Ellen Clayton | Vanderbilt University (original) (raw)

Papers by Ellen Clayton

European Journal of Human Genetics, 2015

The advent and refinement of sequencing technologies has resulted in a decrease in both the cost ... more The advent and refinement of sequencing technologies has resulted in a decrease in both the cost and time needed to generate data on the entire sequence of the human genome. This has increased the accessibility of using whole-genome sequencing and whole-exome sequencing approaches for analysis in both the research and clinical contexts. The expectation is that more services based on these and other high-throughput technologies will become available to patients and the wider population. Some authors predict that sequencing will be performed once in a lifetime, namely, shortly after birth. The Public and Professional Policy Committee of the European Society of Human Genetics, the Human Genome Organisation Committee on Ethics, Law and Society, the PHG Foundation and the P3G International Paediatric Platform address herein the important issues and challenges surrounding the potential use of sequencing technologies in publicly funded newborn screening (NBS) programmes. This statement presents the relevant issues and culminates in a set of recommendations to help inform and guide scientists and clinicians, as well as policy makers regarding the necessary considerations for the use of genome sequencing technologies and approaches in NBS programmes. The primary objective of NBS should be the targeted analysis and identification of gene variants conferring a high risk of preventable or treatable conditions, for which treatment has to start in the newborn period or in early childhood.

Genetics in Medicine, 2013

Personalized medicine holds significant promise for enhancing health care. Although some applicat... more Personalized medicine holds significant promise for enhancing health care. Although some applications of genetic information have yet to be proven, others-such as pharmacogenetic testing to avoid severe adverse effects of medication or identify optimal cancer therapies, or testing for known familial cancer syndromes-are already being implemented. 1-3 As the cost of sequencing continues to decrease, whole-genome or largepanel approaches may replace current genetic-testing modalities. 4,5 Optimal use of such results will depend, in part, on the development of effective clinical decision support (CDS) tools within the electronic health record (EHR). 6,7 Stakeholder engagement-involving those affected by changes in policy in the development of that policy-is critical for successful implementation of systems and processes that can support the use of genomic information. As Carman et al. 8 note, engagement occurs both along a continuum-from consultation and involvement to partnership and shared leadership-and at different levels within a health-care organization. In the clinical integration of genomic information, clinicians, patients, staff, scientists, policy makers, citizens, industry, and domain experts from genetics, informatics, and bioethics, and related fields all have a role to play. 6,9 Their input can address key challenges, including how to keep current with a rapidly growing knowledge base; determining the clinical implications of complex genetic results and their relative priority in patient care; and managing the privacy, security, and confidentiality of personal genomic data. Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine.

Behavior Genetics

We conducted in-depth, semi-structured interviews with LGBTQ+-identified individuals (n = 31) to ... more We conducted in-depth, semi-structured interviews with LGBTQ+-identified individuals (n = 31) to explore the range of LGBTQ+ perspectives on genomic research using either sexual orientation or gender identity (SOGI) data. Most interviewees presumed that research would confirm genetic contributions to sexual orientation and gender identity. Primary hopes for such confirmation included validating LGBTQ+ identities, improved access to and quality of healthcare and other resources, and increased acceptance in familial, socio-cultural, and political environments. Areas of concern included threats of pathologizing and medicalizing LGBTQ+ identities and experiences, undermining reproductive rights, gatekeeping of health or social systems, and malicious testing or misuse of genetic results, particularly for LGBTQ+ youth. Overall, interviewees were divided on the acceptability of genomic research investigating genetic contributions to sexual orientation and gender identity. Participants emph...

Genetic Testing and Molecular Biomarkers, 2012

This study examines psychological determinants and effects of participating in genetic testing am... more This study examines psychological determinants and effects of participating in genetic testing among persons diagnosed with or at risk for developing primary pulmonary arterial hypertension. Longitudinal data were drawn from orally administered surveys with 70 affected or at-risk individuals concerning their thoughts, feelings, and decision making about testing for mutations in BMPR2. Distress was measured by use of the Impact of Events Scale. Variations in tolerance for ambiguity were also examined. Although uptake of testing was low, as is common for incompletely penetrant mutations that lack clear therapeutic interventions, we found that those who participated in testing evidenced greater reduction in distress compared to those who had not participated in testing, irrespective of test result. No differences in tolerance for ambiguity by testing status were found. Participation in genetic testing, irrespective of test results, may be particularly beneficial to individuals who may have genetic mutations and who are experiencing high levels of distress.

Houston law review / University of Houston, 1992

as well as a bibliography of genetics and the law). In scientific and medi.

Fetal Diagnosis and Therapy, 1993

Analysis of current law demonstrates that the responses of state and federal governments and the ... more Analysis of current law demonstrates that the responses of state and federal governments and the legal system to reproductive genetic testing both have shaped the development of and reflect society's views about these techniques. Access to testing has been increased by governmental provision of services and enactment of insurance requirements and by the state courts' frequent approval of individual litigants' claims that they were inappropriately denied genetic information. Many state legislatures, however, have tried to limit testing by failing to provide funds, by forbidding private lawsuits and by limiting access to abortion.

Genetics in Medicine, 2012

Return of individual genetic results to research participants, including participants in archives... more Return of individual genetic results to research participants, including participants in archives and biorepositories, is receiving increased attention. However, few groups have deliberated on specific results or weighed deliberations against relevant local contextual factors. methods: The Electronic Medical Records and Genomics (eMERGE) Network, which includes five biorepositories conducting genomewide association studies, convened a return of results oversight committee to identify potentially returnable results. Network-wide deliberations were then brought to local constituencies for final decision making. Results: Defining results that should be considered for return required input from clinicians with relevant expertise and much deliberation. The return of results oversight committee identified two sex chromosomal anomalies, Klinefelter syndrome and Turner syndrome, as well as homozygosity for factor V Leiden, as findings that could warrant reporting. Views about returning findings of HFE gene mutations associated with hemochromatosis were mixed due to low penetrance. Review of electronic medical records suggested that most participants with detected abnormalities were unaware of these findings. Local considerations relevant to return varied and, to date, four sites have elected not to return findings (return was not possible at one site). conclusion: The eMERGE experience reveals the complexity of return of results decision making and provides a potential deliberative model for adoption in other collaborative contexts.

BMC Medical Genomics, 2011

Introduction: The eMERGE (electronic MEdical Records and GEnomics) Network is an NHGRI-supported ... more Introduction: The eMERGE (electronic MEdical Records and GEnomics) Network is an NHGRI-supported consortium of five institutions to explore the utility of DNA repositories coupled to Electronic Medical Record (EMR) systems for advancing discovery in genome science. eMERGE also includes a special emphasis on the ethical, legal and social issues related to these endeavors. Organization: The five sites are supported by an Administrative Coordinating Center. Setting of network goals is initiated by working groups: (1) Genomics, (2) Informatics, and (3) Consent & Community Consultation, which also includes active participation by investigators outside the eMERGE funded sites, and (4) Return of Results Oversight Committee. The Steering Committee, comprised of site PIs and representatives and NHGRI staff, meet three times per year, once per year with the External Scientific Panel. Current progress: The primary site-specific phenotypes for which samples have undergone genome-wide association study (GWAS) genotyping are cataract and HDL, dementia, electrocardiographic QRS duration, peripheral arterial disease, and type 2 diabetes. A GWAS is also being undertaken for resistant hypertension in ≈2,000 additional samples identified across the network sites, to be added to data available for samples already genotyped. Funded by ARRA supplements, secondary phenotypes have been added at all sites to leverage the genotyping data, and hypothyroidism is being analyzed as a cross-network phenotype. Results are being posted in dbGaP. Other key eMERGE activities include evaluation of the issues associated with cross-site deployment of common algorithms to identify cases and controls in EMRs, data privacy of genomic and clinically-derived data, developing approaches for large-scale meta-analysis of GWAS data across five sites, and a community consultation and consent initiative at each site. Future activities: Plans are underway to expand the network in diversity of populations and incorporation of GWAS findings into clinical care. Summary: By combining advanced clinical informatics, genome science, and community consultation, eMERGE represents a first step in the development of data-driven approaches to incorporate genomic information into routine healthcare delivery.

Genetics in Medicine, 2012

Published guidelines suggest that research results and incidental findings should be offered to s... more Published guidelines suggest that research results and incidental findings should be offered to study participants under some circumstances. Although some have argued against the return of results in research, many cite an emerging consensus that there is an ethical obligation to return at least some results; the debate quickly turns to issues of mechanics (e.g., which results? who discloses? for how long does the obligation exist?). Although commentators are careful to distinguish this as an ethical rather than legal obligation, we worry that return of results may unjustifiably become standard of care based on this growing "consensus, " which could quickly lead to a legal (negligence-based) duty to offer and return individualized genetic research results. We caution against this and argue in this essay that the debate to date has failed to give adequate weight to a number of fundamental ethical and policy issues that should undergird policy on return of research results in the first instance, many of which go to the fundamental differences between research and clinical care. We confine our comments to research using data from large biobanks, the topic of the guidelines proposed in this symposium issue.

American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2021

Patients with hypermobile Ehlers-Danlos syndrome, an hereditary disorder of the connective tissue... more Patients with hypermobile Ehlers-Danlos syndrome, an hereditary disorder of the connective tissue, often face a long and difficult diagnostic odyssey in pursuit of a name for their condition. Clinicians may dismiss subjective symptoms of chronic pain, thus prolonging patients' odysseys and worsening their care and satisfaction and creating antagonisms in the patient-provider relationship. A greater understanding of patient experiences is necessary in order to decrease burdens of this relationship and to improve care. To that end, we conducted 22 in-depth, semistructured interviews with individuals who had undergone this diagnostic odyssey. We focused on the impact that the odyssey had on their lives, both inside and outside the clinic. Through narrative analysis, we found a sort of "hero's journey" in the description of their cases, highlighting issues of uncertainty and integration as well as honoring their struggles. Interviewees had encountered difficulties in working with clinicians, in multiplying symptoms, and in negative psychosocial consequences. Attention to patients' lived experience may help to build empathy and understanding for the difficult and complex clinical situation presented by Ehlers-Danlos syndrome. Using the hero's journey as a lens onto this experience allows for a more patient-centered approach to this understanding and has potential value for comprehension of other complex diseases and invisible illnesses.

Genetics in Medicine, 2020

Genetics in Medicine, 2013

Genetics in Medicine, 2013

In 2009, only 1.5% of American hospitals utilized comprehensive EHR systems capable of clinical d... more In 2009, only 1.5% of American hospitals utilized comprehensive EHR systems capable of clinical decision support applications. 15 The inclusion of genomic data in the electronic health record raises important ethical, legal, and social issues. In this article, we highlight these challenges and discuss potential solutions. We provide a brief background on the current state of electronic health records in the context of genomic medicine, discuss the importance of equitable access to genome-enabled electronic health records, and consider the potential use of electronic health records for improving genomic literacy in patients and providers. We highlight the importance of privacy, access, and security, and of determining which genomic information is included in the electronic health record. Finally, we discuss the challenges of reporting incidental findings, storing and reinterpreting genomic data, and nondocumentation and duty to warn family members at potential genetic risk.

American Journal of Medical Genetics, 2021

Patients with hypermobile Ehlers-Danlos syndrome, an hereditary disorder of the connective tissue... more Patients with hypermobile Ehlers-Danlos syndrome, an hereditary disorder of the connective tissue, often face a long and difficult diagnostic odyssey in pursuit of a name for their condition. Clinicians may dismiss subjective symptoms of chronic pain, thus prolonging patients' odysseys and worsening their care and satisfaction and creating antagonisms in the patient-provider relationship. A greater understanding of patient experiences is necessary in order to decrease burdens of this relationship and to improve care. To that end, we conducted 22 in-depth, semistructured interviews with individuals who had undergone this diagnostic odyssey. We focused on the impact that the odyssey had on their lives, both inside and outside the clinic. Through

PLOS ONE

Direct-to-consumer genetic testing is marketed as a tool to uncover ancestry and kin. Recent stud... more Direct-to-consumer genetic testing is marketed as a tool to uncover ancestry and kin. Recent studies of actual and potential users have demonstrated that individuals’ responses to the use of these tests for these purposes are complex, with privacy, disruptive consequences, potential for misuse, and secondary use by law enforcement cited as potential concerns. We conducted six focus groups with a diverse sample of participants (n = 62) who were aware of but had not used direct-to-consumer genetic tests, in an effort to understand more about what people considering these tests think about the potential value, risks, and benefits of such testing, taking into account use by third parties, such as potential kin and law enforcement. Participants differed widely in the perceived value of direct-to-consumer genetic tests for ancestry and kinship information for their own lives, including the desirability of contact with previously unknown relatives. Some perceived ancestry testing as mere c...

American journal of pharmacogenomics : genomics-related research in drug development and clinical practice, 2003

Pharmacogenomic research promises to permit the development and delivery of safer and more effect... more Pharmacogenomic research promises to permit the development and delivery of safer and more effective drugs. If children are to receive these benefits, as justice would demand that they should, children must be included in trials that assess the impact of genetic variation, changing patterns of gene expression over time, and the effects of administering drugs. The ethical and legal challenges to conducting the necessary research include concerns about vulnerability and issues of consent, the scientific validity of the studies and the larger policy question of priority setting. Proposed strategies for ensuring the appropriate conduct of this research include analysis of the ethics based on risks and harms rather than presence or absence of a disorder, the development of model substrates to conduct physiological testing more safely, and the consideration of the disposition and impact of individual study results. With appropriate study, ultimately the use of pharmacogenomic testing can ...

The Pharmacogenomics Journal

Clinician attitudes toward multiplexed genomic testing may be vital to the success of translation... more Clinician attitudes toward multiplexed genomic testing may be vital to the success of translational programs. We surveyed clinicians at an academic medical center about their views on a large pharmacogenomics implementation, the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) program. Participants were asked about test ordering, major factors influencing use of results, expectations of efficacy and responsibility for applying results to patient care. Virtually all respondents (99%) agreed that pharmacogenomics variants influence patients' response to drug therapy. The majority (92%) favored immediate, active notification when a clinically significant drug-genome interaction was present. However, clinicians were divided on which providers were responsible for acting on a result when a prescription change was indicated and whether patients should be directly notified of a significant result. We concluded genotype results were valued for tailoring pr...

Cancer Epidemiology Biomarkers & Prevention, Feb 1, 2012

I appreciate Drs. Yassin, Weil, and Lockhart (the authors) giving me the opportunity to respond t... more I appreciate Drs. Yassin, Weil, and Lockhart (the authors) giving me the opportunity to respond to their article. I understand the source of the National Cancer Institute's concern. The NCI has many multicenter trials in which local sites submit tumor samples, which are then reviewed centrally by expert pathologists. Some of these central reviews reveal that the original diagnosis was incorrect and that the real disease requires radically different therapy. In such cases, returning the result to the patient and her treating physician is emotionally ...

Return of individual genetic results to research participants, including participants in archives... more Return of individual genetic results to research participants, including participants in archives and biorepositories, is receiving increased attention. However, few groups have deliberated on specific results or weighed deliberations against relevant local contextual factors. methods: The Electronic Medical Records and Genomics (eMERGE) Network, which includes five biorepositories conducting genomewide association studies, convened a return of results oversight committee to identify potentially returnable results. Network-wide deliberations were then brought to local constituencies for final decision making. Results: Defining results that should be considered for return required input from clinicians with relevant expertise and much deliberation. The return of results oversight committee identified two sex chromosomal anomalies, Klinefelter syndrome and Turner syndrome, as well as homozygosity for factor V Leiden, as findings that could warrant reporting. Views about returning findings of HFE gene mutations associated with hemochromatosis were mixed due to low penetrance. Review of electronic medical records suggested that most participants with detected abnormalities were unaware of these findings. Local considerations relevant to return varied and, to date, four sites have elected not to return findings (return was not possible at one site). conclusion: The eMERGE experience reveals the complexity of return of results decision making and provides a potential deliberative model for adoption in other collaborative contexts.

In 2007, the National Human Genome Research Institute (NHGRI) established the Electronic MEdical ... more In 2007, the National Human Genome Research Institute (NHGRI) established the Electronic MEdical Records and GEnomics (eMERGE) Consortium (www.gwas.net) to develop, disseminate, and apply approaches to research that combine DNA biorepositories with electronic medical record (EMR) systems for large-scale, high-throughput genetic research. One of the major ethical and administrative challenges for the eMERGE Consortium has been complying with existing data-sharing policies. This paper discusses the challenges of sharing genomic data linked to health information in the electronic medical record (EMR) and explores the issues as they relate to sharing both within a large consortium and in compliance with the National Institutes of Health (NIH) data-sharing policy. We use the eMERGE Consortium experience to explore data-sharing challenges from the perspective of multiple stakeholders (i.e., research participants, investigators, and research institutions), provide recommendations for researchers and institutions, and call for clearer guidance from the NIH regarding ethical implementation of its data-sharing policy.

European Journal of Human Genetics, 2015

The advent and refinement of sequencing technologies has resulted in a decrease in both the cost ... more The advent and refinement of sequencing technologies has resulted in a decrease in both the cost and time needed to generate data on the entire sequence of the human genome. This has increased the accessibility of using whole-genome sequencing and whole-exome sequencing approaches for analysis in both the research and clinical contexts. The expectation is that more services based on these and other high-throughput technologies will become available to patients and the wider population. Some authors predict that sequencing will be performed once in a lifetime, namely, shortly after birth. The Public and Professional Policy Committee of the European Society of Human Genetics, the Human Genome Organisation Committee on Ethics, Law and Society, the PHG Foundation and the P3G International Paediatric Platform address herein the important issues and challenges surrounding the potential use of sequencing technologies in publicly funded newborn screening (NBS) programmes. This statement presents the relevant issues and culminates in a set of recommendations to help inform and guide scientists and clinicians, as well as policy makers regarding the necessary considerations for the use of genome sequencing technologies and approaches in NBS programmes. The primary objective of NBS should be the targeted analysis and identification of gene variants conferring a high risk of preventable or treatable conditions, for which treatment has to start in the newborn period or in early childhood.

Genetics in Medicine, 2013

Personalized medicine holds significant promise for enhancing health care. Although some applicat... more Personalized medicine holds significant promise for enhancing health care. Although some applications of genetic information have yet to be proven, others-such as pharmacogenetic testing to avoid severe adverse effects of medication or identify optimal cancer therapies, or testing for known familial cancer syndromes-are already being implemented. 1-3 As the cost of sequencing continues to decrease, whole-genome or largepanel approaches may replace current genetic-testing modalities. 4,5 Optimal use of such results will depend, in part, on the development of effective clinical decision support (CDS) tools within the electronic health record (EHR). 6,7 Stakeholder engagement-involving those affected by changes in policy in the development of that policy-is critical for successful implementation of systems and processes that can support the use of genomic information. As Carman et al. 8 note, engagement occurs both along a continuum-from consultation and involvement to partnership and shared leadership-and at different levels within a health-care organization. In the clinical integration of genomic information, clinicians, patients, staff, scientists, policy makers, citizens, industry, and domain experts from genetics, informatics, and bioethics, and related fields all have a role to play. 6,9 Their input can address key challenges, including how to keep current with a rapidly growing knowledge base; determining the clinical implications of complex genetic results and their relative priority in patient care; and managing the privacy, security, and confidentiality of personal genomic data. Integrating genomic information into clinical care and the electronic health record can facilitate personalized medicine through genetically guided clinical decision support. Stakeholder involvement is critical to the success of these implementation efforts. Prior work on implementation of clinical information systems provides broad guidance to inform effective engagement strategies. We add to this evidence-based recommendations that are specific to issues at the intersection of genomics and the electronic health record. We describe stakeholder engagement strategies employed by the Electronic Medical Records and Genomics Network, a national consortium of US research institutions funded by the National Human Genome Research Institute to develop, disseminate, and apply approaches that combine genomic and electronic health record data. Through select examples drawn from sites of the Electronic Medical Records and Genomics Network, we illustrate a continuum of engagement strategies to inform genomic integration into commercial and homegrown electronic health records across a range of health-care settings. We frame engagement as activities to consult, involve, and partner with key stakeholder groups throughout specific phases of health information technology implementation. Our aim is to provide insights into engagement strategies to guide genomic integration based on our unique network experiences and lessons learned within the broader context of implementation research in biomedical informatics. On the basis of our collective experience, we describe key stakeholder practices, challenges, and considerations for successful genomic integration to support personalized medicine.

Behavior Genetics

We conducted in-depth, semi-structured interviews with LGBTQ+-identified individuals (n = 31) to ... more We conducted in-depth, semi-structured interviews with LGBTQ+-identified individuals (n = 31) to explore the range of LGBTQ+ perspectives on genomic research using either sexual orientation or gender identity (SOGI) data. Most interviewees presumed that research would confirm genetic contributions to sexual orientation and gender identity. Primary hopes for such confirmation included validating LGBTQ+ identities, improved access to and quality of healthcare and other resources, and increased acceptance in familial, socio-cultural, and political environments. Areas of concern included threats of pathologizing and medicalizing LGBTQ+ identities and experiences, undermining reproductive rights, gatekeeping of health or social systems, and malicious testing or misuse of genetic results, particularly for LGBTQ+ youth. Overall, interviewees were divided on the acceptability of genomic research investigating genetic contributions to sexual orientation and gender identity. Participants emph...

Genetic Testing and Molecular Biomarkers, 2012

This study examines psychological determinants and effects of participating in genetic testing am... more This study examines psychological determinants and effects of participating in genetic testing among persons diagnosed with or at risk for developing primary pulmonary arterial hypertension. Longitudinal data were drawn from orally administered surveys with 70 affected or at-risk individuals concerning their thoughts, feelings, and decision making about testing for mutations in BMPR2. Distress was measured by use of the Impact of Events Scale. Variations in tolerance for ambiguity were also examined. Although uptake of testing was low, as is common for incompletely penetrant mutations that lack clear therapeutic interventions, we found that those who participated in testing evidenced greater reduction in distress compared to those who had not participated in testing, irrespective of test result. No differences in tolerance for ambiguity by testing status were found. Participation in genetic testing, irrespective of test results, may be particularly beneficial to individuals who may have genetic mutations and who are experiencing high levels of distress.

Houston law review / University of Houston, 1992

as well as a bibliography of genetics and the law). In scientific and medi.

Fetal Diagnosis and Therapy, 1993

Analysis of current law demonstrates that the responses of state and federal governments and the ... more Analysis of current law demonstrates that the responses of state and federal governments and the legal system to reproductive genetic testing both have shaped the development of and reflect society's views about these techniques. Access to testing has been increased by governmental provision of services and enactment of insurance requirements and by the state courts' frequent approval of individual litigants' claims that they were inappropriately denied genetic information. Many state legislatures, however, have tried to limit testing by failing to provide funds, by forbidding private lawsuits and by limiting access to abortion.

Genetics in Medicine, 2012

Return of individual genetic results to research participants, including participants in archives... more Return of individual genetic results to research participants, including participants in archives and biorepositories, is receiving increased attention. However, few groups have deliberated on specific results or weighed deliberations against relevant local contextual factors. methods: The Electronic Medical Records and Genomics (eMERGE) Network, which includes five biorepositories conducting genomewide association studies, convened a return of results oversight committee to identify potentially returnable results. Network-wide deliberations were then brought to local constituencies for final decision making. Results: Defining results that should be considered for return required input from clinicians with relevant expertise and much deliberation. The return of results oversight committee identified two sex chromosomal anomalies, Klinefelter syndrome and Turner syndrome, as well as homozygosity for factor V Leiden, as findings that could warrant reporting. Views about returning findings of HFE gene mutations associated with hemochromatosis were mixed due to low penetrance. Review of electronic medical records suggested that most participants with detected abnormalities were unaware of these findings. Local considerations relevant to return varied and, to date, four sites have elected not to return findings (return was not possible at one site). conclusion: The eMERGE experience reveals the complexity of return of results decision making and provides a potential deliberative model for adoption in other collaborative contexts.

BMC Medical Genomics, 2011

Introduction: The eMERGE (electronic MEdical Records and GEnomics) Network is an NHGRI-supported ... more Introduction: The eMERGE (electronic MEdical Records and GEnomics) Network is an NHGRI-supported consortium of five institutions to explore the utility of DNA repositories coupled to Electronic Medical Record (EMR) systems for advancing discovery in genome science. eMERGE also includes a special emphasis on the ethical, legal and social issues related to these endeavors. Organization: The five sites are supported by an Administrative Coordinating Center. Setting of network goals is initiated by working groups: (1) Genomics, (2) Informatics, and (3) Consent & Community Consultation, which also includes active participation by investigators outside the eMERGE funded sites, and (4) Return of Results Oversight Committee. The Steering Committee, comprised of site PIs and representatives and NHGRI staff, meet three times per year, once per year with the External Scientific Panel. Current progress: The primary site-specific phenotypes for which samples have undergone genome-wide association study (GWAS) genotyping are cataract and HDL, dementia, electrocardiographic QRS duration, peripheral arterial disease, and type 2 diabetes. A GWAS is also being undertaken for resistant hypertension in ≈2,000 additional samples identified across the network sites, to be added to data available for samples already genotyped. Funded by ARRA supplements, secondary phenotypes have been added at all sites to leverage the genotyping data, and hypothyroidism is being analyzed as a cross-network phenotype. Results are being posted in dbGaP. Other key eMERGE activities include evaluation of the issues associated with cross-site deployment of common algorithms to identify cases and controls in EMRs, data privacy of genomic and clinically-derived data, developing approaches for large-scale meta-analysis of GWAS data across five sites, and a community consultation and consent initiative at each site. Future activities: Plans are underway to expand the network in diversity of populations and incorporation of GWAS findings into clinical care. Summary: By combining advanced clinical informatics, genome science, and community consultation, eMERGE represents a first step in the development of data-driven approaches to incorporate genomic information into routine healthcare delivery.

Genetics in Medicine, 2012

Published guidelines suggest that research results and incidental findings should be offered to s... more Published guidelines suggest that research results and incidental findings should be offered to study participants under some circumstances. Although some have argued against the return of results in research, many cite an emerging consensus that there is an ethical obligation to return at least some results; the debate quickly turns to issues of mechanics (e.g., which results? who discloses? for how long does the obligation exist?). Although commentators are careful to distinguish this as an ethical rather than legal obligation, we worry that return of results may unjustifiably become standard of care based on this growing "consensus, " which could quickly lead to a legal (negligence-based) duty to offer and return individualized genetic research results. We caution against this and argue in this essay that the debate to date has failed to give adequate weight to a number of fundamental ethical and policy issues that should undergird policy on return of research results in the first instance, many of which go to the fundamental differences between research and clinical care. We confine our comments to research using data from large biobanks, the topic of the guidelines proposed in this symposium issue.

American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 2021

Patients with hypermobile Ehlers-Danlos syndrome, an hereditary disorder of the connective tissue... more Patients with hypermobile Ehlers-Danlos syndrome, an hereditary disorder of the connective tissue, often face a long and difficult diagnostic odyssey in pursuit of a name for their condition. Clinicians may dismiss subjective symptoms of chronic pain, thus prolonging patients' odysseys and worsening their care and satisfaction and creating antagonisms in the patient-provider relationship. A greater understanding of patient experiences is necessary in order to decrease burdens of this relationship and to improve care. To that end, we conducted 22 in-depth, semistructured interviews with individuals who had undergone this diagnostic odyssey. We focused on the impact that the odyssey had on their lives, both inside and outside the clinic. Through narrative analysis, we found a sort of "hero's journey" in the description of their cases, highlighting issues of uncertainty and integration as well as honoring their struggles. Interviewees had encountered difficulties in working with clinicians, in multiplying symptoms, and in negative psychosocial consequences. Attention to patients' lived experience may help to build empathy and understanding for the difficult and complex clinical situation presented by Ehlers-Danlos syndrome. Using the hero's journey as a lens onto this experience allows for a more patient-centered approach to this understanding and has potential value for comprehension of other complex diseases and invisible illnesses.

Genetics in Medicine, 2020

Genetics in Medicine, 2013

Genetics in Medicine, 2013

In 2009, only 1.5% of American hospitals utilized comprehensive EHR systems capable of clinical d... more In 2009, only 1.5% of American hospitals utilized comprehensive EHR systems capable of clinical decision support applications. 15 The inclusion of genomic data in the electronic health record raises important ethical, legal, and social issues. In this article, we highlight these challenges and discuss potential solutions. We provide a brief background on the current state of electronic health records in the context of genomic medicine, discuss the importance of equitable access to genome-enabled electronic health records, and consider the potential use of electronic health records for improving genomic literacy in patients and providers. We highlight the importance of privacy, access, and security, and of determining which genomic information is included in the electronic health record. Finally, we discuss the challenges of reporting incidental findings, storing and reinterpreting genomic data, and nondocumentation and duty to warn family members at potential genetic risk.

American Journal of Medical Genetics, 2021

Patients with hypermobile Ehlers-Danlos syndrome, an hereditary disorder of the connective tissue... more Patients with hypermobile Ehlers-Danlos syndrome, an hereditary disorder of the connective tissue, often face a long and difficult diagnostic odyssey in pursuit of a name for their condition. Clinicians may dismiss subjective symptoms of chronic pain, thus prolonging patients' odysseys and worsening their care and satisfaction and creating antagonisms in the patient-provider relationship. A greater understanding of patient experiences is necessary in order to decrease burdens of this relationship and to improve care. To that end, we conducted 22 in-depth, semistructured interviews with individuals who had undergone this diagnostic odyssey. We focused on the impact that the odyssey had on their lives, both inside and outside the clinic. Through

PLOS ONE

Direct-to-consumer genetic testing is marketed as a tool to uncover ancestry and kin. Recent stud... more Direct-to-consumer genetic testing is marketed as a tool to uncover ancestry and kin. Recent studies of actual and potential users have demonstrated that individuals’ responses to the use of these tests for these purposes are complex, with privacy, disruptive consequences, potential for misuse, and secondary use by law enforcement cited as potential concerns. We conducted six focus groups with a diverse sample of participants (n = 62) who were aware of but had not used direct-to-consumer genetic tests, in an effort to understand more about what people considering these tests think about the potential value, risks, and benefits of such testing, taking into account use by third parties, such as potential kin and law enforcement. Participants differed widely in the perceived value of direct-to-consumer genetic tests for ancestry and kinship information for their own lives, including the desirability of contact with previously unknown relatives. Some perceived ancestry testing as mere c...

American journal of pharmacogenomics : genomics-related research in drug development and clinical practice, 2003

Pharmacogenomic research promises to permit the development and delivery of safer and more effect... more Pharmacogenomic research promises to permit the development and delivery of safer and more effective drugs. If children are to receive these benefits, as justice would demand that they should, children must be included in trials that assess the impact of genetic variation, changing patterns of gene expression over time, and the effects of administering drugs. The ethical and legal challenges to conducting the necessary research include concerns about vulnerability and issues of consent, the scientific validity of the studies and the larger policy question of priority setting. Proposed strategies for ensuring the appropriate conduct of this research include analysis of the ethics based on risks and harms rather than presence or absence of a disorder, the development of model substrates to conduct physiological testing more safely, and the consideration of the disposition and impact of individual study results. With appropriate study, ultimately the use of pharmacogenomic testing can ...

The Pharmacogenomics Journal

Clinician attitudes toward multiplexed genomic testing may be vital to the success of translation... more Clinician attitudes toward multiplexed genomic testing may be vital to the success of translational programs. We surveyed clinicians at an academic medical center about their views on a large pharmacogenomics implementation, the PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment) program. Participants were asked about test ordering, major factors influencing use of results, expectations of efficacy and responsibility for applying results to patient care. Virtually all respondents (99%) agreed that pharmacogenomics variants influence patients' response to drug therapy. The majority (92%) favored immediate, active notification when a clinically significant drug-genome interaction was present. However, clinicians were divided on which providers were responsible for acting on a result when a prescription change was indicated and whether patients should be directly notified of a significant result. We concluded genotype results were valued for tailoring pr...

Cancer Epidemiology Biomarkers & Prevention, Feb 1, 2012

I appreciate Drs. Yassin, Weil, and Lockhart (the authors) giving me the opportunity to respond t... more I appreciate Drs. Yassin, Weil, and Lockhart (the authors) giving me the opportunity to respond to their article. I understand the source of the National Cancer Institute's concern. The NCI has many multicenter trials in which local sites submit tumor samples, which are then reviewed centrally by expert pathologists. Some of these central reviews reveal that the original diagnosis was incorrect and that the real disease requires radically different therapy. In such cases, returning the result to the patient and her treating physician is emotionally ...

Return of individual genetic results to research participants, including participants in archives... more Return of individual genetic results to research participants, including participants in archives and biorepositories, is receiving increased attention. However, few groups have deliberated on specific results or weighed deliberations against relevant local contextual factors. methods: The Electronic Medical Records and Genomics (eMERGE) Network, which includes five biorepositories conducting genomewide association studies, convened a return of results oversight committee to identify potentially returnable results. Network-wide deliberations were then brought to local constituencies for final decision making. Results: Defining results that should be considered for return required input from clinicians with relevant expertise and much deliberation. The return of results oversight committee identified two sex chromosomal anomalies, Klinefelter syndrome and Turner syndrome, as well as homozygosity for factor V Leiden, as findings that could warrant reporting. Views about returning findings of HFE gene mutations associated with hemochromatosis were mixed due to low penetrance. Review of electronic medical records suggested that most participants with detected abnormalities were unaware of these findings. Local considerations relevant to return varied and, to date, four sites have elected not to return findings (return was not possible at one site). conclusion: The eMERGE experience reveals the complexity of return of results decision making and provides a potential deliberative model for adoption in other collaborative contexts.

In 2007, the National Human Genome Research Institute (NHGRI) established the Electronic MEdical ... more In 2007, the National Human Genome Research Institute (NHGRI) established the Electronic MEdical Records and GEnomics (eMERGE) Consortium (www.gwas.net) to develop, disseminate, and apply approaches to research that combine DNA biorepositories with electronic medical record (EMR) systems for large-scale, high-throughput genetic research. One of the major ethical and administrative challenges for the eMERGE Consortium has been complying with existing data-sharing policies. This paper discusses the challenges of sharing genomic data linked to health information in the electronic medical record (EMR) and explores the issues as they relate to sharing both within a large consortium and in compliance with the National Institutes of Health (NIH) data-sharing policy. We use the eMERGE Consortium experience to explore data-sharing challenges from the perspective of multiple stakeholders (i.e., research participants, investigators, and research institutions), provide recommendations for researchers and institutions, and call for clearer guidance from the NIH regarding ethical implementation of its data-sharing policy.

Vand. L. Rev., Jan 1, 1990

WE: When organizing this Symposium on the topic of" Law, Literature,... more WE: When organizing this Symposium on the topic of" Law, Literature, and Social Change," we asked whether current trends in literature and in literary, social, and legal theory actually could play a role in bringing about social change. The authors gathered at this ...