Ethical Considerations Related to Return of Results from Genomic Medicine Projects: The eMERGE Network (Phase III) Experience

Fossey, Robyn; Kochan, David C.; Winkler, Erin; Pacyna, Joel E.; Olson, Janet E.; Thibodeau, Stephen N.; Connolly, John J.; Harr, Margaret; Behr, Meckenzie; Prows, Cynthia A.; Cobb, Beth L.; Myers, Melanie F.; Leslie, Nancy; Namjou‐Khales, Bahram; Rasouly, Hila Milo; Wynn, Julia; Fedotov, Alexander; Chung, Wendy K.; Gharavi, Ali G.; Williams, Janet L.; Pais, Lynn; Holm, Ingrid A.; Aufox, Sharon; Smith, Maureen E.; Scrol, Aaron; Leppig, Kathleen A.; Jarvik, Gail P.; Wiesner, Georgia L.; Li, Rongling; Stroud, Mary; Smoller, Jordan W.; Sharp, Richard R.; Kullo, Iftikhar J.

doi:10.3390/jpm8010002

Cited by 46 publications

(44 citation statements)

References 30 publications

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“…Each clinical site had custom requirements for the report content, that reflected local preferences for data to be returned to patients. Each SC also had different reporting requirements – for example, some sites requested negative reports, others only returned positive reports 16 . Most sites also requested data in structured formats to enable direct integration onto their local EHRs.…”

Section: Resultsmentioning

confidence: 99%

Harmonizing Clinical Sequencing And Interpretation For The Emerge III Network

Zouk

Lennon

Rehm

et al. 2018

Preprint

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36Background: The eMERGE III Network was tasked with harmonizing genetic testing protocols linking multiple 37 sites and investigators. 38Methods: DNA capture panels targeting 109 genes and 1551 variants were constructed by two clinical 39 sequencing centers for analysis of 25,000 participant DNA samples collected at 11 sites where samples were 40 linked to patients with electronic health records. Each step from sample collection, data generation, 41 interpretation, reporting, delivery and storage, were developed and validated in CAP/CLIA settings and 42 harmonized across sequencing centers. 43Results: A compliant and secure network was built and enabled ongoing review and reconciliation of clinical 44 interpretations while maintaining communication and data sharing between investigators. Mechanisms for 45 sustained propagation and growth of the network were established. An interim data freeze representing 15,574 46 sequenced subjects, informed the assay performance for a range of variant types, the rate of return of results 47Conclusions: This study established processes for different sequencing sites to harmonize the technical and 51 interpretive aspects of sequencing tests, a critical achievement towards global standardization of genomic 52 testing. The network established experience in the return of results and the rate of secondary findings across 53 diverse biobank populations. Furthermore, the eMERGE network has accomplished integration of structured 54 genomic results into multiple electronic health record systems, setting the stage for clinical decision support to 55 enable genomic medicine. 56 57 58 59 60 61 62The identification, interpretation and return of actionable clinical genetic findings is an increasing focus of 63 precision medicine. There is also growing awareness that the discovery of genes underlying human diseases is 64 dependent upon access to samples from carefully phenotyped individuals with (and without) clinical conditions. 65As clinical visits provide the ideal opportunity to record patient phenotypes, with appropriate consent, the medical 66 care of specific patient groups can drive the accumulation of clinical data and knowledge of the genetic 67 underpinnings of disease and the penetrance of DNA risk variants. This 'virtuous cycle' of data flow from the 68 bench to the bedside and back to the bench will be a key driver of progress in genetic and genomic translation. 69 70 While conceptually straightforward, there are many challenges that must be overcome for integrating clinical and 71 research agendas across global populations. Clinical visits are often brief, focused upon measurement related 72 to specific symptoms and constrained by fiscal and practical concerns. On the other hand, ascertainment for 73research is often open ended, longitudinal, and accompanied by rigorous consent procedures. The types of data 74 that are recorded for each purpose can be different in both depth and quality. As a result, ideal research and 75 clinical records often diverge. 76 77A second group of ...

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Section: Resultsmentioning

confidence: 99%

Harmonizing Clinical Sequencing And Interpretation For The Emerge III Network

Zouk

Lennon

Rehm

et al. 2018

Preprint

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“…An iterative process with the Mayo Clinic IRB led to approvals for English and Spanish documents and procedures that occurred outside of the academic institution. 17 A list of potentially eligible individuals who participated in the SPS Biobank (N=1621) with phenotypes of interest (hyperlipidemia and/or colorectal neoplasia) was generated. From this list, 500 participants provided written informed consent for sequencing their DNA, returning results, and scanning results into their electronic health record (EHR).…”

Section: Methodsmentioning

confidence: 99%

Returning genomic results in a Federally Qualified Health Center: the intersection of precision medicine and social determinants of health

Shaibi

Kullo

Singh

et al. 2020

Genetics in Medicine

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Purpose: This report describes the return of sequencing results to low-income Latino participants recruited through a Federally Qualified Health Center (FQHC). We describe challenges in returning research results secondary to social determinants of health and present lessons learned to guide future genomic medicine implementation studies in low resource settings. Methods: 500 Latino adults (76% women) consented to research sequencing for a predetermined panel of actionable genes. Providers and staff from the FQHC were engaged to align processes with the practice and a Community Advisory Board grounded the project in the local community. Results: A pathogenic/likely pathogenic variant was present in 10 participants (2%). Challenges in return of results included the time lag (582±53 days) between enrollment and returning actionable results, difficulty reaching participants, missed appointments, low health literacy, lack of health insurance, and reconciling results with limited information on family history. Return of one actionable result was deferred due to acute emotional distress secondary to recent traumatic life events. Conclusion: The social determinants of health influence the implementation of genomic medicine in low-income populations in low-resource settings. Considering non-biological factors that contribute to disparities will be necessary to better appreciate how genomic medicine may fit within the context of health equity.

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“…Although the ethical, legal, and social implications of genomic RoR from research studies have been described [2][3][4] , little is known about the extent to which challenges may be encountered when conducting return of clinical genomic findings in large research cohorts such as biobanks. To address this gap in knowledge, the eMERGE Network is conducting several genomic medicine implementation studies which involve RoR from a targeted sequencing panel at each of the ten Network sites 5 . These eMERGE Network studies straddle the boundary between research and clinical practice, and as such, may offer valuable insights into the RoR process in population scale genome sequencing efforts.…”

Section: Introductionmentioning

confidence: 99%

“…At the Mayo Clinic, an eMERGE Network site, the Return of Actionable Variants Empiric (RAVE) study 5,6 aimed to characterize challenges related to genomic RoR and help establish basic guidance for RoR in large-scale genomic sequencing projects. Participants were recruited from Mayo Clinic biobanks in Rochester, Minnesota and Phoenix, Arizona on the basis of hypercholesterolemia and/or colon polyps to enrich for familial hypercholesterolemia (FH) and hereditary colorectal cancer-two conditions labeled by the Office of Public Health Genomics, Centers for Disease Control and Prevention 7 as Tier 1 genomic applications due to the potential for positive impact on public health based on available evidence-based guidelines and recommendations 8 .…”

Section: Introductionmentioning

confidence: 99%

Challenges in returning results in a genomic medicine implementation study: the Return of Actionable Variants Empirical (RAVE) study

et al. 2020

Self Cite

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To inform the process of returning results in genome sequencing studies, we conducted a quantitative and qualitative assessment of challenges encountered during the Return of Actionable Variants Empiric (RAVE) study conducted at Mayo Clinic. Participants (n = 2535, mean age 63 ± 7, 57% female) were sequenced for 68 clinically actionable genes and 14 single nucleotide variants. Of 122 actionable results detected, 118 were returnable; results were returned by a genetic counselor-86 in-person and 12 by phone. Challenges in returning actionable results were encountered in a significant proportion (38%) of the cohort and were related to sequencing and participant contact. Sequencing related challenges (n = 14), affecting 13 participants, included reports revised based on clinical presentation (n = 3); reports requiring corrections (n = 2); mosaicism requiring alternative DNA samples for confirmation (n = 3); and variant re-interpretation due to updated informatics pipelines (n = 6). Participant contact related challenges (n = 44), affecting 38 participants, included nonresponders (n = 20), decedents (n = 1), and previously known results (n = 23). These results should be helpful to investigators preparing for return of results in large-scale genomic sequencing projects.

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Ethical Considerations Related to Return of Results from Genomic Medicine Projects: The eMERGE Network (Phase III) Experience

Cited by 46 publications

References 30 publications

Harmonizing Clinical Sequencing And Interpretation For The Emerge III Network

Harmonizing Clinical Sequencing And Interpretation For The Emerge III Network

Returning genomic results in a Federally Qualified Health Center: the intersection of precision medicine and social determinants of health

Challenges in returning results in a genomic medicine implementation study: the Return of Actionable Variants Empirical (RAVE) study

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