ABSTRACT: Importance:A critical bottleneck in clinical genomics is the mismatch between large volumes of results and the availability of knowledgeable professionals to return them. Objective: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. Interventions: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. Main Outcomes and Measures:The primary outcomes and noninferiority margins (?NI) were knowledge (0 to 8, ?NI?=?-1), test-specific distress (0 to 30, ?NI?=?+1), and decisional conflict (15 to 75, ?NI?=?+6). Results: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; ?NI?=?-1), test-specific distress (median group difference, 0; upper limit of 97.5% CI, 0; ?NI?=?+1), and decisional conflict about choosing to learn results (mean group difference, 1.18; upper limit of 97.5% CI, 2.66; ?NI?=?+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). Conclusions and Relevance: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. Trial Registration:clinicaltrials.gov Identifier: NCT00410241.
