Amy McGuire Lab

As wastewater research and monitoring programs develop and evolve beyond SARS-CoV-2 to a wide range of possible pathogens (viruses, bacteria, and protozoa), one critical challenge is determining what information ought to be shared, with whom, and how.
Wastewater research and monitoring can provide early warning of the spread of known diseases of public health importance and inform public health responses, but it can also provide highly sensitive and potentially stigmatizing information, raising ethical, legal, and social issue (ELSI), including how to communicate information in a way that maximizes benefits and builds public trust while protecting privacy and avoiding the exacerbation of health inequities. EMPOWER is an innovative embedded ELSI research project that will directly impact the development and implementation of strategies for communicating information from a statewide wastewater research and monitoring program in Texas. This project will collect critical empirical data from stakeholders and engage diverse members of the community to identify and develop strategies to address the ELSI considerations of communicating information from public health research.
The overall objective of EMPOWER is to develop a strategy for responsible reporting of information from wastewater monitoring in the state of Texas that is feasible and reflects community members’ values and perspectives. We will collaborate with the Texas Epidemic Public Health Institute (TEPHI) Wastewater Consortium (TWC) and its Action Plan Working Group to: (1) identify facilitators and barriers to results disclosure, (2) assess community members’ perspectives about results disclosures, and (3) generate evidence-based recommendations and a communication platform for community members’ review and feedback.

Supported by: R01ES036232, National Institute of Environmental Health Science, Office of the Director, National Human Genome Research Institute

Role: MPI (with Jennifer Deegan)

After nearly a 50-year hiatus, there has been a resurgence of research on the use of psychedelics to treat a wide range of neuropsychiatric conditions. The FDA designated MDMA and psilocybin breakthrough therapies for PTSD and severe depression, respectively and is anticipated to approve the first psychedelic drug within the next two few years. The therapeutic potential of psychedelics has been widely publicized, and patients are now inquiring about the availability and advisability of psychedelic use. Meanwhile, several US cities and both Oregon and Colorado have decriminalized or deprioritized enforcement for at least some psychedelics, with many others considering similar legislation. This growing public enthusiasm, combined with bipartisan advocacy for regulatory reform, has led to an increase in the number of companies offering private or group psychedelic retreats, often without the involvement of licensed healthcare professionals. Yet little is known about how these retreats are run, and because they typically take place in other countries, there is no oversight of their practices. Ethical concerns are mounting regarding potential for off-label and unregulated use of psychedelics without a corresponding evidence-base, leap-frogging established and safe interventions, and commercial abuse. Unchecked, such issues pose clear risk for the responsible and safe uptake of psychedelic therapies that could affect consumer safety, have legal implications, and deleteriously impact patient trust in psychiatric practice. Despite these concerns, no studies to date have systematically examined the use of psychedelics in these unregulated settings or the ethical, legal, and social implications of such use.  

The overall goal of this research is to examine the appropriate role (scope, value, and legitimacy) of healthcare gatekeeping for ensuring safe and responsible use of psychedelics. We will accomplish this by: (1) assessing the current state of unregulated psychedelic retreats that are advertised in the U.S.; (2) examining the ethical, legal, and social implications of these programs from the perspective of those participating in them; and (3) providing recommendations for healthcare gatekeeping in the context of unregulated psychedelic retreats, informed by the results of the first two aims. 
 

Supported by: The Ortus Foundation

Role: PI

Amid today’s psychedelic renaissance, more IRBs will find themselves responsible for oversight of psychedelic research. In this gatekeeping role, IRBs must ensure appropriate participant protection without inhibiting important science. Yet neither IRB perspectives on psychedelic research nor psychedelic investigator experiences with IRBs have been studied. Through qualitative interviews with psychedelic investigators and a survey of IRB chairpersons, this project aims to promote high-quality ethics review of psychedelic research by developing empirically informed resources for both IRBs and investigators.

Supported by: The Greenwall Foundation (PI Fernandez Lynch)

Role: Collaborator (unpaid) 

The NIH BRAIN Initiative has been ongoing since 2013. The Initiative “is aimed at revolutionizing our understanding of the human brain” through the “development and application of innovative technologies” to deepen our understandings of how the brain and neural circuits interact in health and disease (The BRAIN Initiative, NIH, 2021).
Data sharing is essential to promote equity and maximize the impact of the significant public investment in the BRAIN Initiative. Data sharing plans are now required for BRAIN funding, but there is an urgent need to develop specific policies and practices that are empirically informed and address ethical challenges and concerns related to sharing human data from BRAIN research. Our own experience and research with investigators conducting BRAIN Initiative studies of closed loop or adaptive deep brain stimulation, for instance, suggests that the practice of sharing data is inconsistent and incomplete, despite broad agreement that it is important. Some ethical challenges relate to privacy, consent, the interoperability of data types and sharing platforms, and competing commercial and processional interests.

The BRAINshare Project aims to engage key stakeholders through interviews and a modified policy Delphi process to identify challenges and concerns specific to sharing human BRAIN data and to generate empirically informed policy and practice options to facilitate responsible sharing of these data.

Supported by: R01MH126937, National Institute of Mental Health (BRAIN Initiative)
Role: mPI (with Sameer Sheth)

Supplement: A Case Study on Autism in Data Sharing Practices

Project Description

This one-year supplement project aims to conduct a case study on ethical data sharing challenges in autism research and how to address data sharing practices that lack diversity, equity, and inclusion considerations. Data will be collected through a literature review and in-depth interviews with diverse stakeholders to explore challenges and potential solutions to address such ethical and policy challenges in data sharing. This case study will serve as an additional research input to informs the ongoing Delphi process in the BRAINshare Project and shapes the Project’s broader policy recommendations.  

Supported by:  R01MH126937-03S1, National Institute of Mental Health (Research Supplement to Promote Diversity in Health-Related Research Program)

Despite largescale government and private investment in commercializing space travel, it remains too dangerous and too impractical for most civilians.
We are working to fill critical policy gaps that advance The Translational Research Institute for Space Health (TRISH) mission of translating responsible research on commercial space travel by developing an ethical framework for involving civilians in spaceflight research and formalizing an ethics review service for TRISH researchers. This will occur through a new collaborating partnership between TRISH and the Center for Medical Ethics and Health Policy (CMEHP) at Baylor College of Medicine called METEORS (Mission to enhance Ethics Education, Outreach, and Research in Space). Taken together, METEORS advances the TRISH mission by developing tools to enable the ethical translation of cutting-edge biomedical research and technology development and supports education on how to proportionately balance real human risks with tangible benefits of human space exploration missions moving forward.

Supported by: TRISH’s Space Health Expeditionary Research Projects Assets (SHERPA) program

Add Role: mPI (with Vasiliki Rahimzadeh)

In 2018, the arrest of the alleged Golden State Killer made headlines around the world. He was identified using a controversial new technique called investigative genetic genealogy (IGG). This technique involves uploading crime scene DNA to genetic genealogy databases with the intention of identifying a criminal offender’s genetic relatives and, eventually, locating the offender in their family tree. Since 2018, according to one expert, IGG has helped lead to the successful identification of over 1,000 violent criminal suspects.

At the same time, the technique has been challenged by those who argue it violates fundamental privacy interests of database participants and their families. Some believe that these privacy concerns are so compelling that IGG threatens to undermine public participation in clinical and research genetic databases, especially those maintained by the government.
Past studies—including our own—have demonstrated that individuals are concerned about genetic privacy, yet they are willing to share their genetic data with certain individuals, for particular reasons, and under specific conditions. But all of these studies pre-date IGG and none probed participation by law enforcement in genetic genealogy or other recreational genetic databases. Understanding the complex trade-offs that the public makes when assessing the value and acceptability of law enforcement use of genetic data will be important in ensuring that IGG-relevant policies and practices that are adopted strike a balance between safety and privacy that is acceptable to the public.

This project involves: (1) qualitative interviews to characterize and forecast law enforcement participation in genetic genealogy databases, (2) focus groups and a discrete choice experiment to measure preferences related to law enforcement participation in genetic genealogy databases, and (c) a modified policy Delphi to develop best practices related to law enforcement participation in genetic genealogy databases.
Additional project materials available at: DOI 10.17605/OSF.IO/N9TFU.

Supported by: R01HG011268, National Human Genome Research Institute
FORENSEQ is a trademark of Verogen, Inc. and Qiagen, N.V. The ForenSeq Study is not affiliated with the FORENSEQ mark.

Role: mPI (with Christi Guerrini)
   
Supplement: IGG on the Internet: Characterizing Public Perspectives on Law Enforcement Use of Genetic Genealogy Data in Social Media  
This supplement builds on the ForenSeq Project to collect and analyze social media coverage of IGG. 
Supported by: R01HG011268-S1, National Human Genome Research Institute

Role: mPI (with Christi Guerrini; Supplement lead: Sarah Katsanis)

Developing Evidence-Based Guidance for Engaging Rural Residents in the Deep South in Genomics Research: A Stakeholder-Driven Perspective
Supported by: K01HG011495, National Human Genome Research Institute (PI Fletcher)
Role: Faculty mentor
 

The BabySeq2 Project builds on the template established in the first phase of the BabySeq Project to study the psychological impact, medical utility, and cost effectiveness of genome sequencing (GS) in healthy newborns. In the second phase, a diverse cohort of newborns are being enrolled to screen for genetic childhood disease risk. After the return of GS results (including pathogenic GS and copy number variation results), the impact on families and HCPs, as well as the medical and economic impact, are studied. Through this research we will develop, implement, and evaluate a sustainable approach to GS as screening that leverages underserved community engagement to minimize distrust and maximize benefit. This study provides a distinct opportunity to determine medical, behavioral, and economic outcomes in an under-represented population of infants at diverse sites, modeling the vision of GS as a part of healthcare implemented early in childhood.

Supported by: U01TR003201, National Center for Advancing Translational Sciences, NIH 

The Precision Medicine for Alzheimer’s Disease and Related Dementias Project is a joint project conducted in collaboration with the Center for Alzheimer’s and Neurodegenerative Disease (CAND) at Baylor College of Medicine. This project aims to integrate precision medicine (cognitive testing, genomic testing, and neuroimaging) into Alzheimer’s research and care to increase early detection of Alzheimer’s disease and related dementias (ADRD) and improve clinical outcomes. In this project, at-risk patient-participants enroll together with study partners to receive cognitive testing, genetic testing, and neuroimaging (MRI, PET), and a comprehensive profile of their risk of developing ADRD. In conjunction with CAND, the Center for Medical Ethics and Health policy is assessing the impact of precision medicine testing and disclosure on both patient-participants and their study partners to facilitate ethical and effective implementation of precision medicine disclosure.

The project is enrolling 250 patient-participants and their study partners in the Houston area. The diverse settings of the study allow us to evaluate the impact of precision medicine on a diverse community, including both English and Spanish-speaking populations.  

Patient-participants and study partners complete pre-disclosure surveys to assess their expectations around results prior to receiving them. At follow-up, both patient-participants and study partners provide information about their understanding of and reaction to their results. Study partners also provide information about their caregiver burden and gains in dementia caregiving.

Supported by: a private foundation (PI Shulman)

Role: Co-I

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder. Worldwide, its prevalence is ~2% and its etiology is mostly unknown. Identifying biological factors contributing to OCD will elucidate underlying mechanisms and might contribute to improved treatment outcomes. Genomic studies of OCD are beginning to reveal long-sought risk loci, but >95% of the cases currently in analysis are of homogenous European ancestry. If not addressed, this Eurocentric bias will result in OCD genomic findings being more accurate for individuals of European ancestry than other ancestries, thereby contributing to health disparities in potential future applications of genomics.

LATINO is a new network of investigators from across Latin America, the United States, and Canada who have begun to collect DNA and clinical data from 5,000 richly-phenotyped OCD cases of Latin American ancestry in a culturally sensitive and ethical manner. This project utilizes trans-ancestry genomic analyses to accelerate the identification of OCD risk loci, fine-map putative causal variants, and improve the performance of polygenic risk scores in diverse populations. The project capitalizes on rich clinical data to examine the genetics of treatment response, biologically plausible OCD subtypes, and symptom dimensions. 

We are collaborating with the LATINO team to examine the use of psychedelics and attitudes about psychedelic assisted therapy for OCD among participants in Latin America and the U.S.

Role: Collaborator

The LATINO Project is supported by:  U01MH125050 (PI Crowley) and U01MH125062 (PI Storch), National Institute of Mental Health

Genetic Data Partnerships: Enabling Equitable Access within Academic/Private Data Sharing Agreements
“Precision medicine” and other advances in genetic research require access to massive amounts of genetic and related health data, but private genetic datasets are growing rapidly in both value and size and pose a challenge to the public genetic data market. This research proposes to characterize and evaluate the factors influencing these genetic data partnerships (beginning with academics), compare market drivers to current existing governance structures, and offer a model for best practices. Findings will inform current academic and governmental genetic data-sharing policy, as well as build a longitudinal analysis and conceptual model to stabilize this market moving forward.

Supported by: K01HG010496, National Human Genome Research Institute (PI Spector-Bagdady)
Role: Faculty mentor
 

Building on the previous success of the BASIC3 study, over four years, KidsCanSeq enrolled 627 pediatric patients and their parents at several diverse healthcare setting across Texas. The diverse settings of the study allowed us to evaluate our novel, culturally sensitive approaches to the informed consent process – including informational videos in English and Spanish - and return of results that includes communicating complex genomic information to families and physicians.

Supported by: U01HG006485, National Human Genome Research Institute, National Cancer Institute, NIH

Building on the previous success of the BASIC3 study, over four years, KidsCanSeq is enrolling 1100 pediatric patients and their patients at several diverse healthcare setting across Texas. The diverse settings of the study allow us to evaluate our novel, culturally sensitive approaches to the informed consent process – including informational videos in English and Spanish - and return of results that includes communicating complex genomic information to families and physicians.

We are exploring utility from a broad range of perspectives including:

• Clinical utility of the ES testing to impact treatment decisions, and the impact of germline diagnostic and/or actionable findings on surveillance and testing recommendations for family members.
• Parents' perceived utility, including clinical and personal utility of the ES information.
• Oncologists' perceived and actual utility of the ES information.
  
  Parents complete longitudinal surveys to assess their perceived utility of and feelings about their child’s genomic results. At follow-up, parents also provide information about whether other family members followed up on any testing and surveillance recommendations, as well as barriers to doing so. Oncologists enrolled in the study complete multiple surveys to assess the clinical utility of genomic testing and its effect on treatment decisions, as well as their perceived utility of the information.

Supported by: U01HG006485, National Human Genome Research Institute and National Cancer Institute, NIH

Supplement Project: Measuring Perceptions of Utility of Clinical Genome Sequencing: Instrument Development and Validation

Project Description

A major goal of the CSER consortium is to generate evidence regarding the utility of genomic sequencing (GS). Specifically, the aim is to understand what clinical utility (e.g., impact on diagnosis, treatment, and management) and other dimensions of utility beyond those captured in medical records (e.g., psychological and pragmatic utility) clinicians, patients, families and society experience with GS information. We are developing a survey instrument to assess patients' and families' perceived utility using a rigorous methodological approach in order to generate comprehensive evidence of the broad dimensions of utility of GS. To develop this survey instrument, we are:

Developing a typology of how different stakeholders define utility through a systematic literature review. Conducting interviews with adult patients and parents of pediatric patients who received GS across diverse clinical settings that comprise the CSER consortium studies (n=60, 10 at each of 6 sites). Triangulating data from the typology and interviews to develop a comprehensive conceptual model of the relevant dimensions of perceived patient utility. This model will guide the generation of an item pool for survey instrument development that will be refined and pilot tested according to established practices for measuring patient-reported outcomes and instrument development.

Supported by: U01HG006485-S1, National Human Genome Research Institute, NIH

Publications

Gutierrez AM, Robinson JO, Raesz-Martinez R, Canfield I, Majumder MA, Scollon S, Desrosiers LR, Hsu RL, Allen-Rhoades W, Parsons DW, Plon SE, McGuire AL, Malek J. Views of Adolescents and Young Adults with Cancer and Their Oncologists Toward Patients' Participation in Genomic Research. J Adolesc Young Adult Oncol. 2023 Oct;12(5):773-781. doi: 10.1089/jayao.2022.0066. Epub 2023 Jan 2. PMID: 36595372; PMCID: PMC10611971.

Muenzen KD, Amendola LM, Kauffman TL, Mittendorf KF, Bensen JT, Chen F, Green R, Powell BC, Kvale M, Angelo F, Farnan L, Fullerton SM, Robinson JO, Li T, Murali P, Lawlor JMJ, Ou J, Hindorff LA, Jarvik GP, Crosslin DR. Lessons learned and recommendations for data coordination in collaborative research: The CSER consortium experience. HGG Adv. 2022 May 20;3(3):100120. doi: 10.1016/j.xhgg.2022.100120. PMID: 35707062; PMCID: PMC9190054.

Kraft SA, Russell H, Bensen JT, Bonini KE, Robinson JO, Sahin-Hodoglugil N, Renna K, Hindorff LA, Kaufman D, Horowitz CR, Waltz M, Zepp JM, Knight SJ. Conducting clinical genomics research during the COVID-19 pandemic: Lessons learned from the CSER consortium experience. Am J Med Genet A. 2022 Nov 7. doi: 10.1002/ajmg.a.63033. Epub ahead of print. PMID: 36341765.

Goddard KAB, Angelo FAN, Ackerman SL, et al. Lessons learned about harmonizing survey measures for the CSER consortium. Journal of Clinical and Translational Science. 2020;4(6):537-546. doi:10.1017/cts.2020.41.

Smith HS, Brothers KB, Knight SJ, Ackerman SL, Rini C, Veenstra DL, McGuire AL, Wilfond BS, Malek J. Conceptualization of utility in translational clinical genomics research. Am J Hum Genet. 2021 Nov 4;108(11):2027-2036. doi: 10.1016/j.ajhg.2021.08.013. Epub 2021 Oct 22. PMID: 34687653; PMCID: PMC8595895.

Plon, Sharon et al. Physician recommendations after germline sequencing in pediatric cancer patients: Texas KidsCanSeq study, Genetics in Medicine, 2022. Volume 24, Issue 3, S344.

Gutierrez AM, Robinson JO, Outram SM, Smith HS, Kraft SA, Donohue KE, Biesecker BB, Brothers KB, Chen F, Hailu B, Hindorff LA, Hoban H, Hsu RL, Knight SJ, Koenig BA, Lewis KL, Lich KH, O’Daniel JM, Sasaki SO, Tomlinson GE, Waltz M, Wilfond BS, Ackerman SL, Majumder MA. Examining Access to Care in Clinical Genomic Research and Medicine: Experiences from the CSER Consortium. Journal of Clinical and Translational Science. Epub ahead of print; 2021.

Smith HS, Morain SR, Robinson JO, Canfield I, Malek J, Rubanovich CK, Bloss CS, Ackerman SL, Biesecker B, Brothers KB, Goytia CN, Horowitz CR, Knight SJ, Koenig B, Kraft SA, Outram S, Rini C, Shipman KJ, Waltz M, Wilfond B, McGuire AL. Perceived Utility of Genomic Sequencing: Qualitative Analysis and Synthesis of a Conceptual Model to Inform Patient-Centered Instrument Development. The Patient. Epub ahead of print; 2021.

Lindberg NM, Gutierrez AM, Mittendorf KF, Ramos M, Anguiano B, Angelo F, Joseph G. Challenges and Lessons Learned in Creating Accessible Study Materials for Spanish-speaking Participants in CSER Consortium Projects. Personalized Medicine. 2021 Aug; 18(5).

Horowitz CR, Orlando LA, Slavotinek AM, Peterson J, Angelo F, Biesecker B, Bonham VL, Cameron LD, Fullerton SM, Gelb BD, Goddard KAB, Hailu B, Hart R, Hindorff LA, Jarvik GP, Kaufman D, Kenny EE, Knight SJ, Koenig BA, Korf BR, Madden E, McGuire AL, Ou J, Wasserstein MP, Robinson M, Leventhal H, Sanderson SC. The Genomic Medicine Integrative Research Framework: A Conceptual Framework for Conducting Genomic Medicine Research. Am J Hum Genet. 2019 Jun 6;104(6):1088-1096. doi: 10.1016/j.ajhg.2019.04.006. Epub 2019 May 16.

Robinson JO, Wynn J, Biesecker B, Biesecker L, Bernhardt B, Brothers KB, Chung WK, Christensen KD, Green RC, Kaufman D, McGuire AL, Hart MR, Griesemer I, Patrick DL, Rini C, Veenstra D, Cronin AM, Gray SW. Psychological Outcomes Related to Exome and Genome Sequencing Result Disclosure: A Meta-Analysis of Seven Clinical Sequencing Exploratory Research (CSER) Consortium Studies. Genetics in Medicine 2019.

Amendola, L.M., Berg, J.S., Horowitz, C.R., Angelo, F., Bensen, J.T., Biesecker, B.B., Biesecker, L.G., Cooper, G.M., East, K., Filipski, K. and Fullerton, S.M., 2018. The clinical sequencing evidence-generating research consortium: integrating genomic sequencing in diverse and medically underserved populations. The American Journal of Human Genetics, 103(3), pp.319-327.

Presentations

Malek J, Robinson J,  Smith HS, Gutierrez A, Classen S,  Scollon S, Parsons DW, Plon S, McGuire A. How useful is genome sequencing to parents of pediatric cancer patients? Findings from the Texas KidsCanSeqStudy. ELSIcon2022: Innovating for a Just and Equitable Future. (2022).

Gutierrez A, Robinson J, Recinos A, Desrosiers L, Majumder M, Scollon S. Families’ experiences accessing follow-up care after receiving significant germline results through a pediatric cancer research study. ELSIcon2022: Innovating for a Just and Equitable Future. (2022).

Gutierrez AM, Robinson JO, Scollon S, Majumder MA, Street RL, Parsons DW, Plon SE, McGuire AL. “Spanish-preferring parents' perceptions of and satisfaction with communication in a pediatric cancer genomic setting.” American Public Health Association Annual Meeting. October 23-27, 2021.

Gutierrez AM, Robinson JO, Scollon S, Majumder MA, Street RL, Parsons DW, Plon SE, McGuire AL. “Perspectives and preferences of adolescent and young adult cancer patients related to their participation in genomic research.” American Society for Bioethics and Humanities Annual Conference. October 13-16, 2021.

Malek J, Robinson JO, Gutierrez AM, Wang T, Smith HS, Raesz-Martinez R, Scollon S, Recinos A, Majumder MA, Parsons DW, Plon SE, McGuire AL. Great Expectations: Parents’ Perceptions of Genomic Sequencing in Pediatric Cancer Patients. American Society for Bioethics and Humanities Annual Conference. October 13-16, 2021.

Malek J, Smith H, Islam R, Robinson JO, Hsu RL, Canfield I, Raesz-Martinez R, Recinos A, Scollon S, Majumder MA, Parsons DW, Plon SE, McGuire AL. Parents’ Expected Utility of Genomic Sequencing for Pediatric Cancer Patients in the Texas KidsCanSeq Study. American College of Medicine Genetics. March 17-21, 2020.

McGuire AL (Moderator), Malek J, Smith H, Brothers Kyle. Utility of Genomic Testing: A Multidisciplinary Perspective. American Society for Bioethics and Humanities Annual Meeting. Pittsburgh, PA, US. October 24-27, 2019. Accepted as panel presentation

Gutierrez AM, Robinson JO, Malek J, Majumder M, Street RL, Parsons DW, Plon SE, McGuire AL. Implications and considerations for engaging diverse participant populations in genome research: Emerging lessons from the Texas KidsCanSeq Study. American Public Health Association Annual Meeting. Philadelphia, PA, US. November 2-6, 2019. Accepted as poster presentation.

Plon S, Amendola L, Horowitz C, Joseph G. Addressing Literacy and Language to Equitably Deliver on the Promise of Precision Medicine. American College of Medical Genetics Annual Meeting. April 2-6, 2019. Workshop.

Gutierrez AM, Robinson JO, Hsu RL, Petersen DK, Malek J, Majumder MA, Street RL, Parsons DW, Plon SE, McGuire AL. The Texas KidsCanSeq Study: Enrolling Diverse Patient Populations into Genome Research. American Society for Bioethics and Humanities Annual Meeting. Anaheim, CA, US. October 18-21, 2018. Oral presentation.

Supplement Project: Adolescent and Young Adult Cancer Patients’ Attitudes toward and Decision-Making Preferences about Clinical

Project Description

The purpose of this supplement is to examine whether and how adolescent and young adult (AYA) patients with a cancer diagnosis want to be involved in decision making about genomic sequencing. Six months after receiving their genetic test results, we ask AYA patient-participants enrolled in the KidsCanSeq study to complete a 5-minute online survey about their attitudes toward and perceived utility of their results, as well as their satisfaction with the return of results process and preferences for making decisions about their study enrollment and cancer care.

Supported by: U01HG006485-S2, National Human Genome Research Institute, NIH

The BabySeq project seeks to safely test a new approach to newborn screening using whole genome sequencing. Healthy and sick newborns’ parents, and their pediatricians, will be enrolled into this study and randomized to either receive current standard newborn screening methods or undergo whole genome sequencing plus standard newborn screening methods. A genetic counselor will provide the genomic sequencing information and newborn screening results to the families and the families’ doctors.

Through quantitative longitudinal surveys, parents will be asked about the psychosocial impact of receiving genomic sequencing results and whether the information was useful to them. Physicians will be surveyed at multiple time points to assess the perceived utility of the information and whether and how the information is actually used to manage a patient’s health.

The study will focus on the long-term implications for the health of these babies, as well as the potential impact of receiving this genetic information on the parents, the child, and the family.

Supported by: U19HD077671, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Human Genome Research Institute, NIH

Publications

Green RC, Shah N, Genetti CA, et al. Actionability of unanticipated monogenic disease risks in newborn genomic screening: Findings from the BabySeq Project. Am J Hum Genet. 2023;110(7):1034-1045. doi:10.1016/j.ajhg.2023.05.007

Pereira S, Gutierrez AM, Robinson JO, et al. Parents' decision-making regarding whether to receive adult-onset only genetic findings for their children: Findings from the BabySeq Project. Genet Med. 2023;25(3):100002. doi:10.1016/j.gim.2022.100002

Armstrong B, Christensen KD, Genetti CA, et al. Parental Attitudes Toward Standard Newborn Screening and Newborn Genomic Sequencing: Findings From the BabySeq Study. Front Genet. 2022;13:867371. Published 2022 Apr 27. doi:10.3389/fgene.2022.867371

Pereira S, Smith HS, Frankel LA, et al. Psychosocial Effect of Newborn Genomic Sequencing on Families in the BabySeq Project: A Randomized Clinical Trial. JAMA Pediatr. 2021;175(11):1132-1141. doi:10.1001/jamapediatrics.2021.2829

Schwartz TS, Christensen KD, Uveges MK, et al. Effects of participation in a U.S. trial of newborn genomic sequencing on parents at risk for depression. J Genet Couns. 2022;31(1):218-229. doi:10.1002/jgc4.1475

Ceyhan-Birsoy, O., Murry, J.B., Machini, K., Lebo, M.S., Timothy, W.Y., Fayer, S., Genetti, C.A., Schwartz, T.S., Agrawal, P.B., Parad, R.B. and Holm, I.A., 2019. Interpretation of Genomic Sequencing Results in Healthy and Ill Newborns: Results from the BabySeq Project. The American Journal of Human Genetics, 104(1), pp.76-93.

Pereira S, Robinson JO, Gutierrez AM, Petersen D, Hsu RL, Lee CH, Schwartz TS, Holm IA, Beggs AH, Green RC, McGuire AL, for The BabySeq Project Group. Perceived Benefits, Risks, and Utility of Newborn Genomic Sequencing in the BabySeq Project. Pediatrics. 2019; 143(s1): S6-S13. https://doi.org/10.1542/peds.2018-1099C

Holm IA, McGuire AL, Pereira S, Rehm H, Green RC, Beggs AH, for the BabySeq Project Group. Returning a genomic result for an adult-onset condition to the parents of a newborn: Insights from the BabySeq Project. Pediatrics. 2019; 143(s1): S37-S43. https://doi.org/10.1542/peds.2018-1099H

VanNoy, G.E., Genetti, C.A., McGuire, A.L., Green, R.C., Beggs, A.H., Holm, I.A. and Group, T.B.P., 2019. Challenging the Current Recommendations for Carrier Testing in Children. Pediatrics, 143(Suppl 1), p.S27.

Genetti CA, Schwartz TS, Robinson JO, VanNoy GE, Petersen D, Pereira S, Fayer S, Peoples HA, Agrawal PB, Betting WN, Holm IA, McGuire AL, Waisbren SE, Yu TW, Green RC, Beggs AH, Parad RB. Parental Interest in Genomic Sequencing of Newborns: Enrollment Experience from the BabySeq Project. Genetics in Medicine. 2018; 21(30: 622-630. https://doi.org/10.1038/s41436-018-0105-6

Holm IA, Agrawal PB, Ceyhan-Birsoy O, Christensen KD, Fayer S, Frankel LA, Genetti CA, Krier JB, LaMay RC, Levy HL, McGuire AL, Parad RB, Park PJ, Pereira S, Rehm HL, Schwartz TS, Waisbren SE, Yu TW, Green RC, Beggs AH. The BabySeq Project: Implementing Genomic Sequencing in Newborns. BMC Pediatrics. 2018; 18(225). https://doi.org/10.1186/s12887-018-1200-1

Murry, J.B., Machini, K., Ceyhan-Birsoy, O., Kritzer, A., Krier, J.B., Lebo, M.S., Fayer, S., Genetti, C.A., VanNoy, G.E., Timothy, W.Y. and Agrawal, P.B., 2018. Reconciling newborn screening and a novel splice variant in BTD associated with partial biotinidase deficiency: a BabySeq Project case report. Molecular Case Studies, 4(4), p.a002873.

Berg JS, Agrawal PB, Bailey DB, Beggs AH, Brenner SE, Brower AM, Cakici JA, Ceyhan-Birsoy O, Chan K, Chen F, Currier RJ, Dukhovny D, Green RC, Harris-Wai J, Holm IA, Iglesias B, Joseph G, Kingsmore SF, Koenig BA, Kwok PY, Lantos J, Leeder SJ, Lewis MA, McGuire AL, Milko LV, Mooney SD, Parad RB, Pereira S, Petrikin J, Powell BC, Powell CM, Puck JM, Rehm HL, Risch N, Roche M, Shieh JT, Veeraraghavan N, Watson MS, Willig L, Yu TW, Urv T, Wise AL. Newborn Sequencing in Genomic Medicine and Public Health. Pediatrics. 2017;139(2): e20162252. https://doi.org/10.1542/peds.2016-2252

Ceyhan-Birsoy, O., Machini, K., Lebo, M.S., Tim, W.Y., Agrawal, P.B., Parad, R.B., Holm, I.A., McGuire, A., Green, R.C., Beggs, A.H. and Rehm, H.L., 2017. A curated gene list for reporting results of newborn genomic sequencing. Genetics in Medicine, 19(7), p.809.

Frankel LA, Pereira S, McGuire AL. Potential Psychosocial Risks of Sequencing Newborns. Pediatrics, 137, 2016: 24-9.

Waisbren, S.E., Bäck, D.K., Liu, C., Kalia, S.S., Ringer, S.A., Holm, I.A. and Green, R.C., 2015. In the Early Postpartum Period, Parents are Interested in Newborn Genomic Testing. Genetics in medicine: official journal of the American College of Medical Genetics, 17(6), p.501.

Select Presentations

Blout CL, Christensen KD, Smith HS, Pereira S, Robinson JO, Genetti CA, Fayer S, Betting WN, Schwartz TS, Holm, IA, Beggs, AH, McGuire, AL, Green, RC. Physician Perceived Utility and Preparedness for Newborn Genomic Sequencing: Findings from the BabySeq Project. American College of Medical Genetics Annual Meeting. April 2019, Seattle, WA. Oral presentation.

Christensen KD, Dukhovny D, Agrawal P, Genetti CA, Holm IA, Mackay Z, McGuire AL, Pereira S, Schwartz TS, Yu T, Beggs AH, Green RC, Parad R. Screening Newborns with Genomic Sequencing Increases Short-Term Downstream Health Care Costs: Preliminary Findings from the BabySeq Project. American College of Medical Genetics Annual Meeting. April 2019, Seattle, WA. Poster presentation.

Pereira S, Petersen D, Robinson JO, Frankel L, Christensen KD, Waisbren SE, Holm IA, Beggs AH, Green RC, McGuire AL. The impact of newborn genomic sequencing on families: Findings from the BabySeq Project. American Society of Human Genetics Annual Meeting. October 2018, San Diego, CA. Oral presentation.

Holm, IA, Genetti, CA, Pereira, S, Green, RC, Beggs, AH, McGuire, AL. BRCA2, ELSI, and the Return of Genomic Results in the BabySeq Project. 4th ELSI Congress, June 2017. Poster presentation.

HA Peoples, AM Gutierrez, S Pereira, JO Robinson, L Frankel, MC Towne, M Helm, CA Genetti, IA Holm, AH Beggs, RC Green, AL McGuire. Benefits, Risks, and Perceived Utility of Newborn Genomic Sequencing: Comparing Clinicians' and Physicians' Baseline Attitudes in the BabySeq Project. American Society of Human Genetics Annual Meeting. Vancouver, Canada. October 2016. Poster presentation.

Pereira S, Frankel L, Robinson JO, Weipert CM, Towne MC, Gutierrez A, Lee K, Holm IA, Dukhovny D, Beggs AH, Green RC, McGuire AL. Genomic Sequencing of Newborns: Exploring Psychosocial Risks to Families. American Society of Human Genetics Annual Meeting. Baltimore, MD. October 2015. Poster presentation.

This project is part of the NIH’s Clinical Sequencing Exploratory Research program. The project’s goal is to integrate genomic sequence data into the care of childhood cancer patients with high-risk solid tumors and brain tumors. With clinical colleagues at Texas Children’s Cancer Center and genetic scientist at BCM’s Whole Genome Laboratory, the project is assessing the impact of reporting whole exome sequence data through physicians to participating parents. The project is evaluating physician-parent communication and clinical decision-making to explore:

• How the availability of tumor whole exome sequence data affects physician recommendations regarding enrollment on specific clinical trials and the treatment plans chosen in the scenario of tumor recurrence.
• How the availability of germline whole exome sequence data affects cancer surveillance for patients and genetic testing and cancer surveillance for family members.

Additionally, this project will address parental understanding, preferences for receiving genomic sequence data, and ethical issues related to the appropriate use and reporting of this information, including possible incidental findings in a pediatric setting.

Supported by: U01HG006485, National Human Genome Research Institute, NIH

Publications

Scollon S, Bergstrom K, McCullough LB, McGuire AL, Gutierrez S, Kerstein R, Parsons DW, Plon SE. Pediatric cancer genetics research and an evolving preventive ethics approach for return of results after death of the subject. The Journal of Law, Medicine & Ethics. 2015 Sep;43(3):529-37.

McCullough LB, Slashinski MJ, McGuire AL, Street Jr RL, Eng CM, Gibbs RA, Parsons DW, Plon SE. Is whole‐exome sequencing an ethically disruptive technology? Perspectives of pediatric oncologists and parents of pediatric patients with solid tumors. Pediatric Blood and Cancer. 2016 Mar;63(3):511-5.

Gutierrez AM, Statham EE, Robinson JO, Slashinski MJ, Scollon S, Bergstrom KL, Street Jr RL, Parsons DW, Plon SE, McGuire AL. Agents of empathy: How medical interpreters bridge sociocultural gaps in genomic sequencing disclosures with Spanish-speaking families. Patient Education and Counseling. 2019 May 1;102(5):895-901.

Scollon S, Majumder MA, Bergstrom K, Wang T, McGuire AL, Robinson JO, Gutierrez AM, Lee CH, Hilsenbeck SG, Plon SE, Parsons DW. Exome sequencing disclosures in pediatric cancer care: Patterns of communication among oncologists, genetic counselors, and parents. Patient Education and Counseling. 2019 Apr 1;102(4):680-6.

Malek J, Pereira S, Robinson JO, Gutierrez AM, Slashinski MJ, Parsons DW, Plon SE, McGuire AL. Responsibility, culpability, and parental views on genomic testing for seriously ill children. Genetics in Medicine. 2019 Dec;21(12):2791-7.

Hsu RL*, Gutierrez AM*, Schellhammer SK, Robinson JO, Scollon S, Street Jr RL, Salisbury AN, Pereira S, Malek J, Parsons DW, Plon SE, McGuire AL. “Pediatric oncologists’ experiences returning and incorporating genomic sequencing results into cancer care.” Journal of Personalized Medicine. 2021 Jun; 11(6): 570. *These authors contributed equally to this work.

Gutierrez AM, Robinson JO, Statham EE, Scollon S, Bergstrom KL, Slashinski MJ, Parsons DW, Plon SE, McGuire AL, Street RL. Portero versus Portador: Spanish Interpretation of Genomic Terminology during Whole Exome Sequencing Results Disclosure. Personalized Medicine 14(6), 2017: 503-514.

Malek, J, M Slashinski, JO Robinson, Gutierrez AM, Parsons DM, Plon SE, McCullough LB, McGuire AL. Parental Perspectives on Whole Exome Sequencing in Pediatric Cancer: A Typology of Perceived Utility. Journal of Clinical Oncology: Precision Oncology, 2017. [Epub ahead of print]

Parsons DW, Roy A, Yang Y, Wang T, Scollon S, Bergstrom K, Kerstein RA, Gutierrez S, Petersen AK, Bavle A, Lin FY, López-Terrada DH, Monzon FA, Hicks MJ, Eldin KW, Quintanilla NM, Adesina AM, Mohila CA, Whitehead W, Jea A, Vasudevan SA, Nuchtern JG, Ramamurthy U, McGuire AL, Hilsenbeck SG, Reid JG, Muzny DM, Wheeler DA, Berg SL, Chintagumpala MM, Eng CM, Gibbs RA, Plon SE. Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors. JAMA, 2016. [Epub ahead of print]

Scollon S, Bergstrom K, Kerstein R, Wang T, Hilsenbeck SG, Ramamurthy U, Gibbs RA, Eng CM, Chintagumpala MM, Berg SL, McCullough LB, McGuire AL, Plon SE, Parsons DW. Obtaining Informed Consent for Clinical Tumor and Germline Exome Sequencing of Newly Diagnosed Childhood Cancer Patients. Genome Medicine, 6(9), 2014: 69.

Clayton EW, McCullough LB, Biesecker LG, Joffe S, Ross LF, Wolf SM, for the Clinical Sequencing Exploratory Research (CSER) Consortium Pediatrics Working Group. Addressing the Ethical Challenges in Genetic Testing and Sequencing of Children. Am J Bioeth, 14(3), 2014: 3-9.

McGuire AL, Joffe S, Koenig BA, Biesecker BB, McCullough LB, Blumenthal-Barby JS, Caulfield T, Terry SF, Green RC. Ethics and Genomic Incidental Findings. Science, 340, 2013: 1047-1048.

McGuire AL, Robinson JO, Ramoni RB, Morley DS, Joffe S, Plon SE. Returning Genetic Research Results: Study Type Matters. Personalized Medicine, 10(1), 2013: 27-34.

Ramoni RB, McGuire AL, Robinson JO, Morley DS, Plon SE, Joffe S. Experiences and Attitudes of Genome Investigators Regarding Return of Individual Genetic Test Results. Genetics in Medicine, 15(11), 2013: 882-887.

McGuire AL, McCullough LB, Evans JP. The Indispensable Role of Professional Judgment in Genomic Medicine. JAMA, 309, 2013: 1465-1466.

Presentations

Hsu RL, Gutierrez AM, Schellhammer S, Robinson JO, Pereria S, Scollon S, Malek J, Parsons DW, Plon SE, McGuire AL. Was Implementing Genomic Sequencing in Pediatric Cancer Care Disruptive? Oncologists’ Views After Returning Genomic Results in The BASIC3 Study. American College of Medicine Genetics. March 17-21, 2020. Poster Presentation.

Gutierrez AM, Robinson JO, Slashinski MJ, Statham EE, Street RL, Parsons DW, Plon SE, McGuire AL, McCullough LB. More than Just Translation: The Role of Medical Interpreters in the Disclosure of Whole Exome Sequencing Results for Spanish-Speaking Families. American Society for Bioethics and Humanities Annual Conference. Washington, DC. October 2016.

Malek, J. Culpability and Responsibility in Parents’ Experiences with Genome Sequencing for Pediatric Cancer Patients. American Society for Bioethics and Humanities Annual Conference. Washington, DC, October 2016.

Malek, J. Parental Perspectives on Whole Exome Sequencing in Pediatric Cancer: A Typology of Perceived Utility. American Society of Human Genetics Annual Meeting. Vancouver, CA, October 2016.

Gutierrez AM, Robinson JO, Statham EE, Slashinski MJ, Scollon S, Bergstrom KL, Street RL, Parsons DW, Plon SE, McGuire AL, McCullough LB. Lost in Translation: How Medical Interpreters Modify the Communication of Whole Exome Sequencing Results during Translation for Spanish-Speaking Families. National Society of Genetic Counselors Annual Education Conference. Seattle, WA. September/October 2016. Poster Presentation.

McCullough LB, Slashinski MJ, Wycliff J, McGuire AL, Street Jr. RL, Parsons DW, Plon SE. Do Pediatric Oncologists and Parents Experience Whole Exome Sequencing of Solid Organ Tumors in Children as a Disruptive Technology? The American Society for Bioethics and Humanities Annual Meeting, San Diego, CA. October 2014.

This study is a collaborative partnership between the human genetics programs at Baylor College of Medicine and Johns Hopkins University School of Medicine, forming the Baylor-Hopkins Center for Mendelian Genomics. Mendelian disorders are caused by an inherited mutation in a single gene.

The goal of the project is to find and recruit samples representing rare (Mendelian) disorders by creating and utilizing a worldwide network of colleagues and former trainees to identify and recruit thousands of patients and families with unexplained Mendelian phenotypes or with undiagnosed disease that segregates in their families as Mendelian traits. Dr. Amy McGuire, co-investigator, and a committee of experts are overseeing the ethical issues arising in the conduct of this research.

Supported by: U54HG006542, National Human Genome Research Institute, NIH

Publications

Gambin T, Jhangiani SN, Below JE, Campbell IM, Wiszniewski W, Muzny DM, Staples J, Morrison AC, Bainbridge MN, Penney S, McGuire AL, Gibbs RA, Lupski JR, Boerwinkle E. Secondary Finding and Carrier Test Frequencies in a Large Multiethnic Sample. Genome Med, 7, 2015; 54.

Many national and international public and private initiatives are forming to collect and share data on a large scale for research and clinical use. Collectively, these efforts may lead to the creation of a medical information commons.

Through this project, we aimed to inform policy decisions about effective governance for data sharing, and ensure that the values, rights and interests of individuals whose data may populate the information commons are represented. Specifically we aimed to:

• Identify and analyze existing models for collecting diverse sources of data into a medical information commons to enable large scale research and clinical application
• Evaluate the effectiveness of existing models and develop new approaches to address key policy issues from the perspective of expert stakeholders
• Solicit informed public input on existing models and innovative approaches from individuals whose data may populate a medical information commons.
• Describe incentives to share BRCA variant data and obstacles hindering the sharing of those data, and incorporate BRCA previvors and survivors into the governance and oversight structures for the emergent BRCA data commons.

Over the past four years, we carried out the following:

• A landscape analysis of existing data-sharing efforts
• In-depth interviews with multiple stakeholders from various sectors (e.g., academia, government, and private industry)
• Deliberative sessions with members of the public at three U.S. cities
• In-person meetings with a multidisciplinary external advisory committee

Supported by: DI-2017C2-7726, Patient-Centered Outcomes Research Institute

Special Issue in the Journal of Law, Medicine & Ethics

Where scientists and ethicists look to address and propose solutions to many of the questions that surround medical data sharing.

Check It Out

Publications

Bollinger JM, Sanka A, Dolman L, Liao RG, Cook-Deegan R. BRCA1/2 Variant Data-Sharing Practices. J Law Med Ethics. 2019;47(1):88-96. doi:10.1177/1073110519840487

Deverka PA, Gilmore D, Richmond J, et al. Hopeful and Concerned: Public Input on Building a Trustworthy Medical Information Commons. J Law Med Ethics. 2019;47(1):70-87. doi:10.1177/1073110519840486

McGuire AL, Roberts J, Aas S, Evans BJ. Who Owns the Data in a Medical Information Commons? J Law Med Ethics. 2019;47(1):62-69. doi:10.1177/1073110519840485

Majumder MA, Bollinger JM, Villanueva AG, Deverka PA, Koenig BA. The Role of Participants in a Medical Information Commons. J Law Med Ethics. 2019;47(1):51-61. doi:10.1177/1073110519840484

Bollinger JM, Zuk PD, Majumder MA, et al. What is a Medical Information Commons? J Law Med Ethics. 2019;47(1):41-50. doi:10.1177/1073110519840483

Villanueva AG, Cook-Deegan R, Robinson JO, McGuire AL, Majumder MA. Genomic Data-Sharing Practices. J Law Med Ethics. 2019;47(1):31-40. doi:10.1177/1073110519840482

Villanueva AG, Cook-Deegan R, Koenig BA, et al. Characterizing the Biomedical Data-Sharing Landscape. J Law Med Ethics. 2019;47(1):21-30. doi:10.1177/1073110519840481

McGuire AL, Majumder MA, Villanueva AG, et al. Importance of Participant-Centricity and Trust for a Sustainable Medical Information Commons. J Law Med Ethics. 2019;47(1):12-20. doi:10.1177/1073110519840480

Cook-Deegan R, Majumder MA, McGuire AL. Introduction: Sharing Data in a Medical Information Commons - Robert Cook-Deegan, Mary A. Majumder, Amy L. McGuire, 2019. The Journal of Law, Medicine & Ethics. 2019;47(1):7-11.

Majumder MA, Zuk PD, McGuire AL. Medical Information Commons. In: Hudson B, Rosenbloom J, Cole D, eds. Routledge Handbook of the Study of the Commons. 1st ed.

Deverka PA, Majumder MA, Villanueva AG, et al. Creating a data resource: what will it take to build a medical information commons? Genome Med. 2017;9(1):84. doi:10.1186/s13073-017-0476-3

Majumder MA, Guerrini CJ, Bollinger JM, Cook-Deegan R, McGuire AL. Sharing data under the 21st Century Cures Act. Genet Med Off J Am Coll Med Genet. May 2017. doi:10.1038/gim.2017.59

Cook-Deegan R, McGuire AL. Moving beyond Bermuda: sharing data to build a medical information commons. Genome Res. 2017;27(6):897-901. doi:10.1101/gr.216911.116

Majumder MA, Cook-Deegan R, McGuire AL. Beyond Our Borders? Public Resistance to Global Genomic Data Sharing. PLoS Biol. 2016;14(11):e2000206. doi:10.1371/journal.pbio.2000206

Presentations

Majumder MA. Back to the Future: A Snapshot of Current Genomic Data-Sharing Practices. Presented at the: American Society for Bioethics and Humanities Annual Conference; October 2018; Anaheim, CA.

Majumder MA. What Role for Participants? Views of Expert Stakeholders Influencing Data-Sharing Policies and Practices. Presented at the: American Society for Bioethics and Humanities Annual Conference; October 2017; Kansas City, MO.

Villanueva AG. The Challenges of Collecting and Sharing Environmental Data in the Current Genomics Era. Poster presented at the: American Society for Bioethics and Humanities Annual Conference; October 2017; Kansas City, MO.

Villanueva AG. Hashtag Who's Missing? Lessons for Participant-Centric and Pediatric Genomic Databases. Presented at the: ELSI Congress; June 2017; Farmington, CT.

McGuire AL. What Does it Mean to Own the Data in a Medical Information Commons? Presented at the: ELSI Congress; June 2017; Farmington, CT.

Villanueva AG. The Data Ecosystem: Current Data-Sharing Policies and Practices. Presented at the: ELSI Congress; June 2017; Farmington, CT.

Majumder MA. Big data sharing in precision medicine. Presented at the: World precision Medicine Congress; May 2017; London, UK.

Majumder MA, Garrison NA, Bonham V, Villanueva AG. Critical Distance in ELSI Genomics Research - More Than Advocacy for the "All-Frills Yuppie Health Care Boutique"? Presented at the: American Society for Bioethics and Humanities Annual Conference; October 2016; Washington, DC.

McGuire AL, Goldstein MM, Rodriguez LL, O'Donnell CJ. Building a Medical Information Commons: Ethical, Policy and Practical Challenges. Presented at the: American Society for Bioethics and Humanities Annual Conference; October 2016; Washington, DC.

Villanueva AG, McGuire AL, Majumder MA. Genes and the Environment: Current Data Collection, Sharing and Privacy Protection Practices. Poster presented at the: American Public Health Association's Annual Meeting; November 2016; Denver, CO.

McGuire AL. Building the Medical Information Commons: Data Sharing Ethics and Policy. Human Genome Meeting; 2016; Houston, TX.

Substantial resources have been devoted to policy evaluation of clinical genomic sequencing that hinge on the conceptualization and measurement of utility. However, most evaluations fail to capture the full utility of genomic sequencing because they do not account for impact on family members. Pediatrics is a clinical area in which study of family impact is imperative due to the clinical nature of genetic disorders that manifest in childhood and the patient-parent-physician decision-making context, in addition to potential identification of patients biologic relatives who may benefit from genetic screening.

Although traditional decision science methods for health economic evaluation produce evidence in the form decision-makers rely upon, they tend to focus on the individual patient and do not consider the ethical, legal, and social implications (ELSI) of testing for families. Cross-disciplinary effort is necessary integrate ELSI issues that influence clinical implementation and family preferences using decision science methods for robust modeling and outcomes assessment.

The goal of the proposed research is to develop a clinically relevant and ELSI-informed model to assess family-level impact of genomic sequencing in the context of pediatric clinical care.

Supported by: National Institute of Health (NIH) National Human Genome Research Institute (NHGRI) Career Transition Award (K99) Project: 1K99HG011491-01

The Human Genome Sequencing Center at Baylor College of Medicine supports a broad range of activities that address biomedical questions using high-throughput sequencing.

The ethics core, led by Dr. Amy McGuire, provides ongoing consultation on issues as they arise, including ethical and policy issues related to individual whole genome sequencing, broad data sharing, return of individual research results, and informed consent for biobanking and large scale genomic research.

Supported by: U54HG003273, National Human Genome Research Institute, NIH

Publications

Pereira S, Robinson JO, McGuire AL. Return of individual genomic research results: What do consent forms tell participants. European Journal of Human Genetics 2016, [PubMed ahead of print]

Curnette MA, Frumovitz KL, Bollinger JM, Cook-Deegan RM, McGuire AL, Majumder MA. Developing context-specific next-generation sequencing policy. Nat Biotechnol. 2016 34(5): 466-470.

Green RC, Goddard KA, Jarvik GP, Amendola LM, Appelbaum PS, Berg JS, Bernhardt BA, Biesecker LG, Biswas S, Blout CL, Bowling KM, Brothers KB,Burke W, Caga-Anan CF, Chinnaiyan AM, Chung WK, Clayton EW, Cooper GM, East K, Evans JP, Fullerton SM, Garraway LA, Garrett JR, Gray SW,Henderson GE, Hindorff LA, Holm IA, Lewis MH, Hutter CM, Janne PA, Joffe S, Kaufman D, Knoppers BM, Koenig BA, Krantz ID, Manolio TA, McCullough L,McEwen J, McGuire A, Muzny D, Myers RM, Nickerson DA, Ou J, Parsons DW, Petersen GM, Plon SE, Rehm HL, Roberts JS, Robinson D, Salama JS,Scollon S, Sharp RR, Shirts B, Spinner NB, Tabor HK, Tarczy-Hornoch P, Veenstra DL, Wagle N, Weck K, Wilfond BS, Wilhelmsen K, Wolf SM, Wynn J, Yu JH;CSER Consortium. Clinical sequencing exploratory research consortium: Accelerating evidence-based practice of genomic medicine. Am J Hum Genet. 2016, 98(6): 1051 - 1066.

Messner D, Naber J, Koay P, Cook-Deegan R, Majumder M, Javitt, Deverka P, Dvoskin R, Bollinger J, Curnutte J, Mcguire A. Barriers to clinical adoption of next generation sequencing: Perspectives of Delphi Panel. Applied & Translational Genomics, 2016.

Gambin T, Jhangiani SN, Below JE, Campbell IM, Wiszniewski W, Muzny DM, Staples J, Morrison AC, Bainbridge MN, Penney S, McGuire AL, Gibbs RA, Lupski JR, Boerwinkle E. Secondary Finding and Carrier Test Frequencies in a Large Multiethnic Sample. Genome Med, 7, 2015; 54.

The MedSeq Project is one of the nine projects funded by the NIH’s Clinical Sequencing Exploratory Research program. MedSeq is exploring and comparing the impact of using whole genome sequencing (WGS) in two distinct clinical settings, primary care and cardiology. This randomized controlled trial is enrolling primary care physicians and their healthy, middle-aged patients, and cardiologists and their patients presenting with cardiomyopathy. Enrolled patients are randomly assigned to either undergo WGS or receive current standard of care.

Major goals of the project include creating standards for genetic variant disclosure to physicians and their patients, a careful examination of the preferences and motivations of physicians and patients enrolled, evaluating the flow and utilization of genomic information within the clinical interactions, and assessing the understanding, behavior, medical consequences and healthcare costs associated with the use of WGS in these models of medical practice.

Supported by: U01HG006500, National Human Genome Research Institute, NIH

Publications

Roberts JS, Robinson JO, Diamond PM, Bharadwaj A, Christensen KD, Lee KB, Green RC, McGuire AL. Patient understanding of, satisfaction with, and perceived utility of whole-genome sequencing: findings from the MedSeq Project. Genet Med. 2018. [Epub ahead of print]

Vassy JL, Davis JK, Kirby C, Richardson IJ, Green RC, McGuire AL, Ubel PA. How Primary Care Providers Talk to Patients about Genome Sequencing Results: Risk, Rationale, and Recommendation. J Gen Intern Med. 2018. [Epub ahead of print]

Robinson JO, Carroll TM, Feuerman LZ, Perry DL, Hoffman-Andrews L, Walsh RC, Christensen KD, Green RC, McGuire AL. Participants and Study Decliners' Perspectives About the Risks of Participating in a Clinical Trial of Whole Genome Sequencing. J Empir Res Hum Res Ethics 11(1), 2016: 21 - 30.

Lupo PJ, Robinson JO, Diamond PM, Jamal L, Danysh HE, Blumenthal-Barby J, Lehmann LS, Vassy JL, Christensen KD, Green RC, McGuire AL. Patients' perceived utility of whole-genome sequencing for their healthcare: findings from the MedSeq project. Per Med, 13(1), 2016: 13-20.

Christensen KD, Vassy JL, Jamal L, Lehmann LS, Slashinski MJ, Perry DL, Robinson JO, Blumenthal-Barby J, Feuerman LZ, Murray MF, Green RC, McGuire AL. Are Physicians Prepared for Whole Genome Sequencing? A Qualitative Analysis. Clin Genet, 89(2), 2016: 228-34.

Vassy JL, Christensen KD, Slashinski MJ, Lautenbach DM, Raghavan S, Robinson JO, Blumenthal-Barby J, Feuerman LZ, Lehmann LS, Murray MF, Green RC, McGuire AL. Someday it will be the norm': physician perspectives on the utility of genome sequencing for patient care in the MedSeq Project. Per Med, 12(1), 2015: 23-32.

Green RC, Lautenbach D, McGuire AL. GINA, Genetic Discrimination, and Genomic Medicine. N Engl J Med, 372(5), 2015: 397-399.

Vassy JL, McLaughlin HL, MacRae CA, Seidman CE, Lautenbach DM, Krier J, Lane WJ, Kohane IS, Murray MF, McGuire AL, Rehm HL, Green RC. A One-Page Summary Report of Genome Sequencing for the Healthy Adult. Public Health Genomics, 18(2), 2015: 123-129.

Blumenthal-Barby JS, McGuire AL, Green RC, Ubel PA. How behavioral economics can help to avoid 'The last mile problem' in whole genome sequencing. Genome Med, 7(1), 2015: 13.

Blumenthal-Barby JS, McGuire AL, Ubel PA. Why Information Alone is Not Enough: Behavioral Economics and the Future of Genomic Medicine. Ann Intern Med, 161(8), 2014: 605-606.

Vassy JL, Lautenbach DM, McLaughlin HM, Kong SW, Christensen KD, Krier J, Kohane IS, Feuerman LZ, Blumenthal-Barby J, Roberts JS, Lehmann LS, Ho CY, Ubel PA, MacRae CA, Seidman CE, Murray MF, McGuire AL, Rehm HL, Green RC. The MedSeq Project: A Randomized Trial of Integrating Whole Genome Sequencing into Clinical Medicine. Trials, 15(1), 2014: 85.

Gray SW, Martins Y, Feuerman LZ, Bernhardt BA, Biesecker BB, Christensen KD, Joffe S, Rini C, Veenstra D, McGuire AL. Social and Behavioral Research in Genomic Sequencing: Approaches from the Clinical Sequencing Exploratory Research Consortium Outcomes and Measures Working Group. Genetics in Medicine 16(10), 2014: 727-735.

McGuire AL, Joffe S, Koenig BA, Biesecker BB, McCullough LB, Blumenthal-Barby JS, Caulfield T, Terry SF, Green RC. Ethics and Genomic Incidental Findings. Science, 340, 2013: 1047-1048.

Green RC, Berg JS, Grody WW, Kalie SS, Korf BR, Marin CL, McGuire AL, et al. ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing. Genetics in Medicine 15(7), 2013: 565-574.

McGuire AL, McCullough LB, Evans JP. The Indispensable Role of Professional Judgment in Genomic Medicine. JAMA, 309, 2013: 1465-1466.

Lewis MH, Scheurer ME, Green RC, McGuire AL. Research Results: Preserving Newborn Blood Samples. Science Translational Medicine, 4(159), 2012: 159cm12.

Green RC, Berg JS, Berry GT, Biesecker LG, Dimmock D, Evans JP, Grody WW, Hegde M, Kalia S, Korf BR, Krantz I, McGuire AL, Miller DT, Murray MF, Nussbaum R, Plon SE, Rehm HL, Jacob HJ. Exploring Concordance and Discordance for Return of Incidental Findings from Clinical Sequencing. Genetics in Medicine, 14(4), 2012: 405-410.

Presentations

Christensen KD, Lupo P, Robinson JO, Blumenthal-Barby J, Vassy JL, Lehmann LS, Ubel PA, Roberts JS, Green RC, McGuire AL. Patient Perceptions about the Utility of Family History Review during Whole Genome Sequencing: Initial Findings from the MedSeq Study. The American Society of Human Genetics Annual Meeting, San Diego, CA. October 2014.

Vassy JL, Davis K, Robinson JO, Blumenthal-Barby J, Christensen KD, Green RC, McGuire AL, Ubel PA for the MedSeq Project. Contextualization and Recommendation: How Doctors and Patients Discuss Whole-Genome Sequencing and Results. The American Society of Human Genetics Annual Meeting, San Diego, CA. October 2014.

Jamal L, Robinson JO, Lupo P, Blumenthal-Barby J, Feuerman LZ, Vassy JL, Christensen KD, Slashinski MJ, Wycliff J, Green RC, McGuire AL for the MedSeq Project. Patients’ Perceptions of Whole Genome Sequencing Results and Plans to Use Non-Actionable Findings. The American Society of Human Genetics Annual Meeting, San Diego, CA. October 2014. The American Society for Bioethics and Humanities Annual Meeting, San Diego, CA. October 2014. The National Society of Genetic Counselors Annual Education Conference, New Orleans, LA. September 2014.

McGuire A, Henderson G, Gray S, Rini C, Bernhardt B. Whole Genome/Exome Sequencing: Patient Expectations, Literacy, and Preferences for Genome Information. The American Society of Human Genetics Annual Meeting, San Diego, CA. October 2014.

Vassy JL, Christensen KD, Slashinski MJ, Lautenbach D, Robinson JO, Blumenthal-Barby J, Feuerman LZ, Green RC, McGuire AL. "Someday it will be the Norm:" Physician Perceptions of the Clinical Utility of Whole Genome Sequencing. Society of General Internal Medicine National Meeting, San Diego, CA. April 2014.

Carroll T, Robinson JO, Feuerman LZ, Lautenbach DM, Green RC, McGuire AL. ELSI Concerns of Participants and Decliners in the MedSeq Project: A Randomized Trial of Whole Genome Sequencing. The National Conference on Undergraduate Research, Lexington, KY. April 2014. The American College of Medical Genetics Annual Meeting, Nashville, TN. March 2014.

Christensen KD, Green RC, Vassy JL, Murray MF, McGuire AL. "Somebody Translate this Information for Me:" Physician Perceptions of their Preparedness to Disclose Full Genome Sequencing Results. The American College of Medical Genetics Annual Meeting, Nashville, TN. March 2014.
 

Enabling Personalized Medicine through Exome Sequencing in the U.S. Air Force (the MilSeq Project) is a pilot study examining the process of incorporating genome sequencing (GS) into the United States Air Force (USAF) military health system. Active-duty service members of the USAF (Airmen) are enrolled into the study to undergo GS. Results are returned directly to Airmen by military healthcare providers who are also study participants, and are placed in their electronic health records by the study genetic counselor. Healthcare providers participate in an education session about genomic medicine and are supported by the study genetic counselor.

Through pre- and post-disclosure surveys, we ask Airmen about their motivations and barriers to undergoing GS, the impact of receiving their sequencing results, and their thoughts on integrating this type of information into the USAF military health system. Healthcare providers complete surveys about the genomic education session, their genetic knowledge and feelings of preparedness to communicate this information, and their perceived utility of the information. We are also assessing how the information is used to inform the management of the Airmen’s health.

We are interested in gaining knowledge about the barriers to and medical, behavioral, and economic implications of implementing genomic sequencing information into clinical care in the military health system through the perspectives of USAF Airmen and healthcare providers.

Supported by: FA8650-17-2-6704, U.S. Department of Defense

Disclaimer

This material is based on research sponsored by Air Force Medical Support Agency, Research and Acquisition Directorate AFMSA/SG5 under cooperative agreement number FA8650-17-2-6704. The U.S. Government is authorized to reproduce and distribute reprints for Governmental purposes notwithstanding any copyright notation thereon.

The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing the official policies or endorsements, either expressed or implied, of Air Force Medical Support Agency, Research and Acquisition Directorate AFMSA/SG5 or the U.S. Government.

The voluntary, fully informed consent of the subjects used in this research was obtained as required by 32 CFR 219 and AFI 40-402, Protection of Human Subjects in Biomedical and Behavioral Research.

Publications

De Castro M, Biesecker L, Turner C, Brenner R, Witkop C, Mehlman M, Bradburne, Green RC. Genomic Medicine in the Military. Genomic Medicine. 2016: 1:15008.

Presentations

Hsu RL, Pereira S, Robinson JO, Islam R, Majumder M, Parasidis E, Mehlman MJ, Christensen K, Maxwell MD, Blout C, Lebo M, Killian JK, De Castro M, Green RC, McGuire AL. US Air Force Airmen's Perceptions after Receiving Genome Sequencing: Preliminary Results from the MilSeq Project. American Society for Bioethics and Humanities Annual Meeting. Pittsburgh, PA, US. October 24-27, 2019. Accepted as oral presentation.

Blout CL, Sirotich E, Zoltick E, Christensen K, Robinson JO, Pereira S, Petersen DK, Maxwell MD, Gardner C, De Castro M, Lebo M, McGuire AL, Brenner R, Green, RC. Healthy Genomic Sequencing: What Airmen Want to Know? Findings from the MilSeq Project. National Society of Genetic Counselors Annual Meeting. Atlanta, GA, US. November 14-17, 2019. Poster presentation.

Pereira S, Robinson JO, Hsu, RL, Petersen DK, Majumder MA, Parasidis E, Mehlman MJ, Christensen KD, Maxwell MD, Blout CL, Lebo M, Brenner R, Gardner C, De Castro M, Green RC, McGuire AL. Airmen's Attitudes Toward Genomic Sequencing In The US Air Force: Results From The Milseq Project. American Society for Bioethics and Humanities Annual Meeting. Anaheim, CA, US. October 18-21, 2018. Oral presentation.

Hsu RL, Pereira S, Robinson JO, Petersen JK, Majumder M, Parasidis E, Mehlman M, Christensen K, Maxwell MD, Blout C, Lebo M, Brenner R, Gardner C, De Castro M, Green RC, McGuire AL. Airmen's Attitudes toward Genomic Sequencing in the US Air Force: Results from The MilSeq Project. American Society for Human Genetics Annual Meeting. San Diego, CA, US. October 16-20, 2019. Poster presentation.

Maxwell, MD. Robinson JO, Gardner CL, De Castro M, Lebo M, Blout CL, Vassy JL, Christensen KD, Krier JB, Pereira S, McGuire AL, Mehlman MJ, Parasidis E, Brenner R, Green RC. Pharmacogenomics in the US Air Force: Development of a Tailored Panel for the MilSeq Project. American College of Medical Genetics and Genomics. Charlotte, NC. April 2018.

Press Release

US Air Force Studying Impact of Exome Sequencing in Routine Care, Genomeweb Clinical Sequencing. October 2017.

As a co-investigator on this project, Dr. Amy McGuire is providing ethical oversight and consultation on ethical issues as they arise, including challenges regarding banked biospecimens.

The scientific purpose of the study is to explore the underlying factors influencing a woman’s risk of preterm birth. With a longitudinal, case-cohort based approach, investigators will use whole-genome shotgun sequencing to study women’s metagenomic DNA sequencing, metatranscriptomics, and metabolomics of the oral, vaginal, placental and stool microbiome. In addition to characterizing the multi’omics generated data, the project will lead toward the development of a community resource (i.e., a rich dataset) for future large-scale studies on host and microbe biomarkers acquired in this set of preterm, near term, and term births.

Supported by: R01NR014792, National Institute of Nursing Research, NIH

Publications

Chandresekaran S, McGuire AL, Van den Veyver IB. Do recent US Supreme Court rulings on patenting of genes and genetic diagnostics affect the practice of genetic screening and diagnosis in prenatal and reproductive care? Prenatal Diagn, 34(10), 2014; 921-926.

The PeopleSeq Consortium, funded by the NIH, is conducting a longitudinal study of healthy adults by surveying those who plan to, or have already received, their own genomic sequence information. Genomic sequencing, including genome sequencing (GS) and exome sequencing (ES), are available to and being utilized by physicians and their patients in both research and clinical settings. The use of genomic sequencing in healthy populations to screen for disease variants is conceptually different from anything practiced today in medical genetics. Instead of using genomic technology in the hopes of identifying a cause for a specific condition, genomic sequencing in healthy individuals would follow a model of “predispositional" genomic testing. Genomic sequencing of healthy individuals could grow to resemble current population-based preventative screening measures, such as newborn screening (the "heel price" test).

PeopleSeq participants have received their GS information through various commercial and research avenues, many of which follow different return of results models. Our longitudinal surveys focus on the medical, behavioral, and economic impact of performing genomic sequencing in healthy adults, and were built by drawing upon our prior experience in designing and implementing rigorous studies of the outcomes of genetic testing and results disclosure, including the Impact of Personal Genomics (PGen) Study and the MedSeq Project.

We are also conducting interviews with participants who received unanticipated disease risk results to explore the impact of this information, and participant's decision making processes, informational needs, and sharing preferences after receiving such information.

Despite the promise of genomic sequencing for personalized medicine, there remain significant challenges and concerns that must be addressed. Some consider the utilization of genomic sequencing in healthy individuals to be controversial; the short and long-term outcomes of providing genomic sequencing information to healthy adults are not yet known.

The PeopleSeq Consortium enables us to collect valuable empirical data on the medical, behavioral, and economic impact of performing genomic sequencing in healthy adults.

Supported by: R01-HG009922, R01HG011268, National Human Genome Research Institute, NIH

Participating Institutes in the PeopleSeq Consortium

• Genomes2People
• PeopleSeq Scientific Team
• Baylor College of Medicine
• GeneDx
• Genos/NantOmics
• Harvard Personal Genome Project
• HudsonAlpha Institute for Biotechnology
• Illumina
• Invitae
• Mayo Clinic
• Mt. Sinai School of Medicine
• OpenSNP
• *PerkinElmer
• SoundRocket/Survey Sciences Group
• University of Vermont
• *Veritas Genetics
• *Formal affiliation pending

View more detailed information about the PeopleSeq Consortium or email us at peopleseq@partners.org.

Publications

Zoltick, E.S., Linderman, M.D., McGinniss, M.A., Ramos, E., Ball, M.P., Church, G.M., Leonard, D.G., Pereira, S., McGuire, A.L., Caskey, C.T. and Sanderson, S.C., 2019. Predispositional genome sequencing in healthy adults: design, participant characteristics, and early outcomes of the PeopleSeq Consortium. Genome medicine, 11(1), p.10.

Linderman, M., Nielsen, D. and Green, R., 2016. Personal genome sequencing in ostensibly healthy individuals and the PeopleSeq Consortium. Journal of personalized medicine, 6(2), p.14.

Presentations

Zoltick, ES, Linderman, MD, Nielsen, DE, Betting, WN, McGinniss, MA, Ramos, E, Ball, MP, Leonard, DGB, Pereira, S, Sanderson, SS, Crawford, SD, Green, RC, the PeopleSeq Consortium. Temporal Differences in Concerns, Motivations, and Attitudes regarding Predispositional Genome Sequencing among Healthy Adults: Findings from the PeopleSeq Consortium. Poster presented at the American Society of Human Genetics Annual Meeting, October 2018, San Diego, CA.

Sutti, S, Zotick, E, Linderman, M, Nielsen, D, McGinnis, M, Ramos, E, Ball, M, Leonard, D, Pereira, S, Sanderson, S, Crawford, S, Green, RC. Participant Perspectives in Discussing Predispositional Genome Sequencing Results with Healthcare Providers: Findings from the PeopleSeq Consortium. Poster presented at the American College of Medical Genetics and Genomics Annual Meeting, April 2018, Charlotte, NC.

Zoltick, E, Linderman, M, Nielsen, D, McGinnis M, Ramos, E, Ball, M, Leonard, D, Pereira, S, Sanderson, S, Crawford, S, Green, RC. Motivations, Outcomes, and Attitudes Following Predispositional Genome Sequencing among Healthcare Professionals and Non-Healthcare Professionals: Findings from the PeopleSeq Consortium. Poster presented at the American College of Medical Genetics and Genomics Annual Meeting, April 2018, Charlotte, NC.

Green RC, Hambuch T, Ball M, Church G, Linderman M, Pearson N, Roberts JS, Sanderson S, Weipert C, Helm M, Schadt E. Predispositional Genome Sequencing in Healthy Adults: Preliminary Findings from the PeopleSeq Study. American College of Medical Genetics Annual Meeting. Salt Lake City, UT, US. March 24-28, 2015. Poster presentation.

The clinical integration of next generation sequencing (NGS) has brought to light challenging policy concerns such as oversight of test quality and services, patenting and licensing issues, privacy and data sharing, and insurance coverage and reimbursement. A team of legal and policy experts came together to identify, prioritize and deliberate the most important and tractable policy barriers and solutions to the clinical adoption of NGS.

This involved three major research activities:

1. Landscape analysis of current and emerging NGS companies and qualitative interviews with industry leaders, to understand how the industry is developing in an uncertain policy climate (see Nature Biotechnology publication and check out the list of next generation sequencing companies we developed using crowdsourcing methods).
2. Legal analysis of key policy issues related to regulation, reimbursement, intellectual property and data sharing (see Journal of Law, Medicine & Ethics special issue).
3. Modified Delphi process involving a series of four surveys to identify and prioritize the unique policy challenges involved in translating the health benefits of NGS (see Applied & Translational Genomics publication).

Supported by: R01HG006460, National Human Genome Research Institute, NIH

Publications

Guerrini CJ, McGuire AL, Majumder MA, Bollinger JS, Rowan PJ. Constraints on Gene Patent Protection Fuel Secrecy Concerns: A Qualitative Study, J. Law & Biosciences 4(3), 2017: 542-564.

Guerrini CJ, McGuire AL, Majumder MA. Myriad Take Two: Can Private Genomic Databases Remain Secret? Science 356(6338), 2017: 586-587.

Curnutte MA, Frumovitz KL, Bollinger JM, Cook-Deegan RM, McGuire AL, Kaufman DJ, Majumder MA. Developing context-specific next-generation sequencing policy. Nat Biotechnol 34, 2016: 466-470.

Messner DA, Naber JA, Koay P, Cook-Deegan R, Majumder M, et al. Barriers to clinical adoptions of next generation sequencing: Perspectives of a policy Delphi panel. Appl Trans Genom 10, 2016: 19-24.

Guerrini CJ, Majumder M, McGuire AL. Persistent confusion and controversy surrounding gene patents. Nat Biotechnol 34(2), 2016: 145-7.

Deverka PA, Kaufman D, McGuire AL. Overcoming the Reimbursement Barriers for Clinical Sequencing. JAMA 312(18), 2014: 1857-1858.

Special Issue for the Journal of Law, Medicine & Ethics 42(3), 2014 includes articles from:

• Amy McGuire, Margaret Curnutte, and David Kaufman. Clinical Integration of Next Generation Sequencing: A Policy Analysis
• Gail Javitt and Katherine S. Carner. Regulation of Next Generation Sequencing
• Patricia Deverka and Jennifer Dreyfus. Clinical Integration of Next Generation Sequencing: Coverage and Reimbursement Challenges
• Robert Cook-Deegan and Subhashini Chandrasekharan. Patents and Genome-Wide DNA Sequence Analysis: Is it Safe to Go into the Genome?
• Barbara J. Evans. Economic Regulation of Next-Generation Sequencing

Curnutte MA, Frumovitz KL, Bollinger JM, McGuire AL, Kaufman DJ. Development of the Clinical NGS Industry in a Shifting Policy Climate. Nature Biotechnology 32(10), 2014: 980-982.

Chandrasekharan S, McGuire AL, Van den Veyver IB. Do Recent US Supreme Court Rulings on Patenting of Genes and Genetic Diagnostics Affect the Practice of Genetic Screening and Diagnosis in Prenatal and Reproductive Care? Prenatal Diagn 34(10), 2014: 921-926.

Selected Presentations

Guerrini C. The New Landscape of Patent Eligibility: Empirical Findings. BioCanRx Summit for Cancer Immunotherapy. Ottawa, ON. June 2017.

Guerrini C. The New Legal Landscape of Genomics Patents: A Qualitative Study. The American Society of Human Genetics Annual Meeting, Washington, DC. October 2016.

McGuire AL, Kaufman DJ, Javitt GH, Deverka PA, Messner D, Cook-Deegan R, Curnutte MA, Bollinger J, Dvoskin R, Chandrasekharan S, Evans BJ. Clinical Integration of NGS: A Policy Analysis. The American Society of Human Genetics Annual Meeting, San Diego, CA. October 2014.

Curnutte MA, Frumovitz KL, Bollinger J, McGuire AL, Kaufman DJ. Tracking the Development of the Clinical Next Generation Sequencing Industry. The American Society of Human Genetics Annual Meeting, San Diego, CA. October 2014.

McGuire AL. Stakeholder Views of Regulatory Issues Related to Next Generation Sequencing. Legal Issues in Genomic Medicine Session, Clinical Sequencing Exploratory Research (CSER) Meeting, Bethesda, MD. October 2014.

Curnutte MA. The Next Generation Sequencing Industry: A Critique of the Policy-Lag Narrative. 13th Annual Science & Democracy Network Meeting, Vienna, Austria, June 2014. Department of Social Science, Health & Medicine, King’s College London, United Kingdom. June 2014.

Curnutte MA. Genetic Information in Context. Center for Genomics and Society, University of North Carolina, Chapel Hill, NC. April 2014.

Curnutte MA. Development of the Clinical NGS Industry in a Shifting Policy Climate. Clinical Genetics Conference, sponsored by Baylor College of Medicine, Houston, TX. April 2014.

Curnutte MA. Genetic Information is as Genetic Information Does. American Anthropological Association Annual Meeting, Chicago, IL. November 2013.

Curnutte MA, Frumovitz KL, Bollinger J, Javitt GH, Carner KS, Cook-Deegan R, Chandrasekharan S, Messner D, Deverka P, Kaufman DJ, McGuire AL. Mapping the Next Generation Sequencing Industry. The American Society of Human Genetics Annual Meeting, Boston, MA. October 2013.

Curnutte MA. Mapping the Next Generation Sequencing Industry. The Clinical Genome Conference, San Francisco, CA. June 2013.

As the whole genome sequencing industry continues to grow, it is imperative that policy challenges arising from the utilization of this technology are identified and addressed in a timely manner. Through a modified Delphi process, a methodology used to iteratively engage a diverse group of stakeholders, this project identifies and prioritizes the unique policy challenges involved in translating WGS into health benefits in the United States. Using a mixed methods approach, such as a landscape analysis of the current and emerging WGS industry and qualitative interviews with industry leaders, the study team is developing an initial list of policy questions to be distributed to key stakeholders who will help refine and prioritize the resulting issues by importance and tractability.

Returning Research Results of Pediatric Genomic Research to Participants

Returning genomic research results to participants is rife with ethical issues, especially when the research participants are children. This study explores the legal implications of returning pediatric genomic research results to participants. By using standard legal analytic tools, study investigators are developing criteria to govern the ethical return of incidental findings and results of pediatric genomic research. US laws and international guidelines regarding decision making for and by minors are included in the analysis to provide a foundation for developing these criteria.

Supported by: R21HG006612, National Human Genome Research Institute, NIH

Publications Related to Genome Law and Policy

McGuire AL, Wang MJ, Probst FJ. Identifying consanguinity through routine genomic analysis: Reporting requirements. The Journal of Law, Medicine, and Ethics. 2012; 40 (4): 1040-6.

Clayton EW, McGuire AL. The Legal Risks of Returning Results of Genomics Research. Genetics in Medicine 14(4), 2012:473-477.

McGuire AL, Joffe S, Koenig BA, Biesecker BB, McCullough LB, Blumenthal-Barby JS, Caulfield T, Terry SF, Green RC. Ethics and genomic incidental findings. Science. 2013; 340 (6136): 1047-8.

Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O’Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MC, Biesecker LG. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genetics in Medicine. 2013; 15(7): 565-74.

Meet Our Team

The Center for Medical Ethics and Health Policy team is led by Director Amy L. McGuire, J.D., Ph.D.

View Faculty And Staff Listing

This CSER-related project is aiming to develop and test an approach to examine how individuals and physicians make benefit-risk trade-off decisions about whole genome sequencing and the implications of these decisions in the healthcare system and society. The project will explore this issue using conjoint analysis comparing two populations, participants of the MedSeq project as well as a nationally representative sample of the general public.

Supported by: R01GH007063, National Human Genome Research Institute, NIH

John Sulston, the projects namesake, was a champion of sharing scientific data to improve science and inform clinical decisions. Fittingly, he helped establish the 1996 Bermuda Principles with goals of rapid, electronic sharing of data generated by the Human Genome Project to benefit science and society. Today, sharing of genomic data has become more commonplace and yet still incredibly challenging to do.

Despite a growing norm of open science, concerns about proprietary rights remain a barrier to collecting and sharing data on a large scale for research and clinical use for all inherited cancer variants, or what could be called a cancer genomic variant commons. As more efforts to create cancer genomic variant commons that provide open access to data pooled from multiple sources are underway, such as the National Cancer Institute Genomic Data Commons, policies are evolving that could become a model for genomic data sharing more generally.

The overarching goal of the Sulston Project is to develop empirically-informed policy options to address the challenges of the nascent cancer genomic variant commons. We will engage relevant stakeholders to accomplish this work and inform policy in a way that balances proprietary and commercial interests with the generation of a public good -- information and knowledge about cancer-risk variants -- for public health benefit.

We aim to:

• Describe data sharing structures and practices for inherited cancer-risk variants.
• Identify the challenges of developing a sustainable commons for inherited cancer-risk variants.
• Formulate policy options to address the most important challenges identified, and map policy options to institutions and actors who can act on them.
• Translate findings and policy options by engaging with policy-makers and other actors.

Supported by: R01CA237118, National Cancer Institute, NIH, 2019 - 2023

Additional Project Information

Read more about our related work by visiting the webpage for two related studies: the PoliSeq project (McGuire R01 HG006460) examined the clinical integration of next generation sequencing technologies using a modified policy Delphi process, and Building the Medical Information Commons (McGuire R01 HG008918) examined issues confronted in fulfilling the aspirations of the 2011 NASEM report on Precision Medicine, which called for the creation of medical information commons.

Visit the Sulston Project website for more information.

Follow us on Twitter and Facebook for updates about this and other projects.

Publication

Robinson JO, Daoud A, Geary J, et al. Policy options to facilitate cancer genomic variant data sharing: outcomes of a modified policy Delphi. J Law Biosci. 2023;10(2):lsad022. Published 2023 Jul 14. doi:10.1093/jlb/lsad022  

Deverka P, Geary J, Mathews C, et al. Payer reimbursement practices and incentives for improving interpretation of germline genetic testing. J Law Biosci. 2023;10(2):lsad020. Published 2023 Jul 9. doi:10.1093/jlb/lsad020

Majumder MA, Blank ML, Geary J, Bollinger JM, Guerrini CJ, Robinson JO, Canfield I, Cook-Deegan R, McGuire AL. Challenges to Building a Gene Variant Commons to Assess Hereditary Cancer Risk: Results of a Modified Policy Delphi Panel Deliberation. Journal of Personalized Medicine. 2021 Jul 8;11(7):646.

Presentations

Fresh Air for Genetic Data Sharing. ELSIcon2022: Innovating for a Just and Equitable Future. Guerrini C, McGuire A, Robinson J, Blank M, Cook-Deegan R, Bollinger J, Geary J, Majumder M (2022).

Majumder MA, Gutierrez AM, Geary J, McGuire AL. “Equity considerations, challenges, and policy options for creating an effective knowledge commons for hereditary cancer risk.” American Society for Bioethics and Humanities Annual Conference. October 13-16, 2021. Panel presentation.

Supplement Project: A Case Study on Latinx Community Perspectives about Creating a Cancer Genomic Variant Commons

This qualitative case study is a Sulston supplement project that aims to explore the experiences of Hispanic/Latino communities in the U.S. with genetic testing for hereditary cancer risk. To do this, we are conducting 60 interviews across the U.S. with three stakeholder groups: genetics experts, patient advocates, and patients/members of the community. Through these stakeholder interviews, we will identify challenges and potential policy options related to improving access to genetic testing among Hispanic/Latino groups, with special attention to the heterogeneity of the US Hispanic/Latino population. This study includes a focus on policy translation, where we will communicate our empirical findings and policy implications to stakeholders, policymakers, and the scientific community. This project complements the goals of the Sulston Project by helping propose policy options for more effective inclusion of underserved groups in a cancer genomic variant commons.

Supported by: R01CA237118-S1, National Cancer Institute, NIH

Publication

Gutierrez AM, McGuire AL, Cook-Deegan R. “Disparities in access to genetic testing for hereditary cancer risk among Hispanic/Latino populations: Stakeholders’ views of barriers and potential solutions.” American Public Health Association Annual Meeting. October 23-27, 2021. Poster presentation.

Adaptive deep brain stimulation (aDBS) systems can record neural activity and adjust stimulation in real time. These systems have emerged as a promising alternative to address significant limitations in conventional open-loop DBS treatment of neuropsychiatric and movement disorders. The BRAIN Initiative and others have made substantial investments in studies to accelerate the development of aDBS. However, neuromodulation using DBS that can alter mood or motor outputs, has raised num   erous ethical, legal, and social (neuroethics) concerns (e.g., dehumanization, threats to autonomy/agency, changes in personal identity). aDBS systems may exacerbate these concerns and raise novel neuroethics issues (e.g., privacy, use, and ownership of neural data). Although theoretical bioethics work has explored ethical implications of conventional open-loop DBS for treating various disorders, there is little empirical neuroethics research in this area, and there is a severe lack of neuroethics research about aDBS. These issues need to be empirically examined and addressed to responsibly research and translate aDBS to clinical care. The long- term goal of this research program is to develop an ethically-justified and empirically-informed policy framework for the responsible research and translation of aDBS systems. The objective of this proposal, which was the first step in pursuit of that goal, was to identify the most pressing neuroethics issues related to aDBS research and translation from the perspective of diverse stakeholders across multiple clinical research contexts. Identifying and understanding aDBS neuroethics issues can help develop management plans to promote the responsible research and translation of aDBS, and maximize its social utility.

Supported by: R01MH114854; National Institute of Mental Health (BRAIN Initiative)

Role: mPI (with Gabe Lazaro-Munoz and Wayne Goodman)

This project developed a conceptual model to identify data release options that could be incorporated into a model informed consent document. This conceptual model was informed by focus groups with research participants and led to the creation of three types of informed consent documents that were tested in a pilot focus group study (BCM Basic & Clinical Collaborative Research Project Award) and which were used later in a lager, randomized study (R01HG004333).

Supported by: Greenwall Foundation Faculty Scholars Program
Role: PI

This project explored patients’ attitudes, needs, and decision-making about participating in genomic sequencing research through focus group studies, with a particular focus on their desired level of control over public data release. The results of this project led to the development of model informed consent documents, which were empirically tested as a randomized intervention in a subsequent funded study (R01HG004333).

Supported by: BCM Basic & Clinical Collaborative Research Program, supported by the Gillson Longenbaugh Foundation and the ARCO Foundation Young Teach-Investigator Award
Role: mPI (with Alica Goldman)

Using the model informed consent documents developed and refined through two pilot studies (Greenwall Foundation Faculty Scholars Program and BCM Basic & Clinical Collaborative Research Project Award), we conducted a randomized study of the informed consent documents to assess the impact on an individual’s willingness to participate in the genomic study and how broadly one was willing to share their genomic information.  Along with this intervention impact assessment, some participants were surveyed and interviewed to explore their attitudes and judgments about sharing genome sequence information in scientific databases, both publicly accessible and restricted.

Supported by: R01HG004333, National Human Genome Research Institute
Role: PI