Mildred Cho, PhD

All Publications

• Moral Engagement and Disengagement in Health Care AI Development. AJOB empirical bioethics Nichol, A. A., Halley, M., Federico, C., Cho, M. K., Sankar, P. L. 2024: 1-10

  Abstract

  Machine learning (ML) is utilized increasingly in health care, and can pose harms to patients, clinicians, health systems, and the public. In response, regulators have proposed an approach that would shift more responsibility to ML developers for mitigating potential harms. To be effective, this approach requires ML developers to recognize, accept, and act on responsibility for mitigating harms. However, little is known regarding the perspectives of developers themselves regarding their obligations to mitigate harms.We conducted 40 semi-structured interviews with developers of ML predictive analytics applications for health care in the United States.Participants varied widely in their perspectives on personal responsibility and included examples of both moral engagement and disengagement, albeit in a variety of forms. While most (70%) of participants made a statement indicative of moral engagement, most of these statements reflected an awareness of moral issues, while only a subset of these included additional elements of engagement such as recognizing responsibility, alignment with personal values, addressing conflicts of interests, and opportunities for action. Further, we identified eight distinct categories of moral disengagement reflecting efforts to minimize potential harms or deflect personal responsibility for preventing or mitigating harms.These findings suggest possible facilitators and barriers to the development of ethical ML that could act by encouraging moral engagement or discouraging moral disengagement. Regulatory approaches that depend on the ability of ML developers to recognize, accept, and act on responsibility for mitigating harms might have limited success without education and guidance for ML developers about the extent of their responsibilities and how to implement them.

  View details for DOI 10.1080/23294515.2024.2336906

  View details for PubMedID 38588388

• Not in my AI: Moral engagement and disengagement in health care AI development. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing Nichol, A. A., Halley, M. C., Federico, C. A., Cho, M. K., Sankar, P. L. 2023; 28: 496-506

  Abstract

  Machine learning predictive analytics (MLPA) are utilized increasingly in health care, but can pose harms to patients, clinicians, health systems, and the public. The dynamic nature of this technology creates unique challenges to evaluating safety and efficacy and minimizing harms. In response, regulators have proposed an approach that would shift more responsibility to MLPA developers for mitigating potential harms. To be effective, this approach requires MLPA developers to recognize, accept, and act on responsibility for mitigating harms. In interviews of 40 MLPA developers of health care applications in the United States, we found that a subset of ML developers made statements reflecting moral disengagement, representing several different potential rationales that could create distance between personal accountability and harms. However, we also found a different subset of ML developers who expressed recognition of their role in creating potential hazards, the moral weight of their design decisions, and a sense of responsibility for mitigating harms. We also found evidence of moral conflict and uncertainty about responsibility for averting harms as an individual developer working in a company. These findings suggest possible facilitators and barriers to the development of ethical ML that could act through encouragement of moral engagement or discouragement of moral disengagement. Regulatory approaches that depend on the ability of ML developers to recognize, accept, and act on responsibility for mitigating harms might have limited success without education and guidance for ML developers about the extent of their responsibilities and how to implement them.

  View details for PubMedID 36541003

• The ELSI Virtual Forum, 30 Years of the Genome: Integrating and Applying ELSI Research. The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics Moore, C. B., Dolan, D. D., Yarmolinsky, R., Cho, M. K., Soo-Jin-Lee, S. 2023; 51 (3): 661-671

  Abstract

  This paper reports our analysis of the ELSI Virtual Forum: 30 Years of the Genome: Integrating and Applying ELSI Research, an online meeting of scholars focused on the ethical, legal, and social implications (ELSI) of genetics and genomics.

  View details for DOI 10.1017/jme.2023.109

  View details for PubMedID 38088602

• Developer Perspectives on Potential Harms of Machine Learning Predictive Analytics in Health Care: Qualitative Analysis. Journal of medical Internet research Nichol, A. A., Sankar, P. L., Halley, M. C., Federico, C. A., Cho, M. K. 2023; 25: e47609

  Abstract

  Machine learning predictive analytics (MLPA) is increasingly used in health care to reduce costs and improve efficacy; it also has the potential to harm patients and trust in health care. Academic and regulatory leaders have proposed a variety of principles and guidelines to address the challenges of evaluating the safety of machine learning-based software in the health care context, but accepted practices do not yet exist. However, there appears to be a shift toward process-based regulatory paradigms that rely heavily on self-regulation. At the same time, little research has examined the perspectives about the harms of MLPA developers themselves, whose role will be essential in overcoming the "principles-to-practice" gap.The objective of this study was to understand how MLPA developers of health care products perceived the potential harms of those products and their responses to recognized harms.We interviewed 40 individuals who were developing MLPA tools for health care at 15 US-based organizations, including data scientists, software engineers, and those with mid- and high-level management roles. These 15 organizations were selected to represent a range of organizational types and sizes from the 106 that we previously identified. We asked developers about their perspectives on the potential harms of their work, factors that influence these harms, and their role in mitigation. We used standard qualitative analysis of transcribed interviews to identify themes in the data.We found that MLPA developers recognized a range of potential harms of MLPA to individuals, social groups, and the health care system, such as issues of privacy, bias, and system disruption. They also identified drivers of these harms related to the characteristics of machine learning and specific to the health care and commercial contexts in which the products are developed. MLPA developers also described strategies to respond to these drivers and potentially mitigate the harms. Opportunities included balancing algorithm performance goals with potential harms, emphasizing iterative integration of health care expertise, and fostering shared company values. However, their recognition of their own responsibility to address potential harms varied widely.Even though MLPA developers recognized that their products can harm patients, public, and even health systems, robust procedures to assess the potential for harms and the need for mitigation do not exist. Our findings suggest that, to the extent that new oversight paradigms rely on self-regulation, they will face serious challenges if harms are driven by features that developers consider inescapable in health care and business environments. Furthermore, effective self-regulation will require MLPA developers to accept responsibility for safety and efficacy and know how to act accordingly. Our results suggest that, at the very least, substantial education will be necessary to fill the "principles-to-practice" gap.

  View details for DOI 10.2196/47609

  View details for PubMedID 37971798

• Stronger regulation of AI in biomedicine. Science translational medicine Trotsyuk, A. A., Federico, C. A., Cho, M. K., Altman, R. B., Magnus, D. 2023; 15 (713): eadi0336

  Abstract

  Regulatory agencies need to ensure the safety and equity of AI in biomedicine, and the time to do so is now.

  View details for DOI 10.1126/scitranslmed.adi0336

  View details for PubMedID 37703349

• Innovating for a Just and Equitable Future in Genomic and Precision Medicine Research. The American journal of bioethics : AJOB Dolan, D. D., Cho, M. K., Lee, S. S. 2023; 23 (7): 1-4

  View details for DOI 10.1080/15265161.2023.2215201

  View details for PubMedID 37353052

• Re-envisioning community genetics: community empowerment in preventive genomics. Journal of community genetics Wand, H., Martschenko, D. O., Smitherman, A., Michelson, S., Pun, T., Witte, J. S., Scott, S. A., Cho, M. K., Ashley, E. A., Preventive Genomics Program Co-Design Working Group, Goldberg, E., Knepper, L., Michelson, S., Osborne, J., Sanders, V. 2023

  Abstract

  As genomic technologies rapidly develop, polygenic scores (PGS) are entering into a growing conversation on how to improve precision in public health and prevent chronic disease. While the integration of PGS into public health and clinical services raises potential benefits, it also introduces potential harms. In particular, there is a high level of uncertainty about how to incorporate PGS into clinical settings in a manner that is equitable, just, and aligned with the long-term goals of many healthcare systems to support person-centered and value-based care. This paper argues that any conversation about whether and how to design and implement PGS clinical services requires dynamic engagement with local communities, patients, and families. These parties often face the consequences, both positive and negative, of such uncertainties and should therefore drive clinical translation. As a collaborative effort between hospital stakeholders, community partners, and researchers, this paper describes a community-empowered co-design process for addressing uncertainty and making programmatic decisions about the implementation of PGS into clinical services. We provide a framework for others interested in designing clinical programs that are responsive to, and inclusive and respectful of, local communities.

  View details for DOI 10.1007/s12687-023-00638-y

  View details for PubMedID 36765027

• Trustworthiness matters: Building equitable and ethical science. Cell Reardon, J., Lee, S. S., Goering, S., Fullerton, S. M., Cho, M. K., Panofsky, A., Hammonds, E. M. 2023

  Abstract

  Trustworthy science requires research practices that center issues of ethics, equity, and inclusion. We announce the Leadership in the Equitable and Ethical Design (LEED) of Science, Technology, Mathematics, and Medicine (STEM) initiative to create best practices for integrating ethical expertise and fostering equitable collaboration.

  View details for DOI 10.1016/j.cell.2023.01.008

  View details for PubMedID 36724788

• Paging the Clinical Informatics Community: Respond STAT to Dobbs v Jackson's Women's Health Organization. Applied clinical informatics Arvisais-Anhalt, S., Ravi, A., Weia, B., Aarts, J., Ahmad, H. B., Araj, E., Bauml, J. A., Benham-Hutchins, M., Boyd, A. D., Brecht-Doscher, A., Butler-Henderson, K., Butte, A., Cardillo, A. B., Chilukuri, N., Cho, M. K., Cohen, J. K., Craven, C. K., Crusco, S. J., Dadabhoy, F., Dash, D., DeBolt, C., Elkin, P. L., Fayanju, O. A., Fochtmann, L., Graham, J. V., Hanna, J., Hersh, W., Hoffard, M. R., Hron, J., Huang, S. S., Jackson, B. R., Kaplan, B., Kelly, W., Ko, K., Koppel, R., Kurapati, N., Labbad, G., Lee, J., Lehmann, C. U., Leitner, S., Liao, Z. C., Medford, R. J., Melnick, E. R., Muniyappa, A. N., Murray, S., Neinstein, A., Nichols-Johnson, V., Novak, L., Ogan, W. S., Ozeran, L., Pageler, N., Pandita, D., Perumbeti, A., Petersen, C., Pierce, L., Puttagunta, R., Ramaswamy, P., Rogers, K. M., Rosenbloom, T., Ryan, A., Saleh, S., Sarabu, C., Schreiber, R., Shaw, K. A., Sim, I., Sirintrapun, S. J., Solomonides, A., Spector, J. D., Starren, J. B., Stoffel, M., Subbian, V., Swanson, K., Tomes, A., Trang, K., Unertl, K. M., Weon, J. L., Whooley, M., Wiley, K., Williamson, D. F., Winkelstein, P., Wong, J., Xie, J., Yarahuan, J. K., Yung, N., Zera, C., Ratanawongsa, N., Sadasivaiah, S. 2022

  Abstract

  n/a.

  View details for DOI 10.1055/a-2000-7590

  View details for PubMedID 36535703

• Words matter: The language of difference in human genetics. Genetics in medicine : official journal of the American College of Medical Genetics Cho, M. K., Duque Lasio, M. L., Amarillo, I., Mintz, K. T., Bennett, R. L., Brothers, K. B. 2022

  Abstract

  Diversity, equity, and inclusion efforts in academia are leading publishers and journals to re-examine their use of terminology for commonly used scientific variables. This reassessment of language is particularly important for human genetics, which is focused on identifying and explaining differences between individuals and populations. Recent guidance on the use of terms and symbols in clinical practice, research, and publications is beginning to acknowledge the ways that language and concepts of difference can be not only inaccurate but also harmful. To stop perpetuating historical wrongs, those of us who conduct and publish genetic research and provide genetic health care must understand the context of the terms we use and why some usages should be discontinued. In this article, we summarize critiques of terminology describing disability, sex, gender, race, ethnicity, and ancestry in research publications, laboratory reports, diagnostic codes, and pedigrees. We also highlight recommendations for alternative language that aims to make genetics more inclusive, rigorous, and ethically sound. Even though norms of acceptable language use are ever changing, it is the responsibility of genetics professionals to uncover biases ingrained in professional practice and training and to continually reassess the words we use to describe human difference because they cause harm to patients.

  View details for DOI 10.1016/j.gim.2022.11.011

  View details for PubMedID 36524987

• Epistemic Rights and Responsibilities of Digital Simulacra for Biomedicine. The American journal of bioethics : AJOB Cho, M. K., Martinez-Martin, N. 2022: 1-12

  Abstract

  Big data and AI have enabled digital simulation for prediction of future health states or behaviors of specific individuals, populations or humans in general. "Digital simulacra" use multimodal datasets to develop computational models that are virtual representations of people or groups, generating predictions of how systems evolve and react to interventions over time. These include digital twins and virtual patients for in silico clinical trials, both of which seek to transform research and health care by speeding innovation and bridging the epistemic gap between population-based research findings and their application to the individual. Nevertheless, digital simulacra mark a major milestone on a trajectory to embrace the epistemic culture of data science and a potential abandonment of medical epistemological concepts of causality and representation. In doing so, "data first" approaches potentially shift moral attention from actual patients and principles, such as equity, to simulated patients and patient data.

  View details for DOI 10.1080/15265161.2022.2146785

  View details for PubMedID 36507873

• Latinx attitudes, barriers, and experiences with genetic counseling and testing: A systematic review. Journal of genetic counseling Dron, H. A., Bucio, D., Young, J. L., Tabor, H. K., Cho, M. K. 2022

  Abstract

  As genetics is increasingly used across clinical settings, there is a need to understand the impact and experiences of diverse patients. This review systematically examined research literature on Latinx experiences with genetic counseling and genetic testing (GC/GT) in the United States, synthesizing key themes and knowledge gaps pertaining to both patient experience and hypothetical scenarios. Findings were based on a systematic search, inclusion, and thematic analysis of 81 empirical peer-reviewed articles published from January 1990 to July 2019 pertaining to Latinx populations and GC/GT. Studies most commonly addressed Latinas' perspectives on GC/GT in prenatal settings or for hereditary breast and ovarian cancer (HBOC). Costs, referrals, and communication were significant barriers to accessing genetic services for many Latinx patients, particularly those with low English proficiency (LEP). Studies highlighted difficulties accessing and communicating in healthcare settings, and how medical context and prior experience with healthcare workers and institutions influenced GC/GT decision-making. Providers' implicit biases about Latinx patients negatively impacted their care and impeded communication. Despite low awareness of cancer GT, Latinx patients often reported interest in learning more about GC/GT or unmet needs for GT discussion and provider involvement. This systematic review identified areas where providers can take action to improve Latinx experiences with GC/GT. Clinicians should elicit and respond to patient preferences about shared decision-making. For patients with low numeracy or LEP, providers should consider tailored educational and communication techniques. Most studies focused on HBOC and prenatal testing, and Latinx patients are heterogeneous, leaving many research questions about Latinx experience with GT/GC in other clinical areas.

  View details for DOI 10.1002/jgc4.1632

  View details for PubMedID 36301246

• Data sharing and community-engaged research. Science (New York, N.Y.) Sabatello, M., Martschenko, D. O., Cho, M. K., Brothers, K. B. 2022; 378 (6616): 141-143

  Abstract

  Data sharing must be accompanied by responsibility sharing.

  View details for DOI 10.1126/science.abq6851

  View details for PubMedID 36227983

• Three decades of ethical, legal, and social implications research: Looking back to chart a path forward. Cell genomics Dolan, D. D., Lee, S. S., Cho, M. K. 2022; 2 (7)

  Abstract

  More than thirty years ago in the United States, the National Center for Human Genome Research (NCHGR) at the National Institutes of Health (NIH) and its partner in the Human Genome Project (HGP), the Department of Energy (DOE), called for proposals from social scientists, ethicists, lawyers, and others to explore the ethical, legal, and social implications (ELSI) of mapping and sequencing the human genome. Today, nearly twenty years after the completion of the HGP, the ELSI Research Program of the National Human Genome Research Institute (NHGRI) continues this support. It has fostered the growth of ELSI research into a global field of study, uniquely positioned at the nexus of many academic disciplines and in proximity to basic and applied scientific research. We examine the formation of the first ELSI program and consider whether science policy in the public interest can exist within the confines of a set-aside from the NHGRI budget.

  View details for DOI 10.1016/j.xgen.2022.100150

  View details for PubMedID 35935917

• Bridging the AI Chasm: Can EBM Address Representation and Fairness in Clinical Machine Learning? The American journal of bioethics : AJOB Martinez-Martin, N., Cho, M. K. 2022; 22 (5): 30-32

  View details for DOI 10.1080/15265161.2022.2055212

  View details for PubMedID 35475967

• A mixed-methods protocol to develop and validate a stewardship maturity matrix for human genomic data in the cloud. Frontiers in genetics Rahimzadeh, V., Peng, G., Cho, M. 2022; 13: 876869

  Abstract

  This article describes a mixed-methods protocol to develop and test the implementation of a stewardship maturity matrix (SMM) for repositories which govern access to human genomic data in the cloud. It is anticipated that the cloud will host most human genomic and related health datasets generated as part of publicly funded research in the coming years. However, repository managers lack practical tools for identifying what stewardship outcomes matter most to key stakeholders as well as how to track progress on their stewardship goals over time. In this article we describe a protocol that combines Delphi survey methods with SMM modeling first introduced in the earth and planetary sciences to develop a stewardship impact assessment tool for repositories that manage access to human genomic data. We discuss the strengths and limitations of this mixed-methods design and offer points to consider for wrangling both quantitative and qualitative data to enhance rigor and representativeness. We conclude with how the empirical methods bridged in this protocol have potential to improve evaluation of data stewardship systems and better align them with diverse stakeholder values in genomic data science.

  View details for DOI 10.3389/fgene.2022.876869

  View details for PubMedID 36313457

• Values and Practices to Strengthen Genetic Research Partnerships with Indigenous Communities PROGRESS IN COMMUNITY HEALTH PARTNERSHIPS-RESEARCH EDUCATION AND ACTION Burke, W., Beans, J. A., Cho, M. K., Garrison, N. A., Hiratsuka, V., Hopkins, S., Spicer, P. G., Tsosie, K. S., Woodahl, E. L., Yracheta, J. M., Thummel, K. 2022; 16 (4): 583-592

  Abstract

  Genetic datasets lack diversity and include very few data from Indigenous populations. Research models based on equitable partnership have the potential to increase Indigenous participation and have led to successful collaborations. We report here on a meeting of participants in four Indigenous community-university partnerships pursuing research on precision medicine. The goal of the meeting was to define values and practices that strengthen opportunities for genetic research. The group accorded the highest priority to developing trusting relationships, ensuring respect for Indigenous community authority, and pursuing research that has the potential to lead to community benefit. Supporting priorities included incorporation of Indigenous expertise in research planning, transparent communication, and development of community capacity, including capacity to participate in formulating research questions, informing research methodology, and leading research projects. Participants also noted the importance of attention to social determinants of health so that genetic contributors to health are evaluated in the appropriate context.

  View details for DOI 10.1353/cpr.2022.0079

  View details for Web of Science ID 000907533300003

  View details for PubMedID 36533507

• Rising to the challenge of bias in health care AI. Nature medicine Cho, M. K. 2021

  View details for DOI 10.1038/s41591-021-01577-2

  View details for PubMedID 34893774

• Diverse experts' perspectives on ethical issues of using machine learning to predict HIV/AIDS risk in sub-Saharan Africa: a modified Delphi study. BMJ open Nichol, A. A., Bendavid, E., Mutenherwa, F., Patel, C., Cho, M. K. 2021; 11 (7): e052287

  Abstract

  OBJECTIVE: To better understand diverse experts' views about the ethical implications of ongoing research funded by the National Institutes of Health that uses machine learning to predict HIV/AIDS risk in sub-Saharan Africa (SSA) based on publicly available Demographic and Health Surveys data.DESIGN: Three rounds of semi-structured surveys in an online expert panel using a modified Delphi approach.PARTICIPANTS: Experts in informatics, African public health and HIV/AIDS and bioethics were invited to participate.MEASURES: Perceived importance of or agreement about relevance of ethical issues on 5-point unipolar Likert scales. Qualitative data analysis identified emergent themes related to ethical issues and development of an ethical framework and recommendations for open-ended questions.RESULTS: Of the 35 invited experts, 22 participated in the online expert panel (63%). Emergent themes were the inclusion of African researchers in all aspects of study design, analysis and dissemination to identify and address local contextual issues, as well as engagement of communities. Experts focused on engagement with health and science professionals to address risks, benefits and communication of findings. Respondents prioritised the mitigation of stigma to research participants but recognised trade-offs between privacy and the need to disseminate findings to realise public health benefits. Strategies for responsible communication of results were suggested, including careful word choice in presentation of results and limited dissemination to need-to-know stakeholders such as public health planners.CONCLUSION: Experts identified ethical issues specific to the African context and to research on sensitive, publicly available data and strategies for addressing these issues. These findings can be used to inform an ethical implementation framework with research stage-specific recommendations on how to use publicly available data for machine learning-based predictive analytics to predict HIV/AIDS risk in SSA.

  View details for DOI 10.1136/bmjopen-2021-052287

  View details for PubMedID 34321310

• Ethical Development of Digital Phenotyping Tools for Mental Health Applications: Delphi Study. JMIR mHealth and uHealth Martinez-Martin, N., Greely, H. T., Cho, M. K. 2021; 9 (7): e27343

  Abstract

  BACKGROUND: Digital phenotyping (also known as personal sensing, intelligent sensing, or body computing) involves the collection of biometric and personal data in situ from digital devices, such as smartphones, wearables, or social media, to measure behavior or other health indicators. The collected data are analyzed to generate moment-by-moment quantification of a person's mental state and potentially predict future mental states. Digital phenotyping projects incorporate data from multiple sources, such as electronic health records, biometric scans, or genetic testing. As digital phenotyping tools can be used to study and predict behavior, they are of increasing interest for a range of consumer, government, and health care applications. In clinical care, digital phenotyping is expected to improve mental health diagnoses and treatment. At the same time, mental health applications of digital phenotyping present significant areas of ethical concern, particularly in terms of privacy and data protection, consent, bias, and accountability.OBJECTIVE: This study aims to develop consensus statements regarding key areas of ethical guidance for mental health applications of digital phenotyping in the United States.METHODS: We used a modified Delphi technique to identify the emerging ethical challenges posed by digital phenotyping for mental health applications and to formulate guidance for addressing these challenges. Experts in digital phenotyping, data science, mental health, law, and ethics participated as panelists in the study. The panel arrived at consensus recommendations through an iterative process involving interviews and surveys. The panelists focused primarily on clinical applications for digital phenotyping for mental health but also included recommendations regarding transparency and data protection to address potential areas of misuse of digital phenotyping data outside of the health care domain.RESULTS: The findings of this study showed strong agreement related to these ethical issues in the development of mental health applications of digital phenotyping: privacy, transparency, consent, accountability, and fairness. Consensus regarding the recommendation statements was strongest when the guidance was stated broadly enough to accommodate a range of potential applications. The privacy and data protection issues that the Delphi participants found particularly critical to address related to the perceived inadequacies of current regulations and frameworks for protecting sensitive personal information and the potential for sale and analysis of personal data outside of health systems.CONCLUSIONS: The Delphi study found agreement on a number of ethical issues to prioritize in the development of digital phenotyping for mental health applications. The Delphi consensus statements identified general recommendations and principles regarding the ethical application of digital phenotyping to mental health. As digital phenotyping for mental health is implemented in clinical care, there remains a need for empirical research and consultation with relevant stakeholders to further understand and address relevant ethical issues.

  View details for DOI 10.2196/27343

  View details for PubMedID 34319252

• A Typology of Existing Machine Learning-Based Predictive Analytic Tools Focused on Reducing Costs and Improving Quality in Health Care: Systematic Search and Content Analysis. Journal of medical Internet research Nichol, A. A., Batten, J. N., Halley, M. C., Axelrod, J. K., Sankar, P. L., Cho, M. K. 2021; 23 (6): e26391

  Abstract

  BACKGROUND: Considerable effort has been devoted to the development of artificial intelligence, including machine learning-based predictive analytics (MLPA) for use in health care settings. The growth of MLPA could be fueled by payment reforms that hold health care organizations responsible for providing high-quality, cost-effective care. Policy analysts, ethicists, and computer scientists have identified unique ethical and regulatory challenges from the use of MLPA in health care. However, little is known about the types of MLPA health care products available on the market today or their stated goals.OBJECTIVE: This study aims to better characterize available MLPA health care products, identifying and characterizing claims about products recently or currently in use in US health care settings that are marketed as tools to improve health care efficiency by improving quality of care while reducing costs.METHODS: We conducted systematic database searches of relevant business news and academic research to identify MLPA products for health care efficiency meeting our inclusion and exclusion criteria. We used content analysis to generate MLPA product categories and characterize the organizations marketing the products.RESULTS: We identified 106 products and characterized them based on publicly available information in terms of the types of predictions made and the size, type, and clinical training of the leadership of the companies marketing them. We identified 5 categories of predictions made by MLPA products based on publicly available product marketing materials: disease onset and progression, treatment, cost and utilization, admissions and readmissions, and decompensation and adverse events.CONCLUSIONS: Our findings provide a foundational reference to inform the analysis of specific ethical and regulatory challenges arising from the use of MLPA to improve health care efficiency.

  View details for DOI 10.2196/26391

  View details for PubMedID 34156338

• Genetic counseling and testing for Asian Americans: a systematic review. Genetics in medicine : official journal of the American College of Medical Genetics Young, J. L., Mak, J., Stanley, T., Bass, M., Cho, M. K., Tabor, H. K. 2021

  Abstract

  PURPOSE: Asian Americans have been understudied in the literature on genetic and genomic services. The current study systematically identified, evaluated, and summarized findings from relevant qualitative and quantitative studies on genetic health care for Asian Americans.METHODS: A search of five databases (1990 to 2018) returned 8,522 unique records. After removing duplicates, abstract/title screening, and full text review, 47 studies met inclusion criteria. Data from quantitative studies were converted into "qualitized data" and pooled together with thematic data from qualitative studies to produce a set of integrated findings.RESULTS: Synthesis of results revealed that (1) Asian Americans are under-referred but have high uptake for genetic services, (2) linguistic/communication challenges were common and Asian Americans expected more directive genetic counseling, and (3) Asian Americans' family members were involved in testing decisions, but communication of results and risk information to family members was lower than other racial groups.CONCLUSION: This study identified multiple barriers to genetic counseling, testing, and care for Asian Americans, as well as gaps in the research literature. By focusing on these barriers and filling these gaps, clinical genetic approaches can be tailored to meet the needs of diverse patient groups, particularly those of Asian descent.

  View details for DOI 10.1038/s41436-021-01169-y

  View details for PubMedID 33972720

• Taking an anti-racist posture in scientific publications in human genetics and genomics Brothers, K., Bennett, R., Cho, M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2021: S299-S300

  View details for Web of Science ID 000639219800459

• Taking an antiracist posture in scientific publications in human genetics and genomics. Genetics in medicine : official journal of the American College of Medical Genetics Brothers, K. B., Bennett, R. L., Cho, M. K. 2021

  Abstract

  From its earliest days, the field of human genetics has had a complex, and at times troubling, connection with racist ideologies. Although the modern field of human genetics and genomics has come a long way from those earlier errors, systemic racism remains ingrained in its institutions and practices. Although a variety of efforts are needed to excise systemic racism, we focus in this commentary on the work that must be done in scientific publishing in genetics and genomics. We propose eight principles that are both scientifically grounded and antiracist that we hope will serve as a foundation for the development of policies by publishers and editorial boards that address the unique needs of the field of genetics and genomics. Publishers and journals must go beyond mere policies, however. Editors and reviewers will need training on these policies and principles, and will benefit from resources like rubrics that can be used for evaluating the adherence of submissions to these guidelines.

  View details for DOI 10.1038/s41436-021-01109-w

  View details for PubMedID 33649579

• Use of Korean dramas to facilitate precision mental health understanding and discussion for Asian Americans. Health promotion international Ta Park, V. M., Park, C. J., Kim, C., Nguyen, N. C., Tran, A. T., Chiang, A., Rho, S. J., Olaisen, R. H., Vuong, Q., Rosas, L. G., Cho, M. K. 2021

  Abstract

  Precision mental health holds great potential for revolutionizing care and reducing the burden of mental illness. All races and ethnicities such as Asian Americans, the fastest growing racial group in the United States (U.S.), need to be engaged in precision mental health research. Owing to its global popularity, Korean drama ('K-drama') television shows may be an effective educational tool to increase precision mental health knowledge, attitudes and behaviors among Asian Americans. This qualitative study examined the participants' perspectives about and acceptance of using K-dramas to educate and engage Asian Americans about precision mental health. Twelve workshops were conducted in English, Vietnamese and Korean with a convenience sample in the San Francisco Bay Area in the U.S. (n=122). Discussions were coded for themes. Findings revealed that all language groups reported positive reactions to using K-dramas to learn about precision health, genetics and mental health. Overall, participants shared that they learned about topics that are not generally talked about (e.g. precision health; genetic testing; mental health), from other people's perspectives, and the importance of mental health. Participants expressed how much they enjoyed the workshop, how they felt relieved due to the workshop, thought the workshop was interesting, and had an opportunity for self-reflection/healing. This pilot test demonstrated that K-dramas has promise to be used as a health educational tool in a workshop format focused on mental health among a diverse group of Asian Americans. Given the widespread access to K-dramas, they present a scalable opportunity for increasing awareness about specific health topics.

  View details for DOI 10.1093/heapro/daab012

  View details for PubMedID 33582752

• The Invisibility of Asian Americans in COVID-19 Data, Reporting, and Relief. The American journal of bioethics : AJOB Young, J. L., Cho, M. K. 2021; 21 (3): 100–102

  View details for DOI 10.1080/15265161.2020.1870767

  View details for PubMedID 33616487

• Ethical issues in using ambient intelligence in health-care settings. The Lancet. Digital health Martinez-Martin, N., Luo, Z., Kaushal, A., Adeli, E., Haque, A., Kelly, S. S., Wieten, S., Cho, M. K., Magnus, D., Fei-Fei, L., Schulman, K., Milstein, A. 2020

  Abstract

  Ambient intelligence is increasingly finding applications in health-care settings, such as helping to ensure clinician and patient safety by monitoring staff compliance with clinical best practices or relieving staff of burdensome documentation tasks. Ambient intelligence involves using contactless sensors and contact-based wearable devices embedded in health-care settings to collect data (eg, imaging data of physical spaces, audio data, or body temperature), coupled with machine learning algorithms to efficiently and effectively interpret these data. Despite the promise of ambient intelligence to improve quality of care, the continuous collection of large amounts of sensor data in health-care settings presents ethical challenges, particularly in terms of privacy, data management, bias and fairness, and informed consent. Navigating these ethical issues is crucial not only for the success of individual uses, but for acceptance of the field as a whole.

  View details for DOI 10.1016/S2589-7500(20)30275-2

  View details for PubMedID 33358138

• Digital Contact Tracing, Privacy, and Public Health HASTINGS CENTER REPORT Martinez-Martin, N., Wieten, S., Magnus, D., Cho, M. K. 2020; 50 (3): 43–46

  Abstract

  Digital contact tracing, in combination with widespread testing, has been a focal point for many plans to "reopen" economies while containing the spread of Covid-19. Most digital contact tracing projects in the United States and Europe have prioritized privacy protections in the form of local storage of data on smartphones and the deidentification of information. However, in the prioritization of privacy in this narrow form, there is not sufficient attention given to weighing ethical trade-offs within the context of a public health pandemic or to the need to evaluate safety and effectiveness of software-based technology applied to public health.

  View details for DOI 10.1002/hast.1131

  View details for Web of Science ID 000609626200020

  View details for PubMedID 32596893

  View details for PubMedCentralID PMC7361453

• Partial Entrustment in Pragmatic Clinical Trials AMERICAN JOURNAL OF BIOETHICS Richardson, H. S., Cho, M. K. 2020; 20 (1): 24–26

  View details for DOI 10.1080/15265161.2019.1687784

  View details for Web of Science ID 000505296200011

• Partial Entrustment in Pragmatic Clinical Trials. The American journal of bioethics : AJOB Richardson, H. S., Cho, M. K. 2020; 20 (1): 24–26

  View details for DOI 10.1080/15265161.2019.1687791

  View details for PubMedID 31896335

• Perspectives on Precision Health Among Racial/Ethnic Minority Communities and the Physicians That Serve Them. Ethnicity & disease Rosas, L. G., Nasrallah, C., Park, V. T., Vasquez, J. J., Duron, Y., Garrick, O., Hattin, R., Cho, M., David, S. P., Evans, J., McClinton-Brown, R., Martin, C. 2020; 30 (Suppl 1): 137–48

  Abstract

  Background: In order for precision health to address health disparities, engagement of diverse racial/ethnic minority communities and the physicians that serve them is critical.Methods: A community-based participatory research approach with mixed methods was employed to gain a deeper understanding of precision health research and practice among American Indian, African American, Latino, Chinese, and Vietnamese groups and physicians that serve these communities. A survey assessed demographics and opinions of precision health, genetic testing, and precision health research. Focus groups (n=12) with each racial/ethnic minority group and physicians further explored attitudes about these topics.Results: One hundred community members (American Indian [n=17], African American [n=13], Chinese [n=17], Latino [n=27], and Vietnamese [n=26]) and 14 physicians completed the survey and participated in the focus groups. Familiarity with precision health was low among community members and high among physicians. Most groups were enthusiastic about the approach, especially if it considered influences on health in addition to genes (eg, environmental, behavioral, social factors). Significant concerns were expressed by African American and American Indian participants about precision health practice and research based on past abuses in biomedical research. In addition, physician and community members shared concerns such as security and confidentiality of genetic information, cost and affordability of genetic tests and precision medicine, discrimination and disparities, distrust of medical and research and pharmaceutical institutions, language barriers, and physician's specialty.Conclusions: Engagement of racial/ethnic minority communities and the providers who serve them is important for advancing a precision health approach to addressing health disparities.

  View details for DOI 10.18865/ed.30.S1.137

  View details for PubMedID 32269455

• Resource Allocation in COVID-19 Research: Which Trials? Which Patients? The American journal of bioethics : AJOB Wieten, S. n., Burgart, A. n., Cho, M. n. 2020; 20 (7): 86–88

  View details for DOI 10.1080/15265161.2020.1779392

  View details for PubMedID 32716767

• Informed Consent in the Genomics Era. Cold Spring Harbor perspectives in medicine Rego, S., Grove, M. E., Cho, M. K., Ormond, K. E. 2019

  Abstract

  Informed consent, the process of gathering autonomous authorization for a medical intervention or medical research participation, is a fundamental component of medical practice. Medical informed consent assumes decision-making capacity, voluntariness, comprehension, and adequate information. The increasing use of genetic testing, particularly genomic sequencing, in clinical and research settings has presented many new challenges for clinicians and researchers when obtaining informed consent. Many of these challenges revolve around the need for patient comprehension of sufficient information. Genomic sequencing is complex-all of the possible results are too numerous to explain, and many of the risks and benefits remain unknown. Thus, historical standards of consent are difficult to apply. Alternative models of consent have been proposed to increase patient understanding, and several have empirically demonstrated effectiveness. However, there is still a striking lack of consensus in the genetics community about what constitutes informed consent in the context of genomic sequencing. Multiple approaches are needed to address this challenge, including consensus building around standards, targeted use of genetic counselors in nongenetics clinics in which genomic testing is ordered, and the development and testing of alternative models for obtaining informed consent.

  View details for DOI 10.1101/cshperspect.a036582

  View details for PubMedID 31570382

• Disposition toward privacy and information disclosure in the context of emerging health technologies JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION Schairer, C. E., Cheung, C., Rubanovich, C., Cho, M., Cranor, L., Bloss, C. S. 2019; 26 (7): 610–19

  View details for DOI 10.1093/jamia/ocz010

  View details for Web of Science ID 000474273800006

• Using Korean Dramas as a Precision Mental Health Education Tool for Asian Americans: A Pilot Study. International journal of environmental research and public health Ta Park, V. M., Olaisen, R. H., Vuong, Q., Rosas, L. G., Cho, M. K. 2019; 16 (12)

  Abstract

  Precision mental health (MH) holds great potential for revolutionizing MH care and reducing the burden of mental illness. Efforts to engage Asian Americans in precision MH research is necessary to help reduce MH disparities. Korean drama ("K-drama") television shows may be an effective educational tool to increase precision MH knowledge, attitudes, and behaviors (KAB) among Asian Americans. This study determined whether KAB improved after participating in a K-drama precision MH workshop, and examined the participants' perspectives about K-dramas' utility as an educational tool. A K-drama precision MH workshop in English/Vietnamese/Korean was conducted with a convenience sample (n = 122). Pre-/post-tests on precision MH KAB (genetics and genetic testing, and MH and help-seeking) and a survey on K-dramas' utility as an educational tool were administered. Findings revealed a significant difference in the pre- and post-test KAB scores overall, by genetics and genetic testing, and by MH and help-seeking. There were also significant increases in the overall post-test KAB scores by workshop (language) participation. Overall, participants responded positively on the utility of K-dramas as a precision MH educational tool. This study demonstrates the feasibility of K-drama as an innovative and widely available health education tool to educate communities about precision MH.

  View details for DOI 10.3390/ijerph16122151

  View details for PubMedID 31216626

• Physical activity, sleep and cardiovascular health data for 50,000 individuals from the MyHeart Counts Study SCIENTIFIC DATA Hershman, S. G., Bot, B. M., Shcherbina, A., Doerr, M., Moayedi, Y., Pavlovic, A., Waggott, D., Cho, M. K., Rosenberger, M. E., Haskell, W. L., Myers, J., Champagne, M., Mignot, E., Salvi, D., Landray, M., Tarassenko, L., Harrington, R. A., Yeung, A. C., McConnell, M. V., Ashley, E. A. 2019; 6

  View details for DOI 10.1038/s41597-019-0016-7

  View details for Web of Science ID 000464198800001

• Physical activity, sleep and cardiovascular health data for 50,000 individuals from the MyHeart Counts Study. Scientific data Hershman, S. G., Bot, B. M., Shcherbina, A., Doerr, M., Moayedi, Y., Pavlovic, A., Waggott, D., Cho, M. K., Rosenberger, M. E., Haskell, W. L., Myers, J., Champagne, M. A., Mignot, E., Salvi, D., Landray, M., Tarassenko, L., Harrington, R. A., Yeung, A. C., McConnell, M. V., Ashley, E. A. 2019; 6 (1): 24

  Abstract

  Studies have established the importance of physical activity and fitness for long-term cardiovascular health, yet limited data exist on the association between objective, real-world large-scale physical activity patterns, fitness, sleep, and cardiovascular health primarily due to difficulties in collecting such datasets. We present data from the MyHeart Counts Cardiovascular Health Study, wherein participants contributed data via an iPhone application built using Apple's ResearchKit framework and consented to make this data available freely for further research applications. In this smartphone-based study of cardiovascular health, participants recorded daily physical activity, completed health questionnaires, and performed a 6-minute walk fitness test. Data from English-speaking participants aged 18 years or older with a US-registered iPhone who agreed to share their data broadly and who enrolled between the study's launch and the time of the data freeze for this data release (March 10 2015-October 28 2015) are now available for further research. It is anticipated that releasing this large-scale collection of real-world physical activity, fitness, sleep, and cardiovascular health data will enable the research community to work collaboratively towards improving our understanding of the relationship between cardiovascular indicators, lifestyle, and overall health, as well as inform mobile health research best practices.

  View details for PubMedID 30975992

• Disposition toward privacy and information disclosure in the context of emerging health technologies. Journal of the American Medical Informatics Association : JAMIA Schairer, C. E., Cheung, C., Kseniya Rubanovich, C., Cho, M., Cranor, L. F., Bloss, C. S. 2019

  Abstract

  OBJECTIVE: We sought to present a model of privacy disposition and its development based on qualitative research on privacy considerations in the context of emerging health technologies.MATERIALS AND METHODS: We spoke to 108 participants across 44 interviews and 9 focus groups to understand the range of ways in which individuals value (or do not value) control over their health information. Transcripts of interviews and focus groups were systematically coded and analyzed in ATLAS.ti for privacy considerations expressed by respondents.RESULTS: Three key findings from the qualitative data suggest a model of privacy disposition. First, participants described privacy related behavior as both contextual and habitual. Second, there are motivations for and deterrents to sharing personal information that do not fit into the analytical categories of risks and benefits. Third, philosophies of privacy, often described as attitudes toward privacy, should be classified as a subtype of motivation or deterrent.DISCUSSION: This qualitative analysis suggests a simple but potentially powerful conceptual model of privacy disposition, or what makes a person more or less private. Components of privacy disposition are identifiable and measurable through self-report and therefore amenable to operationalization and further quantitative inquiry.CONCLUSIONS: We propose this model as the basis for a psychometric instrument that can be used to identify types of privacy dispositions, with potential applications in research, clinical practice, system design, and policy.

  View details for PubMedID 30938756

• Developing a conceptual, reproducible, rubric-based approach to consent and result disclosure for genetic testing by clinicians with minimal genetics background GENETICS IN MEDICINE Ormond, K. E., Hallquist, M. G., Buchanan, A. H., Dondanville, D., Cho, M. K., Smith, M., Roche, M., Brothers, K. B., Coughlin, C. R., Hercher, L., Hudgins, L., Jamal, S., Levy, H. P., Raskin, M., Stosic, M., Uhlmann, W., Wain, K. E., Currey, E., Faucett, W. 2019; 21 (3): 727–35

  View details for DOI 10.1038/s41436-018-0093-6

  View details for Web of Science ID 000460274400028

• 2017 NIH-wide workshop report on "The Human Microbiome: Emerging Themes at the Horizon of the 21st Century" MICROBIOME Alm, E., Borenstein, E., Britton, R. A., Bultman, S. J., Chang, E. B., Cho, M., Dantas, G., Dominguez-Bello, M., Donovan, S. M., Dorrestein, P., Douglas, A. E., Gewirtz, A., Ghannoum, M., Goodman, A. L., Gordon, J. I., Huffnagle, G. B., Jenq, R. R., Jia, W., Knight, R., Koropatkin, N., Lampe, J. W., Lu, T., Ochman, H., Pamer, E. G., Patterson, A. D., Philpott, D., Pollard, K. S., Rawls, J. F., Salzman, N. H., Sears, C. L., Stappenbeck, T., Taga, M. E., Turnbaugh, P. J., Wang, H. H., Wu, G. D., Xavier, R. J., 2017 NIH-Wide Microbiome Workshop 2019; 7: 32

  Abstract

  The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Institutes and Centers which now fund this area, and the technical challenges and knowledge gaps which will need to be addressed in order for this field to advance over the next 10 years. This report summarizes the key points in the talks, round table discussions, and Joint Agency Panel from this workshop.

  View details for DOI 10.1186/s40168-019-0627-4

  View details for Web of Science ID 000459927100002

  View details for PubMedID 30808401

  View details for PubMedCentralID PMC6391828

• Consent insufficient for data release. Science (New York, N.Y.) Nicol, D., Eckstein, L., Bentzen, H. B., Borry, P., Burgess, M., Burke, W., Chalmers, D., Cho, M., Dove, E., Fullerton, S., Ida, R., Kato, K., Kaye, J., Koenig, B., Manson, S., McGrail, K., Meslin, E., O'Doherty, K., Prainsack, B., Shabani, M., Tabor, H., Thorogood, A., de Vries, J. 2019; 364 (6439): 445–46

  View details for DOI 10.1126/science.aax0892

  View details for PubMedID 31048483

• Understanding Ethical, Legal and Societal Issues (ELSIs) in Human Biobanking and Genomics for Research and Healthcare in Zimbabwe: The Genomics Inheritance Law Ethics and Society GILES initiative. AAS open research Matimba, A., Chimatira, A., Kuguyo, O., January, J., Mupambireyi, Z., Marimbe-Dube, B., Chikwasha, V., Nyati-Jokomo, Z., Muteti, S., Mangezvo, P., Kangwende, A., Chingono, A., Chidzonga, M., Gandari, J., Hakim, J., Nathoo, K., Samkange, C., Mangezi, W., Lee, S., Gwanzura, L., Cho, M., Ndebele, P. 2019; 2: 1

  Abstract

  Biobanks and human genomics applications are key for understanding health, disease and heredity in Africa and globally. Growing interest in these technologies calls for strengthening relevant legal, ethical and policy systems to address knowledge disparities and ensure protection of society, while supporting advancement of science. In Zimbabwe there is limited understanding of ethical, legal, and societal issues (ELSI) for biobanking and genomics. The Genomics Inheritance Law Ethics and Society (GILES) initiative was established in 2015 to explore the current status and gaps in the ethical and legal frameworks, knowledge among various stakeholders, and to establish capacity for addressing ELSI of biobanking and genomics as applied in biomedical and population research, and healthcare. A multi-methods approach was applied including document reviews, focus group discussions and in-depth interviews among health and research professionals, and community members in six provinces comprising urban, peri-urban and rural areas. Emerging findings indicates a need for updating guidelines and policies for addressing ELSI in biobanking and genomics research in Zimbabwe. Emerging terminologies such as biobanking and genomics lack clarity suggesting a need for increased awareness and educational tools for health professionals, research scientists and community members. Common concerns relating to consent processes, sample and data use and sharing, particularly where there is trans-national flow of biospecimens and data, call for nationally tailored ELSI frameworks aligned to regional and international initiatives. This paper describes the strategy undertaken for the development and implementation of the GILES project and discusses the importance of such an initiative for characterisation of ELSI of human biobanking and genomics in Zimbabwe and Africa. Conducting this explorative study among a wide range of stakeholders over a countrywide geographical regions, established one of the most comprehensive studies for ELSI of human biobanking and genomics in Africa.

  View details for DOI 10.12688/aasopenres.12917.1

  View details for PubMedID 32382699

• "I don't want to be Henrietta Lacks": diverse patient perspectives on donating biospecimens for precision medicine research GENETICS IN MEDICINE Lee, S., Cho, M. K., Kraft, S. A., Varsava, N., Gillespie, K., Ormond, K. E., Wilfond, B. S., Magnus, D. 2019; 21 (1): 107–13

  View details for DOI 10.1038/s41436-018-0032-6

  View details for Web of Science ID 000455403400016

• In support of mitochondrial replacement therapy. Nature medicine Adashi, E. Y., Caplan, A. L., Capron, A. n., Chapman, A. R., Cho, M. n., Clayton, E. W., Cohen, I. G., Cook-Deegan, R. n., Faden, R. R., Friedmann, T. n., Gostin, L. O., Greely, H. T., Johnston, J. n., Juengst, E. n., King, P. A., Knowles, L. P., Lyerly, A. D., McGuire, A. L., Moreno, J. D., Rothenberg, K. n., Truog, R. D., Walters, L. n. 2019

  View details for DOI 10.1038/s41591-019-0477-4

  View details for PubMedID 31160819

• Data mining for health: staking out the ethical territory of digital phenotyping. NPJ digital medicine Martinez-Martin, N., Insel, T. R., Dagum, P., Greely, H. T., Cho, M. K. 2018; 1

  Abstract

  Digital phenotyping uses smartphone and wearable signals to measure cognition, mood, and behavior. This promising new approach has been developed as an objective, passive assessment tool for the diagnosis and treatment of mental illness. Digital phenotyping is currently used with informed consent in research studies but is expected to expand to broader uses in healthcare and direct-to-consumer applications. Digital phenotyping could involve the collection of massive amounts of individual data and potential creation of new categories of health and risk assessment data. Because existing ethical and regulatory frameworks for the provision of mental healthcare do not clearly apply to digital phenotyping, it is critical to consider its possible ethical, legal, and social implications. This paper addresses four major areas where guidelines and best practices will be helpful: transparency, informed consent, privacy, and accountability. It will be important to consider these issues early in the development of this new approach so that its promise is not limited by harmful effects or unintended consequences.

  View details for DOI 10.1038/s41746-018-0075-8

  View details for PubMedID 31211249

  View details for PubMedCentralID PMC6550156

• Data mining for health: staking out the ethical territory of digital phenotyping NPJ DIGITAL MEDICINE Martinez-Martin, N., Insel, T. R., Dagum, P., Greely, H. T., Cho, M. K. 2018; 1

  View details for DOI 10.1038/s41746-018-0075-8

  View details for Web of Science ID 000453910600001

• Developing a conceptual, reproducible, rubric-based approach to consent and result disclosure for genetic testing by clinicians with minimal genetics background. Genetics in medicine : official journal of the American College of Medical Genetics Ormond, K. E., Hallquist, M. L., Buchanan, A. H., Dondanville, D., Cho, M. K., Smith, M., Roche, M., Brothers, K. B., Coughlin, C. R., Hercher, L., Hudgins, L., Jamal, S., Levy, H. P., Raskin, M., Stosic, M., Uhlmann, W., Wain, K. E., Currey, E., Faucett, W. A. 2018

  Abstract

  PURPOSE: In response to genetic testing being widely ordered by nongenetics clinicians, the Consent and Disclosure Recommendations (CADRe) Workgroup of the Clinical Genome Resource (ClinGen; clinicalgenome.org ) developed guidance to facilitate communication about genetic testing and efficiently improve the patient experience. Considering ethical, legal, and social implications, and medical factors, CADRe developed and pilot tested two rubrics addressing consent for genetic testing and results disclosure. The CADRe rubrics allow for adjusting the communication approach based on circumstances specific to patients and ordering clinicians.METHODS: We present results of a formative survey of 66 genetics clinicians to assess the consent rubric for nine genes (MLH1, CDH1, TP53, GJB2, OTC; DMD, HTT, and CYP2C9/VKORC1). We also conducted interviews and focus groups with family and patient stakeholders (N=18), nongenetics specialists (N=27), and genetics clinicians (N=32) on both rubrics.RESULTS: Formative evaluation of the CADRe rubrics suggests key factors on which to make decisions about consent and disclosure discussions for a "typical" patient.CONCLUSION: We propose that the CADRe rubrics include the primary issues necessary to guide communication recommendations, and are ready for pilot testing by nongenetics clinicians. Consultation with genetics clinicians can be targeted toward more complex or intensive consent and disclosure counseling.

  View details for PubMedID 29976988

• "I don't want to be Henrietta Lacks": diverse patient perspectives on donating biospecimens for precision medicine research. Genetics in medicine : official journal of the American College of Medical Genetics Lee, S. S., Cho, M. K., Kraft, S. A., Varsava, N., Gillespie, K., Ormond, K. E., Wilfond, B. S., Magnus, D. 2018

  Abstract

  PURPOSE: To determine whether patients distinguish between biospecimens and electronic health records (EHRs) when considering research participation to inform research protections.METHODS: We conducted 20 focus groups with individuals who identified as African American, Hispanic, Chinese, South Asian, and non-Hispanic white on the collection of biospecimens and EHR data for research.RESULTS: Our study found that many participants did not distinguish between biospecimens and EHR data. However, some participants identified specific concerns about biospecimens. These included the need for special care and respect for biospecimens due to enduring connections between the body and identity; the potential for unacceptable future research, specifically the prospect of human cloning; heightened privacy risks; and the potential for unjust corporate profiteering. Among those who distinguished biospecimens from EHR data, many supported separate consent processes and would limit their own participation to EHR data.CONCLUSION: Considering that the potential misuse of EHR data is as great as, if not greater than, for biospecimens, more research is needed to understand how attitudes differ between biospecimens and EHR data across diverse populations. Such research should explore mechanisms beyond consent that can address diverse values, perspectives, and misconceptions about sources of patient information to build trust in research relationships.

  View details for PubMedID 29887604

• Anticipating uncertainty and irrevocable decisions: provider perspectives on implementing whole-genome sequencing in critically ill children with heart disease. Genetics in medicine : official journal of the American College of Medical Genetics Char, D. S., Lee, S. S., Magnus, D. n., Cho, M. n. 2018

  Abstract

  PurposeTo investigate the potential impacts of whole-genome sequencing (WGS) in the pediatric critical-care context, we examined how clinicians caring for critically ill children with congenital heart disease (CHD) anticipate and perceive the impact of WGS on their decision-making process and treatment recommendations.MethodsWe conducted semistructured in-person and telephone interviews of clinicians involved in the care of critically ill children with CHD at a high-volume pediatric heart center. We qualitatively analyzed the transcribed interviews.ResultsIn total, 34 clinicians were interviewed. Three themes emerged: (i) uncertainty about the accuracy of WGS testing and adequacy of testing validation; (ii) the use of WGS to facilitate life-limiting decisions such as futility, rationing, and selective prenatal termination; and (iii) moral distress over using WGS with a lack of decision support.ConclusionDespite uncertainty about WGS testing, the interviewed clinicians were using, and anticipated expanding the use of, WGS results to justify declarations of futility, withdrawal of care, and rationing in critically ill children with CHD. This situation is causing moral distress in providers who have to make high-stakes decisions involving WGS results, with only partial understanding of them. Decision support for clinicians, and discussion with families of the risks of using WGS for rationing or withdrawal, is needed.Genet Med advance online publication, 1 March 2018; doi:10.1038/gim.2018.25.

  View details for PubMedID 29493583

• Protect NIH's DNA advisory committee. Science (New York, N.Y.) Adelman, Z. N., Albritton, L. M., Boris-Lawrie, K., Buchmeier, M. J., Cannon, P., Cho, M., DiGiusto, D., Donahue, J. K., Federoff, H. J., Hammarskjold, M., Hardison, A. D., Hearing, P., Lee, B., Lee, D. A., Porteus, M. H., Ross, L. F., Ross, S. R., Wooley, D. P., Zoloth, L. 2018; 362 (6413): 409–10

  View details for PubMedID 30361364

• Trustworthiness in Untrustworthy Times: Response to Open Peer Commentaries on Beyond Consent AMERICAN JOURNAL OF BIOETHICS Kraft, S. A., Cho, M. K., Gillespie, K., Varsava, N., Ormond, K. E., Wilfond, B. S., Lee, S. 2018; 18 (5): W6–W8

  View details for PubMedID 29697352

• Beyond Consent: Building Trusting Relationships With Diverse Populations in Precision Medicine Research AMERICAN JOURNAL OF BIOETHICS Kraft, S. A., Cho, M. K., Gillespie, K., Halley, M., Varsava, N., Ormond, K. E., Luft, H. S., Wilfond, B. S., Lee, S. 2018; 18 (4): 3–20

  View details for DOI 10.1080/15265161.2018.1431322

  View details for Web of Science ID 000429342200006

  View details for PubMedID 27996908

• The Emergence of Clinical Research Ethics Consultation: Insights From a National Collaborative AMERICAN JOURNAL OF BIOETHICS Porter, K. M., Danis, M., Taylor, H. A., Cho, M. K., Wilfond, B. S., Clinical Res Ethics Consultation 2018; 18 (1): 39–45

  Abstract

  The increasing complexity of human subjects research and its oversight has prompted researchers, as well as institutional review boards (IRBs), to have a forum in which to discuss challenging or novel ethical issues not fully addressed by regulations. Research ethics consultation (REC) services provide such a forum. In this article, we rely on the experiences of a national Research Ethics Consultation Collaborative that collected more than 350 research ethics consultations in a repository and published 18 challenging cases with accompanying ethical commentaries to highlight four contexts in which REC can be a valuable resource. REC assists: 1) investigators before and after the regulatory review; 2) investigators, IRBs, and other research administrators facing challenging and novel ethical issues; 3) IRBs and investigators with the increasing challenges of informed consent and risk/benefit analysis; and 4) in providing flexible and collaborative assistance to overcome study hurdles, mediate conflicts within a team, or directly engage with research participants. Institutions that have established, or plan to establish, REC services should work to raise the visibility of their service and engage in open communication with existing clinical ethics consult services as well as the IRB. While the IRB system remains the foundation for the ethical review of research, REC can be a valuable service for investigators, regulators, and research participants aligned with the goal of supporting ethical research.

  View details for PubMedID 29313771

• Defining the Scope and Improving the Quality of Clinical Research Ethics Consultation: Response to Open Peer Commentaries About the National Collaborative AMERICAN JOURNAL OF BIOETHICS Porter, K. M., Danis, M., Taylor, H. A., Cho, M. K., Wilfond, B. S. 2018; 18 (2): W13–W15

  View details for PubMedID 29393779

• Consent and engagement, security, and authentic living using wearable and mobile health technology NATURE BIOTECHNOLOGY Kreitmair, K. V., Cho, M. K., Magnus, D. C. 2017; 35 (7): 617–20

  View details for PubMedID 28700542

• A randomized study of multimedia informational aids for research on medical practices: Implications for informed consent CLINICAL TRIALS Kraft, S. A., Constantine, M., Magnus, D., Porter, K. M., Lee, S. S., Green, M., Kass, N. E., Wilfond, B. S., Cho, M. K. 2017; 14 (1): 94-102

  Abstract

  Participant understanding is a key element of informed consent for enrollment in research. However, participants often do not understand the nature, risks, benefits, or design of the studies in which they take part. Research on medical practices, which studies standard interventions rather than new treatments, has the potential to be especially confusing to participants because it is embedded within usual clinical care. Our objective in this randomized study was to compare the ability of a range of multimedia informational aids to improve participant understanding in the context of research on medical practices.We administered a web-based survey to members of a proprietary online panel sample selected to match national US demographics. Respondents were randomized to one of five arms: four content-equivalent informational aids (animated videos, slideshows with voice-over, comics, and text) and one no-intervention control. We measured knowledge of research on medical practices using a summary knowledge score from 10 questions based on the content of the informational aids. We used analysis of variance and paired t-tests to compare knowledge scores between arms.There were 1500 completed surveys (300 in each arm). Mean knowledge scores were highest for the slideshows with voice-over (65.7%), followed by the animated videos (62.7%), comics (60.7%), text (57.2%), and control (50.3%). Differences between arms were statistically significant except between the slideshows with voice-over and animated videos and between the animated videos and comics. Informational aids that included an audio component (animated videos and slideshows with voice-over) had higher knowledge scores than those without an audio component (64.2% vs 59.0%, p < .0001). There was no difference between informational aids with a character-driven story component (animated videos and comics) and those without.Our results show that simple multimedia aids that use a dual-channel approach, such as voice-over with visual reinforcement, can improve participant knowledge more effectively than text alone. However, the relatively low knowledge scores suggest that targeted informational aids may be needed to teach some particularly challenging concepts. Nonetheless, our results demonstrate the potential to improve informed consent for research on medical practices using multimedia aids that include simplified language and visual metaphors.

  View details for DOI 10.1177/1740774516669352

  View details for Web of Science ID 000394652700010

• Feasibility of Obtaining Measures of Lifestyle From a Smartphone App: The MyHeart Counts Cardiovascular Health Study. JAMA cardiology McConnell, M. V., Shcherbina, A., Pavlovic, A., Homburger, J. R., Goldfeder, R. L., Waggot, D., Cho, M. K., Rosenberger, M. E., Haskell, W. L., Myers, J., Champagne, M. A., Mignot, E., Landray, M., Tarassenko, L., Harrington, R. A., Yeung, A. C., Ashley, E. A. 2017; 2 (1): 67-76

  Abstract

  Studies have established the importance of physical activity and fitness, yet limited data exist on the associations between objective, real-world physical activity patterns, fitness, sleep, and cardiovascular health.To assess the feasibility of obtaining measures of physical activity, fitness, and sleep from smartphones and to gain insights into activity patterns associated with life satisfaction and self-reported disease.The MyHeart Counts smartphone app was made available in March 2015, and prospective participants downloaded the free app between March and October 2015. In this smartphone-based study of cardiovascular health, participants recorded physical activity, filled out health questionnaires, and completed a 6-minute walk test. The app was available to download within the United States.The feasibility of consent and data collection entirely on a smartphone, the use of machine learning to cluster participants, and the associations between activity patterns, life satisfaction, and self-reported disease.From the launch to the time of the data freeze for this study (March to October 2015), the number of individuals (self-selected) who consented to participate was 48 968, representing all 50 states and the District of Columbia. Their median age was 36 years (interquartile range, 27-50 years), and 82.2% (30 338 male, 6556 female, 10 other, and 3115 unknown) were male. In total, 40 017 (81.7% of those who consented) uploaded data. Among those who consented, 20 345 individuals (41.5%) completed 4 of the 7 days of motion data collection, and 4552 individuals (9.3%) completed all 7 days. Among those who consented, 40 017 (81.7%) filled out some portion of the questionnaires, and 4990 (10.2%) completed the 6-minute walk test, made available only at the end of 7 days. The Heart Age Questionnaire, also available after 7 days, required entering lipid values and age 40 to 79 years (among 17 245 individuals, 43.1% of participants). Consequently, 1334 (2.7%) of those who consented completed all fields needed to compute heart age and a 10-year risk score. Physical activity was detected for a mean (SD) of 14.5% (8.0%) of individuals' total recorded time. Physical activity patterns were identified by cluster analysis. A pattern of lower overall activity but more frequent transitions between active and inactive states was associated with equivalent self-reported cardiovascular disease as a pattern of higher overall activity with fewer transitions. Individuals' perception of their activity and risk bore little relation to sensor-estimated activity or calculated cardiovascular risk.A smartphone-based study of cardiovascular health is feasible, and improvements in participant diversity and engagement will maximize yield from consented participants. Large-scale, real-world assessment of physical activity, fitness, and sleep using mobile devices may be a useful addition to future population health studies.

  View details for DOI 10.1001/jamacardio.2016.4395

  View details for PubMedID 27973671

• Fairness and Transparency in an Expanded Access Program: Allocation of the Only Treatment for SMA1. The American journal of bioethics : AJOB Burgart, A. M., Collier, J. n., Cho, M. K. 2017; 17 (10): 71–73

  View details for PubMedID 29020542

• Modern Pregnancies and (Im)Perfect Babies AMERICAN JOURNAL OF BIOETHICS Kraft, S. A. 2017; 17 (1): 1–2

  Abstract

  With the growth of precision medicine research on health data and biospecimens, research institutions will need to build and maintain long-term, trusting relationships with patient-participants. While trust is important for all research relationships, the longitudinal nature of precision medicine research raises particular challenges for facilitating trust when the specifics of future studies are unknown. Based on focus groups with racially and ethnically diverse patients, we describe several factors that influence patient trust and potential institutional approaches to building trustworthiness. Drawing on these findings, we suggest several considerations for research institutions seeking to cultivate long-term, trusting relationships with patients: (1) Address the role of history and experience on trust, (2) engage concerns about potential group harm, (3) address cultural values and communication barriers, and (4) integrate patient values and expectations into oversight and governance structures.

  View details for PubMedID 29621457

• Metaphors matter: from biobank to a library of medical information. Genetics in medicine : official journal of the American College of Medical Genetics Cho, M. K., Varsava, N. n., Kraft, S. A., Ashwal, G. n., Gillespie, K. n., Magnus, D. n., Ormond, K. E., Thomas, A. n., Wilfond, B. S., Lee, S. S. 2017

  View details for PubMedID 29267267

• A comparison of institutional review board professionals' and patients' views on consent for research on medical practices. Clinical trials Kraft, S. A., Cho, M. K., Constantine, M., Lee, S. S., Kelley, M., Korngiebel, D., James, C., Kuwana, E., Meyer, A., Porter, K., Diekema, D., Capron, A. M., Alicic, R., Wilfond, B. S., Magnus, D. 2016; 13 (5): 555-565

  Abstract

  In the context of research on medical practices, which includes comparative effectiveness research and pragmatic clinical trials, empirical studies have begun to raise questions about the extent to which institutional review boards' interpretations and applications of research regulations align with patients' values. To better understand the similarities and differences between these stakeholder groups, we compare and contrast two surveys: one of institutional review board professionals and one of patients, which examine views on consent for research on medical practices.We conducted online surveys of two target populations between July 2014 and March 2015. We surveyed 601 human subjects research professionals out of 1500 randomly selected from the Public Responsibility in Medicine and Research membership list (40.1% response rate), limiting analysis to 537 respondents who reported having had institutional review board experience. We also surveyed 120 adult patients out of 225 approached at subspecialty clinics in Spokane, Washington (53.3% response rate). Our survey questions probed attitudes about consent in the context of research on medical practices using medical record review and randomization. The patient survey included three embedded animated videos to explain these concepts.A majority of institutional review board professionals distinguished between consent preferences for medical record review and randomization, ranked clinicians as the least preferred person to obtain participant consent (54.6%), and viewed written or verbal permission as the minimum acceptable consent approach for research on medical practices using randomization (87.3%). In contrast, most patients had similar consent preferences for research on medical practices using randomization and medical record review, most preferred to have consent conversations with their doctors rather than with researchers for studies using randomization (72.6%) and medical record review (67.0%), and only a few preferred to see research involving randomization (16.8%) or medical record review (13.8%) not take place if obtaining written or verbal permission would make the research too difficult to conduct. Limitations of our post hoc analysis include differences in framing, structure, and language between the two surveys and possible response bias.Our findings highlight a need to identify appropriate ways to integrate patient preferences into prevailing regulatory interpretations as institutional review boards increasingly apply research regulations in the context of research on medical practices. Dialogue between institutional review boards and research participants will be an important part of this process and should inform future regulatory guidance.

  View details for DOI 10.1177/1740774516648907

  View details for PubMedID 27257125

  View details for PubMedCentralID PMC5025342

• A randomized study of multimedia informational aids for research on medical practices: Implications for informed consent. Clinical trials Kraft, S. A., Constantine, M., Magnus, D., Porter, K. M., Lee, S. S., Green, M., Kass, N. E., Wilfond, B. S., Cho, M. K. 2016

  Abstract

  Participant understanding is a key element of informed consent for enrollment in research. However, participants often do not understand the nature, risks, benefits, or design of the studies in which they take part. Research on medical practices, which studies standard interventions rather than new treatments, has the potential to be especially confusing to participants because it is embedded within usual clinical care. Our objective in this randomized study was to compare the ability of a range of multimedia informational aids to improve participant understanding in the context of research on medical practices.We administered a web-based survey to members of a proprietary online panel sample selected to match national US demographics. Respondents were randomized to one of five arms: four content-equivalent informational aids (animated videos, slideshows with voice-over, comics, and text) and one no-intervention control. We measured knowledge of research on medical practices using a summary knowledge score from 10 questions based on the content of the informational aids. We used analysis of variance and paired t-tests to compare knowledge scores between arms.There were 1500 completed surveys (300 in each arm). Mean knowledge scores were highest for the slideshows with voice-over (65.7%), followed by the animated videos (62.7%), comics (60.7%), text (57.2%), and control (50.3%). Differences between arms were statistically significant except between the slideshows with voice-over and animated videos and between the animated videos and comics. Informational aids that included an audio component (animated videos and slideshows with voice-over) had higher knowledge scores than those without an audio component (64.2% vs 59.0%, p < .0001). There was no difference between informational aids with a character-driven story component (animated videos and comics) and those without.Our results show that simple multimedia aids that use a dual-channel approach, such as voice-over with visual reinforcement, can improve participant knowledge more effectively than text alone. However, the relatively low knowledge scores suggest that targeted informational aids may be needed to teach some particularly challenging concepts. Nonetheless, our results demonstrate the potential to improve informed consent for research on medical practices using multimedia aids that include simplified language and visual metaphors.

  View details for PubMedID 27625314

• Toward a Predictive Understanding of Earth's Microbiomes to Address 21st Century Challenges. mBio Blaser, M. J., Cardon, Z. G., Cho, M. K., Dangl, J. L., Donohue, T. J., Green, J. L., Knight, R., Maxon, M. E., Northen, T. R., Pollard, K. S., Brodie, E. L. 2016; 7 (3)

  Abstract

  Microorganisms have shaped our planet and its inhabitants for over 3.5 billion years. Humankind has had a profound influence on the biosphere, manifested as global climate and land use changes, and extensive urbanization in response to a growing population. The challenges we face to supply food, energy, and clean water while maintaining and improving the health of our population and ecosystems are significant. Given the extensive influence of microorganisms across our biosphere, we propose that a coordinated, cross-disciplinary effort is required to understand, predict, and harness microbiome function. From the parallelization of gene function testing to precision manipulation of genes, communities, and model ecosystems and development of novel analytical and simulation approaches, we outline strategies to move microbiome research into an era of causality. These efforts will improve prediction of ecosystem response and enable the development of new, responsible, microbiome-based solutions to significant challenges of our time.

  View details for DOI 10.1128/mBio.00714-16

  View details for PubMedID 27178263

  View details for PubMedCentralID PMC4895116

• "This lifetime commitment": Public conceptions of disability and noninvasive prenatal genetic screening. American journal of medical genetics. Part A Steinbach, R. J., Allyse, M., Michie, M., Liu, E. Y., Cho, M. K. 2016; 170A (2): 363-374

  Abstract

  Recently, new noninvasive prenatal genetic screening technologies for Down syndrome and other genetic conditions have become commercially available. Unique characteristics of these screening tests have reignited long-standing concerns about prenatal testing for intellectual and developmental disabilities. We conducted a web-based survey of a sample of the US public to examine how attitudes towards disability inform views of prenatal testing in the context of these rapidly advancing prenatal genetic screening technologies. Regardless of opinion toward disability, the majority of respondents supported both the availability of screening and the decision to continue a pregnancy positive for aneuploidy. Individuals rationalized their support with various conceptions of disability; complications of the expressivist argument and other concerns from the disability literature were manifested in many responses analyzed.

  View details for DOI 10.1002/ajmg.a.37459

  View details for PubMedID 26566970

• The Role of Patient Perspectives in Clinical Research Ethics and Policy: Response to Open Peer Commentaries on "Patient Perspectives on the Learning Health System". American journal of bioethics Kelley, M., James, C., Alessi Kraft, S., Korngiebel, D., Wijangco, I., Joffe, S., Cho, M. K., Wilfond, B., Lee, S. S. 2016; 16 (2): W7-9

  View details for DOI 10.1080/15265161.2015.1125967

  View details for PubMedID 26832115

• "This lifetime commitment": Public conceptions of disability and noninvasive prenatal genetic screening. American journal of medical genetics. Part A Steinbach, R. J., Allyse, M., Michie, M., Liu, E. Y., Cho, M. K. 2016; 170 (2): 363-374

  Abstract

  Recently, new noninvasive prenatal genetic screening technologies for Down syndrome and other genetic conditions have become commercially available. Unique characteristics of these screening tests have reignited long-standing concerns about prenatal testing for intellectual and developmental disabilities. We conducted a web-based survey of a sample of the US public to examine how attitudes towards disability inform views of prenatal testing in the context of these rapidly advancing prenatal genetic screening technologies. Regardless of opinion toward disability, the majority of respondents supported both the availability of screening and the decision to continue a pregnancy positive for aneuploidy. Individuals rationalized their support with various conceptions of disability; complications of the expressivist argument and other concerns from the disability literature were manifested in many responses analyzed.

  View details for DOI 10.1002/ajmg.a.37459

  View details for PubMedID 26566970

• Engineering Values Into Genetic Engineering: A Proposed Analytic Framework for Scientific Social Responsibility AMERICAN JOURNAL OF BIOETHICS Sankar, P. L., Cho, M. K. 2015; 15 (12): 18-24

  View details for DOI 10.1080/15265161.2015.1104169

  View details for PubMedID 26632356

• Impact of Psychiatric Information on Potential Jurors in Evaluating High-Functioning Autism Spectrum Disorder (hfASD) JOURNAL OF MENTAL HEALTH RESEARCH IN INTELLECTUAL DISABILITIES Berryessa, C. M., Milner, L. C., Garrison, N. A., Cho, M. K. 2015; 8 (3-4): 140-167

  View details for DOI 10.1080/19315864.2015.1040176

  View details for Web of Science ID 000364548700003

• Reporting Race and Ethnicity in Genetics Research: Do Journal Recommendations or Resources Matter? SCIENCE AND ENGINEERING ETHICS Sankar, P., Cho, M. K., Monahan, K., Nowak, K. 2015; 21 (5): 1353-1366

  View details for DOI 10.1007/s11948-014-9596-y

  View details for PubMedID 25407312

• Patient Perspectives on the Learning Health System: The Importance of Trust and Shared Decision Making AMERICAN JOURNAL OF BIOETHICS Kelley, M., James, C., Kraft, S. A., Korngiebel, D., Wijangco, I., Rosenthal, E., Joffe, S., Cho, M. K., Wilfond, B., Lee, S. S. 2015; 15 (9): 4-17

  Abstract

  We conducted focus groups to assess patient attitudes toward research on medical practices in the context of usual care. We found that patients focus on the implications of this research for their relationship with and trust in their physicians. Patients view research on medical practices as separate from usual care, demanding dissemination of information and in most cases, individual consent. Patients expect information about this research to come through their physician, whom they rely on to identify and filter associated risks. In general, patients support this research, but worry that participation in research involving randomization may undermine individualized care that acknowledges their unique medical histories. These findings suggest the need for public education on variation in practice among physicians and the need for a collaborative approach to the governance of research on medical practices that addresses core values of trust, transparency, and partnership.

  View details for DOI 10.1080/15265161.2015.1062163

  View details for Web of Science ID 000360555700002

• Building a Central Repository for Research Ethics Consultation Data: A Proposal for a Standard Data Collection Tool CTS-CLINICAL AND TRANSLATIONAL SCIENCE Cho, M. K., Taylor, H., McCormick, J. B., Anderson, N., Barnard, D., Boyle, M. B., Capron, A. M., Dorfman, E., Havard, K., Reider, C., Sadler, J., Schwartz, P., Sharp, R. R., Danis, M., Wilfond, B. S. 2015; 8 (4): 376-387

  View details for DOI 10.1111/cts.12268

  View details for Web of Science ID 000360585200024

• Building a Central Repository for Research Ethics Consultation Data: A Proposal for a Standard Data Collection Tool. Clinical and translational science Cho, M. K., Taylor, H., McCormick, J. B., Anderson, N., Barnard, D., Boyle, M. B., Capron, A. M., Dorfman, E., Havard, K., Reider, C., Sadler, J., Schwartz, P., Sharp, R. R., Danis, M., Wilfond, B. S. 2015; 8 (4): 376-387

  Abstract

  Clinical research ethics consultation services have been established across academic health centers over the past decade. This paper presents the results of collaboration within the CTSA consortium to develop a standard approach to the collection of research ethics consultation information to serve as a foundation for quality improvement, education, and research efforts. This approach includes categorizing and documenting descriptive information about the requestor, research project, the ethical question, the consult process, and describing the basic structure for a consult note. This paper also explores challenges in determining how to share some of this information between collaborating institutions related to concerns about confidentially, data quality, and informatics. While there is much still to be learned to improve the process of clinical research ethics consultation, these tools can advance these efforts, which, in turn, can facilitate the ethical conduct of research.

  View details for DOI 10.1111/cts.12268

  View details for PubMedID 25758372

• Preventive Genomic Sequencing in the General Population: Do PGS Fly? The American journal of bioethics : AJOB Cho, M. K. 2015; 15 (7): 1-2

  View details for DOI 10.1080/15265161.2015.1054160

  View details for PubMedID 26147253

  View details for PubMedCentralID PMC4786440

• Impact of Psychiatric Information on Potential Jurors in Evaluating High-Functioning Autism Spectrum Disorder (hfASD). Journal of mental health research in intellectual disabilities Berryessa, C. M., Milner, L. C., Garrison, N. A., Cho, M. K. 2015; 8 (3-4): 140-167

  Abstract

  During a trial involving an offender with a mental disorder, jurors are often required to evaluate information on the disorder and its characteristics. This evaluation relies on how jurors understand and synthesize psychiatric and other evidence on the disorder and this information's impact on the case, an offender's culpability, and the rendered verdict. The importance of this evaluation is further highlighted when jurors are faced with evaluating a disorder that may be associated with criminal actions of diagnosed offenders, such as high-functioning autism spectrum disorder (hfASD). We designed a three-part survey to assess potential jurors' attitudes concerning an offender's diagnosis with hfASD in terms of perceptions and decisions surrounding legal and moral responsibility, personal characteristics of the offender, the introduction of psychiatric and genetic information, and the condition's influence on the facts of the case. A sample of 623 jury-eligible U.S. adults completed the survey. We found the majority of participants were influenced by the information provided on hfASD. Most respondents indicated that hfASD diagnosis should generally not affect the legal responsibility of an offender, but many reported the disorder as a mitigating factor when evaluating moral responsibility and legal consequences for criminal actions. Respondents reported favorable and sympathetic perceptions of individuals with autism and associated characteristics but were unsure, even after the presentation of psychiatric information on hfASD, if these disorders should be classified as "mental illness." Further, the majority reported their views were in some way influenced by the fact that hfASD has potential genetic origins.

  View details for DOI 10.1080/19315864.2015.1040176

  View details for PubMedID 26843900

  View details for PubMedCentralID PMC4733480

• Genomics in the clinic: ethical and policy challenges in clinical next-generation sequencing programs at early adopter USA institutions. Personalized medicine Milner, L. C., Garrison, N. A., Cho, M. K., Altman, R. B., Hudgins, L., Galli, S. J., Lowe, H. J., Schrijver, I., Magnus, D. C. 2015; 12 (3): 269-282

  Abstract

  Next-generation sequencing (NGS) technologies are poised to revolutionize clinical diagnosis and treatment, but raise significant ethical and policy challenges. This review examines NGS program challenges through a synthesis of published literature, website and conference presentation content, and interviews at early-adopting institutions in the USA. Institutions are proactively addressing policy challenges related to the management and technical aspects of program development. However, ethical challenges related to patient-related aspects have not been fully addressed. These complex challenges present opportunities to develop comprehensive and standardized regulations across programs. Understanding the strengths, weaknesses and current practices of evolving NGS program approaches are important considerations for institutions developing NGS services, policymakers regulating or funding NGS programs and physicians and patients considering NGS services.

  View details for DOI 10.2217/pme.14.88

  View details for PubMedID 29771644

• Attitudes Toward Risk and Informed Consent for Research on Medical Practices: A Cross-sectional Survey. Annals of internal medicine Cho, M. K., Magnus, D., Constantine, M., Lee, S. S., Kelley, M., Alessi, S., Korngiebel, D., James, C., Kuwana, E., Gallagher, T. H., Diekema, D., Capron, A. M., Joffe, S., Wilfond, B. S. 2015; 162 (10): 690-696

  Abstract

  The U.S. Office for Human Research Protections has proposed that end points of randomized trials comparing the effectiveness of standard medical practices are risks of research that would require disclosure and written informed consent, but data are lacking on the views of potential participants.To assess attitudes of U.S. adults about risks and preferences for notification and consent for research on medical practices.Cross-sectional survey conducted in August 2014.Web-based questionnaire.1095 U.S. adults sampled from an online panel (n = 805) and an online convenience river sample (n = 290).Attitudes toward risk, informed consent, and willingness to participate in 3 research scenarios involving medical record review and randomization of usual medical practices.97% of respondents agreed that health systems should evaluate standard treatments. Most wanted to be asked for permission to participate in each of 3 scenarios (range, 75.2% to 80.4%), even if it involved only medical record review, but most would accept nonwritten (oral) permission or general notification if obtaining written permission would make the research too difficult to conduct (range, 70.2% to 82.7%). Most perceived additional risk from each scenario (range, 64.0% to 81.6%).Use of hypothetical scenarios and a nonprobability sample that was not fully representative of the U.S. population.Most respondents preferred to be asked for permission to participate in observational and randomized research evaluating usual medical practices, but they are willing to accept less elaborate approaches than written consent if research would otherwise be impracticable. These attitudes are not aligned with proposed regulatory guidance.National Center for Advancing Translational Sciences at the National Institutes of Health.

  View details for DOI 10.7326/M15-0166

  View details for PubMedID 25868119

• Attitudes Toward Risk and Informed Consent for Research on Medical Practices A Cross-sectional Survey ANNALS OF INTERNAL MEDICINE Cho, M. K., Magnus, D., Constantine, M., Lee, S. S., Kelley, M., Alessi, S., Korngiebel, D., James, C., Kuwana, E., Gallagher, T. H., Diekema, D., Capron, A. M., Joffe, S., Wilfond, B. S. 2015; 162 (10): 690-?

  Abstract

  The U.S. Office for Human Research Protections has proposed that end points of randomized trials comparing the effectiveness of standard medical practices are risks of research that would require disclosure and written informed consent, but data are lacking on the views of potential participants.To assess attitudes of U.S. adults about risks and preferences for notification and consent for research on medical practices.Cross-sectional survey conducted in August 2014.Web-based questionnaire.1095 U.S. adults sampled from an online panel (n = 805) and an online convenience river sample (n = 290).Attitudes toward risk, informed consent, and willingness to participate in 3 research scenarios involving medical record review and randomization of usual medical practices.97% of respondents agreed that health systems should evaluate standard treatments. Most wanted to be asked for permission to participate in each of 3 scenarios (range, 75.2% to 80.4%), even if it involved only medical record review, but most would accept nonwritten (oral) permission or general notification if obtaining written permission would make the research too difficult to conduct (range, 70.2% to 82.7%). Most perceived additional risk from each scenario (range, 64.0% to 81.6%).Use of hypothetical scenarios and a nonprobability sample that was not fully representative of the U.S. population.Most respondents preferred to be asked for permission to participate in observational and randomized research evaluating usual medical practices, but they are willing to accept less elaborate approaches than written consent if research would otherwise be impracticable. These attitudes are not aligned with proposed regulatory guidance.National Center for Advancing Translational Sciences at the National Institutes of Health.

  View details for DOI 10.7326/M15-0166

  View details for Web of Science ID 000355015200018

  View details for PubMedID 25868119

• Research Ethics Consultation: Ethical and Professional Practice Challenges and Recommendations ACADEMIC MEDICINE Sharp, R. R., Taylor, H. A., Brinich, M. A., Boyle, M. M., Cho, M., Coors, M., Danis, M., Havard, M., Magnus, D., Wilfond, B. 2015; 90 (5): 615-620

  Abstract

  The complexity of biomedical research has increased considerably in the last decade, as has the pace of translational research. This complexity has generated a number of novel ethical issues for clinical investigators, institutional review boards (IRBs), and other oversight committees. In response, many academic medical centers have created formal research ethics consultation (REC) services to help clinical investigators and IRBs navigate ethical issues in biomedical research. Key functions of a REC service include assisting with research design and implementation, providing a forum for deliberative exploration of ethical issues, and supplementing regulatory oversight. As increasing numbers of academic research institutions establish REC services, there is a pressing need for consensus about the primary aims and policies that should guide these activities. Establishing clear expectations about the aims and policies of REC services is important if REC programs are to achieve their full potential. Drawing on the experiences of a Clinical and Translational Science Award Research Ethics Consultation Working Group, this article describes three major ethical and professional practice challenges associated with the provision of REC: (1) managing multiple institutional roles and responsibilities, (2) managing sensitive information, and (3) communicating with consultation requestors about how these issues are managed. The paper also presents several practical strategies for addressing these challenges and enhancing the quality of REC services.

  View details for DOI 10.1097/ACM.0000000000000640

  View details for Web of Science ID 000353879700022

  View details for PubMedID 25607942

  View details for PubMedCentralID PMC4414686

• Whole genome sequencing in critically ill children. The Lancet. Respiratory medicine Char, D. S., Cho, M., Magnus, D. 2015; 3 (4): 264-266

  View details for DOI 10.1016/S2213-2600(15)00006-5

  View details for PubMedID 25704991

• "What Is the FDA Going to Think?": Negotiating Values through Reflective and Strategic Category Work in Microbiome Science SCIENCE TECHNOLOGY & HUMAN VALUES Darling, K. W., Boyce, A. M., Cho, M. K., Sankar, P. L. 2015; 40 (1): 71-95

  View details for DOI 10.1177/0162243914545405

  View details for Web of Science ID 000345762200003

• Genomics in the clinic: ethical and policy challenges in clinical next-generation sequencing programs at early adopter USA institutions PERSONALIZED MEDICINE Milner, L. C., Garrison, N. A., Cho, M. K., Altman, R. B., Hudgins, L., Galli, S. J., Lowe, H. J., Schrijver, I., Magnus, D. C. 2015; 12 (3): 269-282

  View details for DOI 10.2217/PME.14.88

  View details for Web of Science ID 000355751600011

• Demographic and Experiential Correlates of Public Attitudes Towards Cell-Free Fetal DNA Screening JOURNAL OF GENETIC COUNSELING Sayres, L. C., Allyse, M., Goodspeed, T. A., Cho, M. K. 2014; 23 (6): 957-967

  View details for DOI 10.1007/s10897-014-9704-9

  View details for Web of Science ID 000345079800010

• Demographic and experiential correlates of public attitudes towards cell-free fetal DNA screening. Journal of genetic counseling Sayres, L. C., Allyse, M., Goodspeed, T. A., Cho, M. K. 2014; 23 (6): 957-967

  Abstract

  This study seeks to inform clinical application of cell-free fetal DNA (cffDNA) screening as a novel method for prenatal trisomy detection by investigating public attitudes towards this technology and demographic and experiential characteristics related to these attitudes. Two versions of a 25-item survey assessing interest in cffDNA and existing first-trimester combined screening for either trisomy 13 and 18 or trisomy 21 were distributed among 3,164 members of the United States public. Logistic regression was performed to determine variables predictive of interest in screening options. Approximately 47% of respondents expressed an interest in cffDNA screening for trisomy 13, 18, and 21, with a majority interested in cffDNA screening as a stand-alone technique. A significantly greater percent would consider termination of pregnancy following a diagnosis of trisomy 13 or 18 (52%) over one of trisomy 21 (44%). Willingness to consider abortion of an affected pregnancy was the strongest correlate to interest in both cffDNA and first-trimester combined screening, although markedly more respondents expressed an interest in some form of screening (69% and 71%, respectively) than would consider termination. Greater educational attainment, higher income, and insurance coverage predicted interest in cffDNA screening; stronger religious identification also corresponded to decreased interest. Prior experience with disability and genetic testing was associated with increased interest in cffDNA screening. Several of these factors, in addition to advanced age and Asian race, were, in turn, predictive of respondents' increased willingness to consider post-diagnosis termination of pregnancy. In conclusion, divergent attitudes towards cffDNA screening--and prenatal options more generally--appear correlated with individual socioeconomic and religious backgrounds and experiences with disability and genetic testing. Clinical implementation and counseling for novel prenatal technologies should take these diverse stakeholder values into consideration.

  View details for DOI 10.1007/s10897-014-9704-9

  View details for PubMedID 24715419

• Innocent Fun or "Microslavery"? AN ETHICAL ANALYSIS OF BIOTIC GAMES HASTINGS CENTER REPORT Harvey, H., Havard, M., Magnus, D., Cho, M. K., Riedel-Kruse, I. H. 2014; 44 (6): 38-46

  View details for DOI 10.1002/hast.386

  View details for Web of Science ID 000345510900014

• Translating personalized medicine using new genetic technologies in clinical practice: the ethical issues. Personalized medicine Ormond, K. E., Cho, M. K. 2014; 11 (2): 211-222

  Abstract

  The integration of new genetic technologies into clinical practice holds great promise for the personalization of medical care, particularly the use of large-scale DNA sequencing for genome-wide genetic testing. However, these technologies also yield unprecedented amounts of information whose clinical implications are not fully understood, and we are still developing technical standards for measuring sequence accuracy. These technical and clinical challenges raise ethical issues that are similar to but qualitatively different from those that we are accustomed to dealing with for traditional medical genetics. The sheer amount of information afforded by genome sequencing requires rethinking of how to implement core ethical principles including, but not limited to: informed consent, privacy and data ownership and sharing, technology regulation, issues of access, particularly as new technology is integrated into clinical practice, and issues of potential stigma and impact on perceptions of disability. In this article, we will review the issues of informed consent, privacy, data ownership and technology regulation as they relate to the emerging field of personalized medicine and genomics.

  View details for DOI 10.2217/pme.13.104

  View details for PubMedID 25221608

  View details for PubMedCentralID PMC4160120

• Views of genetics health professionals on the return of genomic results. Journal of genetic counseling Grove, M. E., Wolpert, M. N., Cho, M. K., Lee, S. S., Ormond, K. E. 2014; 23 (4): 531-538

  Abstract

  As exome and whole genome sequencing become clinically available, the potential to receive a large number of clinically relevant but incidental results is a significant challenge in the provision of genomic counseling. We conducted three focus groups of a total of 35 individuals who were members of ASHG and/or NSGC, assessing views towards the return of genomic results. Participants stressed that patient autonomy was primary. There was consensus that a mechanism to return results to the healthcare provider, rather than patient, and to streamline integration into the electronic health record would ensure these results had the maximal impact on patient management. All three focus groups agreed that pharmacogenomic results were reasonable to return and that they were not felt to be stigmatizing. With regard to the return of medically relevant results, there was much debate. Participants had difficulty in consistently assigning specific diseases to 'bins' that were considered obligatory versus optional for disclosure. Consensus was reached regarding the importance of informed consent and pretest counseling visits to clarify what the return of results process would entail. Evidence based professional guidelines should continue to be developed and regularly revised to assist in consistently and appropriately providing genomic results to patients.

  View details for DOI 10.1007/s10897-013-9611-5

  View details for PubMedID 23728783

• Genetic testing of children for predisposition to mood disorders: anticipating the clinical issues. Journal of genetic counseling Erickson, J. A., Kuzmich, L., Ormond, K. E., Gordon, E., Christman, M. F., Cho, M. K., Levinson, D. F. 2014; 23 (4): 566-577

  Abstract

  Large-scale sequencing information may provide a basis for genetic tests for predisposition to common disorders. In this study, participants in the Coriell Personalized Medicine Collaborative (N = 53) with a personal and/or family history of Major Depressive Disorder or Bipolar Disorder were interviewed based on the Health Belief Model around hypothetical intention to test one's children for probability of developing a mood disorder. Most participants (87 %) were interested in a hypothetical test for children that had high ("90 %") positive predictive value, while 51 % of participants remained interested in a modestly predictive test ("20 %"). Interest was driven by beliefs about effects of test results on parenting behaviors and on discrimination. Most participants favored testing before adolescence (64 %), and were reluctant to share results with asymptomatic children before adulthood. Participants anticipated both positive and negative effects of testing on parental treatment and on children's self-esteem. Further investigation will determine whether these findings will generalize to other complex disorders for which early intervention is possible but not clearly demonstrated to improve outcomes. More information is also needed about the effects of childhood genetic testing and sharing of results on parent-child relationships, and about the role of the child in the decision-making process.

  View details for DOI 10.1007/s10897-014-9710-y

  View details for PubMedID 24651919

• Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age. Journal of perinatology Allyse, M., Sayres, L. C., Goodspeed, T. A., Cho, M. K. 2014; 34 (6): 429-434

  Abstract

  Objective:To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake.Study Design:A national sample of 1861 US-based adults was surveyed using a validated online survey instrument. The survey was administered by a commercial survey research company. Respondents were randomized to receive a survey about prenatal testing for trisomy 13 and 18 or trisomy 21. Participants were asked to select among testing modalities, including cffDNA testing, and rank the features of testing that they considered most important to decision making.Result:There was substantive interest in the use of cffDNA testing rather than traditional screening mechanisms, with a minority of respondents reporting that they would support the use of both methods in combination. The lower rates of false-negative and false-positive test results and the ability to use the test earlier in the pregnancy were the most highly rated benefits of cffDNA testing. Participants expressed strong support for diagnostic confirmation via invasive testing after a positive result from either screening or cffDNA testing. However, almost one-third of participants reported that they would not endorse the use of either invasive or non-invasive prenatal testing.Conclusion:There appears to be support for uptake of non-invasive prenatal tests. Clinical guidelines should therefore go forward in providing guidance on how to integrate non-invasive methods into the current standard of care. However, our findings indicate that even when accuracy, which is rated by patients as the most important aspect of prenatal testing, is significantly improved over existing screening methods and testing is offered non-invasively, the number of individuals who reported that they would decline any testing remained the same. Attention should therefore be directed at ensuring that the right of informed refusal of prenatal testing is not impacted by new, non-invasive methods.

  View details for DOI 10.1038/jp.2014.30

  View details for PubMedID 24603453

• Open-label extension studies: are they really research? The American journal of bioethics : AJOB Cho, M. K. 2014; 14 (4): 60-1

  View details for DOI 10.1080/15265161.2014.889958

  View details for PubMedID 24730503

• Ethics and empiricism in the formation of professional guidelines. The American journal of bioethics : AJOB Cho, M. K. 2014; 14 (3): 1-2

  View details for DOI 10.1080/15265161.2014.890426

  View details for PubMedID 24592827

• Translating personalized medicine using new genetic technologies in clinical practice: the ethical issues PERSONALIZED MEDICINE Ormond, K. E., Cho, M. K. 2014; 11 (2): 211-222

  View details for DOI 10.2217/pme.13.104

  View details for Web of Science ID 000337311700014

• Translating personalized medicine using new genetic technologies in clinical practice: the ethical issues Personalized Medicine Ormond, K. E., Cho, M. K. 2014; 11
• Focusing on Cause or Cure?: Priorities and Stakeholder Presence in Childhood Psychiatry Research. AJOB primary research Milner, L. C., Cho, M. K. 2014; 5 (1): 44-55

  Abstract

  Biomedical research is influenced by many factors, including the involvement of stakeholder groups invested in research outcomes. Stakeholder involvement in research efforts raise questions of justice as their specific interests and motivations play a role in directing research resources that ultimately produce knowledge shaping how different conditions (and affected individuals) are understood and treated by society. This issue is highly relevant to child psychiatry research where diagnostic criteria and treatment strategies are often controversial. Biological similarities and stakeholder differences between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) provide an opportunity to explore this issue by comparing research foci and stakeholder involvement in these conditions.A subset of ADHD and ASD research articles published between 1970-2010 were randomly selected from the PubMed database and coded for research focus, funding source(s), and author-reported conflicts of interest (COIs). Chi-square analyses were performed to identify differences between and within ADHD and ASD research across time.The proportion of ADHD research dedicated to basic, description, and treatment research was roughly similar and remained stable over time, while ASD research showed a significant increase in basic research over the past decade. Government was the primary research funder for both conditions, but for-profit funders were a notable presence in ADHD research, while joint-funding efforts between non-profit and government funders were a notable presence in ASD research. Lastly, COIs were noted more frequently in ADHD than in ASD research.Our study shows significant differences in research foci and funding sources between the conditions, and identifies the specific involvement of for-profit and non-profit groups in ADHD and ASD, respectively. Our findings highlight the relationship between stakeholders outside the research community and research trajectories and suggest that examinations of these relationships must be included in broader considerations of biomedical research ethics.

  View details for PubMedID 24729931

• Ethics and empiricism in the formation of professional guidelines. American Journal of Bioethics Cho, M. K. 2014; 14
• Genetic testing of children for predisposition to mood disorders: anticipating the clinical issues. Journal of Genetic Counseling Erickson, J. A., Kuzmick, L., Ormond, K. E., Gordon, E., Christman, M. F., Cho, M. K., Levinson, D. F. 2014
• Open-Label Extension Studies: Are They Really Research? American Journal of Bioethics Cho, M. K. 2014; 14
• Demographic and experiential correlates of public attitudes towards cell-free fetal DNA screening. Journal of Genetic Counseling Sayres, L. C., Allyse, M., Goodspeed, T. A., Cho, M. K. 2014
• Reflections on the cost of "low-cost" whole genome sequencing: framing the health policy debate. PLoS biology Caulfield, T., Evans, J., McGuire, A., McCabe, C., Bubela, T., Cook-Deegan, R., Fishman, J., Hogarth, S., Miller, F. A., Ravitsky, V., Biesecker, B., Borry, P., Cho, M. K., Carroll, J. C., Etchegary, H., Joly, Y., Kato, K., Lee, S. S., Rothenberg, K., Sankar, P., Szego, M. J., Ossorio, P., Pullman, D., Rousseau, F., Ungar, W. J., Wilson, B. 2013; 11 (11)

  Abstract

  The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy.

  View details for DOI 10.1371/journal.pbio.1001699

  View details for PubMedID 24223516

• Reflections on the Cost of "Low-Cost" Whole Genome Sequencing: Framing the Health Policy Debate PLOS BIOLOGY Caulfield, T., Evans, J., McGuire, A., McCabe, C., Bubela, T., Cook-Deegan, R., Fishman, J., Hogarth, S., Miller, F. A., Ravitsky, V., Biesecker, B., Borry, P., Cho, M. K., Carroll, J. C., Etchegary, H., Joly, Y., Kato, K., Lee, S. S., Rothenberg, K., Sankar, P., Szego, M. J., Ossorio, P., Pullman, D., Rousseau, F., Ungar, W. J., Wilson, B. 2013; 11 (11)

  Abstract

  The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy.

  View details for DOI 10.1371/journal.pbio.1001699

  View details for Web of Science ID 000330352200001

  View details for PubMedID 24223516

  View details for PubMedCentralID PMC3818164

• The Henrietta Lacks legacy grows. EMBO reports Greely, H. T., Cho, M. K. 2013; 14 (10): 849-?

  View details for DOI 10.1038/embor.2013.148

  View details for PubMedID 24030280

• Awareness and Acceptable Practices: IRB and Researcher Reflections on the Havasupai Lawsuit. AJOB primary research Garrison, N. A., Cho, M. K. 2013; 4 (4): 55-63

  Abstract

  In 2003, Havasupai tribe members in Arizona discovered that their DNA samples, collected for genetic studies on Type II diabetes, had been used for studies on schizophrenia, migration, and inbreeding without their approval. The resulting lawsuit brought by the Havasupai reached a settlement in April 2010 in which tribe members received monetary compensation and the return of DNA samples. In this study, we examine the perceptions of Institutional Review Board (IRB) chairpersons and human genetic researchers about the case and its impact on the practice of research.Twenty-minute semi-structured interviews were conducted with 26 Institutional Review Board (IRB) chairs and researchers at six top NIH-funded institutions. Participants were questioned about their knowledge and perceived impact of the Havasupai case and their perceptions of informed consent in genetic research studies.We found that most study participants did not perceive that the Havasupai case had a large impact. However, we identified key concerns and opinions of the case, in particular, increased awareness of culturally sensitive issues with informed consent and secondary uses of samples.The results provide a deeper understanding of how informed consent issues are understood by IRB members and human genetic researchers and the implications for research ethics education.

  View details for PubMedID 24089655

• Ethical, legal, social, and policy implications of behavioral genetics. Annual review of genomics and human genetics Berryessa, C. M., Cho, M. K. 2013; 14: 515-534

  Abstract

  The field of behavioral genetics has engendered a host of moral and social concerns virtually since its inception. The policy implications of a genetic basis for behaviors are widespread and extend beyond the clinic to the socially important realms of education, criminal justice, childbearing, and child rearing. The development of new techniques and analytic approaches, including whole-genome sequencing, noninvasive prenatal genetic testing, and optogenetics, has clearly changed the study of behavioral genetics. However, the social context of biomedical research has also changed profoundly over the past few decades, and in ways that are especially relevant to behavioral genetics. The ever-widening scope of behavioral genetics raises ethical, legal, social, and policy issues in the potential new applications to criminal justice, education, the military, and reproduction. These issues are especially critical to address because of their potentially disproportionate effects on vulnerable populations such as children, the unborn, and the incarcerated. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 14 is . Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

  View details for DOI 10.1146/annurev-genom-090711-163743

  View details for PubMedID 23452225

• Best ethical practices for clinicians and laboratories in the provision of noninvasive prenatal testing. Prenatal diagnosis Allyse, M. A., Sayres, L. C., Havard, M., King, J. S., Greely, H. T., Hudgins, L., Taylor, J., Norton, M. E., Cho, M. K., Magnus, D., Ormond, K. E. 2013; 33 (7): 656-661

  Abstract

  OBJECTIVE: The goal of this study is to provide an ethical framework for clinicians and companies providing noninvasive prenatal testing using cell-free fetal DNA or whole fetal cells. METHOD: In collaboration with a National Institutes of Health-supported research ethics consultation committee together with feedback from an interdisciplinary group of clinicians, members of industry, legal experts, and genetic counselors, we developed a set of best practices for the provision of noninvasive prenatal genetic testing. RESULTS: Principal recommendations include the amendment of current informed consent procedures to include attention to the noninvasive nature of new testing and the potential for a broader range of results earlier in the pregnancy. We strongly recommend that tests should only be provided through licensed medical providers and not directly to consumers. CONCLUSION: Prenatal tests, including new methods using cell-free fetal DNA, are not currently regulated by government agencies, and limited professional guidance is available. In the absence of regulation, companies and clinicians should cooperate to adopt responsible best ethical practices in the provision of these tests. © 2013 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pd.4144

  View details for PubMedID 23613322

• Commercial landscape of noninvasive prenatal testing in the United States PRENATAL DIAGNOSIS Agarwal, A., Sayres, L. C., Cho, M. K., Cook-Deegan, R., Chandrasekharan, S. 2013; 33 (6): 521-531

  Abstract

  Cell-free fetal DNA-based noninvasive prenatal testing (NIPT) could significantly change the paradigm of prenatal testing and screening. Intellectual property (IP) and commercialization promise to be important components of the emerging debate about clinical implementation of these technologies. We have assembled information about types of testing, prices, turnaround times, and reimbursement of recently launched commercial tests in the United States from the trade press, news articles, and scientific, legal, and business publications. We also describe the patenting and licensing landscape of technologies underlying these tests and ongoing patent litigation in the United States. Finally, we discuss how IP issues may affect clinical translation of NIPT and their potential implications for stakeholders. Fetal medicine professionals (clinicians and researchers), genetic counselors, insurers, regulators, test developers, and patients may be able to use this information to make informed decisions about clinical implementation of current and emerging noninvasive prenatal tests.

  View details for DOI 10.1002/pd.4101

  View details for Web of Science ID 000319222400003

  View details for PubMedID 23686656

• Interest, rationale, and potential clinical applications of genetic testing for mood disorders: A survey of stakeholders JOURNAL OF AFFECTIVE DISORDERS Erickson, J. A., Cho, M. K. 2013; 145 (2): 240-245

  View details for DOI 10.1016/j.jad.2012.05.046

  View details for Web of Science ID 000314092100014

  View details for PubMedID 23021819

• Translating cell-free fetal DNA technology: structural lessons from non-invasive RhD blood typing. Trends in biotechnology Goodspeed, T. A., Allyse, M., Sayres, L. C., Norton, M. E., Cho, M. K. 2013; 31 (1): 7-9

  View details for DOI 10.1016/j.tibtech.2012.09.001

  View details for PubMedID 23040170

• Awareness and Acceptable practices: IRB and Researcher reflections on the Havasupai Lawsuit. AJOB Primary Research Garrison, N., Cho, MK 2013: doi:10.1080/21507716
• Patenting and Commercialization of Noninvasive Prenatal Testing- Implications for Providers and Patients. Prenatal Diagnosis Agarwal, A., Sayres L, Cho M, Cook-Deegan R, Chandrasekharan S 2013: DOI:10.1002/(ISSN)10
• Focusing on cause or cure? Priorities and stakeholder presence in child psychiatry research. AJOB Primary Research Milner, L., Cho, MK 2013: DOI: 10.1080/2150771
• Genetic Counseling for Prenatal Testing: Where is the Discussion About Disability? JOURNAL OF GENETIC COUNSELING Farrelly, E., Cho, M. K., Erby, L., Roter, D., Stenzel, A., Ormond, K. 2012; 21 (6): 814-824

  Abstract

  There are little data revealing how genetic counselors talk about disability in the prenatal setting. We performed a qualitative analysis of 93 existing transcripts from simulated patient (SP) genetic counseling sessions conducted in 2003–4 through the Genetic Counseling Video Project. We found that most genetic counselors (95%) focused on the physical aspects of disability while fewer (27%) discussed the social aspects. In addition, few genetic counselors (38%) asked patients about personal experiences with disability. When discussing options available if a pregnancy were diagnosed with a disability, most genetic counselors mentioned termination (86%) while fewer mentioned the continuation of the pregnancy (37%) or adoption (13%). Only half of the genetic counselors asked the SP if she had thought about how she might use the results of prenatal screening. To better facilitate informed decision-making that is consistent with patient values, we recommend genetic counselors engage prenatal patients in a deeper discussion about their ability and willingness to parent a child with a disability.

  View details for DOI 10.1007/s10897-012-9484-z

  View details for Web of Science ID 000311509200012

  View details for PubMedID 22898882

• Cell-free fetal DNA testing for fetal aneuploidy and beyond: clinical integration challenges in the US context HUMAN REPRODUCTION Allyse, M., Sayres, L. C., King, J. S., Norton, M. E., Cho, M. K. 2012; 27 (11): 3123-3131

  Abstract

  The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field. Ongoing research portends the arrival of a wide range of cffDNA tests. However, it is not yet clear how these tests will be integrated into well-established prenatal testing strategies in the USA, as the timing of such testing and the degree to which new non-invasive tests will supplement or replace existing screening and diagnostic tools remain uncertain. We argue that there is an urgent need for policy-makers, regulators and professional societies to provide guidance on the most efficient and ethical manner for such tests to be introduced into clinical practice in the USA.

  View details for DOI 10.1093/humrep/des286

  View details for Web of Science ID 000310218300001

  View details for PubMedID 22863603

• Customers or research participants?: Guidance for research practices in commercialization of personal genomics GENETICS IN MEDICINE Tobin, S. L., Cho, M. K., Lee, S. S., Magnus, D. C., Allyse, M., Ormond, K. E., Garrison, N. A. 2012; 14 (10): 833-835

  View details for DOI 10.1038/gim.2012.64

  View details for Web of Science ID 000309645900001

  View details for PubMedID 22699154

• In the Public Interest? SCIENCE TRANSLATIONAL MEDICINE Sayres, L. C., Allyse, M., Goodspeed, T. A., Cho, M. K. 2012; 4 (144)

  Abstract

  Restrictive patenting and licensing for cell-free fetal DNA testing has serious consequences for technology advances and benefits to public health.

  View details for DOI 10.1126/scitranslmed.3003612

  View details for Web of Science ID 000306968700001

  View details for PubMedID 22837535

• Integrating stakeholder perspectives into the translation of cell-free fetal DNA testing for aneuploidy GENOME MEDICINE Sayres, L. C., Allyse, M., Cho, M. K. 2012; 4

  View details for DOI 10.1186/gm348

  View details for Web of Science ID 000314572100001

• Integrating stakeholder perspectives into the translation of cell-free fetal DNA testing for aneuploidy. Genome medicine Sayres, L. C., Allyse, M., Cho, M. K. 2012; 4 (6): 49

  Abstract

  ABSTRACT: BACKGROUND: The translation of novel genomic technologies from bench to bedside enjoins the comprehensive consideration of the perspectives of all stakeholders who stand to influence, or be influenced by, the translational course. Non-invasive prenatal aneuploidy testing that utilizes cell-free fetal DNA (cffDNA) circulating in maternal blood is one example of an innovative technology that promises significant benefits for its intended end users; however, it is currently uncertain whether it will achieve widespread clinical implementation. We conducted qualitative interviews with 18 diverse stakeholders in this domain, including prospective users of the technology and healthcare personnel, researchers and developers, and experts in social, legal, and regulatory aspects of genetic technology, and a pilot survey of 62 obstetric healthcare providers. Analysis of interview and survey data was combined with a review of the proceedings of a full-day, multidisciplinary conference on the topic and published scientific and ethics literature surrounding this and other relevant technologies. DISCUSSION: We constructed potential pathways for technological implementation, identified broad stakeholder classes party to these translational processes, and performed a preliminary assessment of the viewpoints and interrelations among these diverse stakeholders. Some of the stakeholders whose priorities are critical to understand and integrate into translation include pregnant women and their families; healthcare providers; scientists, their institutions or companies, and the funding agencies that support them; regulatory and judicial bodies; third-party payers; professional societies; educational systems; disability rights communities; and other representatives from civil society. Stakeholder interviews, survey findings, and conference proceedings add complexity to these envisioned pathways and also demonstrate a paramount need to incorporate an iterative stakeholder analysis early and throughout the translational endeavor. We believe that the translational framework that we have developed will help guide crucial future stakeholder mapping and engagement activities for cffDNA aneuploidy testing and inform novel methods of technology assessment for other developments in the growing field of genomic medicine. SUMMARY: Mapping potential pathways for implementation and exploring the attitudes and interrelations of diverse stakeholders may lead to more effective translation of a novel method of prenatal aneuploidy testing.

  View details for DOI 10.1186/gm348

  View details for PubMedID 22720727

• Informational risk, institutional review, and autonomy in the proposed changes to the common rule. IRB Allyse, M., Karkazis, K., Lee, S. S., Tobin, S. L., Greely, H. T., Cho, M. K., Magnus, D. 2012; 34 (3): 17-19

  View details for PubMedID 22830179

• Managing incidental findings and research results in genomic research involving biobanks and archived data sets GENETICS IN MEDICINE Wolf, S. M., Crock, B. N., Van Ness, B., Lawrenz, F., Kahn, J. P., Beskow, L. M., Cho, M. K., Christman, M. F., Green, R. C., Hall, R., Illes, J., Keane, M., Knoppers, B. M., Koenig, B. A., Kohane, I. S., LeRoy, B., Maschke, K. J., McGeveran, W., Ossorio, P., Parker, L. S., Petersen, G. M., Richardson, H. S., Scott, J. A., Terry, S. F., Wilfond, B. S., Wolf, W. A. 2012; 14 (4): 361-384

  Abstract

  Biobanks and archived data sets collecting samples and data have become crucial engines of genetic and genomic research. Unresolved, however, is what responsibilities biobanks should shoulder to manage incidental findings and individual research results of potential health, reproductive, or personal importance to individual contributors (using "biobank" here to refer both to collections of samples and collections of data). This article reports recommendations from a 2-year project funded by the National Institutes of Health. We analyze the responsibilities involved in managing the return of incidental findings and individual research results in a biobank research system (primary research or collection sites, the biobank itself, and secondary research sites). We suggest that biobanks shoulder significant responsibility for seeing that the biobank research system addresses the return question explicitly. When reidentification of individual contributors is possible, the biobank should work to enable the biobank research system to discharge four core responsibilities to (1) clarify the criteria for evaluating findings and the roster of returnable findings, (2) analyze a particular finding in relation to this, (3) reidentify the individual contributor, and (4) recontact the contributor to offer the finding. We suggest that findings that are analytically valid, reveal an established and substantial risk of a serious health condition, and are clinically actionable should generally be offered to consenting contributors. This article specifies 10 concrete recommendations, addressing new biobanks as well as those already in existence.

  View details for DOI 10.1038/gim.2012.23

  View details for Web of Science ID 000302565600003

  View details for PubMedID 22436882

• Secondary researchers' duties to return incidental findings and individual research results: a partial-entrustment account GENETICS IN MEDICINE Richardson, H. S., Cho, M. K. 2012; 14 (4): 467-472

  Abstract

  Existing attempts to explain why secondary researchers might have any obligation to return findings to the contributors of genetic samples falter because of the lack of any direct interaction between the secondary researchers and the contributors. The partial-entrustment account of these obligations defended here circumvents this problem by explaining how a chain of special responsibilities can be forged even in the absence of any direct interaction.Genet Med 2012:14(4):467-472.

  View details for DOI 10.1038/gim.2012.12

  View details for Web of Science ID 000302565600017

  View details for PubMedID 22361900

• Human evolutionary genomics: ethical and interpretive issues TRENDS IN GENETICS Vitti, J. J., Cho, M. K., Tishkoff, S. A., Sabeti, P. C. 2012; 28 (3): 137-145

  Abstract

  Genome-wide computational studies can now identify targets of natural selection. The unique information about humans these studies reveal, and the media attention they attract, indicate the need for caution and precision in communicating results. This need is exacerbated by ways in which evolutionary and genetic considerations have been misapplied to support discriminatory policies, by persistent misconceptions of these fields and by the social sensitivity surrounding discussions of racial ancestry. We discuss the foundations, accomplishments and future directions of human evolutionary genomics, attending to ways in which the interpretation of good science can go awry, and offer suggestions for researchers to prevent misapplication of their work.

  View details for DOI 10.1016/j.tig.2011.12.001

  View details for Web of Science ID 000301635300005

  View details for PubMedID 22265990

• Genetic Counseling for Prenatal Testing: Where is the Discussion About Disability? Journal of genetic counseling Farrelly, E., Cho, M. K., Erby, L., Roter, D., Stenzel, A., Ormond, K. 2012

  Abstract

  There are little data revealing how genetic counselors talk about disability in the prenatal setting. We performed a qualitative analysis of 93 existing transcripts from simulated patient (SP) genetic counseling sessions conducted in 2003-4 through the Genetic Counseling Video Project. We found that most genetic counselors (95%) focused on the physical aspects of disability while fewer (27%) discussed the social aspects. In addition, few genetic counselors (38%) asked patients about personal experiences with disability. When discussing options available if a pregnancy were diagnosed with a disability, most genetic counselors mentioned termination (86%) while fewer mentioned the continuation of the pregnancy (37%) or adoption (13%). Only half of the genetic counselors asked the SP if she had thought about how she might use the results of prenatal screening. To better facilitate informed decision-making that is consistent with patient values, we recommend genetic counselors engage prenatal patients in a deeper discussion about their ability and willingness to parent a child with a disability.

  View details for DOI 10.1007/s10897-012-9484-z

  View details for PubMedID 22297411

• Triggers for Research Ethics Consultation SCIENCE TRANSLATIONAL MEDICINE Havard, M., Cho, M. K., Magnus, D. 2012; 4 (118)

  Abstract

  Research ethics consultation services are designed to help scientists address ethical and societal issues that may not be considered in the context of existing regulatory frameworks, such as institutional review boards. Here, we identify some types of biomedical research for which the research process can benefit from consultation with ethicists.

  View details for DOI 10.1126/scitranslmed.3002734

  View details for Web of Science ID 000299539500001

  View details for PubMedID 22277965

• Human evolutionary genomics: ethical and interpretive issues. Trends in Genetics Vitti JJ, Cho MK, Tishkoff SA, Sabeti PC 2012; 28: 137-145
• Barriers to Considering Ethical and Societal Implications of Research: Perceptions of Biomedical Scientists AJOB Primary Research McCormick, J., Ladd, JM, Boyce, AM, Cho, MK 2012; 3 (3): 40-50
• Integrating stakeholder perspectives into the translation of cell-free fetal DNA testing for aneuploidy Genome Medicine Sayres LC, Allyse M, Cho MK 2012
• Secondary Researchers? Duties to Return Incidental Findings and Individual Research Results: A Partial-Entrustment Account. Genetics in Medicine Richardson HS, Cho MK 2012
• Managing incidental findings and research results in genomic research involving biobanks and archived data sets Genetics in Medicine Wolf, S., Crock, BN, Van Ness, B, Lawrenz, F, Kahn, JP, Beskow, LM, Cho, MK, Christman, MF, Green, RC, Hall, R, Illes, J, Keane, M, Knoppers, BM, Koenig, BA, Kohane, IS, LeRoy, B, Maschke, K J, McGeveran, W, Ossorio, P, Parker, LS, Petersen, GM, Richardson, HS, Scott, JA, Terry, SF, Wilfond, BS, Wolf, WA 2012
• Cell-free fetal DNA testing: a pilot study of obstetric healthcare provider attitudes toward clinical implementation PRENATAL DIAGNOSIS Sayres, L. C., Allyse, M., Norton, M. E., Cho, M. K. 2011; 31 (11): 1070-1076

  Abstract

  To provide a preliminary assessment of obstetric healthcare provider opinions surrounding implementation of cell-free fetal DNA testing.A 37-question pilot survey was used to address questions around the translation and use of non-invasive prenatal testing using cell-free fetal DNA. The survey was distributed and collected at a Continuing Medical Education course on obstetrics and gynecology.Of 62 survey respondents, 73% were female and 87% held MD/DO degrees. Respondents generally agreed that patients want prenatal diagnostic information to help make decisions about a pregnancy and that cell-free fetal DNA testing would encourage the testing of more patients for more conditions. However, there was an overall lack of knowledge or conviction about using this technology. Genetic counseling and professional society approval were deemed important to implementation, whereas the possibility of direct-to-consumer testing and government regulation produced mixed responses. Respondents indicated that they would be more likely to offer cell-free fetal DNA testing for chromosomal abnormalities and single-gene disorders, but would be cautious with respect to determination of sex and behavioral or late-onset conditions.Preliminary assessment indicates uncertainty among obstetric providers about the details of implementing cell-free fetal DNA testing and suggests expanded research on perspectives of this stakeholder group.

  View details for DOI 10.1002/pd.2835

  View details for Web of Science ID 000298261200009

  View details for PubMedID 21793012

  View details for PubMedCentralID PMC3200428

• Ethics watch THE GI GENOME: ETHICAL IMPLICATIONS OF GENOME SEQUENCING IN THE MILITARY NATURE REVIEWS GENETICS Allyse, M., Milner, L. C., Cho, M. K. 2011; 12 (9): 589-589

  View details for DOI 10.1038/nrg3063

  View details for Web of Science ID 000294004100005

  View details for PubMedID 21808260

• Cell-Free Fetal Nucleic Acid Testing: A Review of the Technology and Its Applications OBSTETRICAL & GYNECOLOGICAL SURVEY Sayres, L. C., Cho, M. K. 2011; 66 (7): 431-442

  Abstract

  Cell-free fetal nucleic acids circulating in the blood of pregnant women afford the opportunity for early, noninvasive prenatal genetic testing. The predominance of admixed maternal genetic material in circulation demands innovative means for identification and analysis of cell-free fetal DNA and RNA. Techniques using polymerase chain reaction, mass spectrometry, and sequencing have been developed for the purposes of detecting fetal-specific sequences, such as paternally inherited or de novo mutations, or determining allelic balance or chromosome dosage. Clinical applications of these methods include fetal sex determination and blood group typing, which are currently available commercially although not offered routinely in the United States. Other uses of cell-free fetal DNA and RNA being explored are the detection of single-gene disorders, chromosomal abnormalities, and inheritance of parental polymorphisms across the whole fetal genome. The concentration of cell-free fetal DNA may also provide predictive capabilities for pregnancy-associated complications. The roles that cell-free fetal nucleic acid testing assume in the existing framework of prenatal screening and invasive diagnostic testing will depend on factors such as costs, clinical validity and utility, and perceived benefit-risk ratios for different applications. As cell-free fetal DNA and RNA testing continues to be developed and translated, significant ethical, legal, and social questions will arise that will need to be addressed by those with a stake in the use of this technology. Target Audience: Obstetricians & Gynecologists and Family Physicians Learning Objectives: After participating in this activity, physicians should be better able to evaluate techniques and tools for analyzing cell-free fetal nucleic acids, assess clinical applications of prenatal testing, using cell-free fetal nucleic acids and barriers to implementation, and distinguish between relevant clinical features of cell-free fetal nucleic acid testing and existing prenatal genetic screening and diagnostic procedures.

  View details for DOI 10.1097/OGX.0b013e31822dfbe2

  View details for Web of Science ID 000295319900021

  View details for PubMedID 21944155

• Medical and graduate students' attitudes toward personal genomics GENETICS IN MEDICINE Ormond, K. E., Hudgins, L., Ladd, J. M., Magnus, D. M., Greely, H. T., Cho, M. K. 2011; 13 (5): 400-408

  Abstract

  Medical schools are being approached by direct-to-consumer genotyping companies about genotyping faculty or trainees as a method to "teach" them about the potential implications of genotyping. In thinking about the future incorporation of genotyping into a graduate level genetics course, the purpose of this study was 2-fold: first, to assess knowledge, attitudes, and beliefs of students toward personal genomics as it related to themselves as both as customers and future physicians and as it related to consumers at large, and second, to determine the impact of the course (as taught without genotyping) on knowledge, attitudes, and beliefs.We surveyed first-year medical students and graduate students before and after a core genetics course.After the course, students were less likely to believe that genotyping information would be useful to physicians, patients, or consumers; genotyping would provide information to improve their own personal health; or personal genomic testing services are diagnostic of medical conditions. They were more likely to answer knowledge questions accurately after the course but still had difficulty with clinical interpretation. Despite these changes, a slight majority of students were, and remained, interested in undergoing genotyping themselves. Of note, the number who believed genotyping "would help them understand genetic concepts better than someone else's data" decreased. General curiosity was the most commonly chosen reason for interest in undergoing genotyping, and approximately 50% of respondents expressed concern about confidentiality of results.In conclusion, even without the genotyping process, an educational program about genotyping increased knowledge, particularly about the clinical limitations of genotyping, but student interest in genotyping did not significantly change. Institutions thinking about offering genotyping to their students as part of a learning experience should consider the pros and cons of doing so.

  View details for DOI 10.1097/GIM.0b013e31820562f6

  View details for Web of Science ID 000290435700005

  View details for PubMedID 21270640

• Ethical Considerations and Risks in Psychiatric Genetics: Preliminary Findings of a Study on Psychiatric Genetic Researchers. American Journal of Bioethics Primary Research Erickson, J., Cho, MK 2011; 2: 52-60
• Not yet in sequence: Clinical, technical, ethical questions linger over personal genomics. Modern healthcare Cho, M., Wolpert, M. 2010; 40 (47): 24-?

  View details for PubMedID 21137125

• Patently unpatentable: implications of the Myriad court decision on genetic diagnostics TRENDS IN BIOTECHNOLOGY Cho, M. 2010; 28 (11): 548-551

  Abstract

  The recent decision in the case Association for Molecular Pathology et al. v. United States Patent and Trademark Office et al. shocked the biotechnology industry. Although the case could be overturned on appeal, it will probably change how gene patents are written. The effects of the decision might be most strongly felt in the short term by clinical laboratories that develop new genetic tests based on single genes. However, evidence suggests that patents are less effective as an incentive to innovate in the field of genetic diagnostics than for pharmaceuticals. In addition, as genomic technologies move towards whole-genome analysis, policy arguments for patent protection for single genes become less compelling. It is clear that the intellectual property model challenged by the Myriad decision will have to be replaced if new genetic technologies are to achieve their full potential in promoting 'the progress of science and useful arts'.

  View details for DOI 10.1016/j.tibtech.2010.08.005

  View details for Web of Science ID 000283703300002

  View details for PubMedID 20832881

• Genetic technologies. Synthetic "life," ethics, national security, and public discourse. Science Cho, M. K., Relman, D. A. 2010; 329 (5987): 38-39

  View details for DOI 10.1126/science.1193749

  View details for PubMedID 20595601

• Research Ethics in the Era of Personalized Medicine: Updating Science's Contract with Society PUBLIC HEALTH GENOMICS Meslin, E. M., Cho, M. K. 2010; 13 (6): 378-384

  Abstract

  With the completed sequence of the human genome has come the prospect of substantially improving the quality of life for millions through personalized medicine approaches. Still, any advances in this direction require research involving human subjects. For decades science and ethics have enjoyed an allegiance reflected in a common set of ethical principles and procedures guiding the conduct of research with human subjects. Some of these principles emphasize avoiding harm over maximizing benefit. In this paper we revisit the priority given to these ethical principles - particularly the principles that support a cautious approach to science - and propose a reframing of the 'social contract' between science and society that emphasizes reciprocity and meeting public needs.

  View details for DOI 10.1159/000319473

  View details for Web of Science ID 000281518700009

  View details for PubMedID 20805701

• The "how'' and "whys'' of research: life scientists' views of accountability JOURNAL OF MEDICAL ETHICS Ladd, J. M., Lappe, M. D., MCCORMICK, J. B., BOYCE, A. M., Cho, M. K. 2009; 35 (12): 762-767

  Abstract

  To investigate life scientists' views of accountability and the ethical and societal implications of research.Qualitative focus group and one-on-one interviews.45 Stanford University life scientists, including graduate students, postdoctoral fellows and faculty.Two main themes were identified in participants' discussions of accountability: (1) the "how" of science and (2) the "why" of science. The "how" encompassed the internal conduct of research including attributes such as honesty and independence. The "why," or the motivation for conducting research, was two-tiered: first was the desire to positively impact the research community and science itself, and second was an interest in positively impacting the external community, broadly referred to as society. Participants noted that these motivations were influenced by the current systems of publications, grants and funding, thereby supporting a complex notion of boundary-setting between science and non-science. In addition, while all participants recognised the "how" of science and the two tiers of "why," scientists expressed the need to prioritise these domains of accountability. This prioritisation was related to a researcher's position in the academic career trajectory and to the researcher's subsequent "perceived proximity" to scientific or societal concerns. Our findings therefore suggest the need for institutional change to inculcate early-stage researchers with a broader awareness of the implications of their research. The peer review processes for funding and publication could be effective avenues for encouraging scientists to broaden their views of accountability to society.

  View details for DOI 10.1136/jme.2009.031781

  View details for Web of Science ID 000272210500012

  View details for PubMedID 19948933

• Biomedical Scientists' Perceptions of Ethical and Social Implications: Is There a Role for Research Ethics Consultation? PLOS ONE McCormick, J. B., Boyce, A. M., Cho, M. K. 2009; 4 (3)

  Abstract

  Research ethics consultation programs are being established with a goal of addressing the ethical, societal, and policy considerations associated with biomedical research. A number of these programs are modelled after clinical ethics consultation services that began to be institutionalized in the 1980s. Our objective was to determine biomedical science researchers' perceived need for and utility of research ethics consultation, through examination of their perceptions of whether they and their institutions faced ethical, social or policy issues (outside those mandated by regulation) and examination of willingness to seek advice in addressing these issues. We conducted telephone interviews and focus groups in 2006 with researchers from Stanford University and a mailed survey in December 2006 to 7 research universities in the U.S.A total of 16 researchers were interviewed (75% response rate), 29 participated in focus groups, and 856 responded to the survey (50% response rate). Approximately half of researchers surveyed (51%) reported that they would find a research ethics consultation service at their institution moderately, very or extremely useful, while over a third (36%) reported that such a service would be useful to them personally. Respondents conducting human subjects research were more likely to find such a service very to extremely useful to them personally than respondents not conducting human subjects research (20% vs 10%; chi(2) p<0.001).Our findings indicate that biomedical researchers do encounter and anticipate encountering ethical and societal questions and concerns and a substantial proportion, especially clinical researchers, would likely use a consultation service if they were aware of it. These findings provide data to inform the development of such consultation programs in general.

  View details for DOI 10.1371/journal.pone.0004659

  View details for Web of Science ID 000265489900002

  View details for PubMedID 19252737

  View details for PubMedCentralID PMC2645500

• Translating genomics into the clinic: moving to the post-Mendelian world. Genome medicine Cho, M. K. 2009; 1 (1): 7-?

  Abstract

  The challenge of genome medicine is not to make a significant move into the clinic over the next five years. The floodgates of genomic research have been opened, and the hopes are that the rising tide will spill over into medical practice in the form of diagnostic tests, risk assessment tools and therapeutics. The ability to perform genome-wide analyses using several different approaches has already provided tantalizing new clues to disease causation and therapeutic targets. Companies have sprung up to use these new technologies to provide information to individuals about predicted health and disease, and about behavioral traits. As exciting as these prospects are, it is far too soon to promise clinically useful information from genomic analyses. We have far to go to assure basic levels of analytical validity or clinical validity of the diagnostic or predictive tools on offer, and to determine their clinical utility in the medical context.

  View details for DOI 10.1186/gm7

  View details for PubMedID 19348694

• Direct-to-consumer genetic tests: beyond medical regulation? GENOME MEDICINE Magnus, D., Cho, M. K., Cook-Deegan, R. 2009; 1

  Abstract

  The availability of personalized genomic tests, ordered directly by consumers, is rapidly growing. These tests are unlike other genetic or biochemical tests in the sheer amount of data they provide, but interpretation of these genome-wide analyses for health remains uncertain because of the lack of information about environmental and other factors, and because for the vast majority of genetic loci the associations with disease are weak. Although these tests could provide value to customers by offering tools for social networking or genealogy, there are questions about whether and how to regulate these tests and about the extent to which they provide medical information.

  View details for DOI 10.1186/gm17

  View details for Web of Science ID 000208627000017

  View details for PubMedCentralID PMC2664950

• Direct-to-consumer genetic tests: beyond medical regulation? Genome medicine Magnus, D., Cho, M. K., Cook-Deegan, R. 2009; 1 (2): 17-?

  Abstract

  The availability of personalized genomic tests, ordered directly by consumers, is rapidly growing. These tests are unlike other genetic or biochemical tests in the sheer amount of data they provide, but interpretation of these genome-wide analyses for health remains uncertain because of the lack of information about environmental and other factors, and because for the vast majority of genetic loci the associations with disease are weak. Although these tests could provide value to customers by offering tools for social networking or genealogy, there are questions about whether and how to regulate these tests and about the extent to which they provide medical information.

  View details for DOI 10.1186/gm17

  View details for PubMedID 19341488

• Research ethics consultation: the Stanford experience. IRB Cho, M. K., Tobin, S. L., Greely, H. T., McCormick, J., Boyce, A., Magnus, D. 2008; 30 (6): 1-6

  View details for PubMedID 19119757

• Understanding incidental findings in the context of genetics and genomics Symposium on Findings in Human Subjects Research - From Imaging to Genomics Cho, M. K. WILEY-BLACKWELL PUBLISHING, INC. 2008: 280-?

  Abstract

  Human genetic and genomic research can yield information that may be of clinical relevance to the individuals who participate as subjects of the research. It has been common practice among researchers to notify participants during the informed consent process that no individual results will be disclosed, "incidental" or otherwise. However, as genetic information obtained in research becomes orders of magnitude more voluminous, increasingly accessible online, and more informative, this precedent may no longer be appropriate. There is not yet consensus on the responsibilities of researchers to disclose individual research results to research participants. Empirical research suggests that participants want to know individual research results. On the other hand, the increased resolution and power afforded by new genomic analyses may lead to findings of statistical, but not necessarily clinical, significance. This paper addresses the issues to be considered in deciding whether and how to disclose "incidental" findings or other findings of clinical significance that arise in the course of human genomic and genetic research. What research results should be offered, and what should not be offered? For which research should individual results be offered to research participants, when should they be offered, how, and to whom?

  View details for Web of Science ID 000256411400006

  View details for PubMedID 18547195

• Science and Society - Research ethics and the challenge of whole-genome sequencing NATURE REVIEWS GENETICS McGuire, A. L., Caulfield, T., Cho, M. K. 2008; 9 (2): 152-156

  View details for Web of Science ID 000252455400013

• Research ethics and the challenge of whole-genome sequencing. Nature reviews. Genetics McGuire, A. L., Caulfield, T., Cho, M. K. 2008; 9 (2): 152-156

  Abstract

  The recent completion of the first two individual whole-genome sequences is a research milestone. As personal genome research advances, investigators and international research bodies must ensure ethical research conduct. We identify three major ethical considerations that have been implicated in whole-genome research: the return of research results to participants; the obligations, if any, that are owed to participants' relatives; and the future use of samples and data taken for whole-genome sequencing. Although the issues are not new, we discuss their implications for personal genomics and provide recommendations for appropriate management in the context of research involving individual whole-genome sequencing.

  View details for PubMedID 18087293

  View details for PubMedCentralID PMC2225443

• Practical approaches to incidental findings in brain imaging research NEUROLOGY Illes, J., Kirschen, M. P., Edwards, E., Bandettini, P., Cho, M. K., Ford, P. J., Glover, G. H., Kulynych, J., Macklin, R., Michael, D. B., Wolf, S. M., Grabowski, T., Seto, B. 2008; 70 (5): 384-390

  Abstract

  A decade of empirical work in brain imaging, genomics, and other areas of research has yielded new knowledge about the frequency of incidental findings, investigator responsibility, and risks and benefits of disclosure. Straightforward guidance for handling such findings of possible clinical significance, however, has been elusive. In early work focusing on imaging studies of the brain, we suggested that investigators and institutional review boards must anticipate and articulate plans for handling incidental findings. Here we provide a detailed analysis of different approaches to the problem and evaluate their merits in the context of the goals and setting of the research and the involvement of neurologists, radiologists, and other physicians. Protecting subject welfare and privacy, as well as ensuring scientific integrity, are the highest priorities in making choices about how to handle incidental findings. Forethought and clarity will enable these goals without overburdening research conducted within or outside the medical setting.

  View details for PubMedID 18227420

• Strangers at the Benchside: Research ethics consultation AMERICAN JOURNAL OF BIOETHICS Cho, M. K., Tobin, S. L., Greely, H. T., McCormick, J., Boyce, A., Magnus, D. 2008; 8 (3): 4-13

  Abstract

  Institutional ethics consultation services for biomedical scientists have begun to proliferate, especially for clinical researchers. We discuss several models of ethics consultation and describe a team-based approach used at Stanford University in the context of these models. As research ethics consultation services expand, there are many unresolved questions that need to be addressed, including what the scope, composition, and purpose of such services should be, whether core competencies for consultants can and should be defined, and how conflicts of interest should be mitigated. We make preliminary recommendations for the structure and process of research ethics consultation, based on our initial experiences in a pilot program.

  View details for DOI 10.1080/15265160802109322

  View details for Web of Science ID 000257030400004

  View details for PubMedID 18570086

  View details for PubMedCentralID PMC2585006

• The ethics of characterizing difference: guiding principles on using racial categories in human genetics GENOME BIOLOGY Lee, S. S., Mountain, J., Koenig, B., Altman, R., Brown, M., Camarillo, A., Cavalli-Sforza, L., Cho, M., Eberhardt, J., Feldman, M., Ford, R., Greely, H., King, R., Markus, H., Satz, D., Snipp, M., Steele, C., Underhill, P. 2008; 9 (7)

  Abstract

  We are a multidisciplinary group of Stanford faculty who propose ten principles to guide the use of racial and ethnic categories when characterizing group differences in research into human genetic variation.

  View details for DOI 10.1186/gb-2008-9-7-404

  View details for Web of Science ID 000258773600005

  View details for PubMedID 18638359

  View details for PubMedCentralID PMC2530857

• Research Ethics Recommendations for Whole-Genome Research: Consensus Statement PLoS Biology Caulfield, T., my L. McGuire, Mildred Cho, Janet A. Buchanan, Michael M. Burgess, Ursula Danilczyk, Christina M. Di 2008; 6: e73
• Ethical implications of array comparative genomic hybridization in complex phenotypes: points to consider in research GENETICS IN MEDICINE Tabor, H. K., Cho, M. K. 2007; 9 (9): 626-631

  Abstract

  As with many new diagnostic technologies, the recent rapid emergence of array comparative genome hybridization in clinical genetics provides the power to observe new biological phenomena before their clinical significance is well understood. This raises ethical issues for clinicians when applying the technologies. However, at this early stage of research and development on array comparative genome hybridization, the ethical implications of the conduct of research, as well as how research findings are presented and interpreted, should also be considered by the research, clinical, and ethics communities. These considerations are especially important in the use of array comparative genome hybridization to study complex and common traits. We examined recent publications on autism as an example of the application of array comparative genome hybridization to a complex phenotype. Our goal was to identify points to consider for researchers, clinicians, and patients/families to ensure responsible and ethical design, presentation, and interpretation of these kinds of studies.

  View details for DOI 10.1097/GIM.0b013e3181485688

  View details for Web of Science ID 000249640800010

  View details for PubMedID 17873651

  View details for PubMedCentralID PMC2220022

• Race and ethnicity in genetic research AMERICAN JOURNAL OF MEDICAL GENETICS PART A Sankar, P., Cho, M. K., Mountain, J. 2007; 143A (9): 961-970

  Abstract

  Use of race and ethnicity terms in genetic research continues to generate controversy. Despite differing opinions about their basis or relevance, there is some agreement that investigators using these terms should: explain why the terms or categories were used, define them carefully, and apply them consistently. An important question is whether these recommendations are reflected in practice. Here we addressed this question based on 330 randomly selected articles published between 2001 and 2004 that reported on genetic research and used one or more words from a defined list of race, ethnicity, or population terms. The recommendation that authors using race or ethnicity terms explain the basis for assigning them to study populations was met infrequently (9.1%), and articles that used race and ethnicity as variables were no more likely than those that used them only to label a sample to provide these details. No article defined or discussed the concepts of race or ethnicity. With limited exceptions, current practice does not reflect repeated recommendations for using race or ethnicity terms in genetic research. This study provides a baseline against which to measure future trends.

  View details for DOI 10.1002/ajmg.a.31575

  View details for Web of Science ID 000246168100009

  View details for PubMedID 17345638

  View details for PubMedCentralID PMC2271134

• Race and Ethnicity in Genetic Research American Journal of Medical Genetics Sankar, P., Cho MK, Mountain J 2007; 143A: 961-970
• The Future of Personal Genomics Science McGuire, A., Cho MK, McGuire SE, Caulfield T 2007; 317 (5845): 1687
• Thinking about the human neuron mouse AMERICAN JOURNAL OF BIOETHICS Greely, H. T., Cho, M. K., Hogle, L. F., Satz, D. M. 2007; 7 (5): 27-40

  View details for DOI 10.1080/15265160701290371

  View details for Web of Science ID 000246830100009

  View details for PubMedID 17497502

  View details for PubMedCentralID PMC2220020

• Research ethics and the challenge of whole genome sequencing. Nature Reviews Genetics McGuire AL, Caulfield T, Cho MK 2007: doi:10.1038/nrg2302
• Response to open peer commentaries on "Thinking about the human neuron mouse'' AMERICAN JOURNAL OF BIOETHICS Greely, H. T., Cho, M. K., Hogle, L. F., Satz, D. M. 2007; 7 (5): W4-W6

  View details for DOI 10.1080/15265160701372674

  View details for Web of Science ID 000246830100020

  View details for PubMedID 17497495

• Racial and ethnic categories in biomedical research: There is no baby in the bathwater Conference on Proposals for the Responsible Use of Racial and Ethnic Categories in Biomedical Research Cho, M. K. WILEY-BLACKWELL. 2006: 497-?

  Abstract

  The use of racial categories in biomedicine has had a long history in the United States. However, social hierarchy and discrimination, justified by purported scientific differences, has also plagued the history of racial categories. Because "race" has some correlation with biological and genetic characteristics, there has been a call not to "throw the baby out with the bathwater" by eliminating race as a research or clinical category. I argue that race is too undefined and fluid to be useful as a proxy for biology or genetics.

  View details for Web of Science ID 000240230700004

  View details for PubMedID 17144171

• ELSI priorities for brain imaging AMERICAN JOURNAL OF BIOETHICS Illes, J., de Vries, R., Cho, M. K., Schraedley-Desmond, P. 2006; 6 (2): W24-W31

  Abstract

  As one of the most compelling technologies for imaging the brain, functional MRI (fMRI) produces measurements and persuasive pictures of research subjects making cognitive judgments and even reasoning through difficult moral decisions. Even after centuries of studying the link between brain and behavior, this capability presents a number of novel significant questions. For example, what are the implications of biologizing human experience? How might neuroimaging disrupt the mysteries of human nature, spirituality, and personal identity? Rather than waiting for an ethical agenda to emerge from some unpredictable combination of the concerns of ethicists and researchers, the attention of journalists, or after controversy is sparked by research that cannot be retracted, we queried key figures in bioethics and the humanities, neuroscience, media, industry, and patient advocacy in focus groups and interviews. We identified specific ethical, legal and social issues (ELSI) that highlight researcher obligations and the nonclinical impact of the technology at this new frontier.

  View details for DOI 10.1080/15265160500506274

  View details for Web of Science ID 000235709700040

  View details for PubMedID 16500831

  View details for PubMedCentralID PMC1560342

• Ethics - Incidental findings in brain imaging research SCIENCE Illes, J., Kirschen, M. P., Edwards, E., Stanford, L. R., Bandettini, P., Cho, M. K., Ford, P. J., Glover, G. H., Kulynych, J., Macklin, R., Michael, D. B., Wolf, S. M. 2006; 311 (5762): 783-784

  View details for DOI 10.1126/science.1115429

  View details for PubMedID 16469905

• Research conduct - Lessons of the stem cell scandal SCIENCE Cho, M. K., McGee, G., Magnus, D. 2006; 311 (5761): 614-615

  View details for DOI 10.1126/science.1124948

  View details for Web of Science ID 000235257400030

  View details for PubMedID 16456065

• How do women decide? Accepting or declining BRCA1/2 testing in a nationwide clinical sample in the United States. Community Genetics Sankar P, Wolpe PR, Jones NL, Cho, M 2006; 9: 78-86
• How do women decide? Accepting or declining BRCA1/2 testing in a nationwide clinical sample in the United States COMMUNITY GENETICS Sankar, P., Wolpe, P. R., JONES, N. L., Cho, M. 2006; 9 (2): 78-86

  Abstract

  To examine the role of the practitioner, informed consent, and genetic counseling in genetic testing decisions and to assess their relative influence on women's decision to have clinical BRCA1/2 testing.Qualitative study using in-depth open-ended interviews with 68 women who had considered clinical BRCA1/2 testing.Slightly less than half of the women who had considered BRCA1/2 testing were found to have had a clear and preexisting desire to test or not to test, irrespective of practitioner attitude or advice.The decision to accept or decline genetic testing is the result of a complex process that goes beyond interactions between health care providers and patients, indicating a caution against exclusive reliance on informed consent or counseling encounters.

  View details for DOI 10.1159/000091484

  View details for Web of Science ID 000236688200002

  View details for PubMedID 16612057

• A commentary on oocyte donation for stem cell research in South Korea AMERICAN JOURNAL OF BIOETHICS Magnus, D., Cho, M. K. 2006; 6 (1): W23-W24

  View details for DOI 10.1080/15265160500496666

  View details for Web of Science ID 000235709600029

  View details for PubMedID 16423767

• What is in a cause? Exploring the relationship between genetic cause and felt stigma GENETICS IN MEDICINE Sankar, P., Cho, M. K., Wolpe, P. R., Schairer, C. 2006; 8 (1): 33-42

  Abstract

  Concern over stigma as a consequence of genetic testing has grown in response to the recent increase in genetic research and testing resulting from the Human Genome Project. However, whether a genetic or hereditary basis necessarily confers a stigma to a condition remains unexamined.We performed a qualitative interview study with 86 individuals with one of four conditions: deafness or hearing loss, breast cancer, sickle cell disease, and cystic fibrosis. The first two groups were divided approximately between people who ascribed their conditions to a genetic or hereditary cause and those who did not.Respondents interpreted genetic or hereditary causes and nongenetic causes in a variety of ways. Subjects with breast cancer reported the most consistently negative interpretation of genetic cause. This response concerned future ill health, not an enduring sense of stigma. Deaf and hard of hearing subjects provided the most consistently positive comments about a genetic or hereditary basis to their condition, casting familial hearing loss as a vital component of group and individual identity. Respondents with sickle cell disease and cystic fibrosis offered similar and positive interpretations of the genetic cause of their condition insofar as it meant their conditions were not contagious.Although some subjects report feeling stigmatized as a result of their condition, this stigmatization is not uniformly associated with the condition's cause, genetic or otherwise. Instead, stigma emerges from a variety of sources in the context of the lived experience of a particular condition.

  View details for DOI 10.1097/01.gim.0000195894.67756.8b

  View details for Web of Science ID 000234850900005

  View details for PubMedID 16418597

• Issues in oocyte donation for stem cell research SCIENCE Magnus, D., Cho, M. K. 2005; 308 (5729): 1747-1748

  View details for DOI 10.1126/science.1114454

  View details for Web of Science ID 000229926800039

  View details for PubMedID 15905363

• What are gene patents and why are people worried about them? Community Genetics Merz JF, Cho MK 2005; 8: 203-208
• What are gene patents and why are people worried about them? COMMUNITY GENETICS Merz, J. F., Cho, M. K. 2005; 8 (4): 203-208

  Abstract

  This article examines what it means to patent a gene. Numerous ethical concerns have been raised about the effects of such patents on clinical medical practice as well as on research and development. We describe what kinds of inventions are covered by human gene patents, give several examples and summarize the small body of empirical research performed in the US examining the effects of these patents. There is little evidence that early fears about gene patenting placing substantial restraints on research and clinical medicine have come to fruition. Nonetheless, there are areas of concern, and policy makers, physicians and the public should be alert to ensure that the net social benefits of patenting human genes are maintained.

  View details for DOI 10.1159/000087956

  View details for Web of Science ID 000232839300002

  View details for PubMedID 16244473

• Forensic genetics and ethical, legal and social implications beyond the clinic NATURE GENETICS Cho, M. K., Sankar, P. 2004; 36 (11): S8-S12

  Abstract

  Data on human genetic variation help scientists to understand human origins, susceptibility to illness and genetic causes of disease. Destructive episodes in the history of genetic research make it crucial to consider the ethical and social implications of research in genomics, especially human genetic variation. The analysis of ethical, legal and social implications should be integrated into genetic research, with the participation of scientists who can anticipate and monitor the full range of possible applications of the research from the earliest stages. The design and implementation of research directs the ways in which its results can be used, and data and technology, rather than ethical considerations or social needs, drive the use of science in unintended ways. Here we examine forensic genetics and argue that all geneticists should anticipate the ethical and social issues associated with nonmedical applications of genetic variation research.

  View details for DOI 10.1038/ng1434

  View details for Web of Science ID 000224854000004

  View details for PubMedID 15510102

• Genetic research and health disparities JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Sankar, P., Cho, M. K., Condit, C. M., Hunt, L. M., Koenig, B., Marshall, P., Lee, S. S., Spicer, P. 2004; 291 (24): 2985-2989

  Abstract

  Alleviating health disparities in the United States is a goal with broad support. Medical research undertaken to achieve this goal typically adopts the well-established perspective that racial discrimination and poverty are the major contributors to unequal health status. However, the suggestion is increasingly made that genetic research also has a significant role to play in alleviating this problem, which likely overstates the importance of genetics as a factor in health disparities. Overemphasis on genetics as a major explanatory factor in health disparities could lead researchers to miss factors that contribute to disparities more substantially and may also reinforce racial stereotyping, which may contribute to disparities in the first place. Arguments that promote genetics research as a way to help alleviate health disparities are augmented by several factors, including research funding initiatives and the distinct demographic patterns of health disparities in the United States.

  View details for Web of Science ID 000222184600028

  View details for PubMedID 15213210

  View details for PubMedCentralID PMC2271142

• A pilot survey on the licensing of DNA inventions JOURNAL OF LAW MEDICINE & ETHICS Henry, M. R., Cho, M. K., Weaver, M. A., Merz, J. F. 2003; 31 (3): 442-449

  View details for Web of Science ID 000186143900011

  View details for PubMedID 14626552

  View details for PubMedCentralID PMC2225444

• Financial conflict-of-interest policies in clinical research: Issues for clinical investigators ACADEMIC MEDICINE Boyd, E. A., Cho, M. K., Bero, L. A. 2003; 78 (8): 769-774

  Abstract

  As industry sponsorship of clinical research grows, investigators' personal financial relationships with those sponsors are under increasing scrutiny. The federal government, some states, and many universities have enacted conflict-of-interest policies to monitor and regulate investigators' financial relationships. Little is known, however, about investigators' awareness of or support for these policies or their attitudes toward regulatory efforts. To explore the possible implications of conflict-of-interest policies for clinical researchers, the authors interviewed active clinical investigators at two institutions where the conflict-of-interest policies differ. The most striking feature of the interviews was the range of perceptions and attitudes expressed by clinical investigators and their implications for administrators, professional societies, and policymakers concerned with conflicts of interest. Fewer than half of the interviewed investigators could accurately describe their campus' conflict-of-interest policy. Many investigators felt that professional societies, the public, and individual investigators were appropriate monitors of conflicts of interest. Many investigators recognized the general risks associated with conflicts of interest, but felt that they personally were not at risk. A fundamental challenge facing administrators and policymakers is to demonstrate to all investigators, both clinical and nonclinical, that the potential for bias, pressure and conflict is relevant to all investigators with industry relationships.

  View details for Web of Science ID 000220070500002

  View details for PubMedID 12915362

• Privacy issues in personalized medicine PHARMACOGENOMICS Vaszar, L. T., Cho, M. K., Raffin, T. A. 2003; 4 (2): 107-112

  Abstract

  Pharmacogenomics is the emerging study of why individuals respond differently to drugs. It aims to replace the current 'one size fits all' therapeutic approach with 'personalized medicine' that will use pharmacogenomic tests to predict drug response. In a simple conceptualization, these tests challenge privacy as a result of two factors: how comprehensive is the test and how is the access to samples or digital information controlled. Point-of-care tests are likely to be limited in scope, fit seamlessly into medical records and do not raise qualitatively new ethical and privacy challenges. In order to define practically relevant pharmacogenomic predictive patterns however, large-scale clinical trials and research on human specimens will be required, resulting in large databases of genomic information. The genomic scans' magnitude, stability, implications to kin and ease of dissemination together represent a qualitatively different challenge compared to traditional, self-limited and often temporally transient medical information.

  View details for Web of Science ID 000181475000001

  View details for PubMedID 12605543

• Effects of patents and licenses on the provision of clinical genetic testing services JOURNAL OF MOLECULAR DIAGNOSTICS Cho, M. K., Illangasekare, S., Weaver, M. A., Leonard, D. G., Merz, J. F. 2003; 5 (1): 3-8

  Abstract

  The growth of patents that include genetic sequences has been accompanied by concern about their impact on the ability of physicians to provide clinical genetic testing services and to perform research. Therefore, we conducted a survey of clinical laboratory directors that perform DNA-based genetic tests to examine potential effects. We performed a telephone survey between July and September in 2001 of all laboratory directors in the United States who were members of the Association for Molecular Pathology or who were listed on the GENETESTS:org website. One hundred thirty-two of 211 (63%) laboratory directors were interviewed. Ten of these were excluded because they did not conduct DNA-based genetic tests. Almost all performed genetic tests for clinical purposes. Half performed tests for research purposes as well. Twenty-five percent of respondents reported that they had stopped performing a clinical genetic test because of a patent or license. Fifty-three percent of respondents reported deciding not to develop a new clinical genetic test because of a patent or license. In total, respondents were prevented from performing 12 genetic tests, and all of these tests were among those performed by a large number of laboratories. We found 22 patents that were relevant to the performance of these 12 tests. Fifteen of the 22 patents (68%) are held by universities or research institutes, and 13 of the 22 patents (59%) were based on research funded by the United States Government. Overall, respondents reported that their perceptions of the effects of patents on the cost, access, and development of genetic tests, or data sharing among researchers, were negative. In contrast, most respondents felt that patents did not have an effect on the quality of testing. We conclude that patents and licenses have had a significant effect on the ability of clinical laboratories to develop and provide genetic tests. Furthermore, our findings suggest that clinical geneticists feel that their research is inhibited by patents. The effects of patents and licenses on patients' access to tests, and the costs and quality thereof, remains to be determined.

  View details for Web of Science ID 000180631100002

  View details for PubMedID 12552073

• Toward a new vocabulary of human genetic variation SCIENCE Sankar, P., Cho, M. K. 2002; 298 (5597): 1337-1338

  View details for Web of Science ID 000179223100022

  View details for PubMedID 12434037

• Genetics: DNA patenting and licensing SCIENCE Henry, M. R., Cho, M. K., Weaver, M. A., Merz, J. F. 2002; 297 (5585): 1279-1279

  View details for Web of Science ID 000177573900022

  View details for PubMedID 12193770

• Industry opposes genomic legislation NATURE BIOTECHNOLOGY Merz, J. F., Leonard, D. G., Kriss, A. G., Cho, M. K. 2002; 20 (7): 657-657

  View details for DOI 10.1038/nbt0702-657

  View details for Web of Science ID 000176494800010

  View details for PubMedID 12089543

• Conflicts of interest in magnetic resonance imaging: issues in clinical practice and research. Topics in magnetic resonance imaging Cho, M. K. 2002; 13 (2): 73-77

  Abstract

  In the use of magnetic resonance imaging (MRI) in medicine and in the conduct of MRI research, conflicts of interest are routinely generated. These conflicts are not necessarily unique to MRI and are not necessarily considered malpractice or misconduct. It is important, however, for clinicians and researchers to understand what constitutes a conflict of interest and how to mitigate the potential adverse effects of those conflicts on patients and on the integrity of research. It also is important for medical professionals to understand the changes in the clinical and research environments that make conflicts of interest more prevalent and more of a concern to policy makers. Finally, it is important for medical professionals who work with MRI to understand some of the characteristics of MRI that might increase the prevalence of conflicts of interest in clinical practice and research.

  View details for PubMedID 12055451

• Protecting subjects' interests in genetics research AMERICAN JOURNAL OF HUMAN GENETICS Merz, J. F., Magnus, D., Cho, M. K., Caplan, A. L. 2002; 70 (4): 965-971

  Abstract

  Biomedical researchers often assume that sponsors, subjects, families, and disease-associated advocacy groups contribute to research solely because of altruism. This view fails to capture the diverse interests of many participants in the emerging research enterprise. In the past two decades, patient groups have become increasingly active in the promotion and facilitation of genetics research. Simultaneously, a significant shift of academic biomedical science toward commercialization has occurred, spurred by U.S. federal policy changes. The concurrent rise in both the roles that subjects play and the commercial interests they have presents numerous ethical challenges. We examine the interests of different research participants, finding that these interests are not addressed by current policies and practices. We conclude that all participants should be given a voice in decisions affecting ownership, access to, and use of commercialized products and services, and that researchers and institutions should negotiate issues relating to control of research results and the sharing of benefits before the research is performed.

  View details for Web of Science ID 000174252100013

  View details for PubMedID 11870592

  View details for PubMedCentralID PMC379126

• Diagnostic testing fails the test. Nature Merz, J. F., Kriss, A. G., Leonard, D. G., Cho, M. K. 2002; 415 (6872): 577-579

  View details for PubMedID 11832913

  View details for PubMedCentralID PMC2220021

• Integrating genotype and phenotype information: an overview of the PharmGKB project. Pharmacogenetics Research Network and Knowledge Base. pharmacogenomics journal Klein, T. E., Chang, J. T., Cho, M. K., Easton, K. L., FERGERSON, R., Hewett, M., Lin, Z., Liu, Y., Liu, S., Oliver, D. E., Rubin, D. L., SHAFA, F., Stuart, J. M., Altman, R. B. 2001; 1 (3): 167-170

  View details for PubMedID 11908751

• Patenting human genetic material: refocusing the debate NATURE REVIEWS GENETICS Caulfield, T., Gold, E. R., Cho, M. K. 2000; 1 (3): 227-231

  Abstract

  The biotechnology industry has become firmly established over the past twenty years and gene patents have played an important part in this phenomenon. However, concerns have been raised over the patentability of human genetic material, through public protests and international statements, but to little effect. Here we discuss some of these concerns, the patent authorities' response to them, and ways in which to address these issues and to move the debate forward using current legal structures.

  View details for Web of Science ID 000165763700016

  View details for PubMedID 11252752

• Policies on faculty conflicts of interest at US universities JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Cho, M. K., Shohara, R., Schissel, A., Rennie, D. 2000; 284 (17): 2203-2208

  Abstract

  Despite federal regulations on faculty conflicts of interest in federally funded research, academic-industry ties are common, and evidence exists that financial considerations bias the research record. Public scrutiny of these ties is increasing, especially in cases where researchers have financial interests in the corporate sponsors of their clinical research.To review policies on conflict of interest at major biomedical research institutions in the United States.Cross-sectional survey and content analysis study conducted from August 1998 to February 2000.The 100 US institutions with the most funding from the National Institutes of Health in 1998 were initially sampled; policies from 89 institutions were available and included in the analysis.Process for disclosure, review, and management of conflicts of interest and specified management strategies or limitations, according to the institutions' faculty/staff conflict of interest policies.Content of the conflict of interest policies varied widely across institutions. Fifty-five percent of policies (n = 49) required disclosures from all faculty while 45% (n = 40) required them only from principal investigators or those conducting research. Nineteen percent of policies (n = 17) specified limits on faculty financial interests in corporate sponsors of research, 12% (n = 11) specified limits on permissible delays in publication, and 4% (n = 4) prohibited student involvement in work sponsored by a company in which the faculty mentor had a financial interest.Most policies on conflict of interest in our sample of major research institutions in the United States lack specificity about the kinds of relationships with industry that are permitted or prohibited. Wide variation in management of conflicts of interest among institutions may cause unnecessary confusion among potential industrial partners or competition among universities for corporate sponsorship that could erode academic standards. It is in the long-term interest of institutions to develop widely agreed-on, clear, specific, and credible policies on conflicts of interest. JAMA. 2000;284:2203-2208.

  View details for Web of Science ID 000090052600028

  View details for PubMedID 11056591

• Guidelines for advertising on health web sites: Who's guarding the Koop? WESTERN JOURNAL OF MEDICINE Cho, M. K. 2000; 172 (4): 230-232

  View details for Web of Science ID 000086286800011

  View details for PubMedID 10778369

• Policy forum: genetics. Ethical considerations in synthesizing a minimal genome. Science Cho, M. K., Magnus, D., Caplan, A. L., McGee, D. 1999; 286 (5447): 2087-?

  View details for PubMedID 10617419

• Survey confirms fears about licensing of genetic tests NATURE Schissel, A., Merz, J. F., Cho, M. K. 1999; 402 (6758): 118-118

  View details for Web of Science ID 000083716400016

  View details for PubMedID 10646997

• Commercialization of BRCA1/2 testing: Practitioner awareness and use of a new genetic test AMERICAN JOURNAL OF MEDICAL GENETICS Cho, M. K., Sankar, P., Wolpe, P. R., Godmilow, L. 1999; 83 (3): 157-163

  Abstract

  It was our purpose to determine the characteristics of practitioners in the United States who were among the first to inquire about and use the BRCA1 and BRCA2 (BRCA1/2) genetic tests outside of a research protocol. Questionnaires were mailed to all practitioners who requested information on or ordered a BRCA1/2 test from the University of Pennsylvania (UPenn) Genetic Diagnostics Laboratory (GDL) between October 1, 1995 and January 1, 1997 (the first 15 months the test was available for clinical use). The response rate was 67% of practitioners; 54% (121/225) were genetic counselors, 39% (87/225) were physicians or lab directors. Most physicians were oncologists, pathologists, or obstetrician/gynecologists, but 20% practiced surgery or internal or general medicine. Fifty-six percent (125/225) had ordered a BRCA1/2 test for a patient; most of the rest had offered or were willing to offer testing. Of those who had offered testing, 70% had a patient decline BRCA1/2 testing when offered. Practitioners perceived that patients' fear of loss of confidentiality was a major reason for declining. Nearly 60% of practitioners reported that their patients had access to a genetic counselor, but 28% of physicians who ordered a BRCA1/2 test reported having no such access, despite the GDL's counseling requirement. The proportion of physicians reporting no access to genetic counselors for their patients increased from 22.4% in the first half of the study to 50% in the last half. Many practitioners have an interest in BRCA1/2 testing, despite policy statements that discourage its use outside of research protocols. Practitioner responses suggest that patient interest in testing seems to be tempered by knowledge of potential risks. An apparent increase in patient concern about confidentiality and inability to pay for testing could indicate growing barriers to testing. Although most practitioners reported having access to counseling facilities, perceived lack of such access among an increasing proportion of practitioners indicates that lab requirements for counseling are difficult to enforce and suggests that an increasing proportion of patients may not be getting access to counseling.

  View details for Web of Science ID 000078879600004

  View details for PubMedID 10096590

• Disease genes are not patentable: A rebuttal of McGee CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS Merz, J. F., Cho, M. K. 1998; 7 (4): 425-428

  View details for Web of Science ID 000075650700014

  View details for PubMedID 9752584

• Familial disclosure in defiance of nonconsent AMERICAN JOURNAL OF HUMAN GENETICS Merz, J. F., Cho, M. K., Sankar, P. 1998; 63 (3): 898-899

  View details for Web of Science ID 000075919000029

  View details for PubMedID 9718355

• Testing for Alzheimer's SCIENCE Merz, J. F., Cho, M. K., Leonard, D. D. 1998; 281 (5381): 1288-1289

  View details for Web of Science ID 000075666800023

  View details for PubMedID 9735044

• Does masking author identity improve peer review quality? - A randomized controlled trial 3rd International Congress on Peer Review in Biomedical Publication Justice, A. C., Cho, M. K., Winker, M. A., Berlin, J. A., Rennie, D. AMER MEDICAL ASSOC. 1998: 240–42

  Abstract

  All authors may not be equal in the eyes of reviewers. Specifically, well-known authors may receive less objective (poorer quality) reviews. One study at a single journal found a small improvement in review quality when reviewers were masked to author identity.To determine whether masking reviewers to author identity is generally associated with higher quality of review at biomedical journals, and to determine the success of routine masking techniques.A randomized controlled trial performed on external reviews of manuscripts submitted to Annals of Emergency Medicine, Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology.Two peers reviewed each manuscript. In one study arm, both peer reviewers received the manuscript according to usual masking practice. In the other arm, one reviewer was randomized to receive a manuscript with author identity masked, and the other reviewer received an unmasked manuscript.Review quality on a 5-point Likert scale as judged by manuscript author and editor. A difference of 0.5 or greater was considered important.A total of 118 manuscripts were randomized, 26 to usual practice and 92 to intervention. In the intervention arm, editor quality assessment was complete for 77 (84%) of 92 manuscripts. Author quality assessment was complete on 40 (54%) of 74 manuscripts. Authors and editors perceived no significant difference in quality between masked (mean difference, 0.1; 95% confidence interval [CI], -0.2 to 0.4) and unmasked (mean difference, -0.1; 95% CI, -0.5 to 0.4) reviews. We also found no difference in the degree to which the review influenced the editorial decision (mean difference, -0.1; 95% CI,-0.3 to 0.3). Masking was often unsuccessful (overall, 68% successfully masked; 95% CI, 58%-77%), although 1 journal had significantly better masking success than others (90% successfully masked; 95% CI, 73%-98%). Manuscripts by generally known authors were less likely to be successfully masked (odds ratio, 0.3; 95% CI, 0.1-0.8). When analysis was restricted to manuscripts that were successfully masked, review quality as assessed by editors and authors still did not differ.Masking reviewers to author identity as commonly practiced does not improve quality of reviews. Since manuscripts of well-known authors are more difficult to mask, and those manuscripts may be more likely to benefit from masking, the inability to mask reviewers to the identity of well-known authors may have contributed to the lack of effect.

  View details for Web of Science ID 000074706000013

  View details for PubMedID 9676668

• Masking author identity in peer review - What factors influence masking success? 3rd International Congress on Peer Review in Biomedical Publication Cho, M. K., Justice, A. C., Winker, M. A., Berlin, J. A., Waeckerle, J. F., Callaham, M. L., Rennie, D. AMER MEDICAL ASSOC. 1998: 243–45

  Abstract

  In a previous study, we found that masking success was higher at a journal that masked reviewers to author identity. We hypothesized that masking policy or other factors could be associated with masking success.To evaluate differences in success of masking reviewers to author identity at 7 biomedical journals and to identify factors associated with these differences.Written questionnaire.Reviewers at 3 journals with a long-standing policy of masking author identity (Annals of Emergency Medicine, Epidemiology, and Journal of the American Geriatrics Society) and 4 journals without a policy of masking author identity (Annals of Internal Medicine, JAMA, Obstetrics & Gynecology, and Ophthalmology).Masking success (percentage of reviewers successfully masked) and reviewer characteristics associated with masking.There was no significant difference in masking success between journals with a policy of masking (60%) and those without (58%) (P= .92). We found no association between masking success and a policy of masking when adjusted for the reviewer characteristics of age, sex, years of reviewing experience, number of articles published, number of articles reviewed, percentage of time spent in research, editorial experience, or academic rank (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.64-2.8; P=.43). In multivariable analysis of reviewer characteristics, reviewers spending a greater percentage of time in research, the only significant predictor of masking success, were less likely to be successfully masked (OR, 1.01; 95% CI, 1.00-1.02) (P=.04).Masking success appears unrelated to a journal policy of masking, but is associated with reviewers' research experience and could be affected by other characteristics. Using reviewers with less research and reviewing experience might increase masking success, but the effect on review quality is unknown.

  View details for Web of Science ID 000074706000014

  View details for PubMedID 9676669

• [Improving the quality of reports on randomized controlled trials. Recommendations of the CONSORT Study Group]. Revista española de salud pública Begg, C., Cho, M., Eastwood, S., Horton, R., Moher, D., Olkin, I., Pitkin, R., Rennie, D., Schulz, K. F., SIMEL, D., Stroup, D. F. 1998; 72 (1): 5-11

  Abstract

  This summary corresponds to the translation into Spanish of the Special Communication published in the Journal of the American Medical Association in August 1996, along with the editorial published in the same issue "How to report Randomized Controlled Trials. The Consort Statement". It describes the Consolidated Standards for Preparation of Controlled Clinical Trials, prepared by a work group made up of members of the SORT Group and of the Asilomar Work Group, along with the director of a magazine and the author of the report on a clinical trial. The work was carried out by means of a Delphi process and the result was a check list and a process diagram. The check list is made up of 21 items that mainly refer to methods, results and discussions on the report of a controlled clinical trial, identifying the necessary information in order to be able to evaluate the internal and external value of the report, judging the improvement to be positive for the patient, the editors and the reviewers of the magazines.

  View details for PubMedID 9477711

• Educational material about genetic tests: Does it provide key information for patients and practitioners? AMERICAN JOURNAL OF MEDICAL GENETICS Cho, M. K., Arruda, M., Holtzman, N. A. 1997; 73 (3): 314-320

  Abstract

  Genetic testing for common conditions will be used increasingly in primary care, but resources for patient counseling are decreasing. It is also necessary that primary care practitioners be better equipped to do basic genetic counseling. Therefore, the quality of informational materials for practitioners and patients is important. It was unknown how often key elements recommended by policy groups were actually included in such material. It was our aim to determine the content of printed informational material for practitioners and patients on genetic testing. We performed (1) a telephone survey of organizations in the United States that developed genetic tests or services and (2) a content analysis of pamphlets obtained from these organizations to determine the presence of 10 critical elements necessary to evaluate the appropriateness and performance of the tests. Almost 95% (169/178) of organizations responded to our survey; 131/169 (78%) reported using informational materials. We analyzed 115 pamphlets collected from 125/131 (95%) organizations. Elements least frequently included in the pamphlets were risks and benefits, patient rights, and intended use or purpose of the test. Most frequently included were descriptions of the conditions detected by the test, and the appropriate patients for testing. Nearly one half of the pamphlets included some statement about the accuracy of the test, but most of these did not specify whether their statements referred to sensitivity, specificity, or predictive value. Overall, pamphlets tended to contain information that would aid in determining a patient's eligibility for a genetic test, but did not contain sufficient information about the tests themselves. Our results suggest that several critical elements need to be added to enhance informed choices by patients and physicians.

  View details for Web of Science ID A1997YH57700016

  View details for PubMedID 9415691

• Disease Gene Patenting Is a Bad Innovation. Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology Merz, J. F., Cho, M. K., Robertson, M. J., Leonard, D. G. 1997; 2 (4): 299-304

  View details for DOI 10.1054/MODI00200299

  View details for PubMedID 10462622

• Calculating coauthors' contributions LANCET Merz, J. F., Gorton, G. E., Cho, M. K., Merz, M. L., Sankar, P. 1997; 350 (9090): 1558-1558

  View details for Web of Science ID A1997YH11500074

  View details for PubMedID 9417483

• Patients and patents NATURE Cho, M. K., Merz, J. F. 1997; 390 (6657): 221-221

  View details for Web of Science ID A1997YG66700024

  View details for PubMedID 9384365

• Conflict of interest and institutional review boards JOURNAL OF INVESTIGATIVE MEDICINE Cho, M. K., Billings, P. 1997; 45 (4): 154-159

  View details for Web of Science ID A1997WW01000004

  View details for PubMedID 9154295

• Improving the quality of reporting of randomized controlled trials - The CONSORT statement JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Begg, C., Cho, M., Eastwood, S., Horton, R., Moher, D., Olkin, I., Pitkin, R., Rennie, D., Schulz, K. F., SIMEL, D., Stroup, D. F. 1996; 276 (8): 637-639

  View details for Web of Science ID A1996VC85300031

  View details for PubMedID 8773637

• The quality of drug studies published in symposium proceedings ANNALS OF INTERNAL MEDICINE Cho, M. K., Bero, L. A. 1996; 124 (5): 485-?

  Abstract

  To compare the quality, relevance, and structure of drug studies published in symposium proceedings that are sponsored by drug companies with 1) articles from symposia with other sponsors and 2) articles in the peer-reviewed parent journals of symposium proceedings; and to study the relation between drug company sponsorship and study outcome.Cross-sectional studies of clinical drug studies published in symposium proceedings or their parent medical journals.The proportion of articles with no methods sections (which are necessary to assess quality); methodologic quality and clinical relevance scores; and the proportion of articles with outcomes favoring the drug of interest.Symposia sponsored by single drug companies had more articles without methods sections (10%; 108 of 1064) than did symposia that had other sponsors (3%; 58 of 2314) or symposia that had no mentioned sponsor (2%; 29 of 1663) (P < 0.001). The mean methodologic quality and relevance scores of articles were similar both by type of sponsorship and between articles published in symposia sponsored by single drug companies and articles from the parent journals. Significantly more articles with drug company support (98%; 39 of 40) than without drug company support (79%; 89 of 112) had outcomes favoring the drug of interest (P = 0.01).Articles in symposia sponsored by single drug companies were similar in quality and clinical relevance to articles with other sponsors and to articles published in the parent journals. Articles with drug company support are more likely than articles without drug company support to have outcomes favoring the drug of interest.

  View details for Web of Science ID A1996TW77300004

  View details for PubMedID 8602706

• A proposal for structured reporting of randomized controlled trials. The Standards of Reporting Trials Group. JAMA : the journal of the American Medical Association 1994; 272 (24): 1926-1931

  View details for PubMedID 7990245

• FAST MYOSIN HEAVY-CHAINS EXPRESSED IN SECONDARY MAMMALIAN MUSCLE-FIBERS AT THE TIME OF THEIR INCEPTION JOURNAL OF CELL SCIENCE Cho, M., Hughes, S. M., KARSCHMIZRACHI, I., Travis, M., Leinwand, L. A., Blau, H. M. 1994; 107: 2361-2371

  Abstract

  Mammalian skeletal muscle is generated by two waves of fiber formation, resulting in primary and secondary fibers. These fibers mature to give rise to several classes of adult muscle fibers with distinct contractile properties. Here we describe fast myosin heavy chain (MyHC) isoforms that are expressed in nascent secondary, but not primary, fibers in the early development of rat and human muscle. These fast MyHCs are distinct from previously described embryonic and neonatal fast MyHCs. To identify these MyHCs, monoclonal antibodies were used whose specificity was determined in western blots of MyHCs on denaturing gels and reactivity with muscle tissue at various stages of development. To facilitate a comparison of our results with those of others obtained using different antibodies or species, we have identified cDNAs that encode the epitopes recognized by our antibodies wherever possible. The results suggest that epitopes characteristic of adult fast MyHCs are expressed very early in muscle fiber development and distinguish newly formed secondary fibers from primary fibers. This marker of secondary fibers, which is detectable at the time of their inception, should prove useful in future studies of the derivation of primary and secondary fibers in mammalian muscle development.

  View details for Web of Science ID A1994PH54500002

  View details for PubMedID 7531198

• INSTRUMENTS FOR ASSESSING THE QUALITY OF DRUG STUDIES PUBLISHED IN THE MEDICAL LITERATURE 2nd International Congress on Peer Review in Biomedical Publication Cho, M. K., Bero, L. A. AMER MEDICAL ASSOC. 1994: 101–4

  Abstract

  To develop valid and reliable instruments to assess the methodologic quality and clinical relevance of drug studies.We developed an instrument to assess the methodologic quality of articles reporting clinical research and an instrument to measure nonmethodologic measures of quality, such as clinical relevance, generalizability, and adherence to ethical standards. Each instrument was pretested by seven independent, masked reviewers and modified based on interrater agreement and content validity of individual items. We determined correlational validity of the final methodologic quality instrument by comparing quality scores assigned to 10 articles by means of our instrument and a previously published one.Clinical drug studies published in symposium proceedings and peer reviewed biomedical literature.Interrater reliability of overall quality scores, measured by intraclass correlation (r) and Kendall's coefficient of concordance (W), and interrater reliability of individual items, by percentage agreement.The interrater reliability of the pretest methodologic quality instrument was high (r = .89 [95% confidence interval, .73 to .96]; W = 0.64). Correlational validity of the final instrument was suggested by the high degree of concordance with another previously published one (W = 0.74). The interrater reliability of the pretest clinical relevance instrument was moderate (r = .41 [95% confidence interval, .18 to .64]; W = 0.47). Reviewers confirmed the content validity of both instruments.The two instruments we developed, one measuring methodologic quality and one measuring clinical relevance of articles reporting clinical research, are reliable, valid, and applicable to a variety of research designs.

  View details for Web of Science ID A1994NV42400005

  View details for PubMedID 8015115

• Are clinical trials of cell transplantation for Duchenne muscular dystrophy ethical? IRB Cho, M. K. 1994; 16 (1-2): 12-15

  View details for PubMedID 11652321

• 3 SLOW MYOSIN HEAVY-CHAINS SEQUENTIALLY EXPRESSED IN DEVELOPING MAMMALIAN SKELETAL-MUSCLE DEVELOPMENTAL BIOLOGY Hughes, S. M., Cho, M., KARSCHMIZRACHI, I., Travis, M., Silberstein, L., Leinwand, L. A., Blau, H. M. 1993; 158 (1): 183-199

  Abstract

  Myosin heavy chain (MyHC) isoforms show a striking diversity of expression patterns during mammalian development. Using a set of monoclonal antibodies that recognize different epitopes on myosin heavy chain isoforms we show that there exist in human and rat skeletal muscle at least three isoforms of slow twitch myosin heavy chain. To facilitate a comparison of our results to others obtained using different antibodies or species, we have identified cDNAs encoding the epitopes recognized by the three slow antibodies. Using these reagents, we show that the onset of expression of three slow MyHC isoforms is temporally distinct during early gestation. This result suggests that a sequence of MyHC transitions plays an important role in determining muscle fiber function at fetal, neonatal, and adult stages.

  View details for Web of Science ID A1993LM14800015

  View details for PubMedID 7687223

• EVIDENCE FOR MYOBLAST-EXTRINSIC REGULATION OF SLOW MYOSIN HEAVY-CHAIN EXPRESSION DURING MUSCLE-FIBER FORMATION IN EMBRYONIC-DEVELOPMENT JOURNAL OF CELL BIOLOGY Cho, M., Webster, S. G., Blau, H. M. 1993; 121 (4): 795-810

  Abstract

  Vertebrate muscles are composed of an array of diverse fast and slow fiber types with different contractile properties. Differences among fibers in fast and slow MyHC expression could be due to extrinsic factors that act on the differentiated myofibers. Alternatively, the mononucleate myoblasts that fuse to form multinucleated muscle fibers could differ intrinsically due to lineage. To distinguish between these possibilities, we determined whether the changes in proportion of slow fibers were attributable to inherent differences in myoblasts. The proportion of fibers expressing slow myosin heavy chain (MyHC) was found to change markedly with time during embryonic and fetal human limb development. During the first trimester, a maximum of 75% of fibers expressed slow MyHC. Thereafter, new fibers formed which did not express this MyHC, so that the proportion of fibers expressing slow MyHC dropped to approximately 3% of the total by midgestation. Several weeks later, a subset of the new fibers began to express slow MyHC and from week 30 of gestation through adulthood, approximately 50% of fibers were slow. However, each myoblast clone (n = 2,119) derived from muscle tissues at six stages of human development (weeks 7, 9, 16, and 22 of gestation, 2 mo after birth and adult) expressed slow MyHC upon differentiation. We conclude from these results that the control of slow MyHC expression in vivo during muscle fiber formation in embryonic development is largely extrinsic to the myoblast. By contrast, human myoblast clones from the same samples differed in their expression of embryonic and neonatal MyHCs, in agreement with studies in other species, and this difference was shown to be stably heritable. Even after 25 population doublings in tissue culture, embryonic stage myoblasts did not give rise to myoblasts capable of expressing MyHCs typical of neonatal stages, indicating that stage-specific differences are not under the control of a division dependent mechanism, or intrinsic "clock." Taken together, these results suggest that, unlike embryonic and neonatal MyHCs, the expression of slow MyHC in vivo at different developmental stages during gestation is not the result of commitment to a distinct myoblast lineage, but is largely determined by the environment.

  View details for Web of Science ID A1993LB63800008

  View details for PubMedID 8491773

• BETA-ENOLASE IS A MARKER OF HUMAN MYOBLAST HETEROGENEITY PRIOR TO DIFFERENTIATION DEVELOPMENTAL BIOLOGY Peterson, C. A., Cho, M., Rastinejad, F., Blau, H. M. 1992; 151 (2): 626-629

  Abstract

  In this report, we define a muscle-specific marker, beta-enolase, that distinguishes proliferating myoblasts from different stages of development. Enolase exists as multiple isoforms and in the course of cardiac and skeletal muscle development the beta isoform progressively replaces the alpha isoform. In skeletal muscle, this change in gene expression, unlike most developmental changes in myogenic gene expression, is evident in undifferentiated myoblasts. Whereas myoblasts from fetal tissues express alpha-enolase mRNA, beta-enolase is the predominant mRNA expressed by myoblasts from postnatal tissues. Our results are consistent with the idea that distinct precursor myoblasts contribute to the diversity of fiber types characteristic of muscle tissue at different stages of development.

  View details for Web of Science ID A1992HY74000029

  View details for PubMedID 1339335