Forum on Drug Discovery, Development, and Translation

Forum Membership Meetings

In 2019, 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 clinica 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 and Meetings

Updating Labels for Generic Oncology Drugs: A Meeting

The Forum, in collaboration with the National Academies’ National Cancer Policy Forum, hosted a public meeting, sponsored by FDA, on March 26, 2019, that convened expert stakeholders to discuss the challenges and opportunities for updating labels for generic oncology drugs. The meeting featured discussions about current regulatory requirements for labeling updates, review processes for clinical practice guidelines for oncology, and how outdated drug labeling can impact clinical care. Meeting participants considered potential sources of data and evidentiary standards to guide decision making for labeling updates, including indications for select patient populations (e.g., pediatric oncology), dosing, and adverse events.

Enhancing Scientific Reproducibility Through Transparent Reporting: A Workshop

In collaboration with the National Academies’ Forum on Neuroscience and Nervous System Disorders, National Cancer Policy Forum, and Roundtable on Genomics and Precision Health, the Forum convened a workshop on September 25–26, 2019, to examine the current state of transparency in reporting biomedical research (e.g., disclosure of the availability and location of data, materials, analysis, and methodology) and to explore the possibility of improving the harmonization of guidelines across journals and funding agencies so that biomedical researchers propose and report data in a consistent manner. Workshop participants discussed the challenges and opportunities for the harmonization of guidelines for transparent reporting throughout the biomedical research lifecycle. The agenda included 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. This workshop was sponsored by NIH, Cell Press, The Lancet, and Nature Research.

Sharing  Clinical  Trial   Data:  Challenges  and  a  Way  Forward:  A  Workshop    

In collaboration with the National Academies’ Forum on Neuroscience and Nervous System Disorders, National Cancer Policy Forum, and Roundtable on Genomics and Precision Health, the Forum hosted a public workshop to 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. Workshop participants considered the value and potential risks/ costs of sharing clinical trial data for key stakeholders, including clinical trialists, sponsors, primary and secondary researchers, and patients. The agenda featured use cases from across public and private sectors when it comes to success, failure, lessons learned, and the value of data sharing. This workshop was sponsored by the Wellcome Trust.

Forum Membership Meetings

The Forum membership will meet in March, July, and October 2020 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

The Role of Digital Health Technologies in Drug Development

Digital health technologies (e.g., smartphone apps, wearable sensors, and other remote, sensor-based tools that combine hardware and software) have become increasingly available to consumers, providers, and researchers. They offer new opportunities to address critical challenges or “pain points,” better connect patients and health care providers, and incorporate patient input throughout the drug R&D lifecycle. In collaboration with the National Academies’ Roundtable on Genomics and Precision Health, the Forum will host a workshop on March 24, 2020, to discuss the challenges and opportunities in using digital health technologies to improve the probability of success in drug development. Workshop participants may consider key components for an evidence-based framework for applying digital health technologies toward drug R&D.

Drug Research and Development for Older Adult Populations

Despite the widespread recognition of the “graying of America,” and the need for health care among older adults, there is a dearth of information about the appropriate use of drugs in this population. Older adults are vastly underrepresent- ed in clinical trials. Yet, older adults have higher rates of comorbidities and polypharmacy than the general population and are the majority users of many medications. Additionally, age-related physiological and pathological changes, particularly for adults over age 80, can lead to significant di ferences in the pharmacokinetic and pharmacodynamics of a given drug compared to the general population. There is a void in evidence-based information for making informed decisions on how to best optimize care for older adults,particularly those over age 80. In collaboration with the National Academies’ Forum on Aging, Disability, and Independence and the National Academies’ National Cancer Policy Forum, the Forum will host a workshop to discuss the challenges and opportunities in drug R&D for the over age 65 and over age 80 populations, explore barriers that impede safety and efficacy studies in these populations, and share lessons learned and best practices for better understanding the clinical pharmacology for older adults.

Envisioning a Transformed Clinical Trials Enterprise for 2030

Clinical trials research has changed dramatically over the past decade. The biological, physical, and digital spheres are merging; clinical research and health care are at a critical juncture; and new technologies enable the collection of data in real-world settings. These opportunities hold great promise for advancing our understanding of health maintenance and prevention, disease progression, and developing new therapies for patients. At the same time, 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. Some, but not all, of these challenges and opportunities were predicted in the 2011 Forum- hosted workshop Envisioning a Transformed Clinical Trials Enterprise in the United States: Establishing an Agenda for 2020. There is now a need for stakeholders from across the clinical research lifecycle, including patients, caregivers, regulators, practitioners, and researchers, to examine the challenges and setbacks, lessons learned, and advances from the past decade, and consider the challenges and opportunities that may be coming over the next 10 years. Workshop discussions will focus broadly on how to better integrate community practice and clinical trials, improve patient engagement in clinical trials, align cultural and financial incentives, and support the clinical trials infrastructure. The workshop will provide a venue to discuss goals and key priorities for advancing a clinical trials enterprise that is more efficient, effective, patient-centered, and integrated into the health delivery system of 2030.

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.