Forum on Drug Discovery, Development, and Translation: 2015 Annual Report (2016)

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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 adoption 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 activities: (1) Innovation and the Drug Development Enterprise; (2) Science Across the Drug Development Lifecycle (Basic, Translational, and Regulatory Sciences); (3) Clinical Trials and Clinical Product Development; and (4) Infrastructure and Workforce for Drug Discovery, Development, and Translation. Innovation and the Drug Development 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 translation of those discoveries into life-changing medications. There is also 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 proliferating. The Forum offers a venue to discuss effective collaboration in the drug discovery and develop- ment enterprise and also hosts discussions that could help chart a course through the turbulent forces of disruptive innovation in the drug discovery and development “ecosystem.” January 15 December 19 Workshop Summary Report February 13–14 Action Collaborative Meeting #1: Release: Developing and Workshop: International Regulatory Developing a National Accreditation Strengthening the Global Supply Harmonization Amid Globalization System to Improve Clinical Trial Chain for Second-Line Drugs for February 12 of Biomedical Research and Medical Performance Multidrug-Resistant Tuberculosis Forum Meeting #24 Product Development 2013 January 16–18 June 3 China Workshop: The Global Crisis of Drug- Forum Meeting #25 Resistant Tuberculosis and Leadership of the BRICS Countries 

Substance—What We Aim For Forum Themes and Priorities Innovation & the Enterprise Translating Discoveries Thematic Priorities Science Across the Lifecycle into Medicines SUBSTANCE—What We Aim For The Forum fosters dialogue and Clinical Trials & Product Development collaboration to illuminate and act on potentially breakthrough ideas and visionary approaches to the biomedical innovation Infrastructure & Workforce system of the future. s ve y ecti ge s renc e rsp lly allen s pa n tP ba l Ch n tie lo ica g Tra Pa in gG th tin tin g g ag in gE lita ora En s Fa ci orp d res Inc Ad Guiding Principles Science Across the Drug Development Lifecycle Key gaps remain in our knowledge about science, technology, and methods needed to sup- Innovation & the Enterprise port drug discovery and development. Recent rapid Academia in innovative drug development • advances • Federal research & • Biomedical research foundations Partners science present opportunity for revolutionary developments of new scientificadvocacy • Disease techniques, Priorities Science Across the Lifecycle regulatory agencies • Large pharmaceutical organizations therapeutic products, and applications. The Forum provides a venue to• Patients, ongoing & Clinical Trials & Product Development companies focus consumers, attention • Small biotechnology & research participants and visibility to these important drug development needs and facilitates exploration of new Infrastructure & Workforce emerging companies approaches across the drug development lifecycle. The Forum has held workshops that have contributed to the defining and establishment of regulatory science and have helped inform aspects of drug regulatory on Drug Discovery, IOM Forum evaluation. PROCESS—How We Do It Development, and Translation Activities • Workshops Board on Health Sciences Policy • Working groups • Action collaboratives The Forum provides a unique platform for dialogue and collaboration among May 12 thought leaders and stakeholders from diverse sectors. The Forum convenes February 12 several times each year to identify key problems and strategies; hosts public Workshop: Characterizing and August 21 Workshop: Characterizing and workshops and produces reports; and fosters collaborations among its Communicating Uncertainty in the Action Collaborative Meeting #2: members and constituencies. Communicating Uncertainty in the Assessment of Benefits and Developing a National Accreditation System to Assessment of Benefits and Risks of Risks of Pharmaceutical Products Improve Clinical Trial Performance Strategies Pharmaceutical Products (Day 1) (Day 2) • Facilitating attention, visibility, and continuous discussion • Workshop summaries 2014 • Defining the scope of the field Products • Workshops in brief • Educating and elevating understanding of issues • Discussion papers & October 28–29 expanding areas of agreement • Clarifying and March 3–4 March 11 commentaries • Exploring new approaches to gridlocked areas Forum Meeting #26 Forum Meeting #27 Action Collaborative Meeting #3: • Fostering collaboration *Spinoff consensus studies • Setting the stage for policy action Developing a National Accreditation System to Improve Clinical Trial Performance 

Clinical Trials and Clinical Product Development Clinical research is the critical link between bench and bedside in developing new therapeutics. Significant infrastructural, cultural, and regulatory impediments challenge efforts to integrate clinical trials into the health care delivery system. Collaborative, cross-sector approaches can help articulate and address these key challenges and foster systemic responses. The Forum has convened a multiyear initiative to examine the state of clinical trials in the United States, identify areas of strength and weak- ness in our current clinical trial enterprise, and consider transformative strategies for enhancing the ways in which clinical trials are organized and conducted. In addition to sponsoring multiple symposia and workshops, under this initiative, the Forum is fostering innovative, collaborative efforts to facilitate needed change in areas such as improvement of clinical trial site performance. Infrastructure and Workforce for Drug Discovery, Development, and Translation Considerable opportunities remain for enhancement and improvement of the infrastructure that supports the drug development enterprise. That infrastructure, which includes the organizational structure, framework, systems, and resources that facilitate the conduct of biomedical science for drug development, faces significant challenges. 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 development of a robust work- force. The Forum will also host an initiative that will address needs for a workforce across the transla- tional science lifecycle. January 20–21 March 26–27 Workshop: Financial Incentives to Workshop: Enabling Rapid Medical June 10–11 Support Unmet Medical Needs for Countermeasure Response to Forum Meeting #28 Nervous System Disorders Emerging Threats 2015 October 7–8 March 17–18 June 23–24 Forum Meeting #29 Forum Meeting #30 Forum Meeting #31 

s SUBSTANCE ve y ecti ge s re nc e rsp lly allen s pa n tP ba l Ch n tie lo ica g Tra Pa in gG th tin ting g ag in gE lita ora En s Fa ci orp d res Forum Themes and Priorities Inc Ad Guiding Principles Process—How We Do It Innovation & the Enterprise • Academia • Biomedical research • Federal research & foundations Partners Priorities Science Across the Lifecycle regulatory agencies • Disease advocacy • Large pharmaceutical organizations Clinical Trials & Product Development companies • Patients, consumers, & • Small biotechnology & research participants emerging companies Infrastructure & Workforce IOM Forum on Drug Discovery, PROCESS—How We Do It Development, and Translation Activities • Workshops Board on Health Sciences Policy • Working groups • Action collaboratives The Forum provides a unique platform for dialogue and collaboration among thought leaders and stakeholders from diverse sectors. The Forum convenes several times each year to identify key problems and strategies; hosts public workshops and produces reports; and fosters collaborations among its members and constituencies. Strategies • Facilitating attention, visibility, and continuous discussion • Workshop summaries • Defining the scope of the field Products • Workshops in brief • Educating and elevating understanding of issues • Discussion papers & • Clarifying and expanding areas of agreement commentaries • Exploring new approaches to gridlocked areas • Fostering collaboration *Spinoff consensus studies • Setting the stage for policy action October 20 Workshop: Priorities to Advance the Field of Regulatory Science 2016 October 21 Forum Meeting #32 

Reports Released in 2015 Financial Incentives to Encourage Development of Therapies That Address Unmet Medical Needs for Nervous System Disorders— Workshop Summary (collaboration with the Forum on Neuroscience and Nervous System Disorders) Released: July 6, 2015 The Forum on Neuroscience and Nervous System Disorders, in collaboration with the Forum on Drug Discovery, Development, and Translation, convened a workshop on January 20 and 21, 2015, to explore policy changes that might increase private- sector investment in research and development innovation that fills unmet medical needs for central nervous system (CNS) disorders. Workshop participants strat- egized about how to incentivize companies to fortify their CNS drug development programs, shrinking obstacles that currently deter ventures. Representatives from academia, government agencies, patient groups, and industry gathered to share information and viewpoints and to brainstorm about budget-neutral policy changes that could help widen the pipeline toward drugs that address unmet needs for CNS disorders. This report summarizes the presentations and discussions of the workshop. Rapid Medical Countermeasure Response to Infectious Diseases: Enabling Sustainable Capabilities Through Ongoing Public- and Private-Sector Partnerships—Workshop Summary (collaboration with the Forum on Medical and Public Health Preparedness for Catastrophic Events) Released: October 12, 2015 Emerging infectious disease threats that may not have available treatments or vaccines can directly affect the security of the world’s health because these diseases also know no boundaries and will easily cross borders. Sustaining public and private investment in the development of MCMs before an emerging infectious disease becomes a public health emergency in the United States has been extremely challenging. Interest and momentum peak during a crisis and wane between events, and there is little interest in disease threats outside the United States until they impact people stateside. On March 26 and 27, 2015, the Forum on Medical and Public Health Preparedness for Catastrophic Events, in collaboration with the Forum on Drug Discovery, Development, and Translation, con- vened a workshop in Washington, DC, to discuss how to achieve rapid and nimble MCM capability for new and emerging threats. Public- and private-sector stakeholders examined recent efforts to prepare for and respond to outbreaks of Ebola Virus Disease, pandemic influenza, and coronaviruses from policy, budget, and operational standpoints. Participants discussed the need for rapid access to MCM to ensure national security and considered strategies and business models that could enhance stakeholder interest and investment in sustainable response capabilities. This report summarizes the presentations and discussions from this workshop. 

Forum Themes and Priorities FDA and the Media: Lessons from Tysabri about Communicating Uncertainty—Discussion Paper (By Lisa Schwartz and Steven Woloshin) Released: September 11, 2015 In light of a workshop held by the Forum on Drug Discovery, Development, and Translation in February and May 2014, “Characterizing and Communicating Uncertainty in the Assessment of Benefits and Risks of Pharmaceutical Products,” which explored systematic and structured approaches to the characterization and communication of uncertainty, a discussion paper was developed by Lisa Schwartz and Steven Woloshin to further examine a case study presented at the workshop on the multiple sclerosis drug Tysabri. Despite a rigorous approval process, there is always uncertainty about newly approved drugs: Will the benefits observed in initial approval studies hold up over time? Will side effects emerge? Uncertainty is amplified when drugs receive accelerated approval based on preliminary evidence or surrogate outcomes. Communicating uncertainty about new drugs is an important challenge facing FDA but opportunities exist to create realistic expectations and highlight the inherent uncertainty associated with accelerated approval. In this paper we examine how uncertainty was communicated by major media and FDA in the case of Tysabri, a multiple sclerosis drug, in order to draw lessons on how to improve the communication of uncertainty about new drugs.