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Complete Research Plan Illustration of the human digestive system: Image reprinted from “Your Digestive System and How It Works.” U.S. Department of Health and Human Services. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NIH Publication No. 08-2681, April 2008. Inset images: Top image and third image down—Richard Nowitz for NIDDK; second image down— Used with permission of the NIDDK Weight-Control Information Network; Bottom image—Randy Faris/Corbis. Opportunities and Challenges in Digestive Diseases Research: Recommendations of the National Commission on Digestive Diseases U.S. Department of Health and Human Services National Institutes of Health NIH Publication No. 08-6514 March 2009 TABLE OF CONTENTS EXECUTIVE SUMMARY 1 INTRODUCTION 13 TOPIC-SPECIFIC CHAPTERS Research on the Basic Biology of the Digestive System 25 Functional Gastrointestinal Disorders and Motility Disorders 51 Infections of the Gastrointestinal Tract 69 Cancers of the Digestive System 81 Inflammatory Bowel Diseases 95 Intestinal Failure and Regeneration, Nutritional Disorders and Support, Surgically Modified Gut, and Transplantation 107 Diseases of the Oropharynx and Esophagus 117 Diseases of the Stomach and Small Intestine 129 Diseases of the Colon and Rectum 145 Diseases of the Pancreas 159 Diseases of the Liver and Biliary System 169 Bioengineering, Biotechnology, and Imaging 187 CONCLUSION: COMMON TheMes AND STeps FOR IMPLEMENTATION 195 APPENDICES Appendix 1: Summary List of Recommended Research Goals and Common Themes 207 Appendix 2: Rosters of the National Commission on Digestive Diseases and Its 214 Working Groups Appendix 3: References for Statistical and Epidemiologic Data 220 Appendix 4: Abbreviations and Acronyms 221 INDEX 226 ACKNOWLEDGEMENTS 238 Opportunities and Challenges in Digestive Diseases Research: Recommendations of the National Commission on Digestive Diseases Executive Summary BURDEN OF DIGesTIVE DIseAses IN Health and Human Services, and Education, The UNITED STATes and Related Agencies. The Commission was tasked with reviewing the state of the science The digestive system can be affected by a in digestive diseases research and developing a wide diversity of acute and chronic diseases or 10-year plan for digestive diseases research that conditions that, collectively, place a substantial is consistent with the NIH mission and aimed burden on the U.S. healthcare system. At least at improving the health of the Nation through 60-70 million Americans are affected each year research. The Commission was comprised of by digestive diseases at a cost that exceeds $100 16 members, including academic researchers, billion in direct medical expenses. Annually, medical professionals, and patient advocates, about 10 percent of hospitalizations and 15 who were appointed by the NIH Director after percent of in-patient hospital procedures are a public nomination process. In addition, 22 attributed to the treatment of digestive diseases. representatives of NIH Institutes and Centers, An additional 105 million visits to doctors’ offices as well as other Federal agencies involved in related to digestive diseases occur each year. digestive diseases research, served as ex officio These diseases are associated with significant members of the Commission. Stephen P. James, mortality, morbidity, and loss of quality of life, M.D., Director of the Division of Digestive and they frequently impact patients’ ability Diseases and Nutrition of the National Institute to work or engage in everyday activities. More of Diabetes and Digestive and Kidney Diseases than $44 billion in indirect costs from disability (NIDDK), NIH, chaired the Commission. Working and mortality are associated with digestive groups composed of experts in diverse areas of diseases each year. Digestive diseases in digestive diseases research were formed to aid general can affect individuals of any age, race the Commission in identifying major scientific or ethnicity, gender, or socioeconomic status, advances and formulating high-priority although some diseases disproportionately affect research goals. certain populations. All of these factors provide opportunities and challenges for the National This report, entitled Opportunities and Institutes of Health (NIH) as it develops and Challenges in Digestive Diseases Research: supports research programs aimed, ultimately, Recommendations of the National Commission at reducing the significant public health burden on Digestive Diseases, presents the Commission’s of digestive diseases. long-range plan for digestive diseases research. The Commission offers recommendations in many broad areas of scientific inquiry of NATIONAL COMMIssION ON relevance to digestive diseases, including DIGesTIVE DISEASES fundamental biology of the digestive system, as well as disease-oriented research topics, such as: The National Commission on Digestive Diseases epidemiology; environmental factors; genetics; was chartered by Elias A. Zerhouni, M.D., mechanisms; diagnosis; causes; treatments; Director of the NIH, on July 26, 2005, in response behavioral, social, and psychological factors; to congressional report language accompanying health disparities; prevention; and cures. the FY 2005 appropriations bills in the House The Commission developed specific research and Senate for the Departments of Labor, goals in each of the following 12 scientific topic Executive Summary areas: research on the basic biology of the laboratories. To aid in the development of the digestive system; functional gastrointestinal recommendations in this research plan, lists of disorders and motility disorders; infections grants and other awards comprising the NIH of the gastrointestinal tract; cancers of the portfolio for digestive diseases were provided to digestive system; inflammatory bowel diseases; members of the Commission and to each intestinal failure and regeneration, nutritional working group. disorders and support, surgically modified gut, and transplantation; diseases of the oropharynx In addition to the direct funding of digestive and esophagus; diseases of the stomach and diseases research, the NIH coordinates small intestine; diseases of the colon and research programs within the agency and rectum; diseases of the pancreas; diseases of the with other Federal agencies with an interest liver and biliary system; and bioengineering, in digestive diseases through the Digestive biotechnology, and imaging. In addition, the Diseases Interagency Coordinating Committee Commission identified a set of high-priority, (DDICC). The DDICC brings together common themes for which coordinated research representatives from multiple NIH Institutes planning efforts would accelerate progress and Centers that fund digestive diseases across the digestive disease research field by research, as well as from other agencies, fostering the development and utilization of including the Agency for Healthcare Research state-of-the-science technologies, tools, and and Quality, the Food and Drug Administration, resources to increase fundamental knowledge, the Department of Defense, the Centers improve translation of research advances into for Disease Control and Prevention, the applications for human diseases, and ensure a Department of Veterans Affairs, the Health robust pipeline of talented researchers focused on Resources and Services Administration, the challenges of digestive diseases. Collectively, and the Department of Agriculture. The the Commission’s recommendations will provide NIH also promotes communication and scientific direction for theNIH and all parties collaboration within the digestive diseases engaged in digestive diseases research as they research community through the support of address opportunities and priorities in digestive conferences and workshops on relevant topics. diseases research over the next decade. Finally, the NIDDK-led National Digestive Diseases Information Clearinghouse provides informational materials and other resources NIH SUppORT FOR DIGesTIVE with the goal of increasing knowledge and DIseAses ReseARCH understanding of digestive diseases within the healthcare community and the general public. NIH Funding and Coordination of Digestive Diseases Research Advances in Digestive Diseases Research Twenty NIH Institutes, Centers, and Offices Digestive diseases research supported by the support digestive diseases research on a variety NIH and other public and private organizations of topics with a total expenditure of more than has resulted in many breakthrough discoveries $1.2 billion in FY 2007. The NIH research that have advanced our understanding of portfolio encompasses basic, translational, digestive system biology and function, as well as and clinical research and training on the improved the health and quality of life of many digestive system for normal states and disease people with digestive diseases. conditions and supports extramural researchers and institutions, as well as intramural Opportunities and Challenges in Digestive Diseases Research: Recommendations of the National Commission on Digestive Diseases Examples of research advances include: ß Advances in surgical techniques to lengthen the intestine have enhanced the management ß Molecular signaling pathways have been of infants and children with refractory short uncovered in intestinal crypt progenitor cells bowel syndrome. Intestinal lengthening that are responsible for continual regeneration procedures such as serial transverse of the intestinal lining. Understanding these enteroplasty
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