Forum on Drug Discovery, Development, and Translation: 2016 Annual Report (2017)

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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.” February 12 May 12 August 21 Workshop: Characterizing and Workshop: Characterizing and Action Collaborative Meeting #2: Communicating Uncertainty in the Communicating Uncertainty in the Developing a National Accreditation System Assessment of Benefits and Risks of Assessment of Benefits and Risks of to Improve Clinical Trial Performance Pharmaceutical Products (Day 1) Pharmaceutical Products (Day 2) 2014 October 28–29 March 3–4 March 11 Forum Meeting #26 Forum Meeting #27 Action Collaborative Meeting #3: Developing a National Accreditation System to Improve Clinical Trial Performance 

Forum Themes and Priorities Science Across the Drug Development Lifecycle Key gaps remain in our knowledge about science, technology, and methods needed to sup- port drug discovery and development. Recent rapid advances in innovative drug development science present opportunity for revolutionary developments of new scientific techniques, therapeutic products, and applications. The Forum provides a venue to focus ongoing attention and visibility to these important drug development needs and facilitates exploration of new 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 evaluation. 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, iden- tify areas of strength and weakness in our current clinical trial enterprise, and consider trans- formative 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 improve- ment of clinical trial site performance. January 20–21 March 26–27 Workshop: Financial Workshop: Rapid Medical Countermeasure Incentives to Support Response to Infectious Diseases: Enabling June 10–11 Unmet Medical Needs for Sustainable Capabilities Through Ongoing Forum Meeting #28 Nervous System Disorders Public- and Private-Sector Partnerships 2015 October 7–8 March 17–18 Forum Meeting #29 Forum Meeting #30 

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. October 20 March 22 Workshop: Advancing the Discipline of February 3 Workshop: Deriving Regulatory Science for Medical Product Action Collaborative Drug Discovery Value Development: An Update on Progress Meeting #1: IT/Technical from Large-Scale and a Forward-Looking Agenda Infrastructure for Sharing Genetic Bioresources 2016 June 23–24 October 21 March 23 Forum Meeting #31 Forum Meeting #32 Forum Meeting #33 

Forum Themes and Priorities OVERVIEW The Forum fosters dialogue and collaboration to illuminate and act on potentially breakthrough ideas and visionary approaches to the biomedical innovation system of the future. THEMATIC PRIORITIES ACTIVITIES Innovation & the Enterprise Workshops Science Across the Lifecycle Action Collaboratives Clinical Trials & Product Forum Meetings Development Infrastructure & Workforce ACTIVITIES THEMATIC PRODUCTS PRIORITIES Workshop Proceedings PARTNERS Discussion Papers & Commentaries PRODUCTS Peer-reviewed Journal Articles STR ATEGIES STRATEGIES Facilitate visibility & PARTNERS continuous discussion Foster collaboration Biopharmaceutical Companies Explore innovative & transformative approaches Academic Researchers Educate & elevate understanding of issues Patient & Disease Advocacy Groups Clarify & expand areas of agreement Foundations, Associations, & Consortia Set the stage for policy action Federal Research & Regulatory Agencies July 14 October 19 December 12–13 Action Collaborative Meeting Workshop: Real-World Workshop: The Drug #1: Data Sharing Principles for Evidence Generation and Development Paradigm Nonprofit Clinical Trial Funders Evaluation of Therapeutics in Oncology July 19–20 October 18 Forum Meeting #34 Forum Meeting #35 

Publications Released in 2016 Advancing the Discipline of Regulatory Science for Medical Product Development: An Update on Progress and a Forward-Looking Agenda: Workshop Summary Released: April 20, 2016 The field of endeavors known as “regulatory science” has grown out of the need to link and integrate knowledge within and among basic science research, clinical medicine, and other specific scientific disciplines whose focus, aggregation, and ultimate implementation could inform biomedical product development and regula- tory decision making. On October 20–21, 2015, the Forum held a public workshop to facilitate dialogue among stakeholders about the current state and scope of regulatory sciences, opportunities to address barriers to the discipline’s success, and avenues for fostering collaboration across sectors. The workshop, co-sponsored by the Burroughs Wellcome Fund, also held panels that explored key needs for strength- ening the discipline of regulatory science, including considering what are the core components of regulatory science infrastructure to foster innovation in medical product development. To focus the workshop discussions, the planning committee adopted the theme of innovation in regulatory science through integration of infor- mation. This publication is a summary of the workshop. Deriving Drug Discovery Value from Large-Scale Genetic Bioresources: Proceedings of a Workshop (collaboration with the Roundtable on Genomics and Precision Health) Released: September 9, 2016 Utilizing genetic and phenotypic information collected and stored in bioresources has the potential to enable more efficient drug discovery and precision medicine. Within this context, the Roundtable on Genomics and Precision Health (previously called the Roundtable on Translating Genomic-Based Research for Health) and the Forum hosted a workshop on March 22, 2016, titled Deriving Drug Discovery Value from Large- Scale Genetic Bioresources. The workshop focused on new research and ideas in three primary areas: large-scale genetic cohort studies, the use of genomic data in drug discovery activities, and novel business models that support the development and use of genetic data from bioresources for drug discovery. Throughout the workshop there was robust discussion of short-term and long-term opportunities for collaboration, fostering translational research, and accelerating progress in the area of genomic-enabled drug discovery. This publication summarizes the presentations and discussions held at the workshop. 

Related NAM Perspectives Disruptive Innovation and Transformation of the Drug Discovery and Development Enterprise (By Bernard H. Munos and John J. Orloff) July 20, 2016 Declining or stagnant R&D productivity has led many observers to argue that the current paradigm for drug discovery and development requires disruptive innova- tion to break out of this crisis by identifying and rapidly bringing new discoveries to market. Despite increased investment, the number of new therapies and improve- ments to human health as measured by the growth in life expectancy have remained relatively constant over the past 50 to 60 years. Sustained competition from generic manufacturers and overall negative public reactions to costly prescription drugs only add to the complex challenges facing large pharmaceutical companies today. Critics cite the need for the industry to produce more and better products and affordably innovate if it hopes to sur- vive. To further assess the challenges and reveal potential opportunities, participants of an Action Collaborative convened under the auspices of the Forum engaged thought leaders and key stakeholders within the biomedi- cal research ecosystem, soliciting diverse viewpoints to gain insight into their unique perspectives on the state of the pharmaceutical and biomedical research industries, what could or should change, how those changes might occur, and, generally, what the future might hold. Real-World Evidence to Guide the Approval and Use of New Treatments (By Steven Galson and Gregory Simon) October 18, 2016 Research regarding new treatments (drugs, biological products, and high-risk devices) often begins with a broad assessment of disease epidemiology, disease burden, and the shortcomings of existing treatments. That research may draw from diverse data sources, including real-world data generated by health system opera- tions. The clinical research phase of treatment development typically follows a well-established pathway from initial evaluation of safety to preliminary evaluation of therapeutic efficacy to pivotal trials intended to support regulatory approval for marketing. This trajectory is consistent with the responsibility of FDA for ensuring the safety and efficacy of drugs, biological products, and medical devices at the time of approval. However, the traditional process for evaluating new therapeutics does not produce the evidence that patients, clinicians, and payers need for real-world decisions. This Discussion Paper reviews the current state of real-world evidence generation, how stakeholders can best enable developments for producing high-quality, real-world evidence, case studies highlighting promising practices for the generation and utilization of real-world evidence, and a vision for the desired future state of real-world evidence generation for medical product development. Perspectives, published by the National Academy of Medicine (NAM), are individually authored by Roundtable and Forum members and outside experts in health and health care. The views expressed in these papers are those of the authors and not necessarily of the authors’ organizations or of the NAM. Perspectives are intended to help inform and stimulate discus- sion. They have not been subjected to the review procedures of and are not reports of the NAM or the National Academies of Sciences, Engineering, and Medicine.