Advisory Council Concept Clearances

Concepts describe the basic purpose, scope and objectives of proposed initiatives and represent an early planning stage for potential NCATS activities.

Concept Clearances

Contact

Anna L. Ramsey-Ewing, Ph.D.

Gregory P. Jarosik, Ph.D.

Concepts are discussed with the NCATS Advisory Council and Cures Acceleration Network (CAN) Review Board and through other public venues. Council approval of a concept does not guarantee it will become an initiative. That decision is made based on scientific and programmatic priorities and the availability of funds.

View approved Advisory Council concept clearances by year:

2024

Expanding the Target Landscape by Drugging the Undruggable Concept

Sept. 23

Karlie R. Sharma, Ph.D., presented a new concept on expanding the target landscape by drugging the undruggable. Traditional drug discovery relies on small biological molecules’ binding to proteins for interactions. Many conditions are considered intractable due to pathologies that lack treatment development options or mechanisms that cannot be treated using traditional drug therapy. An intractable disease is not easily treated, relieved, or cured, or it cannot be treated, relieved, or cured through available therapies. Approximately 10 percent of the human genome is druggable, and 5 percent is druggable and disease relevant. Sixty percent of disease-related proteins are understood to be undruggable, and drugs have been launched into the clinic for only 13 percent.

Proteins that are classified as undruggable disease drivers include intrinsically disordered or misfolded proteins and are potential targets for developing treatments. Many diseases can be attributed to Ribonucleic acid (RNA) dysregulations, providing a research opportunity to address upstream targets. Molecular entities, such as lipids and metabolites, also have been linked to diseases. Numerous diseases — including neurological diseases, rare diseases (e.g., myotonic dystrophies), and cancer — are caused by these undruggable targets. Leading researchers in this field of investigating undruggable targets have had success at drugging these targets, leading to promising treatments. NCATS collaborated with three other institutes and centers to host a workshop on innovative molecular treatment modalities for intractable disease targets. The outcome of the workshop, “New approaches for challenging therapeutic targets,” has been published in Drug Discovery Today. The main messages are that this research field is prime for new classes of molecular entities and alternative modalities and proof-of-concept strategies for drugging difficult targets are needed.

NCATS is proposing this concept to explore novel target classes to treat human disease. The overarching objective is to support preclinical development of treatments for diseases that have traditionally undruggable targets. This new initiative will fill gaps and relieve pressure points preventing or slowing the development of treatments for intractable human diseases and those diseases associated with undruggable targets. Each project will serve as a use case that demonstrates modulation of a traditionally undruggable target. Key aspects of this initiative are to expand the therapeutic pool of target classes and diseases, encourage significant process improvement for identifying novel targets for disease, and address patient populations that traditionally have unmet needs.

NCATS anticipates that this initiative would address those target classes with unmet needs and provide proof-of-concept studies, spurring innovation in new treatment modalities. The success of the concept would be the future development of treatment options for patients who endure these intractable diseases.

Project/Program Officer:
Karlie R. Sharma, Ph.D.
Program Director
Office of Drug Development Partnership Programs
National Center for Advancing Translational Sciences
Phone: 301-451-4965
Email: karlie.sharma@nih.gov

Selective Precision Targeting Concept

Sept. 23

Christine M. Happel, Ph.D., presented a new concept for selective precision targeting, which leverages the ExRNA Communication Program and the NCATS Tissue Chips for Drug Screening program. Some interventions require the safe and effective delivery of molecules to specific cells and tissues. These interventions include gene editing, monoclonal antibodies, or gene expression modulation.

NCATS proposes selective precision targeting to determine a mechanism for precise and on-target therapeutic drug delivery to specific hard-to-reach locations within the human body using MPS. Targeted drug-delivery systems, including nanoparticles or focused ultrasound, are methods for delivering medications to a specific area of the body (organ, tissue, or cell) to increase the concentration of the drug in that area. Hard-to-reach locations in the body include the blood–brain barrier, central nervous system, placenta, retina, or a tumor.

Passley Hargrove-Grimes, Ph.D., explained that MPS or tissue chips are small, bioengineered devices capable of growing functional human cells and tissues for testing; specific targeting; and safety, efficacy, and toxicity assessments. MPS contain multiple cell types and are more physiologically relevant and predictive of in vivo biology than traditional models. Once linked to an integrated platform, MPS enable tissue communication across diverse biological barriers.

The objective of this concept is to provide evidence of therapeutic targeting to specific hard-to-reach locations within the human body using predictive multiorgan MPS. The focus will be on elucidating the targeting mechanisms with multiorgan human MPS and testing a broad spectrum of therapeutic cargo, including drugs, RNA, or gene-editing tools. The program goals are fourfold: (1) optimize specific targeting and therapeutics to the target or organ cell of interest, (2) assess biodistribution and off-target effects in a multiorgan human MPS, (3) provide evidence of functional cargo activity, and (4) determine the optimal route of administration.

Metrics for success will include demonstration of the ability to precisely target a cell or a tissue type of interest using the MPS and research activities and results that enable treatments for hard-to-treat diseases. NCATS anticipates the long-term outcome of clinical use of a targeted therapeutic for a highly specific disease context.

Project/Program Officers:
Christine M. Happel, Ph.D.
Program Officer
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-827-9444
Email: christine.happel@nih.gov

Passley Hargrove-Grimes, Ph.D.
Program Officer
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-451-2853
Email: passley.hargrove@nih.gov

Rare Diseases Are Not Rare! (RDANR!) Challenge 3.0 Concept

Sept. 23

Ainslie Tisdale, M.P.H., presented a renewal concept on the RDANR! Challenge 3.0. The collective burden of rare diseases has garnered a groundswell of attention. Four studies published in 2021 conveyed the overall message that rare diseases are costly, both in economic and human terms. Patients with rare diseases are underrecognized and underprioritized in health care systems and databases. These studies illustrate that rare diseases are a public health problem that requires increased attention, awareness, and education.

NCATS hosted RDANR! Challenges in 2018 and 2020 that focused on raising awareness and fostering collaboration across rare disease communities, including patients, caregivers, and advocates. The challenges have resulted in several creative communication pieces, such as posters, videos, and infographics that have been widely shared. The winners and honorable mentions are featured at Rare Disease Day at NIH, and the first-place winner is invited to speak at the event. The RDANR! Challenge 1.0 winner was a parent of a child with a rare disease who created posters raising awareness for rare diseases and the people they affect, emphasizing the message that rare diseases are not rare. Further details can be accessed from NCATS Challenge and Prize Competition Winners webpage. The first-place winner of Challenge 2.0 was a rare disease patient and advocate who submitted a video of himself reciting a poem he wrote to raise awareness of rare diseases; he also received a Zebbie award for the challenge.

Historically, the approach to messaging about rare diseases has focused on developing treatments for one disease at a time and on increasing funds for this research. This message led to the public perception that rare diseases are individual problems rather than as a collective problem that requires a larger solution. Data show that more than 10,000 rare diseases exist and only 5 percent have treatments. The one-disease-at-a-time approach does not lend itself to NCATS’ reaching its audacious goals of more treatments for all people more quickly. Changing the messaging that rare diseases should be approached collectively and in a many-diseases-at-a-time approach will be critical. Public messaging about rare diseases and rare disease research has existed for more than 40 years — starting with the Orphan Drug Act of 1983 — but that message has not been unified, which has widely affected the amount of funding received for rare disease research.

NCATS proposes this concept to raise awareness for rare diseases and all the people they affect collectively. The intent is to highlight the need for crosscutting research and development of new treatments and to increase meaningful engagement with the rare diseases community. The objectives are to seek innovative ways to communicate with others and educate the public through patient-generated art, shift public perception of rare diseases being rare, increase messaging about addressing many rare diseases at a time, and provide an opportunity for patients or patient advocacy groups to be funded by NCATS.

The RDANR! Challenge 3.0 is aligned with NCATS Strategic Plan goals and seeks to impact the research community by fostering innovation and collaboration and increasing awareness about rare diseases. Submissions can include various media types, posters, infographics, or animated graphics. This concept will leverage ongoing activities at NCATS, including the many-diseases-at-a-time programs, and will offer a means to collect and broadcast how this theme is being portrayed and accelerated in the community. The RDANR! Challenge 3.0 also will leverage NCATS Office of Policy, Communications and Education Communications Branch campaigns to educate the community about, and raise awareness of, rare diseases.

NCATS expects this concept to foster innovation and collaboration; increase awareness of and highlight potential funding opportunities; build the community knowledgebase; encourage cross-disciplinary research with broad perspectives and novel approaches; and raise awareness about NCATS’ central role in the rare diseases community. The success of RDANR! Challenge 3.0 will be observed in receiving more than 30 submissions, increasing visits to the NCATS rare disease-related web pages, creating communication mechanisms, releasing social media campaigns, and increasing collaboration and networking.

Project/Program Officer:
Ainslie Tisdale, M.P.H.
Program Analyst
Division of Rare Diseases Research Innovation
National Center for Advancing Translational Sciences
Phone: 301-402-4338
Email: ainslie.tisdale@nih.gov

Prize Competition in Quantum-Enabled Technologies for Biomedical Applications Concept

May 23

Geetha Senthil, Ph.D., presented a new concept for a prize competition in quantum-enabled technologies for biomedical applications. A major challenge in health care is the inability to detect diseases early. The current tools in the field are unable to detect many diseases in early stages and do not accurately diagnose diseases (e.g., cancer, cardiovascular disease, neurological conditions) for timely intervention. Limitations in early detection persist, such as high background noise and low signal capability. Computational limitations include high resource needs, high costs, and the inability to use small data sets. Next-generation quantum technologies are one approach to resolving these problems. NCATS proposes this concept to catalyze the application of innovative quantum-enabled approaches to improve early detection, diagnostics, and therapeutics development.

Quantum-enabled technologies for biomedical applications harness laws of quantum mechanics to engineer and read out quantum states at the subatomic level. This comprises two components. Quantum computing, moving from the classical binary bit to the two-state quantum bit (i.e., qubit), allows for improved speed, molecular dynamic simulations, and AI and machine learning predictions. Quantum sensing provides improved resolution, sensitivity, accuracy, and precision, thus moving from a detection of more than 10,000 cells at once to atomic-scale measurements of a single cell. Next-generation quantum technologies, specifically advanced computing and disease detection, bridge the gap between these two components.

Mature quantum-specific technologies with demonstrated applications in biomedical sciences include optically pumped magnetometers for brain imaging, magnetic encephalography for pediatric epilepsy, and magnetocardiography for fetal cardiac arrythmia. Studies of these technologies are being done through superconducting quantum interference device (SQUID) systems in adults and children. SQUIDs are cryogenic, bulky, expensive, not scalable, and not easy to use in children, especially in those who have rare diseases. The quantum-enabled devices are wearable, portable, and noncryogenic; have improved signal quality; have ease of use in pediatrics; can be deployed in low-resource areas; and are scalable and less expensive.

Quantum computing-specific technology (or the end-type of technology) is in the early stages, is rapidly emerging, and can be useful in accelerating drug discovery. Current drug design tools have limited power and accuracy, require a lengthy process, and are expensive computational resources. With quantum-enabled technologies, the field can accelerate drug discovery with increased accuracy and can simulate drug–target interactions to design safer and more effective drugs.

Several federal-wide activities in fundamental technology research are currently underway related to implementation of the National Quantum Initiative. NIH established the Quantum Information Science (QIS) Working Group that is composed of members from 12 ICs, as well as experts from the U.S. Departments of Energy (DOE) and Defense, National Science Foundation, and National Institute of Standards and Technology. NIH has convened workshops to survey quantum-technology opportunities, including the NIH Virtual Workshop: Near-term Applications of Quantum Sensing Technologies in Biomedical Sciences and the Quantum Computing for Biomedical Computational and Data Sciences: A Joint DOE–NIH Roundtable. NCATS has the opportunity to de-risk the existing quantum technologies and apply them to solve translational problems in early detection and diagnosis by advancing prototypes for real-world applications.

This proposed initiative will consist of prize challenges to catalyze the application of quantum-enabled approaches through multidisciplinary efforts. The aim is to raise awareness and to recognize and reward quantum and biomedical teams that bring innovative quantum technology solutions to biomedical fields. The Quantum Sensing Challenge will solicit applications to develop sensing approaches to enhance preclinical drug discovery using novel scalable assays, enable early detection and accurate diagnosis using ultrasensitive and noninvasive approaches, and improve patient care and health monitoring using wearable and portable technologies. The Quantum Computing Challenge is designed to develop quantum algorithms to accelerate in silico drug discovery and simulations; improve diagnostics, specifically for rare diseases; and perform image and genomic sequence analysis for research and clinical applications. NCATS is partnering with several ICs and offices, including CIT, the National Eye Institute, the National Institute of Biomedical Imaging and Bioengineering and the Office of Data Science Strategy.

In the ideation stage, the plan is to launch prize challenges to identify innovative solutions from a wide pool of innovators (e.g., industry, academia, public). In the implementation stage, NCATS will solicit applications for the Reduction-to-Practice Challenge or other funding mechanisms to implement best solutions to advance existing quantum technologies to useful and usable products for biomedical applications. NCATS expects novel quantum-enabled technologies and devices that are more sensitive and accurate than the current methods and novel quantum algorithms that perform better than currently available classical computing methods for drug discovery and diagnostics applications.

NCATS anticipates building multidisciplinary teams of biomedical and quantum experts. These technological improvements will result in better detection, diagnostics, drug discovery tools, and patient care, which would have a significant impact in the biomedical and public health fields. Also, they will have a positive impact on the national quantum economy ecosystem. The Council was asked for input on any additional areas that should be addressed through this initiative.

Project/Program Officer:
Geetha Senthil, Ph.D.
Deputy Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-594-8064
Email: senthilgs@mail.nih.gov

Prize Competition in Translational Science Education and Training Concept

May 23

Amanda L. Vogel, Ph.D., M.P.H., presented a new concept to establish a prize competition in translational science education and training. A core goal of the Education Branch is to convene, collaborate, disseminate, and amplify community expertise. This concept aligns with this goal and aims to use the prize competition mechanism as an avenue to identify, amplify, and disseminate exceptional models of transitional science education and training that have been generated by this new need. Translational science is still in development. Trailblazers in translational science education and training across academia, industry, and professional societies are developing core content and methods to convey this content to varied audiences. A need exists to identify, amplify, and disseminate exemplary models of translational science education and training from the scientific community. NCATS’ vision for the field of translational science education and training is to equip the workforce with the knowledge and skills needed to improve and accelerate translational research, which is reflected in NCATS Translational Science Principles. OPCE’s recent publication, Advancing Translational Science Education, highlights this vision.

NCATS proposes this concept to (1) raise awareness of translational science education and training and the value it adds and (2) accelerate dissemination of exemplary models of core content, innovative teaching approaches, and ways of reaching diverse learners across training and career stages who have a variety of roles in the translational enterprise. This prize competition will recognize, reward, and disseminate translational science education and training programs that provide content that aligns with NCATS’ understanding of the field of translational science; equip learners with knowledge and skills to overcome common bottlenecks and roadblocks; leverage innovative education and training modalities; reach broad and diverse audiences; and improve access to translational science education and training. The prize competition, unlike a grant, acknowledges that work has been done and aims to broaden the applicant pool to capture diverse approaches.

Regarding the prize competition’s implementation and expected impact, NCATS anticipates that it will contribute to the existing work of developing translational science as a field of study. It is expected to complement existing activities and resources, including extramural funding for translational science training and education (e.g., NCATS’ online courses in translational science and original scholarship). In addition, this prize competition is expected to stimulate interest in this field, promote NCATS’ vision for content and accessibility, and identify and amplify exemplars that may not have been shared broadly and accelerate their dissemination.

The Council was asked to comment on (1) ways to most effectively conduct outreach to colleagues across sectors to solicit applications and (2) approaches for leveraging existing partnerships and stakeholders to solicit applications and disseminate winners’ work.

Project/Program Officer:
Amanda L. Vogel, Ph.D., M.P.H.
Acting Chief
Education Branch
Office of Policy, Communications and Education
National Center for Advancing Translational Sciences
Phone: 301-827-7202
Email: amanda.vogel@nih.gov

Scalable Generation of Organoids Derived From Human iPS Cells SBIR Concept

May 23

Catherine Chen, Ph.D., presented a new SBIR concept on scalable generation of liver and brain organoids derived from human-induced pluripotent stem (iPS) cells. Human iPS cell–derived organoids are widely used as a disease model system for drug development and in research and can be generated from easily obtainable patient samples, such as skin fibroblasts and blood cells. These cells have unlimited expansion capabilities and can be differentiated into various disease-relevant, two-dimensional (2-D) cells and 3-D organoids to study the disease in vitro and to gain an understanding of the efficacy and toxicity of drug candidates. The demand for affordable, high-quality organoids has increased, but a bottleneck exists that can be attributed to labor-intensive production and lack of scalability and batch-to-batch reproducibility.

NCATS DPI proposes this concept to improve efficiency of the methods and reduce the costs in generating iPS cell–derived liver and brain organoids for disease modeling. The objectives of this SBIR contract are to produce liver and brain organoids from iPS cells at scale and with automation, reduce the cost for organoid production over available methods, and have reproducible generation of high-quality organoids with cryopreservation capability. The key areas include generating cryopreserveable liver and brain organoids from human iPS cells and producing cell identity markers that can be confirmed in each type of organoid. The ability to integrate assay readouts (i.e., biosensors) in organoids is desired.

Disease modeling in human iPS cell–derived organoids is a fast-growing area, but a bottleneck to scalable production of high-quality organoids remains, which NCATS aims to alleviate. NCATS anticipates that this concept will enable a broad use of iPS cell–derived organoids for disease modeling and drug screening by facilitating commercial availability of these organoids as off-the-shelf catalog products. Integrating biosensors is expected to facilitate downstream functional assays in organoids. This SBIR effort is expected to benefit the pilot projects of NCATS’ i3D-RARE program.

For this contract concept, reviewers are being asked to consider the scientific, technical, and programmatic significance of the goals of the proposed research and development activity; the availability of the technology and other resources necessary to achieve the required goals; the extent of identified practical, scientific, and clinical uses for the anticipated results; and the adequacy of inclusion of women, minorities, and individuals across the life span in clinical research, if applicable. The Council is being asked for advice on who the early adopters would be and which diseases would benefit most from this research.

Project/Program Officer:
Catherine Chen, Ph.D.
Staff Scientist
Therapeutic Development Branch
Division of Preclinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-827-5365
Email: chenc4@mail.nih.gov

Development of a Versatile Small Footprint Benchtop Device to Perform Batch Evaporation Concept

May 23

Samuel G. Michael presented a new SBIR concept to develop a versatile small footprint benchtop device to perform batch evaporation. In organic chemical synthesis, evaporation plays a crucial role in concentrating and purifying reaction mixtures, isolating products, and removing solvents or other volatile components. The challenge is in integrating an automated evaporation step into a broader workflow for automated chemical synthesis (ACS). NCATS has focused on the automation of high-throughput screen automation of biology for two decades and — coupled with more than 20 years and billions of dollars of investment by industry — has worked to overcome this and other challenges and bottlenecks. Similar investment has not been made in the automation of chemistry.

NCATS proposes this concept to develop a batch evaporation device capable of evaporating multiple high-recovery vials simultaneously for an organic chemical synthesis process. The objective is to develop a batch evaporator that can be used as part of an ACS workflow that can reach 90 percent total evaporation in less than 10 minutes for common solvents used in ACS. The batch evaporator must be able to use high-recovery vials as specified by NCATS, be suitable for use within ACS workflows, and be automation friendly and have an application programming interface.

Regarding implementation and impact, NCATS has patented a batch evaporation prototype device, developed using intramural resources in the ASPIRE program, and interest from other laboratories engaged in similar work remains high. NCATS’ support of a commercial device with improvements will help overcome a key bottleneck in ACS workflows. NCATS anticipates that providing this device to the broader research community would also help overcome the key rate-limiting step in ACS workflows. A successful program would result in the availability of an off-the-shelf device that could be integrated into the ASPIRE Laboratory. NCATS intends to provide nonexclusive licensure to applicants producing a device meeting the criteria previously described.

Project/Program Officer:
Samuel G. Michael
Chief
Information Technology Resources Branch
Director
Research Services Core
National Center for Advancing Translational Sciences
Phone: 301-827-7796
Email: michaelsg@mail.nih.gov

2023

Tissue Chips in Space 2.0—CLDs and Beyond Concept

Sept. 28

Dr. Tagle presented a renewal concept for Tissue Chips in Space 2.0—Commercial Low Earth Orbit (LEO) Destinations (CLDs) and Beyond. The renewal concept of the Tissue Chips in Space program encompasses developing multi-organ integrated platforms closely approximating human body-on-chip systems; establishing the use of induced pluripotent stem cell (iPSC)–derived organ-specific cell types from diverse groups of people, including those from National Aeronautics and Space Administration (NASA) and commercial astronauts to serve as their own avatars; and incorporating advancements in 3-D microfabrication and tissue chip technology—such as culture life beyond 6 months—and automated and miniaturized platforms.

OSI proposes Tissue Chips in Space 2.0 to improve disease outcomes by translating observations from biomedical research experiments in space into interventions that benefit the health of individuals and the public on Earth. This program has resulted in translational benefits of biomedical research in LEO and in space, including the protein crystallization of the KRAS oncogene and improved production processes for the monoclonal antibody Keytruda. Tissue chips have enabled diseases and human conditions to be modeled that may be difficult or would take longer to complete on Earth.

The Tissue Chips in Space program is a partnership among NCATS, NASA, the Center for the Advancement of Science in Space, and the International Space Station (ISS) National Laboratory to model age-related diseases under microgravity and to translate that understanding to improve human health on Earth. With this partnership, automation and miniaturization requirements for spaceflight created technological innovation for tissue chip hardware and instrumentation. The program had several successful launches from 2018 to 2023, with the final launch on March 14, 2023, which evaluated cardiomyopathy. The purpose of this renewal is to further deploy tissue chips as models of accelerated aging and to develop interventions/countermeasures to mitigate aging effects on Earth and in space.

In terms of areas of emphasis, NCATS will partner with NASA (and the European Space Agency), the current ISS National Laboratory and future CLDs, other NIH ICs, and other agencies. OSI will provide support for tissue chips to be deployed in the changing space station landscape for when the current ISS National Laboratory is decommissioned (by 2030) and replaced by CLDs—such as from Axiom Station, Orbital Reef, or Starlab—and will position tissue chips to be the biomedical experiment of choice beyond LEO as discussions are underway between NCATS and NASA for the Artemis III moon landing mission, as well as part of the ExoMars mission to study the effects of long-duration space flight on the human body in preparation for a mission to Mars.

NCATS has been the leader in the United States and internationally in supporting the development and widespread usability and adoption of tissue chips and 3-D microfabricated tissue constructs. NCATS serves as the HHS/NIH liaison to NASA in exploring how space and Earth-based biomedical research can benefit human health here on Earth, as well as address the challenges of health in LEO and during deep space exploration missions.

The expected impact of the Tissue Chips in Space program is a better understanding of human cellular responses to spaceflight and utilizing the LEO environment for disease modeling and to study accelerated aging. It is anticipated that this research will provide key insights into the control and optimization of stem cell differentiation, proliferation, expansion, and maturation and the genomic/epigenomic integrity of stem cell populations; increase use of exosome-based therapies for tissue repair and wound healing; lead to the development of therapeutics and countermeasures for physiological changes associated with the aging process; accelerate the development of personalized avatars or you-on-a chip for precision medicine; and increase 4-D bioprinting capabilities for whole-organ production in regenerative medicine.

Success for this renewal concept will include advancement in the utility of tissue chips to model accelerated aging, development of tissue chip avatars for use in precision medicine, and development of various countermeasures against aging and radiation exposure for terrestrial use.

Project/Program Officer:
Danilo A. Tagle, Ph.D., M.S.
Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-594-8064
Email: danilo.tagle@nih.gov

Biomedical Data Translator Performance Phase Concept

Sept. 28

Tyler Beck, Ph.D., presented a renewal contract concept for the Biomedical Data Translator performance phase. Hundreds of biomedical data sources exist but have not been well aligned to allow researchers to explore and make connections among them. Biomedical researchers do not always know where to go to find critical information relevant to their work. Such processes as drug discovery and drug interaction prediction are not well modeled in software and entail significant upfront preclinical expenses.

NCATS proposes this renewal concept to significantly improve and build on the capabilities of the recently released Biomedical Data Translator System through enterprise-level software engineering and data science research. The objectives of the Biomedical Data Translator performance phase are to incorporate additional templated queries and enhance system functionality. Efforts will focus on developing enterprise-level software, building user trust, and allowing the developer-user to be onboarded.

The expectation is that links from the GARD Information Center website will continue to expand and drive traffic. The LitCoin knowledge graphs will be easily integrated, and monthly active users will grow to nearly 2,000. NCATS recognizes that true translation requires an understanding of biology at all levels, from the molecular level to the population level. The long-term (audacious) goal is that the Biomedical Data Translator will be used by researchers as often as PubMed.

The Biomedical Data Translator is unique within NCATS in both its scope and requirements. Research funding will be provided through other transaction authority. Funding for the Biomedical Data Translator user interface will be provided through a contract. The recent alpha version release showed the potential of and excitement for Translator. Plans are to implement major functionality and quality improvements during the proposed funding period.

Project/Program Officer:
Tyler F. Beck, Ph.D.
Scientific Program Officer
Office of Drug Development Partnership Programs
National Center for Advancing Translational Sciences
Phone: 301-827-1943
Email: tyler.beck@nih.gov

Addressing Health Inequities in Clinical Diagnostics Concept

Sept. 28

Dr. Sharma presented a new Small Business Innovation Research grant concept on Addressing Health Inequities in Clinical Diagnostics. Clinical laboratory assays and point-of-care devices often utilize nonbiological parameters as a proxy for diversity. Self-reported race or ethnicity does not correlate with diversity of populations. The percentage of European contribution to several African American samples within the continental United States varies tenfold, from 3.5 percent in the isolated Gullah-speaking Sea Islanders from South Carolina to 35 percent in Seattle. Clinical laboratory assays and point-of-care devices that utilize nonbiological parameters often fail minority patient populations. Biological attributes of diverse patient populations are often overlooked during assay and device development. Inadequate attention to the biological diversity of patient populations during the development phase has led to the release and utilization of many assays and devices that work best for only select populations.

NCATS proposes this concept to broadly address health inequities and disparities in the clinical assay and point-of-care device space. Investigators will be expected to develop diagnostics that meet or exceed the quality of existing diagnostics and will be encouraged to consider aspects of social determinants of health during the development process.

This research aligns with other health disparities activities across the ICs and addresses a known problem in health care processes. Academies are working to move away from nonbiological parameters in medicine. NCATS expects that this initiative will identify several clinical assays and devices that fail to incorporate diverse patient groups and relevant nonbiological parameters and will correct these to ensure the best and most equitable treatment for all patients. Support would be provided to small businesses that are developing assays and devices to address health inequities, with the long-term outcome being the release of new or corrected assays or devices that address health inequities and disparities in the clinical assay and point-of-care device space broadly.

Project/Program Officer:
Karlie R. Sharma, Ph.D.
Program Officer
Office of Drug Development Partnership Programs
National Center for Advancing Translational Sciences
Phone: 301-451-4965
Email: karlie.sharma@nih.gov

Preclinical Proof-of-Concept Studies for Rare Diseases

Jan. 26

Christine M. Colvis, Ph.D., presented a new concept on preclinical proof-of-concept studies for rare diseases, which are demonstrations of efficacy in a model system prior to conducting regulatory safety studies. A gap exists between early discovery/early preclinical development and investigational new drug (IND)–enabling development due to a lack of funding. The goal of this concept is to bridge the gap between novel compound development and initiation of IND-enabling studies, resulting in identification of meritorious compounds. The aim is to support efficacy testing for repurposing approved therapeutics to treat rare diseases.

NCATS proposes to provide funding to test the efficacy of meritorious compounds in an established rare disease preclinical model. This effort will require partnership with a rare diseases steering committee or oversight committee. NCATS anticipates that such a partnership would strengthen potential applications by bringing the patients’ perspective into the translation process earlier than normal; encourage researchers who work adjacent to drug development to think more intentionally about the translational potential of their research; and increase use of existing rare disease models.

In terms of appropriateness for NCATS funding, this research puts patients first by requiring partnerships with rare diseases experts, patients, and patient advocates; increasing the use of existing rare disease models, on which meritorious compounds and repurposed therapeutics would be tested; and impelling basic scientists to think more intentionally about designing studies that withstand critical evaluation by industry and having more relevance to the patient population in question. The anticipated outcome will be strong preclinical efficacy data to attract subsequent investment in IND-enabling preclinical development within the rare diseases space. The potential impact is that several of the drug candidates will advance through development within other programs at NCATS or NIH and subsequently be used in clinical trials.

Reviewers are being asked to evaluate the number of compounds that transition into full IND-enabling preclinical development and to ensure that major obstacles are addressed (e.g., verifying that drug candidates are evaluated for merit during review, utilizing the best rare diseases models, increasing awareness in the rare diseases community of the partnership opportunities). The concept leverages other NCATS programs and initiatives, including the Division of Rare Diseases Research Innovation (DRDRI) Clinical Trial Readiness for Rare Diseases, Disorders and Syndromes program. In addition, the Division of Preclinical Innovation (DPI) has identified the transition from compound to full IND-enabling development as a “pain point” to be addressed. Strong efficacy data generated in this research would help alleviate this issue.

Project/Program Officer:
Christine M. Colvis, Ph.D.
Director
Office of Drug Development Partnership Programs
National Center for Advancing Translational Sciences
Phone: 301-451-3903
Email: ccolvis@mail.nih.gov

2022

Awards Supporting Cutting-Edge Technology for Translational Science (ASCETTS)

Sept. 22

Tyler F. Beck, Ph.D., presented a new concept on establishing ASCETTS, which is filling a gap in research funding opportunities for translational researchers. NCATS proposes this concept to allow early-stage development of new biomedical technologies, which traditionally have been challenging to fund. A distinct lack of funding for investigator-initiated innovation in translational sciences programs for basic science remains a priority. The framework for this concept is the successful Cutting-Edge Basic Research Awards (CEBRA) sponsored by the National Institute on Drug Abuse (NIDA). Though CEBRA has resulted in several exciting projects’ being funded, they are not in the translational sciences. This funding gap in NIH, as well as National Science Foundation, grants has been recognized by other research groups, such as the University of North Carolina (UNC) Office of Technology Commercialization.

The objectives of this concept are to create a funding opportunity for innovative technology development and stimulate development of technologies that could be further developed under the Small Business Innovation Research (SBIR)/Small Business Technology Transfer (STTR) program or supported by other investors.

Regarding implementation, the aim is to support the development of new technologies leading to translational science advancements, thus bringing more treatments to more people more quickly. The anticipation is that successful ASCETTS should lead to STTR awards or direct engagement with technology and pharmaceutical industry leaders. The long-term outcome would be uptake of new technologies by translational researchers. Examples of potential projects include nanoparticle packaging for alternative drug delivery modalities; dermal implants for monitoring or delivery of drugs; and development of new algorithms to predict threatening drug interactions.

Miniaturization and Automation of Tissue Chip Systems (MATChS)

Sept. 22

Dr. Tagle presented a new SBIR grant concept to establish MATChS, which is addressing a translational science gap. Although tissue chips have been successful, have been widely used, and are well-positioned as an alternative method for drug development, widespread adoption of this methodology by industry, regulatory agencies, and biomedical research has been impeded. This can be attributed to the complexity of the supported instrumentation necessary, and the specialized expertise needed to operate those systems. A partnership among NCATS, the National Aeronautics and Space Administration (NASA), and the Center for Advancement of Science in Space, the Tissue Chips in Space program has made key technological innovations toward the automation and miniaturization required for space flight. Since 2018, NCATS scientists have worked with NASA and Space Exploration Technologies Corp. (commonly called SpaceX) payload developers and space implementation partners (e.g., Techshot, Inc., Space Tango) to reduce tissue chip hardware from the size of a typical refrigerator to the size of a shoebox.

The objectives are twofold: Translate the lessons learned in re-engineering tissue chip platforms toward a smaller footprint and simplification of systems for ease of use and increase commercialization of the improved tissue chip platforms for widespread use in drug development and in biomedical research. Areas of emphasis include creating bench-top, portable, automated, self-contained systems that maintain 3-D tissue constructs and provide biologically relevant outputs of tissue health and function (e.g., fluid sampling, electrode incorporation, microscopy, biosensors). Emphasis also will be on producing demonstrable pathways to commercialization.

NCATS is proposing to use the cooperative agreement small business SBIR/STTR solicitation and will continue to use and implement tissue chips as a promising drug development tool across NIH and other government agencies. NCATS anticipates that more cost savings will be realized in drug development. In its current state, tissue chip technology is estimated to save up to 26 percent of drug development research and development cost in 2024. The success of MATChS will result in the increased availability of automated tissue chip platforms with a smaller and simpler footprint for use beyond drug development and across multiple applications and settings. In the clinical setting, the application will be for personalized patient-specific chips; on the battlefield, for assessment of countermeasures against developing threats; and in drug treatment and spaceflight, in evaluating long-term effects of stressors, including chronic disease.

Project/Program Officer:
Danilo A. Tagle, Ph.D., M.S.
Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-594-8064
Email: danilo.tagle@nih.gov

Small Manufacturing Systems to Produce Research-Grade Pharmaceutical Intermediates

Sept. 22

Dr. Tagle presented the SBIR contract topic Small Manufacturing Systems to Produce Research-Grade Pharmaceutical Intermediates. The development of preclinical drug candidates is time and cost intensive, averaging 10 to 15 years and costing $2.6 billion. Quality and access to pharmaceutical intermediates (i.e., raw chemical ingredients) by medicinal chemists are among the limiting factors. Most preclinical development involves the chemical synthesis of the candidates. NCATS recognizes that chemists’ on-demand access to pharmaceutical intermediates will speed up the design-synthesize-test cycle.

Exploring chemical space in drug development requires two components. The first is access to bulk specialized pharmaceutical intermediates, made in-house or via a contract research organization. The second is focused efforts toward synthesis of drug candidates by medicinal chemists. The hypothesis is that leveraging automation in synthetic chemistry will facilitate access to bulk specialized pharmaceutical intermediates and treatments, with the ability for rapid scale-up.

NCATS proposes this concept to develop tools to increase synthetic chemistry throughput to reduce development time for preclinical candidates. The objectives are to (1) develop automated tools for use by synthetic chemists to improve access to pharmaceutical intermediates and (2) increase the rate of exploration of chemical space by accelerating chemical synthesis in drug discovery. The key areas of emphasis for this contract solicitation include utilization of current automation technology in synthetic chemistry adaptable to multiple chemical methodologies and the rapid scale-up of technology that is amenable to real-time data acquisition and monitoring.

Current activities related to this concept include the ASPIRE Program and NCATS–DARPA Collaboration for Flexible Manufacturing of Fine Chemical Reagents. This research will provide additional support to develop non–good manufacturing practice reagents for laboratory use. NCATS support will recognize that higher throughput synthetic chemistry will improve the rate of development of preclinical candidates. Improving access to pharmaceutical intermediates will increase the rate of drug candidate development and biological data generation for exploring chemical space. The success of this project will be the creation of an automated synthetic chemistry device to prepare pharmaceutical intermediates quickly on-demand, such that a chemist can focus efforts toward preparing drug candidates for biological testing.

For this contract concept, reviewers are being asked to consider the scientific, technical, or programmatic significance of the goals of the proposed research and development activity; availability of the technology and other resources necessary to achieve the required goals; and the extent of identified practical, scientific, or clinical uses for the anticipated results. Comments on each of these features have been provided in the Council materials.

Project/Program Officer:
Danilo A. Tagle, Ph.D., M.S.
Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-594-8064
Email: danilo.tagle@nih.gov

Translational Centers for Microphysiological Systems (TraCe MPS)

May 20

Dr. Tagle presented a new concept to establish TraCe MPS, which leverages the fact that MPS hold promise as a leading new approaches method (NAM). NCATS continues to play a leadership role domestically and internationally in the development, implementation and adoption of this technology for the drug development process. Despite scientific advancements, the need to translate MPS in the direction of industrial use and regulatory acceptance is great.

NCATS proposes this concept to accelerate the translational use of MPS in drug development through regulatory acceptance and adoption for industrial use by drug developers. The aim is to develop tissue chips that are fit-for-purpose for industry needs and have specific context of use (CoU) that will satisfy regulatory approval criteria. The objectives are to establish translational centers focused on regulatory qualification of MPS with active input and engagement from key stakeholders and end users (e.g., FDA and pharmaceutical members of the IQ MPS Affiliate) and engage other NIH ICs in the formation and funding of these translational centers. The expectation is that the translational centers will, through the project period, be able to qualify several MPS models as drug development tools (DDTs).

In terms of key areas emphasis, the MPS models will need to meet end-user criteria for biomarkers and assays as defined by industry. The NIH, FDA, and the IQ Consortium will co-develop study designs for each organ system and MPS model that will be suited to have multiple CoUs, each of which could be the basis for qualification by the FDA as a DDT. In addition, discussions are underway to have FDA serve as a center hub.

This proposed initiative aligns with the Tissue Chips for Drug Screening program and will be the culmination of NCATS’ investments in developing MPS as in vitro models for safety pharmacology, therapeutic efficacy, and precision medicine. NCATS’ support of this concept is important to continue its leadership in this field and to further spur engagement and investments in using MPS as DDTs. NCATS anticipates that this initiative will pave the way for regulatory and industry use of MPS that will address scientific, legislative, and ethical needs for more predictive NAMs.

Project/Program Officer:
Danilo A. Tagle, Ph.D., M.S.
Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-594-8064
Email: danilo.tagle@nih.gov

HEAL LitCoin Pilot Program to Enable Pain and Addiction Research Discoveries

May 20

Tyler F. Beck, Ph.D., presented a new contract concept on establishing an NIH HEAL Initiative LitCoin Pilot Program to enable pain and addiction research discoveries. ODDPP envisions LitCoin as a biomedical publication that allows researchers to share results normally not included in high-impact peer-reviewed journals and to do so computationally and without the burden of additional work. In the LitCoin framework, the authors (i.e., researchers) write an abstract-length description of their work and the conclusions and upload the text to the LitCoin server. The NLP algorithms generate knowledge assertions, which are displayed to the researcher for verification. The publisher partner reviews the assertions and approves them for publication.

Dr. Beck highlighted that the June 2021 NCATS LitCoin Stakeholder Feedback Workshop and LitCoin Natural Language Processing (NLP) Challenge — organized in collaboration with CrowdPlat, Inc., Bitgrit (Tokyo, Japan), and NTL — informed developing the NCATS LitCoin program. The goals of the broader LitCoin program are threefold: Encourage researchers to share their data their data in a computationally accessible manner; generate highly connected knowledge networks from published works with built-in curation; and encourage the reporting of research findings that may be separate from the researcher’s main hypothesis. In addition to the NLP challenge, NCATS soon will sponsor a conceptual challenge for the design of the LitCoin platform.

NCATS is proposing this concept to build a critical component of the LitCoin platform to pilot with pain and addiction research, because it fits with the NIH HEAL Initiative. The proposed platform extends from observation to open data reuse and involves converting human-readable knowledge to machine-readable knowledge. The deliverables of this pilot program and feasibility study are to create a sophisticated web interface that will allow researchers to upload free text describing their findings. A successful system should be able to run NLP algorithms on the text to extract knowledge assertions and display extracted assertions to researchers, allowing confirmations and edits. The system also will need to connect with publisher partners to facilitate easy journal submissions. After confirmation from the publisher of acceptance, the system would deposit the assertions into the LitCoin knowledge graph to allow reuse.

Regarding implementation of the project and its expected impact, this research has the potential to fundamentally change the manner in which researchers publish their work by allowing computational-accessible knowledge to be generated as part of the publication process. NCATS, which is well suited to conduct such pilot studies to assess feasibility of transformational concepts, anticipates that this concept will result in findings that may not have been published or accessible to researchers. In addition, publishing failed drug discovery attempts could improve efficiency in drug development.

NIH HEAL Initiative LitCoin Foundational Knowledge Graph

May 20

Dr. Beck presented the second ODDPP new contract concept, the NIH HEAL Initiative LitCoin Foundational Knowledge Graph, which also is a critical component of the LitCoin platform to pilot with pain and addiction research. The objectives are to extract free text from existing research publications in the pain and addiction research space and generate knowledge assertions using the NLP systems that emerged from the 2022 LitCoin NLP challenge. The NIH HEAL Initiative investigators will review the NLP-generated assertions extracted from their own publications and verify that they are accurate. Some professional curation to ensure accuracy is expected.

The chief deliverable will be a robust knowledge graph with highly accurate knowledge assertions in the pain and addiction research space generated using NLP. This process will involve combining the algorithms received through the 2022 LitCoin NLP challenge into a single system that can generate knowledge assertions and run those assertions on PubMed abstracts in the pain and addition space collected from a portfolio analysis of the NIH HEAL Initiative investigators. The contractor will build a simple web interface to allow researchers to curate their knowledge from prior publications and organize virtual events (e.g., workshops) to engage researchers in the creation of computationally accessible knowledge.

This concept is a continuation of the broader NCATS LitCoin initiative and will support the LitCoin Pilot Program. NCATS anticipates that normalizing the pre-curation of extracted knowledge will provide researchers more agency to ensure that their findings are discovered and widely reused. The generated knowledge graph complements other NCATS programs, such as the Biomedical Data Translator.

Dr. Beck summarized that NCATS proposes two new concepts to pilot a program that could fundamentally change the way that researchers publish their discoveries by providing a new currency of research consistent with present practices. NCATS anticipates that asking researchers to curate their own generated knowledge will energize them and help them understand how NLP can enhance their own work. If successful, this effort could expand to other fields, leading to a fundamental shift in publication practices, with far-reaching consequences for the generation and reuse of biomedical knowledge.

For these contract concepts, the reviewers are being asked to consider the scientific, technical, or programmatic significance of the goals of the proposed R&D activity; availability of the technology and other resources necessary to achieve the required goals; and the extent of identified practical, scientific, or clinical uses for the anticipated results. Comments on each of these features have been provided in the Council materials.

ACTIV-1 Time-Limited Biospecimen Storage and Related Services (COVID19)

May 20

Soju Chang, M.D., M.P.H., presented a contract concept for ACTIV-1 time-limited biospecimen storage and related services. Dr. Chang noted that Cynthia Boucher, M.S., project manager for ACTIV-1 and Samuel A. Bozzette, M.D., Ph.D., Chief Medical Officer, OTM, NCATS, would be available for the discussion of this concept. ACTIV-1 is funded through a task order under the Biomedical Advanced Research and Development Authority (BARDA) contract and is managed by NCATS. The period of performance for the BARDA task order is from Aug. 8, 2020, to Sept. 30, 2022. Research samples of whole blood, serum, and plasma were collected from consented participants during the trial and stored in the ACTIV-1 biospecimen storage facility for future use.

NCATS proposes this new contract concept to continue the support of existing activities under the BARDA task order and provide additional services after the conclusion of the trial. The objectives are to provide (1) time-limited storage and distribution of deidentified biospecimens, (2) regulatory support and data management of clinical data, and (3) additional statistical analyses. The key areas of emphasis are biospecimen management, clinical data management, and biospecimen analyses.

NCATS will manage the biorepository contract funded by OWS. Regarding the expected impact, this resource will permit the medical community to better understand the role of inflammatory markers and cytokines to predict the clinical course of COVID-19 disease and the disease’s response to treatments evaluated in ACTIV-1. The outcome will be publications describing finding related to the results of the biospecimen analyses.

For this contract concept, reviewers are being asked to consider the scientific, technical, or programmatic significance of the goals of the proposed R&D activity; availability of the technology and other resources necessary to achieve the required goals; the extent of identified practical, scientific, or clinical uses for the anticipated results; and the adequacy of the inclusion of women, minorities, and individuals across the lifespan in clinical research. Comments on each of these features have been provided in the Council materials.

Dr. Chang explained that the ACTIV-1 clinical trial recruited hospitalized adults (age 18 and older) who had COVID-19. Enrollments span across the United States and in Latin America. The trial had no exclusions by gender or race and ethnicity; children, however, were excluded because this was the first trial evaluating two repurposed drugs and one experimental drug to treat COVID-19. NCATS will contribute towards the scientific evidence to better understand the clinical course of COVID-19 and treatment response of immunomodulators tested in ACTIV-1.

Project/Program Officer:
Soju Chang, M.D., M.P.H., FACPM
Medical Officer
Division of Clinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-827-9206
Email: soju.chang@nih.gov

Device or Process for the Cleaning of Cell Tissue Culture Flasks

May 20

Sam G. Michael presented a new SBIR contract concept for a device or process for cleaning cell-tissue culture flasks, which addresses an unmet need. The use of consumable plastics is prevalent in biomedical research, with well over 90 percent being used once and then disposed. There are many challenges to such a practice. These products are expensive and generate large quantities of laboratory waste. Supply chain shortages have made these products even more expensive or difficult to acquire, impacting the ability of laboratories to perform research.

NCATS proposes this SBIR contract topic to identify a small business that can develop a device or a process capable of cleaning, sterilizing and treating tissue culture flasks. Such a process would allow repeated use of flasks before they are discarded in a burn box for incineration. A key requirement will be that the device or process has the ability to clean flasks while also applying a surface treatment to make them amenable to cell growth.

NCATS will help draft evaluation criteria, to be included in the solicitation, for verifying the characteristics of the flask after a cleaning process, including the sterility assurance level and cell viability measurements. Another key area of emphasis will be how to handle the caps, which may prove difficult to clean and may require that each flask have a replacement cap. In terms of implementation, this contract concept aligns with existing Information Technology Resources Branch efforts in laboratory sustainability, particularly in saving plates, tips, and reagents.

Regarding the expected impact, NCATS is a proven leader in laboratory sustainability, and its efforts in this space (e.g., IonField Systems SBIR) have saved tons in plastic wastes and hundreds of thousands of dollars. The ability to reuse tissue culture flasks could reduce overall laboratory waste and save laboratories substantial consumable costs, given their general expense. This concept provides an opportunity to a U.S. small business to develop a solution to this problem. The metric of success will be a product or process that can clean flasks for reuse.

For this contract concept, reviewers are being asked to consider the scientific, technical, or programmatic significance of the goals of the proposed R&D activity; availability of the technology and other resources necessary to achieve the required goals; and the extent of identified practical, scientific, or clinical uses for the anticipated results. Comments on each of these features have been provided in the Council materials.

Project/Program Officer:
Samuel G. Michael
Chief Information Officer
Information Technology Resources Branch
Office of Administrative Management
National Center for Advancing Translational Sciences
Phone: 301-827-7796
Email: michaelsg@mail.nih.gov

Botulinum Toxin Potency Assay Using Tissue Chips (BoT PATCh)

May 20

Dr. Tagle presented the SBIR grant topic for BoT PATCh. In terms of the gap or need for this research, the mouse lethality bioassay (MLB) or the model dose that kills 50 percent of the population (LD50) assay has been the standard FDA-approved method to determine the safety and potency of each batch of botulinum toxin manufactured for medical and cosmetic uses since 1928. The challenge is that MLB is laborious and expensive and requires a sophisticated animal facility with a skilled and dedicated workforce. Ethical concerns have led to bans on the sale of cosmetic products or their components, which have been tested in animals. These concerns have resulted in rigorous efforts to develop alternative testing methods for the safe use of botulinum toxin in humans. In partnership with the FDA, NCATS has sought to develop such methods. NCATS has matured and validated human neuromuscular junction tissue chips that can provide a useful alternative platform for a NAM for quantitative analysis and titer evaluation of botulinum neurotoxins.

NCATS proposes to use the Center’s SBIR program to solicit U mechanism grants to develop and commercialize neuromuscular junction tissue chip platforms that will replace the MLB as a potency assay for botulinum toxin. The two main objectives are to develop and qualify neuromuscular junction tissue chips for BoT PATCh in partnership with the FDA and to establish commercialization avenues through the NCATS SBIR program after the platform has qualified as a DDT.

Although several alternative strategies and methodologies have been proposed for botulinum toxin testing, including both ex vivo assays (e.g., mouse phrenic nerve hemidiaphragm tests and non-lethal mouse flaccid paralysis assays) and in vitro assays (e.g., cell-based and nucleic acid tests), all have fallen short of replacing the MLB assay. Qualification as a DDT with the FDA will involve a side-by-side concordance study between the BoT PATCh and the conventional MLB assay.

This proposed initiative would leverage the Tissue Chips for Drug Screening program and complement ongoing activities supported by NCATS in developing MPS as in vitro models for safety pharmacology, therapeutic efficacy, and precision medicine. NCATS support of this concept is important to continue its leadership in this field and to spur engagement and investments in developing MPS as DDTs.

NCATS anticipates that this initiative will have a great impact on the field by replacing the MLB potency assay or LD50 assay for botulinum toxin. The successful outcome of this activity will lead to a DDT for the assessment of botulinum toxin potency during manufacturing, which will not only affect the cost and ease of use for the assay but also support the reduction, refinement, and replacement (known as the three Rs) of animal testing.

For this contract concept, reviewers are being asked to consider the scientific, technical, or programmatic significance of the goals of the proposed R&D activity; availability of the technology and other resources necessary to achieve the required goals; and the extent of identified practical, scientific, or clinical uses for the anticipated results. Comments on each of these features have been provided in the Council materials.

Project/Program Officer:
Danilo A. Tagle, Ph.D., M.S.
Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-594-8064
Email: danilo.tagle@nih.gov

Online Education Modules to Advance Understanding of Translational Science Principles

Jan. 20

Jessica M. Faupel-Badger, Ph.D., M.P.H., presented a new concept to develop online education modules to advance understanding of translational science principles. An extensive literature review that identified gaps in formal translational science education, experience with NCATS’ internal training program, and feedback received from the community speak to the need for curricula and activities that disseminate effective practices in translational science. The Education Branch recently has developed and implemented two online courses that use examples of successful NCATS-led efforts to demonstrate how specific research advances can be examined to offer insight into the translational process and identify common challenges and solutions applicable to research initiatives across the translational science spectrum. Those efforts have informed principles of effective translational science that have been incorporated into these initial courses.

Directly aligning with the NCATS strategic goals, this translational science initiative will increase the capacity of the Education Branch’s teaching experience and educational research and will further develop and formalize core concepts, approaches, and strategies derived from the field’s experience and knowledge. This concept also will increase broad access to translational science and advance innovative evidence-informed approaches to online education. New educational activities will supplement NCATS’ current education and training programs, adding effective practices, and will make progress in establishing translational science as a distinct area of study.

Regarding objectives and areas of emphasis, NCATS proposes to develop a portfolio of extramural research education awards that would result in a suite of online education activities, focusing on teaching effective practices and core principles of translational science. Evaluation criteria of the modules include (but are not limited to) data fields on diversity of the participants across all areas (e.g., training and career) and adherence or scale of participation. NCATS anticipates that this concept will broaden and expand foundational translational science knowledge, maximize online learning, and catalyze development of new translational science curricula.

Project/Program Officer:
Jessica M. Faupel-Badger, Ph.D., M.P.H.
Chief
Education Branch
Office of Policy, Communications and Education
National Center for Advancing Translational Sciences
Phone: 301-827-4342
Email: badgerje@mail.nih.gov

Exosome Therapeutics for Regenerative Medicine (ExTReMe)

Jan. 20

Christine M. Happel, Ph.D., presented a new concept focusing on ExTReMe. Despite advances in regenerative medicine, major challenges remain. For example, stem cell transplantation is currently the main method for tissue regeneration, but progress is limited. Hurdles include ensuring a reliable cell source, tumor formation, inappropriate stem cell migration, immune rejection of transplanted stem cells, and complications during surgery and postoperative infection. To address these challenges, NCATS proposes a novel exosome-based therapeutics paradigm to catalyze regenerative medicine. In terms of the therapeutic potential, exosomes are endogenous, small membrane-enclosed carriers of bioactive molecules used for intercellular signaling. Exosome-based intercellular communication can occur bidirectionally during normal cell homeostasis or as a consequence of pathological development. In a diseased cell indicating distress, the stem cell responds by releasing specific repair exosomes.

This concept is a paradigm shift in that it will use non-living cellular products, rather than stem cells, to promote tissue regeneration. The exosome-based therapies can promote tissue repair and wound healing that can be better translated into the clinic. ExTReMe would expand knowledge and resources developed by the NIH Common Fund’s ExRNA Communication Program, in which exosomes are being investigated as critical mediators of intercellular communication. In addition, the concept would extend the recently concluded NIH Common Fund Regenerative Medicine Program and leverage the expertise of the NCATS Stem Cell Translation Laboratory (SCTL).

The objective of this concept is to transform regenerative medicine through novel exosome-based therapeutics in tissue repair and wound healing, with emphasis on direct exosome therapy (stem cell–isolated, stored as off-the-shelf), as well as designer exosomes (personalized to the individual patient’s needs). This research, when implemented, would focus on investigational new drug (IND)–enabling therapeutics and would involve early engagement with the FDA toward regulatory approval. A milestone-driven approach will be used to ensure that these exosome-based therapeutics for productive regeneration are translated to the clinic. Research activities and results are expected to spur a number of commercial activities beyond the initial NCATS investment.

Project/Program Officer:
Christine M. Happel, Ph.D.
Program Officer
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-827-9444
Email: christine.happel@nih.gov

Rare Diseases Clinical Research Network (RDCRN) – Rare Disease Clinical Research Consortia

Jan. 21

Tiina K. Urv, Ph.D., M.P.H., presented a renewal concept for the RDCRN Rare Disease Clinical Research Consortia (RDCRC). Established by the Rare Disease Act of 2002 to promote highly collaborative, multisite, patient-centric, translational, and clinical research in rare diseases research, the RDCRN, through the RDCRC, has always supported the study of three or more rare diseases at once. This renewal concept addresses several gaps in rare diseases research. The field lacks foundational and translational research that fully describes rare diseases and facilitates the movement of candidate treatments into the clinic. The cost (i.e., time and money) of one‑disease-at-a-time approaches to rare diseases research remains high. Standardized, high-quality data and broad data sharing for rare diseases are needed.

NCATS proposes this renewal concept to advance the diagnosis, management, and treatment of rare diseases by focusing on unmet clinical trial readiness essentials that will advance the research by establishing, maintaining, and supporting Rare Disease Centers of Excellence. The objectives are threefold: (1) Lessen the risk of failure in clinical trials by being well prepared prior to starting a trial, (2) develop an effective and efficient research environment for rare diseases research, and (3) facilitate data sharing. The key areas of emphasis are to (1) conduct research studies that promote clinical trial readiness, such as natural history studies, biomarker identification, and outcome measures development; (2) provide a research environment that delivers support and opportunities for students and early-stage investigators and engages patient advocacy groups as full partners with RDCRN; and (3) develop and maintain a cloud-based research environment with shared tools and cross‑network collaborations.

In terms of implementation and expected impact, the RDCRN currently supports 20 RDCRCs that study 165 different rare diseases and conducts research at 358 sites (144 co-located at Clinical and Translational Science Awards (CTSA) sites) in 12 countries. Currently, 166 Coalition of Patient Advocacy Groups (CPAGs) partner in the consortia. Within the RDCRN4 cohort, 10 will sunset and 10 will be eligible to recompete. The ORDR facilitates and coordinates rare diseases research at NIH, and the RDCRN plays a significant role. The RDCRN program partners with nine other NIH Institutes/Centers (ICs). The RDCRN is a one-of-a-kind translational research network at NIH, establishing partnerships to address multisystemic disorders, supporting research into very low prevalence rare diseases, and advancing the many-diseases-at-a-time approaches.

Success has been, and will continue to be, measured through progress in addressing consortia-specific gaps in clinical trial readiness; publications generated; initiation of longitudinal observational studies and accruals; participation of clinical sites and patient advocacy groups (PAGs) in the research; and the numbers and types of pilot studies and clinical trials conducted.

Project/Program Officer:
Tiina K. Urv, Ph.D.
Program Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-827-2746
Email: tiina.urv@nih.gov

Rare Disease Clinical Research Network (RDCRN) – Data Management and Coordinating Center

Jan. 21

Tiina K. Urv, Ph.D., M.P.H., presented a renewal concept for the RDCRN Data Management and Coordinating Center (DMCC). The objectives are to (1) provide administrative, clinical research, data management, and regulatory support to the individual RDCRCs and the RDCRN; (2) provide a centralized cloud-based research environment with shared resources for the network and participants; and (3) coordinate cross-network activities, such as working group or special interest group meetings. In addition, the DMCC serves as a conduit of information related to the rare diseases research being conducted within the network to both the research community and the general public.

The DMCC has three key areas of emphasis: (1) Promote clinical trial readiness and support and facilitate cross-consortia collaboration; (2) establish and promote standards and good data practices, emphasizing scientific rigor, FAIR (Findable, Accessible, Interoperable, and Reusable) data principles, and data sharing; and (3) develop and maintain a cloud-based research environment with shared tools.

To date, the DMCC has provided services to more than 2,000 authenticated users across five continents and has developed 12 tools for shared network use (e.g., biospecimen tracking tool, pedigree drawing tool, Ambra Health, RStudio), 55 protocols in REDCap databases, several new and legacy forms, numerous new and legacy variables, and 1.5 terabytes of data in Box. The DMCC collaborated with the NCATS Information Technology Resources Branch to develop a two-pronged cloud-based workspace for RDCRN researchers.

The RDCRN is a one-of-a-kind translational research network at NIH. A successful program is one in which the investigators are working in the research environment established by the network and using the tools made available. Success also will be measured by the achievements of the individual RDCRCs and the use and acceptance of DMCC-hosted collaborative tools and activities.

Project/Program Officer:
Tiina K. Urv, Ph.D.
Program Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-827-2746
Email: tiina.urv@nih.gov

2021

Ethical Issues in Translational Science Research

Sept. 24

Elaine Collier, M.D., presented a renewal concept for support of the Ethical Issues in Translational Science Research program. This program seeks to address bioethical, legal, and social questions affecting ongoing and future research and its translation. The Ethical Issues in Translational Science Research program addresses ethical issues that impede the translation of new discoveries and technologies by developing data and evidence in relevant areas, such as synthetic biology chimeras; gene editing; organoids; data collection, sharing, and privacy; machine learning and artificial intelligence; business models; citizen science; do-it-yourself science; and behavioral science. This program has garnered sustained interest from members of the translational science and ethics communities, and it has engaged stakeholders in ethical issues in translation.

Program renewal will continue development of data and evidence to inform ethical issues that affect the translation of new discoveries and technologies and approaches to their application to health. The renewal will expand interest areas to include ethical, legal, and societal challenges related to racial and health disparities in the translation of discoveries at individual, community, institution, and society levels. It also will encourage collaboration among bioethicists, legal scholars, social scientists, and translational scientists.

The renewal will extend the Ethical Issues in Translational Science Research program for an additional 5 years. The program will include two submission rounds per year, with only highly meritorious applications in translational science and bioethics research being selected for NCATS’ support. The expected result of this concept renewal is to foster sustained focus for translational science and bioethics research; increase the knowledge base addressing ethical, legal, and societal implications of translation of discoveries’ application to health; and recognize a professional community of experts.

Project/Program Officer:
Elaine Collier, M.D.
Senior Advisor to the Director
Office of the Director
National Center for Advancing Translational Sciences
Phone: 301-814-4286
Email: colliere@mail.nih.gov

CTSA Collaborative and Innovative Acceleration (CCIA) Award

Sept. 24

The CCIA concept seeks to enhance collaboration with NIH ICs and other stakeholders, emphasize transformative and high-impact projects that address the missions and strategic goals of NCATS and NIH ICs, and support all phases of innovative and high-impact projects. The CCIA program will require the collaboration of at least three CTSA Program Hubs or at least two CTSA Program Hubs plus at least one other eligible organization.

The concept will emphasize work in late-stage translational science—such as clinical implementation and public health—and it seeks to change the funding mechanism to a performance-based approach driven by measurable milestones. The current R21 and U01 funding mechanisms will be replaced with UG3 and UH3 funding mechanisms, and awards will transition from UG3 to UH3 based on performance. UG3 awards will be for 2 years and focus on the development, demonstration, and feasibility assessment of innovative solutions that address scientific and operational barriers. UH3 awards will be for up to 3 years and focus on the dissemination, implementation, and evaluation of these innovative solutions.

The new CCIA concept will advance translational science through evidence-based approaches, enhance collaboration with NIH ICs and other stakeholders, leverage CTSA Program resources, and enhance the translational process so innovative interventions to improve health can be disseminated more efficiently. This concept is intended to support synergistic activities that improve the translational research process through collaboration and innovation while integrating the CTSA Program with NIH-funded translational research networks and activities that advance translational science.

Machine-Assisted Approaches to Shortening the Diagnostic Odyssey for Rare Diseases

Sept. 24

The years-long delay in diagnosis and frequent misdiagnosis of rare diseases (i.e., the diagnostic odyssey) can last decades. NCATS proposes in this concept, via the Small Business Innovation Research (SBIR) program, to accelerate and improve diagnoses for rare diseases using machine learning approaches that are readily usable in front-line clinical settings.

One objective of this concept is to develop machine-assisted approaches that accelerate and improve diagnoses for hard-to-diagnose patients and are applicable to a broad array of rare diseases. The strategies that are proposed or developed must be usable or adaptable to more than one health care setting, EHR, or database. The strategies also ideally would be usable and accessible by front-line clinicians and readily integrated into the clinical workflow of multiple care settings.

Concept coordinators strive to progress in the following key areas:

Permit early identification and escalation of patients at high risk for a rare disease through data mining or via remote assessment in an office or home setting.
Permit collection, integration, or assessment of data points from multiple sources.
Permit more accurate assessment of the rare disease patient’s overall medical utilization through new measures enabled through machine-assisted approaches.

NCATS promotes the idea that small businesses, via the SBIR program, can provide innovative solutions to the identification of patients who are at high risk of having a rare disease or who have been misdiagnosed or are undiagnosed. Success in this area would be achieved via the development of an easy-to-use tool that is valuable to front-line clinicians and integrated into clinical practice, and for which accelerated diagnostic timelines can be shown.

Accelerating rare disease diagnosis using available data in EHR or health care system databases could shorten the diagnostic odyssey, save resources through targeted disease-specific care, limit irreversible complications of disease by enabling timely intervention, and change the research environment for rare diseases such that all patients with a rare disease have a chance for disease-modifying therapy.

Project/Program Officers:
Anne R. Pariser, M.D.
Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-402-4338
Email: anne.pariser@nih.gov

Lili M. Portilla, M.P.A.
Director of Strategic Alliances
Office of Strategic Alliances
National Center for Advancing Translational Sciences
Phone: 301-827-7170
Email: portilll@mail.nih.gov

NIH HEAL: Illuminating the Understudied Druggable Proteome

Sept. 24

The Illuminating the Understudied Druggable Proteome concept will encourage research on understudied proteins within commonly drugged protein families to identify new targets for human disease. This will lay the groundwork for the exploration of these new targets for drug development by providing support for short-term projects that collect preliminary data on understudied proteins. This is a general concept for both NCATS and the NIH HEAL Initiative, and funding likely would come from both sources. The project will be disease agnostic, potentially covering all human diseases but focusing on NCATS and NIH HEAL Initiative priority areas, such as rare diseases and proteins associated with pain, addiction, and overdose.

Successes from the Common Fund IDG program have demonstrated that small research awards around understudied proteins stimulate more research on “new” proteins. The target landscape for drug development would be larger, leading to the development of more treatments for more diseases. Success will be evaluated by monitoring the funding of new grants around targets studied under this initiative and by monitoring publications released around understudied targets.

NCATS proposes this concept to expand the target landscape for drug development by providing a needed opportunity for the collection of preliminary data around the role of understudied druggable proteins in human disease and biologic processes. Identifying new targets associated with human disease is a critical first step in the development of novel, more efficacious treatments.

Project/Program Officer:
Karlie R. Sharma, Ph.D.
Program Officer
Office of Drug Development Partnership Programs
National Center for Advancing Translational Sciences
Phone: 301-451-4965
Email: karlie.sharma@nih.gov

Helping to End Addiction Long-term (HEAL) New Innovator Awards

Sept. 24

HEAL New Innovator Awards will support unusually creative early-career stage investigators from underrepresented backgrounds who propose innovative, high-impact research within the NIH HEAL Initiative domains of pain, addiction, or overdose. The emphasis of these awards is on the idea and the investigator, rather than the specific project. These awards could be applied to basic, translational, or clinical science.

The HEAL New Innovator Award already has been established at the NIH, but this application is the first time that it will be focused on the NIH HEAL Initiative and underrepresented groups. Applications for this award will not contain a detailed experimental plan or preliminary data. Instead, they will focus on the potential of both the innovative idea and individual investigator. The major components of the application will be the significance of the project and the problem that it seeks to address, the general approach that will be applied to address the problem in HEAL domains, an explanation of how the project is unusually innovative, and the qualities and experiences of the investigators that qualify them to pursue such research.

NCATS proposes this concept to foster original ideas from early-stage investigators in the HEAL fields and increase diversity within biomedical science. Success will be evaluated by monitoring the development of innovative approaches to treat pain, addiction, and overdose, as well as by examining the career trajectories of early-stage investigators from underrepresented groups who receive these awards.

Trial Innovation Network Infrastructure for the HEAL Pain Management Effectiveness Research Network

Sept. 24

One way the NIH HEAL Initiative seeks to stem the opioid crisis is through a focused effort on understanding, managing, and treating pain. Using existing TIN infrastructure, the HEAL Initiative established the ERN to conduct clinical trials addressing pain management questions for multiple pain conditions in one network to confront a need for safe and nonaddictive treatments that alleviate pain. NCATS proposes this concept to continue support of TIN infrastructure through a dedicated FOA for ongoing and future trials in the HEAL ERN. Funding for this concept will be provided by the NIH HEAL Initiative.

The HEAL ERN has the following objectives:

Compare the effectiveness of existing safe, nonaddictive therapies or ways to deliver current therapies.
Strengthen and inform current guidelines for pharmacologic and nonpharmacologic treatments for acute and chronic pain.
Provide patients and practitioners with a suite of effective strategies to alleviate pain and reduce reliance on opioids.
Manage acute and chronic pain in people from diverse communities.
Improve patients’ quality of life.

The TIN facilitates the attainment of these objectives by providing infrastructure through three key components: Trial Innovation Centers, Recruitment Innovation Centers, and CTSA Program Hubs. The TIN provides many services to ensure the successful implementation and completion of ERN trials.

The ERN and TIN networks coalesce into a synergistic structure through which individual NIH HEAL Initiative awards support trial study teams and participant costs. Trials address pain management questions that are of interest to multiple NIH ICs. The NCATS TIN provides clinical support, biostatistical coordination, and recruitment and retention support. Trials are conducted within and outside of CTSA Program Hubs to allow the recruitment of diverse patients with multiple pain conditions.

The HEAL ERN currently is conducting five clinical trials:

Effectiveness of an mHealth Psychosocial Intervention to Prevent Transitions from Acute to Chronic Postsurgical Pain in Adolescents
Integrated Treatment for Veterans with Co-occurring Chronic Pain and Opioid Use Disorder
Tailored Non-pharmacotherapy Services for Chronic Pain: Testing Scalable and Pragmatic Approaches
A Sequenced Strategy for Improving Outcomes in Patients with Knee Osteoarthritic Pain
Optimizing the Use of Ketamine to Reduce Chronic Postsurgical Pain

NCATS’ TIN is providing clinical, data, recruitment and retention, and biostatistical support in all clinical trial phases. The trials span multiple demographics, pain conditions, and NIH ICs. Despite COVID-19 delays, all the trials have met their required milestones and have been approved to move forward.

Continued support of TIN infrastructure will enable HEAL ERN study teams to complete ongoing studies and facilitate future NIH HEAL Initiative studies by addressing critical roadblocks innovatively, leveraging the expertise and resources of the CTSA Program, and accelerating the translation of interventions into therapies in real-world settings. Trial results will advance NIH HEAL Initiative efforts to stem the opioid crisis by identifying safe, nonaddictive interventions and management strategies for pain; generating an evidence base to inform treatment guidelines for acute and chronic pain; and providing patients and practitioners with a suite of strategies to alleviate pain and reduce reliance on opioids.

The goal of this concept is to provide continued support of existing TIN infrastructure that is enabling ongoing and new trials in the HEAL ERN. Funding for this concept will be provided by the NIH HEAL Initiative.

Project/Program Officer:
Yolanda F. Vallejo, Ph.D.
Program Director
Division of Clinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-451-1751
Email: yolanda.vallejo@nih.gov

Contract Support for NCATS Intramural R&D Activities

June 11

R. Dwayne Lunsford, Ph.D., presented a renewal concept for contract support of the NCATS intramural research and development (R&D) activities. NCATS proposes to renew this concept to complement in-house scientific capabilities of the DPI scientists—who require a variety of support services—and also to maintain access to mission-critical research services. DPI advances translational science by decreasing the risk of investing (i.e., de-risking) in promising new targets and therapies for indications that otherwise lack private-sector funding.

Since the original concept was approved in 2015, the DPI has generated data for regulatory filings (pre- IND and IND stage), contributing to 19 INDs. The DPI also developed diverse therapeutic targets and drug candidates (e.g., small molecules, peptides, bio-therapeutics). Regarding implementation and impact, NCATS will issue new requests for proposals (RFPs) addressing the relevant technical service areas. It is expected that contracts will allow seamless continuity of operations supporting ongoing and future collaborations and will include a Determination of Exceptional Circumstances (DEC) clause to protect the IP rights of the collaborators.

Project/Program Officer:
R. Dwayne Lunsford, Ph.D.
Deputy Director
Therapeutic Development Branch
Division of Preclinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-402-8462
Email: robert.lunsford@nih.gov

LitCoin Prize Competitions

June 11

Christine M. Colvis, Ph.D., informed the Council that the LitCoin concept was developed with the desire to help researchers share their data in a model that meets NIH requirements and the needs of investigators. NCATS will pilot test the project with the anticipation that the NIH National Library of Medicine and journal publishers will lead the efforts on a broader scale.

Tyler F. Beck, Ph.D., presented the concept for establishing LitCoin prize competitions. This concept addresses three main issues. First, data are not machine-readable. Second, generating computationally accessible data is costly and involves manual curation. Third, few incentives exist to promote data-sharing. In addition, early-career researchers have few mechanisms to share reproducible results outside of their respective disciplines. NCATS proposes to incentivize and enhance the sharing of machine-readable knowledge from biomedical publication free text.

Dr. Beck described the LitCoin conceptual framework, which consists of four key roles of engagement: author, NCATS, publisher, and other researchers. The author makes a discovery, writes a short publication, and uploads the text to the LitCoin server. NCATS facilitates a natural language processing (NLP) tool to build assertions and displays them back to the author, who verifies and then submits to the publisher. The publisher reviews the assertions and approves them for publication. The NLP deposits the information to a dedicated database. Other researchers can then cite the published findings and the data remain available and open to the public.

NCATS proposes two challenge competitions. Challenge 1, LitCoin NLP Challenge, will be a software contest to generate highly accurate, computationally accessible data from free text. The competition is planned for fall 2021 and winners will be required to grant a broad, permissive license to the NIH to use, alter, and redistribute the software. Challenge 2, LitCoin Concept Challenge, will encompass a competition to generate end-to-end plans to build the LitCoin submission platform, commencing in spring or summer 2022. NCATS anticipates combining ideas from multiple winners to inform and plan the next step, a LitCoin Development concept.

To engage stakeholders, NCATS, in collaboration with NLM and four publisher partners, hosted a virtual LitCoin Stakeholder Feedback Workshop June 17–18, 2021. The DDPP sought advice from the Council on key factors to enable success of this program and ideas on enhancing adoption and dissemination of LitCoin.

Clinical and Translational Science Award (UM1)

June 11

Erica K. Rosemond, Ph.D., presented the CTSA UM1 award concept. NCATS proposes this concept to support an integrated research and training environment for clinical and translational science. The objectives and areas of emphasis align with the six main objectives of the Program. This concept addresses the RFI responses to decrease applicant administrative burden, increase CTSA Hub flexibility specialization opportunities, and introduce a distinct clinical and translational science research project.

NCATS proposes to simplify the application and budget, enhance review quality, and streamline award actions. With the UM1 mechanism, applications will be simpler, less repetitive, more organized, and have a single budget. The Hub career development and optional training components will be separate, allowing for independent scores and reviews. The administrative adjustments will speed processing the awards. In terms of flexibility, this concept will require fewer elements, emphasize unique qualities, and create a Hub-specific research project.

The activities of the CTSA will be retained, reorganized and grouped more appropriately, and balanced and focused on the Hub’s activities. These enhancements will allow the Hubs to showcase unique strengths and capabilities. The unique clinical and translational science research project will address existing roadblocks to translational research. This concept builds on the existing CTSA Program and nurtures innovations in clinical and translational science.

Project/Program Officer:
Erica K. Rosemond, Ph.D.
Acting Deputy (Division) Director and Acting (Branch) Chief
Division of Clinical Innovation
Clinical and Translational Science Awards Program Branch
National Center for Advancing Translational Sciences
Phone: 301-594-8927
Email: erica.rosemond@nih.gov

Specialized Innovation Programs (SIPs) (RC2)

June 11

Erica K. Rosemond, Ph.D., presented the new SIPs RC2 concept, which aligns with the RFI responses to increase flexibility and diversity across Hubs to leverage strengths and drive innovation, allow awardees to specialize, and balance local efforts with Consortium efforts. The aim of this concept is to provide support to SIPs through an RC2 funding mechanism, with the goal of catalyzing clinical and translational science locally through the support of unique activities, resources and/or expertise at CTSA Hubs. The proposed innovation ecosystem will consist of a CTSA UM1 Hub (local and national collaborations), RC2, Collaborative Innovation Awards (R21/U01), and Consortium-wide centers (U24), all focusing on improving health.

The goals of the SIPs are to support highly specialized capabilities or resources—with local impact and considerations for early dissemination—and to create a streamlined program-level tracking of outcomes and impact. SIPs will be peer reviewed separately and only Hub awardees will be eligible to apply. Examples of SIPs include telehealth, regulatory science, clinical informatics, genetics and genomics, pragmatic trials, dissemination and implementation, rural health and health disparities, community outreach and engagement, and other specialized programs.

Project/Program Officer:
Pablo Cure, M.D., M.P.H.
Program Director
Division of Clinical Innovation
Clinical and Translational Science Awards Program Branch
National Center for Advancing Translational Sciences
Phone: 301-827-2014
Email: pablo.cure@nih.gov

National Research Service Award (NRSA) Institutional Predoctoral and Postdoctoral Research Training Grants (T32)

June 11

Mercedes Rubio, Ph.D., presented the NRSA Predoctoral and Postdoctoral Research Training Grant (T32) concept, which aligns with NCATS Strategic Goal 3 to develop and foster innovation in translational training and a highly skilled, creative, and diverse translational science workforce.

This NRSA T32, which replaces the CTSA Program TL1, has the objectives to customize research training opportunities, provide high-quality research training, develop characteristics and attributes of successful translational scientists, and promote evidence-informed mentoring practices. In FY 2020, 181 postdoctoral trainees, 305 predoctoral trainees, and 34 short-term/summer training positions were supported. This concept is expected to enhance the career and training education opportunities available to the clinical and translational science workforce and nurture the clinical and translational science field.

Project/Program Officer:
Mercedes Rubio, Ph.D.
Program Director
Division of Clinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-480-8957
Email: rubiome@mail.nih.gov

Institutional Career Development Award (K12)

June 11

Joan Davis Nagel, M.D., M.P.H., presented the K12 concept. The CTSA Institutional Career Development Program (KL2) offers postdoctoral scholars and junior faculty advanced training in clinical and translational science research and allows 75 percent of protected time for research. The proposed K12 will provide customized career development and education opportunities to align with local institutional strengths and resources; and will promote flexible, innovative learning models to engage scholars in team science, individual development plans, and advanced research training. The concept also will promote evidence-informed mentoring practices and includes a leadership and management component. This concept aligns with NCATS Strategic Goal 3 to develop and foster innovation in translational training and a highly skilled, creative, and diverse translational science workforce.

NCATS anticipates that the K12 will nurture the characteristics of a translational scientist, with enhanced tracking of scholar outcomes and measures of impact. The K12 is expected to create a clear and sustainable career pathway for junior faculty, enable scholars to acquire the knowledge and skills needed to cross translational science hurdles, and expand the field of translational science. This concept will support the next generation of diverse clinical and translational scientists who have the knowledge, skill sets, and abilities to advance discoveries across the translational science spectrum to improve health.

Project/Program Officer:
Joan Davis Nagel, M.D., M.P.H.
Medical Officer
Division of Clinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-827-2512
Email: joan.nagel@nih.gov

Research Education Grant (R25)

June 11

Jamie Mihoko Doyle, Ph.D., presented a concept for the CTSA Research Education Grant (R25). The NIH R25 grant supports activities that complement or enhance workforce training; enhance diversity; help recruit individuals with specific specialty or disciplinary backgrounds; and foster a better understanding of biomedical, behavioral, and clinical research and its implications. Currently, 25 R25 funding opportunities are active across the NIH. Very few training programs have short-term agendas. The current CTSA TL1 programs can include predoctoral, postdoctoral, and short-term positions.

This NCATS R25 concept provides an opportunity to expand, enhance, and meet local needs with the objective to support short-term clinical and translational research experiences (10 to 15 weeks) not available through formal NIH training mechanisms. The overarching goal is to build a pathway for a translational science workforce of the future.

Project/Program Officer:
Jamie Mihoko Doyle, Ph.D.
Program Director
Division of Clinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-402-0403
Email: doylejm@mail.nih.gov

Helping to End Addiction Long-term^SM Initiative or NIH HEAL Initiative^SM Translational Science Training

Jan 15

Dr. Colvis presented the NIH HEAL Initiative^SM translational science training concept. The NIH HEAL Initiative, a trans-NIH effort to speed scientific solutions to stem the national opioid public health crisis with a focus on developing novel pharmacotherapies to treat pain, opioid use disorder and overdose. It is well known that therapeutic discovery, development, and deployment is a complex process. Traditional training often occurs within a small segment of this process. In addition, workplace diversity in biomedical research is less than optimal, particularly within therapeutic discovery and development.

The objective of this concept is to provide NIH HEAL Initiative funds to support early- and mid-career scientists who are expert in pain or opioid use disorders research to receive in-depth training in therapeutic development in an academic or government translational research center or in an industry setting. The area of emphasis directly addresses the lack of workplace diversity in drug development by specifically providing translational training to individuals from underrepresented groups. The goal is to build a workforce of investigators better equipped to translate scientific discoveries into clinical breakthroughs.

The NCATS anticipates that this opportunity will provide the fields of pain, dependency, and overdose with scientists better equipped to design experiments with an emphasis on translating discoveries to affect health. Importantly, incorporating a translational perspective in the early- and mid-career stages will promote the guiding NCATS principle of bringing “more treatments to more patients more quickly.”

Project/Program Officers:
Christine M. Colvis, Ph.D.
Director, Drug Development Partnership Programs
Office of the Director
National Center for Advancing Translational Sciences
Phone: 301-451-3903
Email: ccolvis@mail.nih.gov

Steven T. Pittenger, Ph.D.
Program Officer
Office of the Director
Drug Development Partnership Programs
National Center for Advancing Translational Sciences
Phone: 301-827-5810
Email: steven.pittenger@nih.gov

Technological Development and Validation of Remote Measures for Use in Clinical Trials in Individuals with Rare Diseases

Jan 15

Tiina K. Urv, Ph.D., and Lili Portilla, M.P.A., presented an SBIR contract concept on technological development and validation of remote measures for use in clinical trials in individuals with rare diseases. Rare disease patients face significant barriers to participation in clinical trials due to travel limitations, health issues, as well as financial difficulties. Although virtual clinical trials (e.g., remote or decentralized trials) leverage technologies to overcome these barriers, validated measures specific for use in remote clinical trials and studies are missing. This concept proposes to use U.S. small businesses to develop and validate sensitive and specific outcome measures that are technologically viable for use in clinical trials in patients with rare diseases.

The objectives are two-fold: (1) facilitate virtual studies by developing and validating outcome measures that can be assessed remotely and that are suitable for use in clinical trials and (2) develop robust, user-friendly technologies to collect these assessments. This research will capture accurate and replicable data remotely in the patient’s family environment (e.g., adaptive life skills, strength). It also will collect continuous variables and provide a more accurate assessment of the patient’s real condition through new measurements made possible by technology.

Consistent with NCATS mission, this concept supports the three “Ds” to develop, demonstrate and disseminate innovative interventions that benefit public health, enabling a more diverse group of individuals to participate in rare disease clinical trials. Because of the success of NCATS SBIR-funded projects in stimulating technological innovation and meeting research and development needs, commercialization of these technologies is expected to result in significant patient benefit.

Project/Program Officers:
Tiina K. Urv, Ph.D.
Program Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-827-2746
Email: urvtiin@mail.nih.gov

Lili M. Portilla, M.P.A.
Director, Office of Strategic Alliances
National Center for Advancing Translational Sciences
Phone: 301-827-7170
Email: lili.portilla@nih.gov

CTSA Consortium-Wide Centers: Resources for Rapid Demonstration and Dissemination (C3-R2D2)

Jan 15

Audie A. Atienza, Ph.D., presented a concept on establishing the CTSA Consortium-Wide Centers: Resources for Rapid Demonstration and Dissemination (C3-R2D2) initiative, which proposes to leverage capabilities and expertise across the CTSA Program to advance Clinical and Translational Science (CTS). Innovations within CTS require multidisciplinary teams with diverse and unique skill sets. Three centers currently share capabilities and expertise across the consortium: the CTSA Data to Demonstrate Health (CD2H), Centers supported through the Trial Innovation Network (TIN), and the Center for Leading Innovation and Collaboration (CLIC).

Over the past few years, CTSAs’ successes have expanded beyond coordinating communications, facilitating data harmonization and data sharing, and using innovative approaches in clinical trial recruitment. NCATS proposes the C3-R2D2 initiative to build on these successes and focus on research demonstration and dissemination at the consortium level. The administrative tasks for the CTSA Program are in the process of being transferred to a support contract mechanism approved by NCATS Council during the January 2020 meeting.

The objective of this concept will be to leverage subject matter expertise across the CTSA Program to develop and provide consortium-level resources and capabilities for specific categories of innovative approaches. Potential areas of emphasis may include health information technology (e.g., mobile health/telemedicine, electronic health records interoperability and data exchange), research-impact quantification, trial designs and recruitment approaches, and platforms/processes that facilitate satisfying regulatory requirements. This initiative also will be responsive to emerging high-priority topics.

In establishing the C3-R2D2 initiative, NCATS anticipates overcoming clinical and translational science roadblocks; accelerating dissemination methodologies across the CTSA consortium for uptake of knowledge, research tools, methods, and data; and identifying, implementing, and disseminating consortium-wide resources for faster adoption to positively affect patients and public health. The overarching goal is to rapidly accelerate CTSA consortium-wide collaborations toward innovative, game-changing, high-impact clinical and translational science advances.

Project/Program Officer:
Audie A. Atienza, Ph.D.
Program Director
Division of Clinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-435-0198
Email: audie.atienza@nih.gov

Clinical Trial Readiness (CTR) for Rare Diseases

Jan 15

Alice Chen Grady, M.D., presented a renewal concept for the CTR for Rare Diseases, Disorders and Syndromes grants program, aiming to support studies that are addressing critical gaps in rare diseases clinical trials, including lack of (1) validated biomarkers and clinical outcome assessments necessary for selecting appropriate endpoints in rare diseases and (2) a trial readiness priority area needed by regulatory agencies.

NCATS proposes this renewal concept to support projects focused on efficiently and effectively advancing candidate rare diseases therapeutics (or diagnostics) into clinical trials and to increase their likelihood of success in upcoming clinical trials. The program focuses on rare diseases that currently (or soon will have) candidate therapeutics or diagnostics ready for testing in clinical trials and projects that leverage partnerships and existing NCATS resources (e.g., RDCRN).

The first CTR grants were awarded in summer of FY 2019. To date, NCATS and the NICHD have collaborated to fund two Small Research Grant (R03) awards and 16 Exploratory/Developmental Research Grant (R21) awards, through three funding cycles. Regarding accomplishments, nine publications citing this relatively young CTR program have been reported in the NIH Research Portfolio Online Reporting Tools, and several projects show promising data. For example, Children’s Hospital of Philadelphia investigators are working to validate an objective outcome measure of therapeutic response in a pediatric rare disease population.

NCATS and the NICHD recognize an ongoing need to provide FOAs for studies that address specific gaps in understanding the natural history of disease, suitable biomarkers, and appropriate clinical outcome measures.

Project/Program Officer:
Alice Chen Grady, M.D.
Program Officer
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-827-2015
Email: alice.chen2@nih.gov

2020

Small Research Grants for NCATS Clinical and Translational Science Award (CTSA) Program

Sept. 17

Erica K. Rosemond, Ph.D., presented a concept to establish small research grants within the CTSA Program. These grants will address the challenge of speeding up the clinical and translational science research process that typically takes multiple steps and time to deliver a solution to any single operational problem. To speed up this research process, NCATS is proposing small clinical and translational science research projects, which can be leveraged to advance science more quickly and identify “fast-fail” decision points in the project.

The objectives and emphasis will be that these small, self-contained research projects can (1) address general roadblocks in science or operations that limits the efficiency and effectiveness of translation, and (2) develop, demonstrate or disseminate innovative solutions or new or improved treatments that will have an impact on improving the health of patients. In addition, the small research grants will provide an opportunity to support the transition of clinical and translational scientists to achieve independent investigator status.

In implementation, these grants will help research support projects get over a roadblock, catalyze a tangible scientific outcome and allow projects to fail fast resulting in a change in approach. The overall impact will be assisting young (i.e., early-career) investigators in building their independent research portfolios and transitioning to careers as independent academic translational scientists.

Project/Program Officer:
Erica K. Rosemond, Ph.D.
Deputy Director, CTSA Program Hubs
Division of Clinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-594-8927
Email: rosemonde@mail.nih.gov

Translational Ethics Collaboratories

Sept. 17

Elaine Collier, M.D., presented a concept of a translational ethics collaboratories program, a next phase in the NCATS ethics research program. Although novel discoveries and emerging technologies offer potential to improve health, the possibility for harm to health or to the norms of individuals, families and communities—as well as of society—remain. The goals of the concept are threefold: (1) support institution-independent collaborative transdisciplinary teams to conduct research on ethical, legal and societal issues related to the application of a novel discovery or emerging technology to improve health, (2) provide research ethics consultation outreach to the research community in a selected area of emphasis, and (3) collect data on this consultation model.

The collaboratory area of emphasis (e.g., synthetic biology, gene modification or data aggregation) must present an ethical issue involved in translation and requires a research consultation project. NCATS is the only NIH Institute or Center that targets systemic issues agnostic of disease, specialty or age across the entire research spectrum, from basic and clinical research to research focused on health care and public health. The translational ethics collaboratories will fill a gap in the knowledge and practice necessary to advance novel discoveries to improve human health in emerging areas. NCATS anticipates that the collaboration of translational scientists, ethicists, legal scholars and social scientists becomes comfortable and routine and facilitates interdisciplinary translational ethics research and consultation. The outcome will provide evidence on the usefulness of research ethics consultation and the effectiveness of models.

Genetic and Rare Diseases (GARD) Information Center

Sept. 17

Eric Wk Sid, M.D., M.H.A., presented a renewal concept for the GARD Information Center. GARD was launched in response to the Rare Diseases Act of 2002 and congressional mandate to provide consumer health information on rare diseases. Over the past 5 years, the demand for information— with contact center inquiry volume doubling and research evidence exponentially increasing — has outpaced GARD staff’s capabilities to manually maintain and expand content. The GARD Information Center currently is the most visited NCATS webpage, and the traffic (2 million users per month) has at times paralleled that of the NIH home page.

The goal of this concept renewal is to modernize the GARD program and enhance NCATS’ public health role in delivering reliable information about rare diseases to patients and caregivers. The objectives will be to sustainably audit research on the more than 7,000 current and newly identified rare diseases and enhance the ability of GARD to be of maximum use to patients and caregivers. The key areas of emphasis include developing both a research dashboard to quantify and visualize the research evidence in the rare disease portfolio and a translational science framework to educate consumers on rare disease evidence interpretation. A total of 34 public datasets comprising 3.8 million data points are now integrated into GARD’s database from existing NCATS programs and other rare diseases resources. In this next phase, efforts will focus on investigating translational science approaches to leverage these data.

NCATS anticipates that this GARD modernization will clear the contact center’s inquiry backlog by automating processes to stay abreast of new research findings and improve the ability of rare disease patients and caregivers to make decisions using these data, with the outcome of shortening the diagnostic journey for patients with rare diseases.

Project/Program Officer:
Eric Wk Sid, M.D., M.H.A.
Program Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-827-3073
Email: eric.sid@nih.gov

Scanning for Conditions with Electronic Nose Technology (SCENT)

Sept. 17

Danilo Tagle, Ph.D., M.S., presented the SCENT concept. The goal is to develop a noninvasive and portable diagnostic device that provides rapid and accurate diagnosis of a variety of medical conditions, facilitating treatment of patients. The most pervasive method of sensing in nature, detection of scents and odors, has scarcely been used in the diagnosis of disease. This concept aims to reverse engineer a bio-mimic of the sense of smell found in canines for disease diagnostics, involving several steps — from the detection of the smell/odor, to data acquisition and processing, to comparisons of known patterns, and the readout via a mobile device or portable system.

Leah Tolosa Croucher, Ph.D., explained that the objectives of the concept are to use volatile organic compounds (VOCs) that are released through the skin and/or breath as the key substrate, integrate the components of the various SCENT instrumentation and software, and establish VOC signatures unique for each disease. The SCENT devices will adhere to the Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free and Deliverable to end users (ASSURED) criteria outlined by the World Health Organization (WHO). Machine learning and artificial intelligence will be incorporated to rapidly analyze the VOC signatures unique for each disease and condition, and to ensure that the WHO ASSURED criteria are met.

The anticipated result would be a market-ready handheld/wearable, noninvasive diagnostic device that is expected to decentralize diagnostic testing, bringing it closer to patients and resulting in improved care and patient outcomes.

Project/Program Officers:
Danilo A. Tagle, Ph.D., M.S.
Associate Director for Special Initiatives
Office of the Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-594-8064
Email: danilo.tagle@nih.gov

Leah Tolosa Croucher, Ph.D.
Program Officer
Office of the Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 240-701-2580
Email: leah.croucher@nih.gov

Novel Explorations in Rare Diseases (NERD)

Sept. 17

Dr. Pariser presented the novel explorations in rare diseases concept and noted the rationale for such a program. Extracting rare disease patient information from existing health care system databases is exceedingly challenging and often unreliable. The available tools are not readily usable for rare diseases, especially multi-disease explorations/analyses. Data extraction is unique to individual data environments (e.g., electronic health record (EHR) system, region/location). NCATS is proposing this concept to quantify the impact, including cost and health care utilization, of rare diseases on patients and health care systems.

The objectives are threefold: (1) develop methodology to accurately and broadly estimate the prevalence of rare diseases and associated health care utilization, (2) develop patient journey maps across different diseases to objectively describe and quantify the diagnostic odyssey and (3) adapt machine learning software and tools to derive this information directly from primary source data. Key focus areas include identifying, with reproducibility, patients with rare diseases within different health care databases, quantifying the overall impact, and working with partners and/or vendors to develop the necessary methodology and tools.

Regarding implementation, a NERD 14-disease pilot is being conducted intramurally, and some efforts are in progress externally with academic and industry partners in the United States and Western Australia. NCATS envisions this concept as having the transformative potential to improve understanding of the magnitude of rare diseases and their impacts on the health care and research systems and on the well-being of patients and their survival.

Project/Program Officer:
Anne R. Pariser, M.D.
Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-402-4338
Email: anne.pariser@nih.gov

Rare Diseases Informatics Platform (RDIP)

Sept. 17

Dr. Pariser presented a concept to establish a rare diseases informatics platform, which builds on the NCATS GARD and NERD proposals. This concept will address several needs. First, most rare disease information routinely used are estimates and are not easily traceable back to the primary data sources. Second, current data analysis efforts are discrete, siloed and do not comprehensively meet the perquisite for timely rare diseases information. Third, the ability to collect and integrate rare disease information from multiple sources (e.g., insurance, EHR or research) is lacking. To address these needs, NCATS proposes this concept to support the collection, integration and analysis of rare diseases data from diverse sources. This information will inform NCATS’ rare diseases research initiatives and priorities.

The objectives are to create and staff an RDIP or knowledge center; collect, integrate and analyze rare diseases data from diverse sources to provide objective information for multiple purposes; and incorporate ongoing ORDR data initiatives within one central location. NERD is being designed as a model for building the RDIP, which will harmonize approaches or data models to integrate with or leverage other ongoing NCATS informatics programs, such as GARD, DCI-data initiatives and the Biomedical Data Translator.

Project/Program Officer:
Anne R. Pariser, M.D.
Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-402-4338
Email: anne.pariser@nih.gov

Bespoke Gene Therapy Consortium (BGTC) Coordinating Center

Sept. 17

P.J. Brooks, Ph.D., presented a concept on the BGTC Coordinating Center. Many monogenic rare diseases could benefit from gene therapy using adeno-associated virus (AAV) vectors. For diseases of no commercial interest, navigating the multiple steps (e.g., vector production and toxicity testing) necessary to get to a clinical trial, as well as the clinical trial itself, is a major challenge. To address this challenge, NCATS, the FDA Center for Biologics Evaluation and Research, and the Foundation for the NIH (FNIH) are establishing the BGTC, a major component of the FNIH Gene Therapy Accelerated Medicines Partnership (AMP).

NCATS proposes a BGTC Coordinating Center to support these multiple steps using contract mechanisms, all under the direction of the Coordinating Center. The objectives are to coordinate contract activities for the BGTC and evaluate novel collaborative approaches to support gene therapy clinical trials for rare diseases. In addition to accelerating rare diseases clinical trials, other areas of emphasis for this concept include collaboration with multiple stakeholders (e.g., FDA, private industry, nonprofits and rare diseases PAGs) and commitment to ensuring that the diseases chosen for study will include those affecting racial and ethnic minority populations.

The BGTC Coordination Center and its activities are expected to be synergistic with other NCATS programs and initiatives, such as the Platform Vector Gene Therapy (PaVe-GT) project. In the long-term, knowledge gained and best practices will be parlayed into the AAV-based gene therapy clinical trials for rare diseases handbook and broadly disseminated.

Project/Program Officer:
Philip John (P.J.) Brooks, Ph.D.
Program Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-443-0513
Email: pj.brooks@nih.gov

A Specialized Platform for Innovative Research Exploration—ASPIRE-ing Beyond HEAL

May 14

Danilo A. Tagle, Ph.D., M.S., presented a new concept to expand the ASPIRE Program. He reminded the Council that the ASPIRE initiative originally was proposed in September 2017 to address key translational challenges: (1) the uninterrogated vast chemical space (10⁶³) of potential pharmacologically active molecules, (2) the undrugged biological space (5 × 10⁵), and (3) an outdated reaction toolkit for accessing the relevant chemical space. To address these issues, NCATS convened the “Workshop on Automated Chemical Synthesis” on Oct. 19–20, 2017, to identify the associated research opportunities, challenges and roadblocks. Subsequently, NCATS officially launched ASPIRE in 2018, as a pilot program funded by the Helping to End Addiction Long-term^SM Initiative, or NIH HEAL Initiative^SM with an extramural component through prize competitions and challenges, and an intramural component to build an automated chemistry infrastructure.

For this new concept that goes beyond the initial HEAL investment, Dr. Tagle noted the goals will be to establish a collaborative structure involving multidisciplinary expert teams from NCATS intramural and extramural scientists that takes advantage of the validated open-source infrastructure as well as tools and technologies within NCATS Division of Preclinical Innovation toward general translational challenges in synthetic chemistry.

Samuel Michael described the intramural components of the ASPIRE modular platform, which includes automation, informatics, consumables, chemistry, analytical, and biology modules, as well as technology development. The initial platform will be a 16-module design with integrated automation and technology components.

Dr. Tagle highlighted that the outcome will be a disseminatable platform for automated chemical synthesis, biological testing, and machine learning–driven optimization. NCATS anticipates that this platform will broadly enable the identification and synthesis of novel biologically active chemical structures with drug-like characteristics. The potential exists for a much-needed expansion of the chemical space toward new and improved therapeutics, which would catalyze an innovative and collaborative ecosystem.

Samuel G. Michael
Chief Information Officer
Information Technology Resources Branch
Office of Administrative Management
National Center for Advancing Translational Sciences
Phone: 301-827-7796
Email: michaelsg@mail.nih.gov

Extended-Longevity Tissue Chips for Modeling Chronic Exposures

May 14

Lucie A. Low, Ph.D., presented a concept on extended-longevity tissue chips for modeling chronic exposures. Dr. Low noted that NCATS has been the leader in developing and advancing the tissue chip/MPS technology and remains key leaders in the field to guide and facilitate ongoing efforts across the NIH, FDA, industry and other government agencies. As tissue chip technology is becoming more mainstream and industrialized, other funding agencies now are supporting their own tissue chip programs. This initiative would be a joint initiative between two divisions within the National Aeronautics and Space Administration (NASA), the Biomedical Advanced Research and Development Authority and the Translational Research Institute for Space Health. In addition, six NIH Institutes and Centers have expressed interest in joining. The partner agencies are in the process of obligating funds for this initiative. NCATS and NASA recently signed a memorandum of understanding to express interest in this joint initiative.

Tissue chips generally are designed to last up to 28 days of culture per FDA requirements for drug testing. However, participants attending two NCATS and NASA co-sponsored workshops on the “State of the Science” for tissue chips identified the need to extend the tissue chip lifespan beyond 6 months (i.e., extended longevity tissue chips). This enables broader use of tissue chip technology for a number of applications. Therefore, the goals of this concept are to extend the lifespan of tissue chips beyond 6 months and to model their exposure to perturbations (e.g., drugs or compounds, radiation and environmental hazards) during the 6-month period.

The outcome will be reproducible and viable platform operation for long-term tissue chip function with proficiency for continuous monitoring, probing and sampling of the biological tissues. The research will enable in vitro assessment of long-term safety and toxicity studies and provide platforms that can be used for testing drug candidates, drug combinations and drug-drug interactions over extended time periods (e.g., platforms that can give accurate readouts at 18 or 180 days). NCATS hopes the initiative will spur development of robust automated platforms that are amenable to remote operation and sensing of tissue function. A key aim of Cures Acceleration Network (CAN) programs is the “handoff” of mature technologies to new users. In line with this aim, and unique to this tissue chip initiative, is that external partners will provide 75% of funding, and NCATS investments will be minimal.

Project/Program Officer:
Lucie A. Low, Ph.D.
Scientific Program Manager
Office of the Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-594-7609

Drug Screening with Biofabricated 3-D Disease Tissue Models

May 14

Dobrila D. Rudnicki, Ph.D., presented a concept on drug screening with biofabricated 3-D disease tissue models. This concept expands existing NCATS initiatives, including the Pilot Program for Collaborative Drug Discovery Research using Bioprinted Skin Tissue and the Drug Screening with Biofabricated 3-D Skin Disease Tissue Models. The goals and primary objectives are threefold: (1) to synergize extramural and NCATS intramural expertise and resources, (2) to develop physiologically relevant and validated 3-D models that can be incorporated into novel drug screening platforms, and (3) to advance discovery and development of more effective and safe treatments for a number of diseases.

Dr. Rudnicki explained that the program will support intramural-extramural collaborations for the development of these models and will provide important resources and protocols enabling the extramural community to continue development in this area. The program will help shift the paradigm from 2-D to 3-D models for drug screening and enhance the strength and value of intramural-extramural collaborations to advance translation.

Project/Program Officer:
Dobrila D. Rudnicki, Ph.D.
Program Director
Office of the Director
Office of Special Initiatives
National Center for Advancing Translational Sciences
Phone: 301-594-2080
Email: drobrila.rudnicki@nih.gov

Artificial Intelligence in Health Care

May 14

Karlie R. Sharma, Ph.D., presented a concept on advancing artificial intelligence (AI) in health care. The concept was developed in collaboration with Christine M. Cutillo, M.M.C.i. and will leverage NCATS’ existing AI and informatics efforts. The importance of using AI in health care is well emphasized in the clinical community, but translating such innovative tools for clinical applications remains a challenge. In recent weeks, many laboratories and companies have attempted to use AI for COVID‑19 treatments. These, in addition to other recent examples, illustrate the urgent need for new paradigms for the development and application of these innovative AI-based tools before and as they are deployed into clinical care settings, because misdiagnoses from AI systems can result in fatal consequences.

Dr. Sharma highlighted several unique challenges that have impeded the progress of AI in health care; these challenges include barriers to data sharing, ineffective implementation into clinical care workflows, and transparency in ethical issues. To address these issues, NCATS sponsored a workshop focusing on machine intelligence in health care in July 2019. Three key topics emerged from the discussion that rose to the top as timely and aligning with the NCATS purview: testing algorithms in the real world prior to their implementation, prioritizing reproducibility and robustness of AI systems, and improving communication across groups developing these systems and the community that will use them. This concept aims to (1) develop a pipeline for testing algorithms prior to implementation in the clinic, and (2) in the long-term, improve trust in and uptake of AI systems in the health care setting. In a proof-of-concept approach, NCATS will develop and test the pipeline with use case algorithms and demonstration projects (Stage 1), then use the tested pipeline to assess newly developed algorithms focused on urgent clinical needs in a variety of disease areas (Stage 2).

The outcomes of the research will be (1) a fully formed and vetted pipeline equipped with standard operating procedures, creating a framework for comprehensive algorithm assessment in real-world environments; (2) distributable algorithms that can be implemented across health systems worldwide; and (3) dissemination of results and resources to the broader research community to facilitate the creation of other AI pipelines by the community modeled after the initiative-developed pipeline. NCATS anticipates that the incorporation of these algorithms into clinical practice will create new sources of reliable information for clinicians to better diagnose and treat patients.

Project/Program Officers:
Karlie R. Sharma, Ph.D.
Program Officer
Office of the Director
Drug Development Partnership Programs
National Center for Advancing Translational Sciences
Phone: 301-451-4965
Email: karlie.sharma@nih.gov

Christine M. Cutillo, M.M.C.i.
Data Science Lead
Office of the Director
National Center for Advancing Translational Sciences
Phone: 301-402-4006
Email: cutilloc@mail.nih.gov

Multisensory Virtual/Augmented Reality (VR/AR) Systems and Rehabilitation for Rare Disease Patients

May 14

Mr. Michael presented the SBIR contract concept on the topic multisensory VR/AR and rehabilitation for patients with rare diseases. The senses (e.g., audio, visual and hand haptics) are limited in current VR/AR systems but could benefit from taking advantage of other senses that include full-body haptics (e.g., TESLASUIT), smell and taste. Research has shown that VR/AR immersive experience can reduce pain and discomfort in rehabilitation and, potentially, in clinical settings. In addition, the AI and machine learning algorithms can generate individualized immersive experiences, which must be verified for efficacy, user needs, and preferences. The challenge is that individuals respond differently to these environments and systems must be tailored.

This contract concept will support the development of multisensory VR/AR systems that adapt intelligently to each individual for the assessment and rehabilitation of patients with rare diseases. The aim is to assess the efficacy of the systems in clinical and rehabilitation settings for these patients through biofeedback readings and user self-reports. Developing such systems could benefit the ORDR by enabling technology-based applications for the rare diseases community. Applications include pain management and rehabilitation, remote monitoring and data capture for clinical trials, and diagnostic assistance for rare diseases with motor components.

NCATS will solicit SBIR applications to develop a virtual environment proof-of-concept system that incorporates dynamic audio, visual, full-body haptic and olfactory stimuli. The system should incorporate runtime logfile capabilities for remote patient monitoring and performance analytics and a human-in-the-loop system model that addresses patient personalization and biofeedback. The outcome will be a system that provides users a VR/AR pipeline to influence the accessibility, affordability and accuracy of therapeutic treatment and clinical use; design guidelines and efficacy considerations for existing VR/AR platforms; a multisensory tool or suite of tools for remote patient monitoring; and an AI-driven user behavioral model for adapting rehabilitation stimuli. The intent is that these remote-based systems would assist with clinical monitoring and rehabilitation efforts for patients with rare diseases, especially in cases where travel is impossible or difficult. The systems are intended to benefit the entire research community.

Platform for Rapidly Deployable Autonomous Laboratory

May 14

Mr. Michael presented the SBIR contract concept on the topic of a platform for a rapidly deployable autonomous laboratory, which aligns with the NCATS ASPIRE initiative. The COVID-19 pandemic—and subsequent physical distancing and closing of research laboratories—has led to the postponement of critical experiments necessary for developing novel diagnostics and potential therapeutic interventions. The purpose of this SBIR contract concept is to develop next-generation distributed, AI-enabled, fully automated laboratories that are linked to a cloud-based virtual research organization (VRO) to acquire, harmonize, store, analyze and share data generated during experimentation.

The goals are to create a platform consisting of modular automated devices capable of performing laboratory tasks for both diagnostic and therapeutic discovery purposes. NCATS will solicit SBIR applications to develop the following: (1) a distributed, modular, autonomous lab instrumentation platform that focuses on such areas as HTS for drug discovery, next-generation sequencing, high content imaging, and polymerase chain reaction diagnostics and (2) a cloud-based VRO that connects each automated laboratory and AI methods that integrate the lab data into the VRO, allowing real-time data collection and analysis. NCATS will leverage its collaboration with Kebotix, Inc., on AI/machine learning models and HTS.

Carleen Klumpp-Thomas, M.S. described an example of use of the proposed platform. In collaboration with the National Institute of Biomedical Imaging and Bioengineering (NIBIB), one of its a small laboratory without automated equipment was upgraded. The automation increased the laboratory’s analysis capacity from 500 to 10,000 samples, and copious data were collected in real time and exported into a VRO.

Mr. Michael noted that the outcomes of the SBIR contract concept will be a system that provide users (1) a platform that enables the on-demand initiation of physical experiments across laboratories, (2) a cloud‑based VRO that houses data suited for analysis, and (3) a modular platform that can quickly add or scale up additional resources necessary for responding to public health emergencies. NCATS anticipates that using SBIR contract mechanisms will create opportunities for small businesses to facilitate an emergency commercialization for rapidly scalable instrumentation.

Project/Program Officers:
Samuel G. Michael
Chief Information Officer
Information Technology Resources Branch
Office of Administrative Management
National Center for Advancing Translational Sciences
Phone: 301-827-7796
Email: michaelsg@mail.nih.gov

Carleen A. Klumpp-Thomas
Research Services Core Lead
Division of Preclinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-827-1789
Email: klumppc@mail.nih.gov

Clinical and Translational Science Awards Program Operations Support

Jan. 16

Clare K. Schmitt, Ph.D., presented a contract concept for operations support for the CTSA Program–related grantee and NCATS staff activities. The aims of the CTSA Program are to accelerate translation of research discoveries into improved care for patients by addressing systemwide clinical and translational research problems collaboratively; disseminate the expertise, tools, training and clinical research innovations for effective treatments; and support a diverse translational science workforce.

The goal of this operations support contract concept is to provide effective and efficient management of this large, complex national CTSA Program, including the ongoing administrative tasks (e.g., supporting the consortium-wide agendas and large-scale Program deliverables). Specific operations support tasks will include transfer of the NCATS Specific, Measurable, Achievable, Realistic and Timetable (SMART) institutional review board (IRB) platform from the current grantee for long-term management and receipt and distribution of funds from other NIH Institutes and Centers and sister agencies for emergent clinical trial needs. In addition, the operations support contract will provide meeting and conference support and manage data safety monitoring-related activities in clinical trials.

The expected outcomes will be the consolidation of multiple activities under one contract and addition of needed tasks, allowing grantees to focus their intellect and efforts on addressing the CTSA Program goals and, therefore, NCATS goals. Regarding plans to promote and ensure sustainability, the activities and platforms will be hosted on the NCATS cloud platform, so a transition plan is required.

Project/Program Officer:
Clare K. Schmitt, Ph.D.
Deputy Director
Division of Clinical Innovation
National Center for Advancing Translational Sciences
Phone: 301-827-3787
Email: clare.schmitt@nih.gov

Supporting Clinical Trials of a Prime Genome Editor in Multiple Genetic Diseases

Jan. 16

P.J. Brooks, Ph.D., presented the concept of supporting clinical trials of a prime editor (e.g., CRISPR) for the treatment of multiple genetic diseases. The current approach to gene-editing clinical trials is focusing on one disease at a time. This approach is based on commercial considerations, which is not optimal for addressing the thousands of rare monogenic diseases that exist. In 2019, researchers discovered a modified CRISPR Cas9 (CRISPR-associated protein 9) technology that has the potential to correct 90 percent of human disease–causing mutations without introducing double-strand DNA breaks or increasing the risk of cancer. The DCI and ORDR are interested in expanding these findings to NCATS programs and clinical trials.

The concept goals are to assess the feasibility of clinical trials of a prime editor in multiple rare monogenic diseases and identify and overcome any feasibility challenges for such trials. Dr. Brooks emphasized that the concept would leverage ongoing efforts, such as the NCATS CTSA Program and the NIH Common Fund Somatic Cell Genome Editing program. This initiative will use the general framework of the CCIA program and will support clinical trials that focus on defects in a somatic cell type to which a single prime editor can be delivered (e.g., liver hepatocytes). Depending on the technology delivery method, potential regulatory issues involving the FDA Center for Biologics Evaluation and Research may need to be addressed.

Several outcomes are expected, including identifying and overcoming challenges in conducting these types of clinical trials, increasing the number of rare disease patients in trials, and maximizing the clinical impact of somatic genome editing. If successful, this project will fundamentally change the way genome editing in rare diseases clinical trials are conducted. Results will be disseminated to both the gene editing and rare disease research communities via the CTSA Program and publications. Ultimately, the goal is to identify a regulatory pathway for clinical trials of a prime editor that includes rare disease patients.

SaME Therapeutics—Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Rare Diseases

Jan. 16

Dr. Brooks presented the concept of supporting rare diseases clinical trials of drugs targeting SaME therapeutics. Although thousands of rare diseases exist, the number of underlying causes (i.e., etiologies) is small. The SaME approach is the focus of ongoing drug development. In addition, drugs targeting SaME in different cancers are considered state-of-the-art in oncology, and the approach has established a regulatory pathway for these types of FDA drug approvals. Although discussion and interest in SaME for rare diseases have increased in the Collaborative Forum on Rare Diseases and the International Rare Disease Research Consortium, no clinical trials are ongoing.

The goals of the concept are to adapt the oncology SaME approach to rare diseases and identify and overcome any challenges. It is anticipated that recruiting for clinical trials based on SaME will dramatically increase the number of rare disease patients in trials, translating to more treatments delivered to more patients more rapidly. The concept will leverage the RDCRN, and the results will be disseminated to the community via this Network and publications. The expected outcome will be the ability to stratify patients according to underlying etiology rather than traditional clinical characteristics, thus transforming rare disease clinical trials.

2019

Rare Diseases Are Not Rare! Challenge 2.0

Sept. 19

Alice Chen Grady, M.D., explained that the first NCATS rare diseases prize competition, Challenge 1.0, sought creative ways to raise awareness about rare diseases and the need for expanded research, new treatments and patient support. The competition opened in 2018, and nearly 50 submissions were received. Participation was widespread and generated innovative works of art that educated the public about rare diseases. For details on the three winning submissions and honorable mentions, visit the NCATS Rare Diseases Are Not Rare! Challenge Winners and Honorable Mentions page of this site.

The overarching goals of Challenge 2.0 are to change the public perception of “rare” and foster collaborations across the rare disease community. Metrics for success will be defined in advance and could possibly inform ORDR public-facing programs. Children can directly submit entries with the appropriate consent. In addition to increasing public awareness about rare diseases, the many people affected, and common challenges encountered, NCATS could use the Challenge 2.0 submissions to strongly convey the message about the ongoing need for rare diseases research and new treatments. This concept builds on the success of the NCATS 2018 prize competition and aligns with some ongoing rare diseases activities, such as the patient organization-sponsored competitions and the emphasis of the NCATS RDCRN to study multiple diseases at a time and include patient groups as partners in research.

Project/Program Officer:
Alice Chen, M.D.
Medical Officer
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-827-2015
Email: alice.chen2@nih.gov

Ethical, Legal and Societal Implications in Translational Research

May 16

Emerging discoveries and technologies raise potential ethical and legal issues that also may have societal implications. Evidence suggests that the familiarity and collaboration of translational researchers and bioethics and legal scholars can be beneficial. To advance discoveries to impact health responsibly, engagement and collaboration of researchers, scholars, communities and the public are needed. Major obstacles that need to be addressed regarding ongoing research and activities in this area include the establishment of the Neuroethics Working Group within NIH’s Brain Research through the Advancing Innovative Neurotechnologies (BRAIN) Initiative and the National Human Genome Research Institute’s Ethical, Legal and Social Implications Research Program.

The objectives of this initiative are to increase recognition of and research on these issues, encourage research on these challenging questions to collect data, foster collaboration between the two communities, and provide empirical data and frameworks for addressing these issues. The outcomes will be increases in projects, scholarship, research collaborations and stakeholder engagement in these areas.

Non-Viral Delivery Technologies for Somatic Genome Editing Therapeutics

May 16

Somatic genome editing has the potential to treat a large number of rare genetic disorders and has therapeutic implications for common diseases. Therapeutic benefit is maximized if the genome editing machinery has broad coverage in many somatic cell types. For many diseases, the ability to deliver genome editors to relevant cell types is the limiting factor. Non-viral delivery methods allow transient expression of genome editors, which is expected to reduce toxicity.

The objective of this initiative is to support the development of non-viral technologies to deliver genome editing machinery to a wide variety of cells and tissues, especially in cell types with no effective delivery technology currently available.

Alternatives to Commercially Available Cell Culture Insert Membranes and Manufacturing Techniques

May 16

Despite the increased focus on the use of more complex cellular and tissue models (e.g., 3-D tissue printing) to provide physiologically relevant platforms for enhancing the development of therapeutics for patients, challenges exist. Biodegradable cell culture-insert membranes that also provide structural support are needed, as existing commercially available alternatives are insufficient.

The objective of this initiative is to a support a small business, via an SBIR contract mechanism, that can provide a commercial solution to manufacture cell culture insert membranes in an automated and reproducible manner.

Multidisciplinary Approaches to Shortening the Diagnostic Odyssey for Rare Diseases

May 16

Many patients with a rare disease experience years-long delays in receiving a correct diagnosis (i.e., the “diagnostic odyssey”), lending to considerable anxiety and despair for patients and families as well as potential delays in treatment. Current approaches to the rare disease diagnostic odyssey typically occur through idiosyncratic referrals to a small number of disease experts at tertiary care centers.

The objective of this concept is to improve diagnostic accuracy and accelerate diagnosis for these patients through a multidisciplinary process that can be performed at the primary or secondary care levels by front-line providers. Novel approaches need to be developed that should focus on an integrated combination of clinical, computer-assisted and genomics assessments to speed diagnosis and improve accuracy. Some current activity exists in each of these areas, but no comprehensive methods have been developed that are using multiple approaches simultaneously that have been adopted by front-line clinicians. The outcome will be the development of a broadly adaptable, facile process with the potential impact of advancing the International Rare Diseases Research Consortium’s 2027 goals of achieving an accurate diagnosis within one year of a rare disease patient presenting for medical evaluation.

Project/Program Officer:
Anne R. Pariser, M.D.
Director
Office of Rare Diseases Research
National Center for Advancing Translational Sciences
Phone: 301-402-4338
Email: anne.pariser@nih.gov

Advisory Council Concept Clearances

Concept Clearances

Contact

2024

Expanding the Target Landscape by Drugging the Undruggable Concept

Selective Precision Targeting Concept

Rare Diseases Are Not Rare! (RDANR!) Challenge 3.0 Concept

Prize Competition in Quantum-Enabled Technologies for Biomedical Applications Concept

Prize Competition in Translational Science Education and Training Concept

Scalable Generation of Organoids Derived From Human iPS Cells SBIR Concept

Development of a Versatile Small Footprint Benchtop Device to Perform Batch Evaporation Concept

2023

Tissue Chips in Space 2.0—CLDs and Beyond Concept

Biomedical Data Translator Performance Phase Concept

Addressing Health Inequities in Clinical Diagnostics Concept

Preclinical Proof-of-Concept Studies for Rare Diseases

2022

Awards Supporting Cutting-Edge Technology for Translational Science (ASCETTS)

Miniaturization and Automation of Tissue Chip Systems (MATChS)

Small Manufacturing Systems to Produce Research-Grade Pharmaceutical Intermediates

Translational Centers for Microphysiological Systems (TraCe MPS)

HEAL LitCoin Pilot Program to Enable Pain and Addiction Research Discoveries

NIH HEAL Initiative LitCoin Foundational Knowledge Graph

ACTIV-1 Time-Limited Biospecimen Storage and Related Services (COVID19)

Device or Process for the Cleaning of Cell Tissue Culture Flasks

Botulinum Toxin Potency Assay Using Tissue Chips (BoT PATCh)

Online Education Modules to Advance Understanding of Translational Science Principles

Exosome Therapeutics for Regenerative Medicine (ExTReMe)

Rare Diseases Clinical Research Network (RDCRN) – Rare Disease Clinical Research Consortia

Rare Disease Clinical Research Network (RDCRN) – Data Management and Coordinating Center

2021

Ethical Issues in Translational Science Research

CTSA Collaborative and Innovative Acceleration (CCIA) Award

Machine-Assisted Approaches to Shortening the Diagnostic Odyssey for Rare Diseases

NIH HEAL: Illuminating the Understudied Druggable Proteome

Helping to End Addiction Long-term (HEAL) New Innovator Awards

Trial Innovation Network Infrastructure for the HEAL Pain Management Effectiveness Research Network

Contract Support for NCATS Intramural R&D Activities

LitCoin Prize Competitions

Clinical and Translational Science Award (UM1)

Specialized Innovation Programs (SIPs) (RC2)

National Research Service Award (NRSA) Institutional Predoctoral and Postdoctoral Research Training Grants (T32)

Institutional Career Development Award (K12)

Research Education Grant (R25)

Helping to End Addiction Long-termSM Initiative or NIH HEAL InitiativeSM Translational Science Training

Technological Development and Validation of Remote Measures for Use in Clinical Trials in Individuals with Rare Diseases

CTSA Consortium-Wide Centers: Resources for Rapid Demonstration and Dissemination (C3-R2D2)

Clinical Trial Readiness (CTR) for Rare Diseases

2020

Small Research Grants for NCATS Clinical and Translational Science Award (CTSA) Program

Translational Ethics Collaboratories

Genetic and Rare Diseases (GARD) Information Center

Scanning for Conditions with Electronic Nose Technology (SCENT)

Novel Explorations in Rare Diseases (NERD)

Rare Diseases Informatics Platform (RDIP)

Bespoke Gene Therapy Consortium (BGTC) Coordinating Center

A Specialized Platform for Innovative Research Exploration—ASPIRE-ing Beyond HEAL

Extended-Longevity Tissue Chips for Modeling Chronic Exposures

Drug Screening with Biofabricated 3-D Disease Tissue Models

Artificial Intelligence in Health Care

Multisensory Virtual/Augmented Reality (VR/AR) Systems and Rehabilitation for Rare Disease Patients

Platform for Rapidly Deployable Autonomous Laboratory

Clinical and Translational Science Awards Program Operations Support

Supporting Clinical Trials of a Prime Genome Editor in Multiple Genetic Diseases

SaME Therapeutics—Clinical Trials of Drugs Targeting Shared Molecular Etiologies in Rare Diseases

2019

Rare Diseases Are Not Rare! Challenge 2.0

Ethical, Legal and Societal Implications in Translational Research

Non-Viral Delivery Technologies for Somatic Genome Editing Therapeutics

Alternatives to Commercially Available Cell Culture Insert Membranes and Manufacturing Techniques

Multidisciplinary Approaches to Shortening the Diagnostic Odyssey for Rare Diseases

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Helping to End Addiction Long-term^SM Initiative or NIH HEAL Initiative^SM Translational Science Training