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

The emerging multidisciplinary field of regenerative engineering is devoted to the repair, regeneration, and replacement of damaged tissues or organs in the body. To accomplish this it uses a combination of principles and technologies from disciplines such as advanced materials science, developmental and stem cell biology, immunology, physics, and clinical translation. The term "regenerative engineering" reflects a new understanding of the use of tissue engineering for regeneration and also the growing number of research and product development efforts that incorporate elements from a variety of fields. Because regenerative engineered therapies rely on live cells and scaffolds, there are inherent challenges in quality control arising from variability in source and final products. Furthermore, each patient recipient, tissue donor, and product application is unique, meaning that the field faces complexities in the development of safe and effective new products and therapies which are not faced by developers of more conventional therapies. Understanding the many sources of variability can help reduce this variability and ensure consistent results. The Forum on Regenerative Medicine hosted a public workshop on October 18, 2018, in Washington, DC, to explore the various factors that must be taken into account in order to develop successful regenerative engineering products. Invited speakers and participants discussed factors and sources of variability in the development and clinical application of regenerative engineering products, characteristics of high-quality products, and how different clinical needs, models, and contexts can inform the development of a product to improve patient outcomes. This publication summarizes the presentation and discussion of the workshop. Table of Contents Front Matter 1 Introduction and Overview 2 Sources of Variability Associated with Regenerative Therapies: Lessons from Case Studies 3 Factors Contributing to Patient Variability 4 Addressing Variability in Donor Tissues and Cells 5 Addressing Variability and Meeting Quality Expectations in the Manufacturing Setting 6 Exploring Variability and Its Impact on Product Regulation and Outcomes 7 Potential Next Steps to Consider for Addressing Variability References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches 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

Many health care providers do not have either the knowledge or the tools they need in order to apply genetic information in their day-to-day practices. This lack of support is contributing to a substantial delay in the translation of genetic research findings, when appropriate, into improvement in patient outcomes within the health care system. Although the need to improve genetics knowledge among health care providers is clear, the best approaches to educating health care providers in a way that produces meaningful changes in clinical practice are not, especially given the competing coursework and training needs that exist in today's increasingly complex health care settings. To examine the potential and the challenges of providing genetics education, the Roundtable on Translating Genomic-Based Research for Health of the Institute of Medicine hosted a workshop on August 18, 2014. The workshop examined a variety of approaches that could improve the teaching of genetics in the graduate and continuing education of health professionals; these approaches included online and interactive instruction, just-in-time approaches, the development of clinical decision-support tools, and the incorporation of genetics requirements into licensing and accreditation. This report summarizes the presentations and discussion of the event. Table of Contents Front Matter 1 Introduction and Themes of the Workshop 2 Myths and Mistakes in Graduate and Continuing Medical Education 3 Educational Approaches 4 Graduate Health Professional Education and Post-Graduate Training 5 Continuing Medical Education 6 Next Steps to Achieve Effective Genetics Education for Health Professionals References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Many drug developers have examined new strategies for creating efficiencies in their development processes, including the adoption of genomics-based approaches. Genomic data can identify new drug targets for both common and rare diseases, can predict which patients are likely to respond to a specific treatment, and has the potential to significantly reduce the cost of clinical trials by reducing the number of patients that must be enrolled in order to demonstrate safety and efficacy. A key component of the approval of targeted therapeutics is the ability to identify the population of patients who will benefit from treatment, and this has largely hinged on the co-development and co-submission to the FDA of a companion diagnostic test.The co-development process, or the development of the test and drug for the simultaneous submission to FDA, has led to a major alteration in the way that drugs are being developed, with traditionally separate entities-pharmaceutical and diagnostic companies-now working in close collaboration. Refining Processes for the Co-Development of Genome-Based Therapeutics and Companion Diagnostic Tests is the summary of a workshop held by the Roundtable on Translating Genomic-Based Research for Health on February 27, 2013 to examine and discuss challenges and potential solutions for the codevelopment of targeted therapeutics and companion molecular tests for the prediction of drug response. Prior to the workshop, key stakeholders, including laboratory and medical professional societies, were individually asked to provide possible solutions to resolve the concerns raised about co-development of companion diagnostic tests and therapies. Workshop speakers were charged with addressing these solutions in their presentations by providing insight on (1) whether the proposed solutions address the problems described, (2) whether there are other solutions to propose, and (3) what steps could be taken to effectively implement the proposed solutions. Table of Contents Front Matter 1 Introduction 2 Regulatory Perspectives 3 Perspectives from Patients, Providers, and Laboratory Representatives 4 Perspectives of Diagnostic Test and Pharmaceutical Developers 5 Perspectives of Payers and Regulators 6 Concluding Observations References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

The Forum on Regenerative Medicine of the National Academies of Sciences, Engineering, and Medicine convened a two-day virtual public workshop to address knowledge gaps in the understanding of promising approaches to manipulate the immune system and/or the regenerative medicine product to improve outcomes of tissue repair and regeneration in patients. The workshop, titled "Understanding the Role of the Immune System in Improving Tissue Regeneration," explored the role of the immune system in the success or failure of regenerative medicine therapies. Participants considered potential strategies to effectively "prepare" patients' immune systems to accept regenerative therapies and increase the likelihood of successful clinical outcomes and also discussed risks associated with modulating the immune system. This Proceedings of a Workshop highlights the presentations and discussions that occurred during the workshop.

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

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

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

Rapid advances in technology have lowered the cost of sequencing an individual's genome from the several billion dollars that it cost a decade ago to just a few thousand dollars today and have correspondingly greatly expanded the use of genomic information in medicine. Because of the lack of evidence available for assessing variants, evaluation bodies have made only a few recommendations for the use of genetic tests in health care. For example, organizations, such as the Evaluation of Genomic Applications in Practice and Prevention working group, have sought to set standards for the kinds of evaluations needed to make population-level health decisions. However, due to insufficient evidence, it has been challenging to recommend the use of a genetic test. An additional challenge to using large-scale sequencing in the clinic is that it may uncover "secondary," or "incidental," findings - genetic variants that have been associated with a disease but that are not necessarily related to the conditions that led to the decision to use genomic testing. Furthermore, as more genetic variants are associated with diseases, new information becomes available about genomic tests performed previously, which raises issues about how and whether to return this information to physicians and patients and also about who is responsible for the information. To help develop a better understanding of how genomic information is used for healthcare decision making, the Roundtable on Translating Genomic-Based Research for Health of the Institute of Medicine held a workshop in Washington,DC in February 2014. Stakeholders, including clinicians, researchers, patients, and government officials, discussed the issues related to the use of genomic information in medical practice. Assessing Genomic Sequencing Information for Health Care Decision Making is the summary of that workshop. This report compares and contrasts evidence evaluation processes for different clinical indications and discusses key challenges in the evidence evaluation process. Table of Contents Front Matter 1 Introduction 2 How Evidence Is Gathered and Evaluated 3 Patient Care and Health Decisions 4 The Development of Practice Guidelines 5 How Insurers Decide Whether to Pay for Testing 6 Addressing Challenges References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Drug development can be time-consuming and expensive. Recent estimates suggest that, on average, it takes 10 years and at least $1 billion to bring a drug to market. Given the time and expense of developing drugs de novo, pharmaceutical companies have become increasingly interested in finding new uses for existing drugs - a process referred to as drug repurposing or repositioning. Historically, drug repurposing has been largely an unintentional, serendipitous process that took place when a drug was found to have an offtarget effect or a previously unrecognized on-target effect that could be used for identifying a new indication. Perhaps the most recognizable example of such a successful repositioning effort is sildenafil. Originally developed as an anti-hypertensive, sildenafil, marketed as Viagra and under other trade names, has been repurposed for the treatment of erectile dysfunction and pulmonary arterial hypertension. Viagra generated more than $2 billion worldwide in 2012 and has recently been studied for the treatment of heart failure. Given the widespread interest in drug repurposing, the Roundtable on Translating Genomic-Based Research for Health of the Institute of Medicine hosted a workshop on June 24, 2013, in Washington, DC, to assess the current landscape of drug repurposing activities in industry, academia, and government. Stakeholders, including government officials, pharmaceutical company representatives, academic researchers, regulators, funders, and patients, were invited to present their perspectives and to participate in workshop discussions. Drug Repurposing and Repositioning is the summary of that workshop. This report examines enabling tools and technology for drug repurposing; evaluates the business models and economic incentives for pursuing a repurposing approach; and discusses how genomic and genetic research could be positioned to better enable a drug repurposing paradigm. Table of Contents Front Matter 1 Introduction and Themes of the Workshop 2 The State of the Science 3 Enabling Tools and Technology 4 Value Propositions for Drug Repurposing 5 Policy Approaches and Legal Framework 6 Increasing the Efficiency and Success of Repurposing References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Stem cells offer tremendous promise for advancing health and medicine. Whether being used to replace damaged cells and organs or else by supporting the body's intrinsic repair mechanisms, stem cells hold the potential to treat such debilitating conditions as Parkinson's disease, diabetes, and spinal cord injury. Clinical trials of stem cell treatments are under way in countries around the world, but the evidence base to support the medical use of stem cells remains limited. Despite this paucity of clinical evidence, consumer demand for treatments using stem cells has risen, driven in part by a lack of available treatment options for debilitating diseases as well as direct-to-consumer advertising and public portrayals of stem cell-based treatments. Clinics that offer stem cell therapies for a wide range of diseases and conditions have been established throughout the world, both in newly industrialized countries such as China, India, and Mexico and in developed countries such as the United States and various European nations. Though these therapies are often promoted as being established and effective, they generally have not received stringent regulatory oversight and have not been tested with rigorous trials designed to determine their safety and likely benefits. In the absence of substantiated claims, the potential for harm to patients - as well as to the field of stem cell research in general - may outweigh the potential benefits. To explore these issues, the Institute of Medicine, the National Academy of Sciences, and the International Society for Stem Cell Research held a workshop in November 2013. Stem Cell Therapies summarizes the workshop. Researchers, clinicians, patients, policy makers, and others from North America, Europe, and Asia met to examine the global pattern of treatments and products being offered, the range of patient experiences, and options to maximize the well-being of patients, either by protecting them from treatments that are dangerous or ineffective or by steering them toward treatments that are effective. This report discusses the current environment in which patients are receiving unregulated stem cell offerings, focusing on the treatments being offered and their risks and benefits. The report considers the evidence base for clinical application of stem cell technologies and ways to assure the quality of stem cell offerings. Table of Contents Front Matter 1 Introduction and Themes of the Workshop 2 Stem Cell Therapies - Knowns and Unknowns 3 Patients' Experiences 4 Comparative Regulatory and Legal Frameworks 5 The Roles of Professional Societies 6 Moving Forward References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees Appendix E: Glossary

The process for translating basic science discoveries into clinical applications has historically involved a linear and lengthy progression from initial discovery to preclinical testing, regulatory evaluation and approval, and, finally, use in clinical practice. The low rate of translation from basic science to clinical application has been a source of frustration for many scientists, clinicians, investors, policy makers, and patients who hoped that investments in research would result in improved products and processes for patients. Some feel that the anticipated deliverables from the Human Genome Project have not yet materialized, and although understanding of human health and disease biology has increased, there has not been a concomitant increase in the number of approved drugs for patients over the past 10 years. Improving the Efficiency and Effectiveness of Genomic Science Translation is the summary of a workshop convened by the Institute of Medicine Roundtable on Translating Genomic-Based Research for Health in December 2012 to explore ways to improve the efficiency and effectiveness of the translation of genomic science to clinical practice. The workshop convened academic researchers, industry representatives, policy makers, and patient advocates to explore obstacles to the translation of research findings to clinical practice and to identify opportunities to support improvement of the early stages of the process for translation of genetic discoveries. This report discusses the realignment of academic incentives, the detection of innovative ways to fund translational research, and the generation or identification of alternative models that accurately reflect human biology or disease to provide opportunities to work across sectors to advance the translation of genomic discoveries. Table of Contents Front Matter 1 Introduction 2 Connecting Basic Research and Health Care Needs 3 Moving Basic Science Forward 4 Industry and Venture Capital 5 Role of Advocacy in Facilitating Translation of Basic Scientific Research 6 Strategies for Change References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees

Scientific advances such as the sequencing of the human genome have created great promise for improving human health by providing a greater understanding of disease biology and enabling the development of new drugs, diagnostics, and preventive services. However, the translation of research advances into clinical applications has so far been slower than anticipated. This is due in part to the complexity of the underlying biology as well as the cost and time it takes to develop a product. Pharmaceutical companies are adapting their business models to this new reality for product development by placing increasing emphasis on leveraging alliances, joint development efforts, early-phase research partnerships, and public-private partnerships. These collaborative efforts make it possible to identify new drug targets, enhance the understanding of the underlying basis of disease, discover novel indications for the use of already approved products, and develop biomarkers for disease outcomes or directed drug use. While the potential benefits of collaboration are significant, the fact that the relationships among development partners are often financial means that it is vital to ensure trust by identifying, disclosing, and managing any potential sources of conflict that could create bias in the research being performed together. Conflict of Interest and Medical Innovation is the summary of a workshop convened by the Institute of Medicine Roundtable on Translating Genomic-Based Research for Health in June 2013 to explore the appropriate balance between identifying and managing conflicts of interest and advancing medical innovation. A wide range of stakeholders, including government officials, pharmaceutical company representatives, academic administrators and researchers, health care providers, medical ethicists, patient advocates, and consumers, were invited to present their perspectives and participate in discussions during the workshop. This report focuses on current conflict of interest policies and their effect on medical innovation in an effort to identify best practices and potential solutions for facilitating innovation while still ensuring scientific integrity and public trust. Table of Contents Front Matter 1 Introduction and Overview 2 Conflict of Interest Policies: An Overview 3 Perspectives on Conflict of Interest Policies 4 Public Perceptions of Conflict of Interest 5 Managing Conflict and Facilitating Innovation References Appendix A: Workshop Agenda Appendix B: Speaker Biographical Sketches Appendix C: Statement of Task Appendix D: Registered Attendees