Forum on Drug Discovery, Development, and Translation: 2013 Annual Report (2014)

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Forum Themes and Priorities The Forum addresses key problems in the discovery, development, and translation of drugs, covering the full translational continuum from basic discovery to the approval and adop- tion of new therapies into clinical practice. As an overarching and cross-cutting theme, the Forum fosters innovative efforts to identify and highlight potentially breakthrough ideas and visionary approaches to the “drug development and translational science enterprise of the future.” The Forum has also identified four core components of translational science across this continuum that serve as thematic pillars to frame the Forum’s focus areas and activi- ties: Drug Development Enterprise Infrastructure; Workforce Needs for Drug Discovery, Development, and Translation; Science and Technology for Drug Development; and Drug Regulatory Science and Evaluation. Transformational Innovation in the Drug Development and Translational Science Enterprise Despite exciting scientific advances, the pathway from basic science to new therapeutics faces challenges on many fronts. New paradigms for discovering and developing drugs are being sought to bridge the ever-widening gap between scientific discoveries and transla- tion of those discoveries into life-changing medications. The Forum has explored these issues from many perspectives—emerging technology platforms, regulatory efficiency, intellectual property concerns, the potential for precompetitive collaboration, and innova- tive business models that address the “valley of death.” Evidence suggests that industries are almost always disrupted from the outside by new technologies they were slow to embrace, new business models they wrongly dismissed, or policy changes they thought they could keep at bay. Many argue that the current paradigm for drug discovery and development requires disruptive innovation to break out of a crisis in R&D productivity. February 26 March 3–4 Workshop: Building a National South Africa Workshop: The Framework for the Establishment Emerging Threat of Multidrug- of Regulatory Science for Resistant Tuberculosis April 29–30 Drug Development Forum Meeting #15 2010 February 22-24 May 26–27 Workshop: The Public Health Emergency Medical Countermeasures Russia Workshop: The New Profile Enterprise (in collaboration with the Medical Preparedness Forum) of Drug-Resistant Tuberculosis 

Looking Forward: Forum Activities in 2013 Forum Themes and Priorities The Forum hosts collaborative efforts to stimulate and inform a discussion that could help chart a course through the turbulent forces of disruptive innovation in the drug discovery and development “ecosystem.” Drug Development Enterprise Infrastructure Considerable opportunities remain for enhancement and improvement of the infrastruc- ture that supports the drug development enterprise. That infrastructure, which includes the organizational structure, framework, systems, and resources that facilitate the con- duct of biomedical science for drug development, faces significant chal- lenges. The economic and institutional framework for biomedical discovery and translation is inefficient and insuf- ficiently funded, and the nurturing and collaborative research environ- ment necessary for a robust biomedical research enterprise has eroded. There is increasing recognition of the need for new models and methods for drug development and translational science, and “precompetitive collaborations” and other partnerships, including public–private partnerships, are pro- Forum member Christopher Austin, participating in a Forum member liferating. Through its activities, the discussion August 5–6 April 18–19 Discussion Series: India Workshop: Facing the Conflict of Interest Reality of Multidrug-Resistant (Forum Meeting #16) March 28 Tuberculosis Forum Meeting #18 2011 October 29 March 29–30 Discussion Series: Administrative and Regulatory Workshop: Advancing Regulatory Science for Medical Countermeasure Inefficiencies in Clinical Trials (Forum Meeting #17) Development (in collaboration with the Medical Preparedness Forum) 

Forum offers a venue to discuss and develop best practices and principles for effective collaboration in the drug discovery and development enterprise. Among other projects, Forum collaborative participants have addressed core needs for the U.S. clinical trial infrastructure. Workforce Needs for Drug Discovery, Development, and Translation Biomedical product innovation requires the expertise of many kinds of scientists and investi- gators, working across multiple sectors, including academia, industry, research sponsors, and regulatory agencies. The science of drug discovery and development, and its translation into clinical practice, is cross-cutting and multidisciplinary. Career paths can be opaque or lack incentives such as recognition, career advancement, or financial security. The Forum has con- sidered workforce needs as foundational to the advancement of drug discovery, development, and translation. It has convened workshops examining these issues, including consideration of strategies for developing a discipline of innovative regulatory science through the devel- opment of a robust workforce. The Forum will also host a working group that will address infrastructure, resource, cultural, and training needs for a workforce across the translational science lifecycle. Science and Technology for Drug Development Despite breakthroughs in the basic biomedical sciences over the past several decades, those scientific advances have not translated into new therapeutics. Key gaps remain in our knowl- edge about science, technology, and methods needed to support drug discovery and devel- opment. These gaps represent a wide range of opportunity, including, for example, target identification and validation, biomarker development and validation, methods for predicting July 12 South Africa Workshop Summary November 7–8 Report Release: The Emerging Threat of Workshop: Envisioning a Transformed Multidrug-Resistant Tuberculosis: Global Clinical Trials Enterprise in the United June 28–29 October 4–5 States: Establishing an Agenda for 2020 and Local Challenges and Solutions Forum Meeting #19 Forum Meeting #20 2012 June 27–28 September 20–21 Workshop: Public Engagement and Clinical Workshop: Strengthening a Workforce for Innovative Trials: New Models and Disruptive Technologies Regulatory Science in Therapeutics Development 

Forum Themes and Priorities toxicity, improved statistical methods, and other areas of emerging science. The Forum provides a venue to focus ongoing attention and visibility to these important drug development needs and facilitates exploration of new approaches. Among other top- ics, the Forum has addressed cutting-edge drug safety science, development of safety biomarkers, personalized medicine and clinical trial methodologies. Drug Regulatory Science and Evaluation There has been considerable and increasing attention to the need for robust science to under- lay and serve as the basis for regulatory decision making. “Regulatory science” involves the development and application of scientific tools and methodologies to improve the develop- ment, review, and oversight of new therapeutics. Recent rapid advances in innovative drug development science present opportunity for revolutionary developments of new scientific techniques, therapeutic products, and applications. The Forum has focused considerable attention on the need to develop, support, and enhance a discipline of regulatory science as an essential component of the drug discovery enterprise and translational sciences. The Forum has held workshops that have contributed to the defining and establishment of regula- tory science, including in-depth consideration of issues such as adverse event reporting and postmarketing safety surveillance, infrastructure and workforce needs, and collaborative approaches to support and sustain regulatory science and drug development. The Forum has also convened workshops to help inform aspects of drug regulatory evaluation, including dis- cussion of principles and approaches to advance international regulatory harmonization, and methods and strategies for characterizing and communicating uncertainty in the assessment of benefits and risks. October 4-5 June 4-5 Workshop: Sharing Clinical Workshop: Maximizing the Goals of Research Data (in collaboration the Cures Acceleration Network to with the Neuroscience Forum, March 13–14 Accelerate the Development of New June 5 National Cancer Policy Forum, Forum Meeting #21 Drugs and Diagnostics Forum Meeting #22 and Genomics Roundtable) November 15 July 31–August 1 Russia Workshop Summary Report Release: The New Profile Workshop: Developing and Strengthening the Global Supply Chain of Drug-Resistant Tuberculosis: A Global and Local Perspective for Second-Line Drugs for Multidrug-Resistant Tuberculosis 

Reports Released in 2013 Sharing Clinical Research International Regulatory Data: Workshop Harmonization Amid Summary Globalization of Drug Released: March 29, 2013 Development: Workshop Summary Pharmaceutical compa- Released: August 1, 2013 nies, academic researchers, and government agencies The past several decades compile large quantities of have been a time of rapid clinical research data, which, globalization in the develop- if shared more widely both ment, manufacture, market- within and across sectors, ing, and distribution of med- could improve public health, enhance patient ical products and technologies. Demand has been safety, and spur drug development. Despite increasing for globally harmonized, science-based several barriers to data sharing, there is increas- standards to improve the efficiency and clarity ing acknowledgment among researchers of the of the drug development and evaluation process importance and potential benefits to sharing clini- and, ultimately, to promote and enhance product cal research data at various stages of the research, quality and the public health. The IOM’s Forum discovery, and development pipeline. The IOM’s on Drug Discovery, Development, and Translation Forum on Drug Discovery, Development, and hosted a workshop to help identify principles, Translation; Forum on Neuroscience and Nervous potential approaches, and strategies to advance System Disorders; National Cancer Policy Forum; the development or evolution of more harmonized and Roundtable on Translating Genomic-Based regulatory standards for drug development. Research for Health hosted a workshop to explore the benefits of sharing clinical research data, the barriers to such sharing, and strategies to address those barriers to facilitate the development of safe, effective therapeutics and diagnostics. November 26–27 January 15 Workshop: Large Simple Trials and Workshop Summary Report January 16–18 February 13–14 Knowledge Generation in a Learning Release: Developing and China Workshop: The Global Workshop: International Regulatory Health System (in collaboration with Strengthening the Global Supply Crisis of Drug-Resistant Harmonization Amid Globalization the Roundtable on Value & Science- Chain for Second-Line Drugs for Tuberculosis and Leadership of Biomedical Research & Medical Driven Health Care) Multidrug-Resistant Tuberculosis of the BRICS Countries Product Development 2013 December 19 October 23–24 Action Collaborative Meeting #1: Developing a National February 12 June 3 Forum Meeting #23 Accreditation System to Improve Clinical Trial Performance Forum Meeting #24 Forum Meeting #25 

Forum Themes and Priorities Large Simple Trials and The Global Crisis of Drug- Knowledge Generation Resistant Tuberculosis in a Learning Health and Leadership of System: Workshop China and the BRICS: Summary Challenges and Released: September 24, 2013 Opportunities: Summary of a Joint Workshop Despite a robust clinical Released: December 19, 2013 research enterprise, a gap exists between the evidence Although antibiotics to needed to support care deci- treat TB were developed in sions and the evidence avail- the 1950s and are effec- able. Streamlined approaches to clinical research tive against a majority of TB cases, resistance provide options for progress on these challenges. to these antibiotics has emerged over the years, Large simple trials (LSTs), for example, generally resulting in the growing spread of drug-resis- have simple randomization, broad eligibility criteria, tant TB. Since 2008, the IOM’s Forum on Drug and enough participants to distinguish small to Discovery, Development, and Translation has moderate effects; focus on outcomes important hosted or co-hosted six domestic and interna- to patient care; and use simplified approaches to tional workshops to address the global crisis of data collection. Significant opportunities, includ- drug-resistant TB. The Forum, along with the ing the widespread adoption of electronic health Institute of Microbiology of the Chinese Academy records, could accelerate the potential for the use of Sciences, held a workshop to address the cur- of LSTs to efficiently generate practical evidence rent status of drug-resistant TB globally and in for medical decision making and product devel- China as well as identify opportunities for Brazil, opment. To address these opportunities, as well Russia, India, China, and South Africa (the BRICS as challenges, the IOM’s Roundtable on Value & countries) to lead efforts in TB control. Science-Driven Health Care and the Forum on Drug Discovery, Development, and Translation co-hosted a workshop to highlight the pros and cons of the design characteristics of LSTs, explore the utility of LSTs on the basis of case studies of past successes, and consider the challenges and opportunities for accelerating the use of LSTs in the context of a U.S. clinical trials enterprise. March 11 February 12 Action Collaborative Workshop: Characterizing and Meeting #3: Developing August 21 Communicating Uncertainty in the a National Accreditation Action Collaborative Meeting #2: Assessment of Benefits and Risks of System to Improve Clinical Developing a National Accreditation System Pharmaceutical Products (Day 1) Trial Performance to Improve Clinical Trial Performance 2014 October 28–29 March 3–4 Forum Meeting #26 Forum Meeting #27