CAN Review Board Concept Clearances

Concepts describe the basic purpose, scope and objectives of proposed initiatives and represent an early planning stage for potential NCATS activities. 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 CAN Review Board concept clearances by year:

2017

Biomedical Data Translator

Dec. 15, 2017

The objective of the Biomedical Data Translator (Translator) program is to support research to develop a computational platform that enables connections among conventionally siloed data types. Translator is intended to integrate multiple types of existing data sources, including objective signs and symptoms of disease, drug effects and intervening types of biological data relevant to understanding pathophysiology, in an ecosystem that will reveal complex relationships that help scientists better understand disease and generate hypotheses and treatment options.

Current awardees are assessing the feasibility of establishing a computational platform for meeting the goals of the Translator program. In addition to assessing the feasibility of a platform, the awardees are identifying data integration and inclusion barriers, as well as a plan for data quality control and updates. Read the full Concept Clearance (PDF - 99KB).

NCATS Collaborative Rare Disease Platform Vector Gene Therapy Trial

Dec. 15, 2017

NCATS proposes a novel public-private partnership model for explicitly platform-based gene therapy clinical trials. The approach involves using well-characterized viral vectors as gene delivery vehicles for the treatment of at least three rare genetic diseases that share the same therapeutic target tissue or cell type.

The diseases chosen for this gene therapy platform trial should be those currently under study within the Rare Diseases Clinical Research Network, to maximize the benefit of natural history data and disease-specific expertise within the program. The NCATS Office of Strategic Alliances will play a key role in creating agreements and managing interactions and partnership between NCATS, academia and industry partners. Read the full Concept Clearance (PDF - 100KB).

Automated Synthesis Platform for Innovative Research and Execution

Sept. 7, 2017

The Automated Synthesis Platform for Innovative Research and Execution (ASPIRE) will serve as an unprecedented portal for automated rapid testing of hypotheses regarding novel biologically relevant chemical entities designed through computational approaches to interact with specific therapeutic targets. The envisioned platform will have the capacity for remote worldwide access and the ability to support real-time collaborative research that will integrate efforts from diverse investigators all over the world from academia, government and industry to solve complex biomedical challenges.

ASPIRE will be coupled with next-generation computational systems that generate chemical predictions and will, in turn, provide automated small-scale synthesis of said compounds for immediate/in-line biological testing using existing or adopted robotic high-throughput screening and analytic systems. Read the full Concept Clearance (PDF - 56KB).

NIH-CASIS Coordinated Program in Tissue Chip Systems for Translational Research in Space

Sept. 7, 2017

The objective of this initiative is to exploit space-specific phenomena to conduct inflight studies, using tissue chips. Conducting biomedical research at the International Space Station – National Laboratory (ISS-NL), using tissue chip technology, provides unprecedented opportunities to study the effects of microgravity and extreme radiation exposure at the ISS-NL and its effects on many of the human body's systems.

The reissuance of this FOA by NIH and CASIS will further expand the number of projects that delve into the molecular basis, including epigenome changes, for these human conditions and provide information for novel targets for drug development and innovative treatment modalities. Translation of this research to the ISS-NL promises to accelerate the discovery of molecular mechanisms that underlie a range of common human disorders and advance understanding of therapeutic targets and treatments in a reduced fluid-shear, microgravity environment that recapitulates cellular and tissue matrices of Earth. Read the full Concept Clearance (PDF - 55KB).

NextGen Tissue Chip Testing Centers

Sept. 7, 2017

The objective of this reissuance is to continue the support of Tissue Chips Testing Centers (TCTCs) beyond the two-year pilot funding and leverage previous NCATS investment in infrastructure to provide independent validation of tissue chip platforms for various organ systems.

The proposed initiative will involve a co-resourcing partnership with pharma to expand the testing of compounds on Microphysiological Systems (MPS) disease models for safety and efficacy using predefined assays according to U.S. Food and Drug Administration and pharmaceutical industry standards, and to fully utilize tissue chip technology in drug discovery and development through an integrative strategy using MPS to be directed at a critical unmet medical need for which historical approaches have been unproductive (e.g., heart failure therapy). Read the full Concept Clearance (PDF - 52KB).

2016

NIH-CASIS Coordinated Program in Tissue Chip Systems for Translational Research in Space

June 13, 2016

This proposed initiative seeks to leverage recent advances in tissue engineering and microfabrication to create microphysiological systems and organ-on-chip technology platforms that recapitulate human physiology, to better determine the molecular basis of human disease and/or the effectiveness of diagnostic markers and therapeutic intervention for disease treatment. The initiative will focus on the deployment and further development of tissue chip technology to facilitate space-related research at the International Space Station and integrate results from that research into an improved understanding of human physiology. This initiative will advance biomedical research approaches and clinical technologies for use on Earth and in space and for research in Earth- and space-based facilities that could improve human health.

It is now widely known that accelerated aging occurs in space, due to muscle wasting, osteoporosis, reduced cardiopulmonary function, immune response, and other factors, but that these conditions are reversible when astronauts return to Earth. It is anticipated that this initiative by NCATS and the Center for the Advancement of Science in Space will delve into the molecular basis, including epigenome changes, for these human conditions and provide information for novel targets for drug development. Read the full Concept Clearance (PDF - 20KB).

2015

3-D Bioprinting of Human Live Tissues for Drug Screening

Dec. 11, 2015

Bioprinting of architecturally defined and physiologically relevant human live tissues is emerging as a key enabling technology for drug discovery. 3-D bioprinting of human live tissues has the potential to accelerate the drug discovery process, enabling treatments to be developed faster and at a lower cost by bridging the predictability gap between in vitro and in vivo assays and positive clinical outcomes. The major reason for the low success rate in drug development is the lack of efficacy in clinical trials. This failure in the late stages of clinical development is in large part due to the use of simplistic in vitro cell assays and non-predictive in vivo animal models during the drug discovery and development process. 3-D bioprinting of human live tissues derived from human stem cells is expected to provide data that are more relevant to the whole body response than traditional studies with two-dimensional cell cultures.

The purpose of this initiative is to generate architecturally defined human tissues that closely resemble in vivo human tissues for drug screening by integrating groundbreaking tissue bioengineering, 3-D printing, cell development, stem cell and disease biology, and noninvasive detection technologies. This program will create the infrastructure necessary to enable 3-D bioprinting for the fabrication of tissues at NCATS and to establish collaborations with the research community to advance and disseminate its use for drug discovery. Read the full Concept Clearance (PDF - 25KB).

Increasing Access to Compounds and Tox Data

Dec. 11, 2015

The underlying mechanism of toxicity discovered in or after Phase I trials often is not investigated. NCATS would work with multiple pharmaceutical companies, the Food and Drug Administration and companies that develop predictive toxicology tools. This initiative would broker relationships between pharmaceutical companies and academic researchers who could conduct research to better understand and perhaps help to overcome toxicities detected in drugs that gave a safety signal in Phase I trials that were not predicted based on pre-clinical studies. The research would help answer the question of why pre-clinical tools sometimes fail to predict toxicity by providing researchers with access to the compounds, as well as associated pre-clinical and clinical data.

The goal of this initiative is to increase access to compounds that did not have a safety signal in pre-clinical studies but were later shown to have toxicity in humans. The program would investigate underlying mechanisms for the human toxicity and explore potential reasons why pre-clinical tools failed. The information would be incorporated into predictive modeling to benefit drug development. Read the full Concept Clearance (PDF - 33KB).

Proof of Principle (POP) Awards

Dec. 11, 2015

The proposed program is aimed at pre-clinical research projects that develop, demonstrate or deploy interventions to improve human health. Often, prospective grantees have applied for NIH support but did not receive funding because they lack a specific piece of translational data. The program would fund generation of the needed data to make the project more competitive for subsequent funding or otherwise move the project forward.

The program would strengthen applications for programs across NIH, and perhaps at a future stage, across the entire translational research enterprise. Applications to be considered for potential funding will be those that have a broad and significant impact, and each project will be completed in a relatively short time. Read the full Concept Clearance (PDF - 44KB).

Proteome Profiling in the Clinic

Dec. 11, 2015

The Human Genome Project cannot be used fully for precision medicine without profiling the proteome and its dynamically regulated post-translational modifications (e.g., phosphorylation, ubiquitination). Genomic tools do not allow the analysis of post-translational modifications at all. Indeed, the lack of well-established protein markers might explain some of the failures in clinical trials that are solely based on genetic data. New sensitive clinical tests, reliable panels of protein biomarkers and quantifiable assays are urgently needed in the clinic.

The initiative will establish new clinical tests and protein biomarkers based on quantitative proteomics, phosphoproteomics and validated antibodies; optimize technical and analytical tools and easy-to-use resources and databases for physicians and clinical staff; and perform combined analysis of genetic and proteomic data for decision making in personalized health care. Quantitative read-outs will promote better understanding and longitudinal monitoring of pathophysiology and drug effects. Read the full Concept Clearance (PDF - 31KB).

SaME Therapeutics: Targeting Shared Molecular Etiologies Underlying Multiple Diseases to Accelerate Translation

Dec. 11, 2015

While the number of disorders with a known molecular basis continues to increase rapidly, the number with an effective treatment continues to lag far behind. What is needed to overcome this translational roadblock is a fundamental change in the current symptom-based, one-disease-at-a-time approach to drug development and clinical trials. An explicit focus on identifying SMEs for translation represents such a fundamental change, which ultimately will bring more rationally designed treatments to more patients more quickly.

In contrast to the current approach to disease based on clinical presentation, the concept of SaME therapeutics is to focus on shared molecular etiologies underlying multiple diseases using systems biology as a framework for drug development and clinical trials. An important part of this initiative will be to develop a matrix of diseases and molecular etiologies to identify shared molecular etiologies (SMEs) underlying multiple diseases, and to stimulate novel clinical trials of SME-targeted drugs based on grouping patients by SME rather than clinical phenotype. Read the full Concept Clearance (PDF - 41KB).

Sensors and Devices to Detect Clinical Outcomes

Dec. 11, 2015

Many sensors and devices are available; however, the clinical utility of these is limited. This proposal will focus on solving technical, computational, engineering, social and cultural barriers to collecting, integrating and analyzing data from multiple devices and sensors and patients’ health care data in the context of addressing a pilot study of a compelling clinical question that could not be answered without such data integration.

A diverse collaborative team (technology leaders, patients, data scientists, etc.) is required to uniformly collect and analyze sensor and device data for assessing clinical outcomes that could not be answered without data integration. Read the full Concept Clearance (PDF - 31KB).

Tissues-on-Chips: Part II

Dec. 11, 2015

The goal of Part I of the Tissue Chip for Drug Screening program was to develop bioengineered micro-devices that represent functional units of the 10 major human organ systems: circulatory, respiratory, integumentary, reproductive, endocrine, gastrointestinal, nervous, urinary, musculoskeletal and immune. In the first part of this program, several unique and novel in vitro platforms have demonstrated human organotypic physiological functions and responses to drug exposure, ensuring that safe and effective therapeutics are identified sooner and ineffective or toxic ones are rejected early in the drug development process. These micro-fabricated devices also have proven to be useful for modeling human diseases, and they may prove to be sufficient alternatives to animal testing. Despite these successes, there is a clear need to advance the technology to fully exploit the use of the tissues-on-chips not only at the pre-clinical stage but also as a clinical tool.

The purpose of the proposed request for applications is to foster a multitude of new research applications including, but not limited to, studies in personalized medicine, environment exposures, reproduction and development, autoimmune disorders, infectious diseases, cancer, countermeasures for chemical warfare, immune responses and neuro-inflammation. Read the full Concept Clearance (PDF - 123KB).

2014

Micro-Awards for Researchers Who Need to Get Past a Small Hurdle

Sept. 19, 2014

The concept is based on experience with the several NCATS programs, which revealed that some applicants lacked specific critical pieces of data to present competitive proposals. Gap analysis showed that a few programs at NIH exist to meet this need, but they do not focus on the translational space, nor are they aimed at projects that have already undergone the NIH review process.

This concept would provide proof-of-principle (PoP) micro‑awards to investigators who had undergone NIH review to fund the generation of predominantly pre-clinical data needed to make a project more competitive or otherwise move the project forward. Measures of success could include receipt of funding, or achievement of relevant milestones such as the creation of intellectual property or the preparation of an Investigational New Drug package. If PoP awards are successful, the approach could be expanded across the entire translational research spectrum or beyond NIH.

Devices and Sensors to Detect Clinical Outcomes

Sept. 19, 2014

An array of devices and sensors are available to collect physiological, environmental or patient‑reported information in real time, but their use is limited by a lack of information about how to collect, manage, analyze and interpret the data. There also is a need for best practices and standards for the integration of sensor and device data with medical record and other data to describe clinically relevant outcomes.

This concept would focus on integrating real-time data from multiple sources in order to characterize patients or disease status in a clinically meaningful way. The emphasis would be on devices that are already available and the data would be made publicly available at the end of the program.

Access to Compounds, Toxicology/PK Data, Patient Populations

Sept. 19, 2014

The underlying mechanism of toxicity discovered in phase 1 trials often goes without further investigation. This concept would focus on uncovering such toxicity mechanisms, helping answer the question of why pre-clinical tools sometimes fail to predict toxicity. Researchers would be provided with the compounds as well as associated pre-clinical and clinical data. Once the mechanisms are identified, it could be possible to build complementary models, assays, or tools to increase prediction success rates and improve safety.

The concept entails collaboration with pharmaceutical firms, the FDA, and companies that develop predictive toxicology tools. Measurable outcomes could include the number of compounds brought into the program and the number of toxicity mechanisms elucidated.