Forum on Drug Discovery, Development, and Translation

Forum Membership Meetings

Members of the Forum convene several times each year to identify, discuss, and act on key problems and strategies in the discovery, development, and translation of drugs. In 2018, the Forum membership focused on diverse topics related to the Forum’s priorities, including issues for emerging biotech companies; transforming clinical trials through digital health; improving the drug development process through examining late-stage failures; real-world evidence and medical product development; harmonizing clinical trial site standards; data-sharing principles for nonprofit clinical trial funders; the science of patient input in medical product R&D; innovative models to spur translational research and drug discovery; artificial intelligence applications for drug discovery and development; and other policy updates relevant to drug discovery, development, and translation. To supplement the perspectives and expertise of its members, the Forum holds public workshops to focus attention on critical areas of drug development. Summaries of these meetings are disseminated to the public through the Forum website and published proceedings.

Workshops

Examining the Impact of Real-World Evidence on Medical Product Development: A Workshop Series

The Forum convened a three-part workshop series, sponsored by FDA, examining how real-world evidence development and uptake could enhance medical product development and evaluation. The workshops advanced the discussions and common knowledge about complex issues relating to the generation and use of real-world evidence, including fostering the development and implementation of the science and technology of real-world evidence generation and utilization. Workshop One: Incentives (September 19–20, 2017) focused on how to align incentives to support the collection and use of real-world evidence in medical product review, payment, and delivery, including the incentives needed to address barriers impeding the uptake of real-world evidence, such as transparency. Workshop Two: Practical Approaches (March 6–7, 2018) was a "Town Hall" style meeting with in-depth audience discussion and active participation to illuminate which types of data may be appropriate for specific purposes and to discuss practical approaches for data collection and evidence use. Workshop Three: Application (July 17–18, 2018) examined approaches for operationalizing the collection and use of real-world evidence.

Advancing the Science of Patient Input in Medical Product R&D: Towards a Research Agenda: A Workshop

The Forum convened a 1-day workshop on May 9, 2018, focused on the science of patient input for pre-market medical product R&D (including pre-discovery, discovery, pre-clinical development, and clinical development), with consideration of downstream regulatory and post-market decision making. At this workshop, subject-matter experts representing a range of disciplines engaged in presentations and discussions to:

• Examine the current state of the science, including successes and limitations of current efforts, for soliciting and incorporating patient input in pre-market R&D.
• Explore gaps in the knowledge base and other barriers that impede progress, including but not limited to:
• parameters for soliciting and incorporating different types of patient input along the spectrum of medical product R&D;
• availability, accessibility, and applicability of data sources for patient input;
• tools and methodologies for collecting and analyzing patient input to produce scientifically rigorous, credible evidence; and
• understanding of the ethical and value considerations for soliciting and incorporating patient input into medical product R&D decision making.
• Review a potential framework for and components of a research agenda for addressing the gaps or barriers to realizing a science of patient input.

Virtual Clinical Trials: Challenges and Opportunities: A Workshop

The Forum convened a 2-day workshop on November 28–29, 2018, which provided a venue to explore opportunities for a modern clinical trials enterprise capable of more efficiently answering questions about medical products by bringing participants closer to the clinical trial through the use of digital health tools. Clinical trials are a cornerstone of medical product development—supporting the evaluation of efficacy and the identification of safety issues of new drugs and devices—and a necessary regulatory requirement for bringing novel therapies to market. Since 2009, the Forum has been engaged in a focused effort, anchored by a multi-workshop series, to address the challenges facing the U.S. clinical trials enterprise and to engage stakeholders in an ongoing discussion of potentially transformative strategies to improve the efficiency and effectiveness of clinical trials. This workshop built on this work and examined opportunities for a modern clinical trials enterprise in light of digital health tools. Participants highlighted opportunities for systemic improvements in the clinical trials enterprise, considered novel platform designs and digital health tools to increase efficiency and enhance the interface between clinicians and participants in a clinical trial, and discussed digital platforms to facilitate recruitment and maintain diverse participation in clinical trials.

Forum Membership Meetings

The Forum membership will meet in March, July, and October 2019 to continue its discussions of key problems and strategies in the discovery, development, and translation of drugs. Forum workshop planning committees, working groups, and Action Collaboratives will convene to discuss and act on identified priority areas, including the following activities.

Workshops and Meetings

Updating Labels for Generic Oncology Drugs: A Meeting

The Forum, in collaboration with the National Academies’ National Cancer Policy Forum, will host a public meeting, sponsored by FDA, on March 26, 2019. Participants at this meeting will examine the challenges and opportunities for updating labels for generic oncology drugs. The meeting may include discussions on current FDA guidelines regarding the quality and quantity of evidence required to support claims of safety and effectiveness in new drug applications. Additionally, meeting participants may discuss potential criteria and sources of data to guide decision making for generic label updates on indications, dosing, and adverse events, and approaches for addressing specific gaps in labeling, such as for certain patient populations (e.g., pediatric) and for cross-labeling combination therapies.

Enhancing Scientific Reproducibility Through Transparent Reporting: A Workshop

The Forum will convene a workshop on September 25–26, 2019, exploring issues related to transparent reporting (e.g., the disclosure of the availability and location of data, materials, analysis, and methodology) to improve rigor and reproducibility in biomedical research. Workshop attendees will discuss the challenges and opportunities for the harmonization of guidelines for transparent reporting throughout the biomedical research lifecycle. The agenda will include a panel discussion on facilitating the development of consistent guidelines (e.g., a common set of minimal reporting standards) that could be applied across journals and funders to increase transparency in proposing and reporting biomedical research.

Sharing Clinical Trial Data: Reflecting Back and Looking Ahead: A Workshop

This workshop will examine the progress and remaining gaps in clinical trial data sharing following the publication of the 2015 Institute of Medicine (IOM) report Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risk. The public workshop will examine the recent advances, remaining challenges, and new opportunities in clinical trial data sharing. Workshop presentations and discussions may include case studies and trends in clinical trial data sharing and reuse as well as the consideration of best practices and lessons learned.

Advancing the Science of Patient Input in Medical Product R&D

There is growing momentum to incorporate patient input into medical product R&D and regulatory decision-making processes. Converting traditionally anecdotal patient input to rigorous, credible evidence for use by a broad range of stakeholders—including academic and clinical researchers, medical product developers, patient/disease advocacy groups, and regulatory decision makers—could better align medical product development and regulation with patient perspectives on disease experience, burden, management, and treatment. Many efforts have been launched to advance a science of patient input. However, there is a need to identify key gaps in the knowledge base and other barriers that impede progress and to develop an approach for addressing them. This action collaborative launched in 2017 to foster the development of a strategic research framework to advance the science of patient input. During the first phase of work, collaborative participants catalogued current efforts and progress in the science of patient input and identified gaps in the knowledge base and other barriers that impede progress. In the second phase, collaborative participants laid the groundwork for a public workshop hosted by the Forum on May 9, 2018, titled Advancing the Science of Patient Input in Medical Product R&D: Towards a Research Agenda. Topics raised during this discussion-based workshop will help inform the third phase, which will focus on the development of a research framework for advancing the science of patient input.

Clinical Trial Site Standards Harmonization

Mobilized in 2012, this action collaborative set out to explore opportunities to improve clinical trial site functioning with the goal of increasing productivity in medical product development. To date, the collaborative has drawn together a group of diverse stakeholders for four in-person meetings (December 2012, August 2013, March 2014, and September 2018). Collaborative participants published a National Academy of Medicine Discussion Paper in October 2017, which summarizes their perspectives on a proposed launching point for harmonizing the requirements applied to clinical trial sites and the development of standards. In 2018, the collaborative collected, analyzed, and assessed a set of baseline site standards necessary for launching the majority of phase II, III, and IV clinical trials, and which could be considered for broad application across clinical trial sites by research sponsors.

Improving the Drug Development Process Through Examining Late-Stage Failures

The development of new drugs is inherently complex and costly, with sources documenting up to $2.6 billion and more than 9 years in investment to bring a new treatment to market. The high cost is driven, at least in part, by the failure rate for new compounds entering late-stage development, but also encompasses opportunity costs due to time and resources not spent on developing an alternate treatment candidate, as well as investment in clinical trial infrastructure. Most importantly, these failures have an impact on patients—those who participate in the clinical trials associated with the testing of a failed drug candidate and those who will not benefit from having access to treatments that could have been developed instead. The goal of this action collaborative is to examine the contributing factors to late-stage failures and develop a set of key considerations for stakeholders to improve the probability of success in late-stage product development. In 2018, collaborative participants conducted structured, qualitative interviews with subject-matter experts; analyzed and synthesized responses from these interviews; considered information compiled from a literature survey; and held a meeting on October 3, 2018, to discuss and inform the key considerations. In 2019, collaborative participants will continue to prepare and publish a written summary of the key considerations and points identified by this activity.

Sharing Clinical Trial Data

Sharing clinical trial data can help 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 IOM report Sharing Clinical Trial Data: Maximizing Benefits, Minimizing Risk, which 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 Forum, provided momentum and a framework for initiating the consensus study that produced the report and continue to work together to support coordination and collaboration among stakeholders engaged in data-sharing initiatives through convening and other activities.

This action collaborative, in collaboration with Brigham and Women’s Hospital and Harvard University’s Multi-Regional Clinical Trials Center, helped inform the establishment of Vivli—a global data repository, Cloud-based analytics platform, and in-depth search engine. The public launch of Vivli took place at the National Academies on July 19, 2018. The action collaborative also worked to establish data-sharing goals for nonprofit funders of clinical trials. On November 30, 2017, the collaborative convened a meeting of leaders of nonprofit disease advocacy organizations, philanthropic organizations and foundations, federal government, academia, industry, and others to review a draft of the Statement of Data-Sharing Goals for Nonprofit Funders of Clinical Trials, discuss the associated risks and challenges with implementing the goals, and explore the next steps for operationalizing them. In 2019, collaborative participants will continue to work toward publication of this statement of data-sharing goals.

Innovation and the Drug Research and Development Enterprise

Despite exciting scientific advances, the path from basic science to new therapeutics faces challenges on many fronts. Innovative paradigms are needed to bridge the ever-widening gap between scientific discoveries and the translation of those discoveries into life-changing medications. There is increasing recognition of the need for new models and methodologies to advance drug discovery, development, and translational science. The Forum serves as a hub and a catalyst for nurturing new ideas, collaborations, and partnerships and offers a neutral space for stakeholders to help chart a course through the turbulent forces of disruptive innovation and advance critical policy discussions on biopharmaceutical R&D nationally and globally.

Science Across the Biomedical Research Lifecycle

Revolutionary advances in biomedical research and technology applications present new and exciting opportunities for the discovery and development of new therapies for patients. At the same time, key gaps remain in our knowledge about the science, technology, and methodologies needed to support the research that underpins drug discovery and development. The Forum provides a neutral venue to focus attention on key scientific issues across the biomedical research lifecycle and facilitate the exploration of new and more patient-centric approaches to spur innovation. The Forum continues to support activities that contribute toward the defining, establishment, and refinement of biomedical and regulatory science and other critical aspects of drug discovery and medical product development.

Clinical Trials and Medical Product Development

Clinical research provides a critical link between the laboratory bench and patients’ bedside when it comes to developing new therapeutics and advancing understanding of health maintenance and prevention and disease progression. However, the clinical research enterprise faces continued and mounting pressures, strained from all sides by rising costs, an evolving regulatory and economic landscape, increasing clinical trial complexity, difficulties in the recruitment and retention of research participants, and a clinical research workforce that is under tremendous stress. Collaborative, cross-sector approaches that engage patients, providers, academia, industry, federal agencies, payers, nonprofit organizations, and funders can help to effectively address the key challenges and to develop systems-based solutions.

Infrastructure and Workforce for Advancing Drug Discovery, Development, and Translation

Considerable opportunities remain for the improvement and enhancement of the infrastructure—the organizational framework, systems, workforce, and other resources—that supports the drug discovery and development enterprise. The fields of drug discovery and development, clinical research, and clinical practice are intersecting, cross-cutting, and multidisciplinary. However, career paths in these fields are difficult to pursue, training may be lacking, and career opportunities may be limited. The Forum has considered workforce needs as foundational for the advancement of drug discovery, development, and translation and has focused substantial attention on these issues and fostered the development of strategies to improve the discipline of innovative regulatory science through the development of a robust workforce.