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:


Microphysiological Systems (MPS) Database Center

Sept. 19, 2019

Danilo A. Tagle, Ph.D., presented the concept re-issue to continue the Microphysiological Systems (MPS) Database Center (DC) currently hosted and managed by the University of Pittsburgh Drug Discovery Institute. Dr. Tagle noted that establishing the MPS Database Center was first approved on September 7, 2017, by the Council and Board as database support for the Tissue Chip Program. The MPS Database—which is the central archive for aggregate pre-clinical, clinical and experimental MPS data generated in the Tissue Chips Testing Centers (TCTCs)—also is being used by developers and other stakeholders, including the pharmaceutical industry. To date, the database contains 58 MPS (i.e., tissue chips) experimental models covering 11 organ systems, which were developed at 14 TCTCs. Data from 171 studies are being housed, including images and videos deposited by eight data developers. Dr. Tagle emphasized that all data submitted to the MPS DC will be made publicly available to the research community.

Since November 2018, the MPS database usage has steadily increased: 109 users are currently registered and, on average, 86 new users view or download data each month. The MPS database has the potential to transition to a self-sustaining business model after the 2-year funding cycle. Dr. Tagle summarized the ongoing research activities in this area and noted that the MPS Database Center is a collaborative partnership between NCATS, the FDA and the MPS affiliate of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ).

Project/Program Officer:
Danilo A. Tagle, Ph.D., M.S.
Associate Director for Special Initiatives
Office of the Director
National Center for Advancing Translational Sciences
Phone: 301-594-8064

Order of Magnitude Increases in the Efficiency of Adeno-Associated Virus (AAV) Vector Production for Human Gene Therapy

May 16, 2019

Multiple clinical successes in clinical trials using Adeno-Associated Virus (AAV) vectors have been witnessed in recent years. At present, the major limiting factor to extending this approach to other rare diseases is the ability to manufacture clinical-grade AAV vectors.

The objective of this initiative is to develop at least one independently validated technology that increases efficiency of AAV vector production for human gene therapy by a factor of tenfold or more. If successful, this initiative would substantially increase the number of rare disease gene therapy clinical trials. In addition, the developed technology could be used for research projects conducted by NCATS’ Division of Pre-Clinical Innovation.

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

Synthetic Technologies for Advancement of Research and Therapeutics (START) – Engineering Novel Therapeutics

Jan. 10, 2019

The objective of this initiative is to employ synthetic biology (SB) – along with newly available tools in genetic engineering, gene synthesis and metabolomics – to construct and incorporate new biosynthetic or artificial metabolic pathways to accelerate and enable the design and construction of engineered cell therapies for the production of compounds with a strong therapeutic and disease relevance. SB can be applied in a variety of ways for therapeutic development for a number of diseases, such as for metabolic diseases through the construction and clinical implementation of mammalian synthetic gene networks that can accurately detect dysregulated metabolic signals and initiate the production and delivery of appropriate dosage of therapeutic molecules/compounds.

The program will focus on developing desired synthetic therapeutic products in a scalable, cGMP compliant manner; generating a catalog of biologically relevant pathways that can be used in a “plug-and-play” scenario to generate biologics; engineering novel protein motifs that increase bioavailability in currently difficult to target tissue types; and expanding the available catalog of biologics used to treat diseases, such as rare metabolic disorders.

Project/Program Officer:
Danilo A. Tagle, Ph.D., M.S.
Associate Director for Special Initiatives
Office of the Director
National Center for Advancing Translational Sciences
Phone: 301-594-8064


Drug Screening of Biofabricated 3-D Disease Tissue Models

Sept. 27, 2018

Less than 12 percent of the drugs that enter drug trials receive approval. This is often a consequence of using overly simplistic two-dimensional (2-D) testing models that are not good predictors of a drug’s performance in later stages of drug development. Three-dimensional (3-D) biofabrication enables the manufacture of more complex and more physiologically relevant testing models. This program will utilize 3-D biofabrication to develop better models that will be incorporated in novel drug screening platforms.

NCATS already has established a 3-D Bioprinting Laboratory, and its current projects include biofabrication of skin, retina, blood-brain barrier and cancer models. To enhance collaboration between the laboratory and scientist in academia, a pilot program for Collaborative Drug Discovery Research Using Bioprinted Skin Tissue was developed. Skin tissue was selected because it has a relatively simple layered structure. The work with skin can be used to inform development of other tissue with layered structures such as liver and kidney tissue and other disease models. NCATS is working to develop 3-D biofabricated models of psoriasis with Columbia University and squamous cell carcinoma with The Rockefeller University. The next step is to incorporate the models in high-throughput drug screening platforms and extend the program to incorporate 3-D biofabrication of other tissue types.

The ultimate goal of this initiative is to provide strong evidence of success for utilization of 3-D tissue models for drug screening. The program will inform development of 3-D platforms across multiple diseases.

Biofabricated 3-D Tissue Models of Nociception, Addiction and Overdose for Drug Screening

Sept. 27, 2018

NIH has recently launched the HEAL (Helping to End Addiction Long-term) Initiative, a multidisciplinary, trans-agency effort aimed to rapidly advance the development of scientific solutions towards the national opioid public health crisis. This program will be one component of the NCATS-lead and HEAL-supported “Trans-NIH collaborative to develop human-based platforms and novel drugs to treat pain, addiction and overdose.” The initiative aims to apply 3-D biofabrication technologies to develop novel multicellular tissue constructs for drug screening by using human induced pluripotent stem cell (iPSC)-derived cells representing sensory/pain neurons, brain regions and other tissues involved in pain, addiction and/or overdose, including tissue models of the blood-brain barrier.

The proposed initiative will foster strong collaborations among the NCATS intramural 3-D Bioprinting Laboratory and external research community. The goal of the initiative is to establish physiologically and pharmacologically relevant biofabricated 3-D tissue models of pain, addiction and/or overdose in multiwall plate format for drug screening. The ultimate goal of the initiative is to disseminate the acquired knowledge, tools and technologies to scientific community; facilitate application of more physiologically relevant and validated 3-D models for drug screening; and help advance identification of novel, safe and effective treatments for pain, addiction and/or overdose.

Tissue Chips to Model Nociception, Addiction and Overdose: “Tissue Chips to HEAL”

Sept. 27, 2018

NCATS is leading a trans-NIH collaborative to develop human-based screening platforms and novel drugs to treat pain and opioid use disorders as part of the NIH Help End Addiction Long-term (HEAL) initiative, and tissue chips plays a big part in this effort. This initiative will address the lack of valid models in this field by developing and testing tissue chips that can model the mechanisms and/or effects of nociceptive (pain) signaling, addiction or overdose, using human tissues in physiologically relevant in vitro platforms.

The initiative could help to reveal the mechanisms underlying an individual’s pain response to tissue damage or disease, any related opioid use, and potential overdose. It also could provide insights into the impact of physiological comorbidities, therapeutic responses and addiction treatment outcomes.

Areas of interest include the appropriate modeling of a pain/addiction/overdose-relevant organ system, a chip that provides a more useful readout than assays that are already available, and end points that can be demonstrated to correlate with clinical measures of pain, addiction and overdose. The program will include developing quantitative end points that correlate with clinical measures of pain, addiction and overdose and the use mature human-derived tissues for central and peripheral nervous system tissues and non-nervous system tissues. To accomplish this tissue developers will need to partner with pain experts as collaborators.

“Clinical Trials on a Chip”: Tissue Chips to Inform Clinical Trials for Rare Diseases

Sept. 27, 2018

There is a significant gap in developing therapeutics for diseases/disorders that are life-threatening and/or chronically debilitating including for neurological disorders, cancer and rare diseases, especially in pediatric populations. Drug development for these diseases/disorders is challenging, time-consuming and fraught with risk and thus expensive. In particular, failure rates in late-stage clinical trials are disproportionately high for these diseases/disorders, due to complexity, the difficulty of examining the pathophysiology directly in vivo and, in part, inadequately designed clinical trials. This new initiative seeks to build upon previous successes in the use of tissue chips to support the use of this technology to inform clinical trial design and elucidate pathophysiology of the diseases; assist with the selection of best drug candidates for clinical trials; and improve the selection of patient populations and identification of reliable clinical trial endpoints.

Tissue chips can help streamline clinical trials by helping to select and stratify subgroups in pre-clinical and early clinical trial stages and by providing safety and efficacy data. This can be accomplished by populating chips with induced pluripotent stem cell-derived and commercially available cell sources that represent genotypic and phenotypic spectrum of the patient population for various group of diseases and disorders.

Among the goals under this new initiative is the use of data from tissue chips in the clinical trials decision-making process. It also will include production of tissue chips that allow physicians and patients to make informed decisions about appropriate treatment regimens. The project will have broad and significant impact by validating the usefulness of tissue chip platforms in a clinical setting and will be disease-relevant, particularly for rare diseases and other human disorders for which there are no adequate models.


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.

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). 


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).


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).


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.