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

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Reflecting Back Forum Activities in 2016 Forum Meetings The Forum membership met three times in 2016. Discussions at these meetings focused on diverse topics related to the Forum’s priorities, including improving drug development through genomics; seamless drug development; mapping and connecting the biomedical innovation ecosystem; overcoming challenges in biomedical innovation; precision medicine; strategies for the responsible sharing of clinical trial data; and policy updates relevant to drug discovery, development, and translation. In addition, the Forum convened public workshops and collabora- tive activities, described below. (Left to right) Forum director Anne Claiborne and Forum co-chairs Russ Altman and Steven Galson brainstorm during the October 18 Forum meeting. June 29–30 Forum Meeting #2 FORUM ACTIVITIES TIMELINE 2000–2004 2005 Clinical Research Roundtable, March 23–24 predecessor to the Forum Forum Meeting #1 

Reflecting Back: Forum Activities in 2016 Workshops: Deriving Drug Discovery Value from Large-Scale Genetic Bioresources— A Workshop (March 2016) Biopharmaceutical companies continually seek innovative strategies to revitalize and create efficiencies in their drug development processes. One approach has involved the adoption of genetically guided strategies to reduce attrition rates and increase the odds of success. Several large cohort studies have incorporated or begun to incorporate genetic data collection as part of the study design. With the large volumes of genetic and phenotypic data that are planned to be col- lected, these efforts could provide a valuable trove of information for identifying and validating potential targets, elucidating underlying disease and mechanistic biology, and developing biomarker assays and targeted therapies. Questions remain about how large cohort studies could be designed, the types of data that should be collected, and which business models could engage stakeholders most effectively. The Forum, in collaboration with the Roundtable on Translating Genomic-Based Research for Health, convened a workshop that examined and discussed how large-scale genetic data could be used to improve the likelihood of bringing effective and targeted therapies to patients. The workshop assessed the current landscape of genomic-enabled drug discovery and development activi- ties; examined how to enable partnerships and develop better business models; and considered gaps and best practices in how data from populations could be collected with the goal of improving the drug discovery process. November 3– 4 June 13 Workshop: Adverse Drug Event Workshop: Addressing Reporting: The Roles of Consumers March 28–29 the Barriers to Pediatric and Health-Care Professionals Forum Meeting #4 Drug Development 2006 September 8–9 May 30–31 Forum Meeting #3 Workshop: Understanding the Benefits and Risks of Pharmaceuticals 

FDA commissioner Rob Califf (right) delivers the keynote presentation at the October 19 workshop on Real-World Evidence Generation and Evaluation of Therapeutics following remarks from workshop co-chairs (left to right) Gregory Simon and Steven Galson. Real-World Evidence Generation and Evaluation of Therapeutics— A Workshop (October 2016) The traditional process for evaluating new therapeutics does not produce the evidence that patients, clinicians, and payers need for real-world decisions. The volume and complexity of information about individual patients are greatly increasing with the use of electronic health records and personal devices. Potential effects on medical product development in the context of this wealth of real-world data are numerous and varied, April 23–24 October 24–25 Workshop: Emerging Safety Science, FDA October 15–16 Forum Meeting #6 (Forum Meeting #7) Forum Meeting #8 2007 June 27–28 March 12 September 14 Forum Meeting #5 Symposium: The Future of Drug Discussion Series: From Patient Safety: Challenges for FDA Needs to New Drug Therapies 

Reflecting Back: Forum Activities in 2016 ranging from the ability to determine both large-scale and patient-specific effects of treatments to assessing how therapeutics affect patients’ lives through the measurement of lifestyle changes. However, mechanisms to facilitate the efficient use of real-world data to meet the decision-making needs of myriad stakehold- ers have not been established. This workshop, held in October 2016, examined opportunities and challenges for incorporating real-world evidence into the evaluation of medical products, including consideration of quality, relevance, and validity of real-world data sources; methodologies and best practices for incor- poration of real-world data throughout the product lifecycle; and use of novel approaches such as Web-based or other digital technologies. A National Academy of Medicine (NAM) Discussion Paper authored by the workshop co-chairs was made available in conjunction with the workshop. The Drug Development Paradigm in Oncology—A Workshop (December 2016) In collaboration with the National Cancer Policy Forum, the Forum convened a workshop in December 2016 to examine the challenges of the traditional cancer drug development process and explore opportunities to promote seamless cancer drug development. The workshop facilitated discussion about strategies to improve the collection of information across the lifecycle of cancer therapies; streamline and adapt drug development based on compelling evidence; and consider ethical and regulatory implications for a seamless cancer drug develop- ment paradigm. June 23 February 20–21 Workshop: Breakthrough Business Discussion Series: Comparative Models: Drug Development for Rare Effectiveness (Forum Meeting #9) and Neglected Diseases 2008 November 30 April 21 June 23–24 Discussion Series: Discussion Series: Science at FDA: Symposium: Diseases and Individualized A Conversation with Tony Fauci Challenges and Opportunities Therapies (Forum Meeting #10) 

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 participants to encourage further innovation. It could also facilitate ongoing discussion 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. This Collaborative enabled discussion to identify rate-limiting steps in order to facilitate process improvement efforts. In 2016, Collaborative participants prepared two process maps showing the development of small molecules and biologics, which will be released to the public to aid in the identification of inputs, bottlenecks, and system gaps. Collaborative participants will author a peer-reviewed journal article and accompa- nying NAM Discussion Paper to inform and help guide future dialogue and progress. 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 research and development (R&D) pro- ductivity. Evidence suggests that industries are almost always disrupted from the outside by new technologies they were slow to embrace, new business models they wrongly October 24 November 5 March 13 Workshop: Assessing and Workshop: Addressing the Threat of Discussion Series: FDA Community Accelerating Development of Drug-Resistant Tuberculosis: A Realistic Update on Personalized Medicine and Biomarkers for Drug Safety Assessment of the Challenge the Genetic Basis of Adverse Events 2009 November 3 February 23 Forum Meeting #11 Capitol Hill Briefing: Growing Threat of Drug-Resistant Tuberculosis 

Reflecting Back: Forum Activities in 2016 Forum member Chris Austin, middle, discusses the Mapping and Connecting Collaborative at the October 18th Forum meeting, alongside (left to right) invited David Altarac (Shire), Michael Rosenblatt (Merck), Richard Murray (Merck), Taylor Gilliland (NIH), and Freda Lewis-Hall (Pfizer). 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 a Collaborative that identified and highlighted potentially breakthrough ideas and visionary approaches to the “drug development and translational science enterprise of the future.” The effort addressed new technolo- gies (e.g., biosensors, apps and telemetry, synthetic biology, new delivery tech- nologies); new business models (e.g., crowdsourcing platforms, drug repurposing, virtual companies, clinical trials); and policy issues (e.g., pricing/reimbursement, patent law, data transparency). The effort included a data-gathering phase and review phase involving the Forum membership and culminated in the release of an NAM Discussion Paper. April 27 September 2 Workshop: Streamlining Discussion Series: FDA Clinical Trial and Material Community Update on October 15–16 Transfer Negotiations Post-Market Drug Safety Forum Meeting #14 April 27–28 July 10 October 7–8 Forum Meeting #12 Symposium: Drug Regulation with Workshop: Transforming Clinical FDA Commissioner Peggy Hamburg Research in the United States (Forum Meeting #13) 

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 attention to issues around clinical trials. This Collaborative is an ad hoc convening activity under the auspices of the Forum, which provides a venue for joint and collaborative activities among participants to advance the development of standards or a system to improve clinical trial performance through the accreditation of clinical trial sites. Participants, who are drawn from multiple sectors and disciplines, are preparing an NAM Discussion Paper that will summarize their perspectives on a process for standards development and on the establishment of a mechanism to facilitate the coordination of an experimen- tal approach to align existing standards and improve clinical trial site standards based on continuous data collection. Collaborative participants have also undertaken a second phase of the Collaborative activity, which includes the collection, analysis, and assess- ment of how clinical trial site standards that are 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 challenges were laid out in the February 22–24 Workshop: The Public Health Emergency Medical Countermeasures Enterprise (in collaboration April 29–30 with the Medical Preparedness Forum) Forum Meeting #15 2010 February 26 March 3–4 May 26–27 Workshop: Building a National Framework South Africa Workshop: The Russia Workshop: The New for the Establishment of Regulatory Science Emerging Threat of Multidrug- Profile of Drug-Resistant for Drug Development Resistant Tuberculosis Tuberculosis 

Reflecting Back: Forum Activities in 2016 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 sectors. Four National Academies forums and roundtables, including the Drug Forum, provided momentum and a framework for initiating the IOM consensus study that produced the report, and are working together again to provide a platform to support coordination and collaboration among stakeholders engaged in data sharing initiatives through convening and other activities. The first workstream from this Collaborative is focusing on Building an IT and Technical Infrastructure and is a collaboration with Harvard’s Multi-Regional Clinical Trials Center (MRCT) to convene stakeholders with relevant technical, legal, and content expertise to define a framework for the key issues in building and sustaining a global technical infrastructure. The work- ing group convened on February 3, 2016, at the National Academies and then released its suggested way forward at a meeting at the Wellcome Trust in London in March 2016. Also launched in 2016 under the auspices of the Collaborative is a workstream addressing Data Sharing Principles for Nonprofit Clinical Trial Funders, which is convening nonprofit funders of research, focusing on disease advocacy and patient-focused organizations, to develop standards and policies for foster- ing, promoting, or requiring data sharing by grantees. This working group of the Collaborative met in July 2016 to discuss principles and strategies for nonprofit funders to share clinical trial data, including associated risks and challenges. March 29–30 August 5–6 Workshop: Advancing Regulatory Science for Medical Discussion Series: Conflict of Interest Countermeasure Development (in collaboration with (Forum Meeting #16) the Medical Preparedness Forum) 2011 October 29 March 28 April 18–19 Discussion Series: Administrative Forum Meeting #18 India Workshop: Facing and Regulatory Inefficiencies in the Reality of Multidrug- Clinical Trials (Forum Meeting #17) Resistant Tuberculosis