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 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.2–4 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).
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.
Community engagement (Barbara Koenig, Joel Wu, and Amy Lemke)
Communities have been involved to greater and lesser degrees in the governance, planning, and oversight of genetics and genomics research for many years,5–10 including prominently in the International HapMap Project.4,11 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
Data sharing (Amy McGuire)
Although data sharing has always been part of the scientific ethos, it has been particularly important in genomics research.13,14 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
Identifiability of DNA and electronic medical record data (Brad Malin)16–21
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.
Informed consent (Laura Beskow)
Drawing on examples of existing consent language, including some that has been the subject of empirical research22–24 and best practice guidelines,25 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 (Maureen Smith)
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.26,27 The eMERGE IRB group, working with investigators at NHGRI Centers of Excellence in ELSI Research at Case Western Reserve University and the University of Washington, surveyed IRB professionals to learn about their practices and challenges in genomic research review.28 This broader group of investigators will develop best practices for the review of GWAS and obtaining certification for data sharing as well as educational materials of IRBs.
Return of results (Malia Fullerton and Wylie Burke)
This group is bringing together literature review29–42 with empirical studies of participants' preferences, and the experience of scientists and clinicians participating in other GWAS consortia, such as GENEVA,43 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.
References
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.
National Institutes of Health. Human microbiome project. Available at: http://nihroadmap.nih.gov/hmp/. Accessed July 19, 2010.
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.
International HapMap Consortium Integrating ethics and science in the International HapMap Project. Nat Rev Genet 2004; 5: 467–475.
Foster MW, Eisenbraun AJ, Carter TH . Communal discourse as a supplement to informed consent for genetic research. Nat Genet 1997; 17: 277–279.
Foster MW, Sharp RR, Freeman WL, Chino M, Bernsten D, Carter TH . The role of community review in evaluating the risks of human genetic variation research. Am J Hum Genet 1999; 64: 1719–1727.
Sharp RR, Foster MW . Involving study populations in the review of genetic research. J Law Med Ethics 2000; 28: 41–51, 3
Sharp RR, Foster MW . Community involvement in the ethical review of genetic research: lessons from American Indian and Alaska Native populations. Environ Health Perspect 2002; 110( Suppl 2): 145–148.
Sharp RR, Foster MW . Grappling with groups: protecting collective interests in biomedical research. J Med Philos 2007; 32: 321–337.
Godard B, Marshall J, Laberge C . Community engagement in genetic research: results of the first public consultation for the Quebec CARTaGENE project. Community Genet 2007; 10: 147–158.
Rotimi C, Leppert M, Matsuda I, International HapMap Consortium et al. Community engagement and informed consent in the International HapMap project. Community Genet 2007; 10: 186–198.
McCarty CA, Chapman-Stone D, Derfus T, Giampietro PF, Fost N, Marshfield Clinic PMRP Community Advisory Group Community consultation and communication for a population-based DNA biobank: the Marshfield clinic personalized medicine research project. Am J Med Genet A 2008; 146A: 3026–3033.
Collins FS, Morgan M, Patrinos A . The Human Genome Project: lessons from large-scale biology. Science 2003; 300: 286–290.
Common consent. Nature 2009; 460: 933.
Lemke AA, Wolf W, Hebert-Beirne J, Smith M . Public and biobank attitudes toward genetic research participation and data sharing. Public Health Genomics 2010; 13: 368–377.
Brownstein JS, Cassa CA, Mandl KD . No place to hide—reverse identification of patients from published maps. N Engl J Med 2006; 355: 1741–1742.
Homer N, Szelinger S, Redman M, et al. Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays. PLoS Genet 2008; 4: e1000167.
Jacobs KB, Yeager M, Wacholder S, et al. A new statistic and its power to infer membership in a genome-wide association study using genotype frequencies. Nat Genet 2009; 41: 1253–1257.
Loukides G, Denny J, Malin B Do clinical profiles constitute privacy risks for research participants? Paper presented at 2009 American Medical Informatics Association Annual Symposium, San Francisco, California.
Malin B Re-identification of familial database records. Paper presented at Proceedings of the 2006 American Medical Informatics Association Annual Symposium, Washington, D.C.
Malin B, Sweeney L . How (not) to protect genomic data privacy in a distributed network: using trail re-identification to evaluate and design anonymity protection systems. J Biomed Inform 2004; 37: 179–192.
Beskow LM, Dean E . Informed consent for biorepositories: assessing prospective participants' understanding and opinions. Cancer Epidemiol Biomarkers Prev 2008; 17: 1440–1451.
Ormond KE, Cirino AL, Helenowski IB, Chisholm RL, Wolf WA . Assessing the understanding of biobank participants. Am J Med Genet A 2009; 149A: 188–198.
McCarty CA, Nair A, Austin DM, Giampietro PF . Informed consent and subject motivation to participate in a large, population-based genomics study: the Marshfield Clinic Personalized Medicine Research Project. Community Genet 2007; 10: 2–9.
National Cancer Institute, Office of Biorepositories and Biospecimen Research. Best practices for biospecimen resources. Available at: http://biospecimens.cancer.gov/global/pdfs/NCI_Best_Practices_060507.pdf. Accessed October 7, 2009.
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.
National Human Genome Research Institute. NHGRI 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 NHGRI-supported or conducted Medical Sequencing Studies (NHGRI MSP). 2008. Available at: http://www.genome.gov/Pages/Research/SequenceMapsBAC/MedicalSequencing/MSPPtstoConsider03.12.08.pdf. Accessed July 19, 2010.
Lemke AA, Trinidad SB, Edwards KL, Starks H, Wiesner GL, GRIPP Consortium Attitudes toward genetic research review: results from a national survey of professionals involved in human subjects protection. J Empir Res Hum Res Ethics 2010; 5: 83–91.
Knoppers BM, Joly Y, Simard J, Durocher F . The emergence of an ethical duty to disclose genetic research results: international perspectives. Eur J Hum Genet 2006; 14: 1170–1178.
National Bioethics Advisory Commission Research involving human biological materials: ethical issues and policy guidance, Vol. 1. Rockville, MD, National Bioethics Advisory Commission, 1999.
Quaid KA, Jessup NM, Meslin EM . Disclosure of genetic information obtained through research. Genet Test 2004; 8: 347–355.
Clayton EW . Informed consent and biobanks. J Law Med Ethics 2005; 33: 15–21.
Kohane IS, Mandl KD, Taylor PL, Holm IA, Nigrin DJ, Kunkel LM . Medicine. Reestablishing the researcher-patient compact. Science 2007; 316: 836–837.
Wolf SM, Lawrenz FP, Nelson CA, et al. Managing incidental findings in human subjects research: analysis and recommendations. J Law Med Ethics 2008; 36: 219–248, 211
Bookman EB, Langehorne AA, Eckfeldt JH, NHLBI Working Group et al. Reporting genetic results in research studies: summary and recommendations of an NHLBI working group. Am J Med Genet A 2006; 140: 1033–1040.
Fernandez CV, Kodish E, Weijer C . Informing study participants of research results: an ethical imperative. IRB 2003; 25: 12–19.
Miller FA, Christensen R, Giacomini M, Robert JS . Duty to disclose what? Querying the putative obligation to return research results to participants. J Med Ethics 2008; 34: 210–213.
Parker LS . Rethinking respect for persons enrolled in research. ASBH Exch 2006; 9: 6–7.
Murphy J, Scott J, Kaufman D, Geller G, LeRoy L, Hudson K . Public expectations for return of results from large-cohort genetic research. Am J Bioeth 2008; 8: 36–43.
Kaufman D, Murphy J, Scott J, Hudson K . Subjects matter: a survey of public opinions about a large genetic cohort study. Genet Med 2008; 10: 831–839.
Fernandez CV, Taweel S, Kodish ED, Weijer C . Disclosure of research results to research participants: a pilot study of needs and attitudes of adolescents and parents. Paediatr Child Health 2005; 10: 332–334.
Shalowitz DI, Miller FG . Disclosing individual results of clinical research: implications of respect for participants. JAMA 2005; 294: 737–740.
Office of Population Genomics National Human Genome Research Institute. Research programs. 2009. Available at: http://www.genome.gov/27530162. Accessed October 19, 2009.
Acknowledgements
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.
Author information
Authors and Affiliations
Consortia
Corresponding author
Additional information
Disclosure: The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Clayton, E., Smith, M., Fullerton, S. et al. Confronting real time ethical, legal, and social issues in the Electronic Medical Records and Genomics (eMERGE) Consortium. Genet Med 12, 616–620 (2010). https://doi.org/10.1097/GIM.0b013e3181efdbd0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1097/GIM.0b013e3181efdbd0
This article is cited by
-
Security controls in an integrated Biobank to protect privacy in data sharing: rationale and study design
BMC Medical Informatics and Decision Making (2017)
-
Conducting a large, multi-site survey about patients’ views on broad consent: challenges and solutions
BMC Medical Research Methodology (2016)
-
Human genetic research, race, ethnicity and the labeling of populations: recommendations based on an interdisciplinary workshop in Japan
BMC Medical Ethics (2014)
-
Design and Anticipated Outcomes of the eMERGE-PGx Project: A Multicenter Pilot for Preemptive Pharmacogenomics in Electronic Health Record Systems
Clinical Pharmacology & Therapeutics (2014)
-
Biobanking: The Melding of Research with Clinical Care
Current Genetic Medicine Reports (2013)