Returning negative results from large‐scale genomic screening: Experiences from the eMERGE III network

Abstract

Population‐based genomic screening has the potential to improve health outcomes by identifying genetic causes of disease before they occur. While much attention has been paid to supporting the needs of the small percentage of patients who will receive a life‐altering positive genomic screening result that requires medical attention, little attention has been given to the communication of negative screening results. As there are currently no best practices for returning negative genomic screening results, we drew on experiences across the electronic medical records and genomics (eMERGE) III Network to highlight the diversity of reporting methods employed, challenges encountered in reporting negative test results, and “lessons learned” across institutions. A 60‐item survey that consisted of both multiple choice and open‐ended questions was created to gather data across institutions. Even though institutions independently developed procedures for reporting negative results, and had very different study populations, we identified several similarities of approach, including but not limited to: returning results by mail, placing results in the electronic health record via an automated process, reporting results to participants' primary care provider, and providing genetic counseling to interested patients at no cost. Differences in procedures for reporting negative results included: differences in terminology used to describe negative results, definitions of negative results, guidance regarding the meaning of negative results for participants and their family members, and recommendations for clinical follow up. Our findings highlight emerging practices for reporting negative genomic screening results and highlight the need to create patient education and clinical support tools for reporting negative screening results.

Research participants' perspectives about the return of uninformative genomic test results in a clinical research setting

“…Our data suggest that these features of the research environment may introduce specific challenges to the return of results process. Our findings support the conclusion that these aspects of research sequencing may need to be described in plain language materials to accompany uninformative test reports that often include technical jargon (Finn et al, 2021).…”

“…One prior multi-site study found that the most common approach is to return uninformative results to patients via postal mail or secure email without genetic counseling by default. Differences in procedures for returning these results included: variations in terminology used to describe "negative" or uninformative results, differing guidance regarding the meaning of these results for participants and their family members, and varied recommendations for clinical follow-up (Finn et al, 2021). Recent surveys conducted in patients with colon polyps or hypercholesterolemia suggested that when uninformative results are returned to patients by mail without counseling, roughly one-third of patients will erroneously infer a lowered risk of disease based on this information, with almost twice as many women as men lowering their perception of disease risk (Stuttgen, Pacyna, Beck, et al, 2020).…”

Studying the impact of translational genomic research: Lessons from eMERGE

“… 58 In addition, one site returned variants of uncertain significance (VUSs) for one disorder. Negative results were returned to participants at some sites, 64 , 65 , 66 and one site returned carrier status. 35 Sites also varied in whether they re-interpreted results over time in light of new information about clinical significance.…”

“…There was much greater variation across sites in how negative results were returned. 24 , 66 While recipients who were informed that they did not have actionable results were generally content with the process, 77 some of the respondents incorrectly felt that they had less or no residual risk. 74 , 77 …”

The reckoning: The return of genomic results to 1444 participants across the eMERGE3 Network

“…For example, 1 site disclosed heterozygous status for common autosomal recessive conditions, 4 sites disclosed pharmacogenomic information, and 6 sites disclosed null result information. 12 Variants of uncertain significance were disclosed for colorectal cancer at the KPWA/UW site in conjunction with enhanced recruitment at that site for participants with colorectal cancer and colon polyps. Sequencing laboratories began releasing results to clinical sites in November 2017, and for the purposes of this report, were considered complete as of April 2020 (see eMERGE Clinical Annotation Working Group 13 for details on distribution of returned findings).…”