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

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Reflecting Back Forum Activities in 2015 Forum Meetings The Forum membership met three times in 2015. Discussions at these meetings focused on diverse topics relating to the Forum’s priorities, including mapping the biomedical innovation ecosystem; overcoming challenges in biomedical innova- tion; strengthening the regulatory science ecosystem; communicating uncertainty in the assessment of benefits and risks; strategies for responsible sharing of clini- cal trial data; and policy updates relevant to drug discovery, development, and translation. In addition, the Forum convened public workshops and collaborative activities, described below. Workshops: Financial Incentives to Support Unmet Medical Needs for Nervous System Disorders—Workshop (January 2015) The global burden of nervous system disorders is projected to significantly increase over time. Although there have been recent international initiatives to better understand the human brain in order to develop new therapeutics, several large pharmaceutical companies have decreased investment or even withdrawn from their neuroscience research programs. The perceived high risk and low probability of success has made the neuroscience sector less attractive than other therapeutic areas for research and development (R&D), despite the large market potential. As a result, patients are often left with few, if any, options for treat- ment; thus, there is a need to consider policy options to increase private-sector investment in R&D for nervous system disorders. The Forum collaborated with the Forum on Neuroscience and Nervous System Disorders to convene this public workshop, which explored opportunities to foster private-sector innovation by supporting new investments directed toward the development of novel therapeu- tics to meet unmet needs for nervous system disorders. FORUM ACTIVITIES TIMELINE 2000–2004 2005 Clinical Research Roundtable, March 23–24 predecessor to the Forum Forum Meeting #1 

Reflecting Back: Forum Activities in 2015 (Left to right) Guest speaker Sally Rockey (NIH) with Lana Skirboll, Lynn Hudson, Andy Dahlem, Jack Keene, and Richard A. Moscicki at the Forum’s March 2015 meeting. Enabling Rapid Response and Sustained Capability with Medical Countermeasures to Mitigate Risk of Emerging Infectious Diseases— Workshop (March 2015) Global attention to recent large-scale outbreaks and their public health and medi- cal consequences has made clear that the current medical countermeasure (MCM) response system is not well adapted to rapidly respond to a large number of diverse threats through adequate development and production of vaccines, thera- peutics, diagnostic tools, and other non-pharmaceutical interventions. The Forum, in collaboration with the Forum on Medical and Public Health Preparedness for Catastrophic Events, co-convened a public workshop that examined how to better enable rapid and nimble private-sector engagement in the discovery, develop- ment, and translation of MCMs. This workshop explored what policies, guidance, and resources exist to guide decision making within the government and how the business and operational models employed by the private sector are affected by June 29–30 September 8–9 November 3–4 Forum Meeting #2 Forum Meeting #3 Workshop: Adverse Drug Event Reporting: The Roles of Consumers and Health-Care Professionals 

policies and guidance and available resources set forth by the U.S. government. The dis- cussions at this workshop were designed to identify and discuss what is needed to ensure that the private sector can respond in a rapid, nimble manner to ensure the availability of MCMs. The workshop also explored advances made by the Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) to improve MCM development and translation. Priorities to Advance the Field of Regulatory Science: An Update on Progress and a Forward-Looking Agenda—Workshop (October 2015) The Food and Drug Administration (FDA) today has a broad range of responsibilities, regulat- ing approximately 25 percent of the U.S. economy. The agency has assumed an increasingly complex and international reach. In the face of rapid advances in medicine and biomedical science, FDA faces pressure to keep pace with new technologies and develop the expertise necessary to regulate those technologies as they emerge. The Forum, in collaboration with the Burroughs Wellcome Fund, convened a public workshop that discussed issues related to the development of the discipline of innovative regulatory science, focusing on infrastruc- ture, systems, and workforce. The workshop featured invited presentations and discussions that explored current regulatory science priorities and strategies in federal, academic, and private-sector settings; considered the current state of regulatory science as a discipline; explored the core components of a robust discipline of innovative regulatory science; con- sidered gaps and key opportunities to address needs to support the discipline of innovative regulatory science; and examined needs and barriers to collaboration among, across, and within the public and private sectors. June 13 Workshop: Addressing March 28–29 the Barriers to Pediatric October 24–25 Forum Meeting #4 Drug Development Forum Meeting #6 2006 May 30–31 June 27–28 Workshop: Understanding the Forum Meeting #5 Benefits and Risks of Pharmaceuticals 

Reflecting Back: Forum Activities in 2015 Action Collaboratives: Mapping and Connecting the Biomedical Innovation Ecosystem— Action Collaborative The biomedical innovation ecosystem is a dynamic network of activity. Standardizing and bringing clarity to this complex process could help to set a common vocabulary and allow more fluid dialogue among ecosystem partici- pants to encourage further innovation. It could also facilitate ongoing discussion Priorities to Advance the Field of Regulatory Science panelists (left to right) Stephen Ostroff, Alastair Wood, Martin Philbert, John Wagner, Brian Strom, and Darrell Abernethy. April 23–24 Workshop: Emerging Safety Science, October 15–16 FDA (Forum Meeting #7) Forum Meeting #8 2007 March 12 September 14 Symposium: The Future of Drug Discussion Series: From Patient Safety: Challenges for FDA Needs to New Drug Therapies 

(Left to right) FDA Commissioner Robert Califf, Forum Director Anne Claiborne, and Forum Co-Chairs Russ Altman and Steven Galson at the June 2015 meeting of the Forum. to help frame, map, and synergize activities across the biomedical innovation ecosystem. Defining key terms, such as translational science and regulatory science, and locating complex activities within the biomedical innovation ecosystem landscape might help to articulate problem areas and provide opportunities to learn from local environments where the system is efficient and well-integrated with other areas. The goal of this col- laborative is to enable discussion and to identify rate-limiting steps in order to facilitate process improvement efforts. In 2015, collaborative participants adapted two process maps for development of small molecules and biologics to identify inputs, bottlenecks, and needs. They also convened several meetings to discuss bottlenecks with key stake- holders and thought leaders, including Forum members. Collaborative participants are now in the process of authoring a Perspectives paper summarizing and developing a June 23 Workshop: Breakthrough February 20–21 Business Models: Drug Discussion Series: Comparative Development for Rare Effectiveness (Forum Meeting #9) and Neglected Diseases 2008 November 30 April 21 June 23–24 Discussion Series: A Conversation Discussion Series: Science at FDA: Symposium: Diseases and Individualized with Tony Fauci Challenges and Opportunities Therapies (Forum Meeting #10) 

Reflecting Back: Forum Activities in 2015 plan for how these process maps could be used to help inform Forum priority set- ting. In 2016, a priority-setting tool developed from the Mapping initiative will be piloted and improved, and Forum meetings will provide opportunities for infor- mation sharing about key bottlenecks and science policy priorities in the biomedi- cal innovation ecosystem. Disruptive Innovation and the Transformation of the Drug Development and Translational Science Enterprise—Action Collaborative Many argue that the current paradigm for drug discovery and development requires disruptive innovation to break out of a crisis in R&D productivity. 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. The pharma- ceutical industry offers many opportunities for disruption in each of these areas. The Forum convened an action collaborative that set out to identify and highlight potentially breakthrough ideas and visionary approaches to the “drug develop- ment and translational science enterprise of the future.” The effort addressed new technologies (e.g., biosensors, apps and telemetry, synthetic biology, or new delivery technologies); new business models (e.g., crowdsourcing platforms, drug repurposing, virtual companies, or clinical trials); and policy issues (e.g., pricing/ reimbursement, patent law, or data transparency). The effort included a data-gath- ering phase and review phase involving the Forum membership, and will include the preparation of a Perspectives paper. October 24 November 5 Workshop: Assessing and Workshop: Addressing the Threat Accelerating Development of of Drug-Resistant Tuberculosis: A Realistic Biomarkers for Drug Safety Assessment of the Challenge November 3 Forum Meeting #11 

Priorities to Advance the Field of Regulatory Science panelists (left to right) Stephen Ostroff, FDA Commissioner Robert Califf, Martin Landray, and Susan Ward. Clinical Trial Site Standards Harmonization—Action Collaborative Since sponsoring a workshop series on issues relating to the U.S. national clinical trials enterprise from 2009 to 2011, the Forum continues to devote time and atten- tion to issues around clinical trials. This action collaborative is an ad hoc convening activity under the auspices of the Forum, which provides a venue for joint and col- laborative activities among participants to advance development of standards or a system to improve clinical trial performance through accreditation of clinical trial sites. Participants, who are drawn from multiple sectors and disciplines, are preparing a Perspectives paper that will summarize their perspectives on a process for standards development and on the establishment of a mechanism to facilitate coordination of an experimental approach to align existing standards and improve clinical trial site March 13 April 27 Discussion Series: FDA Community Update Workshop: Streamlining on Personalized Medicine and the Genetic Clinical Trial and Material Basis of Adverse Events Transfer Negotiations 2009 February 23 April 27–28 July 10 Capitol Hill Briefing: Growing Forum Meeting #12 Symposium: Drug Regulation with Threat of Drug-Resistant Tuberculosis FDA Commissioner Peggy Hamburg (Forum Meeting #13) 

Reflecting Back: Forum Activities in 2015 standards based on continuous data collection. Collaborative participants have also undertaken a second phase of the collaborative activity, which includes the collection, analysis, and assessment of how clinical trial site standards currently in use by key stakeholders could be harmonized. Sharing Clinical Trial Data—Action Collaborative Sharing clinical trial data can facilitate more efficient and effective development of better medicines, diagnostics, and procedures for the ultimate benefit of patients. At the same time, sharing data presents risks, burdens, and challenges that need to be addressed by a broad set of stakeholders. These opportunities and chal- lenges were laid out in the Institute of Medicine (IOM) report, Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risk. The report calls on stakeholders to foster a culture of sharing and offers a blueprint for action within and across sec- tors. Four Academies Forums, including the this forum, provided momentum and a framework for initiating the IOM consensus study that produced the report, and are working together again to form a platform that could support coordination and collaboration among stakeholders engaged in data-sharing initiatives through con- vening and other activities. In 2015, collaborative participants launched the first workstream from this Data Sharing action collaborative, focusing on Building an IT and Technical Infrastructure, which is a collaboration with Harvard’s Multi Regional Trial Center (MRCT) to convene stakeholders with relevant technical, legal, and content expertise to define a framework for the key issues in building and sustain- ing a global technical infrastructure. September 2 February 22–24 Discussion Series: FDA Workshop: The Public Health Emergency Community Update on October 15–16 Medical Countermeasures Enterprise (in collabo- Post-Market Drug Safety Forum Meeting #14 ration with the Medical Preparedness Forum) 2010 October 7–8 February 26 Workshop: Transforming Clinical Workshop: Building a National Framework Research in the United States for the Establishment of Regulatory Science for Drug Development