样化的人群中进行复制研究，以确立其普遍性。然而，通过基于网络的平台传递结果可能足以满足某些检测结果的需求，将遗传咨询师保留用于具有更大健康威胁的结果传递。
clinicaltrials.gov 标识符：NCT00410241。
