Because of the recent advances in embryo modeling techniques, and at the request of the Office of Science Policy in the Office of the Director at the National Institutes of Health, the National Academies of Sciences, Engineering, hosted a 1-day public workshop that would explore the state of the science of mammalian embryo model systems. The workshop, which took place on January 17, 2020, featured a combination of presentations, panels, and general discussions, during which panelists and participants offered a broad range of perspectives. Participants considered whether embryo model systems - especially those that use nonhuman primate cells - can be used to predict the function of systems made with human cells. Presentations provided an overview of the current state of the science of in vitro development of human trophoblast. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Mammalian Embryo Research and Pluripotent Stem Cells 3 Examining the Development of Extraembryonic Lineages 4 Stem CellBased Models of Human Embryos 5 Comparative Embryonic Development Across Species 6 Exploring Opportunities and Challenges with Mammalian Embryo Model Systems References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Consumer genomics, encompassing both direct-to-consumer applications (i.e., genetic testing that is accessed by a consumer directly from a commercial company apart from a health care provider) and consumer-driven genetic testing (i.e., genetic testing ordered by a health care provider in response to an informed patient request), has evolved considerably over the past decade, moving from more personal utility-focused applications outside of traditional health care to interfacing with clinical care in nontraditional ways. As consumer genomics has increasingly intersected with clinical applications, discussions have arisen around the need to demonstrate clinical and analytical validity and clinical utility due to the potential for misinterpretation by consumers. Clinical readiness and interest for this information have presented educational and training challenges for providers. At the same time, consumer genomics has emerged as a potentially innovative mechanism for thinking about health literacy and engaging participants in their health and health care. To explore the current landscape of consumer genomics and the implications for how genetic test information is used or may be used in research and clinical care, the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine hosted a public workshop on October 29, 2019, in Washington, DC. Discussions included such topics as the diversity of participant populations, the impact of consumer genomics on health literacy and engagement, knowledge gaps related to the use of consumer genomics in clinical care, and regulatory and health policy issues such as data privacy and security. A broad array of stakeholders took part in the workshop, including genomics and consumer genomics experts, epidemiologists, health disparities researchers, clinicians, users of consumer genomics research applications, representatives from patient advocacy groups, payers, bioethicists, regulators, and policy makers. This publication summarizes the presentations and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Workshop Overview 2 Understanding Consumer Genomics Use 3 Exploring the Role of Diversity and Health Disparities in Consumer Genomics 4 Integration Within Scientific and Medical Communities 5 Regulatory and Health Policy Issues 6 How Can Consumer Genomics Be Better Integrated to Improve Health? References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Genomic medicine is defined as the routine use of genomic information about an individual as part of his or her clinical care as well as the health outcomes and policy implications of that clinical use. It is one approach that has the potential to improve the quality of health care by allowing practitioners to tailor prevention, diagnostic, and treatment strategies to individual patients. In recent years, research breakthroughs, technological advances, and the decreasing cost of DNA sequencing have led to the wider adoption of genomic medicine. However, as with the introduction of new technologies into health care, there are concerns that genetic and genomic testing and services will not reach all segments of the population both now and in the near future, and there remains a gap in knowledge regarding potential health care disparities in genomic medicine and precision health approaches. On June 27, 2018, the National Academies of Sciences, Engineering, and Medicine hosted a public workshop to examine the gaps in knowledge related to access to genomic medicine and to discuss health care disparities and possible approaches to overcoming the disparate use of genomic medicine among populations. Workshop participants discussed research on access to genetics and genomics services in medically underserved areas, model programs of care for diverse patient populations, and current challenges and possible best practices for alleviating health care disparities as they relate to genomics-based approaches. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Exploring the Barriers to Accessing Genomic and Genetic Services 3 The Role of Health Systems in Delivering Equitable Access 4 How Can Providers and Payers Make Genomic Medicine More Accessible? 5 Exploring Innovative Solutions and Models of Success 6 Considering Unmet Needs to Alleviate Disparities in Genomic Medicine References Appendix A: Summary of the Pre-Workshop Twitter Chat Appendix B: Workshop Agenda Appendix C: Speaker Biographical Sketches Appendix D: Statement of Task Appendix E: Registered Attendees

Genomic applications are being integrated into a broad range of clinical and research activities at health care systems across the United States. This trend can be attributed to a variety of factors, including the declining cost of genome sequencing and the potential for improving health outcomes and cutting the costs of care. The goals of these genomics-based programs may be to identify individuals with clinically actionable variants as a way of preventing disease, providing diagnoses for patients with rare diseases, and advancing research on genetic contributions to health and disease. Of particular interest are genomics- based screening programs, which will, in this publication, be clinical screening programs that examine genes or variants in unselected populations in order to identify individuals who are at an increased risk for a particular health concern (e.g., diseases, adverse drug outcomes) and who might benefit from clinical interventions. On November 1, 2017, the National Academies of Sciences, Engineering, and Medicine hosted a public workshop to explore the challenges and opportunities associated with integrating genomics-based screening programs into health care systems. This workshop was developed as a way to explore the challenges and opportunities associated with integrating genomics-based programs in health care systems in the areas of evidence collection, sustainability, data sharing, infrastructure, and equity of access. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction 2 Evidence Considerations for Integrating Genomics-Based Programs into Health Care Systems 3 Financial Considerations for Implementing Genomics-Based Screening Programs 4 Exploring Approaches to Optimize Data Sharing Among Early Implementers of Genomics-Based Programs 5 Understanding Participant Needs and Preferences and Improving Diversity and Equity 6 Improving Health Through the Integration of Genomics-Based Programs: Potential Next Steps References Appendix A: Workshop Agenda Appendix B: Speaker Biographies Appendix C: Statement of Task Appendix D: Registered Attendees

Those involved in the drug development process face challenges of efficiency and overall sustainability due in part to high research costs, lengthy development timelines, and late-stage drug failures. Novel clinical trial designs that enroll participants based on their genetics represent a potentially disruptive change that could improve patient outcomes, reduce costs associated with drug development, and further realize the goals of precision medicine. On March 8, 2017, the Forum on Drug Discovery, Development, and Translation and the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine hosted the workshop Enabling Precision Medicine: The Role of Genetics in Clinical Drug Development. Participants examined successes, challenges, and possible best practices for effectively using genetic information in the design and implementation of clinical trials to support the development of precision medicines, including exploring the potential advantages and disadvantages of such trials across a variety of disease areas. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction 2 Overarching Considerations for Implementing Successful Genetics-Enabled Drug Development 3 Case Studies in Precision Drug Development 4 Integrating Genetics into the Drug Development Pathway for Complex Diseases 5 Finding Innovative Ways to Integrate Genetic Research into the Drug Development Process 6 Reflecting Back and Looking Forward: Key Themes and Potential Next Steps in Genetics-Enabled Drug Development Appendix A: References Appendix B: Statement of Task and Workshop Agenda Appendix C: Speaker Biographical Sketches Appendix D: Registered Attendees

Regenerative medicine products, which are intended to repair or replace damaged cells or tissues in the body, include a range of therapeutic approaches such as cell- and gene-based therapies, engineered tissues, and non-biologic constructs. The current approach to characterizing the quality of a regenerative medicine product and the manufacturing process often involves measuring as many endpoints as possible, but this approach has proved to be inadequate and unsustainable. The Forum on Regenerative Medicine of the National Academies of Sciences, Engineering, and Medicine convened experts across disciplines for a 2-day virtual public workshop to explore systems thinking approaches and how they may be applied to support the identification of relevant quality attributes that can help in the optimization of manufacturing and streamline regulatory processes for regenerative medicine. A broad array of stakeholders, including data scientists, physical scientists, industry researchers, regulatory officials, clinicians, and patient representatives, discussed new advances in data acquisition, data analysis and theoretical frameworks, and how systems approaches can be applied to the development of regenerative medicine products that can address the unmet needs of patients. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction 2 Introduction to Systems Thinking Concepts 3 Exploring the Challenges of Critical Quality Attributes: The Role of Systems Thinking 4 Challenges Associated with Data Collection, Aggregation, and Sharing 5 Challenges and Opportunities Associated with Systems-Level Analysis and Modeling 6 Addressing Regenerative Medicine Manufacturing and Supply Chain Challenges with Systems-Level Approaches 7 Exploring Issues of Workforce Development Related to Systems Thinking References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task

On February 26, 2020, the Board on Health Sciences Policy of the National Academies of Sciences, Engineering, and Medicine hosted a 1-day public workshop in Washington, DC, to examine current and emerging bioethical issues that might arise in the context of biomedical research and to consider research topics in bioethics that could benefit from further attention. The scope of bioethical issues in research is broad, but this workshop focused on issues related to the development and use of digital technologies, artificial intelligence, and machine learning in research and clinical practice; issues emerging as nontraditional approaches to health research become more widespread; the role of bioethics in addressing racial and structural inequalities in health; and enhancing the capacity and diversity of the bioethics workforce. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction 2 Ethically Leveraging Digital Technology for Health 3 Ethical Questions Concerning Nontraditional Approaches for Data Collection and Use 4 Understanding the Impact of Inequality on Health, Disease, and Who Participates in Research 5 Bioethics Research Workforce 6 Reflecting on the Workshop and Looking to the Future References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Recognizing the potential design complexities and ethical issues associated with clinical trials for gene therapies, the Forum on Regenerative Medicine of the National Academies of Sciences, Engineering, and Medicine held a 1-day workshop in Washington, DC, on November 13, 2019. Speakers at the workshop discussed patient recruitment and selection for gene-based clinical trials, explored how the safety of new therapies is assessed, reviewed the challenges involving dose escalation, and spoke about ethical issues such as informed consent and the role of clinicians in recommending trials as options to their patients. The workshop also included discussions of topics related to gene therapies in the context of other available and potentially curative treatments, such as bone marrow transplantation for hemoglobinopathies. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Developing First-in-Human Gene Therapy Clinical Trials 3 Understanding the Complexities of Patient Selection, Enrollment, and the Consent Process 4 Developing Endpoints for Gene Therapy Clinical Trials 5 Integrating Gene-Based Therapies into Clinical Practice: Exploring Long-Term Clinical Follow-Up of Patients 6 Reflections on the Workshop and Potential Opportunities for Next Steps References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

On June 26, 2017, the Forum on Regenerative Medicine hosted a public workshop in Washington, DC, titled Navigating the Manufacturing Process and Ensuring the Quality of Regenerative Medicine Therapies in order to examine and discuss the challenges, opportunities, and best practices associated with defining and measuring the quality of cell and tissue products and raw materials in the research and manufacturing of regenerative medicine therapies. The goal of the workshop was to learn from existing examples of the manufacturing of early-generation regenerative medicine products and to address how progress could be made in identifying and measuring critical quality attributes. The workshop also addressed the challenges of designing and adhering to standards as a way of helping those who are working to scale up processes and techniques from a research laboratory to the manufacturing environment. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction 2 Transitioning from Discovery and Development to Manufacturing 3 Identifying and Measuring Critical Quality Attributes 4 Designing Technologies to Meet the Manufacturing Needs of New Regenerative Medicine Therapies 5 Considerations for Improving and Regulating Regenerative Medicine Products 6 Potential Next Steps for Supporting the Development, Manufacture, and Regulation of Regenerative Medicine Therapies References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Regenerative medicine holds the potential to create living, functional cells and tissues that can be used to repair or replace those that have suffered potentially irreparable damage due to disease, age, traumatic injury, or genetic and congenital defects. The field of regenerative medicine is broad and includes research and development components of gene and cell therapies, tissue engineering, and non-biologic constructs. Although regenerative medicine has the potential to improve health and deliver economic benefits, this relatively new field faces challenges to developing policies and procedures to support the development of novel therapies are both safe and effective. In October 2016, the National Academies of Sciences, Engineering, and Medicine hosted a public workshop with the goal of developing a broad understanding of the opportunities and challenges associated with regenerative medicine cellular therapies and related technologies. Participants explored the state of the science of cell-based regenerative therapies within the larger context of patient care and policy. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction 2 Skin and Musculoskeletal Tissues 3 Hematologic and Immunologic Applications 4 Neurological and Ophthalmological Tissues 5 Cardiovascular and Lung Tissues 6 Renal Tissue 7 Looking Toward the Future: Concluding Thoughts References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

The process of discovering and developing a new drug or therapy is extremely costly and time consuming, and recently, it has been estimated that the creation of a new medicine costs on average more than $2 billion and takes 10 years to reach patients. The challenges associated with bringing new medicines to market have led many pharmaceutical companies to seek out innovative methods for streamlining their drug discovery research. One way to increase the odds of success for compounds in the drug development pipeline is to adopt genetically guided strategies for drug discovery, and recognizing the potential benefits of collecting genetic and phenotypic information across specific populations, pharmaceutical companies have started collaborating with healthcare systems and private companies that have curated genetic bioresources, or large databases of genomic information. Large-scale cohort studies offer an effective way to collect and store information that can be used to assess gene?environment interactions, identify new potential drug targets, understand the role of certain genetic variants in the drug response, and further elucidate the underlying mechanisms of disease onset and progression. To examine how genetic bioresources could be used to improve drug discovery and target validation, the National Academies of Sciences, Engineering, and Medicine hosted a workshop in March 2016. Participants at the workshop explored the current landscape of genomics-enabled drug discovery activities in industry, academia, and government; examined enabling partnerships and business models; and considered gaps and best practices for collecting population data for the purpose of improving the drug discovery process. This publication summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction and Themes of the Workshop 2 Maximizing Discovery Capabilities Through Cohort Design 3 Discovery Activities Related to Genetic Bioresources 4 Business Models That Support Bioresource Discovery and Collaboration 5 Potential Next Steps in Using Genomics to Advance Drug Discovery References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Although it is becoming increasingly more common for clinicians to use genomic data in their practices for disease prevention, diagnosis, and treatment, the process of integrating genomic data into the practice of medicine has been a slow and challenging one. Some of the major barriers impeding the incorporation of new genomic technology into clinical practice are: the difficulty of changing routine medical practices to account for the use of genetic testing, the limited knowledge of patients and providers about genomic medicine, assessing sufficient evidence to support the use of genetic tests, privacy and data security issues, and uncertainty about reimbursement. The field of implementation science may be able to provide insights concerning efficient ways to incorporate genomic applications into routine clinical practice. The focus of implementation science studies is to identify integration bottlenecks and optimal approaches for a given setting and ultimately to promote the up-take of research findings. To explore the potential of implementation science to improve the integration of genomics into medicine, the National Academies of Sciences, Engineering, and Medicine held a workshop in Washington, DC, in November 2015. Participants explored the challenges and opportunities of integrating genomic advances into the clinic through the lens of implementation science. This report summarizes the presentations and discussions from the workshop. Table of Contents Front Matter 1 Introduction and Themes of the Workshop 2 Implementation Science: Methods and Approaches 3 Engaging Large and Diverse Populations for Analysis 4 Generating Evidence During Implementation 5 Genomics and Implementation at the Level of Population Health 6 Achieving the Vision References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees Appendix E: Implementation Science: A Background Appendix F: Large Genetic Cohort Studies: A Background