Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

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

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

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

This Notice of Funding Opportunity (NOFO) is to establish the NAMs Data Hub and Coordinating Center (NDHCC) to support the NIH Common Fund’s Complement Animal Research In Experimentation (Complement-ARIE) program. The goal of the NDHCC is to create a centralized data hub, building a searchable repository for NAMs, establishing standards for data reporting and model credibility, developing strategies for interoperability, sustainability, and data reuse, and developing tools for data analytics, dissemination, and sharing. The NDHCC will also serve as the coordinating center for the overall Complement-ARIE program, helping to drive internal program cohesion and fostering community collaborations, including administrative and logistical support while organizing the semi-annual investigators meeting made up of NIH Complement-ARIE award recipients as well as additional support activities.

Background

The 21st century has been a time of accelerated technological advancement. New and evolving methodologies, including gene editing, machine learning, induced pluripotent stem cells (iPSCs), 3D bioprinting, organoids, and microphysiological systems are fundamentally changing the way biomedical science is done. These technologies and other advances have greatly enabled and contributed to the development and application of New Approach Methodologies (NAMs). NAMs can be defined as any in vitro, in chemico, or in silico method, that when used alone, or in concert with others, enables improved disease models, including toxicology as well as complex human-relevant models, and as a result, complement animal models in biomedical research. NAMs hold tremendous promise in understanding various biological processes leading to better assessment of disease risk and progression, and development of precision interventions in the context of personalized medicine. The recent passage into law of the FDA Modernization Act 2.0 enables drug registration without the absolute requirement for the use of animals in safety toxicology assessment where alternative risk assessment tools are available. Similarly, the Toxic Substances Control Act (TSCA) as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act, directs EPA to promote the development and timely incorporation of alternative test methods or strategies that do not require new vertebrate animal testing.  While traditional animal models continue to be vital to advancing scientific knowledge, NAMs offer unique strengths that, when utilized strategically or in combination, can complement animal models in ways that enable researchers to answer previously difficult or unanswerable questions, especially in areas where in vivo models are lacking or have consistently underperformed.

NAMs have proven to be valuable tools in basic, clinical, and toxicology research, and have been used to study the efficacy and toxicity of novel therapeutics. In chemico cell-free platforms use cell-free systems to study the interaction of drugs, toxicants, and other biological molecules. This method requires a prior knowledge about the interaction of the test agent with a biological substance, such as in skin-sensitization assessments. In vitro models are systems that are performed generally outside of living organisms, including various types of cell culture systems, organoids, and tissue culture techniques, such as microphysiological systems (MPS). In silico computational models incorporate biological data with mathematical and computer-based representations to construct models of human biology using methods such as data analyses, data mining, homology models, machine learning, pharmacophores, quantitative structure-activity relationships, and network analysis tools. 

A trans-NIH working group engaged in robust strategic planning activities and outreach focused on establishing a unifying vision for building on ongoing efforts to develop, standardize, validate, and use NAMs. The NIH conducted strategic planning activities to inform the Complement-ARIE program. These included:

• Public listening sessions that brought together key representatives from multiple sectors: 1) industry and academic partners;
• An interagency retreat with federal partners to discuss high-priority areas;
• A landscape analysis to collect and analyze information on ongoing efforts in the NAMs space;
• Complement-ARIE Prize Challenge, a crowdsourcing competition that asked the public to propose novel ideas using NAMs to conduct basic research, uncover disease, and translate knowledge into products and practice. The competition awarded $1,000,000 in total prize money to twenty diverse teams across the competition areas of in silico, in vitro, in chemico, and combinatorial approaches. 

Simultaneous to early planning stages of the Complement-ARIE program, the NIH sought the assistance of the Advisory Committee to the Director (ACD) on catalyzing the development and use of Novel Alternative Methods to Advance Biomedical Research to identify areas in which the development and use of novel alternative methods will provide the most value to biomedical research. The ACD working group recommendations are aligned with Complement-ARIE program goals and have been incorporated into the program planning structure.

The overarching goal of the Complement-ARIE program is to catalyze the development, standardization, validation, and use of human-based NAMs that will transform the way basic, translational, and clinical sciences are done. Specific program goals include: 

• Develop better models and understand human health and disease outcomes across diverse populations.
• Develop NAMs that provide insight into specific biological processes or disease states.
• Validate mature NAMs to support standardization and regulatory and clinical use.
• Complement traditional models and make biomedical research more efficient and effective. 

Complement-ARIE will address current challenges in NAMs, which include: validation and testing in complex systems, and the ability to generate preclinical data needed for first-in-human trials; characterizing long-term, systemic and developmental health effects of environmental and drug exposures; and developing systems that better model the physiology and disease pathology of human diseases or conditions for which current experimental models are lacking (e.g. neuroscience and behavior research). Key focal areas of the NIH Common Fund investment include, but are not limited to:

• Complex in vitro models that emulate human organ structure, function, and response to study both normal physiology and disease pathology.
• In silico multi-scale systems simulating and modeling healthy/diseased individuals through computational approaches.
• In chemico cell-free systems that capture dynamic changes to assess chemical toxicity, chemical hazard and risk assessment, and inform adverse outcome pathways.
• Integrated findable, accessible, interoperable, and reusable (FAIR) datasets and artificial intelligence (AI)-engines to generate testable predictions (i.e., patient digital twins).
• Combinatorial approaches that combine two or more of the above approaches. 

To achieve its goals, Complement-ARIE consists of the following key components and centers: 

• Comprehensive NAMs Technology Development Centers (TDCs) – stimulate the development of NAMs to address areas of greatest need, with emphasis on increased biological complexity and throughput, innovative combinatorial approaches, and data sharing.
• NAMs Data Hub and Coordinating Center (NDHCC) – provide overarching support for the Complement-ARIE Consortium and create integrated data structures, including standards for model credibility, improve FAIRness of NAMs-relevant data, and create a searchable NAMs repository.
• Validation and Qualification Network (VQN) – advise the NDHCC on elements of the data model including the common data elements and data standards; standardized reporting for validation/qualification; apply validation/qualification frameworks, accelerate deployment and regulatory implementation of NAMs.

Within each of the three key program components, training and outreach activities are required to facilitate dissemination, capacity building, and adoption of NAMs. Complement-ARIE will participate in strategic engagement with key partners from other federal agencies including regulatory bodies, industry, non-profits, and other NGOs to advance emerging opportunities in the development and use of NAMs in basic, translational, and clinical research.

Complement-ARIE will play a pivotal role in advancing NAMs and our current understanding of human health and etiology and treatment of human disease. This program will have near-term application in fields such as mechanism elucidation, personalized precision medicine, safety pharmacology, predictive toxicology, and efficacy evaluation of candidate therapeutics.

Trans-NIH Complement-ARIE Working Group

The Complement-ARIE program is led by the trans-NIH Complement-ARIE Working Group , which is responsible for the stewardship of the Complement-ARIE program. The Complement-ARIE NIH Executive Committee consists of the Complement-ARIE Working Group Co-Chairs and Leadership Team, who are responsible for the overall management of Complement-ARIE.

The Complement-ARIE Consortium

The three key components, namely, the TDCs, NDHCC, and VQN, described above, participate in the overall Complement-ARIE Consortium. The Consortium structure is meant to effectively guide all the funded projects to meet the overall goals of the Complement-ARIE program. The Consortium is further comprised of members of the trans-NIH Complement-ARIE Working Group, all award recipients of this Notice of Funding Opportunity (NOFO), the NDHCC, and the VQN, and other relevant scientists and groups. The Consortium is led by the Complement-ARIE Steering Committee (SC). The SC will include a representative Program Director/Principal Investigator (PD/PI) from each awarded TDC, an NIH Project Scientist, the PD/PI of the VQN, and the PD/PI of the NDHCC. Members of the SC will elect the SC co-chairs from among the Complement-ARIE PDs/PIs. The SC Steering Committee (SC) Co-chairs, who will preside at all SC meetings and provide scientific leadership for the Consortium with significant input from NIH staff.

Award recipients agree to governance, through voting and decision making of the consortium through the SC. It is expected that most of the decisions on the activities of the SC will be reached by consensus. Other Consortium subcommittees may be formed as needed, and as deemed appropriate by the SC to further or achieve the goals of Complement-ARIE.

Complement-ARIE Consortium Data Sharing

A central goal of the Complement-ARIE program is the harmonization of NAMs data collection, metadata, and the standardization of NAMs validation frameworks for wider NAMs adoption and use. The NDHCC will provide a centralized data hub, build a searchable repository for NAMs, establish standards for data reporting and model credibility, develop strategies for interoperability, sustainable data reuse, and develop tools for data analytics, dissemination, and sharing. The TDCs will be expected to submit data to the central Complement-ARIE data hub and follow the framework for standards, metadata and common data elements (CDEs) established by the NDHCC and in accordance with the Data Management and Sharing Plans approved by Consortium members.. The NDHCC will be responsible for managing the data generated by the Complement-ARIE program in accordance with the data management and access policies established by the Consortium through the Steering Committee. The NDHCC will assist TDCs in identifying existing repositories, provide guidance on data standards, and help integrate data from public sources as needed. The VQN will collaborate with the NDHCC to develop a framework for standards, metadata and CDEs that apply to all types of data generated to maximize potential for research, data integration, and NAMs benchmarking and evaluation for validation and qualification. The NDHCC and VQN will collectively create a mechanism to support data harmonization and will participate in trans-NIH efforts to support scientific collaboration and data sharing, partnership, and rapid dissemination of the NAMs produced by the Complement-ARIE program. The NDHCC and VQN will provide overall support and guidance to award recipients funded under this NOFO in the following areas: (1) administrative operations and logistics, (2) data collection, curation, and integration, (3) data standardization, metadata development, ontology use, and CDE implementation, and (4) data management, sharing, search and use.

NAMs Data Hub and Coordinating Center (NDHCC)

This NOFO applies only to the NAMs Data Hub and Coordinating Center (NDHCC).

Research Resource Objectives

The mission of the NDHCC is to provide overarching support for the Complement-ARIE Consortium and will serve as the centralized Data Hub and Data Coordinating Center for all Complement-ARIE activities as well as the Coordinating Center for the overall Complement-ARIE program.  The NDHCC will coordinate and manage the collection, archiving, curation, and dissemination of all NAMs-relevant data, metadata, analyses, tools, computational models, and validation and qualification documentation generated by the Complement-ARIE Program and to do so in a manner that ensures maximum interoperability with data from other NAMs-related repositories and consortia. The NDHCC will create and manage an integrated data structure that supports the development, validation, and qualification of NAMs in adherence with the findable, accessible, interoperable, and reusable (FAIR) principles. To the extent needed or where appropriate, the NDHCC will coordinate on standards with NIST and other federal partners, to ensure that all data, tools, and models adhere to nationally and internationally recognized standards, thereby enhancing interoperability and regulatory credibility of NAMs within the broader scientific and regulatory landscape. The NHDCC team must effectively and productively collaborate with other major components of the Complement-ARIE program, particularly the TDCs and VQN, which collectively form the Complement-ARIE Consortium. Additionally, it would be desirable for the NDHCC to develop a data sharing infrastructure that could seamlessly be applied across the global efforts around the development of NAMs. 

Activities directed by the NDHCC include at a minimum the following four core components: NAMs Data hub infrastructure development and maintenance; Data coordination, standardization, harmonization, and integration; Tool and software development for analytics and dissemination; and Overall consortium coordination and outreach:

1. NAMs Data Hub Infrastructure Development and Maintenance

The NDHCC will be responsible for creating and maintaining a centralized NAMs data hub for the Complement-ARIE program. The purpose of the centralized data hub is to support collaboration within the Complement-ARIE consortium, to enable the development, validation, and qualification of NAMs, and to support FAIR sharing of NAMs-related data, standards, models, and code. The data hub is intended to provide a secure, centralized data platform to support consortium data sharing activities for the duration of the Complement-ARIE program. Importantly, the NAMs data hub is not intended to serve as a permanent repository for long-term archive of all data and resources generated and used by the Complement-ARIE program. Rather, the NAMs data hub is intended to provide a unified searchable interface for the Complement-ARIE consortium and the scientific community to locate and access Complement-ARIE datasets and resources during the Complement-ARIE program period, regardless of where the datasets and resources are stored in the long term. 

The exact nature and quantity of data that the NAMs data hub will need to store and manage cannot be known in advance. Given this uncertainty around the amount and type of data generated by Complement-ARIE, it is important that the awardee provide a flexible, yet robust plan and realistic timeline to establish interim infrastructure as quickly as possible and describe an approach that will enable them to rapidly and commensurately scale the infrastructure and capabilities as needed to support the activities of the consortium.  For example, NAMs developers can use existing NAMs data to benchmark the development, validation, and qualification of new, but similar NAMs (e.g., tissue and cell type specific NAMs), to develop approaches more in line with the FDA and EPA regulatory needs, and to develop integrated testing strategies using both existing and newly developed NAMs.  Among the major responsibilities and required functional capabilities for the NDHCC Data Hub are the following areas, including but are not limited to:

• Developing a NAMs Data Hub for user-friendly submission of and access to Complement-ARIE data (both raw data and derived datasets), metadata, tools, standards, and computational models from TDCs and VQN.
• Providing a centralized repository (data storage) for Complement-ARIE consortium members to store and access consortium-generated and related NAMs data. The data hub will be required to catalogue and store diverse data types and digital object types for NAMs, including but not limited to: complex in vitro models, e.g., microphysiological systems (MPS), bioprinted tissues, 3D cell cultures, and organoids, computational and system biology models, including PBPK and QSAR models, machine learning outputs, Adverse Outcome Pathways (AOPs), Standard Operating Procedures (SOPs) and protocols, software code and supporting documentation, and data generated for technical characterization of NAMs developed in the TDCs, as well as from validation and qualification activities through the VQN. The data hub will facilitate the storage of raw and processed data objects generated by the TDCs and data generated through the VQN validation and qualification activities and provide tiered access to consortium members, including the VQN. This may include data from clinical trials used to develop or benchmark NAMs developed in the TDCs.  In addition to data generated by Complement-ARIE consortium members, the data hub may be required to ingest and store proprietary NAMs-related data generated by outside parties in specific instances where those data are required for the validation or qualification of NAMs through the VQN.
• Establishing a federated search interface to ensure transparency and accessibility, as appropriate, of Complement-ARIE data to the general scientific community. The search portal front-end should provide clear and easy search, and retrieval of publicly available data and tools developed with funding from the Complement-ARIE program, regardless of where they are stored. The search portal development team is expected to install Data Repository Service (DRS)-like microservices to link to the dataset locations.
• Ensuring the platform is flexible and extensible to manage and integrate multiple types of data and digital objects.

Other responsibilities and functional capabilities include:

• Developing a tiered structure for data access and security to manage access permissions within theComplement-ARIE Consortium members, , and data use and release as governed by consortia agreements pertaining to sharing and confidentiality and in accordance with NIH Data Management and Sharing Policy. In addition to data generated by Complement-ARIE consortium members, the data hub may be required to ingest and store proprietary NAMs-related data generated by outside parties in specific instances where those data are required for the validation or qualification of a NAMs through the VQN. In such cases, tiered access to manage access and permissions will be required. Data security encompasses confidentiality, data integrity, and availability. Confidentiality includes managing data access to maintain data security and making data accessible to authorized users only for authorized purposes. Data security protection and proper stewardship of NAMs-related data, and other sensitive information stored and distributed is of the utmost importance.  The NIH security best practices for Users of Controlled Access Data  should be implemented to protect the privacy and confidentiality of research participants and prevent unauthorized access to data. Investigators are expected to develop policies and procedures for notifying NIH, managing, and mediating any loss of data or compromise of data confidentiality unless another standard is expected by applicable NIH policy or applicable laws or regulations. . 
•  If the Complement-ARIE Consortium does generate controlled access data, the NDHCC will be responsible for working with the data generators to identify an appropriate repository that can host the data in compliance with all relevant NIH policies and using persistent identifiers, when available, to direct Consortium members to where the data can be accessed.
• Ensuring the data hub infrastructure adopts and implements established Consortium data standards to ensure data submitted by the TDCs are harmonized, interoperable and optimal to facilitate the validation and qualification process as described below.
• Monitoring adherence to the agreed upon standards for data reporting and credibility.
• Establishing data use agreements (DUA) with the appropriate parties and identifying or creating the tools needed to harmonize disparate data formats for ingestion into the data hub. For those pre-existing, proprietary data generated outside the Complement-ARIE consortium that the data hub may need to ingest to facilitate the validation and/or qualification of NAMs through the VQN, the data hub will be responsible for ensuring that proprietary data are retained and archived as described in the DUA.
• Developing and implementing common submission, processing, and curation pipelines for the diverse range of Complement-ARIE data, metadata, models, and code, as well as quality control/quality assurance processes to evaluate and vet the quality of submitted digital resources prior to consortium use and public release.
• Working with the TDCs and NIH staff to identify appropriate long-term public data repositories for the storage, sharing and reuse of Complement-ARIE data submitted to the Data Hub in keeping with the consortia agreements pertaining to data sharing and confidentiality. 

2. Data Coordination, Standardization, Harmonization, and Integration

The NDHCC will be responsible for developing and implementing a coordinated NAMs data management and sharing approach for data harmonization across the overall Complement-ARIE program. The NDHCC in conjunction with the VQN will develop a framework for standards, metadata and CDEs that apply to all types of data gathered by Complement-ARIE awardees to maximize the potential for validation and qualification, the integration with other Complement-ARIE data, and for evaluation of Complement-ARIE program impact. The goal is to facilitate data and metadata standardization, harmonization, and integration across Complement-ARIE projects. Furthermore, interoperability with existing the NIH data ecosystem and other NAMs resources is a priority for the NDHCC to support data-driven research. The NDHCC should align with policies and interoperability standards utilized in existing NIH data and NAMs resources.

The major data coordination-related responsibilities for the NDHCC include but are not limited to the following areas:

• Surveying data standards currently in use among existing NAMs consortiums and development efforts recommending standards, CDEs, and providing a FAIR-compliant centralized repository (data storage) for Complement-ARIE consortium members to store and access consortium-generated and related NAMs data using established ontologies and controlled vocabularies, including but not limited to: the Human Phenotype Ontology (HPO) standardized vocabulary for phenotypic abnormalities, Chemical Entities of Biological Interest (ChEBI) database of molecular entities, and Disease Ontology database of  standardized disease terms that support FAIR data use.
• Convening Complement-ARIE awardees and stakeholders to define appropriate data standards, CDEs and best practices for management and sharing of diverse data sets through a consensus process. The NDHCC will need to coordinate with the VQN, Complement-ARIE Consortium members and the broader NAMs community to define standards for data types, format, quality, curation, annotation, and CDEs so that data sets and metadata are in adherence to the FAIR principles. In particular, standards for representing NAMs model credibility are of critical importance. The NDHCC will need to interact closely with identified informatics and data science experts from the TDCs and VQN during this process.
• Developing standardized metadata that will be required to be submitted with each dataset using well-defined and machine-readable formats and associated controlled vocabularies and CDEs. The Common Fund Data Ecosystem (CFDE) aims to enable broad and FAIR use of Common Fund data through an online search and discovery portal. To the greatest extent possible, NDHCC will adopt metadata standards in alignment with the CFDE’s cross cutting metadata model (C2M2) to facilitate seamless metadata sharing with CFDE. Additional information on C2M2 is available at https://info.cfde.cloud/documentation/C2M2 .   
• Defining, establishing, and implementing data and protocol validation and curation methods, and best practices in collaboration with NIH staff, Complement-ARIE Consortium PIs, and VQN members. Model credibility is critical for trust-worthy use and supporting regulatory decision making.  The NDHCC will establish a generalizable framework for assessing the risk and model credibility, including the selection of appropriate verification and validation methods, and the development of criteria, metrics and a process for determining the rigor, measuring the prediction accuracy, and standardizing regulatory evaluation for the computational models developed by the TDCs via the collaboration with VQN, and regulatory agencies when necessary.
• Developing strategies to enable interoperability with policies and interoperability standards utilized in existing NIH data and NAMs resources, such as the Common Fund Data Ecosystem (CFDE), the NIH Cloud Platform Interoperability (NCPI) effort, and other NAMs resources, including the Integrated Chemical Environment , the NIEHS Drug Matrix, EPA CompTox Chemicals Dashboard,  the Joint Research Centre Data Catalogue and EU ToxRisk
• Developing a framework to enable meaningful comparison and integration across heterogeneous NAMs datasets generated by Complement-ARIE, including individual and population comparative studies. For example, the Complement-ARIE consortium will establish Integrated Testing Strategies (ITS) that involve 1) the integration of data types from various sources, including in vitro assays, in silico models, and chemical structure-activity relationships; 2) working with the VQN in developing guidelines for the design, validation, and use of ITS in the utilization of combinatorial NAMs in risk assessment towards equivalency or better protection for human health and the environment compared to traditional testing methods; and 3) resources for Uncertainty Analysis since ITS inherently involve a degree of uncertainty due to the use of data from different sources and models with varying degrees of complexity. Developing methods for quantifying and communicating the uncertainty associated with ITS predictions is important for their acceptance and use in regulatory decision-making.

The NDHCC will need to develop strategies for sustainability and long-term data reuse. In addition to promoting interoperability, the NDHCC will also need to develop a roadmap to sustainability, ensuring that the data and tools produced by Complement-ARIE remain available and can be utilized beyond the Complement-ARIE program period of support. The NHDCC is not intended to serve as permanent archive of data and resources generated by the Complement-ARIE consortium. Working with the data generators across the Complement-ARIE consortium, the NDHCC will need to ensure that upon completion or termination of the funded work, the study materials, data, models, tools, and protocols stored by the NDHCC are made broadly available, preferably through deposition into a public data repository, or are made available to the research community per an NIH-approved transferring plan in accordance with relevant DUAs and consortium policies.

As part of its sustainability responsibilities, the NDHCC will be responsible for participating in Common Fund Data Ecosystem (CFDE) with the goal of integrating Complement-ARIE datasets and resources into CFDE. CFDE is a program focused on driving scientific discovery through the reuse of data generated by Common Fund programs. The types of activities needed to successfully integrate Complement-ARIE program resources with CFDE may include, but are not limited to: 

• Collaborating with CFDE to develop and standardize metadata fields
• Submitting metadata and digital assets to the CFDE data portal (additional information available at https://data.cfde.cloud/submit)  
• Establishing resolver services and unique identifiers for publicly released datasets and digital resources. CFDE strongly encourages adoption of the GA4GH DRS standard.
• Adopting Application Programming Interfaces  (APIs) recommended by CFDE
• Participating in relevant CFDE Working Groups and Committees
• Attending bi-annual CFDE program meetings
• Working with the CFDE Integration and Coordination Center to provide access to metrics of data and digital resource adoption and use

Additionally, the NHDCC will need to work with NIH staff and Complement-ARIE Consortium members to develop and implement a scheme whereby each submitted data set is uniquely identified and tracked so that data can be properly attributed, referenced and cited by end users. The NDHCC will also be responsible for tracking usage of Complement-ARIE NAMs data and tools by the general research community distinguishing between data citation, validation, and other uses. The NDHCC will also need to provide documentation, technical support, and training as needed to support use of the NHDCC resources among Complement-ARIE consortium members and the public community. Support could include online resources, remote assistance, video teleconferences and webinars as needed and appropriate.   

Models will be an important part of the Complement-ARIE program. The NDHCC will need to maintain an online diary of model predictions that tracks the user base and how the models are being used. The diary should enable the program to track the model versions and parameters, as well as iterative improvement processes.

3. Tool and Software Development for Data Analytics and Dissemination.

The NDHCC will be responsible for developing tools and processes for supporting data analytics, interpretation, and visualization of NAMs models and data, as well as tools and workflows for promoting NAMs reuse and tracking how data and resources generated by the Complement-ARIE program are being used by the research community. 

Examples of software tools that may be appropriate for this NOFO include, but are not limited to, the following:

• User-friendly analysis tools designed for investigators with limited experience in data mining.
• Analytic tools that can perform scalable curation/annotation, automation of metadata capture, terminology mapping, and/or transformation into common formats.
• Tools to promote data AI readiness, build knowledge graphs, and/or enable cloud computing.
• Tools to enable predictive analytics and in-silico modeling.
• A platform and a secure computational environment to enable Complement-ARIE Consortium members to collaboratively build, edit, and run data workflows, perform analysis, and develop computational models.
• Tools and workflows that incorporate relevant external data that would be useful for interpretation and meta-analyses of Complement-ARIE submitted datasets.
• Developing workflows or APIs to facilitate interactions with other NAMs-related efforts and components of the Common Fund Data Ecosystem.

Tool and Software Development Pilot Projects: The NDHCC should set aside 15% of the direct cost budget in years 3-5 for pilot projects to support the development of additional data analysis tools to analyze, interpret and visualize NAMs data to meet additional and growing needs of the Complement-ARIE Consortium. The scale and types of NAMs data generated through the Complement-ARIE program may change, e.g., with new types of data generated from Technology Development Center pilot projects, from potential additional Centers supported by other HHS agencies, and from increasing validation and qualification activities from the VQN. Pilot projects can be designed in collaboration with TDC investigators to develop tools for specific NAMs generated in the TDCs.  Additional data analysis tools may also be needed for data generated through validation or qualification activities conducted through the VQN. Applicants do not need to include these collaborative pilot projects activities as a separate budget item but should include details of potential pilot project activities to meet the evolving needs of the Complement-ARIE consortium as part of their applications. However, specific pilot projects will be determined post-award. The NDHCC, in collaboration with the TDCs and the VQN will submit pilot project requests, as needed, for additional data types generated or collected by the Complement-ARIE consortium. Pilot projects will be reviewed by NIH staff in consultation with the Complement-ARIE SC.

4. Overall Consortium Coordination and Outreach

The NHDCC will serve as the coordinating center for the Complement-ARIE program, organizing and hosting meetings, facilitating communication and coordinating activities across the consortium, and facilitating outreach and training activities for the Complement-ARIE program. As the coordinating center, the NDHCC’s responsibilities will include:

• Leadership and project management for the administrative and data coordinating functions of the Complement-ARIE program.
• Develop an organizational and administrative structure to promote communication among theTDCs, the VQN and the NDHCC, and provide technical assistance, and facilitate interaction across the awardees, including maintaining a Complement-AIRE consortium directory and a web-portal to assist with information sharing.
• Facilitate strategic engagement with key partners from other federal agencies including regulatory bodies, industry, non-profits, and other NGOs to advance emerging opportunities in the development and use of NAMs in basic, translational, and clinical research. Organize across-agency meetings as needed, such as to inform FDA, EPA and other federal partners of the new technologies developed by the consortium, seeking regulatory guidance if needed.
• Developing and maintaining a comprehensive project management plan to track activities, timelines, and milestones across the Complement-ARIE consortium, generating progress reports on a regular basis or as needed to identify and manage risks and dependencies.
• Establishing communication with liaisons from the Technology Development Centers, VQN, and other relevant program initiatives as needed. This includes developing and maintaining the relevant documentation.
• Bringing awardees together to reach consensus around appropriate data standard, CDEs and data sharing methods for management of diverse data sets, such that the development of minimal CDE for data interoperability optimization, or the preparation of de-identified data for public use.
• Organizing Complement-ARIE meetings (e.g., steering committee meetings, working groups, public webinars, etc.). This includes organizing and hosting a Complement-ARIE Kickoff meeting within six months of the award and semi-annual in-person program meetings to be held within the contiguous US, preferably within the Washington DC metro area. Responsibilities will include securing a venue, managing a hybrid meeting platform (for virtual attendees), defining the meeting agendas, identifying, and extending invitations to attendees, coordinating with speakers/presenters, and providing an executive summary of the meetings describing the major discussion points, action items, and decisions.  
• Organizing monthly (or bi-monthly) virtual consortium all-hands meeting to inform NIH policies, provide consortium progress update, identify and discuss emerging needs and issues, share availability of new resources.
• Arranging for and supporting travel costs of approximately three to five NIH-appointed External Program Consultants to the twice-yearly consortium-wide grantee meeting.
• Developing and maintaining Complement-ARIE program documentation, including recordings, videos, agendas, and meeting minutes, and maintain a permission-based access system.
• Reviewing outreach activities across Complement-ARIE to ensure coordination.
• Holding project meetings or office hours to discuss TDC specific needs, provide training on data submission and the adoption of data standardization.
• Coordinating and facilitating the logistics of training and outreach events in coordination with the Technology Development Centers, VQN, other partners and initiatives.
• Evaluating the use of NHDCC resources including tracking how data and resources generated by the Complement-ARIE program are being used by the research community.

Other NDHCC Application Considerations

There are additional issues that applicants should consider when crafting their applications. These include:

Governance of the NDHCC: The award funded under this FOA will be a cooperative agreement (see Section VI. 2. Cooperative Agreement Terms and Conditions of Award). Close interactions among the awardees and NIH will be required to maintain this complex program. All components will be governed by the Complement-ARIE Steering Committee (see Section VI:Terms and Conditions of Cooperative Agreement) 

Performance Requirements: Meet yearly milestones as defined by investigators and NIH Program Official at the time of award. Work with, cooperatively interact with, and actively seek input from NIH.

Evaluation of the Program: As the efficiency of the funded research is an important priority for NIH, representatives from all award projects will be expected to participate in an external evaluation process of the Complement-ARIE coordinated by NIH Program Staff  (see Section VI:Terms and Conditions of Cooperative Agreement), 

Incomplete Applications

The following types of applications are incomplete and will not be reviewed.

Applications that do not address all sub-sections described in the Research Strategy instructions (see Section IV.2: Content and Form of Application Submission - PHS 398 Research Plan).

See Section VIII. Other Information for award authorities and regulations.

Data Sharing

The NDHCC, coordinating the data generated in the Complement-ARIE program, is expected to adhere to a culture of Open Science and Data Sharing that promote the F.A.I.R. principles (see: NIH Strategic Plan for Data Science and abide by the NIH Data Management and Sharing Policy  The NIH expects that datasets and associated data be widely shared with the scientific community for research, while carefully observing established standards. Information is expected to be shared with the Complement-ARIE Consortium, presented at national meetings, and published in scientific literature. 

The NDHCC is required to actively coordinate, collaborate, and share data with all funded projects under Complement-ARIE and with the VQN. Data acquisition, collection, organization, representation, curation and data deposition strategies will be coordinated by the NDHCC.  The VQN will provide guidance on standardization and CDEs, annotation and benchmarking of data, consent for data sharing, and implementation of the schemas proposed. The TDCs, in coordination with the NDHCC, will ultimately be responsible for ensuring the long-term sustainability of the data they generate through Complement-ARIE by identifying and depositing the data in an established public repository, in keeping with the NIH Data Management and Sharing Policy 

Responsiveness

In order to be responsive to this NOFO, applicants must: 

• Include detailed plans for NAMs Data Hub Infrastructure Development and Maintenance, Data Coordination, Standardization, Harmonization, and Integration, and Tool and Software Development for Data Analytics and Dissemination.
• Include a comprehensive plan for Overall Consortium Coordination and Outreach 

Applications will be considered non-responsive and will not be reviewed if:

• Any of the four subsections above are missing.
• PD/PI (the contact PIs if a multi-PI application) does not devote at least 2.4 person months (20%) of full-time calendar month effort to the program. For applications with multiple PDs/PIs, a minimum effort of 1.8 person-months is required for the Contact PD/PI and 1.2 person-months of effort per additional PD/PI is required. 

Pre-application consultation with NIH Program staff is encouraged.  

Plan for Enhancing Diverse Perspectives (PEDP)

The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation.  Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex (including gender identify, sexual orientation, or transgender status) of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions.  Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

The PEDP will be submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP Guidance materials.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Government

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 allowed. 

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information. 

• 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registration; 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 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.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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 NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Daniel Shaughnessy, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3321
Email: [email protected]

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

For this specific NOFO, the Research Strategy section is limited to 30 pages.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed.

Plan for Enhancing Diverse Perspectives (PEDP)

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. 
• Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 2 pages in length and should include:
  • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
  • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
  • Anticipated timeline of proposed PEDP activities;
  • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex (including gender identity, sexual orientation, or transgender status).
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex (including gender identity, sexual orientation, or transgender status).

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP Guidance materials.

All instructions in the How to Apply - Application Guide must be followed.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed.

Leadership Effort Committment: The NDHCC contact PD/PI must commit and maintain through the life of the award a minimum of 2.4 person-months of effort. For applications with multiple PDs/PIs, a minimum effort of 1.8 person-months is required for the Contact PD/PI and 1.2 person-months of effort per additional PD/PI is required.

The NDHCC should set aside 15% of the direct cost budget in years 3-5 for pilot projects to support the development of additional data analysis tools to analyze, interpret and visualize NAMs data to meet additional and growing needs of the Complement-ARIE Consortium.

NDHCC Program Manager: Based on the complex roles the NDHCC will play in organizing the Complement-ARIE consortium the NDHCC PD(s)/PI(s) are strongly encouraged to propose and budget for an NDHCC Program Manager to manage day-to-day operations and work with the NDHCC PD(s)/PI(s), NIH staff, TDC Investigators and the VQN liaison to manage and coordinate the Complement-ARIE program activities.

Travel Funds: The budget should include sufficient funds to support travel for Complement-ARIE activities, including but not limited to supporting the travel and participation of PD(s)/PI(s) and other Complement-ARIE members at twice yearly Complement-ARIE Steering Committee meetings.

The NDHCC is responsible for arranging for and supporting travel expenses for up to three to five external program consultants for the entire Complement-ARIE program to in-person Steering Committee meetings.

The NDHCC is responsible for arranging for a meeting space(s) to accommodate 50-100 investigators for twice yearly in-person Steering Committee meetings one in the Fall for the Complement-ARIE Steering Committee and an annual Complement-ARIE Program Meeting in the Spring. The in-person meetings must be held within the contiguous US, preferably within the Washington DC metro area.

Equipment: If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: Specific Aims should address the five subsections described below (Overall NDHCC Vision and Management; NAMs Data Hub Infrastructure Development and Maintenance; Data Coordination, Standardization, Harmonization, and Integration; Tool and Software Development for Data Analytics and Dissemination; and Overall Consortium Coordination and Outreach. 

Research Strategy: In lieu of the standard sub-sections listed in the SF424 (R&R) Application Guide, the Research Strategy must consist of the following modified sub-sections:

Sub-Section A: Overall NDHCC Vision and Management

Overview and Goals Applicants should describe the ultimate goals/deliverables of the NDHCC Deliverables should be quantitative whenever possible; expressed using a Gannt chart; and should address critical items such as:

• Develop a Complement-ARIE Data Hub and working with the VQN establish a Complement-ARIE wide consensus for standardized NAMs data formats and metadata requirements.
• Establish Complement-ARIE consortium consensus for a data release policy.
• Implement analysis and visualization tools developed by the NDHCC working with the TDC investigators and the VQN.
• Develop and implement data submission, processing, quality control assessment, and download pipelines.
• Coordinate meetings across the Complement-ARIE consortium, maintain documentation of Complement-ARIE consortium activities, and support outreach and training activities for the program.

The exact nature and quantity of data that the NAMs data hub will need to store and manage cannot be known in advance. Given this uncertainty around the amount and type of data generated by the Complement-ARIE, it is important that the awardee provide a flexible, yet robust plan and realistic timeline to establish interim infrastructure as quickly as possible and describe an approach that will enable them to scale the infrastructure and capabilities as needed to support the activities of the consortium.

Leadership Plan: Describe the leadership team and how components of the NDHCC, including key personnel, will interact within the NDHCC itself, the Complement-ARIE consortium, and NIH program staff. Describe prior experience in working as part of a research network or other large-scale collaborative activities to meet individual and group goals, including examples of such prior work. Describe how decisions will be made by the leadership team and carried out. Describe mechanisms to ensure effective internal management of ongoing research activities across the NDHCC.

Milestones and Progress: Applicants should define a clear set of semi-annual milestones with metrics that will document progress towards the achievement of the ultimate goals of the NDHCC. Quantitative milestones are required 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. Examples include, but are not limited to, milestones that track time to develop data standards and formats, turn-around time to collect, store and analyze data submitted to the NHDCC by the TDCs or other components of Complement-ARIE, and development of data analysis and visualization software. Applicants should include plans for critically evaluating and revising these milestones on a regular basis. Applicants should describe how they will prioritize their activities to ensure that the main goals of the NDHCC will be achieved. Milestones may be revised at the time of the award. Applicants should also describe plans to solicit user feedback, monitor metrics of data usage, and otherwise evaluate all aspects of the usability of the NDHCC resources. This plan should describe the frequency of these evaluations and how this information will be used to improve the utility of the NDHCC. 

Management and Communication Plan Applicants should describe the plans for management and integration of the NDHCC activities. Applicants should describe how the NDHCC will manage the proposed project, who will oversee the day-to-day activities (e.g., a NDHCC Administrator if not the PD/PI) and how the management structure will support achievement of the proposed goals and milestones. Useful elements of this description include the organization of the proposed project; its management structure; key personnel and leadership structure; and oversight mechanisms for evaluating progress towards milestones. Applicants should describe plans for ongoing communication within the NDHCC and between the NDHCC and other components of the Complement-ARIE consortium. Plans for addressing some of the anticipated challenges of the NDHCC should also be included. The plan should also describe how the various elements of the proposed production effort will be integrated, and how collaborations or subcontracts, if proposed, will be managed.     

Sub-Section B: NAMs Data Hub Infrastructure Development and Maintenance

• Describe how the Data Hub will provide a centralized repository for NAMs-related data, including metadata, across the Complement-ARIE consortium with the flexibility to manage and integrate multiple types of NAMs data.
• Describe the search portal in detail with respect to easy search, retrieval, and integration of data and tools developed in the Complement-ARIE consortium.
• Describe the proposed structure for tiered access for Complement-ARIE consortium members, including the TDC investigators and members of the VQN according to Complement-ARIE consortium agreements, and the tools and data use agreements needed to ingest data from outside the Complement-ARIE program, including proprietary data.
• Datasets generated by Complement-ARIE may be a mixture of open access and controlled access.  The NDHCC is not required to store controlled access data. Applicants will need to describe how they will work with data generators to identify appropriate repositories for controlled access data.
• Applicants need to describe how they will  ensure controlled-access datasets generated by the Consortium but hosted in other repositories are findable through the NDHCC web interface.
• Describe how the NDHCC web interface will enable appropriate data sharing with the broader scientific community.
• The awardee will be responsible for data security for all data within the NDHCC. The applicant should describe their plans for ensuring confidentiality, data integrity and availability of Complement-ARIE data and to adhere to The NIH security best practices for Users of Controlled Access Data and prevent unauthorized access to data.
• Describe how the Data Hub infrastructure will implement data standards established by the Complement-AIRE consortium.  

Sub-Section C: NAMs Data Coordination, Standardization, Harmonization, and Integration

• Applicants need to describe how they will work with consortium members and stakeholders to develop consensus on metadata standards, CDEs, terminologies, data sharing approaches and other data strategies to support data collection, standardization, integration and sharing, curation, management, and use.
• Describe how the Data Hub will establish metadata standards with controlled vocabularies in machine-readable formats to enable broad and FAIR use of Complement-ARIE data, including adopting metadata standards in alignment with the NIH Common Fund Data Ecosystem.
• Applicants should describe how the NDHCC will track the use of the Complement-ARIE NAMs data and tools by the wider research community and will provide documentation, technical support, and training on the use of NHDCC resources by the Complement-ARIE consortium members, the wider scientific community, and the general public.
• Describe how the NDHCC will develop strategies to enable interoperability of NAMs datasets generated by Complement-ARIE and a strategy to ensure sustainability of the data and tools produced by Complement-ARIE beyond the Complement-ARIE program period.

Sub-Section D: Tool and Software Development for Data Analytics and Dissemination

• Describe how the NDHCC will develop tools, software, and processes for analyzing, interpreting, and visualizing NAMs data, meta-analysis of Complement-ARIE datasets, and workflows to facilitate interactions with other NAMs-related across the Complement-ARIE consortium, including data from the VQN used to benchmark new NAMs technology developed in the TDCs.
• Describe how software tools developed or enhanced through the NDHCC will be shared broadly with relevant scientific communities.
• Applicants should propose general pilot projects to meet additional needs of the Complement-ARIE Consortium. The scale and types of NAMs data generated through the Complement-ARIE may change, e.g., with new types of data generated from Technology Development Center pilot projects, from potential additional Centers supported by other HHS agencies, and from validation and qualification activities from the VQN. Specific projects developed collaboratively with TDC investigators or the VQN post award will be submitted with a separate budget for review by NIH program staff in consultation with the Complement-ARIE SC.

Sub-Section E: Overall Consortium Coordination and Outreach

• Provide a detailed description of the comprehensive management plan to track activities, timelines, and milestones across the Complement-ARIE consortium.
• Describe how the NDHCC will assist the community in developing harmonized standards and best practices for NAMs research, development, validation, qualification, and adoption. This should include plans to seek broad stakeholder input and how such efforts will be disseminated to the broad biomedical research community.
• Describe plans for organizing, and hosting Complement-ARIE in-person program meetings, Steering Committee meetings, working group meetings, and cross-program meetings, e.g., meetings between TDC investigators and end-users of NAMs in the VQN. Plans should include logistical coordination and maintaining meeting documentation, including meeting minutes and executive summaries, recordings, and videos.

Describe how the NDHCC will coordinate and facilitate training and outreach activities across the Complement-ARIE consortium, including providing administrative support for community outreach events.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide with the following additional instructions:

• Ensure all project resources, tools, and methods developed through the NDHCC are broadly available (e.g., putting into the public domain) or made accessible to the research community.
• Software tools developed, extended, or otherwise enhanced through this program should be openly disseminated for broad adoption by the relevant communities, following best practices for sharing research software (https://datascience.nih.gov/tools-and-analytics/best-practices-for-sharing-research-software-faq) as well as FAIR (Findable, Accessible, Interoperable, Reusable; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792175/) principles for associated data and documentation.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

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 How to Apply - Application Guide must be followed.

Delayed Onset Study

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 How to Apply - Application Guide must be followed.

All instructions in the How to Apply - Application Guide must be followed.

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

See Part 2. 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

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply - 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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

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

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected]. 

Applicants are required to follow the instructions for post-submission materials, as described in the policy

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.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).As part of the overall impact score, reviewers should consider and indicate how the Plan for Enhancing Diverse Perspectives affects the scientific merit of the project.

As part of the overall impact score, reviewers should consider and indicate how the Plan for Enhancing Diverse Perspectives affects the scientific merit of the project.

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the proposed NDHCC address the needs of the research within in the Complement-ARIE consortium that it will serve? Is the scope of activities proposed for the NDHCC appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research program/projects/network/consortium/resource?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific to this NOFO:

How well articulated is the proposed overall vision for the NDHCC activities and milestones to track the progress of the NDHCC? Are milestones clear and measurable? Do milestones reflect major accomplishments or decision-points for the proposed center? How well does the research plan address each of the four core components of the NDHCC: Data hub infrastructure development and maintenance; Data coordination, standardization, harmonization, and integration; Tool and software development for analytics and dissemination; and Overall consortium coordination and outreach?  How comprehensive and practical is the proposed plan for establishing a Complement-ARIE data hub for collecting, storing, analyzing, and sharing NAMs-related data across the Complement-ARIE consortium?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the NDHCC? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing NAMs-related data in NAMs research? Do the investigators demonstrate significant experience with coordinating collaborative basic and clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the NDHCC? Does the applicant have experience overseeing selection and management of subawards, if needed?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this NOFO:

To what degree do the applicant, partners and/or collaborators have a strong record of managing a comprehensive data hub resource that will meet the needs of the Complement-ARIE program? What type of expertise does the investigative team have in data management, harmonization and sharing, and in developing innovative data analytic tools and software for the diverse NAMs data types generated by the Complement-ARIE consortium?

Innovation

Does the application propose novel organizational concepts, and management strategies, in coordinating the research in the Complement-ARIE consortium the NDHCC will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Specific to this NOFO:

Does the application propose innovative tools and solutions to manage, analyze, interpret and visualize complex and diverse NAMs datasets that will be generated by Complement-ARIE? Does the application propose a flexible and robust plan to meet the needs of the Complement-ARIE program, as the scale and types of data may change through the program period?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research in the Complement-ARIE consortium the NHDCC will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the Complement-ARIE consortium, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the NDHCC is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the Complement-ARIE consortium? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

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 or 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?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex or gender and race or ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this NOFO:

To what extent does the application describe approaches for data standardization and harmonization in collaboration with the Validation and Qualification Network (VQN) and Comprehensive NAMs Technology Development Centers (TDCs)? What approaches are proposed in the plan for the Data Hub for integrating heterogeneous NAMs datasets generated by Complement-ARIE? Does the application contain acceptable plans for tiered access to Complement-ARIE data within the consortium?

How comprehensive and attainable is the project management plan for coordinating activities across the Complement-ARIE program, including program meeting support, tracking activities, timelines, and milestones or the program and documenting Complement-ARIE meeting minutes and outreach activities?

Environment

Will the institutional environment in which the NDHCC will operate contribute to the probability of success in facilitating the research in the Complement-ARIE consortium it serves? Are the institutional support, equipment, and other physical resources available to the investigators adequate for the NDHCC proposed? Will the NDHCC benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to this NOFO:

How well does the environment promote cross-consortium collaborative activities and the flexibility to meet the data management, integration, harmonization, and sharing needs of the program, including the capacity to meet the changing data management needs over the course of the program?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories 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 or 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 three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals 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

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

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 Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

For [programs/projects/networks/consortia/resources] 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 the Center for Scientific Review, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Environmental Health Sciences Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project, including the PEDP, as determined by scientific peer review
• Availability of funds.
• Relevance of the proposed project to program priorities.

Please note that reviewers will not consider race, ethnicity, age, or gender (including gender identity, sexual orientation or transgender status) of the researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its funding decisions.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

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

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website. 
  • HHS recognizes that NIH 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. 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

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 (HHS) grant administration regulations at 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• Negotiating and agreeing on a final set of approved milestones and re-negotiating milestones during the project period, if needed.
• Participating in regular (monthly) conference calls with all NIH Project Team members.
• Accepting and fully participating in the cooperative nature of the Complement-ARIE Consortium, including participation in the semi-annual consortium meetings organized by NIH and NDHCC.
• Coordinating efforts with other recipients, especially in circumstances where synergy of efforts and resources is beneficial to the overall goals of the Complement-ARIE program.
• Adhering to the NIH policies regarding intellectual property, data release and other policies that might be established during the course of this activity.
• Ensuring the data hub infrastructure protects research data obtained from human subjects and clinical trial data and ensures compliance with data privacy regulations and policies.
• Working with, cooperatively interacting with, and actively seeking input from NIH.
• Identifying and maintaining infrastructure and collaborations needed to support the development of the proposed NAMs.
• Working with the NIH, TDCs, and the VQN, including FDA, EPA, and industry partners, when appropriate, to establish Common Data Elements and FAIR data standards to maximize data sharing across the Complement-ARIE consortium.
• Sharing data, materials, informatics tools, methods, information, and unique resources that are generated by the Complement-ARIE consortium, as appropriate, and in accordance with NIH policies in order to facilitate progress and consistent with achieving the goals of Complement-ARIE.
• Establishing data use agreements (DUA) with the appropriate parties within the Complement-ARIE program and establishing tiered access to proprietary data generated outside the Complement-ARIE consortium that may be submitted to the Data Hub for benchmarking and technical characterization of NAMs developed in the TDCs.
• Ensuring that for activities that involve academic and/or industry collaborations within and outside the Complement-ARIE 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.
• The recipient will be responsible for data security for all data within the NDHCC and will adhere to The NIH security best practices for Users of Controlled Access Data  to protect the privacy and confidentiality of research participants and prevent unauthorized access to data.
• Coordinate data collection and data submission activities with the Complement-ARIE consortium.
• Working with the VQN to establish agreements that address the following issues: (1) adherence to NIH and Complement-ARIE Consortium data sharing policies as approved by Program staff prior to award. This includes data sharing with Complement-ARIE consortium members, as appropriate; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the Complement-ARIE 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 reviewing publications, determining authorship, and industry access to publications.
• Upon completion or termination of the project, ensure all project resources, tools, and methods developed through the NDHCC are broadly available (e.g., putting into the public domain) or made accessible to the research community according to the NIH-approved data management and sharing plan submitted for each project.
• Provide updates at least annually on progress in PEDP implementation.
• Publications The contact Program Director/Principal Investigator (PD/PI) will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD/PI and Project Leaders are requested to submit manuscripts to the NIH Program Official within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under the Cooperative Agreement are the responsibility of the Principal Investigator and will require appropriate acknowledgment of NIH support. Timely publication of major findings is encouraged.
• Recipients(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current DHHS, PHS, and NIH policies.

NIH Program Staff

An NIH Program Official will be responsible for the normal programmatic stewardship of the award and will be named in the award notice. The program official(s) will:

• Assist in enforcing general statutory, regulatory or administrative assistance policy requirements;
• Provide stewardship and administrative oversight of the cooperative agreement;
• Negotiate and agree on a final set of approved milestones.
• Evaluate progress by reviews of technical or fiscal reports or by site visits to determine that performance is consistent with objectives, terms and conditions of the award;
• Ensure that activities proposed for development or implementation do not overlap or duplicate activities supported by other peer reviewed funding mechanisms;
• Review all requests for prior approval as required by the NIH Grants Policy Statement;
• Retain the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award.

NIH Project Scientist(s) will have substantial scientific involvement that is above and beyond the normal stewardship role in awards during the conduct of this activity, through technical assistance, advice, and coordination. NIH Project Scientist(s) will:

• Participate in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols, project milestones or approaches as warranted. The Project Scientist will assist and facilitate the group process but not direct it;
• Monitor progress on the agreed upon milestones and help identify recourses if needed;
• Provide advice on project management and technical performance;
• Serve as a liaison between the recipients, the Advisory Councils for participating Institutes and the larger scientific community;
• Coordinate the efforts of the recipient with others engaged in Complement-ARIE;
• Attend Steering Committee meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action;
• Periodically report progress to the Directors, NIH Institutes and Centers involved in the Complement-ARIE program;
• Serve on subcommittees/working groups of the Steering Committee as appropriate;
• Provide advice in the management and technical performance of the investigation;
• Assist in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
• Assist recipients in the development, if needed, of policies for dealing with situations that require coordinated action.
• Enlist additional scientific experts as necessary from within the NIH and other government agencies, such as the FDA, to assist the recipients in carrying out the goals and aims of the approved studies.

Areas of Joint Responsibility:

• Participate in recurring monthly meetings to discuss progress, obstacles and any other Complement-ARIE related issues and/or activities.
• The NIH will enlist additional scientific 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 PD(s)/PI(s) in carrying out the goals and aims of the approved studies.

Communication Plan

• Participate and present findings at the semi-annual Complement-ARIE Consortium meetings convened by the Complement-ARIE Data Hub and Coordinating Center.
• Coordinate or jointly publish findings in a timely manner, and as to have the broadest impact.
• Make new information and materials known to the research community in a timely manner through publications, web announcements, reports to the NIH.

Performance Requirements

• Meet yearly milestones as defined by investigators and NIH program officials at the time of award.
• Actively coordinate, collaborate, and share data and resources developed by the NDHCC across the Complement-ARIE consortium and sharing NAMs data and resources and with the broader scientific community, and the public, as appropriate under the data use agreements and data sharing strategies developed by the Complement-ARIE consortium   with considerations under tribal IRB processes, as appropriate.
• Work with the TDCs and VQN to collect, store, and share NAMs-related data and tools
• Work with the TDCs and VQN to establish common data elements and harmonized data standards for NAMs-related data across the Complement-ARIE consortium
• Overall coordination of the Complement-ARIE program, including coordinating and hosting Complement-ARIE in-person meetings, Steering Committee and work group meetings, coordinating outreach and training activities and tracking and documenting Complement-ARIE activities.

Complement-ARIE Consortium

Recipients agree to governance, through voting and decision making, of the Complement-ARIE consortium through a Steering Committee (SC). The Steering Committee membership will include a representative PD/PI from each awarded Cooperative Agreement, NIH Project Scientist, the PD/PI of the Validation and Qualification Network (VQN) and the PD/PI of NAM Data Hub and Coordinating Center (NDHCC) PD/PI. The PD/PI of each award (or designee) will have one vote on the SC. A NIH Project Scientist will represent NIH Project Staff and will have single vote. The Steering Committee Chairs will not be NIH staff members. Award recipients will be required to accept and implement policies approved by the SC. Other government staff may attend the Steering Committee meetings if their expertise is required for specific discussions. The Steering Committee will:

• Discuss progress in meeting the goals of Complement-ARIE projects;
• Develop recommendations for uniform procedures and policies necessary to meet the goals of Complement-ARIE;
• The SC will also serve as a venue for coordination for collaborative efforts across the  Complement-ARIE consortium;
• The SC will consider the collective program goals for Complement-ARIE activities.
• NIH staff will work with the Complement-ARIE SC to review and select pilot projects submitted by the NDHCC to meet additional needs of the Complement-ARIE Consortium with respect to new types of data generated across the Complement-ARIE consortium

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 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 recipient. This special dispute resolution procedure does not alter the recipient'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. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting.  To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

• Recipients will provide updates at least annually on implementation of the PEDP.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

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Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (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: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Daniel Shaughnessy, PhD
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3321
Email: [email protected]

Center for Scientific Review (CSR)
Email: [email protected]

Jenny Greer
Chief, Grants Management Branch
National Institute of Environmental Health Sciences (NIEHS)
Telephone: 984-287-3332
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.