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Genet Med. Author manuscript; available in PMC Oct 1, 2011.
Published in final edited form as:
PMCID: PMC3090678
NIHMSID: NIHMS287409

Confronting Real Time Ethical, Legal, and Social Issues in the eMERGE (Electronic Medical Records and Genomics) Consortium

Ellen Wright Clayton, MD, JD,# Maureen Smith, MS, CGC,* Stephanie M. Fullerton, PhD,% Wylie Burke, MD, PhD,% Catherine A. McCarty, PhD,§ Barbara A. Koenig, PhD, Amy L. McGuire, PhD, JD, Laura M. Beskow, MPH, PhD,1 Lynn Dressler, PhD,2 Amy A. Lemke, MS, PhD,* Erin M. Ramos, PhD, MPH, Laura Lyman Rodriguez, PhD, and the Consent and Community Consultation Working Group of the eMERGE Consortium*

Increasingly, genomic research is being conducted through large, multi-site consortia. For example, the eMERGE (Electronic Medical Records and Genomics) 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 (SNPs) 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 as 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: 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 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 preexisting 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 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 (ethical, legal, and social implications) 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).

In order 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:

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)

While 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 upon best practices for sharing genotype data linked to clinical information in the electronic health record, both inter-institutionally within the consortium and also more broadly with other investigators through dbGaP. They are also are examining research participants’ attitudes about these policies, what concerns they have, and what protections they desire.15

Identifiability of DNA and EMR 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 upon examples of existing consent language, including some that has been the subject of empirical research,22-24 as well as 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)

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 institutional review board (IRB) or privacy board and an institutional official from the submitting institution has provided verification that the NIH submission criteria. 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 review 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 Consent and Community Consultation 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.

Acknowledgments

The eMERGE Network was initiated and funded 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).

Footnotes

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References

1. National Institutes of Health Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (GWAS) [7/31/2009]; http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html.
2. National Institutes of Health Human Microbiome Project. [4/20/2101]; http://nihroadmap.nih.gov/hmp/.
3. NHLBI. NHLBI LARGE-SCALE DNA SEQUENCING PROJECT POPULATION STUDIES [4/21/2010];2009 http://www.nhlbi.nih.gov/recovery/media/NHLBI_DNA_cohorts.htm.
4. International HapMap Consortium Integrating ethics and science in the International HapMap Project. Nat Rev Genet. 2004 Jun;5(6):467–475. [PMC free article] [PubMed]
5. Foster MW, Eisenbraun AJ, Carter TH. Communal discourse as a supplement to informed consent for genetic research. Nat Genet. 1997 Nov;17(3):277–279. [PubMed]
6. 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 Jun;64(6):1719–1727. [PMC free article] [PubMed]
7. Sharp RR, Foster MW. Involving study populations in the review of genetic research. J Law Med Ethics. 2000 Spring;28(1):41–51, 43. [PubMed]
8. 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 Apr;110(Suppl 2):145–148. [PMC free article] [PubMed]
9. Sharp RR, Foster MW. Grappling with groups: protecting collective interests in biomedical research. J Med Philos. 2007 Jul-Aug;32(4):321–337. [PubMed]
10. 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(3):147–158. [PubMed]
11. Rotimi C, Leppert M, Matsuda I, et al. Community engagement and informed consent in the International HapMap project. Community Genet. 2007;10(3):186–198. [PubMed]
12. McCarty CA, Chapman-Stone D, Giampietro PF, Fost NC, PMRP Community Advisory Group Community consultation and communication for a population-based DNA biobank: the Marshfield Clinic Personalized Medicine Research Project. American Journal of Medical Genetics. 2008;146A(23):3026–3033. [PMC free article] [PubMed]
13. Collins FS, Morgan M, Patrinos A. The Human Genome Project: Lessons from Large-Scale Biology. Science. 2003;300(5617):286–290. [PubMed]
14. Common consent. Nature. 2009;460(7258):933. [PubMed]
15. Lemke AA, Wolf W, Hebert-Beirne J, Smith M. Public and Biobank Attitudes toward Genetic Research Participation and Data Sharing. Public Health Genomics. 2010 [PMC free article] [PubMed]
16. Brownstein JS, Cassa CA, Mandl KD. No place to hide – reverse identification of patients from published maps. New England Journal of Medicine. 2006;355(16):1741–1742. [PubMed]
17. 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 Aug;4(8):e1000167. [PMC free article] [PubMed]
18. Jacobs Kevin B, Yeager Meredith, Wacholder Sholom, et al. A new statistic and its power to infer membership in a genome-wide association study using genotype frequencies. Nature Genetics. 2009 [PMC free article] [PubMed]
19. 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.
20. Malin B. Re-identification of familial database records.. Paper presented at: Proceedings of the 2006 American Medical Informatics Association Annual Symposium. [PMC free article] [PubMed]
21. Malin B LS. How (not) to protect genomic data privacy in a distributed network: using trail re-identification to evaluate and design anonymity protection systems. Journal of Biomedical Informatics. 2004;37(3):179–192. [PubMed]
22. Beskow LM, Dean E. Informed consent for biorepositories: assessing prospective participants’ understanding and opinions. Cancer Epidemiol Biomarkers Prev. 2008;17(6):1440–1451. [PubMed]
23. Ormond KE, Cirino AL, Helenowski IB, Chisholm RL, Wolf WA. Assessing the understanding of biobank participants. American Journal of Medical Genetics A. 2009;149A(2):188–198. [PubMed]
24. 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 Genetics. 2007;10(1):2–9. [PubMed]
25. National Cancer Institute, Office of Biorepositories and Biospecimen Research Best Practices for Biospecimen Resources. [October 7, 2009]; http://biospecimens.cancer.gov/global/pdfs/NCI_Best_Practices_060507.pdf. http://biospecimens.cancer.gov/global/pdfs/NCI_Best_Practices_060507.pdf.
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). [10/29/1009];2007 http://grants.nih.gov/grants/gwas/gwas_ptc.pdf.
27. 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 http://www.genome.gov/Pages/Research/SequenceMapsBAC/MedicalSequencing/MSPPtstoConsider03.12.08.pdf.
28. Lemke AA, Trinidad SB, Edwards KL, Starks H, Wiesner GL, the 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 Mar;5(1):83–92. [PMC free article] [PubMed]
29. Knoppers BM, et al. The emergence of an ethical duty to disclose genetic research results: international perspectives. Eur J Hum Genet. 2006;14(11):1170–1178. [PubMed]
30. National Bioethics Advisory Commission . Research Involving Human Biological Materials: Ethical Issues and Policy Guidance. Vol. 1. National Bioethics Advisory Commission; Rockville, MD: 1999.
31. Quaid KA, Jessup NM, Meslin EM. Disclosure of genetic information obtained through research. Genet Test. 2004 Fall;8(3):347–355. [PubMed]
32. Clayton EW. Informed Consent and Biobanks. Journal of Law, Medicine, and Ethics. 2005;33(1):15–21. [PubMed]
33. Kohane IS, Mandl KD, Taylor PL, Holm IA, Nigrin DJ, Kunkel LM. Medicine. Reestablishing the researcher-patient compact. Science. 2007 May 11;316(5826):836–837. [PubMed]
34. Wolf SM, Lawrenz FP, Nelson CA, et al. Managing incidental findings in human subjects research: analysis and recommendations. J Law Med Ethics. 2008 Summer;36(2):219–248, 211. [PMC free article] [PubMed]
35. Bookman Ebony B., Langehorne Aleisha A., Eckfeldt John H., et al. Reporting genetic results in research studies: Summary and recommendations of an NHLBI working group. American Journal of Medical Genetics Part A. 2006;140A(10):1033–1040. [PMC free article] [PubMed]
36. Fernandez CV, Kodish E, Weijer I C. Informing study participants of research results: an ethical imperative. IRB. 2003;25(3):12–19. 2003. 25(3): 12. [PubMed]
37. Miller FA, et al. Duty to disclose what? Querying the putative obligation to return research results to participants. J Med Ethics. 2008;34(3):210–213. [PubMed]
38. Parker LS. Rethinking respect for persons enrolled in research. ASBH Exchange. 2006;9(1):6–7.
39. 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 Nov;8(11):36–43. [PMC free article] [PubMed]
40. Kaufman D, Murphy J, Scott J, Hudson K. Subjects matter: a survey of public opinions about a large genetic cohort study. Genet Med. 2008 Nov;10(11):831–839. [PubMed]
41. Fernandez CV, et al. Disclosure of research results to research participants: A pilot study of needs and attitudes of adolescents and parents. Paediatrics & Child Health. 2005;10(6):332–334. [PMC free article] [PubMed]
42. Shalowitz DI, Miller FG. Disclosing individual results of clinical research: implications of respect for participants. JAMA. 2005;294(6):737–740. [PubMed]
43. Office of Population Genomics, National Human Genome Research Institute Research Programs. 2009(10/19/2009). http://www.genome.gov/27530162.
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