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Confronting real time ethical, legal, and social issues in the Electronic Medical Records and Genomics (eMERGE) Consortium

2010; Elsevier BV; Volume: 12; Issue: 10 Linguagem: Inglês

10.1097/gim.0b013e3181efdbd0

1530-0366

Ellen Wright Clayton, Maureen E. Smith, Stephanie M. Fullerton, Wylie Burke, Catherine A. McCarty, Barbara A. Koenig, Amy L. McGuire, Laura M. Beskow, Lynn G. Dressler, Amy A. Lemke, Erin M. Ramos, Laura Lyman Rodriguez,

BRCA gene mutations in cancer

Increasingly, genomic research is being conducted through large, multi-site consortia. For example, the Electronic Medical Records and Genomics (eMERGE) Consortium was funded by the National Human Genome Research Institute to evaluate the scientific feasibility and potential value of performing genome wide association studies (GWAS) using information from electronic medical records together with hundreds of thousands of single nucleotide polymorphisms from samples obtained in the course of existing cohort studies, biorepositories, or from residual tissue or blood samples. This experiment, if successful, will enable a vast amount of research, especially because more and more medical information is stored electronically and as the cost of genotyping and sequencing decreases. However, the ability to use existing clinical information and samples for GWAS, while exciting, raises a number of ethical, legal, social, and policy issues. Examples of some of the issues raised by this type of research include the following: What sort of consent, if any, is required for such research? When might it be necessary to obtain new consent for the use of previously collected samples? Recognizing the value and the cost of obtaining such rich clinical and genetic variation data, and the desirability of combining datasets to permit more robust analysis, the National Institutes of Health (NIH) has strongly encouraged GWAS funded by the NIH, including the eMERGE data, be placed in a central repository called the database of Genotypes and Phenotypes (dbGaP) for use by other qualified investigators.1.National Institutes of Health. Policy for sharing of data obtained in NIH supported or conducted Genome-Wide Association Studies (GWAS). Available at: http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html. Accessed July 31, 2009.Google Scholar To what extent should patients and research participants be able to opt out of having their data shared with the broader research community through government-sponsored databases such as dbGaP? When diverse data sources are combined and then shared beyond the originating institutions, the abilities of investigators or biorepository managers to protect participants' interests, including privacy, necessarily change. Given this shift, do the obligations of those who originally collected samples change, and if so, how? Should investigators' obligations differ depending on whether data and samples come from patients seeking routine care or from participants in a pre-existing research project? When, if ever, should research results, either aggregate or individual, be returned to participants? What about incidental findings? And what role should communities play in long-term oversight and governance of these projects? To address these, and related concerns, each eMERGE site was required to bring together genetic researchers and ethical, legal, and social implications (ELSI) investigators to address the ethical and social challenges of such research. Building an ethics component into large scientific studies provides an opportunity for transdisciplinary ELSI research that is immediately responsive to the emerging issues raised by scientific innovation, an approach that is becoming more common in genomics research.2.National Institutes of Health. Human microbiome project. Available at: http://nihroadmap.nih.gov/hmp/. Accessed July 19, 2010.Google Scholar, 3.NHLBI. NHLBI large-scale DNA sequencing project population studies. 2009. Available at: http://www.nhlbi.nih.gov/recovery/media/NHLBI_DNA_cohorts.htm. Accessed April 21, 2010.Google Scholar, 4.International HapMap Consortium Integrating ethics and science in the International HapMap Project.10.1038/nrg1351Nat Rev Genet. 2004; 5: 467-475Google Scholar The eMERGE Consortium provides a particularly rich landscape in which to pursue such research. The five partner institutions are examining data from a variety of populations that differ in their demographic characteristics, the ways they were recruited, and in the depth and stability of their relationships with the particular research team and institution (Table 1). Each eMERGE site includes investigators who bring particular disciplinary perspectives and approaches to studying the implications of using information from electronic medical records for GWAS (Table 1). (Additional information about each member site and its research can be found at www.gwas.net).Table 1eMERGE sites and ELSI activities Open table in a new tab To maximize what can be learned from the diverse eMERGE research settings, ELSI investigators are not only conducting transdisciplinary research at their own institutions but have also joined together in a Consent and Community Consultation (C&CC) Working Group to share strategies and results and to collaborate on ethical issues and policy related to the conduct of GWAS. To facilitate this work, a number of prominent investigators from non-eMERGE institutions were invited to join the C&CC Working Group. Their names and affiliations are listed at the end of this article. The larger group quickly organized a number of smaller groups to focus on key, cross-cutting topics. The current groups, their leadership, and their goals follow are detailed below. Communities have been involved to greater and lesser degrees in the governance, planning, and oversight of genetics and genomics research for many years,5.Foster M.W. Eisenbraun A.J. Carter T.H. Communal discourse as a supplement to informed consent for genetic research.1:CAS:528:DyaK2sXntVSgtLo%3D10.1038/ng1197-277Nat Genet. 1997; 17: 277-279Google Scholar, 6.Foster M.W. Sharp R.R. Freeman W.L. Chino M. Bernsten D. Carter T.H. The role of community review in evaluating the risks of human genetic variation research.1:STN:280:DyaK1M3msVamtg%3D%3D10.1086/302415Am J Hum Genet. 1999; 64: 1719-1727Google Scholar, 7.Sharp R.R. Foster M.W. Involving study populations in the review of genetic research.1:STN:280:DC%2BD3M%2Fgsl2qsA%3D%3D10.1111/j.1748-720X.2000.tb00315.xJ Law Med Ethics. 2000; 28: 41-51Google Scholar, 8.Sharp R.R. Foster M.W. 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Community engagement in genetic research: results of the first public consultation for the Quebec CARTaGENE project.17575459Community Genet. 2007; 10: 147-158Google Scholar including prominently in the International HapMap Project.4.International HapMap Consortium Integrating ethics and science in the International HapMap Project.10.1038/nrg1351Nat Rev Genet. 2004; 5: 467-475Google Scholar,11.International HapMap Consortium Community engagement and informed consent in the International HapMap project.17575464Community Genet. 2007; 10: 186-198Google Scholar The different eMERGE sites are using a broad range of community engagement approaches, ranging from surveys and focus groups to assess a priori values and concerns, to engagements based on deliberative democracy theories, to studies of population attitudes toward various issues in EMR-linked biobanks, and finally, to creating mechanisms for community involvement in biobank design and oversight based on empirical research findings fully integrated into normative analysis.12.Marshfield Clinic PMRP Community Advisory Group Community consultation and communication for a population-based DNA biobank: the Marshfield clinic personalized medicine research project.10.1002/ajmg.a.32559Am J Med Genet A. 2008; 146A: 3026-3033Google Scholar Although data sharing has always been part of the scientific ethos, it has been particularly important in genomics research.13.Collins F.S. Morgan M. Patrinos A. The Human Genome Project: lessons from large-scale biology.1:CAS:528:DC%2BD3sXislyqtb0%3D10.1126/science.1084564Science. 2003; 300: 286-290Google Scholar,14.Common consent. Nature 2009; 460: 933.Google Scholar eMERGE investigators are working together to establish agreed on best practices for sharing genotype data linked to clinical information in the electronic health record, both interinstitutionally within the consortium and also more broadly with other investigators through dbGaP. They are also examining research participants' attitudes about these policies, what concerns they have, and what protections they desire.15.Lemke A.A. Wolf W. Hebert-Beirne J. Smith M. Public and biobank attitudes toward genetic research participation and data sharing.1:STN:280:DC%2BC3cfgtFWjtQ%3D%3D10.1159/000276767Public Health Genomics. 2010; 13: 368-377Google Scholar Brad Malin has been developing empirical measures of the risk of reidentification within eMERGE, particularly with regard to clinical information. He is also examining the risk of reidentification when individuals within institutions compare clinical records with research datasets as well as the efficacy of data use agreements and data access tracking in preventing reidentification and misuse of information. The Working Group will develop policy recommendations in light of these measures. Drawing on examples of existing consent language, including some that has been the subject of empirical research22.Beskow L.M. Dean E. 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Accessed October 7, 2009.Google Scholar this group drafted model language to describe the major issues posed by GWAS and related genomic studies, which can be found at http://www.genome.gov/27526660. Model language addresses the purpose of the biobank; procedures for the collection of biospecimens and data; duration of storage; data sharing; recontact; risks and benefits; privacy protections; costs and payments; commercialization; participants' access to individual and aggregate research results; and the ability to withdraw. The group also developed optional wording so that the language can be customized depending on the underlying policies and procedures for a particular study. Institutional review boards (IRBs) around the country are struggling to comply with NIH requirements that the procedures used in initial data collection and interaction with human participants have been reviewed by an IRB or privacy board and an institutional official from the submitting institution has provided verification that the NIH submission criteria has been met.26.National Institutes of Health. NIH points to consider for IRBs and Institutions in their review of data submission plans for Institutional Certifications under NIH's policy for sharing of data obtained in NIH Supported or Conducted Genome-Wide Association Studies (GWAS). 2007. Available at: http://grants.nih.gov/grants/gwas/gwas_ptc.pdf. Accessed July 19, 2010.Google Scholar,27.National Human Genome Research Institute. 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Disclosing individual results of clinical research: implications of respect for participants.1:CAS:528:DC%2BD2MXnslKqsb0%3D10.1001/jama.294.6.737JAMA. 2005; 294: 737-740Google Scholar with empirical studies of participants' preferences, and the experience of scientists and clinicians participating in other GWAS consortia, such as GENEVA,43.Office of Population Genomics National Human Genome Research Institute. Research programs. 2009. Available at: http://www.genome.gov/27530162. Accessed October 19, 2009.Google Scholar to identify relevant principles and develop a framework for considering the return individual results in different research settings. In addition, a Return of Results oversight group, headed by Gail Jarvik, is deciding how best to handle specific results generated from Consortium research that may be clinically relevant, including sex chromosome anomalies discovered by the routine quality control processes common to the analysis of GWAS data. The C&CC Working Group, working with eMERGE scientists and actively engaging across institutions, is aiding translational research by considering an array of vital conceptual concerns while simultaneously meeting practical challenges. It is our hope that eMERGE will make significant contributions to the national discussion about longstanding ethical, legal, social, and policy issues posed by the unprecedented new uses of clinical and genetic information, recognizing that if ethically and socially acceptable research practices are not adopted, opportunities to apply the tools of genomics to human health and disease will be hindered. The eMERGE Network was initiated and supported by NHGRI, in conjunction with additional funding from NIGMS through the following Grants: U01-HG-004610 (Group Health Cooperative); U01-HG-004608 (Marshfield Clinic); U01-HG-04599 (Mayo Clinic); U01HG004609 (Northwestern University); U01-HG-04603 (Vanderbilt University, also serving as the Administrative Coordinating Center). The members of the Working Group include from the eMERGE Consortium—Group Health Cooperative/University of Washington: Wylie Burke, Stephanie M. Fullerton, Gail P. Jarvik, Evette Ludman, and Susan B. Trinidad; Marshfield Clinic: Catherine McCarty and Norman C. Fost; Mayo Clinic: Barbara Koenig, Joel Wu, Leah Eisenberg, and Joan Henriksen Hellyer; Northwestern University: Maureen Smith, Amy A. Lemke, and Wendy Wolf; Vanderbilt University: Ellen Wright Clayton, Bradley Malin, and Kyle Brothers. Members from other institutions who were asked specifically to participate in this Working Group include Amy L. McGuire (Baylor College of Medicine); Laura Beskow (Duke University); Carol Somkin (Kaiser Permanente Northern California); Amy Lam (Kaiser Division of Research); Ben Wilfond and Holly Tabor (Seattle Children's Hospital); Lynn Dressler and Gail Henderson (University of North Carolina). Representatives of National Human Genome Research Institute include Laura Lyman Rodriguez, Erin Ramos, and Teri Manolio. Disclosure: The authors declare no conflict of interest.