Strategic Goal 1: Conduct and support innovative research that uncovers fundamental scientific and operational principles of translational science to catalyze the development and dissemination of novel medical interventions.

NCATS conducts and supports collaborative research across the pre-clinical phase of the translational science spectrum to develop new methods, tools and technologies to catalyze pre-clinical research and make it more efficient. In doing so, the Center effectively “de-risks” novel and promising therapeutic and diagnostic discoveries and enables the translation of these innovations to a state where they can attract outside investment for further clinical development. In this way, NCATS serves as an adaptor between academia, nonprofit research institutions, and private sector companies, each with complementary resources and skills to bring new medical interventions to patients faster.

Importantly, NCATS selects and carries out collaborative research projects to not only jump-start new therapeutic or diagnostic development, but also to help uncover general principles of translational science, or to test a new technology or approach. In addition, NCATS creates innovative methods to overcome translational bottlenecks in areas including therapeutic/diagnostic target identification, assay development, medicinal chemistry, drug screening, efficacy and toxicology testing, and implementation of new medical interventions.

NCATS broadly disseminates the innovative tools and technologies it develops to enable all participants in the biomedical science ecosystem to conduct pre-clinical research more efficiently and effectively. By improving our understanding of the principles underlying successful translational science, NCATS makes translational research more likely to deliver upon the ultimate goal of patient benefit.

Example approaches:

• Accelerate therapeutic target identification and validation through advanced gene editing technologies and screening with newly developed small molecule probes.
• Develop innovative biochemical and cellular assay platforms and chemical library screening approaches in the context of disease biology to overcome translational barriers in therapeutic development for underserved diseases.
• Use NCATS expertise in medicinal chemistry and informatics to develop and demonstrate innovations in hit-to-lead optimization of therapeutic candidates.
• Collaborate with academic, nonprofit and industry partners in drug synthesis, formulation, pharmacokinetics and toxicology to support initial regulatory review of interventions in development.
• Develop and integrate new models of human biology to better understand disease physiology and predict candidate drug safety, toxicity and efficacy.
• Develop and disseminate more efficient and effective approaches to predict how chemicals may affect human health, and organize the data collected from such approaches into predictive computational models for toxicity assessment.
• Provide collaborative access to NCATS’ state-of-the-art resources and expertise in automation, compound management, analytical chemistry and informatics, among others.
• Make research data, tools and technologies produced by NCATS broadly accessible and available to the entire translational community. 

NCATS is innovating in the clinical phase of translation through the creation and development of novel processes, sharing of best practices, collaboration, and harmonization of research approaches at the local, regional and national levels. Beginning with a strong foundation of clinical researchers and research institutions, NCATS works to overcome common bottlenecks in clinical and translational research. These bottlenecks include engagement and recruitment of participants in clinical studies, streamlined review of the conduct of clinical studies, methods for measuring clinical outcomes, effective clinical trial design and statistics, and patient adherence to therapeutic regimens. Collaborative clinical research institutions with harmonized network capacity to efficiently and effectively respond to translational science needs will enable a more efficient national clinical research ecosystem with a diverse range of partners ready to quickly launch and complete studies to better understand human diseases and test medical interventions to treat them. NCATS is committed to actively disseminating clinical research innovations to all stakeholders for their use in making their own clinical translation more efficient and effective.

Example approaches:

• Develop innovations that significantly reduce delays in clinical study start-up, such as streamlined institutional review board review processes for multi-site trials.
• Create new community outreach approaches to speed participant recruitment and reach underrepresented communities.
• Implement processes that streamline and harmonize the planning, conduct, comparability, and reporting of clinical research.
• Collaborate to develop and disseminate cutting-edge, efficient, and generally applicable methods for disease characterization and diagnosis, including the use of genetic and environmental health information for use in precision medicine.
• Develop innovative methods and approaches that lead to appropriate clinical outcome measures that can be applied across diseases and for regulatory applications.
• Catalyze the innovation, testing and harmonization of information technologies to enable efficient clinical hypothesis generation and testing, facilitate participant recruitment for research, and enable straightforward cross-comparison of data sets.
• Develop and standardize content for clinical translational workforce education and training, including new emphases on team science, experiential learning, and entrepreneurship. 
• Catalyze new approaches for improving adherence to treatments and interventions and determining the impact of those interventions in relevant communities and populations.

The explosion of data on genes, cells and biological pathways over the last several decades has highlighted the remarkable connectedness of human biology. These relationships have profound implications for translational science, as studying commonalities across diseases presents opportunities for understanding not one but many diseases and can potentially accelerate translational research for several areas of biomedicine. New scientific insights gained from advances in genomics and the widespread use of molecular probes are leading to the discovery of shared genetic and biochemical pathways across diseases, which enable rapid application of the insights gained from the study of one disease to the treatment of others. NCATS therefore takes an integrative approach in all its programs.

Example approaches:

• Develop a publicly available knowledge base of interrelated biological pathways and characteristics across diseases, enabling researchers to identify common therapeutic targets.
• Cluster diseases with common mechanisms and molecular targets to enable multiplex therapeutic development of new therapeutic candidates with the potential for broader utility beyond a single indication.
• Apply knowledge of common molecular origins across diseases to repurpose drugs as new treatments for unmet medical needs.

NCATS has a strategic focus on rare diseases, which are difficult to assess because of the large number of disorders, the complexity of each disease, small patient populations, and the limited availability of data. Rare diseases are devastating and costly for patients, their families, communities and society. The burden of rare diseases is attributable to both disease severity and the toll of the often lengthy and difficult process of diagnosis. NCATS takes an integrated approach to the understanding, diagnosis and treatment of rare diseases, investing resources and expertise across the translational science spectrum to move potential treatments forward for development and clinical testing. By also examining the scientific and operational outcomes of rare disease research for their potential applications to related rare and even common diseases, NCATS seeks to replace the one-disease-at-a-time approach to clinical and translational science with more efficient efforts. Central to the NCATS approach is the involvement of patients, families and caregivers throughout the translational process. Taken together, these approaches exemplify NCATS’ unwavering commitment to accelerating translation in order to bring more effective treatments to all patients. 

Example approaches:

• Apply a disease commonality approach to accelerate rare diseases understanding and treatment.
• Develop, demonstrate, and disseminate innovative and flexible clinical research methods that address the challenges of small patient populations.
• Promote common, scalable and participant-centered patient registry platforms that advance both individual rare diseases research and the understanding of shared characteristics among multiple diseases.
• Develop innovative and generalizable approaches for the conduct of natural history studies of rare diseases that enable the efficient identification of biomarkers, clinical outcomes and other measures required for the development and approval of medical interventions.

Translational science is fundamentally integrative, building on scientific and operational discoveries and processes as a basis for making translation more efficient and effective. Identifying the general principles for effective translation will be aided by the collation and comparison of data across diseases, therapeutic targets, interventions and projects. Such comparisons require not only proactive design and conduct of individual studies to make them compatible, but also biomedical informatics resources that are interoperable for facile data comparison, integration and analysis. Translational science with regards to informatics encompasses a broad range of disciplines including bioinformatics, cheminformatics, computational biology and chemistry, in vivo modeling, statistics, and medical informatics. Development of algorithms, software and technology platforms across these disciplines and their dissemination to the broader community is a key NCATS focus.

Example approaches:

• Create and foster a data-sharing environment that accelerates discovery and enables creation of new knowledge through meaningful integration of diverse biomedical and clinical data sets.
• Support the development of collaborative information technology resources to enable communication across clinical research sites and connect the health data sets they collect, including among others electronic health records, clinical trial outcomes and mobile health data.
• Serve as a clearinghouse and “neutral broker” of information that supports translation by emphasizing standardization and interoperability of current and future datasets.
• Develop and implement policies and practices for broad access to and sharing of informatics resources.

The pace of scientific discovery is accelerating and providing new opportunities for improving our understanding of and applications for translational science. Advances in our understanding of human physiology and behavior continuously fill each phase of the translational spectrum with exciting new therapies to develop, new operational strategies to test, and new technologies to engineer. NCATS will therefore regularly evaluate its research portfolio and identify new strategic opportunities for translational research and translational science.

Example approaches:

• Advance the translation of regenerative medicine by developing scientific and technological innovations to overcome the major limitations currently impeding the clinical application of induced pluripotent stem cells (iPSCs).
• Examine ways for NCATS to stimulate innovation and facilitate translation in the medical device and diagnostic research and development space.
• Expand research into the development and qualification of biomarkers for application in disease diagnosis and measurement of treatment response.
• Explore the therapeutic potential of newly developed technologies for human gene editing.
• Explore opportunities for NCATS’ involvement in research on clinical implementation and social determinants of health. 
• Expand research into novel therapeutic modalities (e.g., chemical libraries of novel scaffolds, structures, and properties) to enable modulation of undrugged genomic targets.
• Analyze scientific and operational failures across the translational spectrum in a systematic manner, and disseminate lessons learned to improve the process in the future.