Part 1. Overview Information

Key Dates

Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

Microphysiological systems (MPS), or tissue chips, are microfabricated devices that mimic human physiological responses, and will be useful tools for predictive toxicology and efficacy assessments of candidate therapeutics. The MPS program started as a five-year partnership among NIH, DARPA and FDA. Previous NIH FOAs (RFA-RM-11-022) and (RFA-RM-12-001) supported the development and integration of bioengineered organ systems, along with the generation of renewable human cell resources to be used as an effective tool for drug development. These organ chip systems consist of scaffolding and multi-cellular tissues with inclusion of mechanical factors (such as flow and stretch) to recreate physiological conditions. Integrating them with other MPS devices to better study organ-organ interaction adds another layer of in vivo-like conditions not available in current in vitro models. Data acquired from this program suggest that tissue chips have the potential to more accurately reflect human responses than current in vitro and animal models, and could have a substantial impact on the safety and efficacy testing of candidate therapeutics. The overarching goal of the NIH Tissue Chip Program is to develop these MPS devices and integrate them to create a Human-on-a-Chip for drug efficacy and safety assessment prior to clinical trials. Current NIH-funded MPS research focuses on modeling various human diseases for efficacy testing (RFA-TR-16-017), and also includes a partnership between NCATS, NASA and the Center for Advancement of Science in Space (CASIS) (RFA-TR-16-019 and RFA-TR-18-001) to develop models of microgravity-induced aging. Through RFA-TR-16-006, Tissue Chip Testing Centers (TCTCs) were established to provide independent validation of tissue chip platforms thereby demonstrating replicability and robustness of tissue chip technology, and to build confidence and promote adoption by the research community. Follow-on FOAs provided additional years of support to these testing centers (see RFA-TR-18-006) and MPS DC (RFA-TR-18-005). It is expected that a successful MPS DC will continue to work closely with NextGen TCTC awardees, tissue chip developers, tissue chip disease modelers, FDA and the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) MPS Affiliate.

Purpose

The purpose of this Limited Competition Funding Opportunity Announcement (FOA) is to invite a renewal cooperative agreement application from the Microphysiological Systems (MPS) Database Center (MPS DC), currently funded through RFA-TR-18-005, to continue database support and to provide analytical tools for the NIH Tissue Chip Consortium. The Consortium facilitates the development, validation and dissemination of tissue chip (TC) technology through support for collaborative research in: 1) development of tissue chips for toxicity and safety testing of promising therapeutics (RFA-RM-11-022); 2) development of tissue chips for disease modeling and efficacy testing (RFA-TR-16-017, RFA-TR-16-019, RFA-TR-18-001); 3) independent validation of tissue chip platforms through the TCTCs (RFA-TR-16-006 and RFA-TR-18-006); and 4) development of tissue chips to inform clinical trial design and its implementation in precision medicine (see RFA-TR-19-014). The MPS DC is expected to be the central clearinghouse for TC data management, and will continue to incorporate novel approaches and technologies for data management, data mining, and data sharing across many organs and tissues, diseases, data types, and TC platforms. The MPS DC is expected to continue to provide different levels of open and tiered access to TC data information for basic, translational and clinical researchers, academic and practicing physicians, the pharmaceutical industry, NIH, FDA and other government agencies, patients, and the lay public. The MPS DC will continue to develop and make available a secure, customizable coordinated data management system for collection, storage, and analyses of diverse data types from multiple TC platforms being developed and used for drug screening, safety and efficacy testing.

The MPS DC should develop and provide a user-friendly system for data mining, and a portal for access and integration of publicly available data resources. The MPS DC should have computational sophistication for scaling the systems and tools to allow incorporation of many different data types. The MPS DC must address confidentiality issues related to database management and distributed computing and allow multiple levels of data sharing. It will work with the TC developers, TC disease modelers, NextGen TCTCs, NIH, FDA, IQ MPS Affiliate and other stakeholders to facilitate data collection and standardization, analyses, and distribution. While NIH-funded Tissue Chip programs are active, the MPS DC will serve as a central data collection, analysis and sharing site, with the vision that it will continue to exist beyond the end of the programs as a critical resource for the scientific community, as part of the business model to be proposed for self-sustainability. By making use of best open science practices and working closely with the Tissue Chip Consortium and the broader scientific community, it is envisioned that the MPS DC will evolve into an extensible and sustainable resource.

Structure of the Tissue Chip Consortium

The NIH Tissue Chip for Drug Screening Program is led and managed by NCATS and utilizes expertise (organ physiology, regulatory science, stem cells, bioengineering, etc.) from more than 60 experts representing over 15 Institutes, Centers and Offices at the NIH and the FDA. NIH interaction with the IQ MPS Affiliate allows for pharmaceutical companies to work with NCATS staff and TC investigators on context of use, marketability and potential stakeholder feedback, elements crucial to move past the discovery/innovation phase. The Tissue Chip Consortium, which comprises all these partnerships, plus several new industry collaborators, meets every 6 months and plays a pivotal role in advancing the MPS technology.

MPS Database Center

The MPS DC will work directly with the Tissue Chip Consortium. The MPS DC will be milestone-driven, and actively work with the TC Consortium and TC developers to facilitate data collection and standardization, and analysis and distribution of data and methodology with the TC Consortium.

Partnerships

A key aspect of this FOA is the interactions among TCTC PD/PI, TC Developers, NIH Officials and Industry Partners. NCATS has executed a Memorandum of Understanding (MOU) with the IQ Consortium (https://iqconsortium.org), with membership consisting of several pharmaceutical companies, and will rely on their feedback regarding vetted reference compounds and functional readouts/assays for each organ system.

Template agreements have been developed for this program to streamline the process: Confidential Disclosure Agreements (CDAs, https://ncats.nih.gov/files/CDA-tissue-chip-validation.pdf) and Collaborative Research Agreements (CRAs, https://ncats.nih.gov/files/CRA-tissue-chip-validation.pdf) provide the framework for partnership between the TC Developer and TCTC PD/PI. TCTCs work with their institutional technology transfer or sponsored research office regarding the terms and conditions of the CDA and CRA with the TC Developers. The MPS DC will be expected to complete a CDA and CRA with partners contributing data to the MPS DC.

Intellectual Property

TC Developers will retain title to any patent or other intellectual property rights in inventions made in the course of the performance of the TC Program. If TC Developers and MPS DC investigators make modifications of TC platforms that significantly change performance and/or function, both parties are expected to discuss ownership interests where applicable and as specified in 37 CFR 401, and to negotiate in good faith the terms of a commercial license. Inventorship for a patent application or a commercialized product based on said inventions will be determined according to United States patent law.

All rights, title and interest in and to any inventions or technologies of TC Developers or of MPS DC investigators, respectively, existing prior to receiving NIH grant funds will be the exclusive property of the respective party. Furthermore, all rights, title and interest in and to any inventions or technologies developed by TC Developers or MPS DC investigators not directly arising from the project plan described in the collaboration agreement will be the exclusive property of the respective party. TC Developers must agree to disclose developed intellectual property promptly and fully to MPS DC investigators.

Section II. Award Information

Section III. Eligibility Information

1. Eligible Applicants

Eligibility is limited to the institution that is currently hosting the existing Microphysiological Systems (MPS) Database Center (MPS DC) which supports the NIH Tissue Chip Consortium.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed. 

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons.Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications  

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101)

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

All instructions in the SF424 (R&R) Application Guide must be followed.

Research Strategy:

The following general items should be addressed by the applicant in the research strategy:

• Describe the proposed data management and coordination within the TC Consortium, indicating the experience in serving as a data management center for a large multi-institution research consortium.
• Describe the nature of the multidisciplinary team necessary to provide the web-based, technical, and statistical resources required to maintain the MPS DC. Include plans and approaches for interacting with the TC consortium members. Specifically, address plans to work with TC investigators, government officials and industry partners to integrate data on reagents and cell sources from TC testing, including, but not limited to iPSC lines, predefined testing compounds, cellular matrices, media, etc.
• Describe the data management for an array of chemicals and reagents needed to perform the various TC assays.
• Describe the ability to manage data on tracking use of reagents, chemicals and tissue sources from TCTCs and TCDs.
• Describe the ability to manage data on tracking and verify quality and control of reagents, chemicals and tissue sources from TCTCs and TCDs.
• Describe the strategy to work with TC investigators, government officials and industry partners to collect, QC and release tiered data from assays used to test each organ system.
• Describe the proposed data stream for information and data coming from NextGen TCTC (RFA-TR-18-006), current and former NIH awardees under the TC program.

Applicants should outline team accomplishments, including any pilot programs or newly developed tools, and discuss their potential impact on the TC Consortium as well as the wider field. Any difficulties in achieving previously proposed specific aims should be addressed. Do not duplicate information provided on individual biosketches. Otherwise, individual expertise and accomplishments belong on biosketches.

Milestones:

Applicants must provide a set of milestones and timelines that demonstrate they will be able to accomplish project objectives, and generate outputs and data needed to provide a robust, secure database service for TC systems. Milestones are intermediate steps towards the completion of the specific aims. They must include clear and quantitative criteria for success. At the minimum, yearly quantitative milestones are required in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. The application should include clearly specified, well-defined milestones, quantitative go/no go decision points, and timelines for assessing progress. A Gantt chart should also be provided that indicates milestone-driven goals and timelines. Possible obstacles and how they will be overcome should also be addressed.

Proposed milestones should address:

• Timely acquisition of organ platform systems data and accompanying hardware/software and cell resources information from the TCTCs and TC Developers;
• How informatics will be used to manage resources, assays, compounds and data, including ensuring availability of source code and format to the Tissue Chip Consortium;
• How outreach and data integration from several organ platforms will be accomplished during the project period;
• How a pace of continuous data integration from testing of new devices by NextGen TCTC(s) will be achieved and maintained;
• How plans to expand and maintain the database over the future years will be formulated, based on new initiatives from the NIH Tissue Chip for Drug Screening program, the expanding Tissue Chip Consortium, and the need for high-quality publicly available TC data sources.

Database Center Functions:

To accomplish the goals of the Tissue Chip for Drug Screening program, the MPS DC must serve as an integrated resource to the Tissue Chip Consortium and be able to perform a number of functions and activities that promote the accomplishment of these goals.

MPS DC applications must document the expertise and experience in how the following functions and activities will be performed:

• Provide a secure, customizable, scalable coordinated data management system for the integration of tissue chip data from many different platforms, across many diseases, and produce readouts for safety and efficacy studies on these tissue chips. This support should include developing and/or adapting new technologies and technological advances to facilitate data collection, storage, and management from Tissue Chip Consortium members. This would entail plans to upgrade database components and architecture to be consistent with current technologies and practices;
• Coordinate with the Tissue Chip Consortium to define standards that adhere to the FAIR (Findable, Accessible, Interoperable, Reusable) guiding principles for data types, format, quality, curation, annotation, and common data elements so that data sets are mineable and comparable. Monitor adherence to those standards. Create tools to harmonize disparate data formats;
• Enhance preclinical and clinical reference data with additional databases and automated data retrieval. Should include capacity to integrate omics data, such as transcriptomic data, into the MPS DC and implement analytical tools with input from the IQ MPS Affiliate and model developers;
• Develop with Tissue Chip Consortium members standard experimental metadata required to be submitted with each dataset, including common data elements, such as clinical phenotypes, using well-defined formats and associated controlled vocabularies;
• Provide a portal and computational modeling tools for integration of developed and publicly available datasets for data mining. To preserve utility to the community, the tools should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so;
• Provide an interactive tool for the analysis of concordance of MPS data and clinical data, and work with the IQ consortium to optimize the concordance analysis;
• Provide a user-friendly resource site, such as Guided User Interfaces, for the public, research scientists, and Tissue Chip Consortium members that allows clear and easy management and retrieval of data and tools from the Tissue Chip program and is accessible to the general scientific community across a variety of platforms. This includes implementing user profiles to allow users to choose and save favorites: MPS models, studies, assays, etc. for customized access. Provide for private user specific annotations of data, MPS models, etc.;
• Provide end-user training (online resources, remote assistance, video teleconferencing), documentation, and technical support;
• Incorporate new approaches to distributed computing and federated databases. plan to manage and disseminate the improvements or customizations of their tools and resources by others. The application may include a plan to incorporate any enhancements into the "official" core software/tools, may involve the creation of an infrastructure for plug-ins, or may describe some other solutions;
• Incorporate new approaches to database support and data management to reduce the burden of rising costs of software;
• Address confidentiality issues and access related to database management and distributed computing and allow multiple levels of data sharing. The application should address security measures to be consistent with those established at pharmaceutical industry, and to ensure integrity of data in the database;
• Manage access permissions across collaborating Tissue Chip Consortium members, the scientific community, and the public. This would include implementing functionality to selectively release all data, partial data, or only aggregated data from user groups including pharma;
• Work with government staff and Tissue Chip Consortium members to define and implement data and protocol validation methods, and a process to evaluate the quality of submitted data prior to Consortium use and public release;
• Provide scalable infrastructure. The Tissue Chip for Drug Screening program is multi-faceted and may expand its size and scope in the future. A successful applicant must have the ability and resources to expand operations to meet such future needs. An example would be specific functionality for use by pharmaceutical companies involved in proprietary studies that enables proprietary data behind a firewall but still have access to functionality and publicly available data in the MPS DC, incorporating compounds of interest to the IQ MPS Affiliate and curate publicly available clinical data for the compounds, establishing a Safe Harbor area in the MPS DC for sharing data between pharma and the FDA;
• Keep the code and resources open source.

Readiness to Undertake Database Activities:

Applicants should address the following:

• The capacity to scale up operations and the approach to doing so if the need arises.
• Documentation that MPS DC investigators have access to an array of software and specialized systems needed to perform the various data imports and analyses; the ability to store, register and track use of reagents, chemicals and tissue sources; the ability to check quality and control of reagents, chemicals and tissue sources; the ability to check data quality and correctness before release to wider circles.
• Have an outreach plan for the scientific community to disseminate the data, tools and resources available from the MPS DC such that MPS DC becomes the go-to resource for MPS technologies including links to other resources and paid links to commercial entities (e.g., MPS model suppliers and services).

Plan for Self-sustaining Operations:

Applicants are expected to seek additional resources to maintain their operations and continue to have an impact after NIH funding ends.

• Plans should indicate other sources of support for program sustainability, and include descriptions of all institutional support, financial and collaborative arrangements, and/or agreements for payment for services. Appropriate documentation should be included in the application.
• Provide any other relevant information about the applicant’s approach for self-sustaining infrastructure and operations.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. This plan must include timely data release to the TC Government Officials and TC Developers as determined by the MPS DC PD/PI during the course of the MPS DC award, and more broadly to the research community at the conclusion of the award as appropriate and consistent with achieving the goals of the program
• The sharing plan must include an agreement that MPS DC investigators will work collaboratively with the TC Consortium to maximize research accomplished by the program, and to implement procedures to provide quality-controlled data and information.
• Applicants must commit to sharing and making protocols/methodologies, data, materials, models, tools, and resources available to the other TC Consortium members as appropriate and consistent with achieving the goals of the program. The terms and timelines for sharing within the MPS DC project; adjustments for coordination of research plans, validation of models, materials, methods and data; and sharing with the research community will be established by the MPS DC PD/PI and approved by the TC Program Director, consistent with achieving the goals of the program and applicable NIH policies and all participants must adhere to these terms as a condition of award.
• Upon completion or termination of the research project(s), the awardees will be responsible for making all data and procedures available to the Tissue Chip Consortium, as well as making them broadly available (e.g., putting them into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for each project. The resource sharing plan must include a plan to accomplish this availability and accessibility no later than at the end of the project period or as negotiated with the TC Program Director.

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by NCATS, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Significance  

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: Does this application provide evidence of significant contributions for the support of the Tissue Chip Consortium activities? If the aims of the application are achieved, how will the activities of the Tissue Chip Consortium be advanced? What will be the effect of these efforts on the methods, technologies, or services provided to the Tissue Chip Consortium? Does the information provided indicate that the MPS DC can be sustained beyond the proposed funding period? If the proposed activities are fully successful, will the MPS DC have a transformative effect in translational research?

Investigator(s)  

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA: Does the applicant have a proven record of database development and integration? Does the PD/PI have experience in managing data from TC platforms? Does the MPS DC infrastructure have the ability to expand operations to meet the needs of an expanding Tissue Chip Consortium?

Innovation  

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA: Does the application develop or employ novel concepts, approaches, methodologies, tools, or technologies to facilitate data collection, storage, and management? Will this approach include developing and/or adapting new technologies and technological advances for distributed computing and federated databases?

Approach  

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific to this FOA: Does the proposed approach provide for a secure, customizable, scalable coordinated data management system? Does the applicant adequately address confidentiality issues? Is the proposed plan appropriate for the state of knowledge, current capabilities and resources? Are adequate plans to assess limits and sensitivity of each TC system, and compare to current in vitro and in vivo gold standards described? Are there appropriate milestones that ensure timely completion of the project? Is there convincing evidence that factors that influence performance metrics and sources of variance are taken into consideration to guarantee reproducibility and reliability of tissue chip data?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment  

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA: Does the applicant have adequate resources at the institution to provide logistical and administrative assistance as well as operational support? Is there convincing evidence that applicants have infrastructure in place to immediately begin data import and integration of organ/tissue chip-specific assays that fit context of use for each organ system? Are resources available from the applicant’s institution to allow expansion of MPS DC activities to accommodate growth of the Tissue Chip Consortium for example server space, data storage capabilities etc.?

Protections for Human Subjects  

For research that involves human subjects but does not involve one of thecategories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan  

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals  

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards  

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions  

Not Applicable.

Renewals  

For Renewals, the committee will consider the progress made in the last funding period.

Revisions  

Not Applicable.

Applications from Foreign Organizations  

Not Applicable.

Select Agent Research  

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans  

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:  

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support  

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NCATS, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

• Will receive a written critique.

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Compliance with resource sharing policies.

3. Anticipated Announcement and Award Dates

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.htmlor call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Defining the details and goals of the project as a whole within the guidelines of this FOA.
• Managing all data acquired in a coherent database that will be available to government and private partners.
• Coordinating, cooperating, and participating with NIH staff in the scientific, technical, and administrative management.
• Designating and maintaining infrastructure for the sole purpose of an MPS database center.
• Working with NIH Program Officials and industry partners to establish context of use, standardizing and validating approaches.
• Managing and performing analyses on data from established standardization and validation milestones.
• Acquiring data generated by microphysiological devices from tissue chip researchers and working with them to understand the perimeters/context of use for each system.
• Ensuring that all MPS DC-affiliated staff will maintain the confidentiality of the information developed by the investigations, including, without limitation, informatics tools, protocols, data analysis, conclusions, etc. per policies approved by the consortium as well as any confidential information received by third party collaborators.
• Analyzing, publishing and/or publicly releasing and disseminating results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and goals of the FOA.
• Ensuring efficient data transfer to a successor (if applicable) at the end of the funding period
• Along with all MPS DC-affiliated staff, participating in a cooperative and interactive manner with NIH staff, TC investigators and one another.
• Sharing data, materials, informatics tools, methods, information and unique resources that are generated by the project as appropriate and in accordance with NIH policies in order to facilitate progress and consistent with achieving the goals of the MPS program.
• Working with the members of Tissue Chip Consortium to establish agreements that address the following issues: (1) procedures for data sharing among consortium members and data sharing with industry partners, as appropriate; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing biospecimens under an overarching MTA amongst consortium members that operationalizes material transfer in an efficient and expeditious manner as appropriate and consistent with achieving the goals of the program; (5) procedures for reviewing publications, determining authorship, and industry access to publications.
• Ensuring that for activities undertaken by the MPS DC that involve academic and/or industry collaborations within the Tissue Chip Consortium there are appropriate research collaboration agreements (e.g. CRA, CDA, MTA etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement terms of award, as well as any additional applicable NIH policies and procedures.
• Ensuring that the research is conducted in accordance with processes and goals as delineated in this Funding Opportunity Announcement.
• Upon completion or termination of the MPS DC project, ensuring all study materials, tools, databases and procedures developed by the MPS DC are broadly available (e.g., putting into the public domain) or making them accessible to the research community according to the NIH-approved plan submitted for each project, for making data and materials available to the scientific community and the NIH for the conduct of research. The data sharing plan should include a plan to accomplish this within 90 days of the end of the study.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards.

The NCATS will designate program staff, including a Program Officer to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer will be named in the Notice of Award (NoA).

An NIH Project Coordinator will be substantially involved in this project as follows:

• Coordinate and facilitate the activities of the MPS DC, attend and participate in all meetings of the TCTC, and act as a liaison between the Awardee and the Cures Acceleration Network Review Board (CAN RB).
• Work with Science Officer(s) from the trans-NIH TC Project Team to review the scientific progress and administrative accomplishments of the MPS DC, and review the project for compliance with operating policies and procedures, including meeting milestones. Based on this review, the Program Officer may recommend to the NIH to continue funding, or to withhold or restrict support for lack of progress or failure to adhere to NIH policies. Review of progress may include regular communications between the Principal Investigator and NIH staff, periodic site visits for discussions with research teams, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic external review of progress.
• Maintain public - private partnerships established under the NCATS Tissue Chip initiative
• Work directly with industry and regulatory partners on maintaining or modifying standardized protocols to test MPS devices
• Provide input into the design of research activities and play a key role in coordinating research efforts.
• Monitor milestone progress and help identify recourses, if needed.
• Ensure that the MPS DC adheres to cooperative agreement data-sharing and other resource-sharing policies.
• Facilitate collaborations with and access to other NIH-supported research resources and services.
• Facilitate negotiations with companies interested in working with the MPS DC.
• Provide advice on project management and technical performance.
• Coordinate and manage Tissue Chip Consortium Steering Committee efforts.
• Provide guidance to the awardees on private-public partnerships and regulatory agency policies.
• Invite experts with relevant scientific expertise to provide feedback on MPS DC activities.
• The NIH reserves the right to curtail or phase out the MPS DC award in the event of (1) a substantial shortfall in accomplishing the management goals and responsibilities as stated in the reviewed application, (2) failure to meet MPS DC procedures and milestones, and/or (3) substantive changes in the management of MPS DC that are not in keeping with the objectives of the FOA.
• The NIH will enlist additional technical experts as necessary from within the NIH, other government agencies, such as the FDA, and from industry partners whose function will be to assist the MPS DC Program Director in carrying out the goals and aims of the approved studies.

Areas of Joint Responsibility include:

• Through the MPS DC awardee and NIH staff, the MPS DC will determine criteria and processes for quality control of information and data to be posted for the research community, consistent with NIH policies and achieving the goals of the program as described in this Funding Opportunity Announcement.
• Participate in recurring monthly meetings to discuss progress, obstacles and any other MPS DC-related issues and/or activities.
• Engage the CAN RB to provide feedback to the NCATS on MPS DC activities. The CAN RB may review the progress of the MPS DC project and may advise NIH staff of opportunities that may enhance the operation and achievements of the MPS DC.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee from the Cures Acceleration Network Review Board chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreementsare required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings.Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

Finding Help Online:http://grants.nih.gov/support/(preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email:GrantsInfo@nih.gov(preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support(Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email:support@grants.gov

Dan Tagle, Ph.D
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-594-8064
Email:tagled@mail.nih.gov

Carol Lambert, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-435-0814
Email:lambert@mail.nih.gov

Erin Davis
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-451-4238
Email: erin.davis@nih.gov

Section VIII. Other Information