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Session


Keywords: Electronic health records (EHRs); Genomics; Public health; Precision medicine; Translational studies and preclinical trials

Authors:
D. Kochan 1; E. Winkler 2; N. Lindor 3; G. Shaibi 4; J. Olson 5; P. Caraballo 6; R. Freimuth 7; J. Pacyna 8; C. Radecki-Breitkopf 8; R. Sharp 8; I. Kullo 1

Affiliations:
1) Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.; 2) Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.; 3) Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona.; 4) Center for Health Promotion and Disease Prevention, Arizona State University, Phoenix, Arizona.; 5) Department of Health Sciences Research - Epidemiology, Mayo Clinic, Rochester, Minnesota.; 6) Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.; 7) Department of Health Sciences Research - Digital Health Sciences, Mayo Clinic, Rochester, Minnesota; 8) Department of Health Sciences Research - Biomedical Ethics Program, Mayo Clinic, Rochester, MN.


Background: To inform best practices for returning actionable results to participants in genome sequencing studies, we describe challenges encountered and lessons learned from the Mayo Return of Actionable Variants Empiric (RAVE) study.

Methods: Participants (n = 2535, mean age 63±7, 57% female) ascertained based on hypercholesterolemia and/or colon polyps were sequenced for actionable genes (n=68) and single nucleotide variants (n=14). To participate, individuals had to consent to receive results related to hypercholesterolemia and colorectal cancer, but could opt out of receiving secondary findings. Participants with actionable results (n=121) were invited to schedule an appointment with a genetic counselor (GC). Neutral results (n=2414) were disclosed via mail. Results were placed in the electronic health record (EHR) following disclosure.

Results: Of those with actionable results, two opted out of receiving secondary findings and one participant died; 84 of 118 returnable results were returned in-person by a GC and 12 were returned via phone. Challenges in RoR could be categorized as: a) sequencing report-phenotype mismatch. These included three reports that were revised after review of the clinical record, and two reports requiring corrections. No gender mismatch was detected in those with actionable results (four were detected in those with neutral results). Three actionable results were probably mosaic requiring alternative DNA samples for confirmation. b) contacting participants: 16 participants were non-responders after four mailed letters. Of these five had previously identified clinically and were already documented in the EHR. In all 23 actionable results were already documented in the EHR. c) EHR integration of results. Ten results were disclosed to care providers prior to inviting the participant for a GC appointment, following an EHR workflow error. Five reports were reclassified due to modified informatics pipelines, four of which required participant re-contact and correction of the sequencing result in the EHR.

Conclusion: With the increasing number of large scale genome sequencing projects, there is a need for greater awareness of potential challenges in RoR. In our study, such challenges were encountered in a significant proportion (24%) of participants.