Understanding the Return of Genomic Sequencing Results Process: Content Review of Participant Summary Letters in the eMERGE Research Network

A challenge in returning genomic test results to research participants is how best to communicate complex and clinically nuanced findings to participants in a manner that is scalable to the large numbers of participants enrolled. The purpose of this study was to examine the features of genetic results letters produced at each Electronic Medical Records and Genomics (eMERGE3) Network site to assess their readability and content. Letters were collected from each site, and a qualitative analysis of letter content and a quantitative analysis of readability statistics were performed. Because letters were produced independently at each eMERGE site, significant heterogeneity in readability and content was found. The content of letters varied widely from a baseline of notifying participants that results existed to more detailed information about positive or negative results, as well as materials for sharing with family members. Most letters were significantly above the Centers for Disease Control-suggested reading level for health communication. While continued effort should be applied to make letters easier to understand, the ongoing challenge of explaining complex genomic information, the implications of negative test results, and the uncertainty that comes with some types of test and result makes simplifying letter text challenging

Harmonizing Outcomes for Genomic Medicine: Comparison of eMERGE Outcomes to ClinGen Outcome/Intervention Pairs

Genomic medicine is moving from research to the clinic. There is a lack of evidence about the impact of genomic medicine interventions on health outcomes. This is due in part to a lack of standardized outcome measures that can be used across different programs to evaluate the impact of interventions targeted to specific genetic conditions. The eMERGE Outcomes working group (OWG) developed measures to collect information on outcomes following the return of genomic results to participants for several genetic disorders. These outcomes were compared to outcome intervention pairs for genetic disorders developed independently by the ClinGen Actionability working group (AWG). In general, there was concordance between the defined outcomes between the two groups. The ClinGen outcomes tended to be from a higher level and the AWG scored outcomes represented a subset of outcomes referenced in the accompanying AWG evidence review. eMERGE OWG outcomes were more detailed and discrete, facilitating a collection of relevant information from the health records. This paper demonstrates that common outcomes for genomic medicine interventions can be identified. Further work is needed to standardize outcomes across genomic medicine implementation projects and to make these publicly available to enhance dissemination and assist in making precision public health a reality

Lessons learned from the eMERGE Network: balancing genomics in discovery and practice

The Electronic Medical Records and Genomics (eMERGE) Network, established in 2007, is a consortium of academic and integrated health systems conducting discovery and implementation research in translational genomics. Here, we outline the history of the network, highlight major impacts and lessons learned, and present the tools and resources developed for large-scale genomic analyses and translation into a clinical setting. The network developed methods to extract phenotypes from the electronic medical record to perform genome-wide and phenome-wide association studies. Recruited cohorts were clinically sequenced off a custom panel for targeted sequencing of variants and monogenic disease risks and returned to participants to investigate the impact of return of genomic results. After generating a 105,000 participant-imputed genome-wide association study (GWAS) dataset for discovery, the network enrolled and sequenced 24,998 participants. Integration of these results into the medical record and the effects of results on participants provided key lessons to the field. These learned lessons inform genetic research in diverse populations and provide insights into the clinical impact of return and implementation of genomic medicine using the electronic medical record. The lessons produced by the eMERGE Network can be utilized by other consortia as translational genomic medicine research evolves