A Model for Genome-First Care: Returning Secondary Genomic Findings to Participants and Their Healthcare Providers in a Large Research Cohort

Abstract

There is growing interest in communicating clinically relevant DNA sequence findings to research participants who join projects with a primary research goal other than the clinical return of such results. Since Geisinger's MyCode Community Health Initiative (MyCode) was launched in 2007, more than 200,000 participants have been broadly consented for discovery research. In 2013 the MyCode consent was amended to include a secondary analysis of research genomic sequences that allows for delivery of clinical results. Since May 2015, pathogenic and likely pathogenic variants from a set list of genes associated with monogenic conditions have prompted "genome-first" clinical encounters. The encounters are described as genome-first because they are identified independent of any clinical parameters. This article (1) details our process for generating clinical results from research data, delivering results to participants and providers, facilitating condition-specific clinical evaluations, and promoting cascade testing of relatives, and (2) summarizes early results and participant uptake. We report on 542 participants who had results uploaded to the electronic health record as of February 1, 2018 and 291 unique clinical providers notified with one or more participant results. Of these 542 participants, 515 (95.0%) were reached to disclose their results and 27 (5.0%) were lost to follow-up. We describe an exportable model for delivery of clinical care through secondary use of research data. In addition, subject and provider participation data from the initial phase of these efforts can inform other institutions planning similar programs.

Healthcare Utilization and Costs after Receiving a Positive BRCA1/2 Result from a Genomic Screening Program

“…The study population was identified from the Geisinger MyCode®Community Health Initiative (MyCode) where adult volunteers from an integrated healthcare delivery system in central Pennsylvania underwent exome sequencing using research protocols detailed in previous publications [1,[18][19][20]. The study cohort was based on a population of 50,726 MyCode participants whose exome sequences were complete, were analyzed to identify potential P/LP variants, and had clinical confirmation of the research result with a report to the EHR to disclose the results between 01/01/2014 and 03/01/2016 [20].…”

Precision Medicine Advancements Using Whole Genome Sequencing, Noninvasive Whole Body Imaging, and Functional Diagnostics

“…All participants underwent a verbal review of the IRB-approved consent (Western IRB). Study results were returned to participants (within [10][11][12] weeks after the visit), who were encouraged to involve their primary care physicians. Additional details of this study can be found in Perkins et al, 2018 20 .…”

“…DiscovEHR findings also showed that ~65% of individuals who carry a pathogenic variant had associated phenotypes observed in their medical records 8 . The initial insights into the delivery of genomic knowledge and approaches for clinical decision and clinical care also have been discussed 9,10,11,12 .…”

Family History Assessment Significantly Enhances Delivery of Precision Medicine in the Genomics Era

“…Several screening programs are initiating genomic sequencing for healthy or unselected populations, irrespective of health status or family history. [3][4][5][6][7][8][9] Amongst these population screening programs there is consensus to return genomic results which are medically significant however there is less concordance regarding which genes fall into this category.…”

“…Some cohort studies collect a three-four generation pedigree at recruitment, 3,10 while others gather family history once a clinically significant genomic variant is detected. 6,8,9 There is emerging evidence that in unselected populations, 48%-60% of individuals identified as having a clinically actionable variant have no associated family history. 8,9,11 A case control study observed a similar prevalence of Ashkenazi Jewish BRCA founder variants amongst individuals with and without breast cancer in their family 12 , and a more recent study found the frequency of clinically actionable variants was similar amongst breast cancer patients who met and did not meet clinical criteria for genetic testing.…”